Vasodilators

Question 1

What are the different mechanisms for relaxing arterial smooth muscle?

Answer 1

• Hyperpolarization (opening Katp channels) -> decrease opening of L channels
• Blockade of Ca2+ L channels
• Increasing cGMP via NO
• Increasing cAMP via inhbition of phosphodiesterase-Pentoxifylline, Cilostazol

Question 2

What is the MOA for organic nitrates?

Answer 2

• Activates Guanylate Cyclase -> increasing cGMP
• Increasing cGMP activates cGMP-dependent protein kinase phosphorylation cascade->-> dephosphorylation of myosin light chain and muscle relaxation

Question 3

What are the CV effects of organic nitrates and nitrites?

Answer 3

Low doses: Capacitance vessel effects-> venodilation; Systemic peripheral resistance maintained
-Decrease diastolic filling pressure
High doses: Resistance vessel effects, decrease in systemic peripheral resistance; reflex cardiac stimulation
Overall effects: Decreased heart size and wall tension during systole; * reflex cardiac stimulation

Question 4

Pharmacokinetics of organic nitrates and nitrites

Answer 4

• 1st pass inactivation by nitrate reductase in liver

- Tolerance, physical dependence

Question 5

Adverse effects of organic nitrates

Answer 5

• Hypotension esp when used with other vasodilators
• Headache, flushing, GI distress
• Sildenafil potentiaates actions of nitrates used for angina->severe hypotension and heart attacks

Question 6

Calcium channel blockers MOA`

Answer 6

• Inhibit calcium selective channels carrying slow inward current during depolarization
• Nifedipine &DHPs bind to closed L-channels and decrease frequency of opening
• Verapamil binds to open channels, thus frequency of opening determines extent of blockade

Question 7

Describe Nifedipine, Usage, Adverse effects, and metabolism

Answer 7

-Prototype dihydropyridine Ca2+ entry blocker
-@ clinical doses-> vasodilator -> systemic vasodilation of resistance but not capacitance vessels
-*** Coronary artery vasodilation & increased blood flow
Adverse effects: Flushing, headaches, hypotension, peripheral edema
Metabolism: Orally effective, undergo large first pass metabolism, half-life 2-5 hours

Question 8

Describe Verapamil, Usage, Adverse effects, and metabolism

Answer 8

• Moderate vasodilation, cardiac suppression balance by reflex act.
  -Contraindicated in severe CHF
  Adverse effects: Flushing GI disturbances, left ventricular dysfunction
  Metabolism: orally effective, large first pass in liver

Question 9

What are the therapeutic advantages of Ca2+ entry blockers?

Answer 9

1. ) No aggravation of diabetes, peripheral vascular disease, no bronchospasm, blood profiles of lipids, glucose or potassium
2. ) Tolerance does not develop

Question 10

Propanolol

Answer 10

• prototypical beta blocker agent

- No cardioselectivity

Question 11

Beta blocker general effects

Answer 11

1. )CV: decrease HR and myocardial contractility
   - short term: decrease CO, incr peripheral resistance (B2 block)
   - Long term: periph. resistance normalize, net effect: decrease myocardial O2 consumption
2. ) BP- no effect on normal, decrease HTN in hypertensives
3. ) PUlmonary: B2 antagonism of bronchodilation- ** dangerous in COPD and asthma
4. )Eye-> decreases aqu. humor production from ciliary epithelium
5. ) Metabolic: blocks glucose mobilization (B2 antagonism of glycogenolysis)
   b. ) slows lipolysis, increase in VLDL, lowers HDL