Pharmacodynamics Flashcards
A clinician wants to calculate the therapeutic index of a drug, but only has information from a graded dose-response curve. Is this possible?
No, a quantal dose-response curve is needed to determine TI
A patient is prescribed two drugs. The effect of taking the two drugs together than each drug individually is much greater. What term describes this relationship?
Synergistic
What term describes a drug response that is not often observed?
Idiosyncratic
What is Kd?
Kd is the dose of a drug necessary for half of the receptors to be bound
What term describes a decreased response to a drug compared to most individuals?
Hyporeactive
True/False. An antagonist has no physiological effect.
True. An antagonist binds the receptor and prevents the agonist from binding, but has no physiologic effect itself.
The heart achieves a maximum effect to catecholamines when only 10% of its receptors are bound. The remaining 90% are termed what kind of receptors?
Spare receptors - that is, extra receptors that need not be bound in order to achieve maximal effect
A drug has a high Kd value. What does this indicate about the drug’s affinity for the receptor?
Kd and affinity are inversely related. A high Kd indicates low affinity for the receptor.
What is an antagonistic drug relationship?
The combined effect of two drugs is less than the sum of the effect of each individual drug
What is a chemical antagonist?
An antagonist that does not bind a receptor. It makes some drug/protein unavailable via ionic binding
What is drug potency?
The amount of drug necessary in order to produce a given effect
True/False. A partial agonist may out-compete a full agonist.
True. In this case, the effect will be diminished.
These types of bonds are responsible for drug-receptor interactions.
Weak ionic bonds
This type of agonist produces a lower response at full receptor occupancy.
Partial agonist - formation of active and inhibitory complexes
What term describes a drug relationship in which neither drug influences the effect of the other?
Additive/Summation
A competitive antagonist causes an increased in EC50, but maintains Emax. What is the effect of a non-competitive antagonists on EC50 and Emax?
Emax will decrease, but EC50 will remain the same assuming no spare receptors are present
What formula is used to calculate therapeutic index?
TI = TD50/ED50
What is the difference between receptor downregulation and tolerance?
Downregulation causes a decrease in the overall number of receptors due to prolonged exposure to an agonist. Tolerance is a gradual loss of response to the agonist after repeated exposure.
This type of receptor regulation leads to increased sensitivity to an agonist.
Receptor upregulation
What is the difference between hyperreactive and hypersensitivity in drug responsiveness?
Hyperreactivity is an increased drug response. Hypersensitivity refers to an immunologic or allergic reaction to a drug.
What is Emax?
Emax is the greatest effect an agonist can produce at the the highest tolerable dose
How do inverse agonists differ from antagonists?
Antagonists have no effect. Inverse agonists form inhibitory complexes that produce an effect below constitutive activity.
What are the four primary roles of receptors?
Detect signals, determine dose-response, mediate actions of drugs, responsible for selectivity
True/False. Partial and inverse agonists behave as competitive antagonists in the presence of a full agonist.
True
These types of bonds are extremely strong and considered unbreakable.
Convalent bonds
What information can be calculated using information from a quantal dose-response curve?
ED50 (dose at which 50% patients exhibit quantal effect), TD50 (toxic dose), LD50 (lethal dose), TI (therapeutic index)
What is a functional/physiological antagonist?
An antagonist that binds to a different receptor in order to exert a response opposite that of the agonist (ex: glucocorticoids increase blood glucose, but insulin decreases blood glucose)
Drug A has an EC50 of 5mg. Drug B has an EC50 of 12mg. Which drug is more potent?
Drug A - lower dose is necessary in order to produce an effect
What receptor state is favored under normal conditions?
Inactive receptor state. A continuous equilibrium always exists between active and inactive receptor, but inactive is favored in the absence of an agonist.
A graph shows a dose-response and drug binding curves. The dose-response curve has a lower Kd than the drug binding curve. What does this indicate?
The presence of spare receptors - the maximum effect of the drug is being achieved before all receptors are bound
What protein is involved in the destruction of receptors by lysosomes?
Beta-arrestin
An antagonist binds to a receptor. The agonist dose is increased, but no change in effect is observed. What type of antagonist is bound to the receptors?
Non-competitive antagonist - irreversible and cannot be overcome
True/False. Receptors may be immediately desensitized following activation.
True. This prevents harmful continuous activation. The desensitization is only temporarily and may last milliseconds.
What type of agonist produces maximal effects?
Full agonist
What is the relationship between Emax and efficacy?
Higher Emax = better clinical efficacy
A researcher wants to compare the Emax of three drugs using a dose-response curve. What type of curve is needed?
Graded dose-response curve
What is tachyphylaxis?
A form of desensitization that occurs very rapidly
What is the therapeutic window?
Dosage range between minimum effective dose and minimum toxic dose
