Final Exam 2nd Semster Q

Question 1

26. Antiarrhythmic drugs II, III and IV classes: group members, features of antiarrhythmic action, indications, side effects. Example of drug prescription.

Answer 1

-DF of AP : in the resting state K+ ions is found mainly intracellular while Na+ and Ca+ extracellular making the intracellular is negative
-phases :
Phase 0 : rapid depolarization of the cells duo to rapid influx of Na+
Phase 1 : short period of Redepolazation duo to slow influx of K+
Phase 2 : Plateu delay in repolarization duo to slow influx of Ca
Phase 3 : second period of Rapid repolarization duo to rapid out influx of K+
Phase 4 : the resting state is restored , Na is extracellular , K+ back to intracellular by Na/K+ pump
- Difference between Phase 4 in Atrium and ventricular : is the slop the atrium consist of Slop duo to pre entering of Ca+ to the cells in this phase
—Pathophysiology of Arrhythmia:
-Df : its disturbance in the normal heart rhythm and its results from :
1-Abnormal impulse generation
2-abnormal impulse conduction
—
- Classification of arrhythmia:
1-Bradyarrhythmia AV block : drugs > Atropin , Adrenaline , isoprenaline
2-tackyarrhythmia : consist of 4 classes
—————— Classes ———
1A class
—its increase the APD by inhibition of Na channel
-Drugs :
1-Quinidine tab
2-Disopyramide tab
3-Procainamide tab
—mechanism:
1-they block Na+ channel leading to decrease the Rate of Phase 0 depolarization which lead to increase The APD
2-decrease the exitibality on the atrial side slop which lead to decrease the firing of SA nodes
—pharmacological effect :
1- Arropine like action duo to blocked of muscranic receptor
2-hypotension duo to block of à receptor
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
-side effect :
1-Atropin like action
2-hypotension
3-small doses cause increase AV conduction
4-negative Iontropic effect
- uses :
1-Supraventrecular Arrhythmia
2-ventricular tachyarrhytmia
—NB : the difference between Procainamide and Quinidine is that Procainamide cause SLE like
–
-1B class
—they are decrease the APD
-drugs :
1-Lidocaine Amp ,
2-Mexiletine Caps
3-Phenytoin tabs
—mechanism: it decrease the APD by increasing K+ in the 3rd phase ( repolarization) which llead to decreas APD
–pharmalogical effect :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
—uses :
1-ventricular tachyarrhythmia
2-Acute MI > lidocaine
3-Arrhythmia with over dose of cardiac glycosides > phenytoin
–
Class 1C
—they have no effect of the APD
-Drugs : Propafenone amp ,Ethacyzin tab
-mechanism: by slowing the influx of sodium ions into the cardiac muscles cells causing decrease in :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
-uses :
1-Supraventrecular
2-ventricular Arrhythmia
———————–
— class 2 are B.Blockers
-Drugs :
1-selective : B1> metoprolol ,Atenolol
2-nonselective : Propranolol tabl
-mechanism: they block Sodium, Potassium, Calcium , channel’s which lead to inhibition of phase 4 and depress Autmoticity and prolong Av conduction , alsodecrease HR , :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
—Side effect :
1-CVS : decrease conductivity, bradycardia , AV block , hypotension
2-Respiratory: bronchispasm
3-GiT : dyspipsia
4- CNS : inly lipophlic drug such as propranolol > depression
-Uses :
1-Supraventrecular
2-And ventrecular tachyarrhythmia
————————
—3rd class
-They are K+ channel blocker
-Drugs :
1- Amiodarone Tab / Amp
2-Sotalol
-mechanism: inhibition of K+ channel in phase 3 which prolongate The Apd also inhibit Na+ and Ca+ , also casue Cornary V.D
-side effect :
1-Bradycardia
2-Arterial hypotension
4-Pulmonary fibrosis
5- photo sensitivity
6-hyperthyroidism
-uses : most type of arrhythmia
-contraindication: Arrhythmia duo to thyrotoxicosis
———————-
-4th class
-They are clacium channel blocker
-Drugs :
1-Verapamil
2-diltiazem
-mechanism:its prolongate the APD through inhibation of Ca+ in phase 2 pleatue ,:
Conductivity ↓
Contractility ↓
Excitability ↓
Automatism:
atria ↓
—Side effect :
1- Decrease conductivity
2-bradycardia
—uses : superventercular tachyarrhythmia

Question 2

27 Antiarrhythmic agents used in bradyarrhythmia and AV-block of the heart. Example of drug prescription.

Answer 2

-Classification:
1-M Cholingric blocker : Atropin high dose
2-B agonist : Isoprenaline amp
3-a,B agonist: NorEpinephrine
-Pharmacological effect :
1- Increase contractility , conductivity,Automatcity ,COP
-Side effect :
1-Tachycardia
2-Atropine like action
3-Cardiac aresst
4-Tremors
5-Hypokalemia

Question 3

28 Principles of pharmacotherapy of coronary artery disease. The main groups of antianginal agents. Nitrates: mechanism of action, indications, side effects. Example of drug prescription.

Answer 3

—DF: impaired blood flow through the coronary Artery duo to :
1-Organic Athresclerosis
2-Thrombosis
—Pathophysiology:
-Types of IHD
1-Chronic Stable angaina
1.1 its duo to atherosclerosis and narrowing of the major branch of the heart
1.2 pain induce by effort
2-Acute Coronary Syndrome:
2.1 unstable Angina: its duo to rupture of the plaque
2.2 MI : its next stage of which above and charectrazed by complete occludes of the Epicardial Coronary Artery
3-Prenzmetal Angina ( vasospasmtic ) : its duo to a receptor overactivity , and its happen even in rest
—Pathogenesis:
- its imbalance between oxygen demand and supply of the heart
—————-
–Classification :
1-Nitrates / Nitrates like agent
2-B adrenergic Blockers
3-Calcium channel blocker
4-Other drugs : Ivaberdini tab 0,005
———
—Drugs :
1-Nitroglycerin tab 0.003
2-Isosorbide Dinitrate
3-Isosorbide Mononitrate
4-Molsidomine
— Classification:
1-Short acting
1.1 Nitroglycerin ( Suplingual )
1.2 Isosorbide Dinitrate (Suplingual)
2- Nitrate like Agent: Molsidomine
3-Intermediate Act
3.1 Isosorbide dinitrate ( tab)
4-long acting
4.1 Isosorbide Mononitrate
—Pharmacokinetics:
-Absorption: good
-FPM: 90% While Mononitrate have no FPM
—Mechanism of Action :
-Nitrate release nitrate Oxide (NO) by the effect of Enzyme called Mitacondrial Aldahyed dehydrogenase 2 , NO stimulate Soluble Guanyly Cyclase and cause increase of the second massenger cGMP which is results of Smooth muscles relaxation by stimulating dephosphorlation of myosin light-chain phosphate which lead to :
1-Arterial dilation > decrease Pulmonary vascular resistance which is decreasing post load = decrease myocardial demand of O2
2-venous dilation > decrease venous return > decrease endosystolic volume > decrease pre load = decrease myocardial O2 demand
3-when Endosystolic decrease leads to decrease ventricular wall tension which lead to increase Sub endocardial blood flow = increase myocardial oxygen supply
4-Coronary vessels dilation > increase myocardial oxygen supply
—Additional effect :
1-relaxation of most smooth muscle ~ git , bronchi
2-decrease aggregations
—Side effect :
1-reflex tachycardia
2-Postural hypotension
3-Fascial flushing > duo to venous dilation
4-headache and dizziness
5-Tolerance
—Uses :
1-HR > Nitroglycerin, Isosorbide dinitrate suplingul
2-IHD > isosorbide mononitrate
3-Acute Coronary syndrome , MI > IV nitroglycerin
—Contraindications:
1- mixed it with drug of PhospateDieastrase type 5 such as Sildenefi its potent the action of nitrate , and cause postural hypotension

Question 4

29. Mechanisms of antianginal action of β-adrenergic blockers and calcium channel blockers, indications, side effects. Example of drug prescription.

Answer 4

–B blockers
—Drugs :
1-Propranolol > lipophilic , 1st gen , no selective
2-Bisoprolol > 2gen , selective B1
3-Metoprolol > lipophilic ,2gen , selective B1
—mechanism of action : They block B adrenergic receptor and decrease
cAMP which lead to decrease Ca result in effect on the heart and kidney which lead to :
1-decrease HR
2-decrease contractility
3-Decrease Renin
—side effect :
1-headache drawnness
2-bradycardia , AV block
3-hypotension
—Uses :
1-chronic classic angina
—Contraindications:
1-Vasospastic angina ( Premzemtal )
2-AV block
3-AHF
3-Bronchial asthma
————————————————————–
CCB blocker
—Drugs :
1-Verapamil 1gen
2-Diltiazem 1gen
3-Amlodipine 3 gen
—mechanism:
-They Block potential-dependent L-Type of calcium channel which decrease transmembrane Ca2+ current to heart and arteries which lead to :
1-Decrease myocardial oxygen demand duo to :
1.1 decrease HR ( verapamil )
1.2 decrease Post load
2-increase myocardial oxygen supply duo to :
2.1 Coronary dilation
2.2 increase subendoccardial blood flow
—Phramalogical effect :
1-Antihypertinsive
2-Antiarrhytmic
3-decrease Platelets aggregations
—Side effect :
1-CVS : bradycardia, AV block , reflex tachycardia
2-GIT : dyspepsia
3-CNS: headache
4-Allergic reaction
—uses :
1-Stable angina
2-Vasospastic Angina
3-hypertension
4-tachyarrhythmia

Question 5

30. Calcium channel blockers: classification, pharmacological effects, indications, side effects. Example of drug prescription.

Answer 5

—Drug groups :
1-Dihydroperiden :1st gen Nifedipine, 3rd gen Amlodipine ,
nicardipine> vascular selective
2-Benzodiazepines: Diltiazem
3-phinylalklamine : Verapamil > Cardio Selective
—mechanism:
1-it decrease peripheral vascular resistance by blocking of potential-dependent L type Ca+ channel which lead to decrease Ca+ in smooth muscles of arteries and result of decreasing vascular tone
2-its also decrease heart rate and Cop negative ion-tropic and chronotropic effect in case of use Verapamil , Diltiazem
—Pharmacological effect :
1-Smoothie muscles relaxtion
2-Cell necrosis: decrease cell necrosis bcs Ca+ is essential for apoptosis
3-decrease insulin release
4-decrease nuronal firing bcs Ca+ is essintial
5-Platelets: decrease platelets aggression because Ca+ is essential
—Side effect :
1- Bradycardia ; verapamil , Diltiazem
2- Reflex tachy : Nifedipine
3-hypotension
4-Constapiation : duo to RAAS reflex
—Uses :
-Verapamil
1-IHD
2-SVT
3-hypertrophic obstractive cardiomyopathy
-Amlodipine
4-ischemic renal failure
5-hypertension im pregnancy : nifedipine
—Contraindications:
1-CHF
2-bradycardia, AV block
3-in combination with digoxin or B.B because all of them nogative iontropic
4-Wolf parkinson syndrome: which the patient have accessory bundle of kent

Question 6

31. Hypolipidaemic drugs: classification, mechanisms of action, side effects. Example of statin prescription.

Answer 6

1- HGM-CoA recutase enzyme inhibitor drugs
—Drugs :
1-Atorvastatin tab
2-Rosuvastatin Tab
—mechanism:
they are competitive inhibitor for HGM-CoA enzyme inhibitor which lead to decrease cholesterol synthesis in the liver and increase uptake of LDL
-side effect :
1-hepatic dysfunction : reversible
2-myopathy,myositis
3-GIT upset
4-Cataracts in the eye
-Uses :
1-hypercholystronemia
—Drug interaction :
1-CYP450 inhibitor , which may induce the myopathy and myositis
2- also combined with Fibrates
——
2- The PCSK9 inhibitor drug
—Drug : Alirocumab Amp S.c
—Alirocumab its monoclonal antibody for PCSK9
-mechanism: PCSK9 its protein synthesis by many tissue in the body including the liver and its promotes lysosomal degeneration of LDL receptor in the liver , So inhibiting of this receptor lead to increase LDL receptors
—Side effect : flu like symptoms
-Uses : hypercholestrolenima
——
3-Fibrates
—Drug : Fenofibrate tab
-mechanism: its act on nuclear receptor called PPAR-a proxisome proliferator activated receptor Alpha leading to increase synthesis of lipoprotein lipase which lead to increase catabolism of VLDL and chylomicrons
—Side effect :
1-GIT upset
2-increase formation of Gall stones
3-reversible hepatic dysfunction
4-myopathy
—Uses :
1-hypertriglyceridnemia
2-Combined hyperlipidnima
3-dysbetalipoprotenima
4-mixed hypertriglycerdenima
—–
4-nictonic acid
—Nicotinic Acid tab SR NB! its Vitamin B3
-mechanism: Niacin inhibit lipolysis of triglycerides from the adipose tissue
which is lead to decrease the catty acids that reach. the liver results of decrease synthesis of LDL and VLDL
-side effect :
1- skin flushing and burning sensations
2-hyperglycemia
4-GIT upset
-uses :
1-Hypercholstrolenima
2-hypertriglycerdneima
3-Combined hyperlipidenima
——–
5- Cholesterol Absorption inhibitor drugs
—Drug : Ezetimibe tab
-mechanism: its selective inhibitor of cholesterol absorption and its effect even in absent of diatry fat becs its inhibit Reabsorption of cholesterol that excreted in the bile
-uses : hypercholstrenemia
——
6-Bile acid sequestrants drugs
-Drug : Cholystyramine tab
-mechanism: its bind to bile acid in the intestine and decrease absorption of cholesterol and decrease cholesterol storage in the body
-Side effect :
1-GiT upest
2-Decrease Absorption of the Fat sulobale drugs or Vitamins
—uses :
1-Hypercholestronima

Question 7

32 Diuretics: classification, comparative characteristics, indications for use, side effects.
Example of drug prescription.

Answer 7

—they are 3 main groups ——
1-loop diuretics
—Drugs :
1-Furosemide amp/tab
2-torasemide amp / tab
3-Ethacrynic acid tab
-mechanism: the location of action is in the ascending loop of henle and they block the transports channel Na/K+/Cl- , also increasing synthesis of PGE1,I2 and improve blood supply of kidney which is lead to excrete :
1-Na/water
2-K+/cl-
3-Ca/mg
4- H+
—pharmacological effect
1-powerful duirsis accompind with loos of K+/Ca/mg
2-Vasodilation
3-increase blood supply of kidney duo to increase synthesis of PgE2,I2
4-VD of pulmonary duo to formation of PG increase
-Side effect:
1-hypovolmia
2-hypotension
3-metabolic alkalosis : duo to loss of H+
4-hyperurecimia : duo to increase uric acid reabsorption in PCT as result of hypovilemia
5-ototoxicty : reversible hearing loss duo to disturbance of ion transportation in inner ear , mostly occurs in high doses
6-allergic reaction : dou to SH group except Ethacryinc acid
-uses :
—Chronic :
1-CHF
2-Liver Cirrhosis
3-RF
—emergency:
1-Pulmonary edema , Cardiac Asthma
2-Acute glucoma attack
3-posinig with water sulable toxins
4-hypertensive crisis : Furosemide IV duo to :
-decrease plasma volume
-decrease vascular smooth muscles
-peripheral VD
———-
2- thiazides drugs
-Drugs :
1-hydrochlorothiazide
2-Clopamide
2-indapamide all tabs
—mechanism: the location of action is the Proximal part of DCT they block
Na/Cl- transport channel and increase Ca reabsorption , and inhibit Carbonic anhydrase enzyme in the PCT , also decrease Na input in smoothie muscles sensitivity to VC
-pharmacological effect :
1-moderate dursis
2-VD
3-decrease production of interocular fluid
4-decrease loos of Ca+
—side effects:
1-hypokalmia
2-hypomagnsimia
3-hyperurecimia ( duo to competition with urates ) ( its ++ uric acid in urine )
4-hyperclacimia
5-hyperglycemia
6-metabolic alkalosis
7-hypotension
—uses :
1-hypertension ( long term treatment )
2-Chronic peripheral edema in :
CHF , liver cirrhosis, miled RF
3-idiopathic hyperclaciuria
——————
3-K+ sparing
—Drugs :
1-Spironolactone tab
2-Amiloride
3-Triamterene
—mechanism: drugs have different mechanism :
1-Spironolactone : its comparative antagonist of aldesteron-dependent-sodium-potassium receptor at the distal site of DCT leading to increase Na/water execration and K+ retention
2-Amiloride/Triamterene : they block the entery of Na/H2o At the distal part of DCT and collecting duct which lead to increase Na/water excration and K+ retention
-side effect :
1-hyperkalamia
2-Acidosis: duo to H+ retention
3-gyncomastia
4-menstrual irregularities
5-erectail dysfunction
-uses of spironolactone:
1-primary hyperaldestornsim ( Cohin syndrome )
2-Secondary hyperaldesttonsim
3-CHF
4-Hypertension
5-hypokalimia
———————–
4- Carbonic anhydrase inhibitor
-drugs :
1-Acetazolamide tab
2-Brinzolamide eye drops
—mechanism: inhibition CAI lead to decrease H+ formation inside the cell , decrease Na/H+ anti-port, increase Na+ and HCO3 in lumen which is lead to increase duress
—mechanism in the eye : its decrease the formation of Aqusomer fluid in the Eye which is lead to decrease IOP
—pharmacological effect:
1-mild duress
2-sever acidosis
3-decrease ICF
4-Decrease IOF
—uses :
1- no druess use anymore duo to acidosis
2-glucoma
3-intercernial hypertension
4-as adjuvant drug for epilepsy
-Contraindications:
1-Liver cirrhosis duo to decrease execration of ammonia which lead to hepatotoxicity
—————————-
NB! tha diffrinses on mechansim , side effect , uses

Question 8

33 Antihypertensive drugs: the main groups, mechanisms of antihypertensive action, indications for use, side effects. Example of drug prescription.

Answer 8

—ACEi , drug groups —–
—Drug groups :
1-Sulfhydrnal group : Captopril tab
2-non SH group : Enalapirl,Enalaprilate tab
—mechanism of Renal hypertension:
-when renal ischemia occurs and RBF , GFR decreased this lead to Acute oliguria that may develop acute tubular necrosis
- As comoplasatory mechanism , renin is released from jaxtaglumular cells as rescue message to stimulate RAAS as its follows :
-Renin > Angitensigen > Angiotensin’s 1 > ACE / kinins > ACE convert Angiotensin to Angiotensin 2 , And kinins metabolis bradykinies .
-Explanation : renin which released from the kidney goes to Angiotisgen which is inactive form and activating it which lead to Angiotensin 1 and with enzyme ACE converted to be Angiotensin 2 , also with ACE there is Another Enzyme called kinins which metabolise bradykinase which is responsible for VD
-Ang 2 : Acts on 2 receptors
1-AT1 : -its cause V.C and thus mentaine Adequate GFR , in another vascular tissue Ang2 act on AT1 casuing systemic V.C , cell hypertrophy, Increase Apoptosis
2-AT2 : V.D
—Mechanism of ACEI : by inhibition of ACE and kinase the affect will be :
1-decrease conversion of Ang1 to Ang2 = decrease vascular tone
2-decrease Aldesteron > decrease Na/water retention = increase K+
3-increase Bradykinin > increase synthesis of PG > decrease vascular tone
—Receptors of Ang2 :
1–AT1 : activating of AT1 : located mostly in efferent and its G-Protein linked receptor when its activated cause V.C duo to :
1-increase intraglumular hydrostatic pressure = Increase GFR
2-Systemic V.C
3-increase Aldesteron release = salt and water retention
4-Increase Vasopressin > V.C
5-increase proapoptotic protein which is lead to Increase apoptosis , so inhibtaion of this enzyme lead to decrease apoptosis and thats useful in IHD
2— AT2 : V.D
—Pharmacological effect :
-CVS :
1-hypotension without reflex tachycardia : duo to resting of baroreceptor
2-direct V.D action in artery and veins which lead to decrease pre/after load
3-increase Cop ( in patient with CHF)
4-decrease cardiac remodeling: duo to decrease apoptosis, and decrease hypertrophy
-side effect :
1-Cough : duo to accumulation of bradykinin
2-Angioedema :
3-protenuria
4-test changes
5-postural hypotension
6-pregnancy tetrognsis
7-skin rush: duo to sh group
8-hyperkalemia
—uses :
1-hypertension duo to RAAS
2-systemic hypertension
3-CHF : bcs its decrease pre/after load , and increase Cop and decrease Cardiac remodelling
4-late stage of MI
—Contraindications:
1-hypotension
2-Severe RF or renal artery stanosis
3-pregnancy : duo to fetal tetroginisis
4-hyperkemia
5-neutrophilina , thrombocytopenia: duo to bonemarrow depression
6-immunological problems
–ARA , Drugs ——-
—Drugs :
1-Losartan
2-Valsartan
-mechanism: they are selectively antagonist of Ang2 receptor AT1 which lead to :
1-decrease vascular tone
2-decrease aldesteron release = salt and water retention
3-increase renin > angiotensin 2 > AT2 lead to VD
4-have no effect of metabolism of Bradykinin
-Side effect :
1-hypotension
2-hyperkalima
3-hypatotoxcity
-uses :
1-hypertension in patient who used ACEI and casue cough or Angioedema
-Contraindications:
1-renal artery stenosis
2-pregnancy

Question 9

34. Classification of antihypertensive agents for localization of action. Central sympatholytics: mechanisms of action, indications, side effects. Example of drug prescription.

Answer 9

-First line drugs :
1-B.B
2-CCB
3-ACEI
4-ARA
5-diuretics
-2nd line :
1-Alpha 1 blocker
2-a+B blockers
3-Adrenergic neruon blocker > methyldopa
4- Vasodilators
——————————–
-Drug: Sodium nitroprusside Amp
-mechanism: it consist of nitric oxide which increases cGMP which result of dilation of both veins and arteries and decrease pre/after load
-side effect :
1- it consist of cyanid so it can convert to toxic form and accumulation could casue toxicity more often happens with RF,LF and its antidot its Sodium thiosulfate
-uses :
-hypertension crisis
—————————————
-Drug : methyldopa Tab
-mechanism: alpha methyldopa convert to methyl norepinephrine centrally to decrease the adrenergic out flow of alpha 2 agonist action from CNS leading to decrease total peripheral resistance and systemic Bp
-uses : hypertension in pregnancy
——————————————-
-drug : Clonidine Amp ( central acting )
-mechanism: its stimulating the presynaptic a2 adrenoreceptor which lead to decrease noradrenaline reales from both central and peripheral sympathetic nerve terminal
-side effect
1-sedation
2-postural hypotension
3-Constipation
-uses : hypertension crisis

Question 10

35. Cardiac glycosides: mechanisms of action, pharmacological effects, comparative
    characteristics of drugs, indications. Symptoms of cardiac glycoside intoxication and
    treatment principals. Example of drug prescription.

Answer 10

—Df: its progressive clinical syndrome in which either structural or functional abnormalities impair the ability of the heart to meet the metabolic demands of the body
—Classification: they are 2
1-Anatomical:
1.1 Anatomical left-sided : usually duo to systemic hypertension
1.2 Anatomical right-sided : caused by to many things such as pre load , left-sided HF cause Pulmonary Conjation which lead to fail of the right side
1.3 in both sided
2-Pathophysiological :
2.1 systolic : ventricle cant pump the blood through systolic phase which is bcs the muscle are week Ex> ischemic heart disease
2.2 diastolic : duo to hypertrophy the heart cant pump the required amount if the blood in the filing phase
—Clinical manifestation:
decrease Cop leads to following mechanism:
1-sympathetic over activity duo to decreased oxygen to brain leading tachycardia
2-renal ischemia : increase of RAAS ( renin angiotensin aldosterone system) lead to V.C and aldosterone lead to salt and water retention which lead to increase after load and preload and more heart failure
–Groups :
1-Positive Iontropic
- Cardiac glycosides > digoxin
- Debutamine ( for short term only )
- phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors
3-V.D
4-B.Blockers
——-
—– glycosides
—Drugs :
1-Digoxin Tab 0.003
2-Strophanthin K Amp
-Chemical structure: it consists of :
1-Steroid nucleus : lipophilic and essential for activity
2-Lacton ring : hydrophilic and essential for activity
3-Series of sugar : linked to C 3 of steroid and isn’t essential for activity , changing in the glucose would lead to changes in the pharmacokinetics
—molecular mechanism:
its inhibit Na+K+ atapse enzyme , Entering of the sodium to the cell is Passive action so we dont need The
Na+/K+atapes pump so accumulation of the Sodium inside the cell and K+ extracellular, Accumulation of intercellular Sodium leads to :
1-increase the Calcium release from the Sarcoplasmic reticulum
2-Displacement of intercellular Calcium from binding site
3-increases intercellular Sodium prevent Calcium explosions from the cell by inhibition of Na+/Ca+ exchanger
—Autonomic effect :
1-increase Vegal activity > bradycardia
2-decrease sympathetic activity duo to better Oxygenation
—Pharmacological effect :
1-increase Contractility duo to accumulation of Calcium
2-decrease RAAS secretion
3-relief of lung conjation
4-decrease HR duo to vegal increase of vegal tone
5-Normalization of of the Bp
—Uses :
1- chronic HF> digoxin
2- Acute HF > Strophanthin K
3-Arterial fibrillation
– sympotoms of glycosides intoxication:
1-CVs ; sevser bradycardia , AV block
2-CNS : fatugi
3-GIT : anuroxia , vomating , nausea
4-Kindeny : decrease durisis
5-hypokalemia and hypercalcima
–Treamtnet of toxicity :
1-Stop digitalis
2-curratrion of hyopkalimia by giving K+
3-Atropine high dose if there is bradycardia or AV block
4-antiarrhythmic drug

Question 11

36. Non-glycoside inotropic agents: mechanisms of action, indications for use, side effects. Example of drug prescription.

Answer 11

1-Positive Iontropic
- Cardiac glycosides > digoxin
- non glycosides - Debutamine ( for short term only )
- non glycosides - phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors
3-V.D
4-B.Blockers
———————
1–Phosphodieastrase inhibitor drugs in HF ( Bipyradins )
-Drug : Milrinone Amp
-mechanism: they inhibit PDE enzyme type 3 which lead to increase cAMP and cAMp leads to Increase Calcium influx in myocardial cells which results of increase the strength of Contraction
—Adverse effect :
1-Thrombocytopenia
2-increase liver toxicity
-uses :
1-they are used IV only for short term treatment of CHF for patient who digoxin doesn’t affect on them
2-For acute AHF ( Acute Atrium Failure)
—————
2–Calcium Sensitizer
-Drug : Levosimendan Falcon 0,25%-5ml
-mechanism:
1-increase the sensitivity of Cardiomyocytes to Calcium by increasing myofilment Calcium by binding to Cardiac troponin in the calcium dependent manner
2- also its selective of Phosphodiestrase enzyme type 3 inhibitor which lead to Accumulation of cAMP which lead to
1-improve contractility
2-and vascular smooth muscle relaxation
—pharmacological effect :
1-V.D
2- decrease pre load and after load
3-Arrhythmoginc effect
-uses :
1-Acute HF
2-Acute decomposition CHF
——————-
3— Dobutamine and Dopamine Amp 0.1 5ml
-mechansim : the CAMP actevates protein kinase which turn on the phosphoralation of Ca2+ channels leades to increase calcium influx and result of increase the cardiac work
-side effect :
1-tachycardia , hypertantion , cardiac arrethmia
-uses acute HF short term only

Question 12

37. Principles of drug therapy for chronic heart failure. The main groups and drugs, mechanisms of action, side effects.

Answer 12

—Df: its progressive clinical syndrome in which either structural or functional abnormalities impair the ability of the heart to meet the metabolic demands of the body
—Classification: they are 2
1-Anatomical:
1.1 Anatomical left-sided : usually duo to systemic hypertension
1.2 Anatomical right-sided : caused by to many things such as pre load , left-sided HF cause Pulmonary Conjation which lead to fail of the right side
1.3 in both sided
2-Pathophysiological :
2.1 systolic : ventricle cant pump the blood through systolic phase which is bcs the muscle are week Ex> ischemic heart disease
2.2 diastolic : duo to hypertrophy the heart cant pump the required amount if the blood in the filing phase
—Clinical manifestation:
decrease Cop leads to following mechanism:
1-sympathetic over activity duo to decreased oxygen to brain leading tachycardia
2-renal ischemia : increase of RAAS ( renin angiotensin aldosterone system) lead to V.C and aldosterone lead to salt and water retention which lead to increase after load and preload and more heart failure
———————–
-Classification of drugs :
1-Positive Iontropic
- Cardiac glycosides > digoxin
- non glycosides - Debutamine ( for short term only )
- non glycosides - phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors : Captopril
3-V.D : Verapamil
4-B.Blockers : propranolol , metoprolol
- the mechansims already known and all of them lead to :
1- Decrease BP
2- decreas aldesteron which is lead to decrease salt and water retntation and lead to decrease PRe/AFter load and Bp
3-perevent mycordial wall thinkness
4-Decrease cardiac remodling by inhbation of RAAS
-Side effect :
1-Hypotnation
2-Bradycardia
3-renal inufficncy
4-hyperkalemia
5-Dry cough and angioedema with ACEI

Question 13

38. Anticoagulants: classification, mechanisms of action, a comparative characteristic of
    anticoagulants of direct and indirect action, indications for use, side effects. Example of
    drug prescription.

Answer 13

—Df: Anticoagulant medication thats help to prevent blood clots formation
—Classification:
1-Directly acting
1.1 Heparin
1.2 low molecular heparin ( dalteparin,Enoxaparin)
1.3 syntactic pentasaccraid : Fondaparinux
2-directly acting factor inhibitor:
2.1 Rivaroxaban ( inhibit factor 10)
2.2 Dabigatran ( inhibit factor 2 )
3-Indirectly acting :
3.1 Warfarin tab
————————-
—-Direct acting :
—Drug:Heparin S.c / IV
-Pharmacokinetics:
1.1 Absorption: no because breakdown by HCL
1.2 distributable: dosnt pass BBB/Placenta
—mechanism: its action depends on the presence of Natural cloting inhibitor called ( heparin cofactor : Antithrombine 3) in the plasma small amount of heparin cofactor can activate Antithrombine 3 which lead to inhibition of several clothing factor especially factor 10 and 2
-pharmacological effect :
1- Anticougulant in vivo and vitro
2- Stimulate lipoproteins which decrease TGs in serum
—Adverse effect :
1-bleeding the most common side effect : Anti dot its Protamine sulfate
2-hematoma
3-osteoprosis : prolonged use of heparin inhibit proteins that stimulate osteoblast
—uses :
1-treatment of established thrombosis : to decrease its expand
2-prevention of thrombosis
—Contraindication:
1-MI
—-
-Low mulecular wight heparin
—Drugs :
1-Enoxaparin Amp s.c
2-Dalteparin Amp s.c
—mechanism: same mechanism of heparin but more specific on Anti factor 10
—–
-low molecular wight heparin Direct Acting on factors
1-Factor 10 inhibitor
1.1 Drug : Fondaparinux amp
- synthetic polysaccharides that has the same mechanism of lwmh selective inhibitor of Factor 10 and long acting
1.2 Drug : Rivaroxaban Tab
-Selective factor 10 inhibitor has. the same mechanism of LwMH
2- Direct Inhibitor of Factor 2 ( thrombin)
-drug: Dabigatran Tab
-synthetic compound thats acts as thrombin inhibitor, its can be used as alternative to heparin to treat patient with heparin-indenednt thrombocytopenia
————————
–indirct acting :
—Drug : Warfarin tab
-pharmacokinetics:
1-Absorption: good bioavailability
2-distribution : Can cross BBB
—mechanism: Warfarin inhibit Vit K epoxied reeducates enzyme in the liver leading to inhibition of formation of the active form of Vit K which is lead to decrease synthesis of Vit k-dependent cloting factor ( 2,7,9,10) which is lead to inhibation of carboxlase resulting in decrease modification of factors
—pharmacological effect :
1-Anticougulant in vivo
2- long acting 3-7 days
—Adverse effect :
1-bleeding of major organs : can be antagonis by Vit K
—uses :
1- treatment and prevention of : DVT,post operative thrombosis , Cerebral veouns thrombosis
-Warfarin Polymorphism : Variation in dose requirements is different for everyone, and genetic factors have an effect on dose variation. Polymorphism of vitamin K epoxide reductase complex 1 (VKORC1) gene is identified as the main genetic factor involved in warfarin dosage requirement variations.
–CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation.

Question 14

39. Antiaggregants (antiplatelet drugs): classification, indications for use, side effects. Example of drug prescription.

Answer 14

—Classification:
1-NSAIDS
2-grel
3-phosphodiestreas inhibitor
4-Monoclonal Antibody
——
1-NSAIDs
—Drug : Acetylsalisalic Acid Tab 0.1
-mechanism: its inhibt Cox irrivarsbaly witch lead to decrease THA2 which is responsible for platelet agg
-Pharmacological effect :
1-in low dose : anti agg
2-in high dose : analgasic and antypyratic , anti inflammatory
—side effect :
1-Git ulceration
2-risk of bleeding
3-bronchospasm
—uses :
1-prophylaxis of thrombosis’s
2-to reduce MI recurrent
—————————-
2-Grel
-Drugs :
1-Clopidogrel Tab
2-Prasugrel
3-Ticagrelor
—mechanism: they bind to receptor in the platelets called P2Y12 in site of the chemical mediator ADP should bind to start the aggression , so they bind to this receptor and inhibit ADP from binding and activate of GP2b/3a which is required for platelets to bind to fibrinogen and each other
—Pharmacokinetics:
1-Ticagerlor : 1-3 h and bind irreversibly
2-prasugrel : 2-4 h bind reversible
3-Clopidogrel : 3-5 days bind reversible
—metabolism: they metabolic by CYP450
-Clopidogrel : this drug is pro drug witch mean is that need to metablose to be active , So clopidogrel is metabolize By CYP2C19 , People with polymorphism of this gene lead to reduce clinical responseof Clopidogrel ,
-Drug such as Omeprazole is inhibit the CYP2C19 which is lead to drug drug interaction
—Side effect : bleeding
-uses : prophylaxis of thrombosis
—————————————————
3-Phophodiestrase
-drug : Dipyridamole tab
-mechanism: they are phosphodiesterase inhibitor which is responsible for converting the cAMP to AMP which is important for increasing Ca2 and increase platelets agg
-Pharmacokinetics:
1-good bioavailability
2-high protein bounded
3-VD
-Side effect :
1-headech
2-hypotension especially in IV
-uses :
1-Protection of stroke with. companion of Aspirin
—Contraindications:
1-Unstabil angania duo to VD effect which can increase the ischemia
—————————
4/Monoclonal Antibody
-Drug : Abciximab Amp ivi
-mechanism: they are monoclonal antibody , binde to Gp3/2a and blocks the binding site which is responsible for fibronogen linking and agg will not occur
-pharmacokinetics:
inhibiton of platelets in 30min
-uses :
in combination with heparin and aspirin for percoutnes Cornary intervantion , and cardiac ischemic complications

Question 15

40. Drugs affecting fibrinolysis: classification, mechanisms of action, indications for use, side effects. Example of drug prescription.

Answer 15

—Drugs :
1-Urokinase iV , : its products from kidney
2-Streptokinase IV : its from streptococcal
3-Alteplase IV : tissue plasminogen activator or TPA made by genatic engeneering
—– all pwoder
—explainion of the mechanism: normally when fiber clot is formed plasminogen get in contact with the clot and becomes activated into plasmin By the help do naturally occurring tissue called
( tissue Plasminogen activator T-PAs)
and plasmin causes fibrolysis
—mechanism:these drugs cause Rapid activation of T-PAs to form plasmin , and cause fibrolysis
-side effect :
1-systemic bleeding
2-allergic reaction , fever , hypotension ( streptokinase)
—uses : Acute MI

Question 16

54. Glucocorticoids. Mechanisms of anti-inflammatory, immunosuppressive and anti-allergic action. Indications and contraindications to the prescription of drugs. Example of natural glucocorticoid prescription.

Answer 16

—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0
5-Drug: Betamethasone oint,Amp
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
———–
-michaism of antiinflammatory action , -michism of antiallrrgic , immunusuprrasive mechansim
-Anti inflammtory , anti immunological
-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction ( immeune supprqasive )
-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines (antiinflammatory )
-3 inhibit macrophages activity and stabilize lysosomes membrane ( immune supprasive )
-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability ( antiallargic )
-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs ( anti inflammatory )
—
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate

Question 17

55. Glucocorticoids: effects, side effects of prolonged glucocorticoid therapy. Example of
    synthetic glucocorticoid prescription.

Answer 17

—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0 ( synthatic )
5-Drug: Betamethasone oint,Amp ( synthatic )
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli ( synthatic )
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
–
-Pharmacological effect :
1-metabolic effect :
1-1 Carbohydrates metabolism: decrease the peripheral glucose utilization which lead to hyperglycemia
1-2 Protein metabolism: increase the proteolysis which lead to decrease muscle mass and then limbs
1-3 Fat metabolism: Increase lipolysis with redistribution of fat which lead to moon face with buffalo hump ( cushing syndrome )
1-4 salt and water retention: which lead to hypoklamia
2- immunological effect :
-Anti inflammtory , anti immunological
2-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction
2-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines
2-3 inhibit macrophages activity and stabilize lysosomes membrane
2-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability
2-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs
3-CVS :
3-1 hypertension: duo to
salt and water retention and increase sensitivity pf BV and heart to circulating catecholamines
3-2 Antishock : duo to hypertensive and CVS effect , and anti inflammatory action
4- haematological effect :
4-1 increase RBCs and neutrophils and decrease lymphocytes and eosinophils
4-2 increase coagulation factors and plasma lipids
5- CNS effect : initial euphoria followed by depression
6- Eye effect : increase IOP
7- effect on bone : decrease bone matrix bcs the bone has proteins and the glucocorticoids are catabolic of protein
8- effect of growth : growth retardation bcs bones and , decreasing the growth hormone
—Adverse effect :
1-immune suppurations; leading to flaring of infection
2-hypertension: duo to SW retention
3-hyperglycaemia
4-peptic ulcer: duo to decrease synthesis of PGs
5-increase IOP which have high risk of glaucoma
6-osteoporosis
7-thrombosis: bcs PLs decrease
8-withdrawal symptoms
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
———————-
example of prolongod therapy in organ transplant to suppraise the immune system

Question 18

56. Non-steroidal anti-inflammatory drugs: classification, mechanisms of action,
    pharmacological effects, indications for prescribing medications, side effects and
    contraindications. Example of drug prescription.

Answer 18

-inflammation : its protective response to cell injury to eliminate the harmful agents by remove the damaged tissue and generate new one
-Dynamics of inflammation :
1- tissue injury
2-hormonal response : by V.d and increase the preamblity , Exudation
3-Cellular Response ( proliferation) : migration to inflammatory site , phagocytosis, tissue reparation
— synthisis of ecosanides :
-Starting from phospholipids (PL) transformed Archadonic Acids (AA) by Phospholipase (PL2) give Us steroid anti inflammatory drugs , then The Archdonic Acid ( AA ) transformed to Protsglandins (PGs) by Cox enzyme so Cox enzyme give us NSAID drugs , in the same time AA transformed by another substance which is Lipooxgnase (Lox ) and give us Leukotins drugs
—Eicosanoids: they are fatty acids derivatives
—Synthesis of Eicosanoids:
its start from phospholipids (PL) transformed to Arachonic Acid (AA) by Phospholapes A2 (PL2) then it have 2 pathway
1-with help of cyclooxgynes (cox) generate :
1-1 Prostaglandins (PGs)
1-2 Thromboxan A2 (TXA2)
2-with help of Lipooxgnase (Lox) generate:
2-1 Liukutmins (LTs)
—types : we have 3 types according to the synthesis :
1-PGs 2-TXA2 3-LTs
— receptor of Cyclooxgnease : first we should know that the Cox only effect the PGs and TXA2 and by that we have 2 types of Cox
—types and features of cyclooxegnes
— types of Cox and its effect :
1- Cox1 :
1-1: expressed in most normal tissue
1-2 physiological function :
gastric protection (pge2) , renal blood flow ( pge2) , platelets agg (TXA2)
1-3 pathological function: non
2– Cox2 :
2-1 expressed in the pathological condition: such as inflammation, carcinogenic
2-2 physiological function:
V.d , Anti agg
2-3 pathological function:
inflammation, fever , pain
———–
-Classification :
—non selective
- prototype Acetylsalicylic Acid
1- drug : Diclofenac Tab and Amp
> its less gastric irritation but more nephrotoxic / wildly used for rheumatoid pain
2- drug : Ibuprofen tab or oint 5%-30.0
> its more safe on children but study showed that women under 30 who used it have relatively hypertension from this drug
3- Drug : Indomethacin tab , Oint , Supp , eyedrops
> its the most potent Cox inhibitor but relatively more nephrotoxic
> the most useful for indomethacin is for ductus arterioles
—— Cox2 inhibitors
- they are 2 drugs
-1- Celecoxib Caps
-2- Meloxicam tab or amp
- mechanism: they inhibit Cox 2 enzyme reversibly
- pharmacological effect : Antipyretic, analgesic, Anti inflammatory
- side effect :
1- gastric irritation less frequent
2- renal side effect : more frequent
3- thrombotic complications : increase duo to increasing the platelets agg
— non NSAID : Paracetamol tab

— the prototype —-
—Drug : Acetylsalicylic Acid Tab 0,05
— Pharmacokinetics:
1- Absorption: is good bcs the drug is Acidic and the stomch HCL is acidic also
2-elimination : its dual root of elimination according to the dose
—mechanism of Action :
Aspirin is non-selective and irreversible Cox enzyme inhibitor leading to inhibit both of PGs and TXA2
NB! the only different between the aspirin and its derivatives its they are reversible and Aspirin is not
—Pharmacological effect and mechanism of each:
1-Analgesic Action : mechanism
1-1 prephrally effect : decrease the synthesis of PGs in prephral tissue
1-2 centrally : decrease the synthesis of PGs in subcortical sites ( hypothalmus and thalamus )
2-Antipyretic: : its not hypothermic but it decreases the elevated temperature Ex:39 to 37
-mechanism:
2-1 decrease the synthesis of PGE2 in hypothalamus
2-2 decrease the hypothalamic response to interleukin
2-3 Coutenous V.D which increase the sweating
3- Anti inflammatory effect :mechanism > by inhibition of Cox enzyme 1 and 2 its decrease the synthesis of PGs and TXa and possible other inflammatory substances
3-1 decrease the inflammatory cell division
3-2 decrease the capillary preamability
3-3 decrease the Hyaluronuides enzyme
3-4 stabilise lysosomes membrane of inflammatory cells
— Side effects :
1- respiratory system:
1-1low toxic dose : produce metabolic acidosis
1-2high toxic dose : produce acidly together with inhibition of R.c leads to death from sever acidosis
1-3increase risk of asthma
2- GIT effect : produce 2 types of gastric ulcer
2-1 acute gastric ulcer : ion trap of aspirin in case of empty stomach
2-2 chronic gastric ulcer : when ingestion of small doses for several years
3- hepatic effect : produce 2 types of hepatic injury
3-1 mild haptic injury : ita dose dependent and asympathomitc there may be increase of serum which is (SGOT and SGPT )
3-2 sever hepatic injury: children under 16 shouldn’t use aspirin bcs its related to Ray syndrome which is liver failure and Encephalopathy
4- hematological effect : by inhibition of Cox its inhibit the platelets agg irreversibly which lead to risk of bleeding
5- kidney: NSAIDs prevent synthesis of PGE2 which responsible for sodium which lead to salt and water retention and Edema

—- Therapeutic Use :
1- As analgesic: for mild or moderate pain
2- As Anti inflammatory
3- Antipyretic

— Contra indication :
1- GIT disorders : such as Peptic ulcer or gastritis
2-hematological disorders: hemophilia
3- Chronic renal disorders: may aggregate the renal failure
4- Gout : small dose may inhibit the uric acid Execration
5-before surgery: risk of uncontrollable bleeding
6-children under 16 : ray syndrome
–Drug drug intraction :
1- Aspirin Antagonist the Urine execration so i. patient with Gout disease which need to execrate the urine and use drug Probenecid they anatagoinse each other
2-Aspirin can replace the Anticoagulant drugs such as Heparin
3-Aspirin Antagonize Anti-acids and decrease the Aspirin Absorption in stomch
———————-
–Paracetamoli tab
—Drug : Paracetamol tab 0.5
—Pharmacokinetics:
1- Absorption: Complete
2-Distribution : goes to all body tissue
3-Metabolism: in liver by
3-1 glucuronic acid 60%
3-2 Sulfate 35%
3-3 hydroxolation by CYP450 , and form toxic form NABQ N-Acetyl-P-Bezoqinon ( can cause liver damage )
— mechanism: has less effect on Cox in peripheral tissue duo peripheral inactivation , Study showed its work centrally on Cox3
—Pharmacological effect :
1- Analgesic
2-Antipyretic
—Side effect :
- Forming Toxic form NABQ
N-Acetyl-P-Benzoqenon which bind to cellular proteins Around the central vein in the hepatocytes and cause > hepatocellular necrosis
—Therapeutic use :
1-Analagisc
2-Antipyretic
- first of all the paracetamol is is very safe and its the first line for children and women who’s in pregnancy
—Antidote: Sulfhydryl > N-AcetylCysteine which contains sulfhdryl form glotatheion to wash the toxic form which is N-Acetyl-P-Benzoqinon

Question 19

57 Immunosuppressive drugs: classification, mechanisms of action, pharmacological effects,
indications, side effects.

Answer 19

Nb! we can use glycocoticoids or we can use anticancer agents which has immunosepprasive effect such as cyclophosphamide

—————-anticancer agents ————————————

— —Drug groups :
1-Nitrogen mustard : Cyclophosphamide tab/Amp
2-Nitrosoureas : Carmustine Amp
—Mechanism: produce highly reactive intermediates which transfer Alkyl group to cellular micro molecules , At the Position 7th of guinin forming covalent bond which lead to DNA cross linking > resulting of inhibition of mitosis or even apoptosis
—Pharmacokinetics: Cyclophosphamide most alkylting agent used and its pro-drug which it’s required biotransformation in the liver by CYP450 to become active form
-Specific side effect :
1-Hemorrghic cystitis : caused by the metabolite called acrolein and can be prevented by increasing fluid intake or sulfhydrl donor such as
N-Acetlycysteine which is washing the bladder from this toxic form
—uses :
1-AntiCancer drug in most types of cancer
2-As immunosuppressants: such as RA,SLE duo to cross linking in T-cells which is in most cases its the reason of Autoimmune disease

———glycocotricoids ———————
—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0 ( synthatic )
5-Drug: Betamethasone oint,Amp ( synthatic )
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli ( synthatic )
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
–
-Pharmacological effect :
1-metabolic effect :
1-1 Carbohydrates metabolism: decrease the peripheral glucose utilization which lead to hyperglycemia
1-2 Protein metabolism: increase the proteolysis which lead to decrease muscle mass and then limbs
1-3 Fat metabolism: Increase lipolysis with redistribution of fat which lead to moon face with buffalo hump ( cushing syndrome )
1-4 salt and water retention: which lead to hypoklamia
2- immunological effect :
-Anti inflammtory , anti immunological
2-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction
2-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines
2-3 inhibit macrophages activity and stabilize lysosomes membrane
2-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability
2-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs
3-CVS :
3-1 hypertension: duo to
salt and water retention and increase sensitivity pf BV and heart to circulating catecholamines
3-2 Antishock : duo to hypertensive and CVS effect , and anti inflammatory action
4- haematological effect :
4-1 increase RBCs and neutrophils and decrease lymphocytes and eosinophils
4-2 increase coagulation factors and plasma lipids
5- CNS effect : initial euphoria followed by depression
6- Eye effect : increase IOP
7- effect on bone : decrease bone matrix bcs the bone has proteins and the glucocorticoids are catabolic of protein
8- effect of growth : growth retardation bcs bones and , decreasing the growth hormone
—Adverse effect :
1-immune suppurations; leading to flaring of infection
2-hypertension: duo to SW retention
3-hyperglycaemia
4-peptic ulcer: duo to decrease synthesis of PGs
5-increase IOP which have high risk of glaucoma
6-osteoporosis
7-thrombosis: bcs PLs decrease
8-withdrawal symptoms
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
———————-
example of prolongod therapy in organ transplant to suppraise the immune system

Question 20

58 Antiallergic agents: classification, mechanisms, pharmacological effects, indications, side effects. Example of antihistaminic drug prescription.

Answer 20

-Histamine formed from amino acid histidine by action of histadine decarboxylase enzyme and stored in the mast cell
-Receptors : there are 4 receptors:
-H1,H2,H3,H4
-Physiological Antagonist of Histamine is : Adrenaline its revert all the actions of Histamine
-Drugs :
1-H1 : Diphenhydramine tab 1gen,Loratadine 2gen
2-H2:Cimetidine , Ranitidine
-H3 and H4 : no clinical use
-Anti-Allirgic drugs are drugs that selctevly inhibit the H1 receptor leading to decreased the action of allergy and its symptoms and they are classified as 2 generation :
-The 2nd generation is more :
1-Selectivky H1 blockers
2-More potent
-Pharmalogical effect :
1-Relive of itching
2-Decrease capillary permeability
3-Decrease bronchial construction
4-Antiemetic only in 1Gen for motion sickness
5-Blocks a receptor only in 1gen
-Side effect :
1-first Gen :
-Sadetion , atropine like action , orthostatic hypotantion
2-2nd gen : they are metabolised by the CYP450 so there is a chance of drug drug intraction and Prolonged QT interval

Question 21

59. Thyroid and antithyroid drugs: classification, mechanisms, pharmacological effects, indications, side effects. Prescribe tiamazole

Answer 21

—synthesis of thyroid glands :
start with activating Uptake of iodide, then oxidation with peroxides enzyme and indentation of tyrosine of theyroglobin to form MIT and DIT
then condensation of MIT and DIT Nd formation of T3 and T4 , then proteolysis of thyroglobulin, then secretion of T3 and T4 into blood stream
—NB! the secretion of T4 and T3 stimulate by TSH , most of T3 is drived from peripheral dioidenation of T4 in the peripheral tissue
-B blockers and corticoids inhibit the peripheral conversation of T4 to T3
—they are used to treat hypothyroidism
—Drugs group :
1-Levothyroxine (T4 )
2-Liothyronine (T3)
all tabs
—hypothyroidism: its clinical syndrome results from high levels of thyroid hormones
-clinical types :
1-Graves disease: its an autoimmune disease in which there abnormal Antibodies > activating TSH receptor in the thyroid gland which lead to enlargement or the gland and softness
2-toxic multinudular goiter : the treatment is usually surgical
—management:
1-graves disease: usually medication
2-multiple nodular goiter : surgical
—Drug : Thiamazole tab 0,005
-mechanism of action: they inhibit the oxidation of Iodides by inhibition of peroxides enzyme
-side effect :
1-agranulocytosis, bone marrow depression duo to formation of antibody that against WBCs
2-hypothyroidism with increased the size of vesicularty of the gland
3-hepatotoxic
4-hypersensitive reaction
–uses : thyrotoxic

Question 22

60. Insulins, insulin analog and oral hypoglycemic drugs: mechanisms, pharmacological effects,
    indications, side effects. Prescribe regular insulin or insulin analog.

Answer 22

—types of insulin:
1- traditional ( animal ) : prepared from animal such as pork and beef , animal insulin may contain animal proteins that could cause allergy and its more antigenic
2-human insulin : its identical to human insulin and its prepared by recombinant DNA technology , its less antigenic and rare development of insulin resistance

—insulin secretion: glucose enters B cells which lead to increase the ATP closure of ATP-dependent k channel which lead to opening of voltage gated C+2 channel which increase the calcium influx and insulin release

—insulin receptor : A tyrosine kinase receptor consist of 2 extracellular (a) and 2 subunits of Beta

—mechanism : binding of insulin to the alpha subunit cause activation of tyrosine kinase enzyme which triggers a series of intercellular effects lead to increase the number of glucose transporters ( GLUT4 ) in the cell membrane and increase the transporter of glucose to cell which lead to&raquo_space;>
1-increase glucose transporter in insulin-dependent tissue in Sk muscles and fat tissue
2-stimulation of glycolysis : break down the glucose
3-stimulation of glycogen synthesis: glycogen is the stored form of glucose
4-inhibition of glaconeogensis in the liver : gluconeoginsis is process in the liver which is making glucose from breaking down of lipids or proteins
5-stimulate pintos phosphate pathway ( PPP ) : its pathway generally regulate the body cell tissue , in glucose its metabolize 30% of glucose by this pathway
6- increase the protein synthesis: by activating of mechneray increase EIFs
7-stimulation of Fat synthesis : which is gone decrease the glucose
8-inhibition of lipolysis

–insulin analogs :
regular insulin
-group : short acting
-onset : 0-30 min
-duration : 5-6 h
its the safest insulin in emergency for example used in hyperglycemic coma I.V
2- insulin Aspart
-group : short acting
-onset : 5-10 min
-duration : 3 h
its insulin analog , created by replacement of proline to aspart and the result its fast acting and short duration insulin’s bcs its monomer
3- insulin isophane
-group : intermediate acting
-onset : 1-3 hour
-duration : 12-24 h
its created by replacement of the zinc with protein for the fishes called protamine and its positive charge and bind with insulin molecules ionic bond which lead to take the body long time time to break this bond , and its hexomor
4-insulin glargine
-group : long acting
-onset : 1-3 h
-duration : 12-24 h
its created by adding 2 more molecules of argin to the insulin which made the insulin 53 amino acid instead of 51 which lead to longer duration
—therapeutic uses :
1-T1DM
2-T2DM : in some cases
2.1 after fail of oral drugs
2.2 if the patient got stress conditions such as surgery, infection, pregnancy
3-hyperglycemia coma
4-hyperkalemia : bca insulin and glucose can shift the potassium from blood to tissue
—adverse effect :
systemic >
1-hypoglycemia: its most common
2-hypoklamia
3-hypersensitive reaction
4-insulin resistance : duo to accumulation of carbohydrates, formation of antibody against insulin , decrease sensitivity
locally >
1-local allergy : maybe bcs the animal insulin
2-lipids dystrophy
3-local infection
———-
-oral insulin :
—-oral drugs :
1-family of Sulfonyurea
-drug: Glibenclamide tab 0,007 ( stimulate insulin secretion)
-mechanism of action : it has 2 type of mechanism>
1.1 pancreatic: binding to the SUR1 receptor on B cells and blocked of ATP-dependent K+ channel which lead to depolarization bcs Ca2+ and increase the insulin secretion
1.2 Extrapancreatic : they increase the insulin receptor sensitivity
-side effect :
1-hypoglycemia
2-increase apitite and weight gain
3-allergic recation
4- renal failure > contraindications
-uses : T2DM
-———————————
2- family of megletunds
-drug: Repaglinide Tab 0,0005 ( stimulate insulin section)
-mechanism of action :the has the same mechanism of sulfynurea
-uses : T2DM used for patient with allergies from sulf or has renal failure
-———————————
3- family of Bigunaides
-drug: metformin tab 0,5
-mechanism of action : Stimulate of AMP-dependent protein kinase of hepatocytes which lead to inhibition of gluconeognesis in the liver , and increase the insulin receptor sensitivity
-pharmacological effect :
no risk of hypoglycemia
-side effect :
1-nausea
2-dihrria
3-lactic acidosis: duo to increase of Anarobic glycolysis
-uses : T2DM , wight loss
-———————————
4- family of Thiazolidinis
-drug: Rosiglitazone tab 0,5(insulin sensteiser)
-mechanism of action : its act on nuclear gene called Perixisom-prolifratir-activated-receptor-gamma ( PPAR-y) bind to this gene in liver and adipose tissue , and increase insulin resistance
-pharmacological effect :
they have slow onset because the mechanism involves gene regulation
-side effect :
1-heptoroxic
2-wight gain
-uses : to improve insulin resistance in T2DM
———————————-
5- family of incretin ( glucagon like peptide 1 )
GLP-1
-drug: Exenatide Amp
-mechanism of action : they increase the insulin secretion by binding to B cells and forcing it to secrete it , and decrease the glucagon , and slow the gastric emptying and decrease apitite
-side effect :
1- nausea 2-vomiting 3-pencreatits
-uses : in T2DM and should be giving before eating by 60 min
————————————
6- family of Dipeptidly peptdens 4 inhibitor ( Dpp-4)
-drug:Saxagliptin tab 0,0025
-mechanism of action : they inhibt the DPP-4 enzyme which is responsible for proteolysis of incretin so its decrease the GLP-1 may improve B-cells function and decrease the glucagon secretion
-side effect :
1- nausea 2- headache
-uses : for T2DM usually combined with metformin
———————————
7- family of sodium-glucose cotransporter 2 inhibitor ( SGLT-2 )
-drug: Dapagliflozin tab 0,005
-mechanism of action : increase the urine glucose and sodium secretion
-pharmacological effect :
1- decrease Bp
2-body wight loss
-side effect :
1-polyuria
2-hypotension
3-hyperkalimia
-uses : in T2DM in case of the patient has renal or haptic failure and cant take metformin

Question 23

62. Bronchodilators: classification, mechanisms of action, pharmacological effects, indications, side effects. Example of drug prescription

Answer 23

— Drugs : B2
1- short acting
1.1Salbutamol tab, aears
1.2 Fenoterol
2- long acting :
2.1 Formoterol Caps
2.2 Salmeterol Aers
— mechanism: by activating the B2 receptor it will increase the CAMP which lead to broncho dilation , and suppress of inflammatory mast cells , mediators secretion and reducing of Ach reales from Nerve Ending
—uses : Quick relief , long term controlling of BA in combaination with Glucocorticoids
-side effect :
1- tolerance
2-tremors
3-hypoglycemia
—
-muscarnic blocker such as :
Atropin and ipratropium bromide
————————————————–
-Drugs : Methylxanthines
1-Theophylline Tab
2-Aminophylline Amp
-mechanism:
1- Adenosine ( A1) receptor: these drugs blocks A1 receptor which lead ti broncho dilation , CNS stimulate , decrease mediator’s that secreted by Mast cells , Increase AV conductivity,
2- they inhibit Phosphodiesterase PDE3 and PDE4 which lead to accumulation of CAMP leading to :
1-B.D
2- increase cardiac conductivity, relaxation of most smooth muscle
-pharmocokintics :
1- absorption : full absorption 90-100%
2-metabolism: in the liver Cyp450 ~ CYP1A2 and metabolite to Cafien
3- cleared by smoking bcs its microsomal inducer
4- decrease cleared by microsomal inhibitor ~ Erythromycin
-side effect : nausea, vomiting , dyspepsia , durisis stimulation
-uses : Chronic BA theophylline
Acute BA aminophylline Amp
——————————————————-
- Drugs : glucocorticoids
- there is two types
1-local effect drugs :
1.1 Beclomethasone
1.2 budesonide
1.3 Fluticasone all aresol
2-systematic effect :
2.1 Prednisolone Tab , Amp
—mechanism: bind to cell surface receptors to the cytoplasm receptor carrier then transferred to nucleus where it interacts with DNA then transcription which results of RNA which lead to decreese the synthisis of Pgs and other inflammatory mediators
—systemic Pharmacological effect : mentioned in crticoids
- local pharmacological effect :
1-reducing the inflammation and hyper reactivity of bronchi
2-reducing frequency and severity of BA
—uses :
-local drugs : BA inflammatory
-systematic drugs : Sever asthma ~ asthmatic status IV
———————————————————

Question 24

63. Drugs used to control bronchial asthma: mechanisms, pharmacological effects, indications, side effects. Example of drug prescription.

Answer 24

• Drugs : glucocorticoids
• there is two types
  1-local effect drugs :
  1.1 Beclomethasone
  1.2 budesonide
  1.3 Fluticasone all aresol
  2-systematic effect :
  2.1 Prednisolone Tab , Amp
  —mechanism: bind to cell surface receptors to the cytoplasm receptor carrier then transferred to nucleus where it interacts with DNA then transcription which results of RNA which lead to decreese the synthisis of Pgs and other inflammatory mediators
  —systemic Pharmacological effect : mentioned in crticoids
• local pharmacological effect :
  1-reducing the inflammation and hyper reactivity of bronchi
  2-reducing frequency and severity of BA
  —uses :
  -local drugs : BA inflammatory
  -systematic drugs : Sever asthma ~ asthmatic status IV
  ———————————————————
• prophylactic drugs ( the main for the quasiton )
  we have 3 families of these drugs
  1-Luktraines
  2-Mast cells stabilizer
  3-MABs
  ———
  1- Leukoutraines inhibitors
  -Drugs :
  1-Zafirlukast tab
  2-Montelukast tab
  -mechanism: they inhibit LTD4 receptor which is responsible for :
  1-plasma exudation
  2-mucous secretion
  3-Esionphilis recurmnet
  4- B. C
  -uses : as adjuvant drugs For BA, and ita a replacement for Glucocorticoids in children bcs the glucocorticoids cause growth retardation
  ———-
  2-Mast cells stebiliazer
  -Drug : Cromoglicic acid ~ Caps for inhalation
  -mechanism: they block Ca2+ entry to the mast cell which lead to membrane stiblazation and inhibit the degranulation
  -Pharmacokinetics: poorly absorbed in GIT
  -uses : only for pervntation
• side effect : Res tract irritation
  ——
  3- Monoclonal antibodies MABs ( long term every 1 mothe )
  -Drugs : Omalizumab Amp S.c
  -mechanism: its antagonist of IGE which is binding to the mast cell , and degranulation , so this drug inhibit the Ige
  -Drug : benralizumab Amp S.c
  -mechanism : Via its Fab fragments, benralizumab specifically binds to IL-5Rα, thereby preventing the interaction between IL-5 and its receptor
• Uses : As adjuvant drug For BA

Question 25

64. Drugs for peptic ulcer: mechanisms, pharmacological effects, indications, side effects. Example of drug prescription.

Answer 25

DF: ulceration of the duodenum or stomach duo to imbalance between local invasive force and protective force
-invasive factors :
1-stress lead to increase HCL
2-Drugs : Such as NSAIDs , corticosteroids, morphine methylexens
3- infection of Helicobacter pylori
—pharmacological therapy of peptic ulcer :
1-drugs that decrease HCL secretion:
1.1 Selective M1 blockers > Pirenzepine
1.2 H2 blockers > Ranitidine , Famotidine
1.3 Proton pump inhibitor > Omeprazole,Pantoprazole
————
-M1 blocker
-Drug: Pirenzepine Tab
-mechanism of action : selectively block M1 receptor which lead to decrease the basal HCL secretion, indirectly inhibit H2 by inhibition Of the signalling from M1 to H2
-adverse effect : high dose lead to atropin like action , dry mouth, bullred vision , tachycardia
-uses : they are week inhibitors of HCL secretion
———————————-
-histamine Blocker
-Drug: Ranitidine , Famotidine Tab
-mechanism of action :they are competitive antagonist of histamine 2 at the parietal cells , which suppress the normal and meal-stimulted Secretion of HCL
-adverse effect :
1-reversible hepatotoxic
2-microsomal inducer
3-CNS symptoms, headache, slurred speach
-uses : duodenal and gastric ulcer
, stress ulcer
———————————–
-proton pump inhibtor
-Drug : Omeprazole caps /pwdr , Pantoprazole caps/A pwrd
-mechanism: At ph less then 5 couventally with SH groups of hydrogen potassium atpese and inactive hydrogen potassium atpese irreversibly , inhibit of HCL occurs with 1 hour maximum 2
NB! omeprazole may inhibit CYP2c19 drug interaction
-adverse effect :
1-dahrria
2-decrease B12 absorption after 12 week
3-decrease or inhibit acidity of stomach which lead to change PKA or bioavailability of other drugs
-Uses : peptic ulcer

Question 26

65 Drugs used in emergency: anaphylactic shock; hypoglycemic coma; hyperglycaemic coma; poisoning with iron.

Question 27

66. Antibiotics. Basic principles of antibiotic therapy. Mechanisms of formation of resistance to antibiotics. Side effects of antibiotics

Answer 27

-Princples of antibiotcs action
1. cell wall mechanism :
The mechanism is for all penicillins groups is the same , Penicillin bind to (PBP - Penicillin binding protein ) on the bacterial cell wall and inhibits the transpeptidse enzyme which is inhibite the transpeptades reaction , which is synthesis the walls of the cell , then it’s activates the autolytic enzyme called autolysin leading to cell rapture which is result of of cell wall inhibition and autolysis
-NB! The penicillin mechanism requires proliferation microorganisms, have no effect of bacteria that not dividing
2.protein synthasis mechasim
3.DNA and RNA mechaism
4.antifolic acid mechansim
5.PFOR mechansim
NB!all these mechasim will be explaned in the further quastions
— resistant:
1.Enzymatic hydrolysis of the beta-lactam ring results in loss
of antibacterial activity. The formation of beta-lactamases
(penicillinases) by most staphylococci and many Gram-negative
organisms is a major mechanism of bacterial resistance. Inhibitors of these bacterial enzymes (eg, clavulanic acid, sulbactam, tazobactam) are often used in combination with penicillins to prevent their inactivation. Structural change in target PBPs is another mechanism of resistance and is responsible for methicillin resistance in staphylococci and for resistance to penicillin G in pneumococci (eg, PRSP, penicillin resistant Streptococcus pneumoniae)
and enterococci. In some Gram-negative rods (eg, Pseudomonas
aeruginosa), changes in the porin structures in the outer cell wall membrane may contribute to resistance by impeding access of penicillins to PBPs
1-MRSA ( methilin resistant staphylococcus aureus )
2-Some E-Coli
3-Psudomons
4-some streptococci
2.Genatic by virtical and horizantal
3.after bactiral death some particals transmeted to another bacteria and form resistant to the drug
–Side effect : most side effect cause these side effects :
1-Allergic reaction : it occurs with all types of penicillin, and its not duo to penicillin it self but to degradation products common to all penicillin it more commonly in parental
2-Diarrhea: disruption of the balance of intestinal
microorganisms. It occurs to a greater extent with those
agents that are incompletely absorbed and have an
extended antibacterial spectrum. Pseudomembranous
colitis from Clostridium difficile may occur with penicillin use
3-Nephritis
4–Neurotoxicity: The penicillins can provoke seizures if injectedintrathecally or if very high blood levels. Epileptic patients are particularly at risk due to the ability of penicillins to cause GABAergic inhibition

Question 28

67. β-lactam antibiotics. Penicillins: biosynthetic and semi-synthetic, mechanisms of antimicrobial action, antimicrobial spectra, side effects. Example of drug prescription

Answer 28

–Classification :
-Natural :
1- Benzylpenicillin ( Penicillin G) short acting -Parenteral
2-Phenoxymethylpenicillin
(penicillin V) Orally - Short acting
3-Benzathine BenzylPencillin ( long acting per 7d - IM)
-Semi - Synthetic :
1-Anti Staphylococci Penicillin: Oxacilln
2-Extended Spectrum Penicillin:
Ampicillin - Amoxicillin
3-Antipsudomonal Pencillin :
Piperacillin , Ticarcillin
———
-Drug : Benzylpenicillin amp 1mlion ED
-Its the original Penicillin
-Spectrum : Narrow spectrum duo to targeting few Gram + bacteria only such as
1-Streptococci
2-P.Coccai
3-Some staphylococci which is not producing B-Lactamse
4-Gono coccai : Gonnoria : Gram-
5-Treponin pellidum ( Sophylis) gram-
-disadvantage:
1-Cant be orally bcs HCL
2-Half life 2-4h ( shorty acting )
3- B-lactamse enzyme sensitivity
4-Narrow spectrum
—-
-Drug : Phenoxymethylpenicillin Tab0.25 Penicillin V
-Its the same as Penicillin G , But its acid stable , Also short acting , and narrow spectrum
———————————
-Drug : Benzathine Benzylpenicillin
-Its the same as penicillin G but with modification which makes it last longer 7-14 days
- its most used in prophylaxis and treatment of syphalis during pregnancy
——————————-
-,Anti-Staphylococcal,
-Drug : Oxacillin Tab/Amp 0,25/0,5
-they are effective against B-Lacatmes producing Staphylococci , But they have no effect or low activity against
other Gram- and Gram+ bacteria: Narrow spectrum .
-They most used staph and may cause MRSA
——
-Extended spectrum penicillins
-Antibiotic drugs : , B-Lctms inhbt
1-Ampicillin + Sulbactam Amp 0,5/0,25
2-Amoxicillin + Clavulanic Acid Tab 0,25/0,6
-Spectrum : they are narrow/moderate spectrum duo to coverage of G+,G- Such as :
1-Slamonila
2-H.influenza
3-Protus
4-Shigella
-ROA : they are acid stable so they can be orally
-resistant: they are sensitive to B-Lactamse , and thats why we give them in combination with B-Lactamse inhibitors
-Mechanism of acting on Gram- :
The ampicillin/Amoxicillin have NH2 group : Amino acid,so it can pass the pores of the outer membrane as nutrients, and destroy the Cell wall and activate Autolysin
———————————
-Ampicillin:
1-oral absorption: +
2-distribution :+
3-Diarrhoea : +++ bcs its not absorbed 100% so it kills the bacteria in the GI
4-Spectrum : shigella , H.influenza
———
Amoxicillin :
1-oral absorption: ++
2-distribution :++ more in lung
3-Diarrhoea :+
4-Spectrum : Salmonila/typhoid fever ,
H,Pylori , Streptococcus pneumonia
————
-AntiPusedumonal penicillin
-Drugs :
1-piperacillin , Ticarcillin Amp
-Spectrum: they are targeting pseudomonal (Mainly) , Also G+ and G- also anaerobic bacteria, so they are broad spectrum
-resistant: they are B-Lactamase sensitive thats why we should combine it with Sulbactam ( b lactamse inhibitor )
———–
—Side effect :
1-Allergic reaction : it occurs with all types of penicillin, and its not duo to penicillin it self but to degradation products common to all penicillin it more commonly in parental
2-Diarrhea: disruption of the balance of intestinal
microorganisms. It occurs to a greater extent with those
agents that are incompletely absorbed and have an
extended antibacterial spectrum. Pseudomembranous
colitis from Clostridium difficile may occur with penicillin use
3-Nephritis
4–Neurotoxicity: The penicillins can provoke seizures if injectedintrathecally or if very high blood levels. Epileptic patients are particularly at risk due to the ability of penicillins to cause GABAergic inhibition
– Drug intractions :
1-bactriostatics : bcs the penicillin need prolofration to act
2-Anti-pesudomonal with aminoglycosides : bcs they are diffreant in charge puting them in one syrngist they will make complex and antagonise each other

Question 29

68. β-lactam antibiotics. Cephalosporins and carbapenems. Mechanisms of antimicrobial action, antimicrobial spectra, side effects. Example of drug prescription.

Answer 29

-Carpabenems :
-Drugs :
1-imipenem/Cilastatin Amp 0,5
2-Ertapenem 0,5 amp
-Structure : uniq changes in the structure, Containing B-Lcatamse ring
-Spectrum: broad spectrum duo to :
1-Gram +
2-Gram -
3-Pusdomonas
4-Anearobic
—Resistant : highly resistant
-Side effect : the imipenem alome cause nephrotoxcicty from its products by enzyme Dyhdryopeptedase , So we administered with Cilastatin inhibits the renal dyhdryopeptadese to prevent formation of toxic formation
-Etrapenem : its without this effect so administered alone

Question 30

69. Bacteriostatic antibiotics. Macrolides, lincosamides, tetracyclines and chloramphenicol. Mechanisms and spectra of antimicrobial action, side effects. Example of drug prescriptio

Answer 30

1— Tetracycline
-Drugs :
1-Tetracycline Tab
2-Doxycycline tab/pwder
-Pharmcokintics:
1-Absorpation : incomplete duo to water sulablety , food decrease teh absorption and they are make complex with the metals ( doxycycline is more absorbed)
2-Distribution:
2.1 BBB : not pass
2.2 Placenta / breast milk :pass and its teratogenic
2.3 body fluids :reach
3-metabolism: liver , and exctinssive metabolism , duo to entrohepato circulation
4-Execration : mainly kidney , but they cant Treat UTI duo to extansive metabolism in liver and the drug becomes inactive , but doxycycline’s 50% renal and 50% bilary which can use with patient with renal impairment, but in the same time they are hepatotoxic duo to entroheptaic circulation
-mechanism of action :they are binding reversiblly to 30s subunyand inhibiting the binding of Aminoacyl-tRNA to The Aminoacyl-Centre which is lead to disrupting the early stage of translocation-imitation
-spectrum: broad spectrum/ bacteriostatic
1-most G+ but not Staph
2-most G- but not pausdomonas
3-most of Anearobic bacteria ( CL difesil )
4-Atypical organisms ( Calm my leg ) + borrlia , Reckissia , Coxilla
5-Protozoa : malaria , Toxoplasma ( bind to 40s )
-Resistant: Cross resistant easily and rapid
-uses :
1-Sexual transmitted infections : in patients who has tolerance to B lactamse
2-Pneumophil ( Ligunla )
3-peptic ulcer
4-dangerous infection; Plague , cholera , Antha
4-Zoomases ( loptosorosis , bracellosis )
5-Intracellular pathogens: such as lyma disease, Ricksosis , Q fever )
6-Acne
-Advera effect :
1-GIT upset
-VIP-2-teeth and bone : ditrubunce of skeleton formation deposition in bone and teeth leading leading to ( Colouring the enamel in yellow-Brown color )
-VIP-3-Cholistatic hepatitis: liver cell injury, hepatotoxic, Hypertophy of the hepatocyte
-VIP-4-Photosensitivity
-C.I :
1-Allergies from tetracycline
2-Children under 8 years
3-Pregnancy
4-Liver impairment
———————————————–
2—- Microlides
-Drugs :
1-Erythromycin tab/pwdr 1gen
2-Clarithromycin tab/pwdr 2gen
3-Azithromycin tab 2gen

-Pharmcokintics:
1-Absorpation : poor and deceased by food
2-Distribution:
2.1 BBB : not pass
2.2 Placenta / breast milk : pass and they are not teratogenic
2.3 body fluids : they reach most body fluids with good concentration ( they have selective distribution to neutrophils and phagocytes
3-metabolism: in liver
4-Execration : they are execrated through liver billary and entrohepatic circulation, thats why they are heptao toxic,
-NB! 1gen is not stable in acid stomach so low bioavailability and short half life , 2nd generation is the opposite
-mechanism of action : they bind reversible to 50s subunits of the ribosomes and inhibit peptide transferase , and inhibit elongation of proteins, which block the translocation of ribosomes to the next Codon on the mRNA
-Spectrum: Bacteriostatic / Concentration dependent, Spectrum:
1-Mainly G +
2-Intercellular pathogens: Calm my leg
3-H.Pylori : Clarithromycin
-Resistant: in the case id macrolides the bacteria becomes resistant in approximately 10 days by changing the 50s binding site
-uses :
1- Gram +
2-Atypical organisms
3-otaits media
4-sinuses
-Advera effect :
1-GIT upset
-VIP-2-Cholistatic hepatitis: duo to accumulation in liver entrohepatic circulation, inhibitory of CYP450
-VIP-3- Ototoxcity
-VIP-4-Prolongation of QT interval : which could cause a ventricular arrhythmia
-C.I : combination of macrolides and penicillins.
———————————-
3——- Lincosamides
-Drugs :
1-Lincomycin Tab/amp ( prototype)
2-Clindamycin tab/amp (synthetic drug )
-Pharmcokintics:
1-Absorpation : complete
2-Distribution:
2.1 BBB : yes / Can treat CNSI
2.2 Placenta / breast milk :pass but mo teratogenic
2.3 body fluids :reach , and has selective distribution on bone and joints ( osteomyelitis)
3-metabolism: liver
4-Execration : through bile
-mechanism of action : its bind in the same site of microlieds in the 50s subunits and inhibits piptiedly transferase which is lead to decrease peptide elongation
-spectrum: bacteriostatic
1-gram + Aerobic bacteria : strepto , stephy , P.cocci
2-gram - Anearobic
3-Protosa : malria , Toxoplasma
-Resistant: easy and rapid and if the bacteria get resistant from macrolids it will be resistant to lincosamides also
-uses :
-VIP-1-Dental infection: because most of oral infections its Anearobic bacteria and duo to selectively bone and joints
-VIP-2-Osteomyelitis
-VIP-3-Toxic shock syndrome : such as staphylococcus produce Exotoxins, we cant use bactriocidal bcs it will spread the Exotoxins
-Advera effect :
1-Clostridium defissil
————————————-
4——————chloramphenicol
-Drugs :
1-Chloramphenicol
—Chemistry :consist of OH group which mean its very lipid suable, also its MW its less then 500 , Consist of 2 Molecules of Chloride which increase the activity against bacteria and increase toxicity
-Pharmcokintics:
1-Absorpation : Complete and the food doesn’t effect
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and teratogenic ( gray beby syndrome)
2.3 body fluids :reach with high concentrations
3-metabolism: in liver by Glucronic transferase , Cant be given to child under 2 years bcs unwill development of Glucrinc transferase enzyme
4-Execration : bilary 90%
-mechanism of action :bind to 50s subunit and inhibit peptidyl transferase enzymes and decrease peptides elongation
-Resistant: cross resistant duo to modifications or blocking proteins which synthesis by bacteria in the binding site or by synthesis of CAT ( Chloramphenicol acetyl transferase ) and bind to the drug which change its structure and cannot bind to the binding site of the ribosomes 50s
-spectrum: bactriostatic ( Braod spectrum)
1-Gram +
2-Gram -
3-Anaerobic bacteria
4-Atypical organisms: calm my leg , BCR
-uses : its only used as 3rd choice
1-atypical organisms
2-typhoid fever
3-meningitis
-Advera effect :
-VIP-1-BM suppression :sever irreversible ( Aplastic anaemia : complete BM failure)
-VIP-2-grey baby syndrome : duo to immaturity of glucronic transferase and the first 2-4 weeks of life and , also functional immaturity of renal tubules impaired execration
-VIP-3-Dermatitis
4-Neurotoxicity : Paychosis , prephrial neuropathy

Question 31

70. Bactericidal antibiotics. Aminoglycosides, vancomycin and polymyxines. Mechanisms and spectra of antimicrobial action, side effects. Example of drug prescription.

Answer 31

1—- Aminoglycosids
-Drugs :
1-Streptomycin Pwdr 1st gen
2-Gentamicin amp 2gen
3-Amikacin pwdr 3 gen ( synthetic drug)
-Chemistry : Consists of NH2+ amino group and glycoside : sugar , And hydroxyle group which is mean ita water sulable
-Pharmacokinetics:
1-Absorption: not orally duo to inozed charge
2-Distribution:
2-1 Not Pass BBB , but pass placenta and its tetaroginic , breast milk Pass ( and its not tetarogenic ) bcs its not absorbed orally
3-Metabolism: in liver
4-Excretion : kidney, high concentration and unchanged and increases alkalinity of urine , Normally Ph of urine is 5.8 so the drug are more used in alklain urine which is needed to treat UTI
—Mechanism of action :
-its inhibit the protein synthesis by binding irriverasbly in the 30s subunit ribosome , which lead to error in the mRNA reaching and formation of functional abnormal proteins
-In details it consists of 3 phases :
1-Attachment: which the amino group NH2+ have positive charge , there will be attraction (Electrostatic Attraction ) bcs the outer membrane of the gram - its consist of negative charge
2-open pores : the outer membrane pores will open only incase of needed of nutrients and the aminoglycosides are similar to the nutrients so the pores will open and the drug molecules will enter
3-irreversible bond : once the drug reached the nucleus there is the ribosomes 30s subunit and it will bind to it irreversibly and inhibit mRNA translation
-Spectrum: they are bactriocidal ( broad spectrum shifted towards Gram -) duo to :
1-Mainly gram - : Entrobactria , Pusdomonas (2gen ,3gen ) , mycobacteria ( 1gen , amikacin )
2- few gram + : staphylococcus
3-TB
-Resistant:
1-P,Coccai
2- Anearobic and intercellular pathogen such as. (Calm my leg )
3-Cant be used for acquired
resp infection
-Uses :
1-Gram - infection: E coli UTI
3-Resp infection
4-Gram - spetecymi
5-TB : Streptomycin , Amikacin
-Side effect :
1-Neohrotoxcity : duo to exacration of this drug in renal , and bcs has + charge and can bind to Kidneys proteins
-VIP-2-Nerve toxicity 8th cranial : the molecule of this drug enters the inner ear and cause toxicity to the 8th cranial nerve ( vitebular and auditory ) and cause deafness duo to accumulate in the endolymph of the inner ear
-VIP-3-NMB : muscle weakness, we can reverse it with Neostagmine
—Dosage : 5mg per kg and its concentration killing dependent
———————————————-
2—–Vancomycin
-Drug : Vancomycin Amp 0,5 iVI
-mechanism: inhibits cell wall synthesis by binding to D-Ala-D-Ala terminal of growing peptide chain during cell wall synthesis resulting inhibitions of the transpeptdese reaction , Prevent further elongation and cross - linking of peptidoglycan
-Spectrum : narrow spectrum duo to :
Only gram + such as :
1-Staphylococci MRSA
2-P.Cocci
3-Entra cocci
4-Anearobic infeaction
-Pharmcokintics:
1-Not absorbed orally
2-Not metabolise in liver
3-Execreted by kidney
-Side effect :
1-Red man syndrome: Histamine reales
2-Nephrotoxcicty
3-Ototoxicity
4-Vein thromphlitis
—Uses :
1-MRSA
2-Culstrirudum diffucel colitis
———————
3———- Polymyxins
-Drug : Polymyxin B Pwder
- Mechanisms—The polymyxins are polypeptides that are
bactericidal against Gram-negative bacteria. These drugs act like
cationic detergents, disrupting bacterial cell membranes. They
also bind and inactivate endotoxin
-Spectrum : most gram nigative inclouding Psudomonal
-Side effect : neurotoxicity (paresthesias,
dizziness, ataxia) and acute renal tubular necrosis (hematuria,
proteinuria, nitrogen retention).
-Uses: resistant Gram-negative infections, including those caused by Enterobacter
and Pseudomonas.

Question 32

71. Synthetic antimicrobial agents. Sulfonamides: mechanisms and spectra of antimicrobial action of sulfonamides and co-trimoxazole, indications and side effects. Example of drug prescription.

Answer 32

-Drugs :
1-Trimethoprim/sulfamethoxazole tab ( Bactriocidal )
2-Sulfadiazine argentum oint 1%-50ml
—Chemistry : they consist of sulfer group and amino acid group ( So2NH2) this what is responsible for the effect but the R chain is only for pharmcokintics
-NB!
1-individual drug : bacteriostatic
2-Combined drug : bactriocidial
-Pharmcokintics:
1-Absorpation :good
2-Distribution:
2.1 BBB : pass and can treat CNSI
2.2 Placenta / breast milk :pass and its tertaoginic
2.3 body fluids :good reach
3-metabolism: liver
4-Execration : renal in acetylation metabolite with good concentration and can treat UTI , but we should alklain the urin first or it will lead to crystallurea
-mechanism of action :they are bacterial metabolites inhibitors of folic acid which us essential for DNA synthesis , in the norm , the bectrai synthesis the folic acid by this pathway :
-Paraaminobenzonic acid with help of Dihydroprotrate synthase transfer into dihydrofolic acid then with help of Dihydrofolate reducatse transfer into tetrahydrofolic acid then to purines then to DNA
- so the sulfa interfers with the first dihydroprotrate synthase but bacteria with time can modify it , but the Trimethoprim interferes with dinydrofolate reductase
- So now we useing the combination called Co-trimoxazol = Trimethoprim +Sulfamathoxazol to interfere the both phases
-spectrum: wide spectrum ( narrow )
1-few G+
2-Few G-
3-Atypical organisms
-uses :
1-UTI
2-Streptococcal
3-Puemocystis carinii ( PCP )
4-Toxoplasma
-Advera effect :
1-Allergy skin rash : Steven Johnson syndrome
2-Crystallurea
3-Kernectrus : displacement of billerubin in the albumen and can pass CNS in childrenunder 2 years the BBB not will developed and can cause permanent brain damage
4-BM suppression
-C.I :
1-Children under 2 years
2-Pregnancy-Drugs :

Question 33

72. Synthetic antimicrobial agents. Fluoroquinolones, nitrofurans and metronidazole. Mechanisms and spectra of antimicrobial action, indications for use and side effects. Example of drug prescription.

Answer 33

1——- Floruquinolons
-Drugs :
1gen-Nalidixic acid tab ( prototype ) -ve
2gen-Ciprofloxacin tab/amp 8h , -ve
3gen-Levofloxacin Tab/amp -ve,+ve,Atypical 12h
4gen-Moxifloxacin tab -ve,+ve,atypical,anaerobic
—Chemistry : consist of Floride , and MW its more then 500 , lipid sulable
-Pharmcokintics:
1-Absorpation : Complete, make complex with metals but not like Tetracycline
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and teratogenic
2.3 body fluids :good accumulation of phagocytes
3-metabolism: liver
4-Execration : renal and unchanged so are capable of treating UTI except Moxifloxacin
-mechanism of action : its inhibit the bacterial Topisomarse which is required for relaxation of The DNA to form a RNA masenger to form a new DNA , we have 4 type of topisomarse 1,2,3,4 these drugs inhibit 2nd ( gyrse ) and 4th especially in :
1-Gram - : gyrase
2-Gram + : topisomarse 4th
-spectrum: bactericidal ( broad spectrum)
1-Nalidixic acid : mainly G-
2-Ciprofloxacin : Mainly G- , few G+
3-Levofloxacin : G-,G+ , Atypical
4-Moxifloxacin : G-,G+,atypical,Anearobic
-resistant: Cross resistant but not raoid duo to point mutation in the gyrase and topisomarese
-uses :
1-UTI
2-Resp infection
3-osteomyelitis
4-meningitis
4–Atypical
-Advera effect :
-VIP-1-Muscloskletal adverse effect : cause arthropathy in the growing cartilage
2-CNS : increase seizures, duo to inhibation of GABA Receptor
3-prolangtion of QT interval : leading to fetal ventricular tachy arrhythmias
-C.I :
2-Pregnancy
2-children under 18
—————————————-
2——–metronidazol
Drugs : Metronidazole tab/Amp
—Chemistry :consist of Nitro group and Mw its 137 ( prodrug )
-Pharmcokintics:
1-Absorpation :Complete
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and not teratogenic
2.3 body fluids :reach
3-metabolism: liver
4-Execration : renal unchanged but cant treat UTI bcs its spectrum only anaerobic bacteria and the UTI its gram - , but can discolour the urin dark brown and its not harmful
-mechanism of action :
NB! :
1-OIL : oxidation is lose of electrons
2-RIG : redaction is gain of electrons
—- the metronidazole uptake by all type of bacteria but its only effect the anaerobic bacteria bcs its mechanism works on PFOR
Pyruvate:ferrodoxine oxido reductase
Which is responsible for generation kf the ATP in the anaerobic bacteria by oxidation and reduction so as we know metronidazole consist of Nitro group so the PFOR reduction the oxygen in the Nitro group and becomes free radical compounds and unstable which is cytotoxic free radical and bind to DNA and damage the DNA
-Resistant: its very slow or by efflux ( pumping out )
-spectrum: bactericidal
1-All Anaerobic bacteria
2-Protozoa :Entomoab hustolytica
3-Tricomons viginitis
-uses :
1-Anaerobic bacteria
2-Clustridum defesil
-Advera effect :
1-GIT upset
-VIP-2-Metallic taste
3-CNS toxicity : headech , increase seizures in epileptic patients
-VIP-4-Steven jhonsn syndrome
-VIP-5- Sever BM suppression
———————-
3——Nitrofurans
* bactericidal
* broad antibacterial spectrum including some protozoa G+,G-
* Oral drug forms
* Uses is limited
–mechnaism : itrofurantoin is activated inside bacteria by reduction via the flavoprotein nitrofurantoin reductase to unstable metabolites, which disrupt ribosomal RNA, DNA and other intracellular components. It is bactericidal, especially to bacteria present in acid urine
-Drugs :
1. Non-absorbable from GIT : Nifuroxazide tab Is used in acute bacterial diarrhea
2.Systemic use
-Furazolidone - intestinal and biliary infections
-Nitrofurantoin - urinary tract infections
-Nifuratel

Question 34

73. Anti-TB drugs. Classification, mechanisms of action, side effects. Prescribe isoniazid

Answer 34

1st line
* Ethambutol
* Pyrazinamide
* Isoniazid (T 0,3; A 10% - 5 ml)
* Rifampin (Caps 0,15; A 0,6 for i.v.)
* Rifabutin
2nd line
* Aminoglycosides
* Paraaminosalicylic acid
* Capreomycin
———————-
-drug : Isoniazid Tab 0.3 Amp
-mechansim : Mechanism of action
* It is a prodrug activated by a mycobacterial catalase–peroxidase.
* It targets the enzymes which are essential for synthesis of mycolic acid.
* Inhibiting mycolic acid leads to a disruption in the bacterial cell wall.
-Antibacterial spectrum: M. tuberculosis
-Side effect :
1.Hepatitis
2.Neurotoxicity (Due to a relative pyridoxine deficiency. This can be avoided by supplementation of 25-50 mg per day of pyridoxine).
* Peripheral neuropathy
* Convulsions in patients prone to seizures.

Question 35

74. Antiviral drugs. Classification, mechanisms of antiviral action, features of application andside effects. Example of drug prescription.

Answer 35

—virus life cycle :
1-Start with attachment : the virus endocyite to the cell
2-Uncouting : by the M2 proton channel
3-Replaction phase : in the nucleus the virus gets 2 pathways
3.1: viral genome to form a new virus
3.2 mRNA : which is for inhibition of host cell raibosm and start synthesis the virus proteins
4-Translation : in the ribosm and synthesis polyproteins of the virus
5-Processing : by enzyne called proatase : and its cutting the polyproteins into proteins
6-Assembly
7-release : normally virus released without enzymes but in influnza its need enzyme called Nueruaminadase

1- HIV :
1-Fusion inhibitors
-Drugs :
-Enfuvirtide : binds to Gp41 subunit of HIV-1 viral envalople that attaches to receptors on CD4 of host cell membranes and prevent the attachment
——-
2-RT inhibitors :
-Drug :
-zidovudine : its nucloside analogue so its competitive inhibtitor of Reverse transcriptase enzyme duo to similar structural components
-Side effect : Animea and myopathy
————
3-Integrase inhibitors :
-Drug : Raltegravir tab
-they inhibit the insertion of proviral DNA into host cell genomes by inhibiting the integrase enzyme
————-
4-Protase inhibitors:
-Drug : Saquinavir Caps
-its peptied like analog that binds to protase enzyme in active site and inhibits the activity of the protase enzyme which is the processing of polyproteins resulting if formation of immature non fractional virus particles
-side effect : metabolism side effect such as hypoglycaemia, hypolipidemia
———————–
2- HBV
-Drugs :
1-Lamivudine tab : its inhibit HBV DNA polymarase by converting inter-cellularly to triphospah form then it competes with cytosine triphosphate for incorporation into developing viral DNA strains resulting of termination of Viral DNA replication
2-Interferon-a A/3milin IU
-mechanism: the exact mechanism are unknown but its through these 3 mechanisms:
1-interfere with viral replication
2-stimulate of apoptosis
3-regulation of immune response
—Side effect :
1-Immune distrbance
2-Fatuge
3-neurotoxicity
4-Anemia and BM depression
————————
3- herpes
-Drugs :
1-Acyclovir tab/oint
2-Ganciclovir tab/A
-mechanism: they are purine analogues, they are pro drugs that are activated inside the viral infected cell Aciclovir is converted by viral
thymidine kinase to aciclovir monophosphate
✔Aciclovir monophosphate is then converted to aciclovir triphosphate by host kinases
✔Aciclovir triphosphate inhibit HSV-specified DNA-polymerases and prevent viral DNA synthesis
-Uses :
1-Acyclovir : Herpes V 1-2
2-Ganciclovir : cytomegalovirus
—————–
4- influnza
1-Uncoating inhibitors:
-Drugs: Rimantadine tab
-its bind to the M2 proton channel of the virus which lead to inhibition of virus uncoating and its active exassivly aginst influza A only
-uses : Influenza A
————-
2-Release inhibitors
-Drug : oseltamivir Caps 0,075
-mechanism: its inhibit the nuroaminadse enzyme with is responsible for budding of the virus
-side effect : neurpsychtric effect ,livedo reticularis
-uses : influenzaA,B

Question 36

75. Synthetic anticancer agents. Alkylating agents and antimetabolites. Mechanisms of action, side effects. Example of drug prescription.

Answer 36

-Cell cycle : its cycle for cell division in normal cases and has several phases :
-Phase 0: the cell in the resting state and its called G0 , then the cell receives Mitogenic signal to start the cell cycle for cell proliferation
-Phase 1: its called G1 which is the cell will increase in size
-Phase 2: this Phase called S phase ( Synthetic ) which is The cell Duplicate its DNA
-Phase 3: its called G2 which is the cell increasing in size again
-Phase 4: This Phase called M phase ( Mitosis ) which is contain 4 Sub-Phases
4.1 : Prophase ( Creating Sentrosoms )
4.2 : Metaphase ( Mitotectic spindles)
4.3 : Anaphase ( pulling the mitotic spindles)
4.4 : Telophase ( mitosis )
——
-Location : G1,S,G2
-Checkpoints: these checkpoints are Proteins Complex and there Function to check the Phases of The cell cycle if there is any abnormalities they will signal the cell to stop the the Cell cycle , And they are done by types of proteins:
1-Ve+ Regulators :such as
1.1 Cyclins and CDKs ( cyclins-dependent kinases )
1.2 Growth factors thats Acts on protein kinase
1.3 Signaling proteins such as : Ras , Raf
2- Ve- regulators :
2.1 P53
2.2 Brca1 , Brca 2
-NB! If there is mutation of the + regulators the cell cycle will keep dividing without entering the resting state , and if there is a mutation in the - regulators the cell cycle will keep dividing even with abnormalities of the cell
————————-
- they are 7 :
1-Myelosuppration
2-impaired Wound healing
3-Alopecia ( hear loss )
4-hepatotoxic
5-Sterility
6-damage of GI epithelium
7-tetrogenicity / Carcigenicity
———————————
1- Alklayting agents :
—Drug groups :
1-Nitrogen mustard : Cyclophosphamide tab/Amp
2-Nitrosoureas : Carmustine Amp
3-Other : Busulfan tab
—Mechanism: produce highly reactive intermediates which transfer Alkyl group to cellular micro molecules , At the Position 7th of guinin forming covalent bond which lead to DNA cross linking > resulting of inhibition of mitosis or even apoptosis
—Pharmacokinetics: Cyclophosphamide most alkylting agent used and its pro-drug which it’s required biotransformation in the liver by CYP450 to become active form
-Specific side effect :
1-Hemorrghic cystitis : caused by the metabolite called acrolein and can be prevented by increasing fluid intake or sulfhydrl donor such as
N-Acetlycysteine which is washing the bladder from this toxic form
—uses :
1-AntiCancer drug in most types of cancer
2-As immunosuppressants: such as RA,SLE duo to cross linking in T-cells which is in most cases its the reason of Autoimmune disease
—————————
2- antimetabolite :
—Drug groups :
1-Folic Antagonist: Methotrexate tab/Amp
2-Purine Analog: MercaptoPurine,Azathioprine tabs
3-Pyrimidine analog : Fluorouracil amp
—General mechanism: Antimetabolites are Analogous related to normal components involved in nucleic Acid synthesis, they comptatevly inhibit utilisation of physiological substrate leading to stop mitosis duo to wrong substrate
—specific mechanism of methotrexate : its folic acid antagonist which is interferes with folic acid which is essential for synthesis DNA cell division in Phase S ( PABA )
-Specific side effect :
1-Megaloblast anemia
2-mucosal ulceration
-uses:
1-AntiCancer drug
2-Autoimmune suppressant
——-
-Specific mechanism of
6-Mercaptopurine : interferes with Purine nucleotide ( Adenin , Gunini ) synthesis thus inhibiting DNA and RNA synthesis in Phase S
-Specific side effect :
1-the enzyme
Thiopurin S-methyltransferes Convert 6-MP into non toxic form people with this enzyme deficiency are subjected to sever myelosuppration
2-The enzyme Xanthin Oxidase breaks down 6-MP , Using a drug such as Allopurinol ( for gout ) which is Xanthin oxidase inhibitor lead to sever toxicity ( Drug interaction )
———
-Cell cycle : its cycle for cell division in normal cases and has several phases :
-Phase 0: the cell in the resting state and its called G0 , then the cell receives Mitogenic signal to start the cell cycle for cell proliferation
-Phase 1: its called G1 which is the cell will increase in size
-Phase 2: this Phase called S phase ( Synthetic ) which is The cell Duplicate its DNA
-Phase 3: its called G2 which is the cell increasing in size again
-Phase 4: This Phase called M phase ( Mitosis ) which is contain 4 Sub-Phases
4.1 : Prophase ( Creating Sentrosoms )
4.2 : Metaphase ( Mitotectic spindles)
4.3 : Anaphase ( pulling the mitotic spindles)
4.4 : Telophase ( mitosis )
——
-Location : G1,S,G2
-Checkpoints: these checkpoints are Proteins Complex and there Function to check the Phases of The cell cycle if there is any abnormalities they will signal the cell to stop the the Cell cycle , And they are done by types of proteins:
1-Ve+ Regulators :such as
1.1 Cyclins and CDKs ( cyclins-dependent kinases )
1.2 Growth factors thats Acts on protein kinase
1.3 Signaling proteins such as : Ras , Raf
2- Ve- regulators :
2.1 P53
2.2 Brca1 , Brca 2
-NB! If there is mutation of the + regulators the cell cycle will keep dividing without entering the resting state , and if there is a mutation in the - regulators the cell cycle will keep dividing even with abnormalities of the cell
————————-
- they are 7 :
1-Myelosuppration
2-impaired Wound healing
3-Alopecia ( hear loss )
4-hepatotoxic
5-Sterility
6-damage of GI epithelium
7-tetrogenicity / Carcigenicity
———————————
1- Alklayting agents :
—Drug groups :
1-Nitrogen mustard : Cyclophosphamide tab/Amp
2-Nitrosoureas : Carmustine Amp
3-Other : Busulfan tab
—Mechanism: produce highly reactive intermediates which transfer Alkyl group to cellular micro molecules , At the Position 7th of guinin forming covalent bond which lead to DNA cross linking > resulting of inhibition of mitosis or even apoptosis
—Pharmacokinetics: Cyclophosphamide most alkylting agent used and its pro-drug which it’s required biotransformation in the liver by CYP450 to become active form
-Specific side effect :
1-Hemorrghic cystitis : caused by the metabolite called acrolein and can be prevented by increasing fluid intake or sulfhydrl donor such as
N-Acetlycysteine which is washing the bladder from this toxic form
—uses :
1-AntiCancer drug in most types of cancer
2-As immunosuppressants: such as RA,SLE duo to cross linking in T-cells which is in most cases its the reason of Autoimmune disease
—————————
2- antimetabolite :
—Drug groups :
1-Folic Antagonist: Methotrexate tab/Amp
2-Purine Analog: MercaptoPurine,Azathioprine tabs
3-Pyrimidine analog : Fluorouracil amp
—General mechanism: Antimetabolites are Analogous related to normal components involved in nucleic Acid synthesis, they comptatevly inhibit utilisation of physiological substrate leading to stop mitosis duo to wrong substrate
—specific mechanism of methotrexate : its folic acid antagonist which is interferes with folic acid which is essential for synthesis DNA cell division in Phase S ( PABA )
-Specific side effect :
1-Megaloblast anemia
2-mucosal ulceration
-uses:
1-AntiCancer drug
2-Autoimmune suppressant
——-
-Specific mechanism of
6-Mercaptopurine : interferes with Purine nucleotide ( Adenin , Gunini ) synthesis thus inhibiting DNA and RNA synthesis in Phase S
-Specific side effect :
1-the enzyme
Thiopurin S-methyltransferes Convert 6-MP into non toxic form people with this enzyme deficiency are subjected to sever myelosuppration
2-The enzyme Xanthin Oxidase breaks down 6-MP , Using a drug such as Allopurinol ( for gout ) which is Xanthin oxidase inhibitor lead to sever toxicity ( Drug interaction )

Question 37

76. Natural anticancer agents. Anticancer antibiotics, mitotic poisons, hormones and their antagonists. Mechanisms of action, side effects. Example of drug prescription.

Answer 37

1- Antiboitcs :
—Drugs :
1-Doxorubicin Amp
-mechanism: its bind to DNA and DNA gyres thus inhibit DNA and RNA synthesis
-main adverse effect : cardio toxicity
—-
2-Actinomycin D Amp
-mechanism: its inhibit transcription By binding to DNA at the transcription initial complex and preventing Elongation of RNA chain by RNA polymerase
-main side effect : black stool , hemtoureia
——————
2-vinca alkaloids
—Drugs :
1-Vinblastine pwder 0.0004
2-Vincristine pwder 0.0004
-mechanism: they are cell cycle specific , they bind to microtubules system ( mitotic spindles ) during the Metaphase and cause Metaphase arrest which lead to prevent cell division
-Specific side effect :
1-Vinastine : more BM depression but less neuropathy
2-Vincristine : More peripheral Neuropathy but less BM depression
———————–
3-Hormons :
-Some Tumours are hormones dependent such as Breast /Prostatic Cancer
—Antiestrogen
-Drug and its mechanism:
1-Tamoxifen tab : its an Oestrogen Antagonist in the Breast but it’s ago so in the uterus and BM
-Side effect : DVT
-uses : breast cancer in female premenopausal
2-Anastrozole Tab : its competitive inhibitor of Aromatase which is responsible for production of Oestrogen from the adrenal cortex And prephrial tissue .
-uses : for breast cancer in female that Postmenopausal which Estrogen receptors positive
——AntiTesteron:
-Drug: Flutamide Tab
-mechanism: its potent blocker of testosterone receptors
-uses : advanced prostatic Cancer
-Specific side effect : Hepatotoxic

Question 38

77. Targeted anticancer drugs. Tyrosine kinase inhibitors, monoclonal antibodies (MABs): mechanism of action. Example of drug prescription.

Answer 38

1- Monoclonal antibody :
-NB1 they Are MABs designed to bind to specific Target on the surface of Cancer cell or immune cells , and they are given by IVI
-mechanism: They block the GF receptor which lead to Arresting proliferation and triggering apoptosis of tumour cells , and recurrent
NK-Cells that Have cytotoxicity, bind complement leading to direct cell toxicity
-Drug,Target,Uses : All amp S.c
1-Rituximab , CD20 ,
B cell non-Hodgkins lymphoma
2-Ibritumomab ,CD20 .
B cells non-Hodgkins lymphoma,
Chronic Mylogenous leukaemia
3-Trastuzumab , EGF receptor , breast cancer
4-Bevacizumab , VEGF ,
Colorectal cancer ,
Breast Cancer ,
,Non- small cell lung cancer
——————————–
2-Tyrosine kinase inhibitors
-NB1 : they are small molecules used to target singling pathway kinase of GF such as EGF ,PDGF thus preventing uncontrolled cell proliferation
-Drugs and its target :
1-Imatinib : its inhibit The BCR-ABL tyrosine kinase , this inhibition blocks proliferation and promotes apoptosis in BCR-ABL positive cell line
-side effect : fluid retention and hepatotoxic
-uses : all tab 0.3
1-to Treat Philadelphia Chromosome positive which is chronic mylogenous leukaemia
2-Erlotinib + Gefitinib : Target EGF in tyrosine kinase receptor
-Uses : non small cell lung cancer
3-Lapatinib : Target EGF in tyrosine kinase receptor
-uses : breast Cancer

Question 39

78. Anti-protozoal agents. Classification, mechanisms of antiprotozoal action and side effects.Example of drug prescription.

Answer 39

-life cycle of Plasmodium :
1-Start with mosquito biting the body
2-Sporozites in the blood stream then to the liver
3-in the liver there is parasities division called dromantic focai ( only in relapse type such as ovale,vivax )
4-then its leaves the liver to blood circulation and called mirozites and attack the RBCs and keep division inside the RBCs
5- the. It have 2 pathway either it’s become Gematocytes for transmission or attack the RBCs again.
——–
1-4-Aminoquinin family
-Drugs :
1-Chloroquine tab
2-Mefloquine tab
Both rapid acting
-mechanism: plasmodium digest the host HB in the same time from digestion of HB heme is toxic for parasite so plasmodium polymarse is transform the Heme into non toxic form , so the 4-aminoquinin inhibt the plasmodium plymarse which is result of cell death from toxicity
-Side effect : mefloqunin less side effect
1-GIT , N,V,D
2-CVS: prolong QT duo to same family of Antiarrthmic drug quinidin
3-bluerd vision : duo to pertacepation of chloride and iode
—Uses :
1-Prophlyxis of malaria
2-Treatments of malaria
3-Ambausis
—CI :
Paitnt with paorsis or prophlia bcs acute attack may occurred
———————
2-Primaquine
-Drug : Primaquine tab
-mechanism: its form quinoline-quinin metabolites which are electron-transferring redox compound thats act as cellular oxidant the drug us tissue Schizonatic and also limit malaria transmission by binding on Gematocytes
-Side effect :
1-GIT
2-headeacg
3-sever toxicyt of G6PD deficiency
-uses :
To pervent relapse by acting on hypnozties and its radical cure
——————–
3-Antufolate
-Drugs : proguanil tab
-mechanism: its sulf counting drug and act as anti metabolites drug of Paraaminobenzonic acid by inhibating dihydroptorate
-Side effect :
1-GIT
2-hypersistivte
3-in high dose its compatative protein binding
-uses : usally combind with pyrimathmine for causal prophylaxis
————————————————————-
———–anti Helmintics infections———-
-types of helmintics :
1-Nematodes
2-Cestods
3-Trematodes

-Drug : Albendazol tab : by inhibiting microtubules assembly
-Spectrum and uses :
Braod spectrum ( all 3 types )
-Side effect : reversable leukpina
———
2-Drug : Praziquantel tab : its increasing membrane permeability to calcium , casuing marked contraction intinally followed by paralysis of the muscle of the helmentics and then vaculazation and parasite death
-spectrum uses : Braod spectrum includes 3 types

Question 40

79. Inhibitor-protected cephalosporin. Example of drug prescription. Mechanisms of antimicrobial action, antimicrobial spectra, side effects.

Answer 40

-Inhibitor-protected cephalosporin :
-we use B-lactames inhibotrs
1- Clavulanic acid ( non betalcatm ring )
2- betalactam ring containing , Avibactam , relebactam ,Sulbactam

-Cephalosporins ————
-Cephalosporin Also a B-lactamse ring have similar mechanism of action As penicillin
-Each newer generation increasingly resistant to B-Lactamse .
-Pharmacoinatic :
-Distribution:They are widely distributed,But 3rd ,4th,5th generation can Penetrate CSF
-Ceftriaxone 3rd gen , are mainly excreted by bile
—————
1St Gen
-Drugs :
1-Cefazolin amp 0.5 2-Cefalexine tab
-Spectrum: narrow spectrum, duo to covering G+ same as Penicillin G with some G- ( E coli klebsiella )
-resistant: Sensitive to B-Lactamse
-BBB : Dont pass
-Allergy : Cross allergy with Penicillin
—————————–
2nd Gen
-Drugs : Cefuroxime Tab/Amp
-Spectrum : Covering G+ and some G- such as ( H.Influenza,Neaseria , Proteus ) but not Pesudomons , Narrow spectrum
-Resistant : Reletavly resistant to B-Lactamse
-BBB: only Cefuroxime Can pss
-Allergy : Cross allergy with penicillin
—————–
3rd Gen
-Drugs :
1-Oral :
-Cefixime
-Ceftibutene
2-Parenteral :
-Cefotaxime
-Ceftriaxone
-Ceftazidime
—Spectrum: mainly Gram- and also a few of Gram+ ,Also active aginst psudomonas , And anaerobic , Moderate spectrum
-Resistant: Resistant to B-Lactramse
-BBB : Pass BBB
-Allergy: No cross allergy with Penicillin
——————
4th Gen
-Drugs : Cefepime Amp 0.5
—Spectrum: Coverse G+,G- , Pusdomonas , Also anaerobic , Broad spectrum
-Resistant: highly resistant to B-Lactamse
-BBB : Pass BBB
-Allergy: No cross allergy with Penicillin
———————
5th Gen
-Drugs : Ceftaroline Amp 0.5
—Spectrum: Coverse G+,G- , Pusdomonas , Also anaerobic ,MRSA, Broad spectrum
-Resistant: highly resistant to B-Lactamse
-BBB : Pass BBB
-Allergy: No cross allergy with Penicillin
——————–
-Most urgent :
1-Meningitis -ve
2-Osteomyelitis
3-Skin infection
4-Typhoid fever
5-UTI : E-Coli -Ve
6-Rsp infection
7-Gannoria
8-ENT
9-intestinal infection
10-Topical
————————
-Side effect :
1-Nephrotoxince : Most of them is 1gen
-VIP-2-Disulferam like action : normally alcohol > Acetyldhayed > Co2 and H2o, by the help of Aldahyed dehydrogenase , so these drugs inhibit aldehyide dehydrogenase which results of bad mood and nause and vomiting is also ( Drug interaction)
-VIP-3-Prothrombin : 3rd generation inhibt the enzyme Vit k exopidese lead to hypoprothrombinemia
—————prescribe Cefepime wiht avibactam :

Question 41

80. Sodium-glucose transporter inhibitor-2. Example of drug prescription. Pharmacological characteristic of the drugs used for CHF (congestive heart failure).

Answer 41

• family of sodium-glucose cotransporter 2 inhibitor ( SGLT-2 )
  -drug: Dapagoiflozin tab 0,005
  -mechanism of action : increase the urine glucose and sodium secretion , By inhibiting SGLT2, dapagliflozin blocks reabsorption of filtered glucose in the kidney, increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of pancreatic β cell function and modulation of insulin sensitivity.
  -pharmacological effect :
  1- decrease Bp
  2-body wight loss
  -side effect :
  1-polyuria
  2-hypotension
  3-hyperkalimia
• Uses :
  1-:in T2DM in case of the patient has renal or haptic failure and cant take metformin
  2- CHF : duo to Increase circulating ketone bodies: SGLT2 inhibitors increase circulating ketones – byproducts of breaking down fat, especially in the fasting state. Ketones are very efficient energy producers for the heart, so in theory, this may decrease oxygen demand and reduce the heart’s workload

Question 42

( extra quastion ) explain Antifungal

Answer 42

–Structre of fungai cell :
1-Outer membrane : its synthsis by enzyme called B-glucan synthase
-Drug effect on this phase is : Echinocandins ( fungin )
2-Ergosterol pathway :
2.1 start with Squlene transform into squlene epoxide by enzyme called squlene epoxidase : drug effecting this enzyme is Allymines
2.2 then from squlene epoxide transform into Lanosterol by enzyme called 14-a-Demithylase : drug effecting this enzyme ( Azoles )
2.3 From lanosterol transform into ergosterol and here the effect on the ergosterol directly by drugs called ( Polynes )
3-Drug effecting the DNA its Griseofulvin
——————-
1-Echinocandine ,( outer membrane inhibitors)
-Drugs :
1-Caspofungin
2-micafungin Pwoder ( systemic use )
-mechanism: they are outer membrane synthesis inhibitors by inhibition of B-(1-3)-D-glucan synthase which is lead to disruption of the glucan formation and destroy cell intergtry
-Spectrums :
1-Candida ; fungcidal
2-Aspergills : Fungostatic
-Pharmcokintics:
-Abs : poor
2-Dist : high concentration in tissue and organ
3-metabolism: in liver without cyp450 ( no drug drug interaction )
-Side effect : Fever , Dyspepsia
-uses :
1-invasive Candida
2-Invasive Asprgillosis ( which resistant to standard therapy )
———————
2- Allymines
-Drugs terbinafine tab / oint
-mechansim : Inhibition of squalene epoxidase
whch is lead to decrease synthesis of ergosterol in the early stages and accumulation of toxic squalene result of abnormality of the cytoplasmic membrane
-Spectrum : Dermatophytes, Candida
-Pharmacokintics :
-abs : 70%
-Dist : high concentraion in skin and nalis
-Metabolsim : in liver
-uses :
1.onychomycosis caused by dermatophytes
2.skin candidiasis
———————-
3- Azoles
-Drugs :
1-imidazol dervativs : miconazole ( systamic)
, ketoconazole (local )
2-triazol dervativs : Fluconazole , itraconazole (systmic )
-Mechaims : they are Selective inhibition CypP450-dependent
α-dimethylase which lead to Inhibit conversion of lanosterol to ergosterol and result of Disruption of growth and death of fungal cells
1- Ketoconazol tab
-Spectrum of action : broad spectrum
1.dermatophytes (Trichophyton, Microsporum, Epidermophyton )
2.Candida .
3.dimorphic fungi
-Pharmacokinetics
-abs : Variable absorption
-metabolism : Biotransformation in the liver with cytP450
-Dist : Poor penetration through the BBB
-side effect : High toxicity (hepatotoxicity, ↓ adrenal cortex, ↓ testosterone, gynecomastia, oligospermia, sexual dysfunction). After itraconazole development - only topically!
-Uses :
1.candidiasis
2.dermatomycosis
3-Prostate cancer

2-Fluconazol Caps
-Spectrum of action
Yeast (Candida spp., Cryptococcus spp.)
NB! Does not work against mold fungi (Aspergillus spp.)
-Pharmacokinetics
-Abs : food does not affect bioavailability
-Dist : penetrates the BBB , high [C] in CSF, skin and urine
-Metabolsim : biotransformation in the liver, inhibit of cytP450 (interaction)
-uses:
1. superficial and invasive candidiasis
2.cryptococcosis