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Pharm > Antihypertensives 2 > Flashcards

Antihypertensives 2 Flashcards

1
Q
  1. What is Aliskiren?
A

Aliskiren is an renin inhibitor used to treat HTN. It inhibits the renin enzyme preventing the conversion of angiotensinogen to angiotensin I. The end result is a decreased in aldosterone production therefore decreased absorption of sodium and water.

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2
Q
  1. What are the adverse side effects of Aliskiren?
A
  1. Hyperkalemia
  2. Hypotension
  3. Angioedema (low risk)
  4. Acute renal failure – pts with bilateral renal artery stenosis
  5. Rash, fever, altered taste
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3
Q
  1. What are the different Ca2+ channel blocker drugs?
A
  1. Verapamil [non-dihydropyrdine]
  2. Diltiazem [non-dihydropyrdine]
  3. Nifedipine [dihydropyrdine]
  4. Amlodipine [dihydropyrdine]
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4
Q
  1. What is Verapamil?
A

Verapamil is one of the least selective calcium channel blockers thereby affecting both the heart and vascular SM. It is used to treat angina, supraventricular tachycardia, HTN, migraine and cerebral vasospasm.

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5
Q
  1. What is Diltiazem?
A

Diltiazem is a calcium channel blocker that affects both the heart and vascular SM. It is said to have a good side-effect profile and is used to treat angina, supraventricular tachycardia, HTN, and cerebral vasospasm.

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6
Q
  1. What are the the dihydropyrdine calcium channel blockers?
A

Nifedipine (1st generation) and Amlodipine (2nd generation) – these drugs have greater affinity for vascular calcium channels versus cardiac calcium channels therefore are more specific. They reduce the calcium entry into SM to cause coronary and peripheral vasodilation which will lower BP. These drugs are primarily used to treat HTN, but can also help with angina. They are not good with treating cardiac arrhythmias.

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7
Q
  1. What is the general mechanism of action for calcium blockers?
A

Calcium blockers block the voltage-sensitive calcium channel (L-type) preventing the entrance of calcium therefore causing myofibril/vascular relaxation.

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8
Q
  1. What are the clinical uses of calcium channel blockers?
A
  1. HTN – esp in black or elderly pts
  2. Useful in pts with asthma, diabetes, peripheral vascular disease
  3. Has intrinsic natriuretic effect therefore there is no need for diuretics
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9
Q
  1. What is a specific side effect to high-doses of short acting dihydropyridine calcium channel blockers?
A

These calcium channel blockers increase the risk of MI by causing excessive vasodilation that leads to reflex cardiac stimulation. Sustained release preparations are preferred.

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10
Q
  1. What are the adverse side effects of Verapamil?
A

Constipation, negative inotropic effects

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11
Q
  1. What are the adverse side effects of dihydropyridines?
A
  1. Hypotension
  2. Peripheral edema (esp in feet and ankles)
  3. Dizziness
  4. Headache
  5. Fatigue
  6. Gingival hyperplasia
  7. Flushing
  8. Reflex tachycardia
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12
Q
  1. What are the contraindications of calcium channel blockers?
A

Non-dihydropyridine (verapamil and diltiazem) should not be given to pts taking B blockers or who have 2nd or 3rd degree AV block, or severe LV systolic dysfunction. This is because there could be an exaggerated negative inotropic effect.

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13
Q
  1. What B blockers can be used to treat HTN and what receptors do each bind?
A
  1. Propranolol → non-selective B1 and B2 receptor antagonist
  2. Metoprolol and Atenolol [most common] → selective B1 receptor antagonists
  3. Pindolol → non-selective B1 and B2 partial agonist with intrinsic sympathomimetic activity [preferred B-blocker in pregnancy]
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14
Q
  1. What is the mechanism of action of B-blockers?
A

B-blockers inhibit the release of NE and renin (B1) decreasing angiotensin II and aldosterone secretion. The decrease in renin indirectly acts on the heart by decreasing CO. B-blockers can also act directly on the heart where they reduce CO , contractility and HR. There can be a blunt sympathetic reflex with exercise.

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15
Q
  1. What are the adverse effects of B-blockers?
A
  1. bradycardia
  2. CNS effects – fatigue, lethargy, insomnia, hallucinations
  3. Hypotension
  4. Decreased libido and impotence
  5. Disturbed lipid metabolism → increased TAGs and decreased HDL
  6. Hypoglycemia (B2 blockers)
  7. Drug withdrawal → therefore there is a need to taper off dose in pts
  8. Propranolol is contraindicated in asthmatics and COPD pts
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16
Q
  1. Which a1-blockers can be used to treat HTN? What is the mechanism?
A

Prazosin and Doxazosin are competitive a1-adrenoceptor blockers. They decrease peripheral vascular resistance and arterial BP by relaxing BOTH arterial and venous smooth muscle. Unlike thiazides and furosemides, there is sodium and water retention to decrease bp and decreased perfusion to kidneys so with chronic use Na+ and water retention needs to be managed. These drugs have more side effects than other antihypertensives, therefore are no recommended as first line treatments.
Because of a1 selective effect, the NE in the synapse is able to create a negative feedback mechanism on the a2 receptors thereby decreasing amt of NE released - this can help decrease the risk of reflex tachycardia.

17
Q
  1. What are the general clinical uses of a1-blockers?
A
  1. HTN
  2. BPH
  3. Heart failure
18
Q
  1. What are the adverse side effects of a1-blockers?
A
  1. orthostatic hypotension upon first dose or large increases in dose
  2. concomitant use of B-blockers may be necessary to blunt reflex tachycardia
  3. dizziness, drowsiness, headache, lack of energy, nausea, palpitations
  4. Doxazosin is shown to increase rate of congestive HF on its own
  5. Na+ and water retention - with chronic administration therefore you should administer with diuretic to minimize potential for edema
19
Q
  1. What is Labetalol?
A

This is a mixed a- and B-blocker that can be administered orally and parenterally. It is used in the management of HTN (even with pregnant women). It is generally given IV for a RAPID REDUCTION in BP during HYPERTENSIVE EMERGENCIES. An advantage of Labetalol is that there is a decrease in BP associated with a1-blockade WITHOUT the reflex tachycardia.

20
Q
  1. What are the adverse effects of mixed a- and B-blockers?
A

Orthostatic Hypotension upon first use

21
Q
  1. What is Clonidine?
A

Central a2-agonist that reduces sympathetic outflow by acting on presynaptic a2-adrenergic autoreceptors. This results in a decrease in peripheral vascular resistance and cardiac output therefore decreasing BP. It DOES NOT decrease renal blood flow or GFR. Clonidine is used in HTN management, including hypertensive crisis.

22
Q
  1. What are the adverse side effects of Clonidine?
A
  1. drowsiness, dry mouth, dizziness, headache, sexual dysfunction
  2. rebound HTN following abrupt withdrawal therefore avoid concomitant use with B-blockers
23
Q
  1. What is Methyldopa?
A

Central a2 agonist that is converted to a-methyldopamine and a-methylnorepinephrine centrally to diminish sympathetic outflow in CNS. By decreasing sympathetic outflow, there is a decrease in peripheral resistance → decrease BP (NO DECREASE IN CO). Renal blood flow also DOES NOT decrease. This is generally the treatment of choice for pregnancy-induced HTN (eclampsia).

24
Q
  1. What are the adverse side effects of Methyldopa?
A
  1. sedation, drowsiness, dizziness, nausea, headache, weakness, fatigue, sexual dysfunction
  2. nightmares, mental depression, vertigo
  3. development of positive Coombs test resulting in hemolytic anemia, hepatitis and drug fever
25
Q
  1. Which drugs are direct vasodilators?
A

Hydralazine and Minoxidil – these are NOT used as first-line anti-hypertensives. They act directly on vascular SM as relaxants. The vascular relaxation produces reflex tachycardia and increases plasma renin causing sodium and water retention. Major side effects can be prevented if combined with diuretic and B-blockers.

26
Q
  1. What is Hydralazine?
A

Direct vasodilator that can be given via IV or orally. It acts mainly on the arterioles and is used to treat pregnancy induced HTN or pre-eclampsia. As for non-pregnant people with HTN it is one of the last-lines of therapy.

27
Q
  1. What are the adverse effects of Hydralazine?
A
  1. fluid retention
  2. reflex tachycardia
  3. reversible lupus-like syndrome
  4. headache, nausea, sweating, flushing
  5. usually administered with B-blocker and thiazide
28
Q
  1. What is Minoxidil?
A

Direct vasodilator that causes direct peripheral vasodilation of arterioles. This is an oral treatment for severe-malignant HTN.

29
Q
  1. What are the adverse effects of Minoxidil?
A
  1. reflex tachycardia
  2. fluid retention
  3. Hypertrichosis → causes excessive hair growth
30
Q
  1. What are the treatments for pulmonary HTN?
A
  1. prostaglandins [epoprostenol]
  2. inhibitors of endothelin synthesis and action [bosentan]
  3. vasodilators [Sildenafil]
31
Q
  1. What is Epoprostenol?
A

Synthetic PGI2 that lower peripheral pulmonary and coronary resistance via a vasodilatory effect. It is given via continuous infusion. Adverse effects include flushing, headache, jaw pain, diarrhea and arthralgias.

32
Q
  1. What is Bosentan?
A

Nonselective endothelin receptor blocker that blocks both the initial transient depressor (ETA) and the prolonged pressor (ETB) responses to endothelin. This medication falls into pregnancy category X [aka DO NOT USE!].

33
Q
  1. What is Sildenafil?
A

Inhibitor of phosphodiesterase 5 (PDE5). It increase the amt of cGMP leading to smooth muscle relaxation. Adverse effects include headache, flushing, dyspepsia and cyanopsia. Contraindications include individuals on nitrates b/c they also give an increase in cGMP leading to a possible hypotensive crisis.

Pharm (28 decks)

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