Vasodilators

Question 1

Nitroglycerin (NGT)

Answer 1

Organic Nitrate

Uses;

• tx stabe and unstable angina
• acute MI
• tx HTN
• tx acute or chronic heart failure
• Coronary vasospasm
• Pulmonary HTN
• controlled hypotension to decrease surgical bleeding
• dilate the sphincter of oddi

MOA;

• in the body organic nitrates are chemically altered into nitric oxide which stimulates cGMP block Ca influx into the cell and causes peripheral and smooth muscle vasodilation
• increases the venous capacitance causing a decrease in preload and decreasing the myocardial 02 demand

Dose; IV 5 - 10 mcg/min up to 200 mcg/min

Pharmacokinetics;

• IV E1/2 t; 5 min
• Vd; large
• Pb; 60%

-Transdermal and sublingual provide a steady state of release for patients with stable CAD

Oral; huge 1st pass effect; low bioavailability

• metabolized rapidly by the liver into metabolites that can cause methemoglobin
• <1% unchanged in urine

Side Effects;

• dizziness
• lightheaded
• synccope
• headache
• reflex tachycardia
• increased bleeding time

Contraindicated;

• severe hypotension
• severe aortic stenosis
• cardiomyopathy (all types)
• severe anemia
• pt who need a high/normal after load
• increased ICP
• glaucoma

Caution;
-liver dysfunction; increased risk of methemoglobinemia

Question 2

Sodium Nitroprusside (SNP)(NTP)

Answer 2

Direct acting NONselective peripheral vasodilator (venous & arterial)

Uses;

• HTN crisis
• Controlled Hypotension; reduce surgical bleeding
• Acute Pulmonary edema
• Hemodynamic stabilization during aortic cross clamping
• ↓ preload and ↓ after-load to ↑ SV and ↑ CO

MOA;

• PROdrug
• combines with oxyhemoglobin and form method; when this occurs cyanide and NO are related
• NO activates guanylate cyclase –> cGMP –> vasodilation of arteries and veins
• vasodilation occurs from ↑ Ca uptake and ↓ Ca entry
• vasodilation ↓ peripheral vascular resistance and ↑ cardiac output by ↓ after-load

Dose;
-Controlled hypotension; 0.3 - 0.5mcg/kg/min
-HTN crisis 1 - 2 mcg/kg/min 
Toxicity risk >2mcg/kg/min
Max dose 10mcg/kg/min 

Pharmacokinetics;

• Onset; Rapid
• E1/2t; 10 min (2 - 7 days for thiocyanate
• Duration; transient

Metabolism requires transferring iron electron from oxyhemoglobin to SNP. Transfer releases methgb and SNP radical (5 cyanide ions). 1 cyanide on reacts with metHgb and form cyano-methgb (not toxic). Other 4 react with rhodanese enzyme –> thiocyanate (less toxic). (this occurs in the liver and kidney)
All other free cyanides interfere with aerobic respiration –> lactic acidosis/ metabolic acidosis

Thiocyanate is slowly cleared by the kidneys over 2 -7 days

Side Effects;

• hypotension
• palpitations
• headache
• N/V
• skeletal muscle weakness
• muscle spasm
• diaphoresis
• cyanide toxicity

Contraindicated;

• renal dysfunction
• hypotension
• ↑ ICP
• MI pt r/t nonselective vasodilation (coronary steal)

Caution;
-pt who need elevated preload and after-load

• *keep protected from light
• *A-line required

** check thiocyanate level with high dose use or if sign of toxicity and decreed responsiveness to drug

Tx cyanide toxicity;

• stop infusion
• give 100% Fi02
• Bicarb t tx metabolic acidosis
• Sodium thiosulfate; 150 mg/kg
• Sodium nitrate; 5 mg/kg

Question 3

Hydralazine

Answer 3

Vasodilator
Direct acting arteriole dilator arteriole > venous

Uses;

• HTN in OR for asthmatic pt
• HTN
• HF
• Pulmonary artery dilator
• Pre-eclampsia
• Combo drug with isosorbide denigrate (Bidil) for hF

*combined with BB to block reflex tachycardia and diuretic to block RAAS response to drop in BP

MOA; activates cGMP blocks Ca into cell causing vasodilation (arterial > venous)

• direct acting arterial vasodilator; preserves blood flow to coronary, cerebral, renal, uterine and splanchnic beds
• tigers reflex tachycardia and RAAS

Dose; 2.5 - 10 mg IV

Pharmacokinetics;

• onset; 5 -20 min
• E1/2; 4 hrs
• Pb; 85 - 90%
• acetylated by the liver (if lack NAT2 can cause Lupus like syndrome)
• 14% excreted unchanged by kidneys

Side Effects;

• reflex tachycardia (give BB)
• reflex RAAS activation (give diuretic)
• increased ICP
• headache
• orthostatic hypotension (rare)
• paradoxical HTN
• SLE
• hepatotoxicity
• palpitations
• N/V
• constipation

Contraindicated;

• hypersensitivity
• CAD (r/t reflex tachycardia)