M1 - Introduction to Medicinal Organic Chemistry

MEDICINAL CHEMISTRY

Branch of chemistry involved in identification, design, synthesis, and development of biologically active compounds.

interdisciplinary science

• Organic Chemistry

• Biochemistry

• Computational Chemistry

• Pharmacology

• Pharmacognosy

• Molecular biology

• Physical Chemistry

DRUGS

are low MW chemical substances that interact with macromolecular targets in the body to produce effect

Pharmacodynamics

• What the drug does to the body

• Design a drug that will interact as powerfully and selectively as possible for the target

ENDOGENOUS COMPOUNDS

body’s own natural chemicals

EXOGENOUS COMPOUNDS

foreign substances (XENOBIOTICS)

XENOBIOTICS

EXOGENOUS COMPOUNDS also known as?

Pharmacokinetics

• What the body does to the drug

• Design the drug so that it is capable of reaching that target

ADME

ABSORPTION DISTRIBUTION METABOLISM EXCRETION

LIBERATION

• When the conventional dosage forms are administered orally or topically, the active drug in the dosage form is immediately released and absorbed into the systemic circulation.

• Diffusion is the most common mechanism controlling drug release.

LUNA

LIPOPHILIC UNIONIZED NON POLAR ABSORBED

HIPE

HYDROPHILIC IONIZED POLAR EXCRETED

• Oral Administration

• Parenteral Administration

• BLOOD BRAIN BARRIER

DRUG ABSORPTION

Oral Administration

The most common and popular route

Stomach

pH 1.5-2 fed state; pH 2-6 fasting state

pH 1.5-2

fed state

pH 2-6

fasting state

Small Intestine

main site of absorption

→ UNIONIZED

Acidic drug +Acidic medium

Basic drug +Basic medium

→ IONIZED

Acidic drug +Basic medium

Basic drug +Acidic mediu

More absorbed >UNIONIZED → A +A

At what medium are acidic drugs readily absorbed?

More excreted >IONIZED → A +B

At what medium are acidic drugs readily excreted?

Parenteral Administration

• Direct to Systemic Circulation

• Rapidly distributed

• IV, IM, SC,Intraspinal, Intracerebral

BLOOD BRAIN BARRIER

Protects the brain from exposure to chemicals and metabolites, due to the presence of tightly joined epithelial cells lining the cerebral capillaries

DRUG DISTRIBUTION

• Drug movement from the systemic circulation going to different organs and tissues

• Blood Flow

PERFUSION

Delivery of drug to the tissue is controlled by the specific blood flow to a given tissue

DRUG METABOLISM (BIOTRANSFORMATION)

• All substances in the circulatory system, including drugs, metabolites, and nutrients, will pass through the liver.

• Most molecules absorbed from the GIT enter the portal vein and are initially transported to the liver.

1. Azathioprine

2. Acyclovir

Bioactivation

Azathioprine

• immunosuppressant

• 6-mercaptopurine

Acyclovir

• antiviral

• Acyclovir triphosphate

First-Pass Effect

• a significant proportion of a drug is metabolized by hepatic enzymes during the initial trip through the liver

• Drug removal by the liver after absorption

LIDOCAINE

• example of First-Pass Effect

• antiarrhythmic (60% is metabolized when given orally)

1. ENZYME INDUCTION

2. ENZYME INHIBITION

Alteration of Enzymic Action

ENZYME INDUCTION

increased metabolism = low Cp

ENZYME INHIBITION

decreased metabolism = high Cp

Enzyme Inducers

Enzyme Inhibitors

ENTEROHEPATIC CIRCULATION

• drug reenters the intestinal tract from the liver through bile duct

• BILIARY RECYCLING

Drug elimination

DRUG EXCRETION

____ into the urine is a major route of elimination for metabolites and unchanged drug.

1. Glomerular Filtration

2. Tubular Secretion

3. Tubular Reabsorption

RENAL CLEARANCE

Glomerular Filtration

unbound drug is passively filtered by the glomerulus.

Tubular Secretion

drug is actively secreted.

Tubular Reabsorption

drug is passively reabsorbed back into the blood.