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19 Cards in this Set
- Front
- Back
Type 1 Adverse Reaction |
Predictable |
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Type 2 Adverse Reaction |
Not predictable |
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Pharmacokinetic genetic polymorphism affects: |
Absorption Metabolism Disposition Excretion |
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Pharmacodynamic genetic polymorphism affects: |
Receptors Ion channels Enzymes Immune system |
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Lack of metabolism |
Increased plasma concentrations Exaggerated pharmacological responses |
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Lack of metabolic pathway |
Compound bioactivated by different enzyme |
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Lack of detoxification pathway |
Enhanced toxicity |
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Lack of bioactivation pathway |
Poor metabolisers at less risk |
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Increased protein expression or catalytic activity |
Increase in the formation of toxic metabolites |
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Lack of detoxification:
Suxamethonium |
-Used for muscle relaxation during surgery -Effects last 2-6 minutes -Hydrolysed rapidly by plasma esterases (pseudocholinesterase, butyrylcholinesterase) -Reduced activity in certain patients --> results in prolonged muscle paralysis and apnea |
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Lack of detoxification:
6-Mercaptopurine |
-Gets S-methylated by thiopurine methyl transferase (TPMT) -Low TPMT activity = high risk of haematopoietic toxicity -Due to accumulation of thioguanine nucleotides in haematopoietic tissues -Therapy: 10-15 fold reduction in dose |
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Lack of detoxification:
Perhexiline |
-Anti-angina drug -Cationic, amphiphilic -Metabolised by CYP2D6 -If not metabolised, can accumulate in lysosomes -Results in hepatotoxicity and neuropathy |
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Genetic Profiling |
Understanding the polymorphisms that dictate how our body deals with a particular drug means we can tailor the drugs we take and dosage for optimal effect |
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Penicillin |
-A very diverse range of reactions -Common nausea, diarrhoea, hairy tongue -Infrequent neuropathy, nephropathy, haemolytic anemia, thrombocytopenia -Hypersensitive reactions anaphylaxis, skin eruptions, laryngeal oedema |
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Ethanol |
-Acts at GABA receptors -Drinking with sedatives, hypnotics and some antihistamines can have additive effects -Too much sedation or coma and death |
|
GABA, GABA, GABA, GABA, GABA.... |
...death. |
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Warfarin |
-Narrow therapeutic index -Cimetidine inhibits warfarin metabolism --> blood concentrations of warfarin increased to toxic levels |
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Terfenadine |
-Metabolised by CYP to fexofenadine -DEATH with ketoconazole (inhibits CYP3A4) --> Increased plasma concentrations
-Interferes with cardiac slow K+ channel, prolonging QT interval and quinidine-like effects on heart |
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Baycol/Lipobay
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-Statin, cholesterol lowering drug -More frequent deaths from rhabdomyolysis than other statins, so was recalled
-Major financial impact on company, they had to cut jobs and drug unit was split in two |