Vasodilator Drugs

Question 1

Guanadrel

Answer 1

• Exogenous fake NT
• Accumulated, stored and released like NE, but no effects
• Concentrated w/in adrenergic storage vesicle
• Initially releases NE when given (Can increase pressure)
  
  • Not noticed b/c slow release and breakdown by MAO
• Contraindicated w/ pheochromocytoma
• Used as Antihypertensive vasodilator

Question 2

Reserpine

Answer 2

• Tightly binds adrenergic storage vesicles
  
  • Remains bound for extended periods
• Inhibits vesicular catecholamine transport
  
  • Blocks reuptake via VMAT
• Lose capacity to concentrate and store NE and dopamine
• Antihypertensive via central and peripheral actions

Question 3

Hydralazine

Answer 3

• Oral arteriolar vasodilator
• Direct relaxation of arteriolar smooth muscle
• Decreases Total peripheral resistance (afterload) and BP
• Reflex increase in HR, contractility, renin, and fluid retention
• MOA unclear
• Limited uses: best as supplemental agent in HTN
• Used for HTN emergencies in pregnancy
• Used to prevent nitrate tolerance (BiDil)
• Adverse effect: reflex increase in HR and contractility
  
  • contraindicated in pts w/ HTN and coronary artery disease

Question 4

Minoxidil

Answer 4

• K+ channel opener (ATP modulated) in arteriolar smooth muscle
  
  • Hyperpolarization and relaxation
  • Little effect on venous and capacitance vessels
• Different mechanism so used to treat HTN refractory to other meds
• Adverse: reflex increase in HR, contractility, renin activity, and fluid retention
  
  • Can lead to cardiac ischemia (contraindicate CAD)
  • Give w/ beta blockers to decrease risks

Question 5

Sodium Nitroprusside

Answer 5

• Nitrate compound w/ nitroso group and cyanide
• Releases NO thru non-enzymatic process
  
  • non-specific: affects arteries and veins
• Dilates arteries and veins
  
  • Decreases TPR (Afterload)
  • Decreases venous return (Preload)
  • Reflex increase in cardiac stimulation (Less than others)
• Used in Hypertensive emergencies and severe cardiac failure
• Adverse: cyanide accumulation can lead to:
  
  • acid-base disturbances
  • cardiac arrhythmias
  • Death
  • Thiocyanate toxicity in impaired renal fxn

Question 6

Nifedipine

Answer 6

• Dihydropyridine Ca2+ channel blockers
  
  • Blocks L type Ca2+ channels
  • Reduce Ca2+/CaM activation of MLCK
• Arterial smooth muscle more responsive than venous
• Huge coronary and peripheral vasodilation
• Reflex increase in HR and contractility
  
  • No change in AV conduction
• Uses: HTN, HTN crisis, Angina, HF
• especially effective in low renin, old, and black patients
• Adverse: Excess vasodilation
• Amlodipine is long acting version

Question 7

Verapamil and Diltiazem

Answer 7

• Non-dihyropyridine Ca2+ channel blockers
  
  • Block L type Ca2+ channels
  • Reduce Ca2+/CaM activation of MLCK
• Arterial smooth muscle more responsive than venous
  
  • Decrease TPR (afterload) and BP
• Decrease HR, AV conduction velocity, contractility
• Use: HTN, HTN crisis, Angina, arrhythmias
  
  • effective in low renin, old, and black populations
• Adverse: excess vasodilation, AVN block, decreased CO, precipitation of CHF
• Adverse:

Question 8

Phosphodiesterase Inhibitors

Answer 8

• Prevent hydrolysis of cAMP to cAMP
• Amrinone and milrinone inhibit PDE3 in cardiac and VSM
  
  • elevates cAMP: positive inotrope and vasodilation
  • Decreases preload and afterload
  • Short term support of failing circulation
  • Adverse: thrombocytopenia, increased mortality
• Sildenafil, vardenafil, tadalefil: selective PDE5 inhibitors
  
  • expressed in erectile smooth muscle, retina, systemic
  • Used to tx erectile dysfunction
  • Adverse: interaction w/ nitrates to cause severe hypotension, MI, and sudden death

Question 9

Drugs for HTN emergencies

Answer 9

• Sodium Nitroprusside: short acting venous and atrial dilator
• Nicardipine: fast acting dihydropyridine Ca2+ blocker
• Fenoldopam: D1 receptor agonist- increase renal profusion too
• Nitroglycerine: venodilator. Used w/ cardiac ischemia
• Phentolamine: non-selective alpha blocker
• Esmolol: fast beta blocker; for aortic dissection or post-op HTN
• Labetalol: alpha and beta blocker. Safe w/ CAD
• Hydralazine: arteriolar dilator. used in pregnancies