Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Uses
Itis used to prevent hypoxaemia.

Measurement
Depending on the sample type, various means are used to measure O 2 .Inamixture
of gases a mass spectrometer, paramagnetic analyzer or fuel cell may be used; when
dissolved in blood a Clarke electrode, transcutaneous electrode or pulse oximetry
may be used; in vitro blood samples may be analyzed by bench or co-oximetry.

Effects
Cardiovascular – if O 2 is being used to correct hypoxaemia then an improvement
in all cardiovascular parameters will be seen. However, prolonged administration
of 100% O 2 will directly reduce cardiac output slightly and cause coronary artery
vasoconstriction. It causes a fall in pulmonary vascular resistance and pulmonary
artery pressure.
Respiratory – in healthy subjects, a high concentration causes mild respiratory
depression. However, in those patients who are truly dependent on a hypoxic drive
to maintain respiration, even a modest concentration of O 2 may prove fatal.

Toxicity
O 2 toxicity is caused by free radicals. They affect the CNS resulting in anxiety, nausea
and seizures when the partial pressure exceeds 200 kPa. The alveolar capillary mem-
brane undergoes lipid peroxidation and regions of lung may collapse. Neonates are
susceptible to retrolental fibroplasia, which may be a result of vasoconstriction of
developing retinal vessels during development.

Nitric oxide
Nitric oxide (NO) is an endogenous molecule but it is potentially a contaminant
in nitrous oxide cylinders. It was formerly known as endothelium-derived relaxing
factor (EDRF).

Synthesis
Nitric oxide is synthesized from one of the terminal guanidino nitrogen atoms of
l-arginine in a process catalyzed by nitric oxide synthase (NOS), which is present in
two forms:
Constitutive – which is normally present in endothelial, neuronal, skeletal mus-
cle, cardiac tissue and platelets. Here NOS is Ca^2 +/calmodulin-dependent and is
stimulated by cGMP.
Inducible – which is seen only after exposure to endotoxin or certain cytokines in
endothelium, vascular smooth muscle, myocytes, macrophages and neutrophils.
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