Anti-hypertensive drugs Flashcards
List the classes of anti-hypertensive drugs (10)
1) Diuretics
2) Angiotensin-converting Enzyme (ACE) inhibitors
3) Angiotensin (AT1) blockers
4) Centrally acting
5) ß-adrenergic blockers
6) ß and α – adrenergic blockers
7) α – adrenergic blockers
8) Calcium Channel Blockers (CCB)
9) K+ Channel activators
10) Vasodilators
Diuretics MOA
diuresis – depletion of Na+ and body fluid volume – decrease in cardiac output
examples of diuretics used in hypertension.
thiazide- hydroclorothiazide
high ceiling-furosemides
potassium sparing diuretics
Thiazide diuretics – adverse effects
hint; hypers and hypoes
hypovolemia
hypokalemia
hyperuricemia
hyperglycemia
hyperlipidemia
K+ sparing diuretics as Anti-HTN
useful in combination therapy with thiazide,
Moduretic (Amiloride + HCT) is popular one
thiazide as Anti-HTN
Modified thiazide: indapamide
Indole derivative, long duration of action, It is a lipid neutral.
Loop diuretics as Anti-HTN
Used only in complicated cases – CRF, CHF marked fluid retention cases
Angiotensin Converting Enzyme (ACE) Inhibitors
Captopril,
Lisinopril
Enalapril
Ramipril
Captopril MOA
and abolishes pressor action of Angiotensin-I and not Angiotensin-II and does not block AT receptors
PKinetics of Captopril
Available only orally, 70% - 75% is absorbed
Partly absorbed and partly excreted unchanged in urine
Food interferes with its absorption
Half life: 2 Hrs, but action stays for 6-12 Hrs
Captopril – Pharmacological actions
Lowers PVR and thereby mean, systolic and diastolic BP
Initially correlates with renin-angiotensin status but chronic administration is independent of renin activity.
No effect on Cardiac output, contractility, heart rate
Postural hypotension is not a problem
Renal blood flow is maintained – greater dilatation of vessels
Indications for ACE inhibitors
diabetic nephropathy
myocardial infraction
heart failure
systolic dysfunction
Captopril – Adverse effects
Cough
Hyperkalemia
Hypotension
Acute renal failure
teratogenic
Angioedema
Rashes, urticaria
altered taste
Neutripenia
Contraindications for captopril
Pregnancy,
bilateral renal artery stenosis,
hypersensitivity
hyperkalaemia
Enalapril
It’s a prodrug – converted to enalaprilat
Advantages over captopril:
Longer half life
only ACE inhibitor available intravenously, Absorption not affected by food.
Ramipril
It is also a pro-drug with long half life
Tissue specific – Protective of heart and kidney
Uses: Diabetes with hypertension, CHF, AMI and cardio protective in angina pectoris
Lisinopril
It’s a lysine derivative
Not a prodrug
Slow oral absorption
Absorption not affected by food and not metabolized – excrete unchanged in urine
Long duration of action
Angiotensin Receptor Blockers (ARBs)
Losartan-specific AT1 blocker
Losartan (ARBs) MOA
These drugs block the AT1 receptors, decreasing the activation of AT1 receptors by angiotensin II and block aldosterone secretion, thus lowering blood pressure and decreasing salt and water retention.
Theoretical superiority over ACEIs
Cough & angioedema is rare –
no interference with bradykinin and other ACE substrates
Complete inhibition of AT1 – alternative remains with ACEs
Result in indirect activation of AT2 – vasodilatation (additional benefit)
Clinical benefit of ARBs over ACEIs – not known
Pharmacokinetic of losartan
Absorption not affected by food but unlike ACEIs its bioavailability is low
High first pass metabolism
Highly bound to plasma protein
ADRs of ARB (losartan)
like ACE Inhibitors
Beta-adrenergic blockers
Non selective: Propranolol, nadolol
Cardioselective: Metoprolol, atenolol
Beta-adrenergic blockers MOA
reduce blood pressure primarily by decreasing cardiac output. They may also decrease sympathetic outflow from the (CNS) and inhibit the release of renin from the kidneys, thus decreasing the formation of angiotensin II and the secretion of aldosterone.
