Pharmacodynamics 1 (ppt 7) Flashcards
Molecular response
Enzyme activity/movement of ion across plasma membrane
Cellular response
Secretion of hormones or neurotransmitters or modulation of cell motility
Organ response
I.e. smooth m. contraction (ach)
Whole animal response
- Behavior changes/response
- Can be lethal
Therapeutic index
- TI=TD50/ED50
- ex: warfarin (small TI) and penicillin (larger TI)
Efficacy vs potency
- efficacy= maximal effect
- potency= strength of dose (ADME factors; drug’s affinity for receptors)
Potency
- EC50 measures it
- x axis
Full agonist
- intrinsic activity= 1
- ex: isoprenaline mimics beta-adrenoreceptors
Partial agonist
- partial response
- intrinsic activity <1
-ex: buprenorphine is partial opioid agonist
Antagonist
- aka “blockers”
- inhibit agonist action
- ex: ranitidine is H2 agonist
- IA=0
Inverse agonist
- produce opposite response to agonist
- intrinsic activity= 0 to -1
Agonist-antagonist
- simultaneously agonist on one set and antagonist on another set
- ex: nalorphine (opioid) activates k-opioid receptor & blocks mu-opioid receptor
What determines the degree of constitutive activity in the absence of drugs
Equilibrium between Ri (inactive r receptor) and Ra (active r receptor)
Affinity of full agonist drugs for Ra compared to Ri
- stronger
-b maximal effect prod. @ sufficiently high drug concentration
Neutral antagonist
- Dant
- equal affinity to both receptor conformations
- prevents binding of agonist
Inverse agonist
- Di
- higher affinity for Ri receptor conformation
- prevents conversion to Ra state
- reduces constitutive activity
Chemical antagonism
Ex: antacids
Functional antagonism
- physiological antagonism
- ex: effects of insulin & glucagon on blood sugar
Dispositional antagonism
- pharmacokinetic antagonism
Receptor antagonism
- pharmacological antagonism
- competitive and non-competitive antagonisms
Receptor binding competitive vs. noncompetitive
- competitive: reversible (van der waals or H2 bonds)
- non competitive: irreversible due to covalent bonds
Competitive vs. noncompetitive antagonism receptor binding sites
- competitive: antagonist binds same receptor site as agonist
- non-competitive: antagonist binds w/ same receptor site as agonist or to allosteric site
Efficacy for competitive vs. non-competitive antagonists
- competitive: remains same
- non competitive: decreases
Slope for competitive vs. non-competitive antagonists
- competitive: remains same
- non-competitive: decreases
Position of competitive vs. non-competitive antagonists on interaction dose response curves
- competitive: shifts right
- non-competitive: remains same
Intensity of response competitive vs. non-competitive antagonists
- competitive: depends on agonist and antagonist conc.
- non-competitive: depends on antagonist conc.
Antagonism comparison between competitive and non-competitive antagonism
- competitive: surmountable
- non-competitive: unsurmountable
Duration of actions for competitive vs. non-competitive antagonists
- competitive: short, depends on drug clearance
- non-competitive: long, depends on new receptor synthesis
Examples of competitive and non-competitive antagonists
- competitive: morphine-naloxone
- non-competitive: diazepam-bicuculline
