3. cvs

Question 1

…………………………………….. is the major direct consequence of diminished cardiac output(CO)

Answer 1

Decreased exercise tolerance with rapid muscular fatigue

Question 2

Therapeutic strategies

Answer 2

Removal of retained salt and water: diuretics
Reduction of after load and salt and water retention: ACEIs
Reduction of excessive sympathetic stimulation: beta blockers
Reduction of preload or after load: vasodilators
Direct augmentation of depressed cardiac contractility: cardiac glycosides

Question 3

Approaches of therapy:2

Answer 3

non-pharmacological and pharmacological

Question 4

Drugs with positive inotropic actions:

Answer 4

Cardiac glycosides(CGs)
Beta agonists, and
Phosphodiesterase inhibitors

Question 5

Drugs without positive inotropic actions:

Answer 5

diuretics,
ACEIs/ARBs,
beta blockers,
vasodilators, and
aldosterone antagonists

Question 6

Drugs for symptomatic relief:

Answer 6

CGs,
beta agonists,
PDE inhibitors,
diuretics

Question 7

Drugs for slowing disease progression:

Answer 7

ACEIs/ARBs,
beta blockers,
aldosterone antagonists,

Question 8

The hydroxyl groups and other substitutions found on the aglycone determine

Answer 8

The hydroxyl groups and other substitutions found on the aglycone determine its polarity
Digoxin has one additional hydroxyl group than digitoxin

Question 9

mechanism of action of digoxin

Answer 9

Mechanism of action: Inhibition of Na+/K+-ATPase → increase in intracellular Na+→ alters the driving force for sodium-calcium exchange by the exchanger→ increase in intracellular calcium → increased contractility

Question 10

digoxin effects in heart

Answer 10

main positive inotropic

Heart rate decreases due to improved performance of the heart and an increased vagal tone(negative chronotropy)

Hinder the conduction of excitation(negative dromotropy)

Promote the formation of heterotopic excitations(positive bathmotropy)—which can lead to ventricular extrasytoles and ventr. tachycardia

Question 11

time takes digoxin to work

Answer 11

Binding CGs to Na+ K+ ATPase is slow
Moreover after Na+ K+ ATPase inhibition, Ca++ loading occurs gradually

Thus inotropic effect of digitalis takes hours to develop, even after i.v. administration

Question 12

effect on blood vessels digoxin

Answer 12

a net decrease in peripheral resistance and improved venous tone

Question 13

effect on kidney digoxin

Answer 13

diuresis secondary to improvement in circulation and renal perfusion(retained salt and water is gradually excreted)
No diuresis occurs in normal individuals or edema due to other causes

Question 14

CNS effects of digoxin

Answer 14

CNS: higher doses cause CTZ activation resulting nausea and vomiting
Still higher doses: hyperapnea, confusion, disorientation, visual disturbances

Question 15

Are also useful in atrial arrhythmias(atrial flutter and fibrillation)

Answer 15

digoxin

Question 16

slow and large doses

Answer 16

Slow approach of digitalization is safe and employed when symptoms are mild
Large loading dose(divided in three or four portions given over 24-36 hours) followed by maintenance doses can be employed when more rapid effect is required

Question 16

Adverse effects
GI
visual
CNS
cardiac

Answer 16

GI disturbances: anorexia, nausea, vomiting, diarrhea(gastric irritation & CTZ activation)
Visual disturbances: disturbed color vision
CNS effects: delirium, fatigue, confusion, dizziness, abnormal dreams
Cardiac effects: different arrhythmias

Question 17

Management of toxicity: 4

Answer 17

Withdrawal of the glycoside for extracardiac effects may be enough

Potassium supplementation corrects tachyarrhythmias caused by chronic use of CGs( in acute CG toxicity plasma K+ is increased and contraindicated)

Use of antiarrhythmic drugs
(lidocaine for ventricular arrhythmias; propranolol supraventricular arrhythmias; atropine for AV-block and bradycardia)

Digoxin antibodies for severe toxicity(binds digoxin and digitoxin and enhances their excretion by kidney

Question 18

Precautions and contraindications:

Answer 18

hypokalemic patients
k competetive inhibits digoxin

Elderly, renal or severe hepatic disease

Myocardial infraction

Thyrotoxicosis

Ventricular tachycardia

Question 19

interactions with
diuretics
calcium
quinidine
antacids
phenobarbitone

Answer 19

Diuretics: cause hypokalemia(K+ supplementation may be given prophylactically)

Calcium: synergizes with digitalis and precipitates toxicity

Quinidine: displaces digoxin from plasma proteins

Antacids: decrease digoxin absorption

Phenobarbitone: enhance metabolism of digitoxin and decrease its half-life

Question 20

Bipyridines

Answer 20

are termed as phosphodiesterase inhibitors
Representatives include inamrinone, milrinone
Increase force of contraction
Produce vasodilatation(arteries and veins)
Act by inhibiting phosphodiesterase isoenzyme III(found in heart & blood vessels)

Question 21

moa of bipyridines

Answer 21

Phosphodiesterase is an enzyme that catalyzes the inactivation of cAMP
PDEIs result in increased concentration of cAMP

Question 22

adverse effects of Bipyridines

Answer 22

Nausea, vomiting, arrhythmia, thrombocytopenia and liver toxicity are adverse effects( but milrinone better tolerated)

Question 23

Beta agonists in HF

Answer 23

dobutamine and dopamine are positive inotropic agents of choice for the short-term support of circulation in advanced heart failure(in ICUs preferred to bipyridines)
Dobutamine has lesser effect on heart rate as compared to other sypmathomimetics
Dopamine improves renal perfusion additionally(advantageous in shock)

Question 24

MOA of beta agonist

Answer 24

Activate beta receptors which activate G-proteins Results in activation of adenylyl cyclase to generate cAMP cAMP dependent protein kinases which phosphorylates voltage-dependent slow calcium channel Increased calcium entry increases contractility

Question 25

Diuretics

Answer 25

Commonly used diuretics are loop diuretics (furosemide for severe); thiazides(hydrochlorothiazide) for mild cases

Question 26

ACEIs

Answer 26

ACEIs: captopril, enalapril, lisinopril, fosinopril,.. ↓angiotensin II and decrease degradation of bradykinin ↓ cardiac remodeling due to angiotensin II Bradykinin exhibits vasodilator actions Decrease aldosterone related volume retention Have positive impact on survival of patients

Question 27

Angiotensin II receptor blockers(ARBs): list when used

Answer 27

Include losartan, candesartan, valsartan,.. Have similar effects Used as a substitute for ACEIs for patients who can not tolerate the latter(dry cough, angioedema)

Question 28

Direct vasodilators:

Answer 28

Nitrates(e.g. nitroglycerin) reduce preload→ reduces size of ventricles→ improved pumping efficiency Hydralazine reduces afterload→ pumping improves by even weaker contraction Combination of both has positive impact on survival of patients

Question 29

aldosterone antagonist

Answer 29

Spironolactone

Question 30

Beta blockers: plus caution

Answer 30

Metoprolol, carvedilol, bisoprolol attenuation of the adverse effects of high conc. of catecholamines (cardiac remodeling, apoptosis) decreased heart rate can precipitate acute decompensation of cardiac function But most patients in stable severe heart failure respond favorably

Question 31

........ and ..........provide symptomatic relief but lack mortality benefit

Answer 31

CG diuretics

Question 32

.............. ,............... ,......................, nitrates plus hydralazine demonstrated mortality benefit

Answer 32

acei b blockers spironolactones

Question 33

Drugs for acute HF

Answer 33

Loop diuretics e.g. furosemide Beta agonists/bipyridines Direct vasodilators

Question 34

Anti-anginal drugs

Answer 34

Nitrates: nitroglycerine(GTN), isosorbide dinitrate, isosorbide mononitrate Beta blockers: propranolol, metoprolol, atenolol, etc Calcium channel blockers: verapamil, diltiazem, nifedipine, amlodipine, nimodipine, etc Others: nicorandil, ranolazine

Question 35

Angina pectoris(AP) plus types

Answer 35

: atherosclerotic disease of the coronary arteries Known as coronary artery disease or ischemic heart disease AP is a characteristic sudden, severe, pressing chest pain radiating to neck, jaw, back, & arms Results from an imbalance in the myocardial oxygen supply-demand relationship Types of angina: 3 principal forms Classical, typical, effort-induced, stable angina advanced atherosclerosis of the coronary vessels→ inadequate coronary perfusion Symptoms occur during physical activity, emotional excitement and other cause Unstable angina: chest pain occurs with increased frequency, duration, and intensity Episodes occur for more than 20 minutes with less effort or even at rest Results from rupture of atheromatous plaques attracting platelet deposition and clot formation Prinzmetal’s, variant, vasospastic, or rest angina results from coronary artery spasm(less common) → decreased blood flow to the heart muscle often in patients with coronary atherosclerosis Anginal attacks unrelated to physical activity(occur at rest) Responds promptly to vasodilators

Question 36

Therapeutic strategies: Goals of therapy:

Answer 36

Therapeutic strategies: Increasing blood flow(oxygen supply) Decreasing work load of the heart(decreasing oxygen demand) Goals of therapy: Relieve symptoms Prevent occurrence of episodes Slow disease progression

Question 37

nitrates type moa se

Answer 37

Mechanism of action: nitrates are changed in the body into reactive free radical nitric oxide(NO) by –SH containing enzymes mainly gluthathione reductase Nitric oxide stimulates guanylyl cyclase which catalyzes the conversion of GTP into cGMP Increased cGMP activates protein kinase which causes dephosphorylation of myosin light chain kinase----relaxation of smooth muscle of vessels ↑cGMP also decreases calcium entry Tolerance develops to high doses or long acting preparations due to: - Exhaustion of –SH stores - Systemic compensation via sympathetic discharge and sodium and water retention Cross-tolerance also occurs, tolerance disappears after about 8-12 hours Monday morning sickness in persons working in explosives industry describes tolerance At very high doses: methemoglobinemia (met-Hgb) → tissue hypoxia and death Low met-Hgb can be used for treatment of cyanide poisoning Met-Hgb + CN-=cyanmet-Hgb+ sodium thiosulfate→ SCN-(readily excreted) Excessive met-Hgb can be treated by methylene blue

Question 38

Beta adren.antagonists plus caution

Answer 38

Important in the prophylaxis of angina(propranolol, metoprolol, atenolol,..) By virtue of their negative inotropic , negative chronotropic effects and reduced BP: reduce myocardial oxygen consumption Lower heart rate is associated with increased diastolic perfusion time(advantageous) Nonselective blockers avoided in variant angina because of the increased risk of vasospasm due to unopposed action of circulating catecholamines on alpha adrenergic receptors Sudden withdrawal of beta blockers may exacerbate angina

Question 39

Calcium channel blockers

Answer 39

Are substances of different chemical classes Phenylalkylamines: Verapamil Benzothiazepines: Diltiazem Dihydropyridines: Nifedipine, nicardipine, amlodipine, felodipine , nimodipine,…. Block voltage-gated L-type calcium channels found predominantly on non dihydro the heart and dihydro smooth muscle (vascular smooth muscle most sensitive)

Question 40

Newer anti-anginal drugs

Answer 40

Ranolazine acts by reducing a late sodium current that facilitates calcium entry via the sodium calcium exchanger Decreased intracellular calcium→ reduced cardiac contractility and work Nicorandil is potassium channel activator and stimulant of guanylyl cyclase to increase cGMP Causes smooth muscle relaxation (hyperpolarization)