Pharmacokinetics and Dynamics Flashcards
Where are water soluble drugs excreted
Urine
Where are lipid soluble drugs excreted
Can cross the lipid membrane so are reabsorbed in the kidney and are changed to water soluble
Which type of drugs will reach the tissue
Free drugs–not bound to protein
CO to lungs
100%
CO to liver
30%
CO to kidney
25%
Bioavailability
How much drug will reach the blood
First pass metabolism by liver
Until all liver enzymes are saturated by the drug, the drug has no effect
What form of drug bypasses the first pass liver effect
Sublingual and IV lidocaine
Fastest route of absorption
Inhalation
Ionized drug
Water soluble–better excretion
Non-ionized drug
Lipid soluble–better diffusion
If pH < Pk
Lots of H+; acidic medium; drug is protonated; non-ionized; lipid-soluble
If pH > pK
Few H+; basic medium; drug is unprotonated; ionized; water soluble
Acidification of urine causes
Increased ionization of weak bases and increased excretion
Alkalization of urine causes
Increased ionization of weak acids and increased excretion
How to make urine more acidic
Cranberry juice, vitamin C, NH4Cl
How to make urine more alkaline
Aspirin
IV administration does not involve
Absorption
100% bioavailability
2 phases of elimination
Rapid decrease in blood concentration due to tissue distribution
Slower decrease in blood concentration due to metabolism and excretion
MEC
Minimum effective concentration
MTC
Minimum toxic concentration
To be bioequivalent…
2 drugs need to have some bioavailability and rate of absorption
Competition between drugs for plasma protein binding sites may
Increase free fraction of drug and might increase the effects of the displaced drug
Sulfonamides and bilirubin competition
Sulfonamides can displace bilirubin from albumin and cause kernicterus in neonates so sulfonamides are contraindicated in newborns
What can cross placental barrier and BBB
Small, lipid soluble drugs
In pregnancy: water soluble alternatives are safer and drugs with highest plasma protein binding
High volume of distribution
Indicates large tissue distribution due to low plasma protein binding
Low volume of distribution
indicates drug primarily found in the blood due to high plasma protein binding
Drug metabolism
Conversion of drug to more water soluble to be more easily excreted
Phases of drug metabolism
Phase 1: modify drug by oxidation, reduction, hydrolytic reactions
Phase 2: conjugation of drug molecule with transferase
Codeine is prodrug for
Morphine
If someone is an ultra-rapid metabolizer they could die
Examples of general inducers
Anti-seizure drugs, Rifampin, HIV drugs, chronic alcohol, glucocorticoids
Increase gene expression of CYP enzymes resulting in increased metabolism of other drugs
Examples of general inhibitors of metabolism
Proton pump inhibitors, azoles and macrolides, grapefruit juice, SSRI’s, acute alcohol
Causes decreased metabolism of other drugs and potential toxicity
Zero-order elimination
Large amount of drugs–toxic level
Saturation kinetics
Body has to eliminate drug at a constant rate regardless of half life
Ex. alcohol, phenytoin, salicylates
First order elimination
Constant fraction is eliminated per unit time
Half life is constant
Most drugs follow this
Clearance
How much blood is completely cleared of drug per unit time
If drug is renally cleared, only the free fraction is filtered by glomerulus
Clinical steady state is reached at
4-5 half lives
Steady state
Rate in= Rate out
Agonist
Has an effect
Antagonist
Has no effect
Inverse agonist
Has opposite effect
Efficacy
Maximal effect a drug can achieve, irrespective of dose
Higher potency=
Less amount of drug needed to reach 100% efficacy
Physiologic antagonism
2 agonists with opposing action antagonize each other
Chemical antagonism
2 chemicals bind to each other and cancel each other (antedotes)
ED
TD
LD
Effective dose
Toxic dose
Lethal dose
Therapeutic index
TD/ED
Phase 1 of FDA oversight
Is drug safe for patients?
Involves healthy volunteers usually young males
Works out toxicity and pharmacokinetics of drug
Phase 2 of FDA oversight
Does the drug work?
Involves patients
Compare to placebo or positive control
Randomized, double-blind
Phase 3 of FDA oversight
how well does drug work and what are common side effects?
Larger group of patients
Phase 4 of FDA oversight
Post marketing surveillance
Schedule 1 Controlled substances
High abuse liability
Low or no medical utility
Heroin, marijuana, LSD, PCP
Schedule 2 Controlled substances
high potential for abuse
Can be prescribed under restricted conditions
Triplicate prescription and no automatic refills
Ex. Opiates, Amphetamines
Schedule 3 Controlled substances
Lower risk
Anabolic steroids
Schedule 4 controlled substances
low potential for abuse
Benzodiazepines
Schedule 5 controlled substances
Lowest abuse potential
Cough medication with codeine
