Module 6 — Drug ADME

Drug absorption

1. Dissolution

2. Passage across cell membrane

is the rate-limiting step that determines release of drug from the dosage form

Dissolution

Dissolution is enhance by administering the drug in?

salt form

• Phenytoin sodium

• Propranolol hydrochloride

Dissolution is enhanced by decreasing the particle size of the drug, the technique is called?

Micronization

Dissolution is enhanced by?

• administering the drug in salt form

• decreasing the particle size

It is the principle site of drug absorption

Gastrointestinal Tract — Small Intestine

Stomach can absorb some drugs, particularly ________

lipid-soluble, non-ionized drugs

Why is the SI the principal site of drug absorption?

Extensive surface area and rich in blood supply

Can remain non-ionized in the acidic environment of the stomach, favoring absorption

Weak acids

Example of Weak Acids

• NSAIDs

• Nalidixic acid

• Barbiturates

• Nitrofurantoin

• Sulfonamides

These are poorly absorbed in the stomach

Weak Bases

Are generally ionized in the acidic stomach, so they are poorly absorbed there

Weak Bases

Weak Bases example

• Opioid analgesics

• Ephedrine

• Quinidine

• Alkaloids

Absorption in the ______ is less

colon

_____________ also affects drug absorption

Rate of Gastric Emptying

Absorption of Drugs may occur in:

• Absorption from the GIT

• Absorption from the Topical Site

• Absorption from Parental Site

For the drug to be absorbed in topical site, it must penetrate the?

Keratin layer of the skin

For the drug to be absorbed in topical site, it needs to reach?

Stratum Basale

Absorption from topical is enhance from?

an oil-in-water base emulsion

Intact skin allows passage of ____________ but retards diffusion of?

passage of small lipophilic substance, but retards diffusion of H2O soluble molecule

Inhalants are absorbed through _______ across the pulmonary alveolar epithelium

diffusion

Inhalants are absorbed through diffusion across the ___________________

pulmonary alveolar epithelium

Drugs in oily vehicle or suspensions should not be given ___

I.V.

Absorption of drug from I.M or S.C. is rapid, if the it is given in?

Aqueous solution

Absorption of drug from I.MI or S.C. is _____, if the it is given in aqueous solution

rapid

In I.M. or S.C. rate of absorption is determined by?

vascularity of the area

After absorption of drug from the blood stream, drug become?

disseminated to all parts of the body

Physiological barrier:

• blood-brain barrier

• pial barrier

• placental-barrier

• mammary-gland-barrier

• ocular

• cochlear

• synovial

• cavities

extent to which a drug administered as a particular dosage form reach/enters the systemic circulation intact.

Biovailability

is rated by the time at which it reached the peack plasma concentrated

Rate of absorption

Drug elimination includes:

• Biotransformation / drug metabolism

• Excretion

Which category of drugs is water-soluble and generally not metabolized to an appreciable extent?

Polar water-soluble drugs

How are polar water-soluble drugs generally excreted?

Unchanged by the kidneys

What is an example of a process that may occur in polar water-soluble drugs?

Hydrolysis of ester

Which category of drugs must first be metabolized before excretion?

Non-polar lipid-soluble drugs

Through which routes are metabolites of lipid-soluble drugs excreted?

Urine or bile

drug which an active drug is converted to an inactive met

Inactivation

during which an inactive drug (pro-drug) is converted to a pharmacologically active 1st me

Activation

What is an inactive drug that is converted into an active metabolite called?

Prodrug

What is the biotransformation consequence in which an active drug becomes another pharmacologically active metabolite?

Modification of activity

molecule that is more polar is attach to apparent compound or to its met. With marked increase in overall H2O – solubility & a complete loss of a pharma activity

Conjugation (detoxification)

What is another term for conjugation?

Detoxification

What is the usual effect of conjugation on pharmacological activity ?

Complete loss of pharmacological activity

What is the biotransformation consequence in which a drug enters a normal cellular metabolic pathway and causes cellular death?

Lethal synthesis

What is another term for lethal synthesis?

Intoxication

Smooth-surfaces endoplasmic reticlum (SER) is broken down into small vesicle known as

Microsomer

Microsomal enzymes has a wide variety of?

oxidative reactions

Microsomal enzymes has a wide variety of oxidative reactions, the most prominent is for metabolism of?

lipid-soluble and steroid drugs

Microsomal enzymes includes

• cytochrome p450

• cytochrome p488

• cytochrome b5

Microsomal enzyme + oxygen ; have been classified as?

mixed-function oxidases (MFO)

cytochrome c reductase is for hydroxylaction

NADPH

cytochrome c reductase is for?

hydroxylaction

Outer layer of mitochondria has _____________ enzyme with can cause oxidation, reduction or deamination of biogenic amine

monoamine oxidase (MAO)

Outer layer of mitochondria has monoamine oxidase (MAO) enzyme with can cause?

oxidation, reduction or deamination of biogenic amine.

is the most important metabolic pathway for endogenous compound

Glucuromide

Glucuromide example

• hormones,

• morphine,

• salicylates,

• acetaminophen,

• chloramohenicol,

• sulfadinethoxine,

• phenylbutazone,

• phenobarbital,

• phenytoin

Glucuronide synthesis requires___________________ through glucuronyl transferase enzyme

conjugation with glucuronic acid

Glucuronide synthesis requires conjugation with glucuronic acid through?

glucuronyl transferase enzyme

is important for metabolism of phenol and aliphatic alcohol

Sulfate conjugation

Sulfate conjugation is important for metabolism of?

phenol and aliphatic alcohol

Sulfate conjugation example

• phenol,

• acetaminophen,

• morphine,

• isoproterenol,

• ascorbic acid

Sulfate conjugation is also needed with?

• chondroitin,

• heparin,

• steroid

Enzyme that catalyzed sulfation is?

phenol sulfotransferase

Acetylation adds what group to amino groups, and what are examples of drugs or compounds that undergo it?

Acetyl group - sulfonamides and aromatic amines

What enzyme catalyzes acetylation?

Arylamine acetyltransferase

Cat lacks which enzyme?

glucuronyl transferase

Dog lacks which enzyme?

arylamine acetylerase

Pig lacks which enzyme?

phenol sulfoerase

principle process of elimination

Renal

ROUTE OF DRUG EXCRETION:

1.Renal = principle process of elimination

2.Biliary excretion - GIT

• i.Enterohepatic circulation

3.Pulmonary excretion = lungs

4.Less important = Milk, saliva, sweat

is defined as time required for the body to eliminate one-body of remaining drug

elimination half-life

volume of plasma cleared of the drug by various elimination processes per unit of time

Body clearance