ABSORPTION OF DRUG

                   ABSORPTION OF DRUG:

 Drug absorption is the transfer of drug molecules from the site of administration to blood stream.

FACTORS MODIFYING THE ABSORPTION OF DRUGS

1. Surface area of GIT

Greater the surface area of GIT greater will be drug absorption. The surface area of small intestine is grater than stomach; therefore most of drug absorption occurs in small intestine.

2. GIT motility

T he motility of GIT is important for drug absorption. If the motility of GIT increases the absorption of drug will be decrease. Similarly when the GIT motility decreases the absorption will increases.

3. PH of GIT

The absorption of drug depends upon the PH of GIT. A drug may be week acid or week base. The acidic drug (Aspirin) will absorb from stomach because stomach is acidic. While week base (Quinine soleplate) will absorb from intestine because intestine is basic.

4. Other substances present in (GIT) stomach

The presence of other substances in the stomach may change the absorption of drug due to the following factors.

5. Changing of GIT PH.

Forming complex with drugs. e.g. Taking of milk decrease the                                                                                                                               stomach PH & forming complex with tetracycline and ciprofloxacin. So decrease the absorption of these drugs. Taking of iron after meal (vit.c) leads increase absorption of iron.

6. Disease State:

Some disease state also change the absorption of drug like pyloric stenosis (intestinal obstruction). There delay stomach emptying so drug absorption increases. In emetic conditions the absorption of drug decreases.

 7. Salt Form:

The absorption of free drug like doxycycline is slow to increase its absorption, its salt form is used or the absorption of morphine is slow while the absorption of morphine sulphate is high.

8. Dosage Form:

Pharmaceutical dosage form also increasing or decreasing the absorption of drug. e.g. the absorption of IM injection is greater than cap, tab & sup etc. similarly the absorption of inhaler is also greater from the oral rout.

9. Particle Size:

Greater the particle size of drug lesser will be the absorption e.g. the absorption of Grasofulvin is lesser than Grasofulvin micronized.

FACTORS INVOLVED IN TRANSFER OF DRUGS OR MECHENISM OF DRUG ABSORPTION

DRUG PERMEATION

The following factors influence the passage of drugs across the cell membrane.

Ø  Molecular size & shape.

Ø  Solubility at the site of absorption.

Ø  Degree of ionization.

Ø  Lipid solubility.

The passage of drug across cell membrane takes place by one of the following process.

A). PASSIVE TRANSPOET:

The passive transport consist of the following process

Simple Diffusion:

The process in which drug molecules move from high concentration to lower concentration is called simple diffusion. This process depends on lipid solubility, greater the lipid solubility greater will be simple diffusion of drug.

Filtration:

Filtration is the passage of drug across cell membrane by means of hydrostatic pressure or osmotic pressure.

  B). SPECIALIZED TRANSPORT:

The specialized transport consist of the following

Active transport:

It is the process in which drug molecules transfer across cell membrane with the help of energy. The drug molecules move from low concentration to high concentration. This transport occurs in renal tubule.

Facilitated Diffusion:

  In this case the movements of drug molecule across cell membrane occur with the help of a carrier molecule. e.g absorption of glucose & amino acid.

Pinocytosis:

This is the ability of cell to engulf fluid materials by local folding of cell membrane.

ABSORPTION FROM OTHER SUTES:

According to rout of drug administration the site for absorption are as follow.

Absorption from skin, lungs, GIT, parenteral & pulmonary absorption.

Absorption From Skin (Topical):

The penetration of drug from skin to the different layers of skin is called topical absorption. The following factors.

(A) Skin condition               (B) Skin age

(C) Skin metabolism           (G) Blood flow

(E) Drug concentration       (F) Molecular size of drug.

Parenteral drug absorption:

This site of absorption provides greater absorption as compared to other routes. This rout depends upon. Blood flow and solubility of drug.

Pulmonary absorption:

Lungs provide a very large surface area for drug absorption. This route is an ideal way for drug action.

DISTRIBUTION:

Drug distribution is the process by which a drug leaves the blood stream and enters to the extra cellular fluid (ECF) or cells of tissue. Some drugs concentrates in specific tissue e.g. Iodine concentrates in thyroid gland. Chloroquine concentrates in liver. Calcium & vitamin D concentrates in bones.

Factors AFFECTING distribution

BLOOD FLOW:

Greater the blood flow greater will be the distribution of drug. Blood flow to the brain, liver, kidney is greater than the skeletal muscle, so there will higher level of distribution towards these specific organs.

DRUG PROTEIN BINDING:

When drug reaches to plasma it binds with plasma protein (albumin). Some drugs are in free form & some drugs are bound to protein. So greater the protein binging greater will be distribution.

DRUG TISSUE BINDING:

Some drugs have high affinity for specific tissue. e.g. antimalarial (chloroquine) have greater affinity for liver. Tetracyclinees in bones as well as teeth, Thiopentone in brain

LIPID SOLUBILTY:

Greater the lipid solubility of drug greater will be its distribution. When drug is lipid soluble it will cross blood brain  barriers (B.B.B) & placental barrier (P.B) . while water soluble drug cannot cross B.B.B & P.B .

BIO AVAILIBILITY

Bioavailability is the fraction of administered drug that reaches the systemic circulation. Bioavailability is expressed as the fraction of administered drug that gains access to the systemic circulation in a chemically unchanged form. For example, if 100 mg of a drug are administered orally and 70 mg of this drug are absorbed unchanged, the bioavailability is 0.7 or seventy percent.

FACTORS AFFECTING BIOAVAILIBILITY(B.A).

The factors which affect the bio availability of a drug are.

1). Rout of drug administration affect bioavailability. E.g. orally administered drug have low bioavailability as compared to IM or IV administered drug.

2). Due to incomplete absorption B.A. of a drug is affected. Incomplete absorption occrued due to

•         Degree of ionization

•          Chemical nature of drug (acidic/basic)

•         Dosage form

•         Surface area of GIT.

3). Solubility of drug also affect the bioavailability of drug i.e. If a drug is lipid soluble the bioavailability will be greater & if a drug is water soluble its bioavailability will decreases.

4). Hepatic metabolism also affect the bioavailability, some drugs are mostly metabolized in the liver after oral administration & very small amount of drugs remains in the blood e.g. propranolol (inderal).

5). Chemical stability.  Some drugs, such as penicillin G, are unstable in the pH of the gastric contents. Others, such as insulin, are destroyed in the GI tract by enzymes.

BIOTRANSORMATION OR METABOLISM

The chemical (STRUCTURAL) change in the drug inside the living system is called biotransformation or metabolism OR

The conversion of lipid soluble drug into water soluble drug in the biological system is called biotransformation or metabolism.

All most all foreign nonfood substance undergo biotransformation. The main function of biotransformaion is as follow.

1. It increases the hydrophilic nature of substance.
2. It terminates the pharmacological activity of drug.
3. It converts micromolecular drugs into macromolecular drugs

Effect of biotransformation on pharmacological activity:

1. Most of the drugs are inactivated i.e their pharmacological activity is lost

Amphetamine→phenylacetone

1.  Some drugs which are inactive give rise to active metabolites after biotransformation.

ENALAPRIL→ENALAPRILATE

1. METABOLITES OF SOME DRUGS RETAINS PHARMACOLOGICAL ACTIVITY oxazepam which is a metabolite of diazepam which is more potent than parent drug.

SITES OF BIOTRANSFORMATION

Biotransformation occure in various parts of the body like liver, blood, intestine, skin, testes, brain & kidney. The most important site for biotransformation is liver. While other major sites including kidney, intestine, blood. Some drugs are also metabolized in gutt due to the presence of normal flora.

Factor affecting Drug metabolism

Age: the enzyme system at birth especially in preterm baby are functionally imature and especially for oxidation and for conjugation with glucuronic acid. The  drugs like chloramphenicol is unable to get conjugated can cause fatal grey baby syndrome in neonates.

Pregnancy: Hepatic metabolism is increased.

Disease: Acute inflammatory disease of liver and cirrhosis affect function of hepatocytes and blood flow through the liver, this results in increased systemic availability of drugs such as propranolol ,labatolol.

ENZYME INDUCTION : Many drugs causes increase of liver microsomal enzymes. These drugs are so called enzyme inducers. The enzyme inducers are

Barbiturates, Carbamazepine , Grisofulvin

Enzyme Inhibition

Many drugs inhibit the enzyme system and reduce their metabolic functions.

Cimetidine inhibits the metabolism of propranolol and causes heart block and bradycardia.

ELIMINATION OF DRUGS

The removal of drugs from body by any route is called elimination or drug excretion. The elimination of drug from body occure by the following routes.

1. RENAL ELIMINATION
2. BILIARY ELIMINATION
3. OTHER ROUTES OF ELIMINATION

This is the most common route of elimination of drug from body. Rnal elimination consist of the following process.

GLUMERULARE FILTRATION :-

The process by which the drug molecules enter from glumerulus into bowman’s capsule is known as glumerular filtration (GF). Only free drugs are filtered by this process .Drugs having molecular weight less than 300 can only be filtered.

•         TUBULAR SECRETION

The process by which  drug & other substances enters from blood into renal tubules is known as tubular secretion e.g. penicilline, , cephalosporin.etc

•         TUBULAR REABSORPTION

In tubular reabsorption the lipid soluble drugs & essential components are transfer from tubules to blood.

•         BILIARY ELIMINATION :-

The liver secretes 0.25 to 1 litre of bile each day. Some drugs and their metabolites are excreted by the liver in bile. Drugs  that are excreted in the bile having molecular weight greater than 300. Drugs that are excreted into  the bile include digitalis glycosides, bile salts, cholestrole, steroid, indomethasine & other components like morphine, chloramphenicol are also excreted by the liver. Some drugs under go enterohepatic circulation. e.g. isoniazid (INH) digitalis, NSAID etc.

OTHER ROUTES OF ELIMINATION

ELINNATIN THROUGH LUNGS

The lungs excrete gaseous (Halothane 8%) & general anesthetics alcohol are also eleminate by means of lungs.

ELIMINATION BY MOUTH (SALIVA) :-

Thiocynate & iodides are excreted in saliva.

ELIMINATION IN MILK.

A large number of drugs eliminated in milk e.g. penicillin and chloramphenicol.

ELIMINATION IN SWEET :-

Some drugs are excreted in sweet e.g. Depson & sulfonamides.

ELIMINATION IN TEARS :-

 Rifampicine is excreted in tears.

VAGINAL FLUIDS

 Rifamicine is excreted in vaginal fluid.

 ARTIFICIAL ROUT:-

            (1) Hemodialysis     (2) Peritoneal dialysis