Metab/Excretion & Drug Specific Pharmokinetics Flashcards
Biotransformation
metabolism of a drug from an active to inactive form
Clearance
removal of drug from the body
1st Pass effect
oral drug passes through the liver for degradation before distribution into tissues
Half-Life
time required for total drug concentration in the body to be reduced by 50%
Prodrug
precursor to an active drug
pKa
describes how acidic (or not) a given hydrogen atom in a compound is, PH OF DRUG
The pH at which half the drug is ionized
*Function of Metabolism
change drug into a water-soluble form
promote excretion
*Function of Excretion
removal of drug from body
*Metabolism Mechanism
-Are enzyme reactions occurring in the liver (CYP enzymes involved in phase 1)
2 phases;
- ) phase 1–drugs become more polar and water soluble (more prone to renal elimination)
- ) phase 2– drugs are conjugated and are inactive, become more water soluble (more prone to renal elimination)
Enzymatic effects on Metab
induction- increases enzyme expression thereby increasing metab
activation- drug binds to enzyme to increase activity of enzyme thereby increasing metab
Inhibition- drug with greater affinity for enzyme competes w/ drug OR enzyme expression is reduced, thereby slowing metabolism
*Elimination Mechanism
Renal Excretion- drugs entering nephron exert action (diuretic), be reabsorbed into blood stream, or progress to collecting duct for EXCRETION.
Biliary/Fecal Excretion- excretion by the liver to the gallbladder= biliary elimination, gallbladder empty into intestines and excreted via feces
Others; sweat, tears, saliva hair, skin breast milk expiration
*Half-Life
determines time to reach steady state
dependent on characteristics of drug (Vd, clearance)
Amount of drug can affect this
*Clearance
final element in elimination process
drugs may be cleared via biliary, renal, or hepatic means
dependent on the volume of distribution and inversely related to half life
Renal clearance
a good indicator of kidney function, measured via creatinine in blood.
poor kidney function»increased serum creatinine»>decreased GFR.
Steady State
equilibrium between amount of drug entering and leaving the body
*Dosing Phenytoin (Loading)
Loading Dose
-oral; not recommended but can be given in 3 doses
-IV; phenytoin max=50mg/min
fosphenytion max=150mg/min
*Bradycardia, hypotension associated with rapid infusion
neonates/infants/child/adult= 15-20mg/kg
*Dosing Phenytoin (Maintenance)
Children- q6h or q12h
Adults- qHS ER caps
*Phenytoin Monitoring
After loading dose:
IV- >2h after infusion end
PO- 24h after dose
Maintenance Doses:
Daily PO- trough
Divided IV- Trough
Divided PO- trough suggested
Phenytion Interactions
inducer of CYP enzymes–> enzyme working more so its breaking down more drug leaving less in your body to work.
Hepatic disease you would reconsider dosage of dilantin to the pt because they do not contain the enzymes to metabolize the drug leading to build up of drug leading to nystagmus or CNS depression
Would not need to reconsider dosage with someone in kidney failure b/c the drug is not metabolized in the kidney.
Gentamicin/Tobramycin Dosage Forms
Gentamicin- injection, topical cream, opthalmic solution
Tobramycin- injection, nebulizer, opthalmic soltution
*Gentamicin/Tobramycin Dosing
Traditional- smaller doses over shorter intervals
Extended interval- larger doses longer intervals
*Gentamicin/Tobramycin Drug Monitoring
Troughs- immediately prior to next dose, traditional dosing 4-5 half lives
**peaks (efficacy)- 30 minutes following end of transfusion, traditionally dosing 4-5 half lives
Only done for IV or IM
Vancomycin Dosing Forms
Injection oral capsules (CDIFF ONLY b/c it concentrates in GI tract)
*Vancomycin Dosing
Adults- loading dose 20-25mg/kg, maintenance dose 10-20mg/kg/dose
Peds- 10-15mg/kg/dose q6h
**Intervals based in renal function, check creatinin to see if you can give another dose of drug.
**Troughs measure efficacy
*Vancomycin Drug Monitoring
Troughs(efficacy)- immediately prior to next dose
Peaks- rarely done
**Monitoring only done when given via injection
Warfarin Dosage Forms
IV or Oral Tablets
*Dosing: WARFARIN
Adults: 2-5mg oral once daily
NOT for pregnant ppl
*Dosing adjusted based on INR
*Drug Monitoring: WARFARIN
INR check 2days after dosage
follow up q1-2day until therapeutic, once therapeutic q2-4wks
*if switching to differ anticoagulant; must overlap therapies fors 1st 5 days
Warfarin Side Effects/Interactions
Bleeding/bruising, Clot formation
CYP Mediated-
- inducer; less warfarin in body
- inhibitor; build up of warfarin in system
Vit. K:
Vit K promotes liver production of clotting proteins. Warfarin works against Vit. K by reducing the livers
Ability to use vit K thereby reducing the synthesis of clotting proteins and makes your blood thinner.
A significant change in vit K can result in a dangerous change in INR. If you reduce vit K. INR will increase
(blood becomes thinner). Good to keep constant levels of vit. K in system so there are not great fluctuations in INR.
Phenytion Interactions
Phenytion is strong inducer of CYP enyzmes meaning: enzyme will work more to break down more drug leaving less in your body to work.
Inhibitor: will make enzyme not work as well(meaning it cant break it down) leading to build up of drug in body
Phenytion Interactions w/ Hepatic Disease and Renal Failure
Hepatic Disease: reconsider dosage of drug b/c pt does not contain enzymes (made by the liver) to metaboilize the drug leading to a build up of the drug in the body….potentially developing nystagmus or CNS depression.
Renal Failure: Does not effect phenytion metabolism because it is metabolized in liver and not kidneys
Vancomycin Disease States?
Redman’s Syndrome- hypotension, erythematous rash
Ototoxicity- tinnitus, vertigo
Nephrotoxicity- acute kidney injury, sepsis
