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Principles of Drug Discovery > Pharmacokinetics 1 > Flashcards

Pharmacokinetics 1 Flashcards

0
Q

what does ADME stand for ?

A

absorption - is the administration of the drug into the systemic circulation
distribution- is the movement of the drug from the systemic circulation to the target tissue
metabolism - breaking down the drug down
excretion - removal of the drug from the body

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1
Q

define pharmacokinetics :

A

it is how the body affects a drug

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2
Q

what is pharmacokinetics important for ?

A

important for constructing dosage and administration regimes
- many drugs fail due to poor kinetics in man

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3
Q

what does an effective drug require a balance between ?

A

between its ADMET properties

  • adsorption
  • distribution
  • metabolism
  • excretion
  • toxicity
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4
Q

what is the Cmax?

A

it is the maximum concentration that a drug achieves in tested area after administration and before second dose

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5
Q

what is Cmin ?

A

it is the minimum concentration achieved in a tested area after administration

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6
Q

what is Tmax ?

A

it is the time at which C max is achieved

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7
Q

what does disposition equal ?

A

absorption, distribution, metabolism and excretion

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8
Q

what is T0.5?

A

it is the time at which half the Cmax is achieved

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9
Q

what are Cmax, Tmax and T0.5 dependent upon after oral administration ?

A

dependent on drug absorption rates and disposition profile of the drug

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10
Q

what does AUC stand for ?

A

area under the curve

the are under the curve of a plot of concentration of drug in plasma against time

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11
Q

what does the AUC show us ?

A

shows the total exposure that the body gets from a single dose
also shows the maximum drug concentration that the body receives and shows the speed of drug metabolism

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12
Q

what is the therapeutic index?

A

= toxicity in 50% of population/ minimum effective dose 50%
also known as therapeutic window
= TD50/ED50

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13
Q

if a drug x can regress cancer cells by binding to R1 receptor and its KD is 2nM and it also binds to R2 causing cell death of healthy cells with a KD of 800nM, what is drug x’s therapeutic index?

A

= 800/2 = 400

this ratio allows us to see at what point a highly beneficial therapeutic becomes a lethal toxin

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14
Q

what does a narrower therapeutic index mean ?

A

the narrower range means it is more likely to cause toxicity/overdose

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15
Q

what is absorption ?

A

it is the movement of drug from the site of administration to systemic circulation - NOT THE SITE OF ACTION

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16
Q

what is bioavailability a measure of ?

A

it is a measurement of the rate and extent to which a drug reaches the systemic circulation(expressed as F) and applies to all routes of administration
- it is defined by the rate it appears in the blood and the relative amount of drug from the administration dosage which enters the systemic circulation

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17
Q

what is the ROA ?

A

route of administration- it is very important and the most appropriate route must be considered

18
Q

describe the different speeds of absorption for different methods of administration :

A

from fasted to slowest

  • intravenous
  • pulmonary
  • intramuscular
  • subcutaneous
  • oral
19
Q

how is bioavailability determined and what is the bioavailability of intravenous drugs ?

A

= AUC(oral)/AUC(i.v)

bioavailability of i.v is 100% beccause 100% is placed in the circulation

20
Q

what information does the Cmax and Tmax provide?

A

gives the rate of absorption

21
Q

what does i.v admin avoid ?

A

it avoids first pass metabolism

22
Q

what are the advantages/disadvantages of i.v. admin ?

A

advantages
- very rapidly acting- 5-10seconds, very useful for pain relief
disadvantages
- not useful for drug compliance
- increased chance of infection, overdose, arterial damage

23
Q

how does oral admin work ?

A

it is the most common and onset is about 10-20mins but it needs to be absorbed
- absorbed by small intestine, which has a large surface area and a rich blood supply

24
Q

what can affect oral avalability ?

A
  • weak acids, the ionized form HA is readily absorbed in the stomach but weakly basic drugs are poorly absorbed
  • problems with empty/full stomach - drug has to be able to survive the gastric enzymes, stomach acid and not bind to calcium ions in food and also cope with gut bacteria
25
Q

what are most oral drugs ?

A

most are weak acids or weak bases
- only the unionised form will be absorbed
for acid- HA- A- + H+ = HA is unionised
for base- B + H+ - BH+ = B is unionised

26
Q

what is good for oral bioavailability?

A

low metabolic clearance

27
Q

what can cause a low bioavailability ?

A

poor absorption or high metabolism

28
Q

what is an indicator of absorption speed?

A

time to reach Cmax

29
Q

what is sublingual admin and what are some examples ?

A

drug is placed under the tongue
- rapid absorption
- no first pass metabolism
- but small surface area
e.g GTN- it cant be taken orally because it will not survive first pass metabolism
buprenorphone- a post operative pain killer

30
Q

what are the problems with sublingual admin ?

A

incorrect usage - patient may swallow it
taste
availability
more expensive to manufacture

31
Q

what are the benefits of rectal admin ?

A

no pH problems
no issues with stomach acid
no damage to stomach lining
good if patients keeps vomiting

32
Q

what are i.m and s.c admin ?

A

i. m.= inrtamuscular admin and s.c.= subcutaneous admin
- drug is placed into the connective tissue matrix and absorbed into local vessels
- they have low impedence (fenestrations) so it allows for paracellular diffusion
- useful for absorption of hydrophilic drugs and large drugs
- generally a low level of fluid is administered- <5ml

33
Q

what are the benefit of aerosol admin ?

A

very rapid
avoids first pass metabolism
large absorption area - inhalation surface area is about 100m2 and it is permeable with low metabolism
- anaesthetics often given this way

34
Q

what is topical admin ?

A

it is targetted to the site of injury
must be lipid soluble to pass through skin
has localised actions
- benefits= avoids first pass metabolism but not always effective at targeting areas distant from application

35
Q

why is distribution important ?

A

it detects tissue sequestration
it determines the loading dose
provide info for adjusting dose

36
Q

what are the 4 compartments of the body which are all linked together and enable drug to distribute between ?

A 
blood
extracellular fluid 
intracellular fluid 
fat 
others= synovial fluid, fetus
37
Q

what does the volume of drug distribution show us and how is Vd calculated ?

A

shows how well a drug is distributed

Vd= plasma clearance(Cl)/elimination rate constant(K) or amount of drug in body/plasma drug concentration

38
Q

how does lipophilicity affect the volume of distribution of a drug ?

A

the higher lipophilicity of a drug the higher the volume of distribution
- desired volumes of distribution change for different drugs

39
Q

how do you calculate volume ?

A

volume= amount/concentration

40
Q

how is the % bound drug to plasma proteins determined?

A

= bound drug/ bound drug + free drug * 100

41
Q

what factors affect distribution of a drug ?

A 
intracellular tissue binding
lipid solubility 
ph vs pKa
intervention of BBB
placental/mamary transfer of drugs
42
Q

what can volume of distribution in a patient also depend on ?

A

depends on body size and can be quoted as L/Kg

43
Q

an analgesic (75mg) is administered by i.v and a blood sample shows the initial concentration in the blood is 0.9 micrograms/ml. what is the Vd of the analgesic ?

A

VD= amount / concentration

= 75000micrograms / 0.9 = 83 litres

Principles of Drug Discovery (20 decks)

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