Lecture 3: Intro to Pharmacodynamics Flashcards
What is the major difference between Pharmacokinetics and Pharmacodynamics?
PK = effects of the body on drugs (ADME)
PD = effects of the drugs on the body
- receptors, response curves, drug action mech.
What do Emax and ED50 on a logarithmic dose-response curve tell us?
Emax (on y-axis) is the maximal effect that can be produced by the drug
ED50 (on x-axis) is the dose of drug that produces 50% of its maximal effect
What does a Graded vs Quantal Dose-Response curve answer?
Graded answers: “How much?”
- usually the mean value in a pop. or single subject
Quantal answers: “Does the response occur or not?” and “How many?”
- usually all-or-none, yes/no, or binary responses
- examines frequency of a response in large pop.
What is the difference between a Non-Cumulative vs Cumulative Quantal Dose Curve?
- non-cumulative shows number/% of pts responding to drug dose ONLY at that dose
- cumulative shows number/% of pts responding to drug dose and at all doses lower than that dose
What is the Therapeutic Index and how is it calculated?
TI = TD50 / ED50 (higher TI = safer drug)
TD50 = median toxic dose ED50 = median effective dose
What is Drug Potency and how is it related to median effective dose? (ED50)
- the amount of drug required to produce a specific pharmacological effect
- lower ED50 means the drug is MORE potent and helps determine the drug does that will be used clinically
What is Drug Efficacy and how is it related to Emax?
- describes the pharmacological effect that a drug can produce (represented as Emax)
- greater Emax means the drug is MORE efficacious and is related to the total number of receptors available to bind a drug
- determines magnitude of clinical effect
What is the difference between a Covalent bond and Non-Covalent bond?
Covalent: irreversible; requires re-synthesis of receptor or enzymatic removal of the drug
Non-Covalent: reversible; most drugs bind to receptors this way
What are the 3 major Non-Covalent bonds from strongest to weakest?
Ionic (electostatic interactions)
Hydrogen
Hydrophobic
What is the difference between a high affinity and low affinity drug?
- HIGH affinity drugs have strong receptor binding and require less drug to produce a response
- LOW affinity drugs have poor receptor binding and require more drug to produce a reponse
What is the Equilibrium Dissociation Constant (Kd) and why is it important for drug interaction?
- Kd represents the drug concentration at which 50% of the drug receptor binding sites are occupied
- LOWER Kd = HIGHER affinity of drug for receptor
- HIGHER Kd = LOWER affinity of drug for receptor
How is drug selectivity measured? How is selectivity related to adverse effects?
- via Kd ratio = Kd (off target) / Kd (on target)
- higher Kd ratio means the a drug is more selective
- more selective drugs have fewer adverse effects, while less selective drugs have more adverse effects
What is Intrinsic Activity and how does it relate to drug Agonists and Antagonists?
- the ability of a drug to change receptor function and produce a physiological response when bound
Agonists - have intrinsic activity
Antagonists - have NO intrinsic activity
bind to receptor but do NOT change its function
What is the difference between Full Agonists, Partial Agonists, and Inverse Agonists?
Full - fully activate receptors (maximal intrinsic activity)
Partial - partially activate receptors (sub-max effects)
Inverse - produce opposite effect to other agonists
- dec. receptor signaling
What is the difference between Pharmacological, Chemical, and Physiological Antagonism?
Pharm - antagonism at receptors
Chemical - chemical antagonist makes other drug unavailable
Phys - endogenous pathway blocks other pathway
