2 Pharmacodynamics Flashcards
Pharmacodynamics
what the med does to the body
Cellular Level
- where drugs exert primary action
- where receptors are (on or within cell)
- # of receptors is finite - can change
Down Regulation
Body pulls out receptors
-ex.) too much stimulus, ephedrine
Up Regulation
Body creates more receptors
-ex.) beta-blocker - cannot abruptly stop!
When do receptor mediated responses plateau?
When receptors are saturated
Affinity
strength of binding between drug and receptor
-stronger affinity can kick off lesser
Dissociation Constant (Kp)
measure of a drugs affinity for a give receptor. The concentration of drug required in solution to achieve 50% occupancy of its receptors
Agonist
drug which alters physiology of cell by binding to plasma membrane or intracellular receptor
- increases natural activity
- ex.) epi, alpha agonist
Strong Agonist
causes maximal effects even though it may only occupy a small fraction of receptors
Weak Agonist
must be bound to many more receptors than a strong agonist to have same effect
Partial Agonist
fails to produce effects, even if all receptors are occupied
Inverse Agonist
Not an antagonist. Binds to receptor site and causes opposite effect of agonist
- forces negative effect
ex. ) H2 “antagonist”
Antagonist
Inhibits or blocks action caused by agonist
Competitive Antagonist
competes with agonist for receptors
ex. ) reversal agents
- can be overcome by high doses of agonist –> surmountable
Noncompetitive Antagonist
can still block agonist, just through different site
- induces conformational change in receptor
- insurmountable - even high doses of agonist cannot overcome antagonism
Irreversible Antagonism
Agent competes with agonists for agonist binding receptor and combine PERMANENTLY
Efficacy
degree to which a drug is able to cause maximal effect
-can compare meds with different mechanisms
Potency
amount of drug required to produce 50% of the maximal response that the drug is capable of causing - dose dependent
ex. ) need less morphine than codeine for pain relief - morphine is more potent
- can compare meds in same chemical class
Drug Response Curves…drive home idea
all drugs have a plateau
-theory that opioids do not –> BS
EC50
Efficacy Concentration 50%
-concentration of drug which induces a specific clinical effect in 50% of subjects
LD50
Lethal Dose 50%
-concentration of drug which induces death in 50% of subjects
Therapeutic Index
measure of the safety of a drug
LD50/EC50 = therapeutic index
Margin of Safety
margin between therapeutic and lethal doses
FDA Registries
- Used to track when medications are given anyways
- evaluated growth and development since studies are unethical
REMS
Risk and Evaluation Mitigation Strategies
-for tracking high risk, dangerous meds
Pregnancy Category A
Safest
-adequate, well controlled studies have been done
Pregnancy Category B
Animal Studies do not show risk to fetus
Pregnancy Category C
- Animal Studies have shown adverse effects, but no human studies
- eval risk vs benefit
Pregnancy Category D
- Positive evidence for human fetal risk based on previous experience.
- risk vs benefits
ex. ) seizure meds –> birth defects
Pregnancy Category X
Animal and human studies show fetal demise
ex.) warfarin, ACE inhibitors
Drug Interaction Addition
1+1=2
response is equal to parts
Drug Interaction Syngergism
1+1=3
response is greater than parts
ex.) Abx
Drug Interaction Potentiation
0+1=2
A drug with no effect enhances effect of second drug
Drug Interaction Antagonism
Drug totally inhibits effect of another drug
Altered Absorption
- inhibited absorption of other drugs across biologic membranes
ex. ) anti-ulcer drugs coating stomach and blocking absorption
Altered Metabolism
-P450 enzymes inhibited or reduced to yeild clinically significant interactions
Plasma Protein Competition
drugs that bind to plasma may compete with other drugs for protein binding sites –> increase in unbound drug by competition
Altered Excretion
-may act on kidneys to reduce excretion, yields a toxicity risk
Tolerance
decrease response to a drug
metabolic or cellular (down-regulation)
Dependence
- patient needs drug to function normally
- physical and/or psychological
Abuse & Addiction
- not using drug for intended effect
- continued use despite negative effects
Withdrawal
- when dependent person does not get drug
- often exact opposite of what drug is supposed to cause
