Question

what are the processes and organs involved in drug metabolism and elimination?

Answer 1

DRUG METABOLISM

Drug metabolism is the process of converting drugs to the product which can easily absorbed buy the body to produce the exact action of drug to the body and it also helps in excretion of drugs from the body. This mechanism happens mainly to convert the lipid soluble drugs to lipid insoluble(inactive drug into active metabolite), thereby enhances the elimination and reducing the toxic effects of drugs. Most of the drugs are lipid soluble, if they are not converted to water soluble it will fully remain in body and cause its effects fully and it may lead to toxicity. Here the importance of metabolism of drugs play a vital role.

Organs of drug metabolism

The main organ for drug metabolism is liver(microsomal enzyme systems of hepatocytes)

Secondary organs are;

• kidney(proximal tubule)
• lungs
• testes(sertoli cells)
• skin(epithelial cells),plasma,nervous tissue(brain),intestines.

Process of metabolism

There are two phases in drug metabolism

1. Phase I
2. Phase II

1. Phase I

• it includes functionalization reactions(a functional group is generated) or non synthetic reactions
• converts the drug to active metabolite by introducing a functional group(-OH,-NH2,-SH)
• This phase includes 5 reactions, that are;

-Oxidation

-Reduction and

-Hydrolysis

-Cyclization

-Decyclization

Oxidation:

Here addition of oxygen(negatively charged radical) or removal of hydrogen(positively charged radical) happens. It is the main process in metabolism. This reactions are carried out by a group of mono-oxygenases in the liver.

There are 9 types of oxidation:

i) oxidation at nitrogen atom,eg: chlorpheniramine

ii) oxidation at sulphur atom,eg: chlorpromazine

iii) aliphatic hydroxylation,eg: ibuprofen

iv) aromatic hydroxylation,eg:phenytoin

v) dealkylaton at oxygen atom,eg: phenacetin to paracetamol

vi) dealkylaton at nitrogen atom,eg: amitriptyline to nortriptyline

vii) dealkylaton at sulphur atom,eg:6methyl thiopurine to mercaptopurine

viii) oxidative deamination,eg:amphetamine

ix) desulfuration,eg: parathion to paraoxon

Reduction

Addition of hydrogen(positively charged radical) or removal of oxygen(negatively charged radical) happens. It includes 2 reduction action.

a. Microsomal reduction

i) Nitro reduction

ii) Keto reduction

iii) AZO reduction

b. Non microsomal reduction

Hydrolysis

Drug is slip to combine with water. There are 2 types

a. Microsomal hydrolysis

b. Non micrososmal hydrolysis

Cyclization

Formation of ring structure from a straight chain compound.

De cyclization

Ring structure opened in this reaction

2. Phase II

• It includes conjugation reaction
• in this phase linkage of functional group or phase I metabolite with endogenous substrate such as glucuronic acid, sulfate,acetate or amino acid.

it includes 7 reactions

i) Conjugation with glucuronic acid

ii) Acetylation

iii) Conjugation with sulfate

iv) Conjugation with glycine

v) Conjugation with glutathione

vi) Methylation

vii) Ribonucleotide synthesis

ELIMINATION OF DRUG

Elimination of drug is the process in which drug metabolites are irreversably transferring from body to the out side environment.

Organs involved for drug elimination

• kidneys
• lungs
• bilary system
• intestines
• saliva
• milk

Process of elimination of drug

There are 2 types of elimination process

1. Renal elimination

2. Non renal elimination

a) Bilary elimination

b) Pulmonary elimination

c) Salivary elimination

d) Mammary elimination

e) Dermal elimination

1. Renal elimination

Kidney is the primary organ for drug elimination. Mainly the water soluble drugs are eliminated through kindeys.

There are 3 process in elimination of drugs through kidneys. That are;

a) Glomarular filtration: Selective filtration or restricting large molecules to filtrate, which prevents the filtration of plasma molecules that are essential to maintain plasma volume.

b) Active tubular secretion: it occurs in proximal tubules. Here protein bound drugs from the blood is transported into tubular fluid.It is a carrier mediated process which needs energy.

c) Active tubular reabsorption: Some substances which are filtered by glomerulus are reabsorbed by passive diffusion and it depends on lipid solubility and ionization. This mechanism is very important to reabsorb small number of drugs also are actively absorbed.

2. Non renal elimination

a) Bilary elimination/ Faeces: Bile juice is secreted by hepatic cells of the liver. mainly larger molecules are eliminated by bile.

b) Pulmonary elimination: Gases and other volatile substances are eliminated by lungs. eg: alcohol

c) Sweat and salivary elimination: un ionized lipid soluble forms of drugs are excreted passively through sweat or saliva. eg: caffeine

d) Milk elimination: low molecular weight un-ionized water soluble drugs are diffused passively across the mammary epithelium and transfer into milk.