Antihypertensive Agents

Question 1

Hypertension definition

Answer 1

Persistently higher than normal blood pressure

Guidelines now state that BP should be measured using ABPM or HBPM

Treatment if mean BP>150/95mmHg

Question 2

Extrinsic regulation

Answer 2

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

Parasympathetic system decreases frequency by decreasing cAMP via M2 receptors.

ANS

Question 3

Regulation TPR

Answer 3

SNS -> NA -> alpha -> 1  IP3  Ca2+ -> constriction
Sympathetic NS

Increases in Ang II -> Increase IP3 ->  increase intracellular [Ca2+]

Causes constriction of arterioles and an increase in total peripheral resistance and an 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

Aldosterone

Answer 5

Activates cytoplasmic receptors which bind to the nucleus to increase expression of Na+ channels and so aid Na+ and water retention

Question 6

Drug treatment choice

Answer 6

Age (<55 ACE inhibitor/angiotensin receptor blocker (ARB); >55 or all Black African/Americans calcium channel blocker)

Race (ACE inhibitors/beta blockers may be less efficacious in black african/amercians).

Question 7

Classes of anti-hypertensives

Answer 7

ACE inhibitors and Angiotensin receptor blockers; Renin Antagonists.
Calcium channel antagonists
Diuretics (no longer frontline)
Beta Blockers (no longer frontline).
Vasodilators

Question 8

ACE inhibitors

Answer 8

Dry cough
1st dose hypotension
Contraindicated in bilateral renal artery stenosis

May cause Hyperkalaemia

No adverse effects on serum glucose or lipids

Egs. RamiPRIL

Question 9

Angiotensin receptor antagonists

Answer 9

Block the actions of Ang II on AT1-R

E.g. Losartan

Side effects minimal.

Question 10

Aldosterone Antagonists

Answer 10

Spironolactone: Used to treat hypertension in patients with primary aldosteronism.

Question 11

Ca2+ channel antagonists

Answer 11

Main class dihydropyridines (amlodipine)

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

Phenylalkylamines (e.g. verapamil) and benzothiazepines (e.g. diltiazem) target L-type channels in the heart and decrease the frequency and force of contraction, less used to treat hypertension.

Question 12

Ca2+ channel antagonists - side effects

Answer 12

Flushing and headaches

Combinations of Ca2+ channel antagonists not recommended

Grapefruit juice enhances action (CYP3A4)

Peripheral Oedema
Preferential dilation of precapillary arteriole and impairment of the function of the pre-capillary sphincter increases hydrostatic pressure across the capillary and reducing fluid reabsorption.

Question 13

Thiazide and Thiazide-like Diuretics

Answer 13

Some diuretic action but also acts via activation of KATP in smooth muscle of blood vessel to dilate arterioles and decrease BP

Question 14

Indapamide

Answer 14

Indapamide hyperpolarises smooth muscle cells causing a relaxation/dilation of the arteriole and a decrease in total peripheral resistance

Question 15

Thiazide and Thiazide-like Diuretics - Side effects

Answer 15

Hypokalaemia
Increase in urate
Increase in glucose
Increase in blood lipids
E.g. bendroflumethiazide

Question 16

Beta blocker side effects

Answer 16

Potential bronchoconstriction
Vasoconstriction via blockade of 2-R
Fatigue
Increase blood lipids
Hypoglycaemia
CNS side effects (nightmares, impotence)
Potentially not as efficacious in black Afri-can/Americans

Smooth muscle cell in the airways or peripheral arterioles perfusing skeletal muscle

Question 17

Hypoglycaemia

Answer 17

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

Leads to tremor, palpitations and sweats

Blocked by Beta Blockers

Combinations of beta blockers and thiazides contraindicated in diabetics

Question 18

Beta blocker types

Answer 18

Non-selective (1 and 2) e.g. propranolol

Selective 1 antagonist e.g. bisoprolol

Question 19

Vasodilators

Answer 19

1-antagonists

NA -> alpha -> 1  IP-> 3  Ca2+  -> constriction

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

Other vasodilators such as minoxidil open K+ channels