Hypertension

Question 1

Goals of treatment and stages of hypertension

Answer 1

Reduce BP: SBP <140mmHg, DBP <90mmHg (or -10 for both in diabetics). Reduce cardiovascular and renal damage, reduce risk of stroke, MI and IHD. Limit left ventricular hypertrophy.

Stage 1 hypertension is BP of >140/90mmHg. Will only give pharmacological management if evidence or organ/renal damage or if diabetic

Stage 2 if BP > 160/100mmHg

Severe if BP > 180/110mmHg

Question 2

Non-pharmacological managements

Answer 2

Reduce alcohol and cigarette consumption.
Weight reduction.
Reduce caffeine
reduce fat and salt intake
increase fruit and omega 3 intake
increase exercise

Question 3

Priority of treatments

Answer 3

First line ACEI (or AT1 antagonist), or Ca blocker for over 55s and black patients. This is due to generally lower renin activity.

Second line: ACEI + ca blocker

Third line: ACEI + ca blocker + thiazide

may also further add a diuretic, a-AR, or B-AR blocker

Question 4

ACEI mechanism

Answer 4

E.g., captopril, enalapril (prodrug), lisinopril, ramipril, etc…

Inhibits the enzyme angiotensin converting enzyme, which produces angiotensin II.

Angiotensin II acts at vascular SM (vasoconstrictive), and the pituitary (releases vasopressin) and adrenal glands (releases aldosterone).

Aldosterone and vasopressin increase the reabsorption of salt and water from the kidneys, which increases BP.

Bradykinin is also metabolised by ACE, and is a vasodilator and increases blood vessel permeability (can cause angioedema). Is known to cause cough though - side effects in 10% of patients.

Question 5

AT1 receptor antagonists for hypertension

Answer 5

e.g., candesartan, losartan, valsartan

Angiotensin II mediates its effects by activating the AT1 receptor. Similar mechanism of blocking angiotensin II’s effects, but does not lead to increased [bradykinin]

Question 6

Renin inhibitor

Answer 6

aliskiren

Inhibits renin, which converts angiotensinogen into angiotensin I.

Same pathway, but inhibits earlier.

Question 7

Aldosterone receptor antagonist for hypertension

Answer 7

Spironolactone

used for resistant hypertension and heart failure.

Inhibits aldosterone mediated reabsorption of water and sodium in the kidneys

Question 8

Calcium channel blockers

Answer 8

e.g., dihydropyridines: nifedipine, felodipine

inhibit VGCCs in smooth muscle. Leads to less calcium-calmodulin mediated SM contraction - vasodilatation.

Cardiac calcium channel blockers like verapamil block the L-type VGCC, to decrease HR and CO -> lower BP. does also have some effect on SM VGCCs.

Side effects include constipstion from GIT SM inhibition, and oedema from veinous SM inhibiton.

Question 9

Thiazide and thiazide like diuretics

Answer 9

Thiazide-like: indapamide, chlortalidone

Thiazide: bendroflumethiazide

Only work in healthy kidneys

inhibits Na+/Cl- reabsorption in the distal convoluted tubule, causing diuresis. Reduces plasma volume -> lower BP.

Also has an unknown vasodilatory mechanism.

May cause hypokalaemia from electrolyte imbalance. postural hypotension may occur

Question 10

B-blockers for hypertension

Answer 10

e.g., atenolol (B1-AR selective), propranolol (B1/2-AR non selevtice). Propranolol as such causes bronchial side effects.

Block NA and adrenaline effect in heart

Blocks B1-AR in SA node and cardiac muscle -> delays contraction rate, and decreases contractile force.

B-ARs in SM mediate vasodilatation , so not first line for hypertension (b blockers block)

Question 11

a-AR blockers

Answer 11

prazosin and doxazosin block a1-ARs in the vascular SM.

the a1-ARs mediate vasoconstriction.

Last choice due to large range of side effects.