EXAM 1 Material Only Week 1 Flashcards
Pharmacokinetics
ADME of drugs
Absorption
Route of administration to body
Routes of Administration
IV, PO, Sublingual, Topical, Opthalmic, Rectal
Bioavailability
Amount of drug available after absorption/metabolism to produce an active effect
Which routes avoid first-pass effect
Iv, Sublingual, Buccal, and Rectal
Distribution
Process of drug movement through the body
Distribution dependant on
Size, Charge, and structure
Drugs can passively diffuse when
Small and uncharged
Weak acids will be trapped in
Basic environments
Weak bases will be trapped in
Acidic environments
Drugs bind to plasma proteins to
Normalize concentration in body
Bypass liver and kidney
Stay in body longer
Plasma Protein concentration affected by
Malnourishment
Liver disease
MI
Stress
Infection
Albumin
Major protein of blood
Normally too large to be excreted by the kidneys
Volume of distribution
Dose of Drug/Plasma concentration of drug
Metabolism
Process of making a drug more hydrophilic for excretion
Phase 1 Metabolism involves what rxn
Reduction, Oxygenation, Hydrolysis
Metabolism primarily occurs in
Smooth Endoplasmic Reticulum in liver cells but can occur throughout body
Phase 2 Metabolism involves what rxn
Conjugation/Synthetic
More polar and easier to excrete
Phase 1 Metabolism uses what main enzyme family
Cyp450 (Primarily CYP3A)
Main Family and Subunits of CYP450?
CYP3 (CYP3A4, 5, 7)
Phase 2 uses what main enzyme family?
UGT
What are SNP
Single Nucleotide Polymorphisms - Minor mutations in a protein that lead to metabolic activity changes
What is a Prodrug
Inactive components that need to be metabolized to become active
Example of a Prodrug (Opioids)
Codeine (inactive) to Morphine (active)
What is a Metabolite
Product of metabolism (Active or inactive)
Lipophilic Drugs can/can’t be excreted?
Can’t
Excretion
Removal of drugs from system
Excretion Organs
Kidney, Lungs, Biliary system, Intestines
Also skin, saliva, breast milk
Metabolites must be ____ to be readily excreted by the kidneys
Water soluble
Normal GFR is
125mL/min
Filtration in Glomerulus dependent on
Molecule, Size, Charge, and % of protein binding
Will blood/protein bound drugs be filtered out by the glomerulus?
No. Too Large
Passive Diffusion is most effective for
Uncharged/Unionized drug
Acidic Urine will increase excretion of ___ and is made acidic by
Basic drugs/metabolites, Ammonium Chloride
Basic urine will increase excretion of ___ and is made basic by
Acidic drugs/metabolites Sodium Bicarb
Tubular Reabsorption/Secretion primarily occurs in
Proximal tubule
Tubular Reabsorption reabsorbs
Ions, Amino Acids, and Glucose
Biliary Excretion occurs through ____
Liver secretions (Eg Digoxin)
Biliary excretion enhanced by
Conjugated Metabolites
Enterohepatic Cycling
Drug excreted in bile, reabsorbed by intestines, excreted in bile again
Extends time drug remains in body
Other sites of Excretion
Pulm - Volatile Ketones
Saliva - Erthromycin
Breast milk accumulates
Basic drugs. It’s more acidic than plasma
First Pass Effect
Metabolism of a drug by the liver after oral admin
First-Order Kinetics
Half-Life Elimination (concentration halved each time)
Med will reach peak and trough in 4-5 HL
Dose to reach Css
Zero-Order Kinetics
Consistent amount of med is eliminated
Slower rate of removal
Phase 1 Metabolism converts drug to
Metabolite (Active or Inactive) by adding polar groups
Makes more hydrophilic
SNP Variations that affect metabolism of drugs
Poor Metabolizer - PM
Intermediate Metabolizer - IM
Extensive Metabolizer - EM
Ultrarapid Metabolizer - UM
CYP3A4 works on what % of drugs
50%
What is CYP450
Most common enzyme system for drug metabolism
Which enzymes have the highest genetic variability
CYP2D6, 2C9, and 3A4
Herbal Medications are used by what % of adults in US
40%
What % of adults tell their physician about herbal use
33.4%
Do herbs fall under FDA medication guidelines?
No, considered a food. They do package based on GMP
Saw Palmetto (Indication)
Decreases symptoms of an enlarged prostate due to BPH.
Saw Palmetto (ADR)
dizziness, headaches, nausea, vomiting, constipation, diarrhea, and slow clotting response have been reported.
Saw Palmetto (Drug Interaction)
Anticoagulation - Use with caution or d/cM
Melatonin
Hormone produced by Pineal gland in 4th stage of REM sleep. Similar action to GABA
Melatonin consumption overtime can lead to
negative feedback and normal secretion
Melatonin (MOA)
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
Melatonin (Use)
Induce sleep
Prevent Jet Lag
Melatonin (ADR)
Altered sleep patterns, confusion, headache, tachycardia, and hypothermia.
Potentiates benzodiazepines and succinylcholine, thereby blocking the action making it dangerous
Used long-term, can increase prolactin secretion, which can decrease luteinizing hormone, progesterone, and estradiol levels. Also resets the sleep–wake cycle and contribute to disturbed sleep cycling.
St John’s Wort (Use)
Depression, Mood regulation
St John’s Wort (ADR)
trouble sleeping, vivid dreams, restlessness, anxiety, irritability, stomach upset, fatigue, dry mouth, dizziness, headache, skin rash, diarrhea, and tingling.
St John’s Wort (Drug Interaction)
SSRIs, cyclosporin, birth control pills, antidepressants, some cancer and HIV medications, warfarin, oxycodone, and digoxin
Glucosamine
Amino acid, stimulates chondrotinin/glucosamine production for production of cartilage
Glucosamine (Use)
Osteoarthritis (comparable to celecoxib)
Glucosamine (ADR)
Minor (Constipation, Diarrhea, Drowsiness, H/a, heartburn, nausea, rash)
