PHARM 2: Mechanisms of Drug Action Flashcards
What are the 4 types of drug antagonism?
- receptor blockade
- physiological antagonists,
- chemical antagonism
- pharmacokinetic antagonism
What is Receptor Blockade?
give an example
- simple antagonist binds to receptor
- prevents binding of agonist
- has property of USE DEPENDENCY of ion channel blockers
e.g local anesthetics
What is Physiological antagonism ?
give an example
- 2 drug act at different receptors to have opposite effects in the same tissue
e. g NA on vasculature binds to adrenoreceptors –> causes vasoconstriction.
if coadminister w histamine –> acts on diff receptors causes vasodilation.
What is Chemical Antagonism?
give and example
- interaction of drugs in solution
e.g dimercaprol = chelating agent which forms heavy metal complexes –> which= more rapidly excreted by kidneys
(useful in lead poisoning)
What is pharmacokinetic antagonism?
give an example
- when one drug reduces conc of the other drug at the site of its action
–> this may reduce the absorption, increase metabolism, or increase the excretion of another drug.
e.g repeated administration of barbiturates –> increase in production of microsomal enzymes
SO
if we administer another drug metabolized by same enzymes e.g warfarin then –> it is metabolized more quickly
–> causes reduction in effect
What is drug tolerance?
- gradual decrease in responsiveness to drug with repeated administration
e. g benzodiazepines
- -> stops seizures
- -> negative side: repeated use – > response decreases
Give 5 causes of drug tolerance.
CLEPP
- Change in receptors
- Loss of receptors
- Exhaustion of mediator stores
- Pharmacokinetic factors
- Physiological adaptation
What is meant by pharmacokinetic factors?
give examples
- when metabolism of drug increases when it is given repeatedly over a period of time.
e. g barbiturates + alcohol
What is meant by loss of receptors?
give examples
- when the cell takes receptors off its members via memb endocytosis
- receptor down regulation
e.g beta adrenoreceptors = susceptible to receptor down regulation.
What is meant by change in receptors?
give examples
- when the no. of receptors on cell surface doest change
BUT
receptors themselves –> undergoes desensitization. - involves conformational change
- so proportion of receptors –> no longer effective.
What is meant by exhaustion of mediator stores?
gives examples
- occurs in amphetamines
- -> amphetamines = central stimulant
- -> main effect = on noradrenergic neurons of brain
- -> causes release of NA
- -> NA increases
–> tolerance develops due to exhaustion of mediator stores e.g NA –> response tails off
NOTE: this happens with amphetamines – they get into the central noradrenaline synthesis system and replaces noradrenaline in the vesicles so you get a big increase in the production of noradrenaline
What is meant by physiological adaption?
- similar to homeostatic response
- whereby the body attempts to maintain a stable internal environment
What are the different types of receptor families?
type 1, 2, 3, 4
What are the receptors families based on?
based on:
- molecular structure
- signal transduction systems
What is Type 1 Receptor families?
TYPE 1 =
- inotropic receptor
- mediates very fast response (ms)
e..g GABA , Nicotinic Acetylcholine Receptor
What is Type 2 Receptor families?
TYPE 2 =
G Protein coupled receptors
- slower response (s)
e.g beta-1 adrenoreceptors in heart
What is Type 3 Receptor families?
TYPE 3 = Kinase linked type
results in phosphorylation of intracellular proteins
- minutes
e.g insulin receptor + growth factor receptors.
What is Type 4 receptor families?
TYPE 4 = Intracellular steroid type receptors
- activated by steroid + thyroid hormones
- regulates DNA Transcription
- drug has to pass through cell memb –> into nucleus to take effect
- hours
How many subunit does each receptor family have?
a) Type 1
b) Type 2
c) Type 3
d) Type 4
How many subunit does each receptor family have?
a) Type 1 - 4/5 subunits
b) Type 2 - 1 subunits (7 transmembrane domains)
c) Type 3 - 1 transmemb domain
d) Type 4 - DNA binding domain = zinc fingers
Describe the defining feature of Type 1 receptor families
Type 1 defining feature = transmembrane sections (alpha helices)
- there is an external binding domain that stimulates + opens the ion channel
Where would you find Type 4 receptor families?
- in the nucleus
- steroid receptors
What type of antagonism is anti venom?
- chemical antagonism
