Anti hypertensive

Question 1

name ACE inhibitors

Answer 1

Captopril
Enalopril
Ramipril

Question 2

Name the ARBs

Answer 2

Losartan
Olmesartan
Telmisartan

Question 3

Name the direct renin blocker

Answer 3

Aliskiren

Question 4

Name the CCB’s

Answer 4

Diltiazem
Verapamil
Amlodipine
Nifedipine

Question 5

Name the diuretics

Answer 5

Thiazides- hydrochlorothiazide
Loop- furosemide
K+ sparing- spironolactone, amiloride

Question 6

Name the Sympatholytics

Answer 6

Centrally acting: clonidine, a-methyl dopa

B- adrenergic: propranolol, timolol, atenolol, butexolol, metoprolol

B+a: carvedilol, labetalol

a adrenergic blocker: selective- prazosin, terazosin
Non selective- phentolamine

Question 7

Name the vasodilators

Answer 7

Arteriolar: hydralazine
A+V : sodium nitroprusside
V: nitroglycerin

Question 8

MOA of ACE inhibitors

Answer 8

1) inhibit generation of angiotensin II
~> no vasoconstriction - ⬇️ PVR - ⬇️ BP
~> no production of aldosterone - ⬇️ retention of Na+ & H2O
~> ⬇️ sympathetic nervous system activity

2) inhibits degradation of Bradykinin (potent vasodilator) by ACE
3) stimulates synthesis of PGs (vasodilators) through bradykinins

Question 9

PK of ACE inhibitors

Answer 9

Given orally
In hypertensive emergency- enaloprilat given IV
Poorly cross BBB- metabolised in liver- excreted in urine

Captopril- food reduces it’s absorption, hence given 1 hr before food.

Question 10

Adverse effects + contraindications of ACE inhibitors

Answer 10

CAPTOPRIL
1) cough- dry brassy ~> due to accumulation of bradykinin in lungs ~> drug should be stopped immediately

2) Angioedema- swelling of nose, mouth, lips, throat ~> airway should be protected ~> antihistamines, glucocorticoid, adrenaline given if reqd
3) Proteinuria- rare- in patients with severe kidney disease
4) teratogenic- contraindicated in pregnancy
5) hypotension- 1st dose causes hypotension ( hence low dose should be given) ~> seen in patients who are volume depleted, have CHF, or treated with diuretics
6) rashes & itching
7) loss of taste sensation (dysgeusia)
8) hyperkalemia- patients with renal insufficiency or who are treated with diuretics
9) Acute renal failure- patients with bilateral renal artery stenosis. (contraindicated)

Question 11

Drug interactions of ACE inhibitors

Answer 11

ACE Inh x thiazides ~> promote loss of Na+ & H2O, ⬆️ anti hypertensive effect

ACE Inh x potassium sparing diuretics ~> severe hyperkalemia

ACE Inh x lithium ~> retard lithium excretion - lithium toxicity

Question 12

Therapeutic uses of ACE inhibitors

Answer 12

1) Hypertension- used in all grades of HT
- FDC with hydrochlorothiazide
- suited for: HT + coexistant [ DM, asthma, gout, angina, CCF, dyslipidemia]
- C/I : bilateral renal artery stenosis, pregnancy, hyperkalemia
- does not cause electrolyte disturbances, hyperuricemia, sexual dysfunction, alterations in lipid levels.

2) Acute MI- ⬇️ load on heart, ⬇️ O2 consumption so that ischemic myocardium survives longer.
- hence should be started within 24 hrs

3) CHF- prescribed to all patients with impaired left ventricular function
1st line drug- ⬇️ after load, ⬇️ workload on heart

4) diabetic nephropathy- ⬇️ systemic BP & dilates renal efferent arterioles
- hence ⬇️ intraglomerular pressure; Inh angiotensin II mediated mesangial cell growth ~> ⬇️ microalbuminuria

5) scleroderma renal crisis- prevent effects of a angiotensin II in renal artery.

Question 13

MOA of ARB’s

Answer 13

• 2 angiotensin II receptors [ AT1 & AT2] ~> most angiotensin II effects are mediated by AT1
• ARB’s inhibit binding of angiotensin II to its receptor and block it’s effects
• effects similar to ACE Inh [except they don’t affect bradykinin production]

Question 14

Adverse effects of ARB’s

Answer 14

Better tolerated than ACE Inh
Headache
Hypotension
Weakness
Rashes
Nausea
Teratogenic effects
Hyperkalemia in patients with renal failure or on K+ sparing diuretics

Question 15

Use of ARB’s

Answer 15

1) Hypertension
2) CCF
3) MI
4) diabetic nephropathy

Indicated in patients who develop cough with ACE Inh

Question 16

MOA of thiazide diuretics

Answer 16

Thiazides- 
Inh Na+ - Cl- symport in the DCT
Promote Na+ & H2O excretion
⬇️ CO
⬇️ BP
on chronic therapy:
⬇️ Na+ conc in the vascular smooth muscle 
⬇️ PVR
⬇️ BP

Question 17

Use of thiazide diuretics

Answer 17

Thiazides- used in mild to moderate HT
- long duration of action
- administered low dose 12.5 to 25 mg/day
Given with K+ sparing diuretics or with ACE Inh
[to counteract loss of K+ and ⬆️ anti HT efficacy]
- well tolerated by elderly patients~> ⬇️ fracture incidence in old ppl due to reduction in Ca 2+ excretion

Question 18

Use of loop diuretics

Answer 18

Short duration of action

to used routinely - except in presence of renal/ cardiac failure

Question 19

MOA of B- blockers

Answer 19

B-blockers block B1 receptors on;
Kidney: ⬇️ renin release ~> ⬇️ BP
Heart: ⬇️HR, ⬇️ FOC, ⬇️CO ~> ⬇️BP
CNS: ⬇️ sympathetic outflow ~> ⬇️ BP

Question 20

B-blockers use & A/E

Answer 20

1) Young hypertensives with ⬆️ renin levels
2) patients with angina, post MI, Migraine, anxiety, tachycardia
3) pregnancy

• May ppt CCF and bronchospasm
• sexual dysfunction & nightmares
• use with caution in diabetics in hypoglycaemic drugs

Sudden stoppage after prolonged therapy can cause withdrawal symptoms

Question 21

Classify anti hypertensive drugs

Answer 21

1) ACE Inhibitors
2) ARB
3) Direct renin blocker
4) CCB
5) Diuretics - thiazides, loop, K+ saving
6) Sympatholytics- centrally acting, B adrenergic blocker, B+a adrenergic blocker, a adrenergic blocker, ganglion, neuron
7) vasodilator- arterioles, venular, A+V

Question 22

MOA + PK of centrally acting sympatholytic- clonidine

Answer 22

Stimulates the a-2A receptors in the VMC ->
⬇️ sympathetic outflow from VMC
On heart- ⬇️ HR &CO ~> ⬇️BP
On blood vessels- ⬇️ PVR ~> ⬇️BP

Highly lipid soluble, crosses the BBB, has a short duration of action

Question 23

Adverse effects of Clonidine

Answer 23

ENT- dryness of mouth and eyes
CNS- depression, sedation
Nausea
Postural hypotension

Sudden stoppage- withdrawal symptoms & rebound HT due to:

• super sensitivity of a-receptors
• precipitous release of large amounts of catecholamine

[ treated with IV nitroprusside or labetalol]

Question 24

Use of clonidine

Answer 24

1) in hypertension
2) to treat withdrawal symptoms- opioid & alcohol addicts, cessation of smoking
3) pre anaesthetic agent
4) antidiarrhoeal in diabetic neuropathy
5) reduce post menopausal hot flushes
6) prophylaxis of migraine

Question 25

MOA of a-methyl dopa

Answer 25

a-methyl dopa (prodrug) ➡️ a- methyl dopamine ➡️ a-methyl noradrenaline (false transmitter released during nerve stimulation instead of NA) ➡️

Stimulates a2 receptors in VMC- ⬇️ central sympathetic outflow- ⬇️ HR, PVR - ⬇️ BP

Question 26

Adverse effects and use if a-methyl dopa

Answer 26

Dryness of mouth, sedation, depression, postural hypotension

Rebound HT on withdrawal (milder)
+ve Coombs test in 1/6 patients

Preferred antiHT in pregnancy

Question 27

MOA of a-blockers

Answer 27

Non selective blockers- block both a1 & a2 receptors in BV
> vasodilation & fall in BP (a1 blockade)
> ⬆️NA release ( due to a2 blockade- tachycardia prominent)
> not preferred in essential HT- useful in HT in pheochromocytoma, clonidine withdrawal, cheese reaction

Selective blockers- block a1 vascular receptors
> vasodilation and ⬇️ BP
> prazosin causes 1st dose phenomenon- postural hypotension after first dose. ( initial dose given at bed time)

Question 28

A/E + use of a-blocker

Answer 28

Postural hypotension, tachycardia, palpitation, diarrhoea, nasal stuffiness, impotence

1) In pheochromocytoma- in pre op to control HT and restore blood volume

2) HT emergencies- IV phentolamine ( because of rapid onset of action)
> controls HT crisis intraoperatively, due to clonidine withdrawal, due to cheese reaction

3) essential HT
4) BPH- selective a1 blockers to reduce resistance to urinary flow
5) tissue necrosis- phentolamine
6) male sexual dysfunction- local injection of phentolamine with papaverine
7) others- CCF, PVD

Question 29

Minoxidil, diazoxide, hydralazine , NTG MOA & A/E

Answer 29

Minoxidil- activates K+ channels- hyper polarises vascular smooth muscle- leads to vasodilation- ⬇️BP
> causes reflex tachycardia & Na+ & water retention ~> hence used with B-blocker and diuretic
> used to promote hair growth in male type baldness

Diazoxide- alt. To Na nitroprusside

Hydralazine- directly acting arteriolar dilator
> > causes reflex tachycardia & Na+ & water retention ~> hence used with B-blocker and diuretic
> headache, hypotension, angina, lupus syndrome

NTG-venodilator used in HT with LVF/MI
Acts rapidly but tolerance develops

Question 30

Sodium nitroprusside

Answer 30

Rapidly acting with short duration of action
Relaxes A- ⬇️TPR by ⬇️ after load
Relaxes V- ⬇️CO by ⬇️ preload

MOA: RBCs split nitroprusside to NO and cyanide (CN)
NO- causes vasodilation

Very unstable and decomposes on exposure to light, hence should be prepared fresh

DOC for HT crisis & also used to improve CO in CCF

Dose: 1.5 mcg/kg/min i.v. Infusion in dextrose

Nausea, vomiting, anorexia, fatigue, disorientation, toxic psychosis ( accumulation of CN)

CN- is metabolised in the liver to thiocyanate and excreted slowly in urine

Question 31

HT treatment

Answer 31

Non pharmacological-
Weight reduction
Sodium restriction, Alcohol restriction, K+ rich diet
Exercise
Cessation of smoking 

Pharmacological- initial treatment- ACE Inh. ARBs, CCBs, thiazides
Therapy started with single agent, if that doesn’t work combination therapy used

Question 32

Hypertensive crisis

Answer 32

Very high BO- 220/120
With progressive end organ damage
BP should be reduced by 25% within the first 2 hours. And then to 160/100 within 2-6 hours.

Sodium nitroprusside- DOC
alt: fenoldopam, enaloprilat, labetalol, esmolol
Pregnancy: hydralazine