Flashcards in Drugs Deck (337):
MOA of mannitol
osmotic diuretic - increased tubular fluid osmolarity, producing increase urine flow, decreases intracranial/intraocular pressure
- uses : drug overdose, and increased ICP/IOP
ADE of mannitol
pulmonary edema, dehydration,
- CI in anuria and CHF
MOA of Acetazolamide
CA inhibitor causing self limited NaHCO3 diuresis and decreases total body HCO3- stores
- uses: glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri
ADE of acetazolamide
Hyperchloremia metabolic acidosis, parethesias, NH3 toxicity, sulfa allergy
MOA of loop diuretic (furosemide, ethancrynic acid, torsemide)
inhibitis NaK2Cl cotransporter in thick ascending limb
- abolishes hypertonicity of medulla, preventing concentration of urine
- stimulates PGE release (vasodilatory effect on affferent arteriole)
- increases Ca excretion (loops lose Ca)
ADE of furosemide
OH DANG - otoxicity, hypokalemia, dehydration, allergy (sulfa), nephritis (interstitial), gout
use of ethacrynic acid
Diuresis in pts allergic to sulfa drugs. It's a phenoxyacetic acid derivative.
- NEVER use to treat gout
MOA of HCTZ
Thiazide diuretic - inhibits NaCl reabsorption in early distal tubule.
- decreases diluting capacity of nephron, decreases Ca excretion
- uses: HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis (saves Ca)
ADE of HCTZ
hypokalemia metabolic alkalosis, hyponatremia
- hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia
- sulfa allergy
MOA of Spironolacton and eplerenone
competitive aldosterone receptor antagonists in cortical collecting tubule
MOA of triamterene and amiloride
block eNa Channels in CCT
ADE of K sparing diuretics
Hyperkalemia (can lead to arrhythmias)
Endocrine effects w/ spironolactone (gynecomastia and antiandrogen effects)
Diuretics and effect on urine NaCl
all increase urine NaCl except acetazolamide, serum NaCl may decrease as a result
Diuretics and effect on urine K
- increases w/ loop/thiazides
serum K may decrease as a result
Diuretics and effects on blood pH
1. decrease (acidemia) - CA inhibitors and K sparing diuretics
2. increase (alkalemia) - loop and thiazides
mechanism via which loops/thiazides causes blood alkalemia
1. volume contraction - increases ATII = increases Na/H exchange in PT = increase HCO3- reabsorption
2. K loss leads to K exiting all cells in exchange for H entering cells
3. low K state, H is exchanged for Na in cortical collecting tubule = alkalosis and paradoxical aciduria
Diuretics and effects on urine Ca
1. increase in loop b/c of decreased paracellular Ca reabsorption
2. decrease w/ thiazide - enhanced paracellular Ca reabsorption in DT
MOA of ACE inhibitors
- decreases ATII and GFR by preventing constriction of efferent arterioles.
- levels of renin increase, prevent inactivation of bradykinin (potent vasodilator)
ADE of ACE inhibitor
Cough, Angioedema, Teratogen (renal malformations), increase Creatinine, Hyperkalemia, Hypotension
- CI in C1 esterase inhibitor deficiency
- avoid in bilateral renal artery stenosis b/c it will further decrease GFR and lead to renal failure
MOA of ARBs
ATII receptor blockers
- no increase in bradykinin so no cough or angioedema
MOA of CCB
block voltage dependent L type calcium channels of cardiac and SM = decrease contractility
- Vascular SM think dihydropyridine
- Heart think verapamil > dilitazem
What are dihydropyridine CCB's used for?
2. Angina - including Prinzmetal
What are the non-dihydropyridine CCB's used for?
3. Atrial fibrillation/flutter
What is Nimodipine used for?
Subarachnoid hemorrhage - prevents cerebral vasospasm
ADE of CCBs
Cardiac depression, AV block, peripheral edema, flushin, dizziness, hyperPRL, constipation
MOA of Hydralazine
Increase cGMP = SM relaxation. Vasodilates arteriole > veins
- decreases afterload
When is hydralazine used?
severe HTN, CHF
- First line therapy for HTN in pregnancy, w/ methyldopa
- usually co-administered w/ a beta blocker to prevent reflex tachycardia
ADE of hydralazine
Compensatory tachycardia (contraindicated in angina/CAD)
Fluid retention, Nausea, HA, angina, SLE syndrome
What is commonly used to treat hypertensive emergeny?
Nitroprusside, nicardipine, clevidipine, labetalol, and fenolodpam
MOA of nitroprusside
short acting; increases cGMP via direct release of NO
- worry about cyanide toxicity (treat w/ sulfur)
MOA of fenolodopam
D1 receptor agonist = coronary, peripheral, renal, and splanchnic vasodilation
- decreases BP and increases natriuresis
MOA of nitroglycerin and isosorbide dinitrate
Vasodilate by increasing NO in vascular SM - increase cGMP and SM relaxation.
- likes to dilate veins >> arteries. Decreases preload
uses for nitroglycerin and isosorbide dinitrate
angina, acute coronary syndrome, pulmonary edema
ADE of Nitroglycerin and isosorbide nitrate
- reflex tachycardia (treated w/ beta blocker), hypotension, flushing, HA
- development of tolerance for vasodilating action during work week and loss of tolerance over the weekend leads to tachycardia, dizziness, and HA upon reexposure
What is the goal for antianginal therapy?
reduce myocardial O2 consumption by decreasing
What effects do nitrates have on the body?
1. decrease EDV, HR, ejection time, MVO2
1. increase contractility and HR - both reflex exposure
What effect do beta blockers have on the body?
1. decrease contractility, BP, HR, MVO2
2. increase EDV and ejection time
What effect do nitrate combined w/ beta blockers have on the body?
1. decrease BP, HR, and MVO2
2. not a huge effect on EDV, contractility, ejection time
What beta blockers are contraindicated in angina?
pindolol and acebutolol - both are partial Beta agonists
MOA of statins
inhibit conversion of HMG-CoA to mevalonate (cholesterol precursor)
lipid effects of statins
decreases LDL mainly
ADE of statins
Liver toxicity (increased LFTS)
rhabdomyolysis (especially when used w/ fibrates and niacin)
MOA of Niacin (vitamin B3)
inhibits lipolysis in fat tissue, decreases hepatic VLDL synthesis
lipid effects of niacin
decrease LDL and increase HDL
slight decrease in TG
ADE of niacin
red, flushed face - decreased by aspirin or long term use
Hyperglycemia (acanthosis nigricans)
Hyperuricemia (worsens gout)
MOA of bile acid resins - cholestryramine, colestipol, colesevelam
Prevents intestinal absorption of bile acids; liver must use cholesterol to make more
Lipid effects of bile acid resins
slightly increases HDL and TG
ADE of bile acid resins
bad taste, GI discomfort, decreases absorption of fat soluble vitamins, cholesterol gallstones
MOA of ezetimibe
prevent cholesterol absorption at small intestine brush border
lipid effects of ezetimibe
ADE of ezetimibe
rare increase in LFT, diarrhea
MOA of fibrates (gemfibrozil, clofibrate, bezafibrate, fenofibrate)
upregulates LPL = increases TG clearance
- Activates PPAR-alpha to induced HDL synthesis
lipid effects of fibrates
decreases TG a lot
decrease LDL, increase HDL
ADE of fibrates
myositis, liver toxicity (LFTs), cholesterol gallstones (esp w/ concurrent bile acid resins)
Pharmacokinetics of digoxin
20-40% protein bound
half life = 40 hours
MOA of digoxin
- direct inhibition of NaKATPase = indirect inhibition of NaCa exchanger = increases IC Ca => positive inotropy. Stimulates vagus nerve = decreases HR
clinical use of digoxin
CHF to increase contractility
Atrial fibrillation - decrease conduction at AV node and depression at SA node
ADE of digoxin
1. cholinergic = N/V, diarrhea, blurry yellow vision
2. ECG = increase PR, decrease QT, ST scooping, T wave inversion, arrhythmia, AV block
- hyperkalemia indicates poor prognosis
What factors predispose to digoxin toxicity
1. renal failure = decreased excretion
2. hypokalemia - allows digoxin to bind to K site at NaKATPase
3. Verapamil, amiodarone, quinidine (decrease digoxin clearance, displaces it from tissue binding site)
Antidote for digoxin toxicity
slowly normalize K, cardiac pacer, anti-digoxin Fab fragments, Mg
What are the classes of antiarrhythmics?
No Bad Boys Keep Clean
- class I - Na channel blockers
- class II - Beta blockers
- class III - K channel blockers
- class IV - CCB
What do type I antiarrhythmics do?
- slow or block conduction especially in depolarized cells
- decrease slope of phase 0 depolarization and increase threshold for firing of abnormal pacemaker cells
- hyperkalemia causes increased toxicity for all class I drugs
What are the class IA antiarrhythmics and their toxicities?
DQP - disopyramide, quinidine, procainamide
1. Disopyramide: heart failure
2. Quinidine - cinchonism
3. Procainamide - SLE syndrome
- Thrombocytopenia, torsades de pointes due to increase QT interval
MOA of Class IA antiarrhythmics
increase AP duraion, increase ERP, increase QT interval
- used to treat atrial and ventricular arrhythmia especially re-entrant and ectopic SVT and VT
What are the class IB antiarrhythmics and their ADEs?
- CNS stimulation/depression, CV depression
Lettuce, Tomato, Mayo, Pickles
MOA of class IB antiarrhythmics
decrease AP duration
- perferentially affect ischemic or depolarized Purkinije and ventricular tissue
- used to treat acute ventricular arrhythmias (especially post MI), digitalis induced arrhythmias
What are the class IC antiarrhythmics and ADEs?
- Fries Please
- proarrhythmic, especially post MI (contraindicated, also CI in structural and ischemic heart disease)
MOA of Class IC antiarrhytmics
- significantly prolongs refractory period in AV node
- minimal effect on AP duration
- used to treat SVTS, including atrial fibrillation
- last resort in refractory VT
MOA of Class II antiarrhythmics
- decrease SA and AV nodal activity by decrease cAMP, decreases Ca current. Suppress abnormal pacemakers by decreasing slope of phase 4.
- AV node is particularly sensitive = increase PR interval
- esmolol is very short acting
- used to treat SVT, slowing ventricular rate during atrial fibrillation and atrial flutter
ADE of Class II antiarrythmics
impotence, exacerbation of COPD and asthma
- CV effects (bradycardia, AV block, CHF)
- CNS effects (sedation, sleep alterations)
- may mask signs of hypoglycemia.
Metoprolol can causes dyslipidemia
Propranolol can exacerbate vasospasm in Prinzmetal angina.
- Beta blockers are contraindicated in cocaine users (risk of unopposed alpha adrenegic receptor agonist activity).
- treat overdose w/ glucagon
What are you Class III antiarrhythmics
Amiodarone, Ibutilide, Dofetilide, Sotalol (AIDS)
- used for atrial fibrillation, atrial flutter, ventricular tachycardia (amiodarone, sotalol)
MOA of class III antiarrhythmics
Increase AP duration, increase ERP
- used when other antiarrhythmics fails
- increase QT interval
ADE of Sotalol
torsades de pointes, excessive beta blockade
ADE of Ibutilide
torsade de pointes
ADE of amiodarone
pulmonary fibrosis, liver toxicity, hypo/hyperTH - check LFT, PFT, and TFT
- corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neuro problems, constipation
- CV Effects (bradycardia, heart block, CHF)
MOA of class IV antiarrhythmics
-Verapamil and dilitiazem
decreases conduction velocity, increase ERP, increase PR interval
- used to prevent nodal arrhythmias, rate control in atrial fibrillation
ADE of class IV antiarrhythmics
constipation, flushing, edema,
- CV effects = CHF, AV block, sinus node depression
MOA of adenosine
increase K out of cells = hyperpolarizes cell and decreases Ca current.
- DOC of dx of SVT.
- Very short acting
ADE of adenosine
flushing, hypotension, chest pain
What can block the effects of adenosine?
theophylline and caffeine
MOA of Mg
effective in torsades de pointes and digoxin toxicity
MOA of leuprolide
GnRH analog w/ agonist properties when used in pulsatile fashion
- antagonist when used in continuous fashion = downregulates GnRH receptors in pituitary = decreased FSH and LH
uses of leuprolide
Prostate cancer (continuous - use w/ flutamide)
uterine fibroids (continuous)
Precocious puberty (continuous)
ADE of leuprolide
MOA fo estrogens
binds estrogen receptors
- used for hypogonadism/ovarian failure, menstrual abnormalities, HRT in postmenopausal women,
- used in men w/ androgen dependent prostate cancer
ADE of estrogens
increase risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, increased risk of thrombi.
What are contraindications for estrogens?
ER positive breast cancer, history of DVTs
MOA of clomiphene
antagonists at E-receptors in hypothalamus
- prevents normal feedback inhibition and increases release of LF and FSH from pituitary = stimulates ovulation.
What is clomiphene used to treat
infertility due to anovulation (PCOS)
ADE of clomiphene
hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances
MOA of tamoxifen
antagonist on breast tissue
Agonist at uterus and bone - associated w/ endometrial cancer and thromboemolic events
treat and prevent recurrences of ER + breast cancer
MOA of raloxifene
Agonist on bone - hence used to treat osteoporosis b/c decreases bone resorption
Antagonist at uterus
- worry about thromboembolic events
Uses of hormone replacement therapy
relief of prevent menopausal symptoms and osteoporosis
- unopposed estrogen replacement therapy increases risk of endometrial caner so progesterone is added.
- possible increased CV risk
MOA of anastrozole/exemestane
Aromatase inhibitors used in postmenopausal women w/ breast cancer
MOA of progestins
bind progesterone receptors to decrease growth and increase vascularization of endometrium
- used in OCP and treatment of endometrial cancer and abnormal uterine bleeding
MOA of mifepristone
competitive inhibitor of progestins at progesterone receptos
- used to terminate pregnancy, usually gived w/ misoprostol (PGE1)
ADE of mifepristone
heavy bleeding, GI effects, ab pain
MOA of oral contraceptions
E and Progestin inhibit LH/FSH and thus prevent estrogen surge. No E surge = no LH surge = no ovulation.
1. Progestins causes thickening of cervial mucus limiting acess of sperm to uterus. Also inhibits endometrial proliferation, making endometrium less suitable for the implantation of embryo.
what are OCP contraindications
Smokers >35 years old, pts w/ history of thromboembolism and stroke, pts w/ history of E-dependent tumor
MOA of terbutaline
Beta 2 agonists that relaxes the uterus, used to decrease contractions frequency in women during labor
MOA of Danazol
synthethic androgen that acts as partial agonist at androgen receptors
- used to treat endmetriosis and hereditary angioedema
ADE of danazol
wt gain, edema, acne, hirsutism, masculinization, decreased HDL levels, liver toxicity
MOA of Testosterone and methylT
agonist at androgen receptors
- treats hypogonadism and promotes development of secondary sexual characteristics, stimulates anabolism to promote recovery after burn or injury
ADE of T and methyl-T
causes masculinization of females
- decreases intratesticular T in males by inhibiting release of LH (via negative feedback) = gonadal atrophy
- premature closure of epiphyseal plates
- increases LDL and decreases HDL
MOA of finasteride
5 alpha reductase inhibitor (less DHT conversion)
- useful in BPH
- also promotes hair growth so used to treat male pattern baldness
MOA of flutamide
nonsteroidal competitive inhibitor of androgens at the T receptor
- used in prostate carcinoma
MOA of ketoconazole
inhibits steroid synthesis - inhibits 17,20 desmolase
MOA of spironolactone for repro
inhibits steroid binding, 17alpha hydroxlase and 17,20 desmolase
What are uses of ketoconazole and spironolactone for repro
PCOS and prevents hirsutism
- both have side effects of gynecomastia and amenorrhea
MOA of tamsulosin
alpha 1 antagonist used to treat BPH by inihibiting SM contraction. Selective for alpha 1A,D receptors found on prostate va vascular alpha 1B receptors
MOA of sildenafil and vardenafil
inhibit PDE 5 = increases cGMP = SM relaxation in corpus cavernosum, increases blood flow and penile erection
ADE of sildenafil and vardenail
HA, flushing, dyspepsia, impaired blue-green color vision
- RISK of life threatening hypotension in patients taking nitrates
What is the treatment strategy for DM1 and DM2? gestational DM
DM1 - low sugar diet, insulin replacement
DM2 - dietary modification and exercise for wt loss, oral agents, non-insulin injectables, insulin replacements
Gestational DM - dietary modifications, exercise, insulin replacement if lifestyle modification fails
What are the rapid acting insulins?
MOA of rapid acting insulins?
bind insulin receptor
1. liver = increase glucose stored as glycogen
2. muscle = increase glycogen, protein synthesis, and K uptake
3. Fat = increase TG storage
ADE of rapid acting insulins?
hypoglycemia, rare HSR rxn
What are the uses for regular insulin and intermediate insulin (NPH)?
1. regular - DM1, 2, GDM, DKA (IV), hyperkalemia (+ glucose), stress hyperglycemia
2. DM1, DM2, GDM
What are the long acting insulins?
Glargine and detemir
- used for DM1, 2, and GDM (basal glucose control)
MOA of biguanides (metformin)
increase peripheral glucose uptake (insulin sensitivity)
- 1st line therapy for DM2. can be used in pts w/out islet function
ADE of metformin
Lactic acidosis (contraindicated in renal failure)
What are you sulfonylureas?
1st Gen = tolbutamide, chlorpropamide
2nd Gen = glyburide, glimepiride, glipizide
MOA of sulfonylureas
Close K channel in beta cell membrane = cell depolarizes triggering insulin release via increase Ca influx
- stimulates release of endogenous insulin in DM2, requires islet function so can't be used in DM1
ADE of sulfonylureas
risk of hypoglycemia increases w/ renal failure
- 1st gen have disulfiram like effects
= 2nd gen have hypoglycemia
MOA of glitazones/thiazolidinediones
increase insulin sensitivty in peripheral tissue
- binds PPAR-gamma nuclear transcription regulator
- used on monotherapy in DM2 or combined
ADE of glitazones/thiazolidinedions
wt gain, edema, liver toxicity, heart failure
MOA of alpha glucosidase ihibitors = acarbose, miglitol
inhibits intestinal brush border alpha glucosidase
- delayed sugar hydrolysis and glucose absoprtion = decrease postprandial hyperglycemia
ADE = GI disturbances
MOA of Amylin analog = pramlintide
decrease gastric emptying , decrease glucagon
MOA of GLP-1 analog = Exenatide, Liraglutide
MOA of DPP-4 inhibitors = Linagliptin, saxagliptin, sitagliptin
Increase insulin and decrease glucagon release
ADE of pramlintide
hypoglycemia, nausea, diarrhea
ADE of exenatide and liraglutide
ADE of gliptins
mild urinary and respiratory infxns
MOA of PTU and methimazole
blocks thyroid peroxidase = inhibits oxidation of I, organification of I = inhibits TH synthesis
- Know that PTU also blocks 5'deiodinase which decreases peripheral conversion of T4 to T3.
- used in HyperTH
Also know that PTU is used in pregnancy
ADE of PTU and methimazole
Skin rash, agranulocytosis (rare), aplastic anemia
- PTU = liver toxicity so check LFTs
- Methimazole = teratogen - can cause aplastic cutis
MOA of levothyroxin and triiodothyronine
- used in hypoTH and myxedema
ADE of levothyroxine and triidothyronine
tachycardia, heat intolerance, tremors, arrhythmia
use of GH
GH deficiency and Turner syndrome
use of somatostatin (octreotide)
acromegaly, carcinoid, gastrinoma, glucagonom, esophageal varicies, VIPoma
use of oxytocin
stimulates labor, uterine contractions, milk let down, controls uterine hemorrhage
use of ADH
pituitary (central) DI
MOA of demeclocycline
ADH antagonist (member of tetracycline family)
used in SIADH
ADE of demeclocycline
nephrogenic DI, photosensitivty, abnormalities of bone and teeth
MOA of glucocorticoids
metabolic, catabolic, anti-inflammatory, immunosuppressive effects mediated by interaction w/ response elements and inhibition of TF such as NFkB
ADE of glucorticoids
Iatrogenic Cushing syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy brusiability, osteoporosis, adrenocortical atrophy, PUD, diabetes if chronic use.
- can get adrenal insufficiency when drug stopped abruptly after chronic use
ADE of octreotide
Nausea, cramps, steatorrhea
MOA of H2 blockers - cimetidine, ranitidine, famotidine, nizatidine
reversible block of H2 receptors to decrease H secretion by parietal cells
- used to treat peptic ulcer, gastritis, mild reflux
ADE of cimetidine
1. potent inhibitor of CYP450
2. anti-androgenic effect; PRL release, gynecomastia, impotence, decreased libidio in males
3. can cross BBB - confusion, dizziness, headache
4. can cross placenta
- both this and ranitidine decrease renal excretion of Cr
MOA of PPIs- prazoles
irreversibly inhibits H/K ATPase in stomach parietal cells
- used for peptic ulcer, gastritis, esophageal reflux, and ZE syndrome
ADE of PPIs
increased risk of C. difficile infxn, pneumonia.
Hip fractures, decreases serum Mg w/ long term use
MOA of bismuth and sucralfate
bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in mucous layer
- use to heal ulcers and traveler's diarrhea
MOA of Misoprostol
PGE1 analog. increases production and secretion of gastric mucous barrier and decreases acid production
uses of misoprostol
1. prevents NSAID induced peptic ulcers
2. maintenance of a PDA
3. induces labor by ripening cervix
can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
- all can cause hypokalemia
Overuse of Aluminum hydroxide leads to what?
proximal muscle weakness, osteodystrophy, and seizures
overuse of Calcium carbonate leads to what?
hypercalcemia and rebound acid increase
- can chelate and decrease effectiveness of other drugs like tetracycline
overuse of MgOH leads to what?
diarrhea, hyporeflexia, hypotension, cardiac arrect
- Mg = must go to bathroom
MOA of osmotic laxative = MgOH, Mg citrate, PEG, lactulose
1. provide osmotic load to draw water out
2. Lactulose = treats hepatic encephalopathy b/c gut flora degrade it into lactic acid and acetic acid that promote nitrogen excretion as NH4+
- these overall are used to treat constipation
ADE of osmotic laxatives
diarrhea, dehydration, may be abused by bulimics
MOA of infliximab
-- treats CD, UC, RA, AS, and psoriasis
ADE of infliximab
infxn incluidng reactivation of latent TB, fever, hypotension
MOA of sulfasalazine
combo of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory)
- used to treat CD and UC
ADE of sulfasalazine
malaise, nausea, sulfonamide toxicity, reversible oligospermia
MOA of ondansetron
5HT3 blocker, decreases vagal stimulation. Powerful central acting antiemetic
- control vomiting posteroperatively and in pts undergoing cancer chemotherapy
ADE of ondansetron
MOA of metoclopramide
D2 receptor block - increases resting tone, contractility, LES tone, motility
-- doesn't influence colon transport time
- used to treat diabetic and post surgery gastroparesis, antiemetic
ADe of metoclopramide
1. increase parkinsonian effects
2. relestness, drowsiness, fatigue, depression, nausea, diarrhea
3. drug interaction w/ digoxin and diabetic agents
4. CI - in pts w/ small bowl obstruction or PD
What are the 1st gen histamine 1 blockers?
Diphenhydramine, dimenhydrinate, chlorpheniramine
What are the 2nd gen histamine 1 blockers?
loratadine, fexofenadine, desloratadine, cetirizine
- used for allergies
- think ends in "-adine"
Uses 1st gen histamine 1 blockers
allergy, motion sickness, sleep aid
ADE of 1st gen H1 blockers
sedation, antimuscarinic, anti-alpha adrenergic (orthostatic hypotension)
MOA of guaifenesin
expectorant - thins respiratory secretions, doesn't suppress cough reflex
MOA of n-acetylcysteine
Mucolytic - loosens mucous plugs in CF patients.
MOA of dextromethorphan
antitussive - blocks NMDA glutamate receptors
- synthetic codeine analog
- has mild opoid effect when used in excess, mild abuse potential
use Naloxone for overdose.
MOA of pseudoephedrine and phenylephrine
alpha agonists nasal decongestants
- used to decrease hyperemia, edema, and nasal congestion
- opens obstructed eustachian tubes
- worried about HTN.
MOA of albuterol, salmeterol, formoterol
Beta 2 agonists, relaxes bronchial SM
1. Albuterol - for acute exacerbation
2. Sal and form - long acting agents for prophylaxis, adverse effect are tremor and arrhythmia
MOA of theophylline
causes bronchodilation by inhibiting PDE = increase cAMP levels
- narrow therapeutic index
- metabolized by CYP450
ADE of theophylline
narrow TI = cardiotoxicity, neurotoxicity
- blocks effect of adenosine
MOA of ipratropium
competitive block of muscarinic receptors, preventing bronchoconstriction
- also use for COPD
MOA of beclomethasone and fluticasone
- inhibits cytokine synthesis
- inactivates NFkB
- 1st line therapy for chronic asthma
MOA of Montelukast and Zafirlukast
- blocks LT receptor
- especially good for Aspirin induced asthma
MOA of zileuton
5LOX pathway inhibitor
- blocks conversion of arachidonic acid to LT
MOA of omalizumab
- binds mostly unbound serum IgE and blocks binding to FceRI
- Used in allergic asthma resistant to inhaled steroids and long acting Beta agonists
MOA of methacholine
muscarinic receptor agonists
- used in bronchial provocation challenge to help dx asthma
MOA of bosentan
Used to treat pulmonary arterial HTN
- competitively blocks endothelin -1 receptor and decreases pulmonary vascular resistance
MOA of Heparin
cofactor for activation of antithrombin - decreases thrombin and factor Xa.
- it has a short half-life
Uses of heparin
Immediate anticoagulation for PE, acute coronary syndrome, MI, DVT. Used during pregnancy b/c doesn't cross placenta
What do you monitor when someone is on heparin?
ADE of heparin
bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions.
What do you give to rapidly reverse heparin toxicity?
Protamine sulfate - it's a positively charged molecule that binds negatively charged heparin)
What is good about LMW heparins? (enoxaparin, dalteparin)
act more on factor Xa, have better bioavailability, and longer half life.
- they can be given subcutaneously and without lab monitoring
What is the bad thing about LMW heparins?
they can't be easily reversed
What is heparin induced thrombocytopenia?
development of IgG antibodies against heparin bound to platelet factor 4. This Ab-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia
What are argatroban and bivalirudin and their MOA?
1. deriatives of hirudin, anticoagulants used by leeches.
2. inhibit thrombin directly
- used instead of heparin for anticoagulating patients w/ HIT
MOA of warfarin (coumadin)
interferes w/ normal synthesis and gamma carboxylation of vitamin K dependent clotting factors 2, 7, 9, 10 and proteins C and S.
What is monitored in pts on warfarin?
PT - extrinsic pathway. INR values
Where is warfarin metabolized and tell me about its half life?
- metabolized by CYP450
- long half life
When is warfarin used?
Chronic anticoagulation (after STEMI, venous thromboemobolism prophylaxis, and prevention of stroke in atrial fibrillation)
When is warfarin not used?
in pregnant women b/c warfarin can cross the placenta
ADE of warfarin
Bleeding, teratogenic, skin/tissue necrosis, drug drug interactions
What do you give for rapid reversal of warfarin overdose?
- then give vitamin K
MOA of apixaban and rivaroxaban
direct factor Xa inhibitors
What are the uses of apixaban and rivaroxaban
treatment and prophylaxis of DVT and PE (rivaroxaban), stroke prophylaxis in pts w/ atrial fibrillation
ADE of apixaban and rivaroxaban
- they have no reversal agent
Why is the onset of action of warfarin slow?
action is limited on half lives of normal clotting factors
What is the site of action of warfarin and heparin?
1. warfarin - work in liver
2. heparin - works in blood
What is the structural difference b/w warfarin and heparin?
1. warfarin - small lipid soluble molecul
2. heparin - large anionic acidic polymer
MOA of alteplase, reteplase, tenecteplase
directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots.
What do the thrombolytics do PT, PTT, and platelet count?
1. increase both PT and PTT
2. no change in platelet count
When are the thrombolytics used?
early MI, early ischemic stroke, direct thrombolysis of severe PE
ADE of thrombolytics
- they are CI in pts w/ active bleeding, hx of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
What do you treat thrombolytic toxicity w/?
aminocaproic acid - inhibitor of fibrinolysis
- FFP and cryoprecipitate can also be used to correct factor deficiencies
MOA of Aspirin
irreversibly inhibits COX 1 and 2 by covalent acetylation.
- platelets can't make new enzymes so effect lasts until new platelets are produced.
What effect do aspirin have on blood mearsuring things?
1. increases bleeding time
2. decreases TXA2 and PGs
3. no effect on PT and PTT
uses for aspirin
antipyretic, antiinflammatory, analgesic, antiplatelet (decreases aggregation)
ADE of aspirin
1. gastric ulceration
2. tinnitus - CN 8
3. chronic use can lead to ARF, intersitital nephritis, and upper GI bleeding
4. Reye syndrome in kids w/ viral infxn
What will aspirin overdose cause?
initially a respiratory alkalosis, then superimposed by metabolic acidosis
MOA of clopidogrel, ticlopidine, prasugrel, ticagrelor
inhibits platelet aggregation by irreversibly blocking ADP receptors
- inhibits fibrinogen binding by preventing GpIIb/IIIa from binding to fibrinogen
Uses of the ADP receptor inhibitors?
acute coronary syndrome, coronary stenting
- there is decreased incidence/recurrence of thrombotic stroke
ADE of ADP receptor inhibitors?
neutropenia w/ ticlopidine
- TTP and HUS may be seen
MOA of cilostazol and dipyridamole
phosphodiesterase III inhibitor = increases cAMP in platelets thus inhibiting platelet aggregaion
- also a vasodilator
uses for cilostazol and dipryidamole
intermittent claudication, coronary vasodilation, prevention of stroke or TIA (combined w/ ASA), angina prophylaxis
MOA of abciximab, eptifibatide, tirofiban
bind to Gp IIb/IIIa on activated platelets preventing aggregation
What are uses of Gp IIb/IIIa inhibitors?
unstable angina, percutaneous transluminal coronary angioplasty
ADE of Gp IIb/IIIa inhibitors?
At what step in the cell cycle do the following drugs interfere?
1. Vinca alkaloids and taxols
1. M phase - affect microtubules
2. G2 phase
3. 2 and G2 phase - inhibits DNA synthesis
3. S phase - inhibit nucleotide syntehsis
What are you antimetabolite cancer drugs?
4. Azathioprine, 6MP, 6TG
MOA of MTX
folic acid analog that inhibits DHF reducatse = decreases dTMP = decreases DNA and protein synthesis
What are the uses of MTX?
1. cancer - leukemias, lymphomas, choriocarcinomas, sarcomas
2. others - abortions, ectopic pregnancy, RA, psoriasis, IBD
ADE of MTX
- myelosuppression which is reversible w/ leucovorin rescue
- Macrovesicular fatty change in liver
MOA of 5FU
pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid.
- this complex inhibits thymidylate synthase = decreased dTMP = decreased DNA and protein synthesis
Uses of 5FU?
colon cancer, pancreatic cancer, basal cell carcinoma (topical use)
ADE of 5FU?
- overdose: rescue w/ uridine
MOA of cytarabine
pyrimidine analog that inhibits DNA polymerase
- used in leukemias and lymphomas
ADE of cytarabine
leukopenia, thrombocytopenia, megaloblastic anemia
- essentially PANCYTOPENIA
MOA of azathioprine, 6MP, 6TG
purine (thiol) analogs that decrease de nove purine synthesis
- activated by HGPRT
uses for azathioprine, 6MP, 6TG
preventing organ rejection, RA, SLE (azathioprine)
- leukemia, IBD (6MP, 6TG)
ADE of azathioprine, 6MP, 6TG
- all lead to BM, GI and liver toxicity
- Azathioprine and 6MP = both metabolized by xanthine oxidase thus both increase toxicity w/ allopurinol which inhibits their metabolism.
What are you antitumor Abx?
2. Doxorubicin, daunorubicin
MOA of dactinomycin
uses for dactinomycin
Wilms tumor, Ewing sarcoma, rhabdomyosarcoma = thinkg kid tumors!
MOA of doxorubicin and daunorubicin
generates free radicals and intercalates in DNA causing breaks and decreasing replication
ADE of doxorubicin/daunorubicin
1. cardiotoxicity = dilated cardiomyopathy
4. toxic to tissues following extravasation
What is used to prevent anthracycine cardiotoxicity?
dexrazoxane - Fe chelating agent
MOA of bleomycin
induces free radical formation which causes breaks in DNA strands
uses of bleomycin
testicular cancer and Hodgkin lymphoma
ADE of bleomycin
pulmonary fibrosis, skin changes, mucositis, minimal myelosuppression
What are you alkylating agents for cancer treatment?
1. cyclophosphamide and ifosfamide
MOA of cyclophosphamide and ifosfamide
covalently X link (interstrand) DNA at guanine N7
- requires bioactivation in liver
ADE of clyclophosphamide and ifosfamide
- hemorrhagic cystitis - can be partially prevents w/ mesna
What is mesna?
used to treat hemorrhagic cystisis
- the thiol group of mesna binds toxic metabolites
MOA of nitrosureas - carmustines, semustine, streptozocin
- requires bioactivation
- cross BBB and cross links DNA
- used to treat brain tumors
ADE of nitroureas
CNS toxicity - convulsions, dizziness, ataxia
MOA of busulfan
cross links DNA
- used treat CML and ablate pt's BM before BMT
ADE of busulfan
- pulmonary fibrosis
MOA of vincristine/blatine
bind Beta tubulin and inhibit polymerization into microtubules - prevent formation of mitotic spindle needed for M phase
ADE of vincristine
1. neurotoxicity (areflexia, peripheral neuritis)
2. paralytic ileus
ADE of vinblastine
MOA of paclitaxel/taxols
hyperstabilize polymerized MT in M phase so that mitotic spindle can't break down (anaphase can't occur)
- used to treat ovarian and breast carcinomas
ADE of taxols
myelosuppression, alopecia, HSR
MOA of cisplatin and carboplatin
cross links DNA
uses of cisplatin and carboplatin
testicular, bladder, ovary, and lung carcinomas
ADE of cisplatin and carboplatin
- nephrotoxicity and acoustic nerve damage
What can you prevent the nephrotoxicity with?
amifostine (free radical scavenger) and chloride diuresis
MOA of etoposide and teniposide
inhibits topoisomerase II --> increases DNA degradation
uses of etoposide and teniposide
solid tumors, leukemias, lymphomas
ADE of etoposide and teniposide
myelosuppression, GI irritation, alopecia
MOA of irinotecan and topotecan
inhibits topoisomerase I and prevent DNA unwinding and replication
uses for the -tecans?
colon cancer - irinotecan
ovarian and small cell lung cancers - topotecan
ADE of -tecans?
severe myelosuppression, diarrhea
MOA of hydroxyurea
inhibits ribonucleotide reductase = decreases DNA synthesis
- S phase specific
uses for hydroxyurea
melanoma, CML, SCD to increase HbF
MOA of trastuzumab (herceptin)
HER2 (tyrosine kinase receptor) mab
- used to kill breast cancer cells that overexpress HER2
ADE of trastuzumab
MOA of imatinib
Y kinase inhibitor of bcr-abl (CML) and c-Kit (common in GI stromal tumors)
Uses of rituximab
Non-hogdkin lymphoma, RA (w/ MTX), and ITP
ADE of rituximab
increase risk of progressive multifocal leukoencephalopathy
MOA of vemurafenib
small molecule inhibitor of forms of B-raf kinase w/ the V600E mutation
- used to treat metastic melanoma
MOA of bevacizumab
- treated for solid tumors to prevent angiogenesis
ADE of bevacizumab
hemorrhage and impaired wound healing
MOA of zanamivir and oseltamivir
inhibits influzena neruaminidase --> stops release of progeny virus
- can be used to treat both influenza A and B
MOA of ribavarin
inhibits synthesis of Guanine nucleotides by competitively inhibiting IMP DH
- used for RSV and Hep C treatment
ADE of ribavarin
hemolytic anemia, severe teratogen
MOA of acyclovir, famciclovir, valacyclovir
- monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cell
- all guanosine analog
- triphosphate formed by cellular enzymes. They preferentially inhibits viral DNA polymerase by chain termination
What are the uses for acyclovir, famciclovir, and valacyclovir for the herpes infxns?
1. can use them to treat HSV, VZV
2. weak activity against EBV
3. no activity against CMV
4. used for HSV induced mucocutaneous and genital lesions as well as for encephalitis
5. Prophylaxis in ICPs
6. no effect on latent forms of HSV and ZVZ
* valcyclovir is a prodrug for acyclovir = has better oral bioavailability
ADE for acyclovir, famiciclovir, and valacyclovir
obstructive crystalline nephropathy and ARF if not adequately hydrated
mechanism of resistance for acyclovir, famiciclovir, and valacyclovir
mutated viral thymidine kinase
MOA of ganciclovir
5'monophosphate formed by CMV viral kinase
- Guanonsine analog
- triphosphate formed by cellular kinases and preferentially inhibits viral DNA polymerase
ADE of gancicloir
pancytopenia, renal toxicity
- more toxic to host enzymes than acyclovir
Mechanism of resistance to ganciclovir
mutated CMV DNA polymerase or lack of viral kinase
When is ganciclovir used?
CMV, especially in ICP.
* Valganciclovir is a prodrug and has better oral bioavailability
MOA of Foscarnet
viral DNA polymerase inhibit that binds to the pyrophosphate binding site of the enzyme.
- doesn't require activation of viral kinase!!!
when is foscarnet used?
1. CMV retinitis in ICP pts when ganciclovir fails
2. acyclovir resistant HSV
ADE of foscarnet
mechanism of resistance of foscarnet
mutated DNA polymerase
MOA of cidofovir
preferentially inhibits viral DNA polymerase
- doesn't require phosphorylation by viral kinase!!!!
when is cidofovir used?
CMV retinitis in ICP pts, acyclovir resistant HSV
- it has a long half life
ADE of cidofovir
What do you give w/ cidofovir to decrease the renal toxicity?
coadminister with probenecid and IV saline to decrease toxicity
What is normal HIV therapy?
HAART - give when pts presents w/ AIDS defining illness, low CD4 cell counts, or high viral load
1. regimen consists of 3 drugs to prevent resistance
Give pt 2 NRTIs + 1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor
What are you HIV protease inhibitors?
MOA of the HIV protease inhibitors
1. assembly of virions depends on HIV-1 protease (from pol gene) which normally cleaves the polypeptide products of HIV mRNA into their functional parts.
2. Protease inhibitors prevent maturation of new virions
ADE of protease inhibitors
1. Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy
2. Indinavir - nephropathy, hematuria, kidney stones
3. Ritonavir can boost other drug concentrations b/c it inhibits CYP450
What are the HIV NRTIs?
MOA of NRTIs
competitively inhibits nucleotide binding to reverse transcriptase and terminates DNA chain (lacks a 3'OH group)
* Tenofovir is a nucleotide; all the others are nucleosides and need to be phosphorylated to be active
* Zidovudine is used for general prophylaxis and during pregnancy to decrease risk of fetal transmission
ADE of NRTIs
1. bone marrow suppression - can be reversed w/ G-CSF and EPO
2. Peripheral neuropathy
3. lactic acidosis w/ nucleosides
4. Rash -
5. Anemia - zidovudine
6. pancreatitis - didanosine and stavudine
What are the HIV NNRTIs?
efavirenz, nevirapine, delavirdine
MOA of HIV NNRTIs
binds to reverse transcriptase at site different from NRTI
- don't require phosphorylation to be active or compete w/ nucleotides!!!!
ADE of NNRTIs
1. rash and liver toxicity common to all
2. Efavirenz - vivid dreams and CNS symptoms
3. Delavirdine and efavirenz are CI in pregnancy
MOA of raltegravir
inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
ADE of raltegravir
MOA of enfurvirtide
binds gp41 inhibiting HIV viral entry
MOA of maraviroc
binds CCR5 on surface of T cells/monocytes inhibiting interaction w/ gp120
ADE of enfuviritide
skin reaction at injection sites
MOA of interferons
glycoproteins normally made by virus infected cells, exhibiting a wide range of antiviral and antitumoral properties
When is IFN alpha used
chronic Hep B and C
Hairy cell leukemia
When is IFN beta used
When is IFN gamma used
chronic granulomatous diease
ADE of Interferons
neutropenia and myopathy
What Abx should be avoided in pregnancy and why?
1. Sulfonamides - kernicterus
2. Aminoglycosides - ototoxicity
3. Fluoroquinolones - cartilage damage
4. Clarithomycin - embryotoxic
5. Tetracyclines - discolored teeth, inhibition of bone growth
6. chloramphenicol - gray baby
What antifungal and antiviral should be avoided in pregnancy?
1. Ribavirin - teratogenic
2. Griseofulvin - teratogenic
3. Delavirdine and efavirenz
MOA of Cox 2 inhibitors
- reversibly inhibits COX2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain
- spares COX1 which helps maintain the gastric mucosa thus should not have the corrosive effects of other NSAIDS on the GI lining
- spares platelet functions as TXA2 production is dependent on COX 1
When are COX 2 inhibitors used?
RA, OA, pts w/ gastritis or ulcers
ADE of COX 2 inhibitors
increase risk of thrombosis, sulfa allergy
MOA of acetaminophen
reversibly inhibits COX mostly in CNS
- inactivated peripherally
When is acetaminophen used?
antipyretic, analgesic but not anti-inflammatory
- used instead of ASA to avoid Reye syndrome in kids w/ viral infxn
ADE of acetaminophen
- overdose produces hepatic necrosis
- it's metabolite (NAPQI) depletes GSH and forms toxic tissue adducts in lvier
- N-acetylcysteine is the antidote - generates GSH
MOA of bisphosphonates
Pyrophosphate analog that binds hydroxyapatite in bone, inhibiting osteoclast activity
uses of bisphosphonates
Osteoporosis, hyperCa, Paget disease of bone
ADE of bisphosphonates
corrosive esophagitis, osteonecrosis of jaw
MOA of allopurinol
inhibits Xanthine oxidase to decrease conversion of xanthine to uric acid
- also used in tumor lysis associate urate nephropathy
- increases concentrations of 6MP and azathioprine
What can't you give at the same time as allopurinol?
- salicylates b/c all but the highest doses depress uric acid clearance. Even high doses (5-6g/day) have only minor uricouric activity
MOA of febuxostat
inhibits xanthine oxidase
MOA of probenecid
inhibits reabsorption of uric acid in PCT
- also inhibits secretion of penicillin
What are the chronic gout drugs?
Allopurinol, febuxostat, probenecid