drug interactions and adverse reactions Flashcards
drug interactions occur at many levels
1) pharmacodynamic interactions
2) opposing effects
3) additive or synergistic effects
- targeting same receptor
4) pharmacokinetic interactions
- drug protein binding
- membrane transporter molecules
- metabolic enzymes
most of GI tract
1) taken up into circulation => HPV => liver => systemic circulation
2) where does metabolism start
- mouth, liver, GI tract
- EVERY SINGLE CELL
metabolism phase I and II
1) phase I
- drug can enter or bypass it
- most drugs are metabolized first here
- create an oxidized/reduced drug (or hydrolyzed)
- makes more polar to mix with water and undergo secondary metabolism
- someone lipophilic drugs excrete in bile after phase I
2) phase II
- add large chunks of molecules onto the drug
- glutathione, sulfation, acetylation, glucuronidation
cytochrome p450
1) mainly attaches to the SER of hepatocytes
2) isolated in the subcellular fraction termed the microsomes
- PACKED with liver microsomal enzymes
3) cytochrome - contain iron
- p450 - absorbed 450 nm of UV light when exposed to CO
P450 isoforms to drug biotransformation
1) be specific to many xenobiotic molecules
2) different isoforms contribute to drug biotransformation
- they are primary metabolic enzymes for different drugs
3) inherent variability of the enzymes and day to day expression of the enzymes
- affect drug levels in patient’s body
phase I oxidized drug
1) hydroxylation
2) primes drug for phase II
3) might result in toxic metabolites
- APAP => benzoquinone amine (toxic)
- must be metabolized in phase II
drugs can be…. of cytochromes
1) substrates
2) inducers
3) inhibitors
some substrates for cytochrome p450
1) benzodiazepines highly metabolized
- benzodiazepine effects potentially INCREASED by macrolide antibiotics, SSRIs, azole antifungals, and grapefruit juice (by reducing their metabolism)
2) narcotic analgesics are produgs activated by CYP, potentially inhibited by quinidine, SSRIs, and NSAIDS
3) lidocaine, little evidence of clinically significant interaction
- metabolism is not so important since it is local injection
some inducers of cytochrome p450
1) barbituates
- less commonly used because therapeutic window is narrow
2) induce CYP synthesis and increase metabolism
3) carbamazepine
- anti-convulsant and neuropathic pain
some inhibitors of cytochrome p450
1) dental drugs that are inhibitors are all antibiotics
2) metronidazole and fluconazole increase blood coumadin and phenytoin levels
3) erythromycin and clarithromycin have broad cytochrome substrate effects increase levels of benzodiazepine
interactions of dental note
1) erythromycin: increases alprazolam, atorvastatin, ondansetron, omeprazole, prednisone
2) hydrocodone: opioids, benzodiazepines, corticosteroids
3) epinephrine and propranolol
- stimulated beta-2 vasodilation
- unopposed alpha-1 vasoconstriction by epi
- acute hypertension
4) NSAIDs and lithium
- prevents excretion of lithium, builds up and is tissue toxic
grapefruit juice interaction
1) many interactions bc it is a metabolite
oral adverse drug events - saliva
1) xerostomia
- anticholinergics, antipsychotics, antidepressants, protease inhibitors
2) sialorrhea: anticholinesterase… etc
mucositis
1) mucosal burns
2) mucositis
3) aphthous like ulcerations
caution
1) don’t administer unnecessary medication
2) interactions may be caused by any drug
3) dental drugs are generally safe
4) polypharmacy only with drugs you know and are comfortable handling
5) interactions are more common in elderly and those less able to compensate
