PK and PD Flashcards
Pharmacology definition?
Describes the interaction between drugs and organisms
Pharmacokinetics definition?
Deals with the effect of the BODY ON THE DRUG, through absorption, distribution, metabolism and excretion
Pharmacodynamics definition?
Deals with the effect of the DRUG ON THE BODY, how a drug acts and its side effect etc.
Difficult “sites” for drugs to reach?
Brain
Bone
Lung (TB cavities)
PK: Determinants of treatment response?
- Concentration dependent (Cmax is NB)
2. Time dependent (area under drug/time curve is NB)
Principles of drug absorption?
Absorption is the process of crossing biological barriers into the blood
Drugs cross cell membranes passivly (by diffusion) or actively (with the aid of endocytosis or transporters)
The bioavailability of the drug is the % of unchanged drug that reaches the systemic circulation after administration (i.e. IV bioavailability is 100%)
Explain ‘first pass metabolism’?
Substantial portion of drug is metabolised in the GIT/liver before netering the systemic circultion
4 primary first pass metabolism systems are:
- enzymes of GIT lumen
- gut wall enzymes
- bacterial enzymes
- hepatic enzymes
Examples of drugs that under substantial first pass metabolism?
Imipramine (TCA) Morphine Cyclosporin Diazepam Lignocaine
Principles of distribution?
Apparent volume of distribution (Vd): relates the plasma concentration to the amount of drug in the body (Vd = amount of drug in body/measured concentration)
Vd helps determine the loading dose (loading dose = Vd x C)
Protein binding is a major determinant of distribution: only UNbound drug can bind to receptor and act, and only the UNbound drug can be metabolised and excreted
Protein binding prolongs the effect of a drug
BBB (22m squared): barrier to penetration of drugs, except for those that are lipid soluble and small
Drug metabolism processes?
Drugs are generally lipophilic allowing them to cross membreanes
Metabolism is necessary to generate hydrophilic metabolites for excretion
High metabolism potential in liver, GIT, kidneys and lungs
Phase 1: introduces or exposes a functional group (e.g. oxidation, hydrolysis)
Phase 2: adds a polar conjugate for excretion into bile or urine (e.g. glucuronide)
Substrates = metabolites
Most metabolites lose activity compared to parent drug/substrate, but some metabolites are more active
Pro-drugs are inactive substrates that need to be metabolised into active drugs
CYT P450 inducers and inhibitors?
Inducers (speeds up metabolism)(maximal at 2-4weeks and wanes in a similar time): Rifampicin NNRTI's (efavirenz*, nevirapine) Phenytoin Carbamazepine
Inhibitors (slows down metabolism)(occurs rapidly): PI's Macrolides Efavirenz* Azoles
First order vs zero order metabolism?
First order metabolism is when the rate of metabolism increases with plasma concentration; dose increase results in linear increase in drug concentration; non-saturable
Zero-order metabolism is when drugs saturate their metabolisms enzymes, and are then metabolised at a rate independent of drug concentration; dose increases result in exponential increased drug concentration
Prinicples of elimination?
Kidney is the most common route of elimination
Drug clearance (CL) = rate of elimination/drug concentration If zero-order, the rate of elimination is constant
Elimination half-life: the time taken for the conentration of the drug to halve
T1/2 is proportional to Vd/C
Determines the dosing interval and time to steady state
Variations in ADME?
Young children: less liver metabolism, smaller size, often can’t tolerate tablets
Elderly: decreased muscle, increased fat (Vd affected), adherence issues, co-morbidities
Pregnancy: increased blood volume, increased volume of distribution, decreased serum concentrations, less protein, increased clearance rates
Malnourished
Severely ill: less perfusion to muscle and liver, multiple drug use
Alcoholics
