Week 1- Study Guide Flashcards
Stages of pharmacokinetics
Absorption, distribution, metabolism, excretion
What is absorption?
How drug moves from site of administration to sign of action
Things that impact route of adminstration
compliance, bioavailability, onset of action and duration
What is bioavailability?
% of administered drug able to produced a pharmacological effect [IV drugs have higher bioavailability]
What is distribution?
Describes the journey of the drug throughout the bloodstream to various tissues of the body and passive diffusion
What does distribution depend on?
Different transport systems including size, charge, and structure (pH too!)
Ion Trapping
build up of higher concentration of unionized and ionized drugs across the membrane based on pH
What is protein binding?
drugs bind to plasma proteins to help normalized concentrations throughout the body, to stay in the body longer
what are plasma proteins impacts by?
poor nutrition, liver disease, kidney disease
Transport systems (distribution)
P glycoproteins and MRP1 (multidrug resistance protein)– both efflux transporters
What is metabolism?
Process of how the body breaks down the drug
What are metabolites?
products of metabolism
Phase 1 metabolism
non-synthetic reactions: oxidation, reduction, hydrolysis
Phase 2 Metabolism
Synthetic or conjugation reactions-metabolites are link/conjugated to polar molecules →making metabolites more water soluble
CYP450
catalyzes metabolism of highly lipid soluable drugs and chemicals, transfer electrons from oxidation of drugsrod
Prodrugs
inactive compound that rely on metabolism to become activated
what is excretion?
How drugs are removed from the body
Organs involved in elimination
kidneys, lungs, biliary, intestines
renal excretion
metabolites need to be water soluable
factors that influence GFR
biliary excretion
1 L of bile a day, conjugated (binding with proteins) to enhance biliary excretion
enterohepatic cycling
Drug excreted in bile→ absorbed from intestines →excreted in the bile again==>extends time that a drug remains in the body
first pass effect (metabolism)
metabolism at specific locationof the body leads to reduction in concentration of active drug before it reaches the site of action or systemic circulation
example of first pass effect
metabolism of the liver after oral administration
first order kinetics
half life elimination, medication will reach peak and trough at 4-5 half-life
zero order kinetics
rate of drug elimination is independent of drug concentration… same amount is eliminated per hour regardless of how much drug is in the body (think of alcohol)
what is the CYP 450 system
collection of enzymes essential for metabolism of drugs, toxins and endogenous compounds
where is the CYP enzymes found
in the liver, but also present in intestines, lungs and brain
where does the CYP work?
mainly in phase 1 metabolism assisting in oxidation, reduction and/or hydrolysis
how does genetic variability play a role in CYP450 enzymes?
variations like polymorphisms scan impact how people metabolize drugs
examples of genetic variability
drug interactions with CYP450 systems- inducers
rifampin and st. john’s wort can INDUCE CYP3A4, leading to decreased levels of drugs metabolized by this enzyme
drug interactions with CYP450 systems- inhibitors
Drugs like ketoconazole and grapefruit juice can inhibit CYP3A4, leading to increased levels of drugs metabolized by this enzyme
importance of CYP3A4
*responsible for up to 50% of drug metabolism
*Works on several classes of drugs: -azole antifungals, calcium channel blockers, antihistamines, anticonvulsants, antimicrobials, and corticosteroids.
*Amiodarone has half life, close to 60 days, and inhibits the CYP450 enzyme system.
Factors that affect metabolism of drugs
single nucleotide polymorphisms, enzymes, half-life, pro-drugs
how do single nucleotide polymorphisms impact metabolism of drugs
minor mutations that can exist in an individual enzyme or protein, can help explain why certain groups of people are sensitive to certain drugs
how do enzymes impact metabolism of drugs
two drugs may be metabolized by the same enzyme and may extend half life of competing drug
how are prodrugs related to metabolism of drugs
inactive compounds that rely on metabolism to become active
herbal medication safety
encourage patients to disclose all supplements used, supplements rated as “food” not same standards as medication
things that impact herbal medication potency
growth, harvesting, processing, storing and shipping
what is saw palmetto?
helps with BPH, decreases symptoms of enlarged prostate
what are ADR of Saw Palmetto
dizziness, headache, nausea, vomiting, constipation, diarrhea and slow clotting response
what is melatonin
hormone produced pineal gland, assists in sleep and prevention of jetlag
how does melatonin work
Produced when serotonin is broken down in the pineal gland with the help of two enzymes; arylalkylamine N-acetyl transferase (AA- NAT) and hydroxyindole-O-methyl transferase
ADRs of melatonin
altered sleep patterns, confusion, headache, tachycardia, and hypothermia.
Potentiates benzodiazepines and succinylcholine, thereby blocking the action making it dangerous
how often should melatonin be used
Should not be used more than 3 times a week
what is st. john wort?
used for depression, mood regulation
what are some ADRs of St John’s Wort
trouble sleeping, vivid dreams, restlessness, anxiety, irritability, stomach upset, fatigue, dry mouth, dizziness, headache, skin rash, diarrhea, and tingling.
Biggest problem with St Johns Wort
Numerous Drug Interactions, which include:
SSRIs, cyclosporin, birth control pills, antidepressants, some cancer and HIV medications, warfarin, oxycodone, and digoxin
What is glucosamine?
It is an amino acid found in mucopolysaccharides and chitin
what is glucosamine used for?
Treatment of OA, stimulate cartilage production and enhance rebuilding of damaged cartilage
what are some ADRs of glucosamine
minor- constipation, diarrhea, drowsiness, headache, heartburn, nausea, and rash
