Basic Principles Flashcards
Define: pharmacology
- Study of substances that interact w/ living system
- Beneficial therapeutic effect
- Toxic effects
Define: toxicology
- Undesirable effects of chemicals on systems
Define: pharmacotherapeutics
Study of therapeutic uses & effects
Define: pharmacokinetics
“What the body does to the drug”
- Absorption, distribution, metabolism, elimination =
“ADME”
Define pharmacodynamics, & what is potency?
“What the drug does to the body”
- Study of the relationship btwn drug [ ] & response of pt
- Potency = Amt of drug needed to produce effect
Define: Bioavailability, & what type of administration is equal to 100%?
- Fraction of dose administered that reaches circulation
- 100% for IV administration
How is bioavailability reduced?
- Incomplete absorption
- 1st pass metabolism
Oral bioavailability (What is the percentage?)
5 - < 100%
Geriatric population (How are drugs & nutrients absorbed?)
- Most drugs absorbed via passive diffusion
- Nutrients absorbed by active transport
- Evidence of decreased 1st-pass effect on hepatic or gut wall metabolism –> increased bioavailability
Define: 1st-pass effect
- [ ] of drug is reduced before reaching circulation
- Fraction lost during absorption
Effect of protein binding
- Fraction unbound can be altered by variables
- Higher drug [ ] & decreased plasma protein can lead to higher fraction unbound
- Clearance increases
Protein-bound molecules are not available to do what?
Exert pharmacologic effects
Define: Volume of distribution (Vd)
Relates amt of drug in body to serum [ ]
What is Vd used to calculate?
The loading dose of a drug that will immediately achieve a steady-state [ ]
PK: Distribution in peds
- ↑ Total body water
- ↑ Extracellular fluid volume
- ↓ Binding of drugs to plasma proteins
- ↓ Amt of body fat
PK: Distribution in pregnancy
- ↑ Body fat
- ↓ Plasma albumin [ ]
PK: Distribution in geriatrics
- ↓ Total body water
- ↓ Lean body mass
- ↑ Body fat
- ↔ or ↓ Serum albumin
- ↑ α1-Acid glycoprotein
- ↓ CO
Define: receptors
Molecules in which drugs interact to produce changes in fxn of the system
Define: agonist
Drugs bind to & activate the receptor, which directly or indirectly brings about the effect
Define: partial agonist
Binds to its receptor but produces a smaller effect at full dosage than a full agonist
Define: antagonist
Drugs, by binding to a receptor, compete w/ & prevent binding by other molecules
Define: allosteric
Drugs bind to the same receptor molecule but do not prevent binding of the agonist
Define Irreversible antagonist
Antagonist that cannot be overcome by increasing the agonist
What are sites of drug metabolism?
- Liver = most important organ for metabolism
- Kidney plays a role
- A few drugs are metabolized in many tissues bc of their enzymes
Describe Phase I Reactions
Convert parent drug to a more polar or more reactive product by unmasking or inserting a polar functional group s/a —OH, —SH, or —NH2
- Usually changed to inactive
Describe Phase II Reactions
- Increase H2O solubility by conjugation of the drug molecule w/ a polar moiety s/a glucuronate, acetate, or sulfate
- Forms a highly polar conjugate
Define: Cytochrome P450 (What phase? Responsible for what?)
- Part of Phase I reactions
- Enzyme species, responsible for much of drug metabolism
Define: substrate
Drug metabolized by 1 of the CYP450 enzymes
Define: inducer
Drug that increases activity of a CYP450 enzyme
Define: inhibitor
Drug that decreases activity of a CYP450 enzyme
What are some inhibitors of P-gp?
- Verapamil
- Furanocoumarin components of grapefruit juice
What drugs are normally expelled by P-gp?
- Digoxin
- Cyclosporine
- Saquinavir
- More toxic when given w/ a P-gp inhibitor
Metabolism in peds
- Slower in infants than in older children & adults
- Sulfation pathway is well developed in infants
- Glucoronidation pathway is undeveloped in infants
Metabolism in pregnancy
Hepatic perfusion increases
Metabolism in geriatrics
- ↓ Hepatic size
- ↓ Hepatic blood flow
- ↓ Phase I metabolism
Define: Steady state
Avg total amt of drug in the body does not change over multiple dosing cycles
What do most drugs follow?
Linear pharmacokinetics
- steady-state serum drug [ ]s change proportionally w/ long-term daily dosing
What kind of drugs follow nonlinear pharmacokinetics?
Those w/ serum [ ]s that change more or less than expected
What is the most important pharmacokinetic parameter?
Clearance
What does clearance determine?
- Steady-state [ ] for a given dosage rate
- Efficiency of the organ extracting the drug from the bloodstream
- Determined by blood flow to the organ that metabolizes/eliminates the drug
What can reduce the clearance of drugs that depend on renal fxn?
- Renal disease
- Reduced CO
- Liver disease (less common)
How does impairment of hepatic clearance occur?
When liver blood flow is reduced
- Ex. HF, severe cirrhosis
Define: GFR
- Total filtration rates of functioning nephrons of kidney
- Cannot be measured directly
- Used for detection, severity, & tx of kidney disease
What are variables of GFR?
- Gender
- Age
- Weight
- Race
Efficiency of renal excretion in pediatric pts is determined by what?
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
- Processes may not develop fully for several weeks to 1 yr after birth
Excretion in pregnancy
- Maternal plasma volume, CO, & glomerular filtration increase by 30% to 50% or higher
- Higher levels of estrogen & progesterone alter liver enzyme activity
Excretion in geriatrics
↓ GFR ↓ Filtration fraction ↓ Tubular secretory function ↓ Renal mass ↓ Renal blood flow
Describe the MDRD equation
- Estimates GFR adjusted for BSA
- More accurate than Cockroft-Gault
- Used by most laboratories as eGFR
Cockroft-Gault equation
- Uses body weight
- Standard for drug dosing
When is ABW (actual body weight) used?
If ABW is less IBW
Define: efficacy
Greatest effect an agonist can produce if the dose is taken to the highest tolerated level
*Partial agonists have lower efficacy than full agonists
Define: P-glycoprotein (Where is it found? What is its fxn?)
ATP-dependent transport molecule
- Found in epithelial & cancer cells
- Expels drug molecules from the cytoplasm into the extracellular space
- In epithelial cells, expulsion is via the external or luminal face
Define: Half life (t1/2)
Time required for serum [ ] to decrease by 1/2 after absorption & distribution are complete
What does half life determine?
Time required to reach steady state & dosage interval
What variables usually alter the clearance of a drug?
Disease, age
What is half life dependent upon?
Clearance & Vd
What is the MAP equation?
(SBP x 1/3) + (DBP x 2/3)
