Anti-hypertensive drugs

Question 1

What are some sequelae of hypertension?

Answer 1

MI
Congestive HF
Renal damage
Cerebrovascular incidents
Hypertensive encephalopathy
Aneurysm (thoracic or abdominal)
Aortic dissection

Question 1

What are the major factors influencing blood pressure?

Answer 1

Cardiac output & peripheral resistance

Question 2

What affects cardiac output and peripheral resistance?

Answer 2

Cardiac output: heart rate, contractility and filling pressure which is determined by venous tone and blood volume

Peripheral resistance: arteriolar tone

Question 3

What are the two kinds of angiotensin inhibitors?

Answer 3

ACE-I inhibitors and AT-1 blockers

Question 4

What are some examples of ACE-I inhibitors?

Answer 4

Lisinopril, captopril, enalapril (basically all the prils)

Question 5

What is the action of ACE-I inhibitors?

Answer 5

Prevents the conversion of angiotensin I to angiotensin II

Question 6

What are the clinical uses of ACE-I inhibitors?

Answer 6

Hypertension
Cardiac failure
Post-MI
Renal insufficiency

Question 7

what are the adverse effects of ACE-I inhibitors?

Answer 7

• Severe hypotension
• Renal failure
• Hyperkalemia due to decreased K+ secretion
• Angioedema and dry cough due to increased bradykinin and substance P activity (ACE breaks them down!)

Contraindicated in pregnancy! (teratogenic among other things)

Question 8

What are the sartans? losartan, valsartan etc

Answer 8

Angiotensin II type I (AT1) blockers

Question 9

what is the action and adverse effects of AT1 blockers?

Answer 9

they block the receptors, preventing the action of angiotensin II at AT1 receptors

also contraindicated in pregnancy but have less/no dry cough

Question 10

What is the MOA of beta blockers?

Answer 10

B1 blockade inhibits adenyl cyclase which ultimately inhibits the opening of calcium channels and decreases contractility

they prevent calcium induced calcium release as well

B2 inhibition also causes bronchoconstriction by decreasing cAMP formation and thus reducing the amount of inactivated MLCK – reducing bronchodilation and thus causing bronchoconstriction

Question 11

What are some non-selective beta-blockers?

Answer 11

Propanolol
Pindolol
Carvedilol

Question 12

What are some B1 selective beta-blockers?

Answer 12

BAM
Bisoprolol
Atenolol
Metoprolol XL (normal metoprolol doesn’t work for HF)

Question 13

What is a mixed/3rd gen beta blocker?

What does being mixed entail?

Answer 13

Nebivolol

• B1 selective in low doses or in people who have fast metabolism
• non-selective in high doses or people w slow metabs
• also has vasodilatory effects through increased NO release

Question 14

What are the clinical uses of beta blockers?

Answer 14

Hypertension
Heart failure
Abnormal heart rhythms
Post MI
Anxiety

Question 15

What are the adverse effects of beta blockers?

Answer 15

Hypotension
Bradycardia
Reduces exercise capacity
AV nodal block
Too much bronchoconstriction (in asthmatics, for e.g.)
CNS effects: vivid dreams, beta blocker blues (clinical depression)

Question 16

how is calcium reabsorbed in the kidneys?

Answer 16

it is reabsorbed by epithelial cells in the distal convoluted tubule
- via an apical Ca2+ channel and a basolateral Na+/Ca2+ exchanger

Question 17

What are some examples of thiazides?

Answer 17

Hydrochlorothiazide and indapamide

Question 18

What is the MOA of thiazides?

Answer 18

Basically diuretics

They inhibit NaCl reabsorption by blocking the Na/Cl transporter – this increases excretion of salt and thus water – thus anti hypertensive

They also enhance Ca2+ reabsorption in the distal convoluted tubule

Impt to note that PGs synthesized by the kidney are somehow needed for thiazides to work. Therefore NSAIDs can interfere with thiazides

Question 19

What are the clinical uses of thiazides?

Answer 19

• Hypertension
• Congestive heart failure
• Nephrolithiasis due to idiopathic hypercalciuria
• Nephrogenic diabetes insipidus

Question 20

What are the adverse effects of thiazides?

Answer 20

1. Hypokalemic metabolic alkalosis
2. Hyponatremia
3. Hypercalcemia
4. Hyperuricemia
5. Hyperglycemia
6. Hyperlipidemia