Antihypertensive Drugs Flashcards
Classification of anti-hypertensives by site or mechanism
A. Sympatholylic drugs
B. Calcium channel blockers (CCB)
C. Angiotensin-converting enzyme Inhibitors(ACEI)
D. Angiotensin II receptor antagonists (ARB)
E. Vasodilators
F. Diuretics
Cardioselective/β1-selective blockers
NABABEM
Nebivolol
Acebutolol
Bisoprolol
Atenolol
Betaxolol
Esmolol
Metoprolol
Special properties of cardioselective drugs
Cardioselective drugs (e.g. atenolol, metoprolol, bisoprolol, nebivolol) inhibit β1-receptors with less effect on bronchial and vascular β2-receptors.
MOA of Beta blockers
- Reduce CO
- Reduce inotropy and chronotropy
- Inhibit renin secretion
MOA of beta agonists
Gs activated
Adenylyl cyclase increased
Increased cAMP
PKA activated
Increased Ca
Adverse effects of beta blockers
Intolerance – fatigue, cold extremities, erectile dysfunction;
Airways obstruction – Contra-indicated in asthma
Decompensated heart failure – β-adrenoceptor antagonists are contraindicated –use cardioselective
β-adrenoceptor antagonists can mask symptoms of hypoglycaemia and the rate of recovery
Heart block – worsen heart block.
Metabolic disturbance - worsen glycaemic control in type 2 diabetes mellitus.
MOA of alpha-1 antagonists
They block ADR and NA in blood vessels; preventing vasoconstriction and reducing peripheral PR and BP
Examples of alpha-1 antagonists
Doxazosin
Prazosin
Tamsulosin
Terazosin
Phenoxybenzamine
MOA of centrally-acting sympatholytics
The alpha-2 ADRs located in the CNS inhibit NE release leading to reduced BP
Examples of centrally-acting sympatholytics
Clonidine
Guanabenz
Guanfacine
Alpha methyldopa
Examples of adrenergic neuron blockers
Reserpine
Guanadrel
Examples of DHP CCB
Amlodipine
Felodipine
Nimodipine
Nicardipine
Examples of non-DHP CCB
diltiazem
verapamil
MOA of CCB
Calcium channel blockers (CCB) are smooth muscle relaxants. They block the entry of calcium into muscle cells in artery walls blocking voltage-dependent L-type Ca2 channels.
Examples of ACEIs
Captopril
enalapril
fosinopril
lisinopril
perindopril
ACEIs MOA
They inhibit the activity of angiotensin-converting enzyme(ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.
ACEIs PK
- All active when administered orally, but are highly polar and are eliminated in the urine.
- Enalapril is a prodrug and requires metabolic conversion to active metabolites (e.g. enalaprilat).
- Many of these agents have long half-lives permitting once daily dosing; captopril is an exception.
How exactly does an ACEI exert its effects?
ACE catalyses the cleavage of a pair of amino acids from short peptides, thereby ‘converting’ the inactive decapeptide angiotensin I to the potent vasoconstrictor angiotensin II. It also inactivates bradykinin – a vasodilator peptide.
- ACEIs lower blood pressure by reducing angiotensin II and perhaps also by increasing vasodilator peptides, such as bradykinin.
Angiotensin II causes aldosterone secretion from the zona glomerulosa of the adrenal cortex and inhibition of this contributes to the antihypertensive effect of ACE inhibitors.
Adverse effects of ACEIs
- First-dose hypotension.
- Cough – Usually dry cough, due to accumulation of bradykinin
- Angio-oedema and Urticaria – due increased kinin
- Proteinuria – attributable to its sulphhydryl group
- Taste abnormality
- Teratogenicity
- Renal failure (Functional) – in bilateral renal artery stenosis
- Rash
Hyperkalaemia - that decrease renal excretion of potassium.
Angiotensin II receptor antagonists examples
candesartan
eprosartan
irbesartan
losartan
Examples of arterial vasodialators
Hydralazine
Minoxidil
diazoxide
Examples of venous vasodilators
Sodium nitroprusside
Potential drug targets for managing HTN
• CNS, ANS: decrease sympathetic tone
• Heart: decrease cardiac output
• Veins: dilate => decrease preload
• Arterioles: dilate => decrease afterload
• Kidneys: increase diuresis; inhibit RAA system
Which drugs are used to reduce LV systolic performance?
Negative inotropes (betablockers (metoprolol, atenolol, propranolol) and calcium channel blockers (verapamil, diltiazem)
Which drugs are used to reduce blood volume and thus drop LVEDV: LV end-diastolic volumes(LVEDV)
diuretics (thiazide – hydrochlorothiazide, loop diuretics – furosemide, bumetanide and potassium sparing diuretics – spironolactone, amiloride, triamterene
Which drugs are used to reduce venous tone and thus venous return?
Central sympatholytics such as clonidine
Which drugs are used to reduce arterial tone (i.e. resistance)?
Effective arterial dilators include:
- angiotensin converting enzyme inhibitors (ACE inhibitors – lisinopril, captopril)
- angiotensin receptor blockers (ARB’s – valsartan, losartan)
- calcium channel blockers (nifedipine, amlodipine)
- potassium channel openers (minoxidil)
- nitric oxide donors (nitroprusside)
- alpha1 blockers (prazosin, terazosin, doxazosin)
- and mixed alpha and beta-blockers (labetalol)
