Pharmacodynamics, Drug Interactions, and Toxicology Flashcards
What are the key concepts of pharmacodynamics?
- Drug concentration and response
- Affinity
- Efficacy
- Potency
What do drugs cause to have their effect?
- Depression
Stimulation - Destruction
- Replacement
What do most drugs interact with to have their effect?
Endogenous proteins
What effect do drugs have on endogenous proteins to have their effect?
- Some activate endogenous proteins
- Some antagonise, block, or inhibit endogenous proteins
Give some examples of unconventional mechanisms of action of drugs
- Disruption of structural proteins
- Act as enzymes
- Covalently linking macromolecules
- Reacting chemically with small molecules
- Binding free molecules/atoms
Where might drugs exert their actions?
- Cell surface receptors
- Nuclear receptors
- Enzymes (inhibition)
- Blocking ion channels
- Inhibiting transport
- Inhibiting signal transduction proteins
What does plotting a drug effect against concentration produce?
A Michaelis-Menten curve, where a rectangular hyperbole is shown as effect increases with concentration, and begins to level out once Emax is almost reached
What will plotting drug effect against logConcentration produce?
A sigmoid curve
What happens when a drug binds to a cell receptor?
It produces a change
What is a complete agonist able to do?
Produce 100% signal as concentration is increased
Can a partial agonist produce 100% signal?
No, even when concentration is increased
What do competitive antagonists do?
Bind to the receptor at its binding site, therefore blocking the binding of agonist molecules
What happens to the reduction in response as the concentration of competitive antagonist is increased?
The reduction in response is also decreased
What can be done to overcome competitive antagonist binding?
Increase the concentration of agonist, which can still produce 100% effect
How do non-competitive antagonists work?
They bind to the receptor away from their binding site, and act by causing a change in the receptor site, which can either prevent agonist binding, or prevent response once the agonist has bound to the receptor. Either way, this reduces the effect agonists can have
What happens when you increase agonist concentration of agonists with non-competitive antagonists?
The maximum level of signal production will stay the same, as the increased concentration will not affect the antagonist binding
Describe the features of an ideal drug, in terms of binding
It interacts at only one site, thus causing no unwanted side effects
What is the reality with binding of drugs?
They will bind at more than one binding site, and thus cause collateral damage
What is the result of a drug being more selective for its target?
It means there is less chance it will interact with different targets, and have less undesirable side effects
Give an example of a selective drug
Penicillin - it targets the bacterial cell wall, thus leaving mammalian cells alone, therefore has minimal side effects
What is meant by specificity of the drug?
How accurate a drug is at binding to a specific receptor or subtype
Give an example of a class of drugs that has side effects due to lack of specificity
Drugs affecting adrenergic receptors, which can cause effect in the heart and lungs
What is affinity?
The tendency of a drug to bind to a specific receptor type
What does a high affinity result in?
A drug is more likely to cause response at a lower concentration
What is efficacy?
The ability of a drug to produce a response as a result of the receptor or receptors being occupied
What does efficacy describe?
The maximum effect of a drug
What is potency?
The dose required to produce the desired biological response
What does potency describe?
The different doses of two drugs required to exact the same effect
What is the therapeutic index?
The relationship between concentrations causing adverse effects and concentrations causing desirable effects
How is therapeutic effect calculated?
EC50 (adverse effect) / EC50 (desired effect)