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 \( \xrightarrow{\text{GC }} \) 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