Respiratory Drugs

Pharmaceutics: colorless, odorless gas. Available as pure compressed gas or liquid oxygen in sealed vessel. Generated by nitrogen adsorption from air AKA "O2 concerntrator", fractional distillation of liquid air, or hydrolysis of water.

Pharmacodynamics:

Mechanism: Oxidizer of terminal cytochrome enzyme in electron transport chain; facilitates oxidative phosphorylation and efficient generation of ATP.

Toxicity:

1. Free radial toxicity
2. Pulmonary effects (PaO2 >100): Lipid peroxidation → alveolar collapse
3. CNS effects (PaO2 >200): Confusion, euphoria, visual changes, seizures
4. Increased peripheral vascular resistance; cerebral and coronary vasospasm
5. Absorption atelectasis (lack of nitrogen in inhaled gas leads to complete absorption of gasseous mixture → alveolar collapse)
6. Decreased respiratory drive (minimally, mostly driven by PaCO2)
7. Increased PaCO2 (by haldane effect)
8. Retinopathy of prematurity in newborns
9. Increased renal PO2 → decreased erythropoiesis

Indications:

1. Supplementation (in hypoxia)
2. Prophylaxis (de-nitrogenagation of FRC perianaesthetic)
3. Antidote (CO poisoning)
4. Treatment of cluster headache, decompression sickness, anaerobic infections

Pharmacokinetics:

Absorption: Absorbed by diffusion across the alveolar membrane. 250mL/min absorbed at FiO2 0.21. Absorbtion increased by increased FiO2 or atmospheric pressure.

Distribution: \(2.2L \cdot 0.21 \approx 0.5L\) in FRC.

\(1.34mL g^{-1} \cdot 150g L^{-1} \cdot 1.0 \cdot \approx 200mL L^{-1} = 1L\) total bound to Hb.

Approximately 200mL bound to myoglobin

Approximately 50mL dissolved in tissues

Metabolism: Converted to CO2 and water in all cells (but especially heart and brain). Mostly by mitochondrial cytochrome enzymes as terminal electron acceptor. Zero-order clearance kinetics.

Elimination: 75% of the oxygen in arterial blood is returned to the left heart in mixed venous blood, where it reequilibrates with alveolar gas.