APEX Pharmacokinetics Flashcards
How long does it take for steady state to be achieved? Can this be altered?
5 half lives
Although, we can achieve a faster steady state by administering a loading dose
A drug with a Vd (volume of distribution that exceeds total body water (>42L or >0.6L/kg) is assumed to be ___
lipophilic- has way more than water to be hydrophillic
Example: prop
A drug with a Vd (volume of distribution) below total body water (42L) is assumed to be ___
hydrophillic, not enough vd to be lipophillic
Example: Roc
How does Vd effect the loading dose?
Higher the Vd, the higher the required loading dose
Vd above 42L, lipophillic, characteristics
Distributes to larger area, water and fat,
Vd below 42L, hydrophillic, characteristics
Distributes into some or all of the body water, but not into the fat
Lower dose required for loading dose
NMBs
What drug characteristics effect Vd?
Size, ionization, protein binding
Vd equation
amount of drug/ desired plasma concentration
Ld equation
[vd x (desired plasma concentration/bioavailability)]
How much water in total body, ICF, ECF, IF, plasma volume
42L
28L
14L
10L
4L
Clearance is directly proportional to
blood flow of clearing organ, extractino ratio, and drug dose
Clearance is inversely proportional to
half life
drug concentration in central compartment
alpha and beta phase of elimination
a- steepest part of curve, represents redistribution from the plasma to the tissues (t1/2a)
b- less steep after a phase, represents elimination from the plasma (t1/2b)
Central compartment vs peripheral compartment
Plasma
Tissues
Rate constants k12 k21 ke
k12 from central to peripheral compartment
k21 from peripheral to central
ke for drug elimination
6 half lives and their % of original doses
1- 50% remaining
2- 25%
3-12.5%
4- 6.25%
5- 3.125%
6- 1.56%
Which opioid has the same (very small) half life regardless of duration of infusion?
Remifentanyl
How does a basic drug pass thru lipid membrane faster? (acidic or basic environment)
Basic environment, when the environments PH is ABOVE the pKa of the drug
Vice verse is true
Acid and base formulas
HA <-> H + A (donates a proton)
B + H <-> BH (accepts a proton)
pKa
Where 50% of the drug is ionized, and 50% is unionized
Low pKa= great acid
High pKa= terrible acid
What name/ title/ positive ion is added to weak acids?
Sodium, calcium, or magnesium
What name/ title/ negative ion is added to weak acids?
Chloride
Sulfate
Characteristics of ionized and unionized drugs
ionized- hydrophillic, renally excreted, does not cross placenta
Non ionized- lipophobic, hydrophobic, crosses BBB
Ion trapping in pregnancies
Biggest danger when mother alkalotic and baby acidotic
Alkalosis increase non ionized form, which allows drug to pass thru placenta,
Acidosis increases ionized form, not letting drug go back to mom
Fetal PH is typically lower than maternal PH
Lidocaine is most likely to be the culpret
Chlorprocaine is least likely
Can be caused from pain by mother, which makes her go into respiratory alkalosis
Plasma proteins
Think of them as a reservoir
Albumin
Alpha 1 acid glycoprotein
beta globulin
Whats effects plasma protein and what is the consequence
Liver disease, renal disease, old age, malnutrition decrease protein- so the unbound drug will increase in these patients
Protein binding fun facts
increase in unbound drug from low protein looks like an increase in potency
protein bound drugs have slower metabolism and elimination
Vd/ protein binding relationship
Inverse
Which metabolism order metabolizes a constant amount of drug per time
Zero order- alcohol
First order kinetics
Constant fraction of the drug is metabolized per unit time- almost all drugs
Examples of 0 order kinetic drugs
alcohol
aspirin
heparin
warfarin
Phenytoin/ theophylline
Phase 1 metabolism
Modification- oxidation (reduces electron), reduction (adds electron), hydrolysis (adds water to a ester drug)
Phase 2 metabolism
Adds a highly polar, water soluble substrate to drug
Conjugation- sulfur, methyl, acetic, glucaronic, glycine
Phase 3 metabolism
Excretion using ATP
Extraction ratio meaning
ER = 1 = 100% of drug delivered to clearing organ is removed
ER .5 = 50% of drug that is delivered to clearing organ is removed
Low extraction ratio= liver has to take drug from blood
High extraction ratio= liver needs blood flow to remove drug
Drugs with liver extraction ratio above 0.7
Fent
Prop
Morphine
Ketamine
Drugs with low extraction ratio below 0.3
Roc
Valium
Methadone
CYP450 inducer
Tobacco/ weed
Alcohol
rifampin
CYP450 inhibitor
Grapefruit juice
SSRIs- leave all the drug inside to help with this depression!
omeprazole
Urine excretion and drug PH
Acid urine increases acidic drug reabsorption
Basic urine increases basic drug reabsorption
How to alter urine PH
To acidify: cranberry juice, ammonium chloride
To basify: acetazolamide, sodium bicarbonate
Drugs that are metabolized by pseudocholinesterase
Succ
mivacurium
cocaine
Drugs that are metabolized by non specific esterases
Remifentanyl (thats why it is different in CTHT)
etomidate
esmolol
Hoffman elimination drugs
Uses PH and temp
nimbex (cisatracurium)
atracurium
When is a change in blood PH most important with regards to a drugs pKa?
When the drugs pKa is closest to PH level (7.45)
