anti-hypertensives

Question 1

Angiotensin converting enzyme inhibitor

Answer 1

Lisinopril, Captopril, Enalapril
MOA: inhibit ACE = decrease AngII = decrease vasoconstriction + decrease aldosterone = decrease peripheral vascular resistance + decrease Na+/H20 retention = decrease bp
Note: ACE-I is also also to prevent the breakdown of bradykinin into its inactive state = NO increases = vasodilation = decrease bp

Clinical uses
Hypertension (first line), cardiac failure, following MI (protective effects to prevent subsequent MI)

Adverse effects
Hypotension, acute renal failure, hyperkalemia (due to decrease aldosterone), angioedema and dry cough (due to bradykinin and substance P)

Contraindicated in pregnancy

Question 2

Ang II type 1 blockers

Answer 2

Losartan, Valsartan, Isosartan
MOA: Binds to AngII receptor to blocks its effects

Contraindicated in pregnancy

Question 3

beta-blockers

Answer 3

cardioselective for beta 1 = bisoprolol, atenolol
non-selective = carvedilol, propranolol
mixed = Nebivolol (beta 1 selective in low dose/ fast metabolisers)

MOA: decrease adenylate cyclase activated = decrease cAMP = decrease PKA = decrease opening of Ca2+ channels = decrease CICR = less activated actin-myosin complexes
note: since cAMP also leads to vasodilation in bronchial smooth muscles, beta blockers are more prone to bronchoconstriction = contraindicated in asthmatics

clinical uses = hypertension, cardiac failure, following MI, abnormal heart rhythms, anxiety disorders

Adverse effects = hypotension, bradycardia, AV nodal block, decrease exercise capacity, bronchoconstriction, “beta-blocker blues” - vivid dreams and clinical depression

Question 4

Calcium channel blockers - Dihydropyridines (DHPs) and Non-DHPs

Answer 4

Non-DHP = verapamil, diltiazem
DHP = nifedipine, amlodipine

note: DHP drugs have dihydropyridine structure that works better on decreasing smooth muscle vascular tone VS Non-DHP drugs have diff structure that works better on AV/SA node

lowering bp: Nifedipine = diltiazem = verapamil
vasodilator: Nifedipine > diltiazem > verapamil
cardiac depressant: verapamil > diltiazem > Nifedipine
amlodipine = stable angina, reduce risk of MI and stroke

Adverse effects
a. DHP = hypotension, heart failure, MI
b. non-DHP = cardiac depression (bradycardia, AV blocker, heart failure)

Question 5

Diuretics

Answer 5

Thiazides - hydrocholothiazide, indapamide

MOA: inhibit NaCl reabsorption by blocking Na+/Cl- transporter = H20 does not get reabsorbed = diuretic effect = reduce bp
note: action of thiazides depend on renal PG synthesis, thus NSAIDs that reduce PG synthesis interfere with thiazide actions

clinical uses: hypertension, congestive heart failure, nephrolithiasis (since Ca2+ is drawn into blood to neutralise charge of Na+ going out), nephrogenic diabetes insipidus

adverse effects
: hypokalemic metabolic acidosis
: hyponatremia
: hyperuricemia (increase risk of gout)
: hyperglycemia (increase risk of diabetes)

Question 6

2nd line antihypertensives

Answer 6

Hydralazine
Mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone)
alpha-blockers (prazosin, alfuzosin, terazosin)

Question 7

Alpha-adrenergic antagonists

Answer 7

Prazoin, Alfuzosin, Terazosin

MOA: oppose alpha-1 mediated vasocnstriction = decrease peripheral vascular resistance = decrease bp

Adverse effects = reflex tachycardia, palpitations, orthostatic hypotension, depression, urinary frequency

note: also indicated for symptomatic relief of urine retention due to BPH