ADME Flashcards
Pharmacodynamics
Pharmacological action of drug
Pharmacokinetics
Factors effefting onset, duration, and termination of drug action.
Routes of drug administration
Oral Sublingual Nasal Rectal Vaginal Epithelial Inhalation Intravenous Subcutaneous Intramuscular Intrathecal.
Drug absoption from the GI tract
Lipophillic, uncharged drugs diffuse easily through bilayer.
Other molecules need carriers (pretty ineffective).
Pinocytosis is also a way to cross but very inefficient.
Most drugs in equilibrium so the uncharged part passes through thus creatkng more uncharged due to shift in equilibrium.
For acids - when pH of the environment increases above pKa by one unit ionisation becomes 10:1
By 2 units ionisation becomes 100:1.
Drug absorption in stomach
pH is about 2
Acidic drugs are mostly unionised therefore readily absorbed.
Neutral drugs are also readily absorbed.
Basic drugs are mainly ionised so poorly absorbed.
Drug absorption in duodenum
pH is about 8.
Basic drugs are mainly unionised therefore readily absorbed.
Acidic drugs are mainly ionised which should restrict absorption but due to huge surface area they will be absorbed as equilibrium is constantly shifting.
First pass effect
Blood from upper GI tract passes first through the hepatic portal vein to the liver where drugs can be Metabolised.
This is to protect the body from things that may pass through the gut but could harm the heart or elsewhere if they reachbsystemic circulation.
It geatly diminishes the amount of drug reaching systemic circulation, some drugs are not orally active because of this, prodrugs made into drugs by this sometimes.
BBB
Prevents entry of large or ionised drugs into CNS
Only lipophillic and transport hijacker drugs can get through.
Blood placental barrier
Prevents entry of large or ionised drugs to foetal bloodstream.
Protein binding
Mainy drugs bind efficiently to plasma protein
The bound fraction is not free to distribute
Only free fraction is active.
Can get drug-drug competition for binding sites (ie aspirin displaces warfarin on albumin).
Distribution away from the site of action
Add a vasoconstrictor (Adr) to slow down diffusion of the drug away from site of action.
Prolonging duration of drug action.
Metabolism
Lipophillic drugs cannot be excreted from the body.
They need to be biotransformed into more water soluble metabolites to permit excretion.
Liver is major, but not only, site of metabolism.
Metabolism occurs in two phases (usually).
Phase one metabolism
Adds a chemically reactive functional group (-OH,-NH2,-COOH).
May involve oxidation, reduction or hydrolysis.
May inactivate the drug (most common) or activate the drug (prodrug).
May produce a toxic metabolite.
Giving a prodrug acts like a slow release drug in the body as it is hydrolysed throughout the day into the active drug.
Most common phase one reaction is oxidation catalysed by cytochrome p450.
Phase one not necessary if drug has a chemically reactive group already.
Phase two drug metabolism
Adds a large water soluble group to aid excretion.
Not always necessary if phase 1 compound can already be excreted (is already water soluble).
Cytochrome P450
Finite ability
Heam containing enzymes.
Metabolises most commonly used drugs.
Mono-oxygenase reaction is most commonly catalysed.
Drug-Drug interactions will occur when two drugs are both Metabolised by the same P450 molecule. One will inhibit/increase the others metabolism.
Some drugs induce expression of P450 whereas otwhers inhibit it.
Inducers - barbiturates, phenytoin, carbamazepine, cigarette smoke and st johns wort.
Inhibitors - cimetidine, disulfiram, quinine, erythromycin, grape fruit.
Commonly a drug will induce its own metabolism leading to drug tolerance and underdosing.
