Glyceryl Trinitrate (GTN)

Chemical

An organic nitrate vasodilator

Use

  1. Hypertension
  2. Angina
  3. 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

  1. Inhibits Ca2+ entry into smooth m. cell
  2. 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