Pharmacokinetics 2 Flashcards
(22 cards)
Who do you love?
Little One!! hehehehe
Lipophilic nature allows:
Passage through biological membranes, access to site of action, BUT hinders excretion
What does lipophilic nature hinder
Excretion
How are lipophilic compounds largely reabsorbed into systemic circulation?
During passage through renal tubules
Drugs and xenobiotics have to be turned into what for elimination from body?
Hydrophilic metabolites
What does metabolism/biotransformation do?
Generates more polar (water soluable) metabolites
Prodrug is what?
Pharmacologically inactive, converted to active metabolite, and maximizes amount of active species that reach site of action
What is the main function of Phase I metabolism?
Prepare the compound for Phase II metabolism
Phase I metabolism includes which 5 reactions?
Oxidation, Reduction, Hydrolysis, Hydration, Isomerization
Phase I metabolism is responsible for?
Functionalization reactions, converting parent drug to more polar metabolite.
Phase I metabolism may result in?
In loss of pharmacological activity, sometimes may be equally of more active than parent.
Where are Phase I oxidative enzymes mostly localized?
Almost exclusively localized in the endoplasmic reticulum.
Phase II metabolism is
conjugation reactions
Phase II enzymes are located?
Predominantly in the cytocol
Name the factors affecting drug metabolism
Environmental Determinants, disease factors, age & sex, genetic variation
Cytochrome P450 monooxygenase system
Superfamily of heme containing proteins, involved in metabolism of diverse endogenous & exogenous compounds which include (drugs, environemental chemicals, other xenobiotics.
Phase I Metabolism Summary..
Final product contains chemical reactive group such as OH, NH2 etc..,functional group can be acted upon by phase II or conjugative enzymes
Is it possible for drugs to undergo phase II followed by phase I?
Yes, isoniazid
CYP 450s
Basis of nomenclature system is divergent evolution-sequence similarity between the cytochrome P450s.
Categorized into 17 families (CYPs)-sequences >40% identical, identified by Arabic number, CYP1
Further into subfamilies-sequences >55% identical, identified by a letter CYP1A
May have different, individual isoforms-identified by another Arabic number, CYP2D6
Phase II (conjugation reactions) are…
Reaction in which a covalent linkage is formed between a functional group on the parent compound or Phase I metabolite and an endogenous substrate.
What are examples of endogenous substrates?
Glucuronic acid (glucuronidation)-most common
Sulfate (sulfation)
Acetic Acid (acetylation)
and amino acid ( glutathione conjugation, glycine conjufation)
Alkyl group (methylation)
Phase II Metabolism is
where highly polar metabolites are formed (excreted in urine & feces, usually inactive)-exception is morphine 6-glucuronide
- the true detoxification of drugs
- occurs mostly in cytosol
- stereoselective reactions( isomers of many drugs are metabolized differently)
