Hypertension

Question 1

list classes of antihypertensive drugs

Answer 1

ABCDV:

• Angiotensin antagonist (ACEI, AT1 blocker)
• Beta blockers
• Ca channel blocker (DHP)
• Diuretics
• Vasodilators

Question 2

determinants of CO

Answer 2

CO = SV x HR

- SV: contractility, filling pressure (BV, venous tone)

Question 3

Effective drug combinations

Answer 3

any 2 of:

• Ca channel blocker
• angiotensin antagonist
• diuretics

Question 4

Not well supported drug combinations

Answer 4

Ca channel blocker and B blocker

Question 5

Drugs contraindicated in diabetic patients

Answer 5

B blocker: masks symptoms of hypoglycemia

Diuretics: worsens diabetes

Question 6

Ca channel blocker MOA

Answer 6

1. Smooth muscle:
   - normal effect of Ca –> increase formation of Ca:calmodulin complex –> activate MLCK
   - phosphorylation of MLC –> causes contraction with actin
2. Heart:
   - normal effect of Ca –> increase contractility
   - also has CICR

Blocking of L type voltage sensitive Ca channel:
=> (1) block vascular smooth muscle tone –> reduce TPR, reduce BP
=> (2) reduce contractility –> reduce CO, reduce BP

Question 7

Ca channel blocker uses

Answer 7

1. Hypertension
2. stable angina (amlodipine)
3. MI and stroke prevention (amlodipine)

Question 8

Name 2 DHP Ca channel blockers

Answer 8

Nifedipine

Amlodipine

Question 9

Ca channel blockers adverse effects

Answer 9

1. hypotension
2. MI (esp first time or increasing dose for first time)
3. bradycardia, AV block

Question 10

Ca channel blocker contraindication

Answer 10

CHF, reduced contractility worsens LV output

Question 11

Name 2 peripheral adrenergic blockers

Answer 11

a blocker: prazosin

B blocker: propranolol

Question 12

B blocker MOA

Answer 12

1. B1 adrenoceptors
   - activate adenylyl cyclase –> convert ATP to cAMP –> activate PKA –> activate Ca channels
   - Ca influx + CICR –> increase contractility of heart
2. B2 adrenoceptors
   - activate adenylyl cyclase –> convert ATP to cAMP –> inactivate MLCK (becomes MLC-bisphosphate) –> dephosphorylation of MLC –> loss of smooth muscle contraction –> vasodilation (for arterioles supplying skeletal muscle)
   - bronchodilation

Blocking B adrenoceptors
=> (1) reduce contractility –> reduce CO, reduce BP
=> (2) vasoconstriction, but not significant as reduced contractility outweighs this effect + bronchoconstriction

Question 13

B blocker clinical uses

Answer 13

1. hypertension
2. cardiac failure
3. following MI
4. arrhythmias
5. anxiety disorders (second line)

Question 14

B blocker adverse effects

Answer 14

1. hypotension
2. bradycardia, AV block
3. reduced exercise capacity
4. bronchoconstriction (esp in asthmatics)

Question 15

B blocker contraindications

Answer 15

asthma, diabetics

Question 16

Nitrates MOA

Answer 16

donate NO –> NO activates guanylyl cyclase –> converts GTP to cGMP –> directly dephosphorylates MLC –> relaxation of vascular smooth muscle. vasodilation

Question 17

Why are angiotensin antagonists not used together

Answer 17

1. Efficacy not additive

2. additive adverse effects

Question 18

Name 4 ACE inhibitors

Answer 18

captopril, enalapril, ramipril, lisinopril

Question 19

ACE inhibitors MOA

Answer 19

1. Inhibit actions of angiotensin II such as:
   - vasoconstriction –> vasodilation
   - aldosterone secretion –> reduced NaCl reabsorption, reducing water retention
2. angiotensin I accumulates –> feedback inhibition on renin
3. activates bradykinin
   - increases production of NO, PGs –> vasodilation

Question 20

ACE inhibitors clinical uses

Answer 20

1. hypertension
2. HF
3. following MI
4. renal insufficiency

Question 21

ACE inhibitors adverse effects

Answer 21

1. hypotension
2. acute renal failure
3. hyperkalemia
4. angioedema (bradykinin and substance P induce “inflammation like” response
5. dry cough (bradykinin and prostaglandin increase sensitivity of bradykinin-dependent airway sensory neurons)

Question 22

ACE inhibitors contraindication

Answer 22

pregnancy (esp late), affects renal function of fetus

Question 23

Name AT1 blockers

Answer 23

losartan, valsartan, candesartan, eprosartan, irbesartan, telmisartan

Question 24

AT1 blocker MOA

Answer 24

prevents angiotensin II from binding to angiotensin II type 1 receptors

Question 25

AT1 blocker adverse effects

Answer 25

same as ACE inhibitors, but less/no dry cough

Question 26

Diuretics MOA

Answer 26

reduce water retention --> reduce blood volume --> reduce CO, reduce BP