Antihypertensive Drugs

Question 1

Classification of anti-hypertensives by site or mechanism

Answer 1

A. Sympatholylic drugs
B. Calcium channel blockers (CCB)
C. Angiotensin-converting enzyme Inhibitors(ACEI)
D. Angiotensin II receptor antagonists (ARB)
E. Vasodilators
F. Diuretics

Question 2

Cardioselective/β1-selective blockers

Answer 2

NABABEM

Nebivolol
Acebutolol
Bisoprolol
Atenolol
Betaxolol
Esmolol
Metoprolol

Question 3

Special properties of cardioselective drugs

Answer 3

Cardioselective drugs (e.g. atenolol, metoprolol, bisoprolol, nebivolol) inhibit β1-receptors with less effect on bronchial and vascular β2-receptors.

Question 4

MOA of Beta blockers

Answer 4

• Reduce CO
• Reduce inotropy and chronotropy
• Inhibit renin secretion

Question 5

MOA of beta agonists

Answer 5

Gs activated
Adenylyl cyclase increased
Increased cAMP
PKA activated
Increased Ca

Question 6

Adverse effects of beta blockers

Answer 6

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.

Question 7

MOA of alpha-1 antagonists

Answer 7

They block ADR and NA in blood vessels; preventing vasoconstriction and reducing peripheral PR and BP

Question 8

Examples of alpha-1 antagonists

Answer 8

Doxazosin
Prazosin
Tamsulosin
Terazosin
Phenoxybenzamine

Question 9

MOA of centrally-acting sympatholytics

Answer 9

The alpha-2 ADRs located in the CNS inhibit NE release leading to reduced BP

Question 10

Examples of centrally-acting sympatholytics

Answer 10

Clonidine
Guanabenz
Guanfacine
Alpha methyldopa

Question 11

Examples of adrenergic neuron blockers

Answer 11

Reserpine
Guanadrel

Question 12

Examples of DHP CCB

Answer 12

Amlodipine
Felodipine
Nimodipine
Nicardipine

Question 13

Examples of non-DHP CCB

Answer 13

diltiazem
verapamil

Question 14

MOA of CCB

Answer 14

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.

Question 15

Examples of ACEIs

Answer 15

Captopril
enalapril
fosinopril
lisinopril
perindopril

Question 16

ACEIs MOA

Answer 16

They inhibit the activity of angiotensin-converting enzyme(ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.

Question 17

ACEIs PK

Answer 17

• 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.

Question 18

How exactly does an ACEI exert its effects?

Answer 18

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.

Question 19

Adverse effects of ACEIs

Answer 19

• 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.

Question 20

Angiotensin II receptor antagonists examples

Answer 20

candesartan
eprosartan
irbesartan
losartan

Question 21

Examples of arterial vasodialators

Answer 21

Hydralazine
Minoxidil
diazoxide

Question 22

Examples of venous vasodilators

Answer 22

Sodium nitroprusside

Question 23

Potential drug targets for managing HTN

Answer 23

• CNS, ANS: decrease sympathetic tone
• Heart: decrease cardiac output
• Veins: dilate => decrease preload
• Arterioles: dilate => decrease afterload
• Kidneys: increase diuresis; inhibit RAA system

Question 24

Which drugs are used to reduce LV systolic performance?

Answer 24

Negative inotropes (betablockers (metoprolol, atenolol, propranolol) and calcium channel blockers (verapamil, diltiazem)

Question 25

Which drugs are used to reduce blood volume and thus drop LVEDV: LV end-diastolic volumes(LVEDV)

Answer 25

diuretics (thiazide – hydrochlorothiazide, loop diuretics – furosemide, bumetanide and potassium sparing diuretics – spironolactone, amiloride, triamterene

Question 26

Which drugs are used to reduce venous tone and thus venous return?

Answer 26

Central sympatholytics such as clonidine

Question 27

Which drugs are used to reduce arterial tone (i.e. resistance)?

Answer 27

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)