1.1 Pharmacokinetics Flashcards

Question

Compartment model

Answer 1

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

Answer 2

Draw (ref page 142 dr pod) Drug admin - even dipserd 1 compartent Elim in exponential manner - over simplification

Answer 3

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

Answer 4

apparent vol drug disperse

Answer 5

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

Answer 6

Dose admin / plasma conc a 0

Answer 7

amount of plsams cleared of drug per unit time | ml/min

Answer 8

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

Answer 9

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

Answer 10

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

Answer 11

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

Answer 12

plasma conc x Vd

Answer 13

Replace amt removed - infusion = elim Rate elim = clearance x conc rate infsuion - clerance x conc

Answer 14

5 T1/2 or 3 Time constants

Answer 15

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

Answer 16

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

Answer 17

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)

Answer 18

Remifentanil Maintained infusion without accumulation stopped - effects rapidly dissapear

Answer 19

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

Answer 20

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

Answer 21

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

Answer 22

Constant amt of drug elim per unit time - 'saturation kinetic' ``` Enz saturated - not influnce by conc Phenytoin Salicylate Theophylline Thiopentone ``` Linear

Answer 23

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.

Answer 24

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.

Answer 25

Reduced hepatic perfusion and ischaemia. | High conc cytochrome P450 isoenzymes

Answer 26

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

Answer 27

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.

Answer 28

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.

Answer 29

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.

Answer 30

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

Answer 31

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.

Answer 32

First pass metabolism when given orally Drug clearance that is 1. Dependent on liver blood flow, 2. 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.

Answer 33

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.

Answer 34

``` Barbiturates Carbamazepine Griseofulvin Phenytoin Rifampicin Alcohol Tobacco Chloral derivatives. ```

Answer 35

fraction by which conc of drug reduces during specifc time period K measured in units of time T-1

Answer 36

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

Answer 37

dont readily cross lipid membrane - low Vd | eg glyco Vd .16L/kg

Answer 38

dose/plasma conc low vd - high protein bound + low lip solub - confined plasma

Answer 39

diazepam - large Vd 1-15l/kg

Answer 40

K = clearance / Vd Time constant = 1/K = vd / clearance l rate constant expon process

Answer 41

suxamethonium mivacurium trac. not cistrac is not - hoffman -> Non spec plasma esterase Esmolol - red cell esterases Remi - met non spec tissue cholinesterase

Answer 42

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

Answer 43

Two given togehter greater affet than expected from additive

Answer 44

both have effecr increased coadmin = dose each reduce midaz propofol

Answer 45

acid environment - absorbed in acidic envirn eg aspirin A- + H+ = AH

Answer 46

in acidic conditions B + H+ = Bh+

Answer 47

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

Answer 48

NON SATURATED ENZYME RXN elim - depend conc drug - exponentiation

Answer 49

saturted - amt elim - constant unit time limted by enzyme low conc - drug can 1st go 1st order then as saturated becomes 0 order

Answer 50

Same atomic formula and bound but different ararangement around chiral centre

Answer 51

Same atomic structure but different bond between molecules