Pharmacokinetics

Question 1

how does the dosing or oral and IV GTN differ?

Answer 1

oral much higher because high first pass metabolism

Question 2

how does protein binding affect Vd?

Answer 2

depends if plasma or tissue proteins
plasma proteins - low Vd
tissue proteins - high Vd

Question 3

can the Vd be larger than total body volume?

Answer 3

yes

Question 4

what is the formula for Vd?

Answer 4

Concentration = mass of dose/Vd.

Question 5

what are the 2 main plasma binding proteins?

Answer 5

albumin and alpha1-acid-glycoprotein

Question 6

is desflurane a good induction inhalation agents?

Answer 6

no because smells and irritant to airways
(however it is fast)

Question 7

how much is desflurane metbaolised?

Answer 7

0.2%

Question 8

all inhalation agents except one are metabolised to trifluoroacetic acid. which one?

Answer 8

sevoflurane

Question 9

what is more soluble in blood N20 or N2?

Answer 9

Nitrous oxide is more soluble than nitrogen in blood

Question 10

what is MAC a measure of and what does it correlate to in terms of physical properties?

Answer 10

MAC is a measure of potency and correlates with lipid solubility (and therefore oil:gas partition coefficient).

Question 11

what determines speed of onset of inhalation agents?

Answer 11

blood:gas coeffiecient - lower blood solubility the quickest

Question 12

which is the most potent inhaled agent?

Answer 12

halothane

Question 13

what does pregnancy do to speed on onset of inhalation anaesthetic?

Answer 13

increases
There are several physiological changes in pregnancy: hyperventilation and reduced FRC will favour a faster onset, but an increased cardiac output would tend to oppose this. Overall the respiratory effects predominantly increase the speed of onset

Question 14

how does emphysema affect speed of onset of inhalation anaesthesia?

Answer 14

Emphysema increases the FRC volume and dilutes the agent in the alveoli.

Question 15

how is thiopentone handled in phase 1 metabolism?

Answer 15

oxidation

Question 16

what is the most common form of phase 1 reaction? what are the other types of reaction for phase 1

Answer 16

oxidation

reduction and hydrolysis are the others

Question 17

list some enzymes involved in phase 1 reactions?

Answer 17

cyp450
monoamine oxidases
monooxygenases
esterases

Question 18

high extraction ratio is dependant on what
low extraction ratio is dependant on what?

Answer 18

high - blood flow

low - protein binding

Question 19

do the following have high or low extraction ratio? Propofol, ketamine, etomidate and morphine

Answer 19

all high

Question 20

how does fat change in elderly?

Answer 20

increase in fat

Question 21

how is half life related to time constant?

Answer 21

half life = 0.693 x time constant

Question 21

how does urine pH change excretion of drugs

Answer 21

weak acids are excreted faster in alkaline urine as alkalinity promotes the dissociation of acid into ion and conjugate base

Question 22

what is the equation for the graph showing concentration of a drug with time in first order kinetics?

Answer 22

C = C0e-k.t
negative exponential - decreases exponentially with time.

Question 23

what is the equation relating clearance to elimination rate constant?

Answer 23

Clearance = Vol of distribution (Vd) x elimination rate constant (Ke).

Question 24

what reactions make up phase 2 metabolism?

Answer 24

sulphation, glucuronidation, acetylation, methylation.

Question 25

list some meds that are prodrugs?

Answer 25

codeine, diamorphine, enalapril

Question 26

which of the following have active metabolites... morphine, diazepam, pethidine, atracurium and pancurium?

Answer 26

all of them

Question 27

which metabolite of morphine is clinically active?

Answer 27

morphine - 6 -glucuronide

Question 28

how is vancomycin elimated?

Answer 28

excreted by kidneys unchanged

Question 29

where are cyp450 enzymes found?

Answer 29

hey are primarily found in the liver, bound to the lipid bilayer of the S endoplasmic reticulum of hepatocytes. also found in the kidneys, and adrenals.

Question 30

what are roles of CYP450

Answer 30

make drugs more hydrophilic for excretion - phase 1 synthesis of physiologically active substances

Question 31

which CYP metabolises fentanyl and midazolam

Answer 31

CYP3A4 is involved in the metabolism of fentanyl

Question 32

how does t1/2 relate to T (half life and time constant)

Answer 32

t1/2=0.693T

Question 33

how does clearance relate to Vd?

Answer 33

clearance = Vd x k (k = rate constant of elimination)

Question 34

how does Time constant relate to rate constant of elimination?

Answer 34

T= 1/k

Question 35

can kidney failure effect bioavailability?

Answer 35

yes as renal failure can have an effect on liver and GIT function

Question 36

what is the intercompartment clearance and elimination clearance equations?

Answer 36

Inter-compartmental clearance is given by V1.k12 or V2.k21. elimination clearance is given by V1.k10

Question 37

what is the following equal too... ln2/k

Answer 37

half life ONLY for first order kinetics, 1 C model

Question 38

how many exponential processes in a 1C , 2C and 3 C model?

Answer 38

1C = 1 2 C = 2 3C =3

Question 39

for propofol how does the intercompartment clearance compare to elimination clearance?

Answer 39

elimination clearance > inter compartment

Question 40

what is the different between a mamillary model and catenary model?

Answer 40

mamillary - V2 and V3 each connected to central compartment caternary V1--> V2-->V3

Question 41

how does the intercompartment clearance of second compartment compare to third ? how do these compare to elimination clearance?

Answer 41

The third compartment has a smaller inter-compartmental clearance than the second compartment Inter-compartmental clearance between the central and second compartment may be greater than elimination clearance e.g. fentanyl and alfentanil (but usually elimination clearance is larger)

Question 42

which of the opioids has smallest Vd?

Answer 42

remifentanil

Question 43

the volume of the 3rd compartment directly reflects lipid solubility true or false

Answer 43

false related but not directly reflected by

Question 44

Why is fentanyl shorter acting than morphine

Answer 44

Very lipophilic. Distributes via intercompartments

Question 45

how does concentration of a drug change with time in first order kinetics

Answer 45

negative expontential decay - the rate of decay changes with time There is a constant proportionality between concentration and rate at which concentration falls: dC/dt = -kC.

Question 46

what has a greater intercompartmental clearance - fentanyl or propofol?

Answer 46

fentanyl for fent intercompart> elimiantion clearance for prop elimination clearance > intercompartment

Question 47

what is the equation for loading dose?

Answer 47

loading dose = Css x Vd Css = plasma conc at steady state i.e. your target

Question 49

A drug behaves according to a single-compartment model. Experimentally you find that it has a half-life of 70 min and a clearance of 100 ml/min. Which one of the following is its approximate volume of distribution?

Answer 49

equations: T1/2 = 0.693 x T T= 1/k Clearance = Vd x k therefore answer is 10L

Question 50

The clearance of a drug is 1.4 L/min. The initial half-life is 10 min. What loading dose is required to give a plasma concentration of 10 mcg/ml?

Answer 50

equations: T1/2 = 0.693 x T T= 1/k Clearance = Vd x k PLUS loading dose = Css x Vd answer = 200mg

Question 51

what info is needed when measuring clearance after an oral dose,

Answer 51

bioavailabilty fraction

Question 52

list factors that can alter pharmacokinetics of a drug ?

Answer 52

age, BMI, other drugs, hepatic or renal failure.

Question 53

how long before the context sensitive half life of propofol is constant

Answer 53

around 70 hours

Question 54

how long does it take a steady state fentanyl infusion to be reached?

Answer 54

60 hours

Question 55

when an infusion is stopped what does the duration of its hypnotic effect depends on?

Answer 55

how much was in the plasma at steady state CSHT

Question 56

what reaches steady state quicker - propofol or remifentanil?

Answer 56

remi as it has a smaller Vd

Question 57

what is the elimination of clearance for propofol and fentanyl?

Answer 57

propofol - 1.9L/min fentanyl 600ml/min

Question 58

how does absorption of drugs in neonates compare to adults?

Answer 58

slower due to longer gastric emptying time

Question 59

when can adult metabolism of drugs in a neonate be similar to adults?

Answer 59

some drugs after 2-4 weeks e.g. barbiturates

Question 60

what is GFR in neonates compared to adults?

Answer 60

20-40%

Question 61

how does aging change the GI absorption of drugs?

Answer 61

Ageing is associated with changes in gastric pH, slowing of gastric emptying, and reduced small bowel surface area

Question 62

how does body water change with age?

Answer 62

decreases with age

Question 63

how is bio-availability affected in elderly?

Answer 63

may be higher due to reduced hepatic flow and thus reduced extraction fraction

Question 64

what factors in pregnancy effect pharmacokinetics?

Answer 64

Hepatic blood flow Hormone levels Placental enzymes - some can metabolise drugs Cardiac output Protein binding

Question 65

how do opioids affect absorption of other drugs?

Answer 65

Opioid analgesics may lead to impaired absorption of enterally administered drugs - changes gastric motility

Question 66

how is the free fraction of drug altered in pregnancy?

Answer 66

increased less PB

Question 67

how does body water compare in neonates?

Answer 67

higher percentage

Question 68

how does obesity affect lorazepam metabolism?

Answer 68

increased metabolism - decreased sedation effect

Question 69

how is pharmacokinetics affected in septic shock ?

Answer 69

decreased plasma proteins - increase in free fraction reduced hepatic activity as making acute phase proteins delayed feeding causes gut atrophy - reduced absorption hepatic blood flow increases when hyperdynamic circulation and then reduces in shock

Question 70

what can the minto model be used for?

Answer 70

remi also propofol 2 separate models by same company - allows use concurrently

Question 71

how does the central compartment vary in schnider?

Answer 71

it doesnt central compartment is fixed

Question 72

which mathematical/ pharm model for propofol uses lean and actual body weight?

Answer 72

schnider - lean marsh - actual

Question 73

what are the mathematical compartment models for TCI for fentanyl and alfentanil and ketamine?

Answer 73

fentanyl - shafer alfentanil - maitre ketamine - domino

Question 74

which 2 CYP 450 enzymes show most pharamacokinetic variation?

Answer 74

CYP2D6 & 2C9

Question 75

which CYP450 enzyme metabolises carvidilol and what can inhibit this?

Answer 75

CYP 2C9 - amiodarone inhibits this

Question 76

what drugs are metabolised by CYP 2C9?

Answer 76

losartan glipizide warfarin carvidilol NSAIDS and selective COX 2 inhibitors fluoxetine, phenytoin

Question 77

polycyclic hydrocarbons in cigarrete smoke induce CYP - which enzyme and which drugs does this effect?

Answer 77

1A2 2E1 caffeine, theophylline and propanolol

Question 78

What is the feature of a sprotte needle that reduces post Dural headache

Answer 78

Sprotte needle = spinal needle Has a bevel to reduce trauma