Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

U5A4 pharmacology quiz > 1 > Flashcards

1 Flashcards

1
Q

1st order kinetics does high dose have a higher half life

A

no. half life and dose is independent. half life is a constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the relationship between dose and plasma concentration? (1st order)

A

they are proportional, high dose will have a high plasma conc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the effect of concentration on the rate of elimination? (1st order)

A

the plasma concentration is proportional to rate of elimination. the high the dose, the higher the plasma conc the faster the rate of elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the relationship between volume of distribution Vd and peak plasma concentration?

A

the lower the volume of distribution, the higher peak plasma concentration. Vd=Dose/Initial plasma conc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the relationship between rate of elimination of the drugs with different volume of Vd?

A

the higher the Vd,the slower the rate of elimination.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

explain how Vd affects half life of a drug?

A
  1. Vd is an apparent volume into which the drug appears to distribute to achieve a given conc. in the plasma
  2. the higher the Vd, the greater the proportions of drug that is distributed outside of the blood stream.
  3. thus, less in plasma and therefore, elimination proceeds at a slower rate giving a longer half life.
    Vd is proportional to half life.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

did dose affect the time for plasma conc. to fall to T1/2?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

did Vd affect the time for plasma conc to fall to T1/2

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

did clearance affect the time for plasma conc to fall to T1/2

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

which parameter that T1/2 is dependent on?

A

Vd and Cl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

which parameter that T1/2 is independent on?

A

DOSE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

give a equation on T1/2 and Vd and Cl

A

T1/2= 0.693 x Vd/Cl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

is clearance dependent on initial plasma conc.

A

no. independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

when is the rate of elimination fastest

A

first order kinetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

when is the rate of elimination slowest

A

when plasma conc. is lowest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

when is the rate of elimination constant

A

always linear in 0 order kinetics, until the elimination enzyme is no longer saturated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

can you determine the half life of 0 order kinetics

A

no. the time for plasma conc. to fall by 1/2 depends on conc. its no possible to determine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the relationship between rate of elimination and clearance ?

A

they are proportional, i.e. the slower the clearance the slower the rate of elimination.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

for the i.v. bolus injection, why the decling phase is exponential? does it reach 0 eventually?

A

the concentration of the drug affect the rate of elimination. it will reach 0 eventually

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

if a drug is giving i.v infusion, what shape is the curve

A

the plasma concentration increases and reach plateau

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

if a drug is giving i.v infusion, why it plateau at the end

A

the rate of accumulation = the rate of elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what shape is i.v bolus ?

A

exponential decay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what shape is single oral dose

A

the Cp increases and reach plateau and then decrease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what shape is i.v bolus injection, saturable elimination

A

the plasma is at peak at the beginning and follow the 0 order kinetics. the Cp decreases linearly. when the enzyme is no longer saturated, it will decrease exponentially due to 1st order kinetics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

oral dose. what is rising, decline phase represent for? and plateau phase?

A

rising phase: the elimination is slower than absorption rate

decline: elimination is higher than absoption rate
plateau: elimination is equal to absorption rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is CYP3A4?

A

the major CYP in liver, work on statins, HIV protease inhibitors, benzodiazepines, calcium channel blockers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what inhibit CYP3A4

A

ritonavir, macrolide antibiotics, grapefruit juice, ketoconazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what induce CYP3A4

A

rifampicin, anticonvulsants, St. John’s wort

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what happen to drug if the CYP3A4 inihibited

A

decrease drug clearance, so T1/2 in the body and the maximal serum conc. are increased which lead to toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is clinical significan of CYP3A4 induction?

A

1, increased clearance of drugs metabolised by CYP3A4
2, diminished theraputic effects
3, decreased systematic exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what is CYP2D6?

A

a debrisoquine hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what are the drug that CYP2D6 act on ?

A

codeine, tamoxifen, antiarrhythemics, tricyclic antidepressants, selective serotonin-reuptake inhibitors (SSRIs), many antipsychotic drugs and beta adrenoceptor antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

which country shows the highest ultrarapid metaboliser for CYP2D6?

A

Ethiopians is the highest, chinese is the lowest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what country have the highest intermediate metaboliser for CYP2D6?

A

chinese have the highest, caucasian is the lowest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what are the major phase II enzymes

A

N-acetyltransferases, UDP-glucuronosyltransferases, Sulfotransferases and glutathione S-transferases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what functional group (4) does glucuronidation act on

and what is the name of this enzyme

A
  1. -OH
  2. -COOH
  3. -NH2
  4. -SH
    UGTs (UDP-Glucuronosyltransferases)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what kind of chemical reaction is glucuronidation?

A

nucleophillic substitution rxn

38
Q

what functional group (3) is sulfation act on

A
  • NH2
  • SO2NH2
  • OH
39
Q

what enzyme does sulfation and cofactor does this enzyme require

A

SULTs (sulfotransferases)

cofactor is PAPS

40
Q

what functional groups (3) undergo actylation

A
    • NH2
    • SO2NH2
  3. -OH
41
Q

what enzyme does acetylation

A

NATs (N-acetyltransferases)

42
Q

which country have the highest incidence on NAT 2 variants for defective alleles

A

mediterranean, caucasian and sub-saharan populations

43
Q

is type A adverse drug rxns depends on dose?

A

yes.

44
Q

can you predict type B ADR from known pharmacology

A

not usually

45
Q

which type of ADR is dependent on genetic factors

A

type A.

type B is dependent on usyally uncharacterised host factors.

46
Q

which type of ADR is more frequent

A

type A with wild severity

47
Q

which type of ADR causing more clinical burden

A

type B with high morbidity and high mortality. Tpe A have high morbidity but low mortality

48
Q

during phase I-III, what ADR can be seen

A

type A

49
Q

when is type B ADR happen,during which phase

A

phase IV, occasionally phase III

50
Q

can be use animal model for typeB ADR

A

no. No known animal models. only Type A is reproducible in animal models.

51
Q

what are the main category for genetic polymorphisms

A

pharmacokinetics and pharmacodynamics

52
Q

what is pharmacokinetics?

A

involve in drug metabolism such as absorption, distribution, metabolism and excretion

53
Q

what is pharmacodynamics

A

involve in drug target e.g. receptors, ion channels, enzymes and immune system

54
Q

what is the percentage that the caucasian carry 2 null allleles for CYP2D6

A

6%

55
Q

what is the most common variants CYP2D6?

A

CYP2D64 and CYP2D65 coding for non-functional products

56
Q

absent or reduced CYP 2D6activity can lead to ADRs by the follow mechanisms (3)

A
  1. decrease 1st pass metabolism and drug elimination
  2. accumulation of the drug as a result of reduced metabolism
    3, re-routing of metabolism
57
Q

which drug is metabolised by CYP2D6 is withdrawed? why?

A

perhexilene, it is associate with a higher risk of hepatotoxicity and neuropathy in CYP2D6 poor metabolisers.

58
Q

what drug treated with CYP2D6 poor metaboliser causing a higher risk of ADR? what effect does it have?

A

with pstchotropic agents.

it will have a prolonged hospital stay and higher treatment costs

59
Q

what metabolise S-enantiomer of warfarin, which is responsible for anticoagulant

A

CYP2C9

60
Q

what are the form of variant for CYP 2C9

A

CYP2C9 *2 where cysteine substitutes for arginine at position 144
CYP2C9 *3 where leucine substitutes for isoleucine at residue 359 in the substrate binding site

61
Q

what is the effect of variant in CYP2C9

A

decreased clearance of warfarin by the allelic variants

62
Q

why not do genotype for the CYP2C9

A
  1. R-warfarin is also metabolised by CYP3A4 AND CYP1A2
  2. pharmacodynamic factors also involve in e.g. Vitamin K status and thyroid disease (alter the sensitivity to anticoagulant)
  3. there are mutations in clotting factors that might alter sensitivity to warfarin
  4. there are other methods of dose titration and dose maintenance with warfarin
  5. genotype required within 24 hours of administrations
63
Q

what is TPMT ( thiopurine methyltransferases)

A

involved in the metabolism of 6-mercaptopurine (6-ML) and its pro-drug azathioprine, TPMT activity reduce the formation of thioguanine nucleotides(cytotoxicity)

64
Q

what is the relationship b/t cellular accumulation of thioguanines and TPMT activity

A

inversely related

65
Q

what are the most common form of TPMT variant (3)

A

TPMT *2, TPMT *3A and TPMT *3C

66
Q

how much percentage of caucasians exhibit intermediate activity?

A

at leat 10%

67
Q

what happen to patients with deficient TPMT with full dose of 6-MP

A

lead to fatal haemopoietic toxicity

68
Q

in children, what does TPMT deficiency lead to higher risk of?

A

secondary myelodysplasia leukaemia

69
Q

what is UGT1

A

do glucuronidation of bilirubin, Gilbert’s syndrome shows decrease in activity in UGT1

70
Q

what is the prodrug for SN-38 and reaction convert this?

A

Irenotecan undergo carboxylesterase to form this

SN-38 have anti-tumour activity

71
Q

what metabolise SN-38

A

glucuronidation by UGT1A1

72
Q

what increase the risk factor for irinotecan toxicity?

does this associate with coding region polymorphosm

A

heterozygous or homozygous genotype for UGT1A1*28 in the promoter region.
it does not relate to gene coding polymorphorism

73
Q

what is p-glycoprotein (PGp)

A

an efflux pump with wide substrate specificity

74
Q

what gene encode the Pgp

A

multi-drug resistance gene (ABCB1)

75
Q

polymorphorism in exon 26 of the ABCB1 gene is functional?

A

it is functional, but the homozygous for this polymorphism had the lowest Pgp expression ad the highest digoxin plasma conc.

76
Q

G6PD deficiency, what mode of inheritance is it?

A

sex-linked

77
Q

what does difiency in G6PD cause

A

haemolysis in the presence of stress

78
Q

what does normal G6PD do?

A

it reduces NADP while oxidizing glucose-6-phosphate, thus providing a source of reducing power that maintains cellular glutathione in the reduced form.

79
Q

what happen if there is absence of reduce glutathione?

A

the red cell is susceptible to xoidative damage from drugs—haemolysis , a fall in haemoglobin, fever ans the formation of dark urine

80
Q

what happen when using drug for treating alzheimers

A

it inhibits the acetylineasterase, in a promotoer polymorphorism, this impairs the transcriptional response..

81
Q

what happen if you have disruption of 2 adjacent HNF3 (hepatocyte nuclear factor 3) binding site?

A

it cause the acetylcholinesterase to increase, which increase the sensitivity to acetylcholinesterase pyridostigmine

82
Q

what subtitution predipose to the occurence of tardtive dyskinesia following treatment with typical neuroleptic agenets.

A

a serine to glycine substitution in the gene encoding the dopamine D3 receptor

83
Q

what is tarditive dyskinesia due to?

A

supersensitivity to dopamine

84
Q

what changes after the serine to glycine substitution in gene encoding for D3 receptor?

A

this nalter the tertiary structure of the D3 receptor and increased affinity for dopamine

85
Q

what mutation account fot 50% of the malignant hyoerthermia?

A

mutations in the gene encoding the ryanodine receptor. the mutation make ryanodine receptor more sensitive, result in enhanced rates of Ca released from S.R/ lead to muscle contraction and glycolytic and anaerobic metabolism that is characteristic of malignant hyperthemia.

86
Q

what restrict the use of terfenadine, cisapride, thioridazine and sertindole ?

A

the prolonged QT-interval in ECG and occasianal torsades de points (TdP). this is due to mutations in various ion channel that are responsible for normal ventricular repolarisation

87
Q

how did the drug cause prolonged QT interval

A

by blocking the rapid delayed rectifier K current

88
Q

if we induce TdP, what mutation can be caused?

A

missense mutation in KCNE2, this alter the K channel such that the affected subunit MinK-related peptide 1 acitivated less readily at baseline and was 3 fold more sensitive to drug inhibition

89
Q

KCNE2 SNP associate with?

A

prolonged QT-interval follow the administration of sulfamethoxazole-trimethoprim, probably by accerlerate the deactivation of the channel.

90
Q

analysis of gene encoding enzymes that are responsobile for drug bioinactivation including microsomal epoxide hydrolase, glutathionine transferases, catechol-O-methyltransferase and quinone reductase failed to reveal an association with CBZ hypersensitivity

A

true

U5A4 pharmacology quiz (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions