L11.2 ADME Flashcards
how does the body deal with drugs that are taken?
ADME
A: Absorption- how a drug gets into the body
D: Distribution- how a drug moves around the body
M: Metabolism- how a drug is changed in the body
E: Excretion- how a drug is removed from the body
what are the routes of administration?
enternal: absorption through the GI tract (oral, rectal)
parenteral: all other routes (injections, sublingual, inhalation, topical)
what are the advantages and disadvantages of oral administration?
advantages: convenient, 75% absorbed in 1-3hr, slow release formulation
disadvantages: some drugs not well absorbed, irritation to gastric/intestinal mucosa, food can delay/affect absorption, much slower absorption than parenteral, inactivation by ‘first pass’ metabolism by the liver
what are the advantages and disadvantages of rectal administration?
advantages: avoids ‘first pass’ metabolism, reduces nauseal/vomitting, good when patient is unconcious/seizures, local inflammation (e.g. haemorrhoids)
disadvantages: inconvenient, absorption often incomplete
describe metabolism by liver hepatocytes
drugs that are absorbed from the gut reach the liver via the hepatic portal vein before entering the systemic circulation. some drugs may have low bioavailability/distribution due to this first-pass effect.
some drugs can be given as pro-drugs, relying on the body’s metabolic processes to make an active metabolite.
some metabolites are active, most are inactive
what is bioavailability?
how much is available to the body after first pass metabolism; fraction of oral dose that reaches systemic circulation
what are the different types of injection methods? advantages? disadvantages?
intramuscular, subcutaneous, intravenous, intradermal
advantages: rapid onset compared to oral; drugs are not broken down by acid/enzymes as in the gut; ‘first-pass’ metabolism in the liver is less of a problem
disadvantages: less convenient (skilled person needed); risk of infection; more toxicities (higher peak blood levels)
what are the non-needled administration
sublingual: dissolve tablet under the tongue
topical: direct application to diseased or injured site
(see notes for more info)
describe the mechanism of passive diffusion for drugs
passive diffusion is the movement of substances across cell membranes without any energy needed.
sufficient concentration and time are needed if the drug molecules can pass through the membrane.
what are the two major types of enzymatic reactions
- phase I reactions: oxidants, reduction, hydrolysis
2. phase II reactions: add water-soluble moiety to drug (glucurondine, gluthathione, sulfate, acetate)
describe the phase I reactions
oxidation:
- more than 50 different forms of cytochrome P450 enzymes exist, with different substrate specificities and mechanisms
- most lipophilic drugs and environmental chemicals are substrates for one or more forms of P450
reduction and hydrolysis:
- each reaction, whether oxidation, reduction or hydrolysis, increases the water solubility of the resulting metabolite
(see notes for phase II reactions)
(see notes for phase II reactions)
what are the factors affecting drug metabolism?
genetics (e.g. metabolism of codeine to morphine), age (aged patients and children may metabolise at different rates compared to adults), gender (e.g. women are slower ethanol metabilisers), other drugs being taken (induction or inhibition of P450s), food (charcoal grill ++ CYP1A2) or grapefruit juice – CYP3A4
describe accumulation and steady state
accumulation: administered drug is not completely eliminated during interval
steady state: drug intake equals elimination during dosing interval
T/F: intramuscular injection of drug is much faster for patient treatment than intravenous injection
F
