Drug action Flashcards
what is a drug?
a chemical substance that interacts with a biological system to cause a physiological effect
what are the four drug target sites?
1) receptors
2) ion channels
3) transport systems
4) enzymes
how are receptors defined?
usually within the cell membrane
by there agonist and antagonist actions
activated by NT or hormones
examples of an agonist and antagonist
agonist- ACh
antagonist- Atropine
what are the two types of ion channels?
voltage sensitive/gated channels e.g. VGCC
receptor linked e.g. nAChR
examples of drugs that target ion channels?
Local anaesthetics (sodium channels) calcium channel blockers
examples of transport systems that can be targeted
Na+/K+ ATPase (by cardiac glycosides e.g. digoxin)
NA re-uptake (e.g TCAs) monoamines in general
examples of drugs that target transport systems
tricyclic anti-depressants (TCAs)
cardiac glycosides e.g digoxin
what are the types of drug interactions with enzymes?
enzyme inhibitors e.g. anticholinesterases
false substrates e.g. methyldopa
prodrugs e.g. choral hydrate–> trichloroethanol
give an example of a drug with non-specific action
drugs that aren’t specific to receptors like paracetamol can have unwanted effects
what is the danger with some non specific drugs?
they bind tightly to plasma proteins and therefore create a dangerous untapped reservoir of the drug e.g. warfarin
examples of non specific drugs
antacids
osmotic purgatives
what is an agonist drug?
it is stimulatory and has an effect
what is an antagonist drug?
it mimics and blocks but does not have an effect
the 2 types of agonist drugs
full agonists
partial agonists- do not produce the full response and can therefore have some antagonist activity
what does potency of a drug depend on?
potency- amount of drug needed to produce a given effect
affinity- strength of the binding between drug and receptor
efficacy- the biological effect of the drug in that it causes a conformational change in the receptor
why is selectivity not specificity?
drugs may not be specific to the same receptors at a higher concentration
what are the 2 types of antagonist?
competitive
irreversible
what are competitive antagonists?
they bind to the same site as the agonists co-administered
they are surmountable
they shift the D-R curve to the right
e. g. atropine
e. g. propranolol
what are irreversible antagonists?
the bind tightly to the active site or they bind elsewhere
they are insurmountable
e.g. hexamethonium
what are the 4 types of antagonism?
- receptor blockade
- physiological
- chemical
- pharmokinetic (drug met by enzymes)
what is the receptor blockade and what activity does it show?
competitive and irreversible antagonist action
displays user-dependency
e.g. local anaesthetics
what is user-dependency?
the more active/often used tissue is, the faster the block is absorbed and becomes effective as there is a higher chance of it entering
e.g. LAs
what is physiological antagonism?
drugs that bind to two or more different receptors to counter the effects of another substance producing different effects on the same tissue
e.g. histamine (dilator) and NA (constrictor) on blood pressure
what is chemical antagonism ?
interaction in solution to negate the effects of another substance
not bound to receptors
e.g. the use of dimercaprol in heavy metal poisoning to clump them together into non-toxic lumps for excretion
chelating agents
anti-venom
what is pharmacokinetic antagonism ?
the clinically important form where the antagonist decreases the concentration of the active drug at the site of action
the body itself antagonises the agonists administered
e.g. barbiturates and their effects of reduced absorption , increased metabolism and increased excretion
what are the 5 types of drug tolerance?
- pharmacokinetic factors
- loss of receptors
- change in receptors
- exhaustion of mediator stores
- physiological adaption
what are the pharmacokinetic factors leading to drug tolerance?
due to increase rate of metabolism
unregulated enzymes so metabolism is quicker
e.g. barbiturates and alcohol
what are the reasons for a loss of receptors leading to drug tolerance ?
this is due to membrane endocytosis of receptors (down regulation)
there can also be upregulation (e.g. denervation super sensitivity)
e.g. beta adrenoreceptors
what sort of change can occur in receptors leading to drug tolerance?
conformational change in receptors (may reduce affinity)
e.g. nAChR at the NMJ
what drug causes an exhaustion of mediator stores lead to drug tolerance?
e.g. amphetamine where the stores of NA that are usually released become exhausted
what is physiological adaption ?
the body adapts physiologically to the administration of drugs over time
e.g. a drug causes BP to fall can cause RAS to activate in response to raise BP
what is drug tolerance?
the gradual decrease in responsiveness to repeated administration
what are the four receptor families and what are they based on?
type 1- ion channel linked R
type 2- GP linked R
type 3- kinase linked R
these are all embedded in membrane
type 4- intracellular steroid type R
based on molecular structure and/or the signal transduction system
type 1 receptors (ICLR)
e.g. nAChR, GABAa
4 or 5 binding domains in the subunit
acts in milliseconds
type 2 receptors (GPLR)
e.g. beta-1-adrenoreceptors (cardiac), mAChR
most receptors of the body are this type
7-TM structure
acts in seconds
type 3 receptors (KLR)
e.g. insulin type growth factor receptor
only one alpha helix subunit
acts in minutes
type 4 receptor (ISTR)
e.g. oestrogen receptor, thryoid
located intracellularly unlike the other 3 types
no alpha helix subunit
uses zinc fingers
affects DNA transcription
acts in hours
what is the difference between an agonist and antagonist?
both have high affinities but antagonists have no efficacy i.e. no biological effect
what is the role of excipients?
added to drug formulations to improve
- chemical and biological stability
- increased acceptability:
improved appearance, flavour, fragrance
what are some formulations for drugs?
- aerosols
- capsule
- cream
- liquid
- syrup
- powder
- soluble tablet
some use the same administrative route e.g. capsule and syrup use oral route
