Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology > 1.1 Pharmacokinetics > Flashcards

1.1 Pharmacokinetics Flashcards

1
Q

Isomers

A

Isomers are molecules with the same atomic formulae but different arrangements

may have identical to markedly different pharmacological effects;

for example dihydrocodeine and dobutamine are structural isomers but have very different effects.

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

Geometric isomers

A

cis- or trans- isomers depending on whether the various groups lie on the same or opposite sides of a double bond.

Mivacurium in the trans trand

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

Enantiomers

A

These are formed when groups are arranged around a chiral centre.
Enantiomers are mirror images of each other but cannot be superimposed

R (rectus) or S (sinister) enantiomers depending on whether the groups ascend in atomic numbers around a chiral centre in a clockwise or anti-clockwise fashion.

levo is the S enant

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

Racemic mix

Are the volatiles?

A

Racemic mixtures are mixtures of different enantiomers in equal proportions. Volatile anaesthetic agents are racemic mixtures except for sevoflurane, which has no isomer.

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

What is pharmacokinetics

A 
How a body handles a drug
Absorption
Distribution
Metabolism
Excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

ROutes admin

A

PO, IV, IM, SC, PR, NG, NJ, Intrathecal, Intraperitoneal

inhal, sl, epidural

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

Bioavailibitly

Measured

A

fraction drug reaching systemic circulation given compared to IV bolus dose (100%)

PO dose AUC
________
IV dose AUC

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

Bioavailbiltiy is influenced by

A

Route
IV 100%
others lower (PO often lowest)

Prep
Particle size
protein binding

Physicochem interactions
Milk w/ tetracyclines

Patient factors
Rate emptying
Malabsoprtion

PK
1st pass

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

What is 1st pass metabolism

avoid by

A

Drug absorb gut - liver (portal)

Metabolsim drug b4 system circ (bowel wall / hepatocytes)

may not reach adeq dose

SL, Rectal, Nasal, transdermal,

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

Hepatic enzymed inducers

A 
Phenytoin
Barbiturates
Carbamazepine
Rifampicin
Griseofulvin
Rifampicin
Chloral derivatives.
Alcohol (chronic use), and
Smoking.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Inhibit Enzymes

A

Cimetidine

Amiodarone

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

Hepatic extraction ratio

A

Fraction removed by liver on 1st pass

  1. Blood flow
  2. Uptake hepatocyte
  3. Enzyme metabolic capability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Transdermal

why

eg

factors

A

Topical effects / steroid / avoid 1st pass
Fentanyl, nitrates, hyoscine & oestrogen

Slow constant release - steady state

Lipid bilar - prevent polar.
Lipid soluble drugs absor

Site - blood suplly
contact surface
concentration drug

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

IM adv

Disadv

A

~100%
Rapid onset
regional perfusion dependent
- good msuslce - delt glut, quad

Poor perfuse - second dose before 1st - large bolus

Pain unplease,
abscess haematoma or site wrong

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

Particle size alveoli

A

<1micron - nebuliser = alveoli
= absorption & systemic effects

> 1micron - airway muscose
brochodilators

may be absored - steroids - cushingoid
tachy/ hypokalaemia salbutaom

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

Distribution

A 
How well cross mebrane
Lipid solutility
protein biinding
ionisation
molecular size
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Metabolised

A

Phase 1 - Synthetic

Most drugs undergo 1st

Oxidation
Reduction
hydrolysis

Majoity - cytp450

Phase 2

Synthetic - increase water solubility - allow excretion urine bile
Glucorindation, sulphation, acetylation , methylation, glycination

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

Exceptions to normal cyt p450 metab

A 
MAOI - Adrean, Norad &amp; dopa
ALc dehydrog - alcohol
Atracurium - hoffman degrad ph * temp dep
Esters - non spec esterases
GTN - gastric mucosa
ACE - metab lung
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Elimination

A

Removal of drug plasma includes distribution & metabolism

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

Excretion

A

Removal of drug from body

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

Main sites of excretion

A

Bile & Urine
Breast milk

General rule - high mol wt too large - kidney - bile

Urine

1 Poor lip sol & not pro bound filter glomerulus -> pass into ultrafiltrate

2 active tport - PCT
Secreted urine vs conc grad using energy

3 Diffusion down conc grad in DCT

Basic drug perfertn excre - acidic - increase amount ioniase - unable reasure
vice versa

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

Biliary excretion

A

secreted hepatocye - canaliculus vs conc grad

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

Renal disease

A

Accumuatlion entirel renal

Dose lateration

Conside VD - n
normal = Normal LD ,

Increase - hgiher

Repeated dosing & Frequency reduced

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

Invx renal impairment

A

Cr Cl - est given degree impairment

Red dose = normal dose x imp clear/ normal

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

Compartment model

A

Principle body divided hypotethc compart - diff size & rate transfer
Understand change conc over time

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

1 compartment

A

Draw (ref page 142 dr pod)

Drug admin - even dipserd 1 compartent
Elim in exponential manner - over simplification

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

Exponential

A

graph 143

fxn occur - physiological systems

Y = e^x
Characterised by fact - rate growth proprtional to value
Non liner rises rapidly
Bact & cell culture

If Y =e^-x
fakkbg cyrve 0 gradient prop to height curve
Expon decay drug washout

Conc drug bloodstream proportion to rate of drug excreted from body

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

Vd - apparent vol drug disperese

A

apparent vol drug disperse

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

Factor affect Vd

A

Lipid solubtility
High - large
Degree plsama prot binding / tissue bind & Reg blood flow

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

Calc VD in 1 compartment

A

Dose admin / plasma conc a 0

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

Clearance

A

amount of plsams cleared of drug per unit time

ml/min

32
Q

Using clear - calculate rate elim

A

Clearance x plasma conc

Rate elim depends how much is cleared - plasma conc At given time

33
Q

T 1/2

A

Plasam conc & time
Drop by half initial value
4 t1/2 - Fallen 93.7%
5 96.8

34
Q

Time constant

A

Time plasma conc drop to 0 if initial rate elimination continued

Reality 0 doesnt continue as initial but decrease expnentially
after 1 time constat - fallen 36.8%
2nd further drop 36.8 = 13.5%
Time constant - drug plasma conc to drop to 36.8% of initial

35
Q

Diff time contsnat and half life

A

Time cosntat - drop 36.8% of initial
t 1/2 drop 50%
t 1/2 = time constnat x .693

36
Q

Loading dose =

A

plasma conc x Vd

37
Q

Maintance calculation

A

Replace amt removed - infusion = elim

Rate elim = clearance x conc

rate infsuion - clerance x conc

38
Q

No loading dose - how long to steady sate

A

5 T1/2 or 3 Time constants

39
Q

Two compartment model

A

Draw
Central - plasma
Peripheral - tissues

Drug admin K01, leaving k10
Redistributed k12, return k21

Drug given centrally - rapid decline - distrub peripheral
Cont - equilib

Slower decline - elimnated
Resditrub conc grad periper to central ‘ terminal elim’

Time log plasma cocn - 2 expnoential process, 1 dis & 1 term elim
Slope - represent rate constants

Reciprocal rate constant - time constant - derive distrub t 1/2 & terminal 1/2

40
Q

3 Compartment

A

Draw

2nd - well perfused - faster
3rd poorly perfused

Time log pl conc - 3 expnential process
1 - distrub 2nd, 2 - distrub 3rd & 3rd phase 3 terminal elim

diagram on 149

41
Q

Context sensitive half life

A

Infusion - compartments
stopped - conc gradient
MEtab & excreted
Redistrib 2nd & 3rd - until equilibrium

Reached - removed excretion = reduction in central compartment - reversal gradient
redistrib back - maintain conc beyond end of infusion

Time drug cocn fall half @ end of infsuion called context sens half life (context length of infusion)

42
Q

Constant context sense t1/2

A

Remifentanil
Maintained infusion without accumulation
stopped - effects rapidly dissapear

43
Q

TIVA - advantages

A

avoid volatile
- ponv, distension fluid filled, toxic effexts fluroide ions, ,diffusion hypoxia
MH
surgery difficulty

44
Q

TCI

A

Computer controlled pump - select targ conc for desire effect
PK model of drug (3 comp for prop)

Contin calculate distrub & elim iv agent - adjust infusion rate
Induction & maintenance target - TCI Calculate dose
Adjust during stimulating if needed / or reduce
Decriment time - est time stop wake up

45
Q

1st order kinetics

A

Constant proportion drug removed / unit time
Rate elim proportional amt drug
Majority 1st order - excess enzymes vs subrstate

Neg exponential

46
Q

0 order kinetics

examples x4

A

Constant amt of drug elim per unit time -
‘saturation kinetic’

Enz saturated - not influnce by conc
Phenytoin
Salicylate
Theophylline
Thiopentone

Linear

47
Q

Polymorphic enzymes

A

genetic variation in structure resulting in variations in metabolism.

Hydralazine is metabolised by N-acetyl transferase and slow acetylators are more likely to develop side effects, particularly drug-induced systemic lupus erythematosus.

Suxamethonium is metabolised by cholinesterase and variation in metabolic characterisitics may produce prolonged neuromuscular paralysis.

48
Q

types

Glucuronyl transferase

what
increased by what drugs

A

The enzyme glucuronyl transferase is found only in vertebrates and approximately
eight types have been identified in humans.

membrane bound
smooth endoplasmic reticulum (and nucleus)

Catalyses the glucuronidation
bilirubin and certain drugs

Several barbiturates (for example, phenobarbital), 
anticonvulsants (for example, carbamazepine),

antihistamines cause proliferation of the smooth ER in the hepatocytes

increase hepatic glucuronyl transferase (HGT) activity.

Steroids and tetracycline have no effect.

49
Q

centrilobular cells

A

Reduced hepatic perfusion and ischaemia.

High conc cytochrome P450 isoenzymes

50
Q

Kupffer cell

A

Macrophages (15% of total liver cells); they comprise 80-90% of total macrophages in the body and are normally located in sinusoidal lumen anchored to the endothelium by a long cytoplasmic process.

periportal, but found in every region of liver. They remove particulate and other foreign material - phagocytosis

51
Q

Which oCYP enzymes is most likely to be subject to genetic variability

A

CYP2D6 is responsible for approximately 25% of phase-1 drug reactions.

1 000-fold difference in the ability to metabolise drugs by CYP2D6

or metabolism of antiemetics, beta-blockers, codeine, tramadol, oxycodone, hydrocodone, tamoxifen, antidepressants, neuroleptics, and antiarrythmics.

52
Q

Michaelis-Menten kinetics

Describes

Is initally - first or 0 then becomes

A

Reaction of substrate (S) and enzyme (E) to form product (P), via an enzyme substrate complex (ES).

Saturatable - initially first order (rate is proportional to substrate concentration), becoming zero order (rate independent of substrate concentration, that is, constant rate) as the enzyme’s active sites become occupied.

The constant Km is the concentration of substrate at half maximal reaction velocity, that is, ½Vmax (not Vmax). The equation may be applied to drug absorption, elimination and distribution.

An enzyme is a protein based catalyst, and as defined it is not consumed by the reaction it catalyses.

53
Q

The constant Km

A

The constant Km is the concentration of substrate at half maximal reaction velocity, that is, ½Vmax (not Vmax). The equation may be applied to drug absorption, elimination and distribution.

54
Q

Biliary excretion drugs - concentration gradient

A

In biliary excretion, drugs are secreted from the hepatocyte into the biliary canaliculi against their concentration gradient.

55
Q

Drugs with a low hepatic extraction ratio have the following pharmacokinetic properties:

A

Drug clearance is insensitive to changes of liver blood flow
Drug clearance is very sensitive to alterations in protein binding, intrinsic metabolism and excretion, and
Have no first pass metabolism when given orally.
Examples of drugs with low hepatic extraction ratios include warfarin and phenytoin.

56
Q

Drugs with a high hepatic extraction ratio have the following pharmacokinetic properties:

examples

A

First pass metabolism when given orally

Drug clearance that is
1. Dependent on liver blood flow,

  1. Drug clearance is less sensitive to alterations in protein binding
    intrinsic metabolism.

Examples of drugs with high hepatic extraction ratios include morphine, lidocaine, propranolol and etomidate.

57
Q

G proteins - made up of
How do opiod work

what does it bind to when active

A

G proteins have three subunits, a-alpha, beta and gamma, which link receptors and intracellular secondary messengers. Many hormones effects are mediated via G proteins. Inhibitory G protein mediate the action of opioids. Some hormone receptors are intracellular.

When the G protein is activated, for example, by a hormone, guanosine diphosphate (GDP) is dissociated from the G protein and rapidly becomes guanosine triphosphate (GTP).

The alpha-GTP subunit is a GTPase enzyme which inactivates itself to alpha-GDP allowing it to recombine with the beta-gamma subunit and turn off the G protein switch.

58
Q

Enzyme inducers include:

x8 please

A 
Barbiturates
Carbamazepine
Griseofulvin
Phenytoin
Rifampicin
Alcohol
Tobacco
Chloral derivatives.
59
Q

Elim rate constant

A

fraction by which conc of drug reduces during specifc time period

K

measured in units of time T-1

60
Q

Time constant

A

time taken drug elim if process continued at initial rate
-coressponds fall 37% of initial value
measure time - mins

61
Q

Highly ionised drugs -

and lipid membrane
Vd

Glyco VD

A

dont readily cross lipid membrane - low Vd

eg glyco Vd .16L/kg

62
Q

Vd fentanyl and propofol

A

4l/kg

63
Q

Vd =

A

dose/plasma conc

low vd - high protein bound + low lip solub - confined plasma

64
Q

Diazpeam Vd

A

diazepam - large Vd 1-15l/kg

65
Q

eqns to calc vd

A

K = clearance / Vd

Time constant = 1/K = vd / clearance

l rate constant expon process

66
Q

Plasma cholinesterases metab what nmb

what about the trans trans of 1

A

suxamethonium
mivacurium
trac.

not

cistrac is not - hoffman -> Non spec plasma esterase

Esmolol - red cell esterases

Remi - met non spec tissue cholinesterase

67
Q

Potentiative -

A

1 drug doesnt have independ action - given combo = overal larger than if active drug given alone
eg gent - no NMBD act but if you give iit with trac = inreased NMD

another eg penicilin + probenecid

68
Q

Synergistic

A

Two given togehter greater affet than expected from additive

69
Q

Summative

A

both have effecr increased coadmin = dose each reduce

midaz propofol

70
Q

Acids more unionised

A

acid environment - absorbed in acidic envirn
eg aspirin

A- + H+ = AH

71
Q

Bases become more ionised

A

in acidic conditions

B + H+ = Bh+

72
Q

If drugs given to pt with high cardiac output

Emergence anaes thio

A

diluted by blood = lower plasma conc

alpha phase
init - conc fat soluble - rich blood supply (brain)
less well perfused absorb - plasma conc drop - drug leave brain + enter plasma down conc grad
fall brain conc = emergence

73
Q

First order kinietics

A

NON SATURATED ENZYME RXN

elim - depend conc drug - exponentiation

74
Q

zero order

A

saturted - amt
elim - constant unit time
limted by enzyme

low conc - drug can 1st go 1st order then as saturated becomes 0 order

75
Q

Stereoisomers

A

Same atomic formula and bound but different ararangement around chiral centre

76
Q

Structural isomers

A

Same atomic structure but different bond between molecules

Pharmacology (15 decks)

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