cardiovascular drugs

Question 1

what are 3 major events to which tx of heart failure is targeted?

Answer 1

1. decreasing cardiac workload 2. controlling excess fluid 3. enhancing myocardial contractility

Question 2

what are 5 groups of drugs that can reduce cardiac workload in heart failure?

Answer 2

1. Angiotensin-converting enzyme (ACE) inhibitors 2. Angiotensin II Receptor Antagonists / ARB-angiotensin receptor blocks 3. Direct vasodilators 4. Beta-blockers 5. Spironolactone/Aldosterone antagonist

Question 3

what are the compensatory or adaptive mechanisms that maintains cardiac reserve in Heart Failure?

Answer 3

• Frank-starling mechanism: the contractility of heart increases in response to an increase in volume of blood filling the heart - activation of sympathetic nervous system - renin-angiotensin-aldosterone mechanism - myocardial hypertrophy and remodeling

Question 4

what is the role of physiologic compensatory mechanism of the progression of HF?

Answer 4

• when cardiac fx is impaired, the compensatory physiologic mechanisms maintain arterial pressure and perfusion of vital organs by maintaining normal cardiac output in face of heart disease. but their capacity to do so may ultimately overwhelmed. moreover, superimposed pathological changes in the heart muscle causes further functional disturbances. - chronic activation of sympathetic nervous system and renin-angiotensin-aldosterone axis is associated with remodeling of cardiac tissue, characterized by loss of myocytes, hypertrophy, and fibrosis. The geometry of heart becomes less elliptical and more spherical, interfering with its ability to efficiently function as a pump. this prompts additional neurohumoral activation, creating a vicious cycle that, if left untreated, leads to death.

Question 5

what are 3 benefits of ACE inhibitors in heart failure patients?

Answer 5

1. improve symptoms 2. slow progression of heart failure 3. prolong survival *also used in tx of hypertension

Question 6

hat is MOA of ACE inhibitors?

Answer 6

-blocks synthesis of angiotensin II, a potent vasoconstrictor -reduce aldosterone secretion from adrenal cortex resulting in net water loss

Question 7

which drugs are examples of ACE inhibitors? what are major side effects of ACE inhibitors?

Answer 7

Captopril (infrequently causes agranulocytosis or neutropenia) Enalapril *ACE inhibitors increase bradykinin in LU, causing chronic dry, irritating cough (other side effects include: HA, dizziness, abdominal pain, confusion, renal failure, impotence)

Question 8

1) which class of drugs are given as response to ACE inhibitors causing cough? 2) what is their MOA? 3) give an example of drug?

Answer 8

1) Angiotensin II Receptor Antagonist / ARB 2) these drugs interfere w binding of angiotensin II with its receptors. they do not produce cough and is also used in tx of hypertension 3) Losartan

Question 9

name a Direct Vasodilator? what is the dual action of this drug?

Answer 9

Minoxidil dual action: 1) vasodilator 2) hair growth (can be found in Rogain)

Question 10

what is MOA of Beta-blockers

Answer 10

-blocks sympathetic nervous system -reduce HT rate and reduce force of contraction

Question 11

1) what is MOA of Sprionolactone? 2) In what stage of Heart Failure is it used?

Answer 11

1) antagonizes aldosterone; stops retention of sodium & water so reduce edema 2) used for advanced cases of heart failure

Question 12

what is the purpose of using Diuretics in heart failure patients?

Answer 12

Heart Failure is associated with retention of sodium and water. Diuretics can control excessive fluid accumulation i and relive symptoms, but it does not stop progression of disease.

Question 13

what are 3 groups of diuretics?

Answer 13

1) Thiazide diuretics 2) Loop diuretics 3) Potassium sparing diuretics

Question 14

1) what is mechanism of Thiazide diuretics? 2) give an example? 3) what are undesirable effects? 4) it is contraindicated for?

Answer 14

1) inhibit sodium and chloride reabsorption in thick ascending loop and early distal tubule. this loss of ions increases urine volume. 2) Chlorthiazide 3) hyponatremia, hypokalemia, hyperglucemia, hyperuricemia, hypercalcemia 4) contraindicated in gout bc of hyperuricemia

Question 15

1) what is MOA of Loop diuretics? 2) give an example? 3) what are undesirable effects?

Answer 15

1) inhibit chloride reabsorption in ascending loop of Henle. used in tx of pulmonary edema bc of their potent and rapid action 2) Furosemide, Ethacrynic acid (most ototoxic) 3) ototoxic (deafness - KD opens to ears), hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, hyperglycemia, hyperuricemia

Question 16

1) what is MOA of Potassium sparing diuretics? 2) give an example? 3) what are undesirable effects?

Answer 16

1) enhance sodium excretion and retain potassium by action in distal tubule. often used in combination with other diuretics to help maintain potassium balance 2) Spironolactone 3) hyperkalemia (*only drug to do this in this group, other two groups cause HYPO-kalemia / potassium)

Question 17

name 3 groups of drugs that enhance contractility of heart in heart failure patients?

Answer 17

1) Cardiac glycosides 2) Sympathomimetics 3) Phosphodiasterase inhibitors

Question 18

1) what is MOA of Cardiac glycosides? 2) give an example? 3) what is the importance of its therapeutic index?

Answer 18

1) more calcium = forceful contraction Inhibits Na+ -K+ -ATPase. this causes increase in level of sodium ions in myocytes, which leads to rise in level of intracellular calcium ions. this occurs bc of sodium/calcium exchanger on the plasma membrane depends on constant inward sodium gradient to pump out calcium. 2) Digoxin : decreases sodium concentration gradient and the subsequent calcium outflow, thus raising calcium concentration in myocardiocytes. thus force of myocardial contraction is increased. (calcium binds to troponin, so contraction is more forceful) 3) has low therapeutic index - which means that the plasma concentration that causes serious toxicity is only slightly higher than the therapeutic dose. * Toxicity can manifest as arrhythmia, anorexia, nausea, diarrhea, drowsiness, fatigue, visual disturbance

Question 19

give examples of Sympathomimetics?

Answer 19

• Dobutamine: β1 agonist - Dopamine: in patients with impaired renal fx, the use of dopamine (instead of dobutamine) may preserve renal blood flow and, as aresult, renal fx

Question 20

what are 3 groups of drugs used in tx of angina pectoris?

Answer 20

1) organic nitrates 2) β - Blockers 3) Calcium channel blockers

Question 21

How does Angina Pectoris occur?

Answer 21

• occurs when coronary blood flow is insufficient to meet the oxygen demands of myocardium leading to ischemia - due to an imbalance bt the supply (perfusion) and demand of heart for oxygenated blood - >90% cases are due to coronary artery atherosclerosis -in the setting of coronary artery obstruction, ischemia can be aggravated by an increase in heart energy demand as occurs in conditions, such as increase heart rate (tachycardia)

Question 22

1) what is mechanism by which organic nitrates cause relaxation of vascular smooth muscle?
2) what are their common side effects
3) what is their interaction with sildenafil?

Answer 22

1) - they dilate the large myocardial arteries to increase blood supply of heart
- they also reduce cardiac preload by reducing venous tone
- increase nitrates –> increase nitric oxide –> increase cGMP –> increase Dephosphorylation of myosin light chain –> vascular smooth muscle relaxation
2) common side effects: HA and postural hypotension are
3) Sildenafil (viagra) potentiates the action of nitrates thereby causing dangerous hypotension. an interval of at least 6 hrs bt ingestion of 2 drugs is recommended.

Question 23

1) what is drug of choice for ACUTE CORONARY SPASM?
2) what is common route of its administration?

Answer 23

1) Nitroglycerine
2) administered SUBLINGUALLY for rapid onset of action (2 min), but it can be applied transdermally for a longer duration of action

Question 24

1) what is the MOA of Beta-blockers in relieving angina pectoris?
2) which group of patients are they particularly useful for?
3) how these drugs should be withdrawn?

Answer 24

1) they decrease oxygen demands of myocardium by lowering both the rate and force of contraction of heart
2) they are particulary useful for tx of patients with myocardidal infarction, and have been shown to prolong survival
3) gradually tapered off over 5 - 10 days to avoid rebound angina or hypotension

Question 25

1) that is MOA of calcium blockers in reliving angina pectoris? 2) give examples?

Answer 25

1) they block calcium influz into smooth muscle cells of arteries causing them to dilate 2) Diltiazem, Amlodipine

Question 26

Give pathogenesis of Hypertension

Answer 26

* HBP develops when blood volume is large compared to avaliable space in blood vessels * control of blood pressure is complex and involves vascular, cardiac, and renal physiology * mean arterial pressure = cardiac output x periphreal resitance * according to this equation, a decrease in either cardiac output or peripheral resistance will decrease blood pressure. Conversely, if HBP is present, something must have increased one of the 2 variables. a number of factors will increase cardiac output, including increased HR, increased contractility, and increased in sodium and water retention. Vasoconstriction will increase peripheral resistance.

Question 27

what is goal of antihypertensive therapy?

Answer 27

* diuretics can be used to decrease blood volume * drugs to interfere with renin-angiotensin system, which is intimately involved in salt and water balance in body * drugs to decrease peripheral vascular resistance or cardiac output. this can be done with direct-acting vasodilators or by using agents that block sympathetic nervous output

Question 28

name 10 groups of drugs used to treat hypertension?

Answer 28

1) Diuretics 2) β-Blockers 3) ACE inhibitors 4) Angiotensin II Receptor Antagonist (ARBs) 5) Calcium channel blockers 6) α - Blockers 7) Central acting adrenergic drugs 8) drugs affecting neurotransmitter uptake or release 9) direct vasodilators 10) drugs used in hypertensive crisis

Question 29

1) what is MOA of diuretics in lowering blood pressure? 2) what is the first line drug therapy for hypertension?

Answer 29

1) eliminates excess salt and water from body 2) diuretics

Question 30

1) what is the MOA of Beta-blockers in lowering blood pressure? 2) what concomitant disease with hypertension, are the beta-blockers particularly useful for? 3) give examples of drugs

Answer 30

1) they prevent sympathetic stimulation of heart thereby causing decreased heart rate and cardiac output; similar to ACE inhibitors, β-blockers may not be effective in lower BP in African American patients 2) particularly useul in patients with angina or those with migraines 3) Atenolol, Metoprolol

Question 31

which 2 groups of hypertensive patient, are the ACE inhibitors particularly useful for?

Answer 31

particularly useful in hypertension that is result of increased renin levels, and in diabetes patients with hypertension (bc they do not affect glucose levels / protects KD in longtern diabetic patients)

Question 32

which group of hypertensive patient is Calcium channel blockers particularly useful for?

Answer 32

African-American hypertensive patients and patient older than 55 yrs old

Question 33

which drug is suitable to tx pregnant hypertensive patients?

Answer 33

Methyldopa [is a Central acting adrenergic drug, it blocks norephinephrine in CNS, so block cardiac center in medulla and thus less sympathetic stimulation; has mininal effect on fetus]

Question 34

1) what is hypertensive emergencies. 2) which drug tx hypertensive emergency and what is the MOA of this drug?

Answer 34

1) diastolic BP is 120 mm Hg or more, and/or systolic BP is 180 mm Hg ore more, with evidence of an associated organ damage, such as stroke, MI, angina pectoris, encephalopathy, cerebral hemorrhage etc 2) **Sodium Nitroprusside** is used * give IV; causes prompt vasodilation; capable of reducing BP in all patients regardless of cause of hypertension * poisonous if given orally bc of its hydrolysis to cyanide, antidote is sodium thiosulfate

Question 35

what is pathomechanism of hemostasis (stopage of bleeding)

Answer 35

* there are 3 phasese: vascular, platelet and coagulation tissue injury --\> transient vasoconstriction --\> platelet aggregation --\> activation of intrinsic and extrinsic pathways of coagulation --\> common pathway --\> formation of insoluble firin clot * fibrinolytic phase that follows prevents the clotting process from spreading out of control beyond the site of injury [plasminogen in blood is converted to plasmin by plasminogen activator] * platelets respond to tissue injury by adhering to site of injury, they then release granules containing chemical mediators that promote aggregation * factors released by platelets and injured tissue cause activation of coagulation cascade. this results in formation of thrombin, which in turn converts fibrinogen to firbin. the subsequent cross-linking of fibrin strands stabilize the clot.

Question 36

what is MOA of Asprine?

Answer 36

* inhibits platelet aggregation by inhibiting thromboxane A2 synthesis in the platelets, and thus prolongs bleeding time * reduce risk of MI and stroke

Question 37

What is MOA if Clopidegrol?

Answer 37

blocks platelet aggregation by irreversibly inhibiting the binding of ADP to its receptors on platelets and, thus inhibit the activation of GP IIb/IIIa receptros required for platelets to bind to fibrinogen; thus it blocks platelet aggregation

Question 38

what is MOA of Abciximab?

Answer 38

prevent platelet aggregation by blocking the binding of fibrinogen to the glycoprotein IIb/IIIa receptor on surface of platelet