Pharma 1 Flashcards
Common SE of muscarinic receptor blockade
> Facial flushing – inhibited eccrine sweat glands and compensatory cutaneous vasodilation.
Pupil dilation – inhibited pupillary constrictor and ciliary muscles.
There are fast and slow acetylators.
What type of genetic changes cause this? What happens?
Pharmacogenetic polymorphisms in drug metabolizing capacity.
Slow acetylators accumulate certain drugs that metabolize via acetylation (isoniazid, dapsone, hydralazine, procainamide).
CYP450 enzymes
Heme-containing proteins in liver – deactivate drugs, facilitate excretion by improving drugs’ H2O solubility.
Genetic polymorphisms may lead to altered expression or activity of these enzymes – different phenotypes (poor, intermediate, rapid metabolizer).
Cyanide toxicity
[Causes, tx]
> Nitroprusside infusion – metabolism of nitroprusside releases NO and cyanide ions.
Cyanide ingestion – mitochondrial toxin; binds to Fe3+ in cytochrome C oxidase – inhibits ETC, aerobic respi.
Tx: sodium sulfate (sulfur donor), sodium nitrate (induces methemoglobin, w/c combines w/ cyanide), hydroxocobalamin (cyanocobalamin excreted).
How is cyanide metabolized in tissues? What is the treatment?
Rhodanese found in tissues transfers sulfur to cyanide –> thiocyanate –> less toxic, excreted.
Cyanide overdose depletes sulfur donors.
Tx: sodium sulfate (sulfur donor)
Patients with renal damage need to take drugs w/ high hepatic clearance. What are the properties of these drugs?
> Highly lipophilic: readily enters hepatocytes to be excreted in bile.
High Vd to other tissues (brain, liver, adipose).
*Drugs w/ low Vd are more plasma protein-bound and hydrophilic – less available for hepatic metab, more likely excreted unchanged in urine.
Why should rodenticide consumption be avoided? How do you treat this?
Rodenticides have brodifacoum (“superwarfarin”) – similar sx to warfarin toxicity – Depletes vit k-dependent clotting factors.
Tx: IV fresh frozen plasma (replenish clotting factors) + vit K
What tx is most effective for warfarin overdose? Heparin overdose?
> Warfarin: fresh frozen plasma, vit K.
>Heparin: Protamine (heparin-specific antidote)
Upon IV administration, how do lipophilic drugs (anaesthetics) distribute and redistribute?
Highly lipophilic drugs will rapidly distribute to organs w/ high blood flow first (brain, liver, kidney, lungs) – then redistribute to poorly vascularized compartments (skeletal muscle, fat, bone).
