4. Anti-hypertensive drugs

Question 1

describe the NICE guidelines for anti-hypertensive prescription (different steps)

Answer 1

Step 1:

• aged <55yrs: ACEi/ARB
• aged >55yrs OR Afro-Caribbean family origin: CCB

Step 2: ACEi/ARB + CCB

Step 3: ACEi/ARB + CCB + thiazide-like diuretic

Step 4 (resistant hypertension): ACEi/ARB + CCB + diuretic + further diuretic/B-blocker/a-blocker

Question 2

name 2 ACEi

Answer 2

ramipril

lisinopril

Question 3

describe the MOA of ACEi

Answer 3

Competitive ACE inhibitors… decreased AngII formation and decreased bradykinin breakdown:

1. arteriolar vasodilation (+ some venodilation) - due to decreased AngII and increased bradykinin
2. decreased aldosterone release (so decreased Na and H2O retention)

Question 4

describe the most common side effect of ACEi

Answer 4

dry cough (10-15%) due to bradykinin accumulation and irritation of lung tissue

Question 5

describe 3 rarer adverse effects of ACEi

Answer 5

1. angio-oedema (rare but more common in black pop.)
2. renal failure (inc. renal artery stenosis)
3. hyperkalaemia

Question 6

describe the MOA of ARBs

Answer 6

Bind to Ang AT1 receptors:

1. vasodilation - due to decreased AngII-mediated vasoconstriction and increased binding at AT2 causing NO release
2. decreseased aldosterone released (so decreased Na and H2O retention)

Question 7

describe the possible adverse effects of ARBs

Answer 7

Well tolerated, few side effects
Less common:
• Renal failure (inc. renal artery stenosis)
• Hyperkalaemia

Question 8

describe the MOA of CCBs

Answer 8

Bind to specific alpha subunit of L-type calcium channels… reduce calcium transport across myocardial and vascular smooth muscle cell membrane… vasodilate peripheral, coronary and pulmonary arteries

Question 9

name the 3 types of CCBs - in which situations would their use be indicated or contraindicated

Answer 9

1. Dihydropyridines (e.g. amlodipine)
   - more commonly used than other CCBs as better at reducing BP
   - good in elderly, ISH
2. Phenylalkylamines (verapamil)
   - good in cases of arrhythmias or angina
   - cannot use in cases of heart block or HF as is a negative inotrope that reduces myocardial contractility
   - caution if using beta blockers as prolongs AP so risk of bradycardia
3. Benzothiazepines (dilitiazem)
   - less negative inotropic effect than verapamil so safer if HF

Question 10

how can thiazide-like diuretics decrease BP

Answer 10

Decrease distal tubular Na+ reabsorption. Effect on BP reduction complex, several mechanisms:

• initial blood volume decresae
• later: TPR falls due to vasodilatory effect

Question 11

why are thiazide diuretics not 1st line drugs in anti-hypertension

Answer 11

Less effective at reducing BP than other drugs and have more adverse effects:

• hypokalaemia
• increased urea and uric acid levels
• impaired glucose tolerance (esp. with beta-blockers)
• increased cholesterol and TAG levels
• activates RAAS

Question 12

name 2 contraindications for thiazide-like diuretics

Answer 12

gout and diabetes

Question 13

how can beta-blockers decrease BP

Answer 13

• decrease HR and CO

- inhibit renin release… decreased RAAS

Question 14

how can alpha-blockers decrease BP

Answer 14

• selective antagonism at post-synaptic alpha1 adrenoRs

- antagonise contractile effects of NA on vascular smooth muscle… decreased TPR

Question 15

what is the main adverse effect of alpha-blockers

Answer 15

postural hypotension (dizziness) as have more effect in upright position

Question 16

which drug can be used to prevent renin activity

Answer 16

aliskirin: binds to renin to prevent cleavage of angiotensiongen to angiotensin I

Question 17

which drug should be used to control BP in pregnancy

Answer 17

a-methyldopa (is converted to a-methyl-noradenaline, a potent a2-adrenoR agonist)

Question 18

describe the main lifestyle changes which can help reduce BP

Answer 18

1. maintain normal body weight (BMI 20-25 kg/m2)
2. diet changes:
   - reduce salt intake to <6g/day
   - reduce intake of total and saturated fat
   - consume >5 portions of fresh fruit/vegetables daily
   - limit alcohol consumption to <3 units/day for men and <2 units/day for women
3. regular aerobic physical exercise for 30 min/day