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Pharmacology > Antihypertensive Drugs > Flashcards

Antihypertensive Drugs Flashcards

1
Q

Major groups of antihypertensive drugs

A

Diuretics (thiazide, loop, potassium-sparing), sympatholytic, angiotensin inhibitors and vasodilators

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2
Q

Thiazide and related diuretics - MoA

A

Mechanism of decrease BP stems from their ability to increase sodium and water excretion.
When they are first administrated, the drug decreases blood volume and thereby decreases cardiac output. When adm is continued over weeks and months they also decrease peripheral vascular resistance (PVR), and this appear to account for much of their long term antihypertensive effect. The decrease PVR may result from a reduction in the sodium content of arteriolar smooth muscle cells, which decrease muscle contraction in response to vasopressor agents such as norepinephrine and angiotensin.

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3
Q

Thiazide and related diuretics - Adverse effects

A

Hypokalemia –> cardiac arrhythmias and muscle weakness.
Elevate plasma levels of: glucose, uric acid and lipids in some pat.
Hematologic toxicity
Aggravate hepatic disease and diabetes
Compensatory increase in renin secretion
Blood cell deficiencies

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4
Q

Thiazide and related diuretics - Interactions

A

Increase serum levels of lithium. Hypotensive effect decreased by NSAIDs and augmented by ACE inh.

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5
Q

Thiazide diuretics

A

Hydrochlorothiazide
Indapamide
Chlorthalidone

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6
Q

Hydrochlorothiazide - Indication

A

Initial treatment of persons with mild to moderate hypertension.
Thiazide diuretic most often used to treat hypertension.

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7
Q

Indapamide - Indication and benefit

A

Hypertension and the risk of stroke and MI.

Causes vasodilation via calcium channel blockade

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8
Q

Loop diuretics - MoA

A

Greater natriuretic effect.
Less effective than thiazide, they are reserved for use in hypertensive pat who have poor renal function and serum creatinine level greater than 2,3mg/dL.

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9
Q

Potassium - sparing diuretics - MoA

A

Mild natriuretic effect and they reduce renal potassium excretion –> prevent hypokalemia by thiazide drugs/ loop diuretics

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10
Q

Potassium - sparing diuretics - Adverse effects

A

Hyperkalemia

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11
Q

Potassium - sparing diuretics - Interactions

A

Hyperkalemic effect increased by ACE inh and potassium supplements.

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12
Q

Potassium - sparing diuretics

A

Amiloride
Spironolactone
Eplerenone
Triamterene

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13
Q

Spironolactone and Eplerenone - Indication

A

Hypertension that cannot be controlled with combinations of three or more other agents.

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14
Q

Alpha-adrenoceptor antagonists

A

Doxazosin
Prazosin
Terazosin

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15
Q

Alpha-adrenoceptor antagonists - MoA

A

Effectively inhibit sympathetic stimulation of arteriolar contraction –> vasodilation and decrease vascular resistance, BUT several disadvantages.

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16
Q

Alpha-adrenoceptor antagonists - Indication

A

Not recommended for the initials treatment of hypertension, but can be added with other drugs when BP is not adequately controlled.

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17
Q

Alpha-adrenoceptor antagonists - Adverse effect

A 
Reflex activation of SNS: increased HR, contractile force, circulating NE --> increased myocardial oxygen requirements
Orthostatic hypotension
“first dose” syncope
Dizziness
Fluid retention
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18
Q

Alpha-adrenoceptor antagonists - Interactions

A

Hypotensive effect increased by beta-blockers and potassium supplements.

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19
Q

Beta-Adrenoceptor antagonists

A 
Nonselective:
Nadolol
Pindolol
Propranolol
Timolol
Selective:
Atenolol
Esmolol
Nebivolol
Mixed alpha and beta: Carvedilol and labetalol
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20
Q

Beta-Adrenoceptor antagonists - MoA

A

Blockade of beta1 receptors reduces cardiac output by decreasing the heart rate and contractility. Block of these receptors in renal juxtaglomerular cells inhibit renin secretion –> reduces the formation of Angiotensin II and the release of Aldosterone.
The drugs also appear to reduce sympathetic outflow from the central nervous system.

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21
Q

Beta-Adrenoceptor antagonists - Indication

A

Beneficial in hypertensive persons with other cardiovascular diseases. In coronary heart disease- reduce myocardial ischemia and lower risk of MI.
In persons with previous MI they are cardioprotective- prevent sudden death, by decreasing HR and the risk of ventricular arrhythmias.
In heart failure: improves symptoms and survival.

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22
Q

Beta-Adrenoceptor antagonists - Adverse effects

A

Fatigue, depression, vivid dreams, decreased exercise capacity
Bradycardia
Bronchoconstriction
Impaired glycogenolysis

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23
Q

Beta-Adrenoceptor antagonists - Contraindications and Interactions

A

Contraindications:
Nonselective: Contraindicated in pt with asthma or COPD
In diabetics, delay recovery from hypoglycemia by blocking glycogenolysis and mask symptoms of hypoglycemia.

Interactions:
Cardiac depression increased by diltiazem and verapamil.
Hypotensive effect decreased by NSAID

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24
Q

Labetalol - Indication

A

Treats both chronic hypertension and hypertensive emergencies.

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25
Q

Carvedilol and Labetalol - Adverse effects

A

Orthostatic hypotension

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26
Q

Esmolol - Indications

A

Treat hypertension in surgical procedures and in persons with hypertensive emergencies.

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27
Q

Nebivolol - Indications

A

Hypertension in pat with heart failure, diabetes and cardiac arrhythmias.

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28
Q

Centrally acting drugs

A

Clonidine
Guanfacine
Methyldopa

29
Q

Centrally acting drugs - MoA

A

Reduce sympathetic outflow from the central vasomotor center to the circulation primarily through the activation of alpha2 adrenoceptors in the brain stem medulla
Lower BP by reducing vascular resistance, while having little effect on HR and CO

30
Q

Centrally acting drugs - Adverse effects

A

Sedation
Dry mouth
Impaired mental acuity
Severe rebound hypertension can occur if they are discontinued abruptly

31
Q

Centrally acting drugs - Interactions

A

Hypotensive effect decreased by tricyclic antidepressants

Sedative effect increased by CNS depressants

32
Q

Clonidine - Indication

A

Hypertensive urgencies in the outpatient setting (slowly reduced BP with one single oral dose)

Reduce SNS symptoms of alcohol, opioid or nicotine withdrawal.

33
Q

Methyldopa - MoA

A

Has to be converted to an active metabolite (methyl norepinephrine) by central neurons, which then activates alpha2.

34
Q

Methyldopa - Indication

A

Hypertension in pregnant women.

35
Q

Methyldopa - Adverse effects

A

Immunologic effects including:
Coombs positive hemolytic anemia
Autoimmune hepatitis

Lupus-like syndrome

36
Q

Methyldopa - Interactions

A

Hypotensive effect increased by levodopa

37
Q

Angiotensin-Converting enzyme inhibitors

A 
Benazepril
Captopril
Enalapril
Fosinopril
Lisinopril
Quinapril
Ramipril
38
Q

Angiotensin-Converting enzyme inhibitors - MoA

A 
Act by binding to zinc atom at the enzyme’s active site. Lower BP by reducing vascular resistance. Decrease both arterial and venous pressure --> reduced CO and cardiac preload.
By reducing angiotensin-stimulated aldosterone secretion: ACE inhibitors prevent the compensatory increase in sodium retention and plasma V that can occur with some other antihypertensive drugs.
Inactivated bradykinin (vasodilator) --> act partly by inhibiting its degradation
Decreases stimulation of growth factors of cells --> decreases cardiac remodeling
39
Q

Angiotensin-Converting enzyme inhibitors - Indication

A

Mild to severe hypertension
Protect against stroke and MI
Hypertension in pat with coexisting heart failure, MI, chronic kidney disease or diabetes mellitus.
They increase cardiac output and survival in persons with heart failure.
Reduce incidence of overt heart failure and increase survival in pt with MI and significant left ventricular dysfunction
Renoprotective effect in diabetic pt who exhbit early signs of renal impairment (albuminuria, increaser serum creatinine).

Reduce risk of primary and secondary stroke

40
Q

Angiotensin-Converting enzyme inhibitors - Adverse effect

A

Hyperkalemia
Hyponatremia
Dry cough (due to increase of bradykinin)
Angioedema (swollen lips, face and throat)
Rash
Abnormal taste sensation
Neutropenia

Fetal and neonatal injury
Renal failure in patients with bilateral renal artery stenosis(due to their dependency on angiotensin II to maintain renal blood flow and glomerular filtration)

41
Q

Angiotensin-Converting enzyme inhibitors - Interaction and Contraindications

A

Interactions
Augmented by diuretics and CCB.
Can interact with potassium sparing diuretics and supplement to increase potassium levels –>hyperkalemia
They also increase lithium levels –> lithium toxicity
NSAIDs (esp Ibuprofen) can impede the effect of ACE inh.

Contraindications:
Pregnancy because of fetal and neonatal injury
Bilateral renal artey stenosis because it can cause renal failure due to the dependency on angiotensin II to maintain renal blood flow and glomerular filtration

42
Q

Enalapril - Indication

A

Pt with left ventricular failure

43
Q

Angiotensin receptor blockers - MoA

A

These drugs selectively block AT1 receptors in various tissues and thereby reduce vasoconstriction, aldosterone secretion, sodium reabsorption by the proximal tubule and norepinephrine release from sympathetic nerve terminals.

44
Q

Angiotensin receptor blockers - Adverse effects and contraindication

A

Hyperkalemia, neutropenia, elevated serum levels of hepatic aminotransferase
Fetal injury and death

Contraindication: pregnancy

Rarely cause dry cough that occurs with ACE inh.

45
Q

Angiotensin receptor blockers - Interactions

A

Serum levels increased by cimetidine and decreased by phenobarbital

46
Q

Angiotensin receptor blockers

A 
Candesartan
Irbesartan
Losartan
Telmisartan
Valsartan
47
Q

Losartan - Indication

A

Greater reduction of left ventricular hypertrophy and risk of stroke and new-onset diabetes

48
Q

Telmisartan - MoA

A

Increase insulin sensitivity by activating peroxisome proliferator-activated receptor-gamma.

49
Q

Direct renin inhibitor

A

Aliskiren

50
Q

Aliskiren - MoA

A

Binds to the active site of renin, preventing cleavage of angiotensinogen and formation of angiotensin I.
Lowers plasma renin activity and levels of angiotensin I and angiotensin II.
Can protect against compensatory increases in angiotensin II evoked by other drugs.

Equal or superior BP-lowering ability compared with other drugs and a placebo-like side effect profile.

51
Q

Aliskiren - Indication and adverse effects

A

High blood pressure

Hyperkalemia

52
Q

Aliskiren - Interactions

A

Reduces serum levels of furosemide

Cyclosporine increases levels of aliskerin

53
Q

Calcium channel blockers - MoA

A

By blocking calcium ion channels in the plasma membranes of smooth muscle, the ccbs relax vascular smooth muscle and causes vasodilation. They have greater effect on arteriolar smooth muscle then venous, effect on BP is mainly because a reduction in PVR.

54
Q

Calcium channel blockers - Indication

A 
Hypertension
Angina pectoris
Peripheral vascular disorders
Cardiac arrhythmias
Hypertension in Asthma 
Protect against: stroke, coronary heart disease, kidney disease.

Hypertensive pt who have asthma or are of African heritage

55
Q

Calcium channel blockers - Adverse effects

A

Dihydropyridine CCB: Reflex tachycardia
Gingival hyperplasia in persons with poor dental care
Dizziness, edema, headache

56
Q

Calcium channel blockers - Interaction

A

Serum levels increased by azole antifungal agents, cimetidine and grapefruit juice

57
Q

Calcium channel blockers

A 
Diltiazem
Verapamil
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
58
Q

Diltiazem and Verapamil - MoA and Indication

A

Significant effect on cardiac tissue and can reduce heart rate and cardiac output.

Reduce protein excretion in patients with kidney disease and may be used with ACE inh or ARB for this purpose.

59
Q

Diltiazem and Verapamil - Adverse effects

A

AV block, bradycardia, constipation, dizziness, edema, gingival hyperplasia, headache, heart failure

60
Q

Diltiazem and Verapamil - Interactions

A

Increases serum levels of carbamazepine, digoxin, theophylline. Decreases serum levels of lithium

61
Q

Nicardipine - Indications

A

Hypertensive emergencies

62
Q

Vasodilators

A

Hydralazine
Minoxidil
Nitroprusside
Fenoldopam

63
Q

Hydralazine

Minoxidil - Indication

A

Moderate to severe hypertension resistant to other drugs, in combo with other antihypertensive drugs.
Minoxidil: alopecia

64
Q

Hydralazine

Minoxidil - Adverse effects

A

Reflex tachycardia
Fluid retention
Precipitate angina in susceptible patients. –> these side effects when given alone, therefor given with diuretics and beta blockers.

Hydralazine- lupus like syndrome
Minoxidil- hypertrichosis(excessive hair growth)- given topical for alopecia.

65
Q

Hydralazine

Minoxidil - Interactions

A

Hypotensive effect decreased by NSAIDs

66
Q

Nitroprusside - Indications

A

Management of Hypertensive emergencies

67
Q

Nitroprusside - Adverse effect

A 
Dizziness
Headache
Increased intracranial pressure
Methemoglobinemia
Thiocyanate and cyanide toxicity
68
Q

Fenoldopam - MoA and Indication

A

Activates vascular dopamine D1 receptors and produces vasodilation in systemic vascular beds including coronary, renal and mesenteric vessels.

Hypertensive emergencies

69
Q

Fenoldopam - Adverse effects

A

Hypokalemia
Headache
Nausea

Pharmacology (55 decks)

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