study d3

Question 1

antihypertensive drugs

Angiotensin Converting Enzyme (ACE) Inhibitors

Answer 1

• these drugs act to reduce the activity of the renin-angiotensin-aldosterone system by
• inhibiting the formation of angiotensin II (AngII)

ACE inhibitors
* captopril, ramipril ,perindopril, enalapril
* almost all ACE inhibitors are eliminated by the kidney

* thus they require a reduction in dosage and/or a longer dosing intervals when administered to patients with decreased renal function

inhibition of converting enzyme leads to :
* decreased conversion of AngI to AngII
* reduced plasma aldosterone levels
..

Question 2

ACE inhibitors physological and adverse effects

captopril, ramipril ,perindopril, enalapril

Answer 2

Physiological Effects:
* vasodilation = decreased blood pressure (afterload)
* decreased Na+ / water retention
* reduced vascular remodelling*
* reduced cardiac remodelling*
tissue remodelling leads to negative long-term problems in blood vessels and the heart

ACE Inhibitors – adverse effects
* hypotension
* dry cough (especially captopril)
* angioedema (rare)
* risk of hyperkaliemia 

* inhibition of AngII, decreased aldosterone

Question 3

ANGII receptor blockers

Answer 3

AngII Receptor Blockers
* A second way of inhibiting the renin-angiotensin-aldosterone system is to block the AngII recpetors directly (antagonism)
* losartan, irbesartan, valsartan, .

Question 4

Beta blockers

Answer 4

• metoprolol, atenolol, bisoprolol

physiological actions:
1. reduced heart rate
2. reduced force of contraction
3. decreased release of renin

Beta blockers: adverse effects
* bradycardia, risk atrio-ventricular block, heart failure, hypotension
* fatigue, nightmares, sexual dysfunction

For non specific beta blockers (e.g. propranolol)
* bronchoconstriction (caution: asthma), hypoglycemia, reduce release of glucose (caution: diabetics)
* slight increase in peripheral resistance (antagonism of β2 mediated relaxation of blood vessels)
* inhibit lipolysis (increase in triglycerides)

Question 5

Diuretics

Answer 5

• used in the treatment of hypertension as well as to relieve symptoms of congestion in heart failure

hypotensive effect is due to 
« increase of the volume of diuresis »

• also reduce peripheral/pulmonary oedema
• increase urinary elimination of sodium (Na+)

different classes of diuretics:

osmotic diuretics
* mannitol

natriuretics: almost all are
* carbonic anhydrase inhibitors –> acetazolamide

loop diuretics
* thiazide diuretics
* potassium-sparing diuretics

Question 6

loop diuretics

Answer 6

Loop diuretics
* block Na+/K+/2Cl- transporter
* act on ascending limb of loop of the nephron
* rapid onset; intense effect

adverse effects:
* volume depletion,
* hypotension,
* hypo K+,
* hypo Mg++
* hypo Ca++
* ↑ uric acid, ↑ plasma lipids,
* ototoxicity (especially when used with aminoglycosides)

Question 7

Thiazide diuretics

Answer 7

thiazide (hydrochlorothiazide, indapamide, chlorthalidone)
* block Na+/Cl- co-transporter
* act on the distal convoluted tubule
* prolonged duration of action; more moderate effect
* less excrétion of Ca++

adverse effects:
* hypo Na+, hypo K+, ↑ plasma: uric acid, glucose, lipids

Question 8

potassium sparing duiretics

Answer 8

potassium sparing 
(spironolactone*, eplerenone) :
* block effect of aldosterone therefore also named mineralocorticoid receptor antagonists (MRA)
* onset of action is 24-48 hours
* act on distal convoluted tubule
* decrease excretion of potassium

adverse effects:
* hyperkalemia,
* gynecomastia
* menstrual irregularities

Question 9

Vasodilator

arterial and mixed

Answer 9

Arterial:
* hydralazine, minoxidil
* used for hypertensive emergencies / refractory
tend to + heart rate
, + retention of Na+ / water
* therefore combined with beta-blockers + diuretics


Mixed (venous and arterial)
* sodium nitroprusside
* hypertensive emergencies; rapid onset
* toxicity: cyanide poisoning

Question 10

Alpha 1 antagonist

Answer 10

prazosin, terazosin, doxazosin
* reduce peripheral vasoconstriction

adverse effects:
* orthostatic hypotension
* dizziness
* reflex tachycardia,
* Na+/H2O retention, fatigue

Non specific adrenergic antagonist
* labetalol
* inhibits alpha1 and beta adrenergic receptors
* used to treat hypertension in pregnant women

Question 11

Alpha 2 agonist and A-methyldopa

Answer 11

clonidine
mechanism of action:
* stimulates negative feedback on NA release
result:
* vasodilation;
* use: refractory hypertension
* adverse effects: sedation, depression

α-Methyldopa
* transformed to α-methyldopamine (DA) then to α-methylnoradrenaline (NA)
* α-methyl-NA stimulate α2 receptors (see previous slide)
* used to treat hypertension in pregnant women

Question 12

Difficulty encountered when dealing with antihypertensives

Answer 12

• no initial symptoms
• adverse effects
• long-term treatment
• dosing frequency (1/day vs tid)
• often involves many drugs
• single pill combination now recommended

Importance of educating the patient well