pharmacology: fundamental principles Flashcards
what are drugs
exogenous molecules that mimic or block the action of endogenous molecules/systems
type of drugs
agonist: bind to receptor specific to it, provoking a response
antagonist: binds to receptor specific to it -> prevents receptor from being activated
what determines if a drug reaction is reversible or irreversible
reversible: ionic attractions + hydrophobic interactions (lipophilic parts)
irreversible: covalent bonds formed
pharmacodynamics vs pharmacokinetics definition
pharmacodynamics: what drug does to an organism
pharmacokinetics: what organism does to the drug (absorption/distribution/metabolism/excretion)
what factors affect absorption of a drug
molecular size
lipid solubility/ionisation
chemical/metabolic vulnerability (how easily it is broken down/altered)
route of administration
pt characteristics (size/weight/fed state/health condition)
routes of administration (15)
inhalational intra-arterial (ia) intracerebroventricular (icv) intradermal intramuscular (im) intrathecal (it; into membranes enclosing spinal cord) intravaginal intravenous (iv) nasal oral (po) rectal subcutaneous (sc) sublingual topical transcutaneous (blasted through skin under pressure)
factors affecting distribution of a drug
solubility
does it stick to proteins/cells (eg wafarin is plasma protein bound-> tends to stay within vascular compartment)
does it concentrate in fats/aqueous compartments (will distribute to adipose or CNS if lipophilic)
does pt have adequate circulation? (blood supply might be cut off to one part of the body)
factors affecting metabolism/excretion
state of liver (unhealthy liver-> 1/2 life increases; clearance decreases)
state of kidneys (unhealthy kidneys-> 1/2 life increases; clearance decreases; plasma levels increases)
are the metabolites active
are the metabolites toxic
3 names that drugs have
proprietary (tradename)
common name
chemical name
how are drugs characterised; eg
3 names, therapeutic use, mechanism
eg disprin/aspirin/acetylsalicylic acid
use: analgesic/anti-pyretic/anti-platelet/anti-inflammatory
mechanism: cyclooxygenase inhibitor
preclinical drug discovery
5-10 years;
natural products + compound libraries + combinatorial chemistry = starting chemicals -> assay systems -> active chemicals + optimisation-> animal models-> drug candidate
clinical development
phase I: 20-80 healthy volunteers; discover side effects/safety/clearance/bioavailability; tolerability and dose-finding
phase II: 100-300 pt volunteers that have condition; discover side effects/safety/effectiveness
phase III: 1000-3000 pt volunteers; discover LT side effects/safety/effectiveness; compare with other meds -> REGISTRATION
phase IV: ongoing post reg studies/LT safety
concentration dose relationship, what happens when you log it
hyperbola-> symmetrical sigmoid
whats Emax and EC50
emax : max response that a drug can produce
ec50: concentration of drug that produces 50% of max response
receptor properties and function
how are they classified
how do pharmacologist design drugs with fewer side effects
protein macromolecules; recognition/detection and transduction
classification according to which drugs they bind
design drugs that are highly specific -> only binds to certain subtypes of receptor
is binding of a drug to receptor reversible?
shape of plot of proportion of receptors occupies vs drug concentration + what happens when you log it
yes
rectangular hyperbola-> sigmoid
affinity and kd definition; their relationship
affinity: the molar concentration of drug required to occupy 50% of receptors at equilibrium
kd: measure of chemical attraction
inverse relationship
affinity vs efficacy
many drugs have affinity, but only agonists have affinity + efficacy because they bind AND cause conformational change, activating the receptor
two types of agonists; response against proportion of receptors occupied graph (and in log form) what does this imply
full agonists have high efficacy; partial agonists have low efficacy
full agnosts have full response even if only some receptors r occupies
partial agonists never react full response, even if all receptors are occupied
log form: symmetrical sigmoid
antagonist types
competitive (reversible/irreversible)
non-competitive: binds to different site/closely associated molecule
how to overcome effects of reversible competitive antagonist?
how does graph (response vs log agonist) move in the presence of an increasing amount of antagonist?
what does the extent of shift imply?
how to measure extent of shift?
increase [agonist];
parallel shift to right;
implies affinity of antagonist for receptor;
dose ratio: [agonist] producing response in presence and absence of antagonist
how does graph (response vs log agonist) move in the presence of an increasing amount of irreversible antagonist?
rightward and downward shift
what is pa2? how to calculate pa2? what does an bigger pa2 imply?
affinity for antagonist
negative log of [antagonist]
implies greater affinity
