Pharmacological treatment of hypertension

Question 1

what are the main classes of antihypertensives

Answer 1

1. ace inhibitors and angiotensin receptor blockers, renin antagonists
2. calcium channel antagonists
3. diuretics
4. beta blockers
5. vasodilators

Question 2

what are the side effects and contraindications of ACE inhibitors

Answer 2

1. dry cough
2. 1st dose hypotension
3. contraindicated in bilateral renal artery stenosis
4. no adverse effects on serum glucose/lipids, so frontline in diabetic patients
5. may not be as efficacious in black African/caribbean patients

Question 3

give examples of ACE inhibitors

Answer 3

enalapril, ramipril

Question 4

what is the role of angiotensin receptor blockers and give an example

Answer 4

1. block the actions of AngII on AT1-R
   - eg. losartan, candesartan
   - no cough

Question 5

give an example of aldosterone antagonists

Answer 5

spironolactone- used to treat hypertension in patients with primary aldosteronism

Question 6

how do aldosterone antagonists work

Answer 6

1. inhibits ability of aldosterone to produce new na+ channels
   - therefore causes loss of na+ and h2o
   - decrease preload and reduce blood pressure

Question 7

give an example of a calcium channel antagonist/blockers

Answer 7

main class dihydropyridines- nimodipine, nifedipine, amlodipine

Question 8

how do calcium channel blockers work

Answer 8

1. target L type Ca2+ channels on smooth muscle of blood vessel
2. phenylalkylamines (verapamil) and benzodiazepines target L type channels in the heart and decrease the frequency and force of contraction
   - less used to treat hypertension

Question 9

what are the side effects and contraindications of calcium channel blockers

Answer 9

1. flushing and headaches
2. peripheral oedema
3. combinations of ca2+ channel antagonists not recommended
4. grapefruit juice enhances action

Question 10

what does peripheral oedema cause

Answer 10

impairment of the function of the pre capillary sphincter increases hydrostatic pressure across the capillary and reducing fluid reabsorption

Question 11

how do thiazide diuretics work

Answer 11

1. some diuretic action but also acts via activation of k+ channels including Katp in smooth muscle of blood vessels to dilate arterioles and decrease blood pressure
   - mechanism of vasodilation is unknown

Question 12

describe the mechanism of action of indapamide

Answer 12

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

Question 13

what are the side effects and contraindications of thiazide diuretics

Answer 13

1. hypokalaemia
2. increase in urate
3. increase in glucose
4. increase in blood lipids
   - eg. bendroflumethiazide
   - newer recommended medicines include chlorthalidone and indapamide

Question 14

when is furosemide used

Answer 14

used only in resistant hypertension

Question 15

what are the side effects and contraindications of beta blockers

Answer 15

1. potential bronchoconstriction
2. vasoconstriction via blockade of B2-R
   - smooth muscle cell in the airways or peripheral arterioles perfusing skeletal muscle
3. fatigue
4. increase blood lipids
5. hypoglycaemia/hyperglycaemia
6. CNS side effects
7. potentially not as efficacious in black African/americans

Question 16

what does hypoglycaemia lead to

Answer 16

1. low blood glucose activates the release of adrenaline, mobilises glucose releases from liver
2. leads to tremor, palpitations and sweats
3. blocked by beta blockers
4. combinations of beta blockers and thiazides use with caution in diabetics

Question 17

what are the 2 types of beta blockers

Answer 17

1. non selective- B1 and B2
   - eg. propranolol
2. selective B1 antagonist
   - eg. atenolol

Question 18

what are vasodilators used for

Answer 18

1. a1 antagonists
   NA –> a1 –> IP3 –> Ca2+ –> constriction
2. used to treat hypertension in patients with benign prostatic hypertrophy
   - eg. doxazosin
3. other vasodilators such as minoxidil open k+ channels