G7ii / 20A02: Describe the pharmacology of glyceryl trinitrate
20A02: Exam Report
Describe the pharmacology of glyceryl trinitrate (GTN).
79% of candidates passed this question.
GTN is a commonly used ‘level 1’ drug. The most comprehensive answers included information on available drug preparations, indications, mechanism of action, pharmacodynamics and pharmacokinetics and its side-effect profile. It was expected that significant detail be included in the pharmacodynamic section (e.g. preferential venodilation, reflex tachycardia, effects on myocardial oxygen demand etc). Common omissions included tachyphylaxis, dosing and its metabolism. Many answers didn’t mention the first pass effect.
G7ii / 20A02: Describe the pharmacology of glyceryl trinitrate (GTN)
Chemical
An organic nitrate vasodilator
Use
- Hypertension
- Angina
- LVF 2° AMI
Presentation
SL tablets
Oral spray
Transdermal patch
Clear solution for injection 50mg/10mL vial
Dose
IV: 10 – 400mcg/min
PO/spray: 400 – 600mcg
Patch: 5 – 10mcg/hr
MoA (mechanism)
PRODRUG → needs to be denitrated to produce active NO i.e. reacts with sulfylhydryl groups/other enzyme reactions to liberate NO
NO → diffuses into smooth m. cell → binds to & activates GUANYLYL CYCLASE → GTP cGMP → ↑cGMP
- Inhibits Ca2+ entry into smooth m. cell
- Activates K+ channels → hyperpolarizes cell (inactive)
- Stimulates “cGMP dependent protein kinases” → activates MLC phosphatases → dephosphorylates MLC → Smooth muscle relaxation
PD
CVS
- Low dose = veno VD
- High dose = veno + art VD
- Vein: ↓HR, ↓LVEDP, ↓PCWP (preL)
- Art: ↓SVR, ↓afterL
- Reflex ↑HR
- Facilitates subendocardial BF & redistribution to ischaemic areas
CNS
- Cerebral VD = ↑ICP
GI
- ↓LES pressure
- Paralytic ileus
PK
A
OBA 3%
High 1st pass
Rapid & efficient SL bioavailability
D
60% PPB
VD 3L/kg
M
Enters RBC → metabolized by hydrolysis into inactive compounds
E
80% urine
t ½ 1 – 2 mins
Adverse Effects
- 80% dose absorbed by giving sets
- CVS: ↓BP & ↑HR
- CNS: headache
- GI: nausea & vomiting
- Haem: MetHb, platelet dysfunction
- Tachyphylaxis
- Author: Krisoula Zahariou