Drug treatments for cardiovascular disease 2

Question 1

Hypertension

Answer 1

Persistently high than normal blood pressure

Treatment if mean BP>150/95mmHg

Question 2

Extrinsic regulation

Answer 2

Sympathetic system increases frequency and force via β1 receptors - cAMP - Ca2+ - increase rate and force

Parasympathetic system decreases frequency by decreasing cAMP via M2 receptors

Question 3

Regulation of TPR

Answer 3

Sympathetic nervous system

SNS - NA - alpha 1 - IP3 - Ca2+ - constriction

Increase in AngII - increase IP3 - increase intracellular Ca2+

Constriction of arterioles and increase in total peripheral resistance and increase in BP

Question 4

Regulation of preload by RAAS

Answer 4

Constriction of venules via AT1-R

RAAS also facilitates Na+ and H2O retention

Question 5

Drug treatment depends on

Answer 5

1. Age (<55 ACE inhibitor/ ARB; >55 or all black african/ americans calcium channel blocker)
2. Race (ACE inhibitors/ beta blockers may be less efficacious in black african/ americans)
3. Co-existing diseases

Question 6

Classes of anti-hypoertensives

Answer 6

ACE inhibitors and angiotensin receptor blockers (renin antagonists)

Calcium channel antagonists

Diuretics (no longer frontline)

Beta blockers (no longer frontline)

Vasodilators

Question 7

Side effects and contraindications

Answer 7

Dry cough with ACE inhibitors

1st dose hypotension

Contraindicated in bilateral renal artery stenosis

Hyperkalaemia

Question 8

Angiotensin receptor antagonists

Answer 8

Block the actions of AngII on AT1- R

Side effects minimal

• losartan

Question 9

Spironolactone

Answer 9

Aldosterone antagonist

Used to treat hypertension patients with primary aldosteronism

Question 10

Ca2+ channel antagonists

Answer 10

Main class dihydropyridines (amlodipine)

Target L-type Ca2+ channels on smooth muscle of blood vessel

Phenylalkylamines (verpamil) and benzothiazepines (diltiazem) target L-type channels in heart and decrease frequency and force contraction

Question 11

Side effects of Ca2+ channel antagonists

Answer 11

Flushing and headaches

Combinations of Ca2+ channel antagonists not recommended

Grapefruit juice enhances action (CYP3A4)

Peripheral oedema

Question 12

Thiazide and thiazide like diuretics

Answer 12

Some diuretic action

Acts via activation of KATP in smooth muscle of blood vessel

Dilate arterioles and decrease BP

Question 13

Indapamide

Answer 13

Hyperpolarises smooth muscle cells

Causes relaxation/ dilation of arteriole

Decrease in total peripheral resistance

Question 14

Side effects and contraindications of thiazide and thiazide like diuretics

Answer 14

Hypokalaemia

Increase in urate

Increase in glucose

Increase in blood lipids

• bendroflumethiazide
• indapamide

Question 15

Side effects and contraindications of beta blockers

Answer 15

Potential bronchoconstriction

Vasoconstriction via blockade of B2-R

Fatigue

Increase blood lipids

Hypoglycaemia

CNS side effects (nightmares, impotence)

Potentially not as efficacious in black african/ americans)

Question 16

Hypoglycaemia

Answer 16

Low blood glucose activates release of adrenaline, mobilises glucose release from liver

Leads to tremor, palpitations and sweats

Blocked by beta blockers

Combination of beta blockers and thiazides contraindicated in diabetics

Question 17

Types of beta blockers

Answer 17

Non-selective (B1 and B2) e.g. propanolol

Selective B1 antagonist e.g. bisoprolol

Question 18

Vasodilators

Answer 18

a1- antagonist

NA - a1 - IP3 - Ca2+ - constriction

Used to treat hypertension in patients with benign prostatic hypertrophy (doxazonin)

Other vasodilators such as minoxidil open K+ channels