F11iii: MOCK Describe the mechanism of action & adverse effects of pulmonary vasodilators administered via the inhalational route

  • Pulmonary hypertension = MPAP ≥ 25mmHg at rest, measured by R) heart catheterisation

Inhalational Route

Rate of Diffusion
  • Rate of diffusion = \(S\over AT\) \(\times\) \(Solubility\over \sqrt{MW}\)\(\times\) \((P_2 – P_1)\)
  • Non-invasive
  • High permeability
  • Large SA for absorption
  • Thin barrier to diffusion
  • Good blood supply
  • Low enzyme activity
  • Avoids 1st pass metabolism
  • Direct delivery for resp disorders
  • ↓Systemic A/E
 Inhaled Pulm. VDs: Nitric oxide, Prostacyclin, Oxygen

Prostacyclin

Definition: A prostaglandin produced by pulmonary endothelium

MoA

  • Binds prostacyclin receptor
  • Activates AC
  • ↑cAMP
  • ↓MLKC activity & Ca2+ availability

Effects

  1. VD
    1. ↓cAMP
    2. Inhibits platelet aggregation + counteracts TXA2 ↑Ca2+ which leads to platelet activation & coagulation
  2. Potent inhibition of smooth m. cell proliferation

A/E

  • Hypotension
  • Flushing
  • Headache
  • Bleeding

Nitric Oxide

Definition: an inorganic gas & free radical

MoA

  • Diffuses into vasc smooth m.
  • Activates enzyme GUANYLYL CYCLASE
  • GC catalyses formation of 2nd messenger cGMP
  • cGMP activates protein kinases
  • ↓intracellular Ca2+ → smooth m. relaxation → VD

A/E

  • MetHb
  • Pulmonary oedema
  • Tachyphylaxis
  • On abrupt cessation, profound ↓PaO2 & ↑PAP
  • Worsens V/Q mismatch

Oxygen

Definition: colourless, odourless, tasteless gas, 21% of atmospheric gas

MoA

  • Prevents HPVC
  • ↓PVR
  • ↑delivery of O2 to alveoli
  • ↑pulmonary BF to these alveoli
  • Improves V/Q matching

A/E

  • Atelectasis
  • Abnormal ciliary transport
  • Free radical production & damage to cap. Membrane
  • Loss of hypoxic drive