Pharmacokinetics and dynamics Flashcards
Define absorbtion
- Transfer of a drug molecule from site of administration to systemic circulation
Which two types of administration have no barriers?
IA
IV
100% dose reaches systemic circulation
State three mechanisms for drug permeation across cell membranes
- Passive diffusion through hydrophobic membrane, e.g. lipid soluble
- Passive diffusion through aqeuous pores, e.g. lithium
- Carrier mediated transport, e.g. neurotransmitters
State two factors affecting drug absorption
- Lipid solubulity
- Drug ionisation
State factors of first pass metabolism
- Degradation by enzymes in intestinal wall
- Absorption from **intestine into hepatic portal vein + metabolism via liver enzymes
Define bioavailability
Proportion of administered drug which reaches the systemic circulation
State factors affecting drug distrubution across compartments
Molecule size –> smaller molecule = more distribution
Lipid solubulity –> lipophillic = more distrubtion
Protein binding, e.g. to albumin –> more protein bound = less distribution
what is Vd
- Theoretical volume of drug distrubuted in the body
- Volume of plasma required to contain the total administered dose
- Well distributed = high Vd
State three ways in which drugs can reach the CNS
- High lipid solubility
- Intrathecal administration, e.g. baclofen in MS
- Inflammation (causes barrier to become leaky)
Define drug elimination
drug becomes no longer available to effect the body
Define metabolism of drugs
Modification of chemical structure to form new chemical entity, or metabolite
State two phases of metabolism
- Oxidation/reduction/hydrolysis to introduce reactive group to chemical structure –> carried out by CYP450 enzymes
- Conjugation of functional group to produce hydrophilic, inert molecule
State the three proceses for renal extraction of drugs
- Glomerular filtration –> free/unbound drug molecules
- Active tubular secretion –> can clear protein binding drugs + drugs transported by OAT + OCT
- Passive reabsorption –> highly polar drugs + hydrophobic drugs
Define the half life of a drug, and what what this is dependant on
- Time taken for plasma drug conc to fall below 50%
- Dependant on clearance (CL) of drug from body by all eliminating orans
- Dependant on volume distribution (drug wtih large Vd is cleared more slowly)
In relation to half life, which drugs are more likely to cause withdrawal symptoms?
- Drugs with short half life increases risk of withdrawal symtoms
- Therefore drugs may need dose weaning on cessation
