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Drugs, Brain and Behaviour > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

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1
Q

What are some routes of administration?

A 
oral
nasal
sublingual
rectal
transdermal
pulmonary
injection
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2
Q

What is sublingual administration?

A

drug is absorbed through the buccal (mucus) membrane under the tongue

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3
Q

What is transdermal administration?

A

through the skin

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4
Q

What is pulmonary administration?

A

inhalation

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5
Q

Which route of administration does not avoid 1st pass metabolism?

A

oral

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6
Q

Which is the safest route of administration and why?

A

oral/peroral

  • the drug is highly metabolised in the liver and a lot is absorbed by the intestines making overdose very unlikely
  • non-invasive administration
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7
Q

What is 1st pass metabolism?

A

the concentration of a drug is greatly reduced before it reaches the blood due to breakdown by the stomach and liver enzymes

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8
Q

How can 1st pass metabolism be used to alter medical use?

A

extended-release formulation

e.g. d-amphetamine coupled to L-lyside; when metabolised the amino acid is cleaved off leaving the active amphetamine

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9
Q

How does the route of administration affect the action of a drug?

A

drug peak concentration and half-life vary by route of administration
e.g. cocaine
inhalation; rapid onset and peak conc, short duration of action
intranasal; slower onset and peak conc, long duration of action

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10
Q

What is half-life?

A

time for a plasma drug concentration to fall to half of its peak level

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11
Q

Give an example of the differing action of drug administration

A

fentanyl; highly potent opiate

  • transdermal; prolonged, steady analgesic effect
  • sublingual; rapid adjustment of pain levels
  • pulmonary; inhalation of gas can cause extremely rapid incapacitation or death
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12
Q

What route of administration will medical professionals tend to use?

A

one with the minimum effective concentration over an extended period of time

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13
Q

What factors affect absorption and distribution?

A

drug lipid solubility
ionisation
blood circulation as site of administration
surface area of absorbing surface
amount of drug destroyed by 1st pass metabolism
number of membrane layers to blood

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14
Q

How does drug solubility affect absorption?

A

some drugs are lipid soluble and will easily diffuse passively
bigger molecules are less likely to diffuse

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15
Q

How does drug ionisation affect absorption?

A

less ionisation = more lipid solubility = more absorption = more effect

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16
Q

How does drug and solvent composition affect absorption?

A

drugs that are weak acids ionise more in basic environments

drugs that are weak bases ionise more in acidic environments

17
Q

How do blood and stomach acid affect ionisation?

A

blood is slightly alkaline

stomach acid is very acidic

18
Q

What is pKa?

A

the pH of the solution in which 50% of the drug is ionised and 50% is not

19
Q

How do ions become trapped?

A

ionised drugs are less effective at crossing membranes
when drugs become too highly ionised they can no longer move forwards or backwards through the membrane becoming stuck in a particular compartment

20
Q

What is the blood brain barrier?

A

a mechanism of keeping the brain environment as stable as possible

21
Q

How do we know there is a blood brain barrier?

A

when dyes were administered IV they spread everywhere except the brain and CSF

22
Q

Which brain areas lie outside the blood brain barrier?

A 
area postrema; detects toxins and initiates vomiting
median eminence (in hypothalamus); allows the release of hormones
23
Q

What is the difference in structure between a typical and a brain capillary?

A

typical; intracellular clefts allow flow of ionised molecules
brain; glial cells and astrocytes pack the capillary preventing intracellular clefts, only lipid-soluble (passive) diffusion

24
Q

What are the different membrane layers available for injection?

A 
subcutaneous; epithelium
intramuscular; muscle
intravenous; blood vessel
intra-peritoneal; intestine cavity
intracranial; brain
intra-cerebro-ventricular; brain
25
Q

How are drugs inactivated?

A

usually through metabolism (biotransformation) which produces ionised molecules that do not have brain access

26
Q

How are drugs expelled?

A

ionised metabolites become trapped in kidney tubules and are then excreted

27
Q

What individual variation can be explained by metabolism differences?

A

e.g. alcohol - acetaldehyde - acetic acid via alcohol dehydrogenase

28
Q

How can variation in alcohol dehydrogenase explain individual variation in the effects of alcohol?

A

alcohol is metabolised by alcohol dehydrogenase

  • women have lower levels
  • alcoholics have higher levels
  • older people have reduced liver function, lower levels
  • genetic variation

Drugs, Brain and Behaviour (6 decks)

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