Pharmacokinetics Flashcards

1
Q

What are the pros and cons of IV administration?

A

very rapid onset but its invasive and requires training

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2
Q

What are routes of administration?

A

ingestion - GI tract -> hepatic portal system ->liver -> systemic circulation -> body

some goes to bile -> GI tract - > absorbed/excreted

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3
Q

What are systemic and local routes of administration?

A

systemic = entire organism exposed to the drug e.d BP lowering drug

local = restricted to one area of organism e.g skin infection

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4
Q

What is enteral and parenteral administration? Why would you use parenteral administration?

A

enteral = via GI tract - orally

parenteral = everything but GI tract - e.g IV

maybe drug isn’t absorbed/has short half life but needs to get into systemic circulation as quickly as possible,

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5
Q

How do drugs get into the systemic circulation?

A

bulk flow transfer - e.g in bloodstream in bulk

diffusion transfer - molecule by molecule over short distance

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6
Q

What are compartments and barriers?

A

compartment = aqeous e.g blood, lymph, ECF

barrier = lipids e.g cell membrane

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7
Q

What does the ratio of ionised to non-ionised form of the drug depend on?

A

pH of the environment and the pKa of the molecule

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8
Q

What form is aspirin in in the stomach?

A

aspirin is acidic and has a pKa of 3.4- in stomach pH is 1 (less than pKa of aspirin) so aspirin is persuaded to be non-ionised -readily diffuses across lipid layer -> intestines which is basic so becomes ionised -> much slower absorption

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9
Q

When would you use enteric coated aspirin?

A

uncoated aspirin for headache - fast absorption

coated for arthritis - resistant to stomach acid -> intestines -slow absorption

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10
Q

What is ion trapping?

A

e.g aspirin
in stomach its un ioninsed, in blood stream (neutral pH) its both ionised and un-ionised - un ionised form is mopped up by protein -> drug -protein complex -> extends half life of drug

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11
Q

What factors affect drug distribution?

A

regional blood flow- well perfused tissues = exposed to higher conc. of drug

extracellular binding (plasma proteins) - 50-80% drug bound to protein, albumin can bind to both ionised and un ionised

capillary permeability - fenestrated = more permeable to drugs, continous had=s water filled gap-junctions, discontinous had large gaps

localisation of tissues - fat isn’t usually highly perfused so its very lipophilic- lipophilic drugs localise in fatty tissue e.g brain

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12
Q

What are the main routes of excretion?

A

liver and kidney (kidney does most of the excretion)

many drugs and metabolites eliminated by kidneys -> converted into water soluble

in liver- large molecular weighted material -> bile -> intestines -> excreted

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13
Q

How do excreted drugs get into the urine?

A

via active secretion (not ultrafiltration) because you can’t filter large. protein bound drug complexes

Glomerulus-drug-protein complexes are NOT filtered
Proximal Tubule-active secretion of acids and bases
Proximal and Distal Tubules-lipid soluble drugs are reabsorbed Urine is an aqueous environment and if you have secretion from the glomerular filtration of a lipid material or the material has become more lipid by becoming unionised because of the pH of the urine -it has the ability to be reabsorbed

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14
Q

Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?

A

I.V. Sodium Bicarbonate increases urine pH
Increase in urine pH ionises the aspirin
This makes it less lipid soluble
Less aspirin is reabsorbed in the proximal and distal tubules
Increase in the rate of excretion of aspirin

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15
Q

How does excretion occur int he liver?

A

Biliary excretion allows the concentration of large molecular weight molecules that are very lipophilic

There are also active transport systems that secrete drugs into bile

The active transport systems are geared for the transport of bile acids and glucuronides into the bile -drugs hitch a ride on this because they are non-polar and have a large molecular weight

Other routes of drug excretion include lungs, skin, GI secretions, saliva, sweat, milk, genital secretions

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16
Q

Why can biliary excretion cause a problem?

A

enterohepatic cycling - drug/metabolite excreted into gut but then can be reabsorbed and returned to liver via enterohepatic circulation -> drug persistance

17
Q

What is bioavailabilty?

A

Proportion of the administered drug that is available within the body to exert its pharmacological effect

This is the post-hepatic concentration -the amount that leaves the liver and enters the systemic circulation

18
Q

What is apparent volume of distribution?

A

The volume in which a drug appears to be distributed -an indicator of the pattern of distribution

This relates to the distribution of the drug

19
Q

What is biological half-life?

A

Time taken for the concentration of the drug (in the blood/plasma) to fall to half its original value

20
Q

What is clearance?

A

The volume of plasma cleared of a drug per unit time

This is related to volume of distribution and the rate at which the drug is eliminated

Clearance incorporates excretion through the bile and the kidneys and all other routes

21
Q

What are first order and zero order kinetics?

A

first order - the rate of elimination of a drug where the amount of drug decreases at a rate that is proportional to the concentration of drug remaining in the body - dependent on the concentration of drug at any given time and applies to most drugs in clinical use
The log of concentration is proportional to time The dose divided by the initial concentration of drug in the plasma is described as the volume of distribution

zero order = a constant amount of drug is removed per unit time
It is very easy to determine the drug concentration at a particular time after administration with zero-order kinetics
Alcohol follows zero-order kinetics because you eliminate alcohol at a constant rate

most drugs follow first-order kinetics