pharmacodynamics Flashcards
what are the 3 different types of naming for drugs?
chemical
generic
trade
drugs can be…
naturally occurring or synthetic
how do drugs work generally?
mimic or block the action of our own signalling molecules
what are the targets of drug action?
proteins - enzymes, transporters, ion channels and receptors
DNA
what are the receptor families?
ligand-gated ion channels
G protein coupled receptors (metabotropic)
kinase-linked receptors
nuclear receptors
how do kinase linked receptors work?
receptor > protein phosphorylation > gene transcription > protein synthesis > cellular effects
how do nuclear receptors work?
receptor in nucleus > binds to receptor > gene transcription > protein synthesis > cellular effects
specificity
drugs bind selectively to particular receptor types
no drug is 100% specific, only selective and bind to one receptor preferentially over another
What do agonist drugs do?
activate receptors
what do antagonist drugs do?
block receptors, often inhibit endogenous agonist action
how do agonist drugs work?
2 phases
what are the phases of agonist drugs
- drug binding/ affinity
2. receptor activation/ efficacy
Drug binding/ affinity
agonist/ drug binds to receptor forming a drug- receptor complex
receptor activation/ efficacy
activated D-R complex causes the biological effect
e.g. opens channel
what are the different agonist types?
full
partial
super
inverse
full agonists
cause 100% effect of the endogenous agonist
partial agonists
cause less than 100% of endogenous effect
super agonists
rarer
cause more than 100% of the endogenous effect
inverse agonists
reduce the basal receptor activity, by causing them to be inactive and so they cannot elicit a response
drug effect
is proportional to drug concentration
both agonists and antagonists elicit effects
agonist drug potency
involves affinity and efficacy
What is EC50
the concentration required to bring about a 50% response
potency curve
further to the left on a % effect vs log[drug] conc. = more potent
what is the target for botox?
glycoprotein, at presynaptic vesicle release of ACh
how does Galpha q work?
activates Phospolipase C which produces DAG and IP3, activates Calcium release and Protein kinase C > vasoconstriction and smooth muscle contraction
how do antagonist drugs work?
bind to receptor and form drug-receptor complex which makes the receptor inactive and prevents endogenous agonist binding causing the biological effect
antagonist potency
only involves affinity not efficacy, as it blocks the receptor
different types of antagonist
reversible/ irreversible
competitive
non-competitive
uncompetitive
are competitive antagonists reversible or irreversible?
reversible
what are uncompetitive antagonists?
requires agonist binding before it can bind to allosteric site of receptor/ enzyme. It then lessens the effect elicited by the substrate
what are the non-receptor antagonists?
chemical antagonists
physiological antagonists
pharmacokinetic - influence the 4 processes
what are chemical antagonists?
reduce concentration of agonist by binding
occupancy and response
often not all receptors need to be occupied for maximum effect to be achieved - spare/ reserve receptors. Therefore a partial agonist may be sufficient over a full one
tolerance
decrease in a drug’s effectiveness over days/ weeks
resistance
adaptive changes making a drug less effective
what causes changes in drug effectiveness?
desensitisation
tolerance
resistance
how does resistance occur?
change in receptors loss of receptors loss of mediators enhanced drug metabolism increased removal from site of action§
pharmacogenomics
genetic variability in the way drugs behave in the body
PK = enzyme polymorphism
PD = receptor variants
what factors are used to guid drug administration?
drug factors and patient factors
what patient factors affect drug administration?
age
weight
gender
disease
what drug factors affect drug administration?
pharmacokinetic and pharmacodynamics
inpredictability
there is always unpredictability in PK and PD responses even if adjustments are made
why might the outcome of drugs not be easily measured?
long delay in seeing result
multi-factorial condition
Kd
relationship between the ability of a drug to bind and to dissociate
concentration required to occupy 50% of receptors
when does EC50 = Kd
when all the receptors need binding to cause maximal response
when there are spare receptors
the EC50 is much less than the Kd, provides degree of tolerance to things going wrong
what happens when a competitive inhibitor and an agonist are used where there are spare receptors
more receptors need to be bound to elicit the 50% response but it can be done . Shifts EC50 to right
what happens when a irreversible inhibitor and an agonist are used where there are spare receptors
shift in EC50 to right and loss of maximal response as receptor reserve is lost and receptors are no longer available so complex formation is reduced.
