Principle of pharmacology Flashcards
Types of receptors
Physiologoical (e.g. for compounds like hormones, neurostransmitters), other proteins (enzymes, ion channels), nucleic acids (drugs may bind to influence gene expression or protein synthesis)
Which type of drug interactions are reversible and which are irreversible
reversible-hydrophobic interactions, ionic interactions
irrreversible-covalent bonding e.g aspirin
Pharmacodynamics define
what drug does to organsim-the sum of all actions of drug
Pharmacokinetic define
what organism does to drug (absorption, distribution, metabolism and exccretion of drug). Determines how quickly drug acts in patient
What are the speed of absorption and how much drug enters the system influenced by
molecular size, lipid solubility, chemical and metabolic vulnerability
Meanings of: icv, it, topical, transcutaneous
icv=injected to cerebral ventricles
im=injected into membranes enclosing spinal cord
topical=applied directly to affected areas
transcutaneous=powder blasted through skin under pressure using deviceor by diffusion from adherent patch
What does pharmaacokinetics determine
how quickly drug acts on patient, whether drug effect systemic or local, how long the effects last
3 name categories of drugs
proprietary name, common name, chemical name
What are drugs grouped according to
therapeutic use (analgesis, anti inflammatory, anti pyretic, anti platelet) or by mechanism of action
Drug discovery flow chart
ref. notes
Drug development phases
Phase 0: fifrst in human trial, sub therapeutic dose. Pharmacokinetic info
Phase 1: 20-80 healthy side effect safety, tolerability and dose finding
Phase 2: 100-300 wide effect safety works out effectiveness
Phase 3: 1000-3000 side effect, safety, effectiveness comparison with current available drug.
What happens after phase 3 drug trials
registration with UK’s MHRA or EU’s EMA or USA’s FDA and ongoing phase IV post registration studies, different populations and long term safetu
Sketch [drug] x response curve and log[drug] x response curve
[drug] x response curve=rectangular hyperbola
and log[drug] x response curve=symmetrical sigmoidal, 20-80%=linear
Emax and EC50 define
Emax=max response that drug can produce
EC50=conc of drug that can produce 50% of max response Both used to quantify potency of drug
Receptor what and functions
protein macromolecules usually inserted in lipid bilayer.
Functions: recognition/detection and transdducction. Selectively bind to certain chemicals
Sketch curve of [D] and proportion of receptors occupied as well as log[D] and proportion of receptors occupied
[D] and proportion of receptors occupied=rectangular hyperbola
log[D] and proportion of receptors occupied=symmetrical sigmoid
How is the affinity for a drug to its receptor quantified
molar conc of drug required to occupy 50% of receptors at equilibrium aka high affinity=slow dissociation rate. This conc given in KD
Do drugs with high affinity have high or low KD
low
What is KD
measure of chemical attraction
Many drugs have ____ but only agonists have ____
affinity, efficacy. Agonists bind and activate receptor as opposed to just occupy it. After bindiing, agonists profuce conformational change
Efficacy define
ability of drug to activate receptor and cause conformational change in receptor structure
what are all agonists
neurotransmitters and hormones
Full and partial agonist difference
full=high efficacy, very efffective result at producing biological response
parial=low efficacy, less effective
Compare p x response line for partial and full agonist. Sketch this and log{agonist}xresponse curve for both
Full agonist produce max response whilst activating only a fraction of available recceptors.
Partial agonists fail to produce full response sdespite occupying all available receptors. ref. notes
why would symmetrical sigmoid from log {agonist} x response not accurately reflect affinity
response to agonist is dependent on both affinity and eefficacy
comment on affinity and efficacy of competitive antagonist
have affinity but no efficacy
what happens to effect of antagonist when agonist concentration increases
the blockade effect of antagonist is surmountable
What happens to log [agonist] x response curve in the presence of antagonist
shifts to right. shifts further to right with more antagonist
How to measure antagonist affinity to receptor
extent of shift in position of agonist curve measured using the dose ratio. aka how many times increase [agonist] to overcome antagonist
pA2 what
affinity of antagonist quantified using this. Negative logartihm of molar conc of antagonist that necessiates that you double the agonist concentration to produce the same response (i.e. dose ratio=2.0)
What do irreversible competitive agonists do to log[agonist] x response curve
This shifts the curve to right but shift i not parallel because block is not surmountable ref. notes
