0utline the drug absorpion process

8/6/2019 0utline the Drug Absorpion Process

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Outline the drug absorptionOutline the drug absorptionprocessprocess


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What is drug absorption?

Absorption is the process by which a drug passesfrom its site of administration into the circulation(bloodstream).

The blood receives a drug from the site ofadministration and carries it to all the organs,including those on which the drug acts

The speed, ease and degree of absorption arerelated to the route of administration.


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Absorption process depend on-

Routes of Administration

Barriers to Diffusion

Factors that affect Drug

Absorption

a. Factors related to drugs

b. Factors related to patientAffect of pH on drug absorption.


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Routes of Administration

Oral

Advantage: Convenient Efficient Absorption (hugesurface area)

Disadvantage: Drug degradation, Requires lipidpermeation, Gastric irritation. First pass effect

InhalationAdvantage: Large surface area ,Access nasal or lungs ,

Rapid delivery to bloodDisadvantage: Requires special properties (vaporized,

atomized)

Nasal proteases , Irritation


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Route of Drug administration


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IntravenousAdvantage: Direct, Rapid ,Programmable

Disadvantage: Hazardous, Requires professional IntramuscularAdvantage: Rapid for aqueous ,Slow depot for oil

Disadvantage: Pain, inflammation at delivery site

Subcutaneous injectionAdvantage: Rapid, no gastric irritation, bypass first pass

effect

Disadvantage: water soluble and irritating drug cant use

sublingualAdvantage: Rapid , Self administered, No first pass effect

Disadvantage: Small doses, unpleasant taste, Drug must belipid soluble and potent


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Rectal:

Advantage: Suitable in extreme ages, avoid gastric irritation

Disadvantage: patients dont like this route, irritate in rectal mucosa

TransdermalAdvantage: Prolonged ReleaseDisadvantage:Lipid permeation, Initial time lag, Dermalenzymes

Others: Intrarteria, Intrathecal, Intraperitoneal


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Barriers to Diffusion

Depending on the chemical properties drugs may be absorbed fromGI tract by passive diffusion, active transport, pinocytosis process.

Passive diffusion:

It is the commonest and important process

Require no energy

Depends on-

i. Conc. Gradient

ii. Lipid /water partition co-efficient

iii. Molecular wt & size of drugs

iv. pKa of the drug and pH of the local fluid

Example- Aspirin, barbiturates, Morphine


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Drug Absorption by passive

diffusion


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Active transport Occurs against concentration gradient.

Requires carrier & energy

Occurs in case of drug resembling natural substrate Specific & relatively unstable

Depends on lipid/ water partition co- efficient

The carrier system may be saturated at high concentration

The process is competitive ( i.e. drugs with same structure may

compete for the same career

Example: Amioacids, Nucleic acid & Iron


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Endocytosis:

Transport process oflarge molecule

Requires energy,calcium, contractile

elements of cell

Independent of lipid/water partition co-efficient.

Example: Sucrose, Insulin


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Active Transport Diffusion


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Factors that affect DrugAbsorption

Factors related to drugs

a. Molecular wt: Drug absorption isinversely proportional to m. w. Lowmolecular wt drug can easily pass throughsmall pores.

b. Molecular size: Drug absorption isinversely proportional to molecular size,smaller the size of drug the more will be

absorption.


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c. Lipid/water partition Co-efficient:

Increase lipid solubility Increase absorption

Increase duration of action

Increase water solubility Decrease absorption

Decrease bio-availability

d. Ionization constant (Pka):

Increase ionization More water solubility

Decrease absorptionDecrease ionization Less water solubility

Increase absorption.


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e. Formulation: Different rate of absorption for different

formulationf. Disintegration time: Increase disintegration time

Decrease absorption

g. Dissolution: Increase dissolution Increase absorption


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Factors that related to patient:

a. pH of the gut:

In acidic Ph, acidic drugs Less ionized


In alkaline ph, basic drugs Less ionized

Increase absorption

b. Time of administration: Increase the rate ofgastric emptying Increase absorption. Empty

stomach

increase absorption of antibiotic

increase bio-availability. Full stomach Increase

absorption of iron increase bio-availability


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c. Bowel transit time: Increase intestinal motilityDecrease absorption

d. Mucosal surface area: Increase surface areaIncrease absorption.

e. Gastrointestinal disease:

Crohns disease, Coeliae disease Increase

absorptionGut oedema with CCF Decrease absorption


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f. Presence of food flow: Food interfere withabsorption of water soluble drugs, again highlipid soluble drugs are better absorbed in

presence of food.g. Regional blood flow: Increase blood flow


h. Inactivation: Inactivation of drug by gut

enzyme Decrease absorption.


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i. Drug interactions: When two ormore drugs are administratedsimultaneously one drug will affect theabsorption of other. Tetracycline+Antacid Decrease the absorption oftetracycline.

j. Area of absorption surface:

Increase surface Increaseabsorption increase bio- availability.


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Affect of pH on drug absorption. The relationship of pKa and the ratio of acid- base

concentrations to pH is expressed by the Henderson -

Hasselbalch equation

This equation is useful in determining how much drug

will be found on either side of a membrane that

separates two compartments that differ in pH.


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Affect of pH on drug absorption.

Drug is weak acid AH A-+H+

Acidic environment : protonated, un-ionized, lipid-

soluble.

Basic environment : un-protonated, ionized, watersoluble

Drug is weak base

BH+ B+H+

Acidic environment : protonated, ionized, watersoluble.

Basic environment : un-protonated, un-ionized, lipid-

soluble.


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0utline the drug absorpion process

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