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Flashcards in Pharmokinetics Deck (19)
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1

ABSORPTION

- Most drugs move around the body by simple diffusion. They must have lipid solubility to pass through membranes and water solubility to be soluble in other compartments
- Very small molecules can pass through pores (aquaporins form a pore)
- A few drugs are absorbed by carrier-mediated transfer

2

CELLULAR BARRIERS

- To transverse cellular barriers (e.g. gastrointestinal mucosa, blood brain barrier) drugs have to cross lipid membranes
- Drugs cross lipid membranes mainly by passive diffusion
- The main factor that determines the rate of passive diffusion across membranes is a drug’s lipid solubility (pH partitioning) Molecular weight is less important

3

Oral 1

- Oral route (enteral) p.o (per os)
- Most common route and safest
- Most convenient and economical
- Surface area, not pH partition is main determinant of site of absorption- villi/microvilli in small intestine

4

Oral 2

So for rapid drug absorption, typically…
Take tablet with a large glass of water (e.g. 200 mL)
Take on an empty stomach (e.g. at least half an hour before food, as long as gastric irritation isn't a problem)

5

Oral 3
Difficulties with oral route 1

- First pass (presystemic) metabolism
- Before entering systemic circulation, blood leaving GI tract passes through liver
- Drugs that are highly metabolised by the liver may attain very low circulating levels relative to those obtained after parenteral administration

6

FIRST PASS METABOLISM

- Drugs taken orally are absorbed in stomach and small intestine
- Blood vessels take the drug directly to the liver
- Drug passes through liver before being distributed round the body

7

Oral 6
Difficulties with oral route

- Gastrointestinal irritation (e.g. aspirin)
- Low pH may inactivate certain drgs (e.g. penicillins, insulin)
- Particle size (small= more rapid absorption )
- Requires patient compliance
- Fraction of orally administered drug that reaches the systemic circulation
- 2 drugs with identical chemical composition that yield different blood concentrations and different effectiveness, differ in bioavailability (and are not bioequivalent)
Varies between individuals

8

SUBLINGUAL (SL)

- Under the tongue
- Rapid absorption
- Avoids exposure of drug to gastric pH
- Avoids first pass metabolism
- Taste could be an issue

9

INTRAVENOUS
Absorption pattern

Precise, accurate and potentially immediate effects (absorption phase is bypassed)
Suitable for large volumes and mixtures

10

INTRAVENOUS
Special utility

- Valuable for emergency use, permits titration of dose
- Usually required for high molecular weight protein and peptide drugs

11

INTRAVENOUS
Limits and precautions

- Greater risk of adverse effects
- High concentration attained rapidly
- Risk of embolism
- Must inject solutions slowly as a rule
- Not suitable for oily solutions or poorly soluble drugs

12

IM AND SUBCUTANEOUS INJECTION
Absorption pattern

Prompt absorption from aqueous solution, but slow and sustained from respiratory preparations

13

IM AND SUBCUTANEOUS INJECTION
Suitable for

- Poorly soluble suspensions and slow release implants
- Moderate volumes and some irritating substances
- Appropriate for self- administration (e.g. insulin)

14

IM AND SUBCUTANEOUS INJECTION
Limits and precautions

- Not suitable for large volumes and pain and necrosis at injection sites for certain drugs
- Recluded during anticoagulant therapy
May interfere with interpretation of certain diagnostic tests

15

DRUG ELIMINATION

- The irreversible loss of drug from the body
- Metabolism or excretion

16

DRUG METABOLISM (LIVER)
Phase 1 reactions (predominate)

- Catabolic reactions (break down)
- Oxidation, reduction or hydrolysis
- Generate a functional, reactive group
- Products can be more reactive or toxic than precursor

17

Phase 2 reactions

- Anabolic reactions (build up)
- Coagulation with hydrophilic groups
- Usually results in inactive compounds
- Drug molecule becomes more polar (ionised) than original molecule

18

DRUG EXCRETION IN THE KIDNEY

- Drugs are filtered in the glomerulus
- If the drug is very water soluble it cannot be re-absorbed into the blood so it will be excreted

19

THE HALF LIFE OF A DRUG

Time taken for the concentration to fall by 50%