Pharmacodynamics Flashcards
Describe pharmacodynamics definition.
-effect of drugs & their mechanism of action in the body
-drug -> body
Describe targets for drug action - physical interaction (non specific effects).
- Osmotic diuretics
- Antacids - direct neutralization of acid in GIT
- Radioactive iodine (I131)
Describe targets for drug action - non receptor interactions.
- Ion channels
-block ion channels by physical obstruction (ex. Lidocaine)
-modulation thru opening/closing of channel - Enzymes
-analogues that compete w real substrate for binding to enzyme - False substrates
-abnormal (inactive) metabolite made - Carrier proteins
-small polar molecules dont cross cell membrane & need transport proteins
>altering proteins -> remove molecules from their site of action -> end effect
-EX: fluoxetine & omeprazole (antacid)
Describe receptor interactions.
specific recognition sites for endogenous chemical messengers = most common PD drug action
1. Ligand gated ion channels
2. G protein coupled
3. Kinase linked receptors
4. Nuclear receptors
Describe up regulation VS down regulation in receptors.
- Receptor up regulation
-inc in # of receptors & drug effect
-need gradual withdrawal of drug (weaning) - Receptor down regulation
-dec in # of receptors & receptor effect
-lead to drug tolerance
-normal cell metabolism
-mechanism: internalization, recycling, sequestration, degradation
Describe tolerance VS tachyphylaxis.
- Tolerance
-dec in responsiveness to drug when given repeatedly (days to months) - Tachyphylaxis
-acute tolerance over a short period of time
-depletion of stored mediator
-high drug dose dont inc drug effect
-EX: inj sedative
Describe drug receptor interactions.
-ligand (drug) binds to recognition site:
>agonist
>antagonist
>inverse agonist
>mixed agonist-antagonist
Describe the different types of agonists.
- Agonist
-mimic effect of endogenous ligand
-affinity & efficacy - Full agonist
-spare receptors
-titration effect - Partial agonist
-bind to receptor but doesnt cause as much effect as full agonist but still blocks that receptor from full agonist binding
-‘ceiling effect’
-IRREVERSIBLE
Describe the different types of antagonists.
- Antagonist
-bind to same receptor & prevent agonist from binding
-inhibits effects of receptor - Competitive antagonism (most common)
-reversible
-conc dependent binding
-agonist can compete for binding site
-net effect depend on drug w higher conc - Non competitive antagonism (less common)
-antagonism binds covalently to receptor = IRREVERSIBLE
-prevent action of agonist at any conc
-agonist cant compete for binding site
Describe inverse receptor agonist.
-bind to same receptor site & makes opp effect of agonist
Describe mixed agonist-antagonist.
-binds to more than one receptor
-acts as agonist on one type of receptor & antagonist on other types of receptors
SUMMARY of drug receptor interactions.
Describe quantification of drug response.
Describe the types of drug effects.
- Therapeutic effects
-desirable
-clinical goal - Side effects
-unintended effects, secondary to use of drug - Adverse effects
-unintended & undesirable
-predictable VS unpredictable (idiosyncratic)
*pharmacovigilance = monitor adverse effects - Toxic effects
-expected to varying degrees
-idiosyncratic
-dose dependent
difference between toxin & drug is the dose
Describe the types of doses.
- Therapeutic (effective/optimal dose)
-minimal therapeutic dose = smallest dose that makes a therapeutic effect (LED)
-maximal therapeutic dose = largest dose tolerated w/o toxic effects - Effective dose 50 (ED50) = dose that causes therapeutic effect in 50% of animals
- Effective dose 99 (ED99) = dose that causes therapeutic effect in 99% of animals
Describe toxic VS lethal dose.
- Toxic = makes adverse clinical, haematological, biochem change -> pathological alterations
- Lethal = dose that causes death
-lethal dose 50 (LD50) = cause death in 50% of animals
-lethal dose 1 (LD1) = cause death in 1% of animals
