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Drug Hypersensitivity - Coggle Diagram
Drug Hypersensitivity
Acute Renal Failure
Drugs are an intrinsic cause of interstitial nephritis
Bactrim, rifampicin, herbal remedies/traditional medications, NSAIDs
Immunologically mediated hypersensitivity reaction to an antigen, classically drug or infectious antigen
Clinical manifesations - rash, joint pain, eosinophilia, eosinophiliuria
Rifampicin - generaly occurs after being reintroduced after an interval, flu-like symtpoms, flank pain, hypertension, oliguria and ARF are common
Treatment - cessation of drug usually resolves problem, if not consider renal biopsy & high dose prednisone
Type 4 spectrum (mainly SCAR)
SCAR = severe cutaneous adverse drug reactions, either confined to skin or multisystem
Stevens-Johnson syndrome and Toxic epidermal necrolysis
Drug rash with eosinophilia & systemis symptoms
Lichenoid drug eruptions
Acute generalised exanthematous pustulosis (AGEP)
Factors
Chemistry
Reversible & irreversible protein binding, metabolism
Pharmacology
Hapten, antigen & immunogen formation
Immunology
Innate (complement, acute phase proteins, neutrophils, macrophages, dendritic cells, NK cells) & adaptive (B & T cells) immune system
Patient factors
Genetics, disease
NSAID hypersensitivity
Classification of NSAIDs
Non-selective COX inhibitors
Preferential COX-2 inhibitors
Selective COX-2 inhibitors
Analgesic-antipyretic with poor anti-inflam action
Most common class of drugs causing hypersensitivity reactions
Rapid aspirin desensitisation - important because of role in managing CAD
Drug Induced Liver Injury (DILI)
Antimicrobials (37%), herbal/dietary supplemetns (14%), lipid lowering agents (5%), antineoplastic drugs & NSAIDS (4%), psychotropics & immunosuppressants (3%)
Genetic variability
N-acetyltransferase 2 & CYP2E - anti-TB therapy
Cytokine polymorphisms - diclofenac
HLA associations - Co-amoxyclav
ACE-induced angioedema
Due to vasodilatory effect of bradykinin & other molecules, it is not immune-mediated
Most common cause of drug-related angioedema in SA
Drugs causing majority of AR
Antibiotics, general anaesthetics, ACE-inhibitors, aspirin (& other NSAIDS), local anaesthetics, radio-contrast media, others (insulin, opiates, vaccines, heparin, plasma expanders)
TB drug-related DRESS syndrome
Penicillin hypersensitivity