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PMP 102 > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

what does area under the curve (AUC) mean?

A

total exposure of the body to a drug over a period of time

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2
Q

what is pharmacodnamocs?

A

what the drug does to the body

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3
Q

what is pharmacokinetics?

A

what the body does to the drug

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4
Q

what is partitioning?

A

process of molecules distributing themselves between two domains

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5
Q

what are the two ways of a drug reaching a target site?

A

direct
indirect (blood)

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6
Q

what are the quantitative significance of pharmacokinetics?

A

dosing regimen
empirical measures
track and trace

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7
Q

what is passive diffusion?

A

– Major mechanism of drug delivery
– Depends on the ability of drug
(physiochemical characteristics)
crossing lipid bilayer membrane

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8
Q

what is the rate of diffusion of passive diffuion determined by?

A

-surface area
-thickness of membrane
-molecular size & lipid solubility
(diffusion constant)

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9
Q

what is the [D] amount transfer relient on in passive diffusion?

A

trasfer rate
residence time at membrane

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10
Q

what is active diffusion?

A

Require transporter/carrier for the
uptake of drug across cell membrane

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11
Q

what is the pH of the mouth?

A

7.4

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12
Q

what is the pH of the stomach?

A

1.5-3

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13
Q

what is the pH of the small intestine?

A

5.3

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14
Q

what is the ionisation state of acidic and basic drugs in the mouth?

A

acid drug: 0.5% unionsed
basic drug: 99.5% unionised

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15
Q

what is the ionisation state of acidic and basic drugs in the stomach?

A

acid drug: 100% unionised
basic drug: 0% unionised

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16
Q

what is the ionisation state of acidic and basic drugs in the small intestine?

A

acid drug: 40% unionised
basic drug: 60% unionised

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17
Q

what are the factors influencing G.i absorption?

A

gi mobility
gi secretions and enzymes
drug-food/ supplemennts interactions

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18
Q

what are the advantages of G.I absorption?

A

– Large surface area for passive diffusion
– Range of pH environments promote uptake of weak acids/bases
– Richly vascularised (high blood supply)
– Long tract and long dwell time
– Some active transport (e.g. Levodopa taken up by phenylalanine
transporter)
– Small intestine is a major site for drug absorption

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19
Q

what is bioavailabilty?

A

measure of proportion of dose absorbed, compared to i.V (same) dose

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20
Q

what is the formula for bioavailability (F)?

A

F=AUC of oral/AUC of IV (for oral drug)

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21
Q

what is time to peak (tmax)?

A

time required to reach maximum drug concentration in plasma (is a measure of rate of absorption

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22
Q

what is partitioning?

A

the distriution of a substance between two immiscible phases

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23
Q

what is a partition coefficient (P)?

A

measure of relative affinity of the solute for an aqueous and a lipid phase at equilibrium

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24
Q

what is log P?

A

gives an indication of the lipophilicity of a drug

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25
Q

what is apparent partition coefficent (formula) ?

A

Papp= [HA]0/ [HA]w+ [A-]w

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26
Q

what is fraction unionised?

A

in the aqueous phase determines the ifference between Papp and P
Papp=P x Funionised
Funionised= HA/HA+A-

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27
Q

what drugs can readily partition into rubber or plastic substances?

A

drugs with high log P
this can be a major problem for storage of lipophilic drugs

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28
Q

what is MAC?

A

minimum alveolar concentration

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29
Q

why is the small intestine better desinged for absortion than the stomach?

A

− Surface area of the small intestines is up to 200 m2 as a result of microvilli
− Drugs have a longer residence time in the small intestines than the stomach
− Small intestines have an excellent blood supply

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30
Q

what are the partition theory limitations?

A

pH of the bulk gastr-intestinal fluid may differ from that at the surface or within the epithelium
degree of ionisation is not the only determinant of absorption from the GI tract
− Molecular weight
− Lipid solubility (log P often used as a proxy)
− Water solubility
− Binding to Ca2+, Mg2+, Al3+ present in milk, antacids etc.
− Ion-pairing
− Presence of active transport mechanisms

31
Q

what plasma proteins do acidic and neutral drugs bind to?

A

albumin

32
Q

what plasma proteins do basic drugs bind to?

A

beta-globulins

33
Q

what are the characteristics of plasma protein binding with drugs?

A
  • [Free] or [bound] drug is in dynamic equilibrium
  • High binding to plasma proteins- less available for target action
  • One drug can displace other drug binding of other drug
  • (Thermodynamic motion, collision; thermal energy dominate the electrostatic forces)
34
Q

what are the barriers of distribution of drugs?

A

cell arrangements
active transporters
size and lipid solubility

35
Q

what are the influencing factors of the distibution of drugs?

A

barriers
blood flow
tissue accumulation

36
Q

what does a Vd of more than 40 litres mean?

A

drug accumulation in tissues

37
Q

what does a Vd of less than 10 litres mean?

A

drug restricted to plasma and interstitial fluid

38
Q

how is absolute bioavailability calculated?

A

by comparing the amount absorbed by one route to the IV route

39
Q

what is the salt factor?

A

the fraction of the dose that is the active drug

40
Q

what is included in phase 1 of drug metabolism?

A

oxidation, reduction, hydrolysis
Catalysed by Cytochrome P450 (haem-containing mono-oxygenase enzymes)
requires oxygen and NADPH
RH(drug)+ O2+NADPH–>(CYP)–>ROH+NADP++H2O

41
Q

what is included in phase 2 of drug metabolism?

A

conjugation
addition of polar groups (OH, NH2, COOH)
Catalysed by UDP (Uridine-diphospho)-glucuronyl transferas (UGTs)

42
Q

where is the major site of drug elimination of water soluble molecules?

A

urinary system (kidney)

43
Q

where is the major site of drug elimination of large molecules?

A

biliary system (entero-hepatic recirculation)
bile
gut
liver
can be blocked by activated charcoal

44
Q

what is CLp?

A

the volume of plasma (ml) that is cleared of drug in unit of time (min)
CLp= CLliver+ CLrenal

45
Q

what are the characteristics of drug excretion?

A
  • Drugs are metabolised to more water soluble
  • Phase I process is catalysed by CytochromeP450 and Phase II process is by UDP glucuronyl transferases
  • The water soluble drug metabolites are excreted via kidneys and large molecules are processed through biliary (entero-hepatic recirculation process).
  • Renal excretion depends on filtration and active transport
  • Lipid solubility modulate the kinetics of drug reabsorption
  • Drug elimination (most) follow first order kinetics.
  • Half-life and plasma clearance rate are commonly used to determine drug elimination kinetics
  • Volume of distribution, plasma clearance and half-life are interrelated.
46
Q

what is the equation for apparent partitioning coefficient?

A

log( (P/Papp)-1)= pH- pKa (weak acids)(flipped if weak bases)

47
Q

what needs to change for a person with liver problems?

A

lower the dose

48
Q

when is it not true that drug is delivered into plasma, and reach steady-state conc.?

A

the drug effect is mediated through a metabolite
the drug effect is irreversible
follow different kinetics in the target compartment

49
Q

what are the factors affecting ionisation?

A

pH
pKa of drug(pH at which 50% of molecules are in each state)

50
Q

what are the steps to practical partitioning?

A
  1. Immiscible liquids added to separating funnel
  2. Drug under investigation added to the mixture
  3. Separating funnel shaken (open tap regularly to release pressure build-up)
  4. Immiscible phases separated and concentration of drug in each liquid determined
  5. Partition coefficient is determined from these values
51
Q

what does the pH-partition theory state?

A

the greater the proportion ionised then the lower the overall absorption will be

52
Q

what is ion-pairing?

A

ion pairing is when opposite charged ions are held together without the formation of a covalent bond
the ion paur behave as a neutral species and may be better able to permeate the gastric mucosa

53
Q

how does active transport mechanisms change pH-partition theory?

A

require energy
therefore molecules may be absorbed even if they are ionised or highly hydrophilic

54
Q

what are the parameters for the degree of drug distribuion into breastmilk?

A

pKa of drug (milk has a pH of 7.2)
degree of plasma protein binding
log P of drug (milk fat content varies from 4-9%)

55
Q

drug excretion in the kidney?

A
  • In the kidney unionised drug may partition from the blood (pH 7.4) → lipid membrane → urine
  • If urine pH favours the ionised (water-soluble) form of the drug → excreted in the urine
  • If unionised form is favoured, the molecule may be reabsorbed back into the circulation by passing back through the lipid membrane in Loop of Henle
  • Drug re-enters the circulatory system, free to exert its therapeutic action again
    renal excretion can be controlled by altering the pH of the urine with salt solutions
56
Q

what are the characteristics of acidic urine?

A

weak basic drugs are more likely to be ionised
decrease in re-absorption and increase in excretion

57
Q

what are the characteristics of alkaline urine?

A

weak basic drugs are more likely to be unionised
therefore increase in re-aborption and decrease in excretion

58
Q

where in the body is there high blood flow?

A

heart, brain, lungs, kidney, glands

59
Q

where in the body is there low blood flow?

A

skin, muscle

60
Q

what happens in the areas with tissue accumulation (fat depots)?

A

highly lipid soluble drugs accumulate

61
Q

what are the characteristics of distribution in the blood brain barrier?

A

diffusion only possible for lipid soluble drugs
the integrity compromised during meningitis
active transport possible

62
Q

what are the characteristics of the blood placental barrier?

A

lipid solubility and size of the drug determines the distrobution to foetus
drug use in pregnancy has a risk of adverse/ toxic teratogenic effects and neonatal toxicity during labour

63
Q

what is Vd?

A

volume of distribution
theoretical volume of plasma that would accommodate total drug amount at the measured plasma concentration

64
Q

what is the equation for Vd?

A

Vd= total amount of drug (Q)/ plasma concentration (Cp)

65
Q

what does IV administration mean?

A

the entire dose reaches the systemic circulation
100% bioavailability

66
Q

what is F?

A

fraction of administered dose of drug which reaches system circulation (intact)

67
Q

what is first pass metabolism?

A

drugs absorbed from the stomach, small intestine and upper colon pass into the hepatic portal system–> liver

68
Q

what is naloxone, and what is it used for?

A

used to combat opiate overdose, rapid onset required, undergoes first pass metabolism

69
Q

what can reduced bioavailability be from?

A

due to incomplete absorption and/or first-pass clearance

70
Q

what is relative bioavailability?

A

comparing the amount absobed from a test formulation to a standard formulation such as a tablet
Frel= AUCtest/ AUC standard

71
Q

relative bioavailability is?

A

used to evaluate bioequivalance of two products containing the same drug
(considered bioequivalent if the ration is between 0.8 to 1.25)

72
Q

what are the 3 major sites of drug elimination in the kidneys?

A

glomerular filtration (passive removal of [free] drugs
tubular secretion (active transport)
reabsorption (depomds on lipid solubilty and pH)

73
Q

what is half-life?

A

time taken to reduce the plamsa drug concentration by half from the administered [drug] or a time at which 50% of drug eliminated from plasma

PMP 102 (29 decks)

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