HL Chemistry D.1: Pharmaceutical Products & Drug Action

5 methods of administering drugs

• Orally

• Injection (parenteral): fastest absorption method

• Pulmonary (through inhalation)

• Topically (through the skin)

• Rectally

3 types of injections

• Subcutaneous (under the skin)

• Intramuscular

• Intravenous

Bioavailability

Portion of drug that enters the bloodstream of body

LD50

• lethal dose for 50% of animal sample

• Only for animal trials

ED50

• Effective dose for 50% of sample (human or animal)

Therapeutic Index

• TD50/ED50 (for humans)

• Bigger therapeutic index ideally

Therapeutic Window

• range of doses between ED50 and TD50

• Give therapeutic effect

Process of testing new drug

in-vitro (cell), animal, human volunteer, humans (suggested by drug regulation body)

TD50

• Toxic dose for 50% of human population

Tolerance

• When body and immune system adapts to presence of a drug

• increases dose to cause biological effect

• increases risk for dependence on drug

Agonistic

• Drug molecule binds to cell receptor

• Acts like normal substrate & induces similar effect

Antagonistic

• Drug molecule blocks active site

• Prevents normal substrate from attaching

Allosteric

• changes shape of enzyme/cell receptor —> leads to change in response to normal ligand/substrate

Ligand

• Small molecule (e.g. drug molecule) that binds to a receptor

Functional groups impacting bioavailability

• Acidic groups (-COOH) more likely to be absorbed in stomach

• Basic groups (-NH2) more likely to be absorbed in intestines

What impacts drug absorption into bloodstream?

• Lipophilic groups (-C6H5): pass more easily through cell membrane

• Hydrophilic groups (-NH2, -COOH, -OH): increase solubility, easily transported through blood plasma

Factors that reduce bioavailability for a drug

• metabolism (in liver) can turn drug into inactive compounds

• Dissolution

• Distribution into tissues

• Excretion via urine

Risk-to-benefit ratio

• Side effects less of an issue if drug is good at treatment

Computer-aided Drug Design

• Finding lead compounds (from plant or synthetic) from library

• structure analysis & comparison

• Identifying action conformations

• Identifying pharmacophores

• Protein and binding site structure

• Design of synthetic drugs

Pharmacophores

Features common to a group of active molecules

Placebo

• Given in trials, no active ingredients

• A “dummy“

• Actual drug compared to this for effectiveness

Placebo Effect

• Psychological effect

• When body heals itself despite being given medicine with no active ingredient