Basic pharmacology Flashcards
what is drug potency?
why do different drugs have different potencies?
the minimum concentration of a drug required to elicit a response
potencies are linked to the drug affinity for its receptor §
what is efficacy of a drug?
how efficacious is a partial agonist, an antagonist and a full agonist?
the ability of a drug to activate a receptor once bound to it
a more efficacious drug will produce a greater maximum response
agonist - 1
antagonist - 0
partial agonist= 0-1
what is selectivity?
a drug can act at more than one receptor site, the selectivity of a drug is the poteny of it to elicit a desired response, compared to its potency to elicit an undesired response
high selectivity drugs have more than 1000 times the potency at desired receptor than other receptors
why are drugs administered at different dosages?
what is chemical specificity?
what is biological specificity?
different dosages because different drugs have different affinities for their targets
chemical specificity means that a simply change in the shape of a molecule could render it ineffective at its target receptor (e.g. - NA is more 1000 more potent that +NA)
biological specificity means that the same molecule can have different effects at different body parts
examples of non - protein targeted drugs
osmotic laxatives
chelators
influximab (antibody for TNF alpha)
describe the structure of nicotinic receptor
give examples of ligand - gated ion channels
it is a five subunit, with four different types of subunits, arranged around a central monovalent cationic channel
the receptor has four helical membrane spanning domains
GLUTAMATE, GABA, purinergic channels
describe the structure of a G-coupled protein
describe how they work
G-coupled proteins have a monomeric or dimeric receptor linked to a G-protein rather than an ion channel
a G-protein has three sub-units A and B/Y
activated form: is dissociated A and B/Y subunits with GTP in the catalytic domain of the alpha sub-unit
inactivated form: all three subunits bound with GDP in the alpha subunit catalytic domain
the subunits can directly interact with ion channels, causing a change in membrane excitability
or they are linked with enzymes which can cause:
1. increase in intracellular calcium levels
2. expression of certain proteins due to phosphorylation
explain the role of adenylate cyclase and phospholipase C as secondary messengers
adenylate cyclase:
- increases intracellular cAMP concentration
- this can activate cAMP dependant kinases - leading to phosphorylation kinases
- enzyme activated by B adrenoreceptors or prostaglandins in the Gs type receptors
- enzyme inhibited by alpha 2 or opioids in the Gi type receptors
phospholipase C:
- hydrolysis a membrane protein
- IP3 causes a release of intracellular calcium
- DAG remains in the cell and causes a phosphorylation cascade via activation of protein kinase C
what are kinase linked receptors?
explain their action and their structure
what is so special about the proteins linked to the tyrosine residues
give examples of products of
guanyly cyclase receptors
tyrosine kinase receptors
structure:
extracellular receptor domain
intracellular tyrosine kinase domain
both domains linked by a single transmembrane helix
mechanism:
ligand binding causes dimerisation of the receptor
this causes the autophosphorylation of the tyrosine residues
this leads to phosphorylation cascades, ending in expression of certain proteins
usually the tryosine residues are docking sites for proteins with SH2 domains
receptors:
gunanylyl cyclase receptors: produce ANP and NO
tyrosine kinase receptors: produce insulin and peptide growth factors
what are nuclear receptors?
what is so special about their ligands?
what makes them different to the kinase linked receptors?
nuclear receptors are not always found in the nucleus, they are found in the cytosol and once their ligand is bound they migrate into the nucleus
these receptors their ligands are lipid soluble, in order to be able to cross the lipid bilayer
the receptors dimerises once hormone is bound, and binds to a specific portion of DNA
this allows transcription or inhibition of transcription of certain genes
e.g. glucocorticoids will inhibit COX2 gene expression, allowing inflammation dampening
receptors are different to kinase receptors, because they directly bind to the DNA to allow gene transcription, the kinase receptors must first phosphorylate proteins to allow gene transcription
compare the time of action and give an example of: ion channels G- coupled proteins Kinase receptors nuclear receptors
ion channels: - ms - nicotinic channels G-coupled: - seconds -adrenoreceptors kinase receptors - hours - Cytokine receptors nuclear receptors: - hours -osterogen receptors
how do drugs bind to their receptor?
what is the dissociation constant of a drug? Ka
how can we calculate receptor occupancy for a given drug?
drugs bind reversibly, via weak bonds to their receptors - this means they’re in equilibrium
the Ka of the drug represents the concentration of the drug at which 50% of the receptors are occupied. if the drug has a higher affinity for the receptor, Ka is lower. Ka is both a property of the receptor and the drug.
we can calculate occupancy using this equation:
p= (A/Ka)/(A/(Ka+1))
What is a binding curve?
what is the shape of a binding curve? why is that important?
what can a binding graph tell us?
a binding curve shows receptor occupancy against LOG of drug concentration
curve obtained is sigmoid, (if log scale is not used graph obtained would be hyperbolic) this is important because
- graph can accommodate a wider range of results
- results can easily be obtained from graph
a binding graph can show:
- potency of a drug
- whether increasing the dosage of a drug will create a greater response
- affinity of a drug to a receptor
what is a dose response curve?
what can it show us?
what can it not show us? why?
a dose response curve: the response plotted against log of drug concentration
- can show us potency of a drug
- drug efficacy, because can show us maximal drug response
cannot show use drug receptor affinity because physiological response is NOT proportional to receptor occupancy
what is a graded and an all or non response?
what is therapeutic index? how accurate is it?
give examples of drugs with low margin of safety
a graded response is something like the increase in BP in response to increasing concentration of administered noradrenaline
EC50: Concentration of drug producing 50% of maximum response
an all or non response: when a drug either produces a response or does not (sleeping pill)
ED50: dose of drug producing desired consequence in 50% of sample size
therapeutic index:
LD50/ED50
this is not a very accurate calculation because it depends on an individual’s liver function and weight
example of low drugs:
- lithium
- digioxin
- barbiturates
- pheyntoin (anti-convulsant drug causing renal impairment)
