Introduction to Pharm Flashcards
Pharmacogenetics
Genetic influences by and on drugs
Pharmacodynamics
Physiological and biochemical mechanism of action of drugs (what the drug does to the body)
Competitive vs noncompetitive drug binding
Competitive: Reversible, most drugs
Noncompetitive: Nonreversible (ex: Aspirin)
ED50
Effective dose in 50% of the population
TD50
Toxic dose in 50% of the population
LD50
Lethal dose in 50% of the population
LD50/ED50
Therapeutic index
- Safety measure of drug
- Higher number = better
TD50/ED50
Therapeutic window
- Estimation of drug dose that can treat disease effectively while staying in safety range (minimal toxicity/side effects)
- Ratio between minimum effective concentration to minimum toxic concentration
- “Margin of safety”
Strongest chemical bond type -> weakest (5 of them)
Covalent, usually is irreversible
Then ionic, hydrogen, hydrophobic, van der waals
4 things a dose response curve lets your determine
Affinity/potency -How much drug is needed/attraction of drug to receptor Efficacy -Can the drug produce 100% of the desired effect? Variability -Difference in living things Slope -Measures the margin of safety/toxicity
ED99
Effective dose in 99% of the population
Down-regulation
Caused by continued stimulation of cells with agonists, leads to desensitization
-Effect that follows continues or subsequent exposure to the same concentration of drug is diminished
Up-regulation
Caused by chronic administration of antagonists
- Number and sensitivity of receptors increase when they’re chronically blocked
- Results in tolerance-higher doses of antagonist are needed to counteract increasing receptor number
Addition effect of drugs
Combined effect of 2 drugs via the same mechanism is equal to what’s expected by adding their individual actions (1+1=2)
Synergism effect of drugs
The combined effect of 2 drugs is greater than the algebraic sum of their individual effects (1+1=3)
Potentiation effect of drugs
The enhancement of the action of one drug by a second drug that has no detectable action of its own (1+0=3)
Antagonism effect of drugs
The action of one drug opposes the action of another (1+1=0)
-Reversal drugs
Bioavailability definition in drug administration
The percentage of drug contained in a drug product that enters the systemic circulation in an unchanged form after administration of the product
- IV: 100%
- Inhalation: 5-<100%
- Oral: 5-<100%, first-pass effect may be significant
pKa
Ionization constant of a chemical compound, pH at with the drug will exist in solution as 50% ionized and 50% non-ionized
-Measures the extent of ionization (not acid/base status)
General absorption of non-ionized drug
- Lipid soluble
- Can be absorbed through GI
- Can cross placenta and blood brain barrier
General absorption of ionized drug
- Water soluble
- Can’t get through phospholipid bilayer to be absorbed GI/placenta/BBB
pH-pKa=0
50/50 ionized/non-ionized
pH-pKa=0.5
75/25 ionized/non-ionized
pH-pKa>1
99/1 ionized/non-ionzed
Determining ionized vs nonionized percentage
Acids -In acidic pH: Non-ionized -In basic pH: Ionized Bases -In acidic pH: Ionized -In basic pH: Non-ionized
Drug metabolism: Phase 1 vs 2 reactions
Phase 1 -Oxidation -Reduction -Hydrolysis Phase 2 -Conjugation -Synthesis
Conjugation metabolism
Coupling the drug molecule to an endogenous substituent group so it has more water solubility
- Leads to enhanced renal or biliary elimination
- Catalyzed by phase 2 drug-metabolizing enzymes
1st pass metabolism (and effect of grapefruit juice)
After the oral administration of a drug
- Absorbed drugs to go liver before systemic circulation
- Decreases their bioavailability
- Grapefruit juice inhibits CYP3A enzymes-increases the bioavailability of the drug
Enzyme induction and inhibition
Induction
-Process when drugs, environmental chemicals, air pollutants, and components of cigarette smoke stimulate the synthesis of drug-metabolizing enzymes
-May elevate the level of hepatic drug-metabolizing enzymes
Inhibition
-Opposite of ^
-Results in less metabolism of drugs, increasing their effects
Ionized drugs that are taken orally (metabolism)
Not absorbed well, may not be metabolized by the liver to a significant extent
-Instead are commonly excreted via the renal system
Main factors (2) that determine the rate of drug passive diffusional transfer across membranes
Lipid solubility of the drug
Concentration gradient
(Molecular weight is less important than ^)
Protein binding (bond strength, proteins, examples where its significant)
- Influences how a drug is distributed
- Protein-bound drug isn’t free to act on receptors
- Proportional to its lipid solubility (more lipid soluble=highly protein bound)
- Bond between drug and protein is usually weak
- Proteins=albumin (most common), AAG
- > 90% protein bound drugs=warfarin, phenytoin, propranolol, Propofol, fentanyl, diazepam (intensification of their effects if they’re displaced from plasma proteins)
Beta half-life
AKA Elimination half-life
- Time necessary for the plasma content of a drug to drop by half
- Drug is fully eliminated when 95% of it has been eliminated from the body (4-5 half-lives)
