Nitroglycerine

Question 1

Broad Category

Answer 1

Direct Vasodilator / Antihypertensive

Question 2

Pharmacological Class

Answer 2

Nitrovasodilator / Organic Nitrate

Question 3

MOA

Answer 3

Undergoes metabolism (prodrug) to release Nitric Oxide. NO activates guanylyl cyclase within vascular smooth muscle, convverting GTP to cGMP. Elevated cGMP activates Protein kinase G, which dephosphorylates myosin light chains, lowers intracellular calsium, and results in smooth muscle relaxation. ALSO NO promotes cellular hyper polarization by stimulating potassium efflux

RESULT
- venous dilation that predominates over arterial dilation
- coronary arterial dilation

Question 4

Indications / Clinical Uses

Answer 4

Angina pectoris
Myocardial Ischemia
reduce preload in CHF
Acute MI
Cardiogenic pulmonary edema

Perioperative control of HTN
induce controlled hypotension (reduce blood loss)

Obstetrics: uterine relaxant for specific procedures
- retained placenta
- uterine inversion
- breech extraction

GI: relaxes narcotic induced biliary spasm

Question 5

IV bolus dosing

Answer 5

50 - 100 mcg

Question 6

IV infusion dosing

Answer 6

0.5 - 5 mcg/kg/min
(or 5 - 100 mcg/min)

• started at 10-20 mcg/ min titrated to effect

Question 7

Sublingual dosing

Answer 7

0.3 mg tabs, up to total of 3 tabs

Question 8

Preparation

Answer 8

50 mg mixed with 250 mL of D5W
- diluted to 100 mcg/mL

Question 9

Onset

Answer 9

very rapid (1-2 mins) IV

Question 10

Duration

Answer 10

Short 3-5 mins or 5-10 mins

Question 11

CV effects

Answer 11

venodilation
coronary arterial dilation (increased myocardial oxygen supply)
reduction in preload
reduction in LV end-diastolic pressure (reduction of O2 demand)
May cause reflex tachycardia
Reduced BP obvi

Question 12

CNS

Answer 12

increased CBF (vasodilator)
Increased ICP (caution with TBI, Trauma, Lesions)
HA

Question 13

Contraindications (absolute)

Answer 13

Avoided if BP less than 90 mmHg
HR < 50 or > 100

Question 14

Precautions

Answer 14

Hypovolemia

Question 15

Drug-Drug interactions

Answer 15

PDE-5 inhibitors
- profound refractory hypotension, myocardial ischemia, or infaction and death

Question 16

Other considerations

Answer 16

Tolerance can build

Methemoglobinemia (can precipitate but rare)
- treated with Methylene blue

Question 17

Metabolism

Answer 17

Rapid reductive hydrolysis in liver by glutathione orgaic nitrate reductase

Question 18

Half-life

Answer 18

Very short approximately 3 mins

Question 19

Vd Considerations

Answer 19

Large Vd (3-5 L/kg)
- highly lipophilic
- extensive tissue uptake
- Rapid distribution