Pharmacology Flashcards
pharmacokinetics
what a body does to a drug
pharmacodynamics
what a drug does to the body
ADME
Administration, Distributions, Metabolism, Elimination
Administration
Enteral - sublingual, swallowing, rectal
Parenteral - topical, intradermal, subcut, IM, IV, inhalation
IV - accurate control of concentration, used for drugs with narrow safety margins
Inhalation - rapid effect, may cough out, dependent on particle size and tidal volume
Distribution
reaches circulation - needs to penetrate tissues
active transport/carrier mediated
passive transport/diffusion
through membrane as pair with ion
can go into fat
must be neutral to cross
cross more rapidly if - neutral, high lipid.water partition in non-ionised compounds, low molecular weight, biological affinity with transporters, small size particles
effect of pH
Metabolism
2 phase - catabolic and anabolic - becomes drug derivative and the a water soluble drug
sometimes only 1 phase
Biotransformation
non lipid soluble drugs –> oxidised by cytochrome P450 enzymes –> either water soluble product or next phase –> broken down to transferase (water soluble)
liver metabolism
broken down by enzymes in the SER of hepatocytes
detoxification
forms inactive metabolites - sometimes metabolites produce similar effects to the drug itself
also can break down toxic metabolites
cats & paracetamol - no UTGs so causes methemoglobinuria
Cytochrome P450s (CYP450s)
enzymes
mosrtly formed in liver but some in intestinal walls
metabolise drugs
need iron - problem if anaemic
Excretion
major routes - renal, biliary, pulmonary
minor routes - mammary, salivary
Drug-drug interactions
levels of one drug altered by another
absorption - affected by pH, bacterial flora, decreased gastric emptying
excretion - urine pH and reduced renal excretion
inhibition or induction of enzymes
CYP450s affected by lots of drugs
Therapeutic window
concentration where we know there is an effect
TMax
maximum effect time
CMax
maximum concentration - needs to be below level of toxicity
Rate vs time graphs
zero order - flat horizontal line - IV infusion
first order - diagonal up - IM, Subcut, oral - absorption rate proportional to amount of drug
elimination rate
amount of drug eliminated per unit time
Initial volume of distribution (Vi)
volume of blood + interstitial fluid
Volume of distribution (Vd)
volume into which a drug appears to be distributed (litres/kg)
low Vd - mainly accumulated in extracellular fluid
high Vd - drug accumulating in another site (Eg. fat)
total body clearance
volume of blood/plasma cleared of parent drug per unit time
bioavailability
% of administered dose that reaches the plasma
compartment models
one compartment - spreads equally around the body
two compartments - vessel rich groups first then other tissues
vessel rich group –> muscle –> fat
loading dose
initial larger dose, followed by constant rate infusion
potency
amount of drug needed to produce 50% of maximum effect
efficacy
maximum therapeutic effwct/how well the drug activated receptors
affinity
tendency of drug to bind a particular receptor
Agonist
produces an effect at a receptor
full agonist - 100% activation
partial agonist - any less than 100% activation
Anatagonist
binds but doesn’t produce an effect
competitive - competes with agonists at binding sites - curve shifts to right
non-competitive - binds to a different site downstream of receptor (ketamine) - curve flattens and moves downward
irreversible - dissociates from receptor very slowly or destroys it
Inverse agonist
acts on receptor that usually fires on its own to reduce activation
therapeutic index
toxic dose/effective dose
EC50 - effective concentration - dose needed to reach 50% maximal effect
ED50 - effective dose - dose that will produce therapeutic effects in 50% of population
receptor types
ion channel cell surface transmembrane receptor
ligand regulated enzymes
g-protein coupled receptors
protein synthesis regulating receptor
tachyphylaxis
reduction in tolerance that develops of short period of time - becomes less effective with repeated doses
