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A1 > APEX Pharmacokinetics > Flashcards

APEX Pharmacokinetics Flashcards

1
Q

How long does it take for steady state to be achieved? Can this be altered?

A

5 half lives
Although, we can achieve a faster steady state by administering a loading dose

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2
Q

A drug with a Vd (volume of distribution that exceeds total body water (>42L or >0.6L/kg) is assumed to be ___

A

lipophilic- has way more than water to be hydrophillic
Example: prop

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3
Q

A drug with a Vd (volume of distribution) below total body water (42L) is assumed to be ___

A

hydrophillic, not enough vd to be lipophillic
Example: Roc

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4
Q

How does Vd effect the loading dose?

A

Higher the Vd, the higher the required loading dose

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5
Q

Vd above 42L, lipophillic, characteristics

A

Distributes to larger area, water and fat,

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6
Q

Vd below 42L, hydrophillic, characteristics

A

Distributes into some or all of the body water, but not into the fat
Lower dose required for loading dose
NMBs

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7
Q

What drug characteristics effect Vd?

A

Size, ionization, protein binding

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8
Q

Vd equation

A

amount of drug/ desired plasma concentration

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9
Q

Ld equation

A

[vd x (desired plasma concentration/bioavailability)]

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10
Q

How much water in total body, ICF, ECF, IF, plasma volume

A

42L
28L
14L
10L
4L

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11
Q

Clearance is inversely proportional to

A

half life
drug concentration in central compartment

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12
Q

alpha and beta phase of elimination

A

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)

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13
Q

Central compartment vs peripheral compartment

A

Plasma
Tissues

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14
Q

Rate constants k12 k21 ke

A

k12 from central to peripheral compartment
k21 from peripheral to central
ke for drug elimination

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15
Q

6 half lives and their % of original doses

A

1- 50% remaining
2- 25%
3-12.5%
4- 6.25%
5- 3.125%
6- 1.56%

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16
Q

Which opioid has the same (very small) half life regardless of duration of infusion?

A

Remifentanyl

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17
Q

Acid and base formulas

A

HA <-> H + A (donates a proton)
B + H <-> BH (accepts a proton)

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18
Q

pKa

A

Where 50% of the drug is ionized, and 50% is unionized
Low pKa= great acid
High pKa= terrible acid

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19
Q

What name/ title/ positive ion is added to weak acids?

A

Sodium, calcium, or magnesium

20
Q

What name/ title/ negative ion is added to weak acids?

A

Chloride
Sulfate

21
Q

Characteristics of ionized and unionized drugs

A

ionized- hydrophillic, renally excreted, does not cross placenta
Non ionized- lipophilic, hydrophobic, crosses BBB

22
Q

Ion trapping in pregnancies

A

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

23
Q

Plasma proteins

A

Think of them as a reservoir
Albumin
Alpha 1 acid glycoprotein
beta globulin

24
Q

Whats effects plasma protein and what is the consequence

A

Liver disease, renal disease, old age, malnutrition decrease protein- so the unbound drug will increase in these patients

25
Q

Protein binding fun facts

A

increase in unbound drug from low protein looks like an increase in potency
protein bound drugs have slower metabolism and elimination

26
Q

Vd/ protein binding relationship

A

Inverse

27
Q

Which metabolism order metabolizes a constant amount of drug per time

A

Zero order- alcohol

28
Q

First order kinetics

A

Constant fraction of the drug is metabolized per unit time- almost all drugs

29
Q

Examples of 0 order kinetic drugs

A

alcohol
aspirin
heparin
warfarin
Phenytoin/ theophylline

30
Q

Phase 1 metabolism

A

Modification- oxidation (reduces electron), reduction (adds electron), hydrolysis (adds water to a ester drug)

31
Q

Phase 2 metabolism

A

Adds a highly polar, water soluble substrate to drug
Conjugation- sulfur, methyl, acetic, glucaronic, glycine

32
Q

Phase 3 metabolism

A

Excretion using ATP

33
Q

Extraction ratio meaning

A

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

34
Q

Drugs with liver extraction ratio above 0.7

A

Fent
Prop
Morphine
Ketamine

35
Q

Drugs with low extraction ratio below 0.3

A

Roc
Valium
Methadone

36
Q

CYP450 inducer

A

Tobacco/ weed
Alcohol
rifampin

37
Q

CYP450 inhibitor

A

Grapefruit juice
SSRIs- leave all the drug inside to help with this depression!
omeprazole

38
Q

Urine excretion and drug PH

A

Acid urine increases acidic drug reabsorption
Basic urine increases basic drug reabsorption

39
Q

How to alter urine PH

A

To acidify: cranberry juice, ammonium chloride
To basify: acetazolamide, sodium bicarbonate

40
Q

Drugs that are metabolized by pseudocholinesterase

A

Succ
mivacurium
cocaine

41
Q

Drugs that are metabolized by non specific esterases

A

Remifentanyl (thats why it is different in CTHT)
etomidate
esmolol

42
Q

Hoffman elimination drugs

A

Uses PH and temp
nimbex (cisatracurium)
atracurium

43
Q

When is a change in blood PH most important with regards to a drugs pKa?

A

When the drugs pKa is closest to PH level (7.45)

44
Q
A
45
Q

How does a basic drug pass thru lipid membrane faster? (acidic or basic environment)

A

Basic environment, when the environments PH is ABOVE the pKa of the drug
Vice verse is true

46
Q

Clearance is directly proportional to

A

blood flow of clearing organ, extractino ratio, and drug dose

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