Anti hypertensives

Question 1

examples of ace inhibitors

Answer 1

ramipril, perindopril, lisinopril

Question 2

mechanism of action of ACEi

Answer 2

ACE-I inhibit the RAAS and stimulate the Kallikrein-Kininogen (KK) system by angiotensin converting enzyme, an enzyme that:
Hydrolyses angiotensin I to angiotensin II
Inactivates bradykinin, a potent vasodilator

Question 3

Pharmacokinetics of ACEi

Answer 3

Bioavailability 28%
Half-life 15 hours
Renal excretion

Question 4

Clinical uses of ACEi

Answer 4

Hypertension
Chronic renal failure:
Diminish proteinuria and stabilise renal function (even in absence of lowering BP)
Recommended in diabetes even in absence of hypertension
CCF
Reduced mortality post-MI

Question 5

Adverse effects of ACEi

Answer 5

• Marked first-dose hypotension
• AKI - especially with bilateral renal artery stenosis or solitary kidney
• Hyperkalaemia, especially with K sparing diuretics, diabetes or CRF
• Dry cough and angioedema (due to bradykinin and substance P)
• Neutropenia or proteinuria if given in high doses to CRF patients
• Minor toxic effects in 10% of patients:
• Altered sense of taste
• Allergic skin rash
• Drug fever

Question 6

Drug interactions with ACEi

Answer 6

• Potassium supplements or potassium sparing diuretics
• NSAIDs can impair the hypotensive effects of ACE-I by blocking bradykinin-mediated vasodilation, which is at least partially prostaglandin mediated
• Lithium –> lithium toxicity
• General anaesthetics –> hypotension
• Other diuretics/anti-hypertensives –> hypotension

Question 7

Precautions with ACEi

Answer 7

Pregnancy - is teratogenic
Dose reduced in renal failure

Question 8

Examples of Angiotensin II receptor blockers

Answer 8

Irbesartan, candesartan, losartan, telmisartan

Question 9

Mechanism of action of ARBs

Answer 9

Competitive selective antagonist of angiotensin II type 1 (AT1) receptor
Causes vasodilation and inhibition of aldosterone secretion
No effect on bradykinin

Question 10

Pharmacokinetics of ARBs

Answer 10

90% protein bound
Half-life 12 hours
Liver metabolism

Question 11

Clinical use of ARBs

Answer 11

Hypertension
CCF
Chronic renal failure:
Diminish proteinuria and stabilise renal function (even in absence of lowering BP)

Question 12

Precautions of ARBs

Answer 12

Non-diabetic renal failure
Pregnancy
Hyperkalaemia
Renal artery stenosis

Question 13

Pharmacodynamics of metoprolol

Answer 13

selective B1-receptor blocker
Equally selective to B1 blockade as propranolol
However, 50-100x less potent than propranolol in blocking B2-receptors
At higher doses, metoprolol is less selective in blockade
Cardiovascular effects:
Negative inotrope and chronotrope
Slows AV conduction (prolongs PR interval)
Suppresses renin release mediated via beta-receptors through catecholamines (decreases blood pressure)

Question 14

Pharmacokinetics of metoprolol

Answer 14

PO or IV administration
Well absorbed orally but bioavailability 50% due to high first pas metabolism
Hepatic metabolism
Large volume of distribution (> 200L)
Moderate lipid solubility
Half-life 3-4 hours

Question 15

Clinical uses of metoprolol

Answer 15

Hypertension
IHD (reduced frequency of anginal episodes and improved exercise tolerance)
Improved survival after MI
Arrhythmias: AF / flutter
CCF

Question 16

Examples of calcium channel blockers

Answer 16

amlodipine, diltiazem, felodipine, nifedipine, nicardipine, and verapamil

Question 17

Verapamil drug class

Answer 17

Calcium channel blocker
Class IV antiarrhythmic

Question 18

Pharmacodynamics of verapamil

Answer 18

Blocks both activated and inactivated L-type calcium channels (alpha-1 subunit)
Reduces frequency of opening when depolarised resulting in decreased transmembrane calcium current and calcium influx

Question 19

Cardiac effects of Verapamil

Answer 19

Slows AV nodal conduction time and ERP
Negative inotrope
Reduced myocardial oxygen demand
Vascular smooth muscle relaxation (less than dihydropyridines) –> reduced coronary artery spasm

Question 20

Extra cardiac effects of verapamil

Answer 20

Peripheral vasodilation
Arterioles are more sensitive than veins, therefore orthostatic hypotension uncommon

Question 21

Pharmacokinetics of verapamil

Answer 21

PO or IV administration
Bioavailability 22% due to high first pass effect
High plasma protein binding
Extensive metabolism
Half-life 6 hours

Question 22

Clinical uses of verapamil

Answer 22

Angina
Hypertension
Supraventricular arrhythmias
Migraine

Question 23

Cardiac adverse effects of verapamil

Answer 23

Bradycardia
AV block
VF/hypotension if used in treatment of VT
Cardiotoxic effects are dose-related

Question 24

Non cardiac adverse effects of verapamil

Answer 24

Flushing
Dizziness
Nausea
Constipation
Peripheral edema

Question 25

Mechanism of action of thiazide diuretics

Answer 25

Inhibit Na/Cl co-transporter in distal convoluted tubule Reduces NaCl reabsorption form luminal side of epithelial cells Leads to increased NaCl excretion and diuresis Enhanced Ca reabsorption (passive)

Question 26

Pharmacokinetics of Thiazide diruetics

Answer 26

Duration of action 8-12 hours Secreted by organic acid secretory system in proximal tubule Compete with uric acid secretion by same system

Question 27

Clinical uses of thiazide diuretics

Answer 27

Hypertension Heart failure Nephrolithiasis due to idiopathic hypercalciuria Nephrogenic diabetes insipidus

Question 28

Adverse effects of thiazide diuretics

Answer 28

Dehydration/hypovolaemia Hypokalaemic metabolic alkalosis (similiar to loop diuretics) Hyperglycaemia Unmask hypercalcaemia due to other causes Hyperlipidaemia Hyponatraemia Hyperuricaemia Hyper GLUC

Question 29

Drug interactions with thiazide diuretics

Answer 29

Increased plasma Lithium level NSAIDs can reduce effects

Question 30

Examples of alpha blockers

Answer 30

prazosin, terazosin, alfuzosin, tamsulosin, and silodosin

Question 31

Pharmacodynamics of Prazosin

Answer 31

Selective alpha-1 receptor blocker in arterioles and venules Affinity 1000-fold greater than that for alpha-2 receptors Reduces BP by dilating both resistance and capacitance vessels Alpha-1 selectivity allows noradrenaline to exert unopposed negative feedback (mediated by presynaptic alpha-2 receptors) on its own release

Question 32

Pharmacokinetics of prazosin

Answer 32

50% first pass metabolism Extensive metabolism Half-life 3 hours

Question 33

Adverse effects of alpha blockers

Answer 33

Postural hypotension Headache, lassitude Reduced prostate smooth muscle tone, thus alleviating prostatic urinary obstruction Positive serum antinuclear factor Increased HDL concentration

Question 34

Clinical uses of alpha blockers

Answer 34

Chronic hypertension Benign prostatic hyperplasia Raynaud’s phenomenon (uncommon)