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Hypersensitivity reactions

Created: 13/4/2004

There are two types:

Type A:  dose-dependent/ predictable/ mechanism-based reactions

There may be random variability and individual variation

i.e. physiological (extremes of age, pregnancy), pathological (renal failure, hepatic impairment)

Morphine is an example of a type A drug

Histamine release (anaphylactoid reaction):

This can be caused by:

- basic drugs

- solubilising agents, e.g. cremophor EL

- radiocontrast media

- colloidal plasma expanders

- polypepetides, e.g. polymixins, vancomycin (red man syndrome)

Most deaths are due to TYPE A reactions!!

Type B:  dose-independent/ unpredictable/ idiosyncratic reactions

(i) reactions due to genetic factors:

Malignant hyperthermia

- triggered by suxamethomium and volatiles (halothane)

- abnormality in the RYR gene, causng an abnormal Ryanodine receptor

- massive Ca release from sarcoplasmic reticulum

- high RR/tachycardia/acidosis

- treatment: dantrolene, which uncouples electrical processes

Prolonged apnoea

- susceptibility to acetylcholinesterase and also mivacurium

- allelomorphic genes E1u, E1a, E1f, E1s

Acute hepatic porphyria

- overproduction of haem

- wide range of drugs including barbiturates, some antibiotics and drugs metabolised by p450

(ii) reactions due to drug hypersensitivity

- type I: immediate, anaphylactic shock, release of IgE causing release of mediators from mast cells

- type II: drug combines with cell components, i.e. antibiotics

- type III: serum sickness (not important)

- type IV: exposure to silver

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