Pharmacodynamics Flashcards
Pharmacodynamics
concerted w/ study of biochemical and physiological effects of drugs and their mechanism of action.
Concerned w/ drug concentration (dose) and magnitude of effect
Drugs produce their effects by 1)
Interacting with receptors
What are examples of a drug interacting w/ receptors?
G-protein coupled receptors (GPCR); G-protein mediate the receptor interaction
Drugs produce their effects by 2)
inhibiting enzymes
What are ways a drug can inhibit enzymes?
Competitive inhibitor binds to same site;
noncompetitive inhibitor binds to different site on enzyme, alters shape.
Drugs produce their effects by 3)
interacting w/ membrane transport proteins
What are ways drugs interact w/ membrane transport proteins?
ion channels - drugs bind and directly compete for the receptor and can also bind to a different site (allosteric) that alters ion channels (increae or decrease the flow of ions).
Neurotransmitter transporters - transport neurotransmitters out of the synapse and back to the neuron (reuptake inhibitors)
Drugs produce their effects by 4)
Act directly on DNA - bind directly to nucleic acids (anticancer agents)
Drugs produce their effects by 5)
act directly on membrane lipids - general anesthetics
Receptor-binding affinity
tendency of a drug to combine w/ its receptor - strength of the interaction between a drug and its receptor.
How is the affinity of a drug mesured
by its dissociation constant (KD)
Signal transduction
describes pathway
- from ligand binding to changes in the receptor
- receptor interaction w/ an effector molecule called second messengers (cyclic AMP, IP3, Diaclyglycerol
This cascade ultimately leads to physiologial effect
Efficacy
Ability of drug to initiate a cellular effect (stimulate the receptor and start the signal tranduction pathway)
Agonist
drug has both affinity and efficacy (produces response)
Antagonist
drug has affinity but lack efficacy (prevents the action of agoinists (ex: anti-histamines)
Full agonist
produce the maximal response - increase the rate of signal tranduction when it binds to the receptor
Partial agonist
produce a submaximal response - will act as an antagnosit in presence of full agonist due to preventing the full agonist from binding the receptor and exerting maximal effect.
Inverse agonist
decreases the rate of signal transduction; works on GABA - inhibitory neurotransmitter that relaxes everything
Effects of antagonist
Can prevent the action of agonists, its effects are surmountable if dose of agonist is increased
Competitive antagonist vs. noncompetitive antagonist
competitive - bind to the same site as agonist but are reversively bond
noncompetitive - antagonist block the agonist site irreversibly.
Receptor regulation
receptors can undergo changes w/ respect to their density (numbers/cell) and their affinity for drugs and other ligands
What happens w/ continuous or repeated exposure to an agonist?
can desensitize receptors (effect called dsensitization or tachyphylaxis; rapid rate of tolerance where you don’t get the same effects anymore.
Down-regulation
longer-term adaptation in which the number of receptors DECREASE; also responsible for tolerance
What can continuous, or repeated exposure to antagonists do?
initially can increase the response of the receptor (super sensitivity)
Up-regulation
chronic exposure that results in an INCREASE number of receptors
Dose-response relationship
relationship between the concentration of drug at receptor and magnitude of response.
Graded dose-response relationship
effect of various drug doses of a drug on an INDIVIDUAL
Quantal dose-response relationship
effect of various doses of a drug on a POPULATION of individuals
What does graded dose-response illustrate?
The relationship between drug dose, receptor occupancy, and magnitude of the resulting effect.
What are 2 important parameters of graded dose-response?
Potency is drug dose that produces 50% of the maximal response (ED50 = median effective dose)
**Largely determined by affinity of drug for receptor
Efficacy
maximal response produced by a drug
How can quantal relationships be defined?
as either present or not present; can be defined for therapeutic effect and toxic ffects
What is TI and CSF? What are they based on?
TI- therapeutic index
CSF - certain safety factor
based on difference between the toxic dose and the therapeutic dose in a population of subjects
Therapeutic index - ED50
(median effective dose); produces an effect in 50% of subjects
Therepeutic index - LD50
(median lethal dose) produces death in 50% of subjects
Therapeutic ratio
between LD50 and ED50 - provides the margin of safety of a drug
CSF ratio
LD1 (lethal in 1%) and ED99 (therapeutic effect in 99%) - more realistic estimate of drug safety.
Thereapeutic index number
the larger the number, the safer the drug is.
the smaller the number, the more toxic the drug is.
Narrow thereapeutic range (index) drugs
containing certain drug substances subject to therapeutic drug concentration or pharmacodynamic MONITORING, and/or where product labeling indicates a narrow therepeutic range designation.
Pharmacodynamic response changes in older patients
- Increased sensitivity to CNS effects of benzodiazepines.
- Enhanced response to anticoagulants.
- Reduced response to beta-agonists and antagonists
- Increased risk of tardive dyskinesia w/ antipsychotic ageents (irreversible, parkinson’s symptoms)
