Brainscape's Knowledge GenomeTM

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


See full index

Block 1 Pharmocology > How drugs act 2 > Flashcards

How drugs act 2 Flashcards

1
Q

What is ADME

A

Absorbtion
Distribution
Metabolism
Excretion

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

What is Pharmacokinetics:

A

Factors that determine the ACTIVE concentration of the drug at the ACTIVE site.

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

What is Absorbtion:

A

The mechanism of accumulation of a drug in a body compartment following administration.

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

What is Distribution

A

The way in which a drug reaches each organ of the body

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

What is Metabolism

A

The chemical alteration of a drug into (ultimately) its inactive forms

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

What is Excretion

A

Removal of the drug/or its metabolites from the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

True or False Most drugs (eventually) pass through lipid membrane
But acids and bases ionise

A

True

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

what do Unionised drug differ in

A

lipophilicity

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

where are drugs ionised?

A

when pH opposite to pKa

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

what type of drugs are absorbed?

A

unionised drugs

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

which drugs are ionised and what is its pKa

A

Pethidine

Weak base pKa 8.6

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

which drugs are not ionised much and what is its pKa

A

Aspirin

Weak acid pKa 3.5

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

pH of the stomach

A

3

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

pH of the jejunum

A

7.5

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

how is the free drug distributed and give an example

A

Free drug is distributed according to lipophilicity eg thiopentone

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

where is disribution found and give an example of the drug

A

Drugs bind to plasma/tissue proteins
Bound drug is inactive
Important site of drug interactions. Warfarin

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

what is Volume of Distribution and what is it measurd in

A

A theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.
in ml

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

what happens in the Volume of Distribution is low

A

if ionised and restricted to plasma water

70 Kg + Heparin =7000mls

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

what happens in the Volume of Distribution is equal to body volume

A

if lipophilic

70Kg + Thiopental=70,000mls

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

what happens in the Volume of Distribution is high

A

if protein bound i.e. apparent

70Kg + Digoxin=350,000mls

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

what different ways can drugs be metabolised in the liver

A

Oxidation Reduction Hydrolysis Hydration

Conjugation Condensation Isomerization

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

what is the principal site of drug metabolism?

A

the liver

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

how does liver metabolism work?

A

Liver metabolism typically inactivates drugs
Drug metabolites however may remain pharmacologically active
And even more active than the parent compound!

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

what is a prodrug and give examples

A

An inactive or weakly active substance that has an active metabolite is called a prodrug (e.g. bambuterol -terbutaline)

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

what is the point of drug metabolism

A

make the drug easier to excrete.

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

what is involved in phase one metabolism?

A

Cytochromes

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

what are Cytochrome P450 (CYP) enzymes

A

haem proteins

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

how many CYP gene families are there

A

74

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

which 3 CYP genes families are involved in metabolism?

A

CYP1, CYP2 and CYP3

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

how do CYP1, CYP2 and CYP3 differ

A

another in amino acid sequence and in the specificity of the reactions that they catalyze

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

what supplies the electrons

A

NADPH–CYP450 reductase

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

what is NADPH–CYP450 reductase

A

a flavoprotein that transfers electrons from NADPH (the reduced form of Nicotinamide Adenine Dinucleotide Phosphate) to CYP450.

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

what happens as a result of the CYP450 enzumes being induced or inhibited by many substances

A

drug interactions in which one drug enhances the toxicity or reduces the therapeutic effect of another drug.

34
Q

What is does induction and give examples of drugs

A

decrease plasma drug conc’n.
ethanol in heavy drinkers
Rifampicin and contraceptive steroids

35
Q

what does inhibition do and give examples of drugs

A

increase plasma drug conc’n

Ketaconazole and terfenadine

36
Q

what is the most common phase 2 metabolism reaction

A

Glucuronidation

37
Q

which is the only part of th phase 2 reacrion that happens in tthe liver microsomal enzyme system

A

Glucuronidation

38
Q

what does conjugation do ergo why is it good

A

makes most drugs more soluble and easily excreted by the kidney

39
Q

where are Glucuronides are secreted

A

bile

40
Q

where are Glucuronides are excreted

A

urine

41
Q

what happens in Amino acid conjugation

A

conjugation with glutamine or glycine produces conjugates that are readily excreted in urine but not extensively secreted in bile.

42
Q

three types of conjugation in phase 2 metabolism

A

Glucuronidation
Amino acid conjugation
Sulfoconjugation

43
Q

what is good about sulfate esters

A

Sulfate esters are polar and readily excreted in urine

44
Q

what happens in terms of amino acid conjugation - in neonates

A

conversion to glucuronide is slow, potentially resulting in serious side effects of some drugs (eg, chloramphenicol)

45
Q

which organ regulates the fluid and electrolyte balance of the body by continually filtering the blood.

A

the kidney

46
Q

why is it vital that the kidney regulates the fluid and electrolyte balance of the body by continually filtering the blood.

A

to maintain a constant extracellular fluid volume and composition

47
Q

the kidney maintains a constant extracellular fluid volume and composition, how does it do this?

A

excrete or conserve salt and water;
control body pH, and
free the body of waste products of metabolism and drugs

48
Q

what are the three main mechanistic processes that enable the kidneys to regulate the chemical constituents of blood?

A

excrete or conserve salt and water;
control body pH, and
free the body of waste products of metabolism and drugs

49
Q

where does elimination happen

A

the kidney

50
Q

what does Pharmacokinetics focus on?

A

on concentration in plasma (Cp).

51
Q

what is Cp

A

Cp is assumed to relate to extracellular fluid surrounding cells.

52
Q

wht is the the target concentration strategy:

A

individual variation in response to drug is greater than Cp variation at that dose.

53
Q

examples of drugs used in therapeutic drug monitoring

A

cyclosporine, digoxin, phenytoin, methotrexate

54
Q

what is Pharmacokinetics used for

A

in therapeutic drug monitoring (TDM)

55
Q

apart from Cp, what else is useful

A

Concentrations in other body fluids may also be useful.

56
Q

how to measure

A

Fit concentration vs. time data to a theoretical model and determine parameters.

57
Q

what is Cmax:

A

maximum plasma concentration following a given dose.

58
Q

what is Tmax:

A

time between drug dose and achieving Cmax.

59
Q

Parameters are used to adjust dosing regimen, what are they based on?

A

experimental estimates, patient data

60
Q

what is slow absorption from administration site into the plasma is equivalent to

A

a slow infusion at a variable rate.

61
Q

what is transfer of drug to central compartment is governed by

A

rate constant, kabs

62
Q

what does varation in rate of absoption assume

A

Assumes that kabs is directly proportional to amount of drug still unabsorbed

63
Q

what is the result of slow absorption

A

reduces Cmax but increases duration of action

64
Q

what happens once absoption is complete?

A

Cp declines with the same t1/2, irrespective of rate of absorption.

65
Q

how can you estimate C0

A

extrapolating semi log plot of Cp vs. time back to time 0.

66
Q

what is the single compartment model

A 
Initial concentration (C0) following bolus dose of Q mg:
C0 = Q/Vd
67
Q

what is elimination half life

A

is the time taken for Cp to fall by 50%.

68
Q

what does elimination half life predict

A

What will happen after drug administration, before reaching steady state
What will happen after stopping infusion, as Cp declines towards 0.

69
Q

what does a longer t1/2 mean

A

longer persistence of drug in body after dosing is stopped.

more time is needed to accumulate drug to steady state therapeutic level.

70
Q

why would clinitians may use a loading dose

A

to achieve therapeutic concentration more rapidly (dependent on Vd).

71
Q

what is the clinical urgency of elimination half life

A

cardiac dysrhythmias, e.g. amiodarone, digoxin

72
Q

what is the effect of repeated dosing

A

More common than single injections or constant infusion.
Same pattern as for IV infusion
Oscillation through range Q/Vd
Steady state achieved after 3-5 half-lives

73
Q

limitation of single compartment model

A

Oversimplification.
Assumes that rates of absorption, metabolism and excretion are directly proportional to drug concentration in the compartment.
Different tissue compartments, e.g. brain, fat, muscle, may affect time courses of drug distribution.

74
Q

Two-compartment model

A

Tissues represent a peripheral compartment.
Drugs enter second compartment via central (plasma) compartment.
Result: add a second exponential component to the Cp time course

75
Q

Double exponential kinetics limintation

A

Limitation: some drugs are not equally soluble across all tissues (e.g. fat soluble drugs)

76
Q

Cp time course has a fast and slow phase.
Often found experimentally.
talk bout the Fast phase

A

represents transfer between central and peripheral compartments (plasma – tissues)
Cp after fast phase is complete allows measure of combined Vd of both compartments.

77
Q

Cp time course has a fast and slow phase.
Often found experimentally.
talk bout the slow phase

A

t1/2 for slow phase (β) provides an estimate of rate of elimination.

78
Q

what happens if metabolism is rapid

A

then α and β are not well separated.

79
Q

which drugs dont follow single or double exponential kinetics for elimination from plasma.

A

ethanol, phenytoin, salicylate

80
Q

discribe how ethanol is secreated and explain why in terms of saturation kinetics

A

: disappearance from plasma is linear, irrespective of dose or Cp.
Explanation: rate of oxidation by alcohol dehydrogenase saturates at low ethanol concentrations.

81
Q

Implications of saturation

A

Duration of action is more dependent on dose.
Relationship between dose and steady state Cp is steep and unpredictable.
Maximum rate of metabolism sets a limit to dosing rate.
Drugs with saturating kinetics are difficult to administer effectively and may be rejected in development.

Block 1 Pharmocology (17 decks)

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