pharmacodynamics Flashcards
pharmacodynamics
study of effect of drugs and mechanism of action on body
“what drug does to the animal”
physical interaction- non specific
- osmotic diuretics
- antacids
- radioactive iodine
non-receptor interactions (biological)
- ion channels– can be physically obstructed (Lidocaine)
- enzymes–analogues may compete with real substrate for binding on enzyme, false substrates
- carrier proteins–small, polar molecules may require transport proteins
receptor interactions (biological)
- recognition sites for endogenous chemical messengers
- Ligand-gated ion channels (ionotropic)- fast
- G-protein coupled receptor (Metabotropic)–slower but allows extracellular signal to be turned into intracellular signal and amplified
G-Protein coupled receptor
- extracellular signal to intracellular signal
- 40% of pharmaceuticals work this way
- intracellular systems: cAMP and PIP2 with PLC
- G alpha subunits: s- stimulatory, i-inhibitory, q-couples to PLC
- s stimulates cAMP pathway, i inhibits cAMP pathway
monoamines
-epinephrine, norepinephrine, dopamine, 5HT, histamine
small neurotransmitters
-Acetylcholine, GABA, glutamate, adenosine
Peptide neurotransmitter and hormones
-opioid, oxytocin, vasopressin
sensory modalities
odorants, tastetants
kinase-linked receptors
- direct activation of enzymes
- extracellular receptor intracellular enzymatic activity
- phosporylation of proteins, activates receptors
- insulin, IGF-1, cytokines, growth promoting hormones
nuclear receptors
-intracellular to nucleus
-transcription factor receptors
-receptors in cytoplasm, get to nucleus
-alter gene transcription from DNA
=steroids, thyroid hormones, inflammatory mediators
True/False– endogenous neurotransmitters are specific to one receptor
false- endogenous NT often bind more than one type of receptor
receptor upregulation
-increase of receptors and drug effect
receptor down regulation
- decrease in number of receptors and effect
- can be by internalizing, recycling, sequestration, degradation
- part of normal cell metabolism
tolerance
-decrease in responsiveness of drug when given repeatedly over days to months
tachyphylaxis
-acute tolerance, develops in short period of time
ligand
-anything that binds to recognition site (agonist, antagonist, inverse agonist, mixed agonist-antagonist)
agonist
mimics effects of endogenous ligand
-ex: fentanyl on mu opiod receptors
full agonist
- ex: morphine
- titrational effect
- full cell/tissue response
partial agonist
- ex: buprenorphine
- binds to receptor, does not cause as much effect as full agonist, blocks receptor from full agonist binding
- ceiling effect
antagonist
binds to same receptor and prevents agonist from binding
competitive agonist (most common)
-reversible, concentration dependent binding
non-competitive agonism (less common)
- irreversible, covalent binding
- prevents action of agonist at any concentration
inverse agonist
-binds to receptor site, produces opposite effect of agonist
mixed agonist antagonist
- binds to more than one receptor
- acts as agonist on one type of receptor and antagonist on others
- ex: butorphanol, agonist on K opioid receptors, antagonist mu opioid receptors
potency
- concentration of drug needed to produce effect
- dose usually accounts for potency of drug (more potent drug will produce same effect with smaller dose/concentration than less potent drug )
slope of drug- concentration-effect curve
linear in ~20-80% range
maximal effect (ceiling)
-point at which increasing concentration does not give greater response
efficacy
- maximal effect a drug can have
- partial agonist may never be able to achieve full efficacy
effective concentration (EC50)
- 50% maximal response in vitro
- relates to concentration of drug at site
effective dose (ED50)
- desired effect in 50% of population
- relates to dose given to individuals and observed effect
- similarly can look at dose that causes toxic effect/death (LD50)
therapeutic index
(TI=LD50/ED50)
- ratio used to evaluate safety of drug
- narrow therapeutic index (small number, closer to 1) dose required to cause death is close to that to cause therapeutic effect
- wide therapeutic effect: dose required to cause death is much higher than that to cause therapeutic effect
standard safety margin
- more comprehensive and accurate assessment of drug safety
- SSM= LD1-ED99/ED99
onset of action
-time required after drug administration for response to be observed (latent period)
duration of action
-length of time that drug is effective (onset to termination of action)
