Pharmacodynamics Flashcards
Pharmacodynamics
What Meds do to the Body
- Most drugs bind to cell receptors where they initiate reactions that alter cell’s physiology
- Some of a drug’s molecules will find target cell, some distributed, metabolized, and excreted
- Drugs exert primary action at cell level
Medication Actions
Pharmacology at
cell level, organism level, and population level
Drug Receptors
- Proteins/Glycoproteins on cell surface, organelle inside cell, or cytoplasm
- Finite mumber - response plateaud once saturated
- Downregulation/Upregulation
What happens after a drug is bound to the receptor?
- Ion channel opens/closes
- Activate biochemical messengers, second messengers (cAMP, cGMP, C++, Inositol Phosphates) - each signal that passes amplified
- Inhibit/Initiate normal cell function
- Steroids move right into cell w/o help
What is Affinity
Strength of binding b/t drug and receptor
Dissociation Constant (Kp)
Measure of a drug’s affinity for a given receptor.
The concentration of a drug needed for 50% receptor occupancy
What is an Agonist
Drugs that alter physiology of a cell by binding to plasma membrane or intracellular receptors
What is a Strong Agonist
Agonist that causes max effects even though it only occupy a small fraction of receptors
What are Weak Agonists
Agonists that need to be bound to many more recptors than a strong agonist does to produce same effect
Partial Agonist
Drug that fails to produce max effect even when all receptors are occupied
What is an Inverse Agonist
Binds to receptor and causes opposite of an agonist. Doesnt block anything from happening, it just reverses what happens
EX: H2 receptor antagonist
What is an Antagonist?
Inhibit/Block actions caused by agonists
Competetive Antagonist
Competes with Agonist for Receptors
- Agonist cant bind to receptor while its occupied by antagonist
- Antagonism can be overcome by high doses of agonists
- EX: Reversal agents
Noncompetitive Antagonist
Binds to site other than the agonist-binding domain.
- Induces form change in receptor so that agonist no longer recognizes agonist binding domain
- Insurmountable - high doses cant defeat this antagonism
- EX: Warfarin
Irreversible Antagonism
Agents compete with agonists for the agonist-binding receptor
- Antagonists bind permanently to receptor
- Rate of antagonism can be slowed by high # of antagonist
Efficacy
Degree that drug is able to cause max effects
Potency
Amount of drug needed to produce 50% of max effect that its capable of causing
Potency vs. Efficacy
- Potency used to compare drugs in same class.
- Drugs in same class usually have same max efficacy
- Efficacy used to compare drugs with different mechanisms.
Drug-Response Curves
- Graphs magnitude of drug action against concentration/dose of drug needed to induce action
- Represents effects and dose of drug within individual rather than population
- Almost all meds plateau at some point
What must be tested on a drug before they are approved for marketing?
Efficacy and Safety must be tested in animal and human population studies
What kind of data is derived from testing a drug’s efficacy and safety?
EC50: Effective Concentration 50%
LD50: Lethal Dose 50%
Therapeutic Index
Margin of Safety
What is Effective Concentration 50%
Effective concentration of drug in 50% of test subjects
What is Lethal Dose 50%
Drug concentration that induces death in 50% of subjects
What is Therapeutic Index
Measure of safety of drug
LD50/ED50
What is Margin of Safety
Margin between therapeutic and lethal dose
Pregnancy Category A
Adequate and Well-Controlled studies have failed to show risk to fetus in first trimester and later trimesters.
Pregnancy Category B
Animal studies failed to show risk to fetus and no studies in pregnant women
Pregnancy Category C
Animal studies show adverse effects on fetus and no studies on humans.
BUT
Potential benefits may warrant use on preggos despite potential risks
Pregnancy Category D
Positive proof human fetal risk, but potential benefits may warrant use of drug on preggos despite potential risks.
Pregnancy Category X
Animal and Human studies show fetal abmormalities and the risks clearly outweigh potential benefits
EX: Warfarin, ACE Inhibitors
Altered Absorption
Drugs may inhibit absorption of other drugs
Altered Metabolism
Important drug interactions can occur when P450 isoenzymes inhbited or induced
Plasma Protein Competition
Drugs that bind to plasma proteins may compete with other drugs for protein binding sites.
EX: Drug A bumped out by Drug B may cause Toxic Drug A Levels
Altered Excretion
Drugs may act on kidney to reduce excretion of specific agents
Types of Drug Interactions
Addition
Synergism
Potentiation
Antagonism
Addition Drug Interaction
Combined drugs EQUALS combined reponses of each drug
1+1 = 2
Synergism Drug Interaction
Combined response GREATER THAN combined response of each drug.
1+1 = 3
Potentiation Drug Interaction
Drug with no effect enhances effect of second drug
0+1 = 2
Antagonism Drug Interaction
Drug inhibits effect of other drug
1 + 1 = 0
Midazolam is siginificant substrate of CYP3A4. Erythromycin is a CYP3A4 inhibitor. How to manage this drug interaction?
You can give same dose, but lingering effects and longer time for awakening
Propofol is a strong CYP3A4 inhibitor. What side effects woud you expect from sedatives that are metabolized by this enzyme when given together?
Synergistic effect if given with versed.
Carbamazepine is a strong CYP3A4 inducer. How might you have to alter dose of Versed if given together?
Give higher dose and change drugs
Tolerance
Decreased response to a drug - dose must be increased for same effect.
What is Metabolic Drug Tolerance
Drug metabolized more rapidly after chronic use
What is Cellular Tolerance
Decreased number of receptors - downregulation
Drug Dependence
- When patient needs drug to function normally
- When cessation of drug = withdrawal symptoms
- Physical and/or Psychological
Abuse and Addiction
Use of meds not for its intended therapeutic use
Use continues despite negative impacts on health, profession, social interactions
Withdrawal
Occurs when drug is not given to a person who is dependent
Symptoms often opposite the effects achieved by drug
Pregnancy Registries
Since it’s unethical for drug testing on preggos, this is where the community can report
REMS - Risk Evaluation and Mitigation Strategy
Way to track drugs with high risk of very dangerous side effects.
