drug mechanisms and receptor interactions Flashcards
what is tolerance?
- measured effect of repeated administration
state the 4 main target sites for drugs
- receptors
- ion channels
- transport systems
- enzymes
describe receptors
- proteins within cell membranes
- activated by NT or hormones
- agonist or antagonist actions
- 4 types of receptors: 1,2,3,4
give an example of an agonist and an antagonist
agonist - ACh
antagonist - Atropine
describe ion channels
- selective pores
- allow transport down electrochemical gradient
what are the 2 types of ion channels?
- voltage-gated e.g. VGCC
- receptor linked e.g. nAChR
describe transport systems
- transport against the concentration gradient
- specificity for certain species
give examples of transport systems and drugs
e.g. Na/K-ATPase, Na Uptake 1
Examples of drugs: TCAs, cardiac glycosides
describe enzymes
catalytic proteins that inc. rate of reaction
name the 3 drug interactions
- enzymes inhibitors (anticholinesterases)
- false substrates (methyldopa)
- prodrugs (choral hydrate –> trichloroethanol)
give an example of an enzyme drug that can have unwanted effect
- paracetamol
- system becomes satured
- switches to a new enzyme to break down drug
- creates toxic-by products
why can warfarin be dangerous?
it is a drug that binds very strongly to plasma proteins and so can provide a dangerous and untapped reservoir of the drug
what is the MoA of ant acids?
simple addition of a base to acidic environment which evens acid-base balance
describe the MoA of osmotic purgatives (laxatives)
draws water into gut to dec. viscosity
how can drugs be described
- agonists/ stimulatory
- antagonists/ mimic and block
- full or partial agonistic effects
what does the potency of a drug depend on?
- affinity
- efficacy
what is affinity?
strength of binding of the drug to the receptor
what is efficacy?
biological effect of drug
what are antagonists?
have affinity but no efficacy
what are the 2 types of receptor antagonism?
- competitive
- irreversible/non-competitive
describe competitive antagonists
e.g. Atropine
same site as agonist
surmountable
shifts dose-response relationship to R
describe non-competitive antagnonists
e.g. Hexamethonium
- bind to active site irreversibly
- changes conformation
insurmountable
what are the 4 types of drug antagonism
- receptor blockade
- physiological antagonism
- chemical antagonism
- pharmacokinetic antagonism
describe receptor blockade
- competitive and irreversile
- display use dependency
what is use dependency?
more the cell is active, the faster the block is absorbed and blocks the ion channels
describe physiological antagonism
drug that counters the effect of another substance by acting on different receptors
give an example of physiological antagonism
if the body has too much NA so too much vasoconstriction, histamine can be delivered to counter vasoconstriction
act on H1 receptors instead of adrenergic receptors
describe chemical antagonism
drugs that interact in solution to antagonise a reaction
give an example of chemical antagonism
if people have heavy metal poisoning, you give dimercaprol to bind the heavy metal and form non-toxic clumps which can be excreted
describe pharmacokinetic antagonism
drugs that are administered, are antagonised by body itself that reduces the conc
- reduced absorption
- blocked distribution
- inc. metabolism
- inc. excretion
what are the 5 reasons for drug tolerance?
- pharmacokinetic factors
- loss of receptors
- change in receptors
- exhaustion of mediator stores
- physiological adaption
describe pharmacokinetic factors
due to inc. rate of metabolism e.g. alcohol
describe loss of receptors
due to membrane endocytosis of receptors e.g. beta adrenoreceptors
describe change in receptors
- conformational change in receptors
- may reduce affinity
- e.g. beta adrenoreceptors
describe the exhaustion of mediator stores
physiological mediators become exhausted e.g. amphetamine - stores of NA that are usually released become exhausted
describe physiological adaption
body physiologically adapts to administration of drug over time
what are the 4 different receptor families?
- ion-channel linked receptors (5 binding domains in subunit, milliseconds)
- GPCR (7-TM structure, seconds)
- Kinase-linked receptor (only one subunit (alpha helix), minutes)
- intracellulae steroid type receptor (intracellular, zinc fingers, houes)
