Pharmacodynamics Flashcards
Receptors determine quantitative relationship between dose of a drug and pharmacological effect
Binding affinity determines concentration required to form drug-receptor complexes, maximal effect of a drug is limited by number of receptors
Receptors are responsible for selectivity of drug action
Drug structures determine affinity for receptor classes, non-selective drugs can cause side effects
Receptors mediate actions of pharmacologic agonists and antagonists
Drugs binding to receptors can activate or interfere with normal physiological processes
Occupancy theory
Intensity of a drug’s response is proportional to the amount of receptors are occupied by that drug, maximal response is achieved when all receptors are occupied
Lock and key model
Shape of the drug must fit the shape of the receptor
Induced fit model
The receptor undergoes conformational change upon binding to better fit the shape of the drug, depending on the change, a better fit will increase drug-receptor affinity and drug efficacy, better fit explains potency
Spare receptor concept
Physiologically, maximal effect can be obtained when only a fraction of the receptors are occupied, spare receptors increase sensitivity for drug binding, less drug is needed to activate effectors for response
Affinity
Low Kd = high affinity (inversely proportional), Kd = free drug concentration at which 50% of the drug is bound
Potency
Depends on the affinity and efficacy, requires two-drug comparison, EC50 = free drug concentration at which 50% of the maximal effect is achieved
Efficacy
Maximal response that can be produced by the drug
Kd
Free drug concentration at which 50% of the drug is bound
EC50
Free drug concentration at which 50% of the maximal effect is achieved
Reversible antagonist
Antagonist does not activate receptor, but competes with the agonist for the binding site
Irreversible antagonist
Antagonist binds to allosteric site to cause conformational change to the receptor
Competitive antagonist
Competes with the agonist for the binding site, more agonist is required to overcome the antagonism, changes potency
Non-competitive antagonist
More agonist cannot overcome the antagonism, antagonist disables receptors so the agonist cannot achieve the full effect, changes efficacy
Functional antagonist
Shows the same kinetic response as non-competitive antagonism, binds to another receptor and antagonizes the response, agonist-receptor effect may reach 100% but is antagonized by a separate receptor and does not get 100%
Partial agonist
May be more or less potent than a full agonist, do not reach 100% efficacy, can be used clinically to blunt the physiological response in a diseased population
Reason for use of partial agonists over full agonists or antagonists
The body will compensate to full agonists and antagonists by upregulation of the receptors, leading to tolerance of the drug, partial agonists do not generate drug tolerance
ED50
Dose at which 50% of subjects exhibit a therapeutic response to a drug
TD50
Dose at which 50% of subjects exhibit a toxic response to a drug
LD50
Dose at which 50% of subjects die
Therapeutic index
relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, narrow TI is more dangerous, wider TI is more favorable
Equation for therapeutic index
Therapeutic index = TD50 / ED50
Margin of safety
Refined from therapeutic index, margin of safety = TD1 / ED99
Factors affecting dose-response curve
Body size, weight, age, sex, route of administration, time of administration, pathological state, tolerance, genetic factors, presence of other drugs
