antihypertensives

Question 1

what are the first line antihypertensives?

Answer 1

1. ACE inhibitors
   - lisinopril, captorpil, enalapril
2. Angiotensin II Type 1 Blockers
   - valsartan, losartan, smth ‘sartan’
3. Beta adrenoreceptor Antagonists
   - [non-selective] propanolol, pindolol, carvedilol
   - [beta-1 selective] atenolol, bisoprolol, metoprolol
   - [mixed - 3rd gen] nebivolol
4. Calcium channel blockers
   - dihydropyridines (nifedipine, amlodipine)
   - non-DHP (verapamil, diltiazem)
5. Diuretics
   - thiazide

Question 2

What are the second line antihypertensives?

Answer 2

1. Alpha adrenoreceptor Antagonists
   - prazosin, smth “zosin”
2. Hydralazine
3. Mineralocorticoid Receptor Blockers
   - spironolactone, smth ‘one’

Question 3

What is the MOA of ACE inhibitors?

Answer 3

• inhibits ACE
• prevents Angiotensin I from converting to Angiotensin II
• decrease in angiotensin II
• decrease vasoconstriction -> decrease peripheral resistance
• decrease aldosterone -> decrease Na+/H2O retention
  => lowers BP
• reduce bradykinin inactivation
• bradykinin increases and starts to accumulate
• increases NO, PG
• increases vasodilation
  => lowers BP

Question 4

Contradictions using ACE Inhibitors (“pril”)?

Answer 4

Pregnancy

Question 5

What is the MOA of Angiotensin II Type 1 blockers (“sartan”)?

Answer 5

• blocks AT1 receptor -> blocks angiotensin II

Question 6

Contraindications using Angiotensin II Type 1 blockers (“sartan”)

Answer 6

Prenancy

Question 7

What beta adrenoreceptor blockers are also heart failure meds?

Answer 7

Carvedilol, Bisoprolol, Metoprolol, Nebivolol

Question 8

MOA of beta adrenoreceptor antagonists (“olol”)

Answer 8

• blocks B1 adrenoreceptor on cardiac myocytes
• decrease adenylate cyclase
• decrease ATP conversion to cAMP
• decrease PKA activation
• decrease opening of Ca2+ channels
• decrease influx of Ca2+ into cardiac myocytes
• decrease cytosolic Ca2+
• decrease calcium induced calcium release
• decrease activation of sarcoplasmic reticulum calcium
• decrease calmodulin activation
• decrease activation of actin-myosin complex
• decrease contractility of cardiac myocytes

Question 9

MOA of calcium channel blocker

Answer 9

• blocks calcium channels
• decrease influx of Ca2+
• decrease cytosolic Ca2+
• decrease calcium induced calcium release
• decrease activation of sarcoplasmic reticulum calcium
• decrease calmodulin activation
• decrease activation of actin-myosin complex
• decrease contractility of cardiac myocytes

Question 10

Effects of calcium channel blocker

Answer 10

• decrease SA and AV nodes -> decrease supra ventricular reentry tachycardia (non-DHP)
• decrease contractility of cardiac myocytes -> decrease O2 demand & CO (DHP)
• decrease vascular smooth muscle tone -> decrease BP (DHP)

Question 11

What calcium channel blockers are preferred for lowering BP?

Answer 11

verapamil = diltiazem = nifedipine

Question 12

What calcium channel blockers are preferred as vasodilator?

Answer 12

nifedipine > diltiazem > verapamil

Question 12

What calcium channel blockers are preferred as cardiac depressant?

Answer 12

verapamil > diltiazem > nifedipine

Question 13

What are NON-DHP

Answer 13

verapamil, diltiazem
- anti-arrhythmic

higher affinity to Ca channels on smooth muscles /electrical conduct of the heart
- blocks SA and AV nodal conduction

Question 14

MOA of diuretics (thiazides)

Answer 14

• Ca2+ is reabsorbed at the distal convoluted tubule epithelial cell via apical Ca2+ channels and basolateral Na+/Ca2+ exchanger
• Thiazides will block Na+/Cl- transporter, inhibiting Na+ reabsorption
• concentration of Na+ in the tubular cells will decrease, increasing the activity of Na+/Ca2+ exchanger, driving the reabsorption of Ca2+ through the Ca2+ epithelial channels
• increased Ca2+ reabsorption -> decrease hypercalciuria

Question 15

Prostaglandins will help the action of thiazides. What counters thiazides?

Answer 15

ADH will counter the action of thiazides
PGs will counter ADH. If prostaglandins are inhibited by NSAIDs, it allows ADH to work strongly against thiazides

Question 16

What are the adverse effects of thiazides?

Answer 16

1. hypokalaemic metabolic alkalosis
2. hyponatremia
3. hyperuricaemia
4. hyperglycaemia
5. hyperlipidaemia
6. hypercalcemia

Question 17

Why is hypokalaemic metabolic alkalosis an adverse effect of using thiazide?

Answer 17

due to an increase of aldosterone-mediated K+ and H+ excretion from the intercalated cells of the collecting duct

Question 18

Why is hyponatremia an adverse effect of using thiazide?

Answer 18

due to decrease in Na+ reabsorption

Question 19

Why is hyperuricaemia an adverse effect of using thiazide?

Answer 19

thiazides increase the reabsorption of urate from proximal convoluted tubules -> increases the risk of developing gout

Question 20

Why is hyperglycaemia an adverse effect of using thiazide?

Answer 20

due to hypokalaemia, there’s a decrease of K+ in the interstitium, K+ channels will open for an extended period of time -> hyperpolarization of the cell -> blocks the opening of voltage gated calcium channels -> decreases the exocytosis of insulin granules which is activated by calcium influx -> insulin response to hyperglycaemia is impaired

Question 21

MOA of alpha adrenoreceptor antagonists (“zosin”)

Answer 21

decrease vasoconstriction
decrease peripheral resistance
=> decrease BP

Question 22

Can alpha adrenoreceptor antagonists be used for renally impaired patients?

Answer 22

Yes as they do not affect GFR or renal blood flow

Question 23

What is alpha adrenoreceptor antagonists (“zosin”) used for?

Answer 23

treat symptoms of benign prostate hyperplasia