Pharmacokinetics/dynamics Flashcards
Describe total body water and breakdown in 70kg patient
TBW: 42 L ECF + ICF
Intracellular 28L
Extracellular: 14L
* Plasma volume: 4L
* Interstitial fluid: 10L
What volume of distribution makes something lipophilic vs hydrophilic?
lipophilic Vd > 0.6L/kg or 42L
hydrophilic Vd < 0.6L/Kg or 42L
If a drug has a long half life, what can you do to reach steady state faster? Why?
Give a loading dose, it takes 5 half lives to reach steady state
What is alpha curve in 2 compartment model?
What afeccts how steep it is?
distribution from central compartment
volume of distrubtion. the greater the Vd the steeper the curve
what is beta curve in 2 compartment model?
elimination from central compartment
What is K12?
central compartment to pheripheral compartment
waht is K21?
pheripheral compartment back to central compartment
Elimation half life?
time for 50% of drug to be removed from BODY
what is elimination half time?
time for 50% to be removed from PLASMA
At what point has the drug been cleared?
when 96.9% eliminated from the plasma
Does half life tell us the off set of anesthetic drugs?
no, way more complicated than that,
What is an acid?
donates a proton (hydrogen ion)
what is a base?
accepts a proton (hydrogen ion)
what do strong acids and bases do in water?
dissociate totally
or ionize completely
what do weak acids and bases do in water?
a fraction is ionized and a fraction is non-ionized
what is Pka?
pH where half the drug is ionized and half is non-ionized
ionized is water soluble or lipid soluble? Active or inactive?
water soluble, inactive
Acid in Acid will be ionized or non-ionized?
non-ionized
acid in base will be ionized or non-ionized?
ionized
Weak acids are usually paired with waht?
+ ion like:
sodium
calcium
magnesium
weak bases are usually paired with what?
(-)ion:
chloride or sulfate
What kind of drugs does albumin bind?
mostly acidic drugs
also some basic and neutral drugs too
what does alpha 1 glycoprotein bind?
basic drugs
what does beta-globulin bind?
basic drugs
are changes in plasma protein binding clinically relevant?
rarely
when are changes in plasma protein binding actually clinically relevant?
CPB: hemodilution and heparinization
ECMO: ceftriaxone, fentanyl, and midazolam
describe zero order kinetics
drug elimination at a constant rate
this occurs when drug>enyzme levels
waht drugs follow zero order kinetics?
aspirin
alcohol
warfarin
heparin
theophyline
phenytoin
describe first order kinetics
drug is eliminated at a constant fraction
this occurs when drug is less than enzymes
what drugs follow first order kinetics?
basically everything
what would happen to first order kinetics if an enzyme pathway became saturated?
it would change to zero order kinetics
3 parts of hepatic metabolism?
modification
conjugation
elimination
What are the three types of hepatic modification? And what happens during modification?
oxidation
reduction
hydrolysis (adds water to split compund?
^ polarity
What happens during conjugation?
adds highly polar water soluble substance to the drug/molecule
how is hepatic elimination carried out?
relies on ATP dependent carrier proteins
what drugs undergo enterohepatic circulation and what is the implication?
diazepam and warfarin
this is why they have a long DOA
What are the two ways things are eliminated renally?
- Glomerular filtration
- Organic anion & cation transporters
what do organic anion transporters (OAT eliminate?
lasix, thiazide diuretics, and penicillin
what do organic cation transporters (OCT) eliminate?
morphine, meperidine, dopamine
what drugs are reabsorbed in acid vs basic urine?
acidic urine reabsorbs acidic drugs
basic urine reabsorbs basic urine
What are two things that will acidify the urine?
cranberry juice or ammmmonium chloride
what two things will alkalize the urine?
sodium bicarb
acetazolamide
name the 4 types of plasma metabolism. Which are enzyme dependent and which are not?
pseudocholinesterase (enzyme)
non-specific esterases (enzyme)
alkaline phosphatase (enzyme)
hoffman elimination (ph and temp dependent)
What drugs undergo metabolism by psuedocholinesterase?
succinylcholine
mivacurium
ester LAs
tetracaine
procaine
chloroprocaine
cocaine
what drugs undergo non specific esterase metabolims?
remifentanil
remimazolam
esmolol (RBC esterases)
etomidate (+hepatic)
atracurium (+hoffman)
clevidipine
what drugs undergo metabolism via alkaline phosphatase?
fospropofol
what drugs undergo hoffman elimination?
cisatracurium
atracurium (+non-specific esterases)
What 2 things determine hepatic clearance?
1.liver blood flow
2. hepatic extraction ratio (ER)
when is hepatic clearance perfusion dependent vs capacity dependent?
if ER >0.7 perfusion dependent (liver blood flow)
if ER < 0.3 capacity dependent (livers ability to extract the drug)
enzyme induction/inhibition only affects what kind of heaptic clearnace?
capacity dependent
Drugs with low hepatic ER?
Roc
diazepam
lorazepam
methadone
thiopental
theophylline
phenytoin
drugs with intermediate hepatic ER
midazolam
vecuronium
alfentanil
methohexital
Which cyp-45 enzyme metabolises 50% of all drugs?
CYP3A4
CYP 2D6 metabolises what drugs?
codeine
oxycodone
hydrocodone
CYP 3A4 Enzyme inducers?
ethanol
rifampin
barbiturates
tamoxifen
carbmazepine
St. Johns wort
CPY 3A4 inhibitors
grapefruit juice
cimetidine
erythromycin
azole antifungals
SSRIs
CYP 2D6 inducers
disulfram
CYP 2D6 Inhibitors
Isoniazid
SSRIs
quinidine
other generic enzyme inhibitors
omeprazole
Other generic enzyme inducers
tabaco smoke
phenytoin
what can happen with continuous admin of an agonist?
down regulation of the receptor
what canhappen with continuous admin of an antagonist?
up regulation of the receptor
name an inverse agonsit
propranolol
it decreases cAMP
how many enantiomers does one chiral carbon have?
2
what does dextrorotaty mean?
rotates light clockwise
what does levorotatory mean?
rotates light counterclockwise
what does racemic mean?
two enantiomers in equal ammounts
name two specific enantiomers and their significance
s-bupivicaine (levobupivicaine) less cardo toxic than r-bupivicaine
s-ketamine: more potent and less likely to cause emergence delirium than r-ketamine
Name a major flaw with the concept of context sensitive half time?
only shows time for central compartment concentration to reach 50%, context sensitive half-time does not show wake up time.
which drug admin route has lowest bioavailability?
intrathecal. 0% bioavailability because drug is delivered directly to affect site.
What is Glucuronidation?
When glucuronic acid is added to a moledulce during phase 2 reaction. I.E. morphine > morphine 3 glucuronide.
Name two drugs that are enantimoers but are not prepared in racemic mixtures?
ropivicane
levobupivicaine
name some medications which are racemic mixtures
ephedrine
ketamine
desflurane
name some medications that are weak bases
ephedrine (sulfate)
morphine (sulfate)
name some medications that are weak acids
(sodium) thiopental
(sodium) methoexidal
