ABSORPTION OF ABSORPTION OF DRUGSDRUGS

Mohini ChaurasiaMohini Chaurasia

BIOLOGICALBIOLOGICAL FACTORS FACTORS

• Gastro intestinal physiology.Gastro intestinal physiology.• Gastro intestinal blood flow.Gastro intestinal blood flow.• Gastro intestinal PGastro intestinal PHH..• Gastric emptying.Gastric emptying.• Effect of food/GI content on drug absorption.Effect of food/GI content on drug absorption.• Mal absorption.Mal absorption.• Disease State.Disease State.• First pass effect.First pass effect.

Gastro Intestinal PhysiologyGastro Intestinal Physiology

STOMACHSTOMACH • It is a pouch like It is a pouch like structure lined by structure lined by smooth epithelial smooth epithelial membrane.membrane.

• Absorption of weekly Absorption of weekly acidic drugs or un acidic drugs or un ionized drugs and week ionized drugs and week basic drugs takes place.basic drugs takes place.

Small intestineSmall intestine

generally carrier generally carrier mediated transport is mediated transport is seen in most drugs.seen in most drugs.

Proximal part-absorption Proximal part-absorption of dietary constituents of dietary constituents includes mono includes mono saccharides, AA, vits, saccharides, AA, vits, minerals etc. minerals etc.

Ileum-Vit B12, bile salts.Ileum-Vit B12, bile salts.

Micro villiMicro villi• The effective surface area The effective surface area

can be made 10 times larger can be made 10 times larger to that of stomach because to that of stomach because of the presence of micro of the presence of micro villi.villi.

• These are finger like These are finger like projections arising from and projections arising from and forming folds in intestinal forming folds in intestinal mucosa.mucosa.

• ESA was decreasing from ESA was decreasing from proximal part to distill part proximal part to distill part of small intestine.of small intestine.

Large intestineLarge intestine • ESA is less.ESA is less.• It is not an effective siteIt is not an effective site• Incomplete absorption Incomplete absorption

occurrs when large amount occurrs when large amount of drug reaches colonof drug reaches colon

• Its an area of absorption Its an area of absorption of escaped drugof escaped drug

• It is recommended for It is recommended for certain drugs whose certain drugs whose metabolism occurred by metabolism occurred by intestinal bacteria for bio intestinal bacteria for bio activation.activation.

BLOOD FLOWBLOOD FLOW• It plays a major role in absorption by It plays a major role in absorption by

continuously maintaing the concentration continuously maintaing the concentration gradient across the epithelial membrane.gradient across the epithelial membrane.

• Absorption of polar molecules doesn’t depends Absorption of polar molecules doesn’t depends on the blood flow.on the blood flow.

• rate of drug absorption is un effected by rate of drug absorption is un effected by mesenteric blood flow.mesenteric blood flow.

• Absorption of lipid soluble molecules highly Absorption of lipid soluble molecules highly depends on the blood flow.depends on the blood flow.

• Enter blood liver systemic circulationEnter blood liver systemic circulation

Gastro intestinal PGastro intestinal PHH

• PPH H varies according to the site.varies according to the site.• Many drugs are week organic acids or bases so Many drugs are week organic acids or bases so

PPH H is the imp factor. is the imp factor.• Gastric fluid retards week basic drugs.Gastric fluid retards week basic drugs. and promotes weekly acidic drugs.and promotes weekly acidic drugs.• Gastric secretions having PGastric secretions having PH H less than 1. less than 1.• It varies because of diet and dilution.It varies because of diet and dilution.• Some drugs (penicillin) under goes degradation Some drugs (penicillin) under goes degradation

because of Pbecause of PH,H, this can be rectified by pro drug this can be rectified by pro drug preparation. preparation.

• ex: ex: penicillin-------------carindacillinpenicillin-------------carindacillin erythromycin--------erythromycinesfolateerythromycin--------erythromycinesfolate

Gastric emptyingGastric emptying

• The passage of food from the stomach to the The passage of food from the stomach to the small intestine is called gastric emptying.small intestine is called gastric emptying.

• This process increases the bioavailability of the This process increases the bioavailability of the drug because mostly the absorption occurs in drug because mostly the absorption occurs in small intestine.small intestine.

• Slow gastric emptying can delay the onset of Slow gastric emptying can delay the onset of effect of the drug effect of the drug Ex: Analgesics& sedativesEx: Analgesics& sedatives

GASTRIC EMPTYING IS GASTRIC EMPTYING IS RECOMENDEDRECOMENDED

WHENWHEN• Rapid onset of action is desirable. Rapid onset of action is desirable. ex: sedativesex: sedatives• Dissolution of drug occur in the intestine. Dissolution of drug occur in the intestine. ex: enteric coated dosage forms.ex: enteric coated dosage forms.• Which are not suits to gastric fluids. Which are not suits to gastric fluids. ex:pencillin and erythromycin.ex:pencillin and erythromycin.• Drug is best absorbed from the distal part of the Drug is best absorbed from the distal part of the

small intestine.small intestine. ex: Vit B12ex: Vit B12

Delayed gastric emptying is recommendedDelayed gastric emptying is recommended

WHENWHEN• Food promotes drug dissolution and absorption.Food promotes drug dissolution and absorption.

ex: gresiofulvinex: gresiofulvin• Drugs irritate gastric mucosa.Drugs irritate gastric mucosa.

ex: aspirin, phenyl butazone.ex: aspirin, phenyl butazone.• Drugs are absorbed from the proximal part of Drugs are absorbed from the proximal part of

the SI & prolonged drug absorption site is the SI & prolonged drug absorption site is desired. Ex:VitB12&Cdesired. Ex:VitB12&C

FACTORS EFFECTING GASTRIC FACTORS EFFECTING GASTRIC EMPTYINGEMPTYING

• Volume of meal.Volume of meal.• DrugsDrugs• PosturePosture• Composition of meal.Composition of meal.• Physical state.Physical state.• Temperature.Temperature.• PPH.H.

• Disease state.Disease state.

Effect of food on drug absorptionEffect of food on drug absorption

• Food has an unpredictable effect which is irreversible.Food has an unpredictable effect which is irreversible.• Food stimulate hepatic blood flow, which have implication for Food stimulate hepatic blood flow, which have implication for

the bioavailability of the drug.the bioavailability of the drug.• Food tends to decrease the rate of gastric emptying which Food tends to decrease the rate of gastric emptying which

effects drugs like effects drugs like penicillinpenicillin• Forms poorly soluble and un absorbable complexes.Forms poorly soluble and un absorbable complexes.• High High proteinprotein food causes poor absorption of drugs. food causes poor absorption of drugs. ex: ex:

levodopalevodopa..• High High fat fat food causes poor absorption of drugs. food causes poor absorption of drugs.

ex:isotertinonin.ex:isotertinonin.• Administration of drug with large fluid volume enhances the Administration of drug with large fluid volume enhances the

dissolution rate and gastric emptying.dissolution rate and gastric emptying.

Mal absorptionMal absorption• It is a disorder with impaired absorption of fat, It is a disorder with impaired absorption of fat,

protein, carbohydrate, vitamin, minerals& waterprotein, carbohydrate, vitamin, minerals& water. . • Drugs which induce mal absorptionDrugs which induce mal absorption

Neomycin.Neomycin.

Phenytoin.Phenytoin.

Amino salicylateAmino salicylate• These drugs mainly damages the gastro intestinal These drugs mainly damages the gastro intestinal

epithelium emphasis the function of mucosa to serve epithelium emphasis the function of mucosa to serve as a barrier to large polar molecule.as a barrier to large polar molecule.