Pharmacodynamics Flashcards
(21 cards)
The biological effect of a drug is directly equivalent to the formation of _____
The biological effect of a drug is directly equivalent to the formation of the amount of drug-receptor complexes that are formed
What are the four major classes of receptors?
- Ligand gated ion channels
- Enzyme linked receptors
- G protein coupled receptors
- Ligand-activated transcription factors
What are the four most common types of drug-receptor interactions (think chemical bonds)
Weak reversible chemical bonds
- Ionic
- Hydrogen
- Hydrophobic
- Van der Waals
Covalent bonds are more rare and are usually undesirable as they are not easy to reverse and may be mutagenic/carcinogenic
What is Kd and why is it a good measure for describing the activity of drugs?
Equilibrium dissociation constant (Kd)
- Gives measure of inherent affinity of a ligand for a given receptor
- Drug concentration at which 1/2 of Bmax is achieved
- Not altered by concentration of drug or receptor number
Define:
- Graded phenomena
- Quantal phenomena
Graded phenomena: Infinite number of intermediate stages (eg. vessel dilation)
Quantal phenomena: All or none (eg. pregnancy, cure, etc.)
Contrast potency versus efficacy
Potency
- Related to the amount of drug needed to produce an effect of a given magnitude
- Usually expressed as ED50 (
Efficacy
- Related to the maximum effect that can be achieved with a particular drug
- Usually expressed as Emax
What are the four types of agonists (according to efficacy/potency)?
Full agonist (gold standard) - Max potency, max efficacy
Partial agonist
- Max potency, reduced efficacy
Full agonist
- Reduced potency, max efficacy
Partial agonist
- Reduced potency, reduced efficacy
A full agonist is one that has maximum efficacy, potency is not a concern for this classification!
What is the main difference between partial and full agonists?
Partial agonists do not produce a maximal response (reduced efficacy), regardless of dose.
Partial agonists have a lower functional impact upon the receptor compared to full agonist (eg. getting an ion gate to open and close intermittently)
What is an inverse agonist?
An inverse agonist blocks biological effects by stabilizing the inactive state, or destabilizing the active state (to reduce constitutive receptor activation)
An example of this, is causing a blood vessel to constrict further than you would achieve with just an antagonist or no agonist (ie. exact opposite activity as observed with agonist)
What conformation is a receptor typically in spontaneously?
A receptor is spontaneously in the inactive state, though it can sometimes spontaneously change to active state conformation (random kinetic fluctuation).
What does an antagonist do?
It impedes receptor activity only in the presence of agonist. It does have a biological effect when there is no agonist around (though inverse agonists do!).
What are three types of antagonism?
Chemical
- Direct interaction of two drugs in solution such that the effect of one or both drugs is lost
- Eg. acid and bases neutralizing each other (and therefore losing biological effect)
Physiological
- Indirect interaction of two drugs with opposing physiological actions (cancelling each other out)
Pharmacological
- Blockage of interaction of one drug with receptor by another drug
What are the two types of pharmacological antagonists?
Competitive antagonists
- Bind reversibly
- Increasing agonist concentration overcomes inhibition
- Affects agonist potency
Non-competitive antagonists
- Bind irreversibly (covalent)
- Inhibition cannot be overcome
- Affects efficacy
What are four different words for desensitization?
- Tachyphylaxis
- Refractoriness
- Resistance
- Tolerance
What are the five types of drug desensitizations?
Receptor mediated
- loss of receptor function (rapid desensitization)
- Reduction of receptor number (slower, long term)
Non-receptor mediated
- Reduction of receptor coupled signalling components (eg. depletion of second messenger)
- Reduction of drug concentration (increased metabolic degradation)
- Physiological adaptation (reduction of drug effects due to opposing homeostatic pressure)
Explain a model for desensitization of G protein coupled receptor (GPCR signalling)
- Give a receptor mediated example and a non-receptor mediated example
- The receptor can be phosphorylated, which reduces ability to couple with G protein
- Happens with persistent stimulation of the receptor
- Phosphorylation can prevent coupling and or cause the receptor to detach from the cell membrane
Alternatively,
- You can deplete the stores of ATP, effectively causing desensitization, without involving change in the receptor itself
What are three types of adverse reactions to drugs?
- Side effects
- Toxic reaction
- Allergic reaction
Define side effects (3)
- Dose dependent
- Not directly related to desired effect of drug
- Action of drug at other sites to produce undesirable effects
Define toxic reactions (3)
- Dose dependent
- DIrectly related to desired effect of drug
- Excessive action of drug at intended target site
Define allergic reactions (3)
- Not dose dependent
- Not related to desired effect of drug
- Immunologic response (largely unpredictable)
When do you have a wide/narrow therapeutic window?
Wide: When the drug is safe and beneficial over a large dose range
Narrow: When a drug is safe and beneficial over a relatively small dose range
