Roselyn A. NaranjoUSPF, College of Pharmacy

www.roselynnaranjo.vze.comroselean@gmail.com

Physicochemical Properties of Drugs in relation to Drug Action

DRUG-RECEPTOR INTERACTIONS

ORAL

IntramuscularSubcutaneousIntravenous

Systemic Circulation

DRUG-RECEPTOR INTERACTIONS

ORAL

IntramuscularSubcutaneousIntravenous

Systemic Circulation

DRUG-RECEPTOR INTERACTIONS

drug

+ =

good fit

Desired pharmacologic response

Favors irreversible reaction

more drug molecules are bounded

receptor

DRUG-RECEPTOR INTERACTIONS

drug receptor

+ =

poor fit

No response

Favors reversible reaction

Small amount of drug molecules are bounded

Ineffective drug

DRUG-RECEPTOR INTERACTIONS

Variables that affects drug binding

Structural class

3D shape of molecule

Type of chemical bonds

- OH – O = \ / C - OH - ll C / \

DRUG-RECEPTOR INTERACTIONS

Drugs with the same Pharmacologic class & structural features

Barbiturates

DRUGSDRUGS RECEPTOR SITERECEPTOR SITE EFFECTEFFECT

Specific CNS receptors

Depressant effects Hydantoin Specific CNS

receptors Anticonvulsant

response

Benzodiazepines

GABA receptors Anxiolytic activity

Penicillin Specific enzymes Inhibit bacterial

cell wall construction

Cephalosporins

Tetracyclines Bacterial wall ribosomes

Inhibit bacterial cell wall construction

DRUG-RECEPTOR INTERACTIONS

RECEPTORS First Receptor Model Enzymes

• Acetylcholinesterase

• Dihydrofolate reductase

• Angiotensin

• HIV protease-converting enzymes

H H O \ l ll N – C – C - OH / lH R

H

DRUG-RECEPTOR INTERACTIONS

RECEPTORS Proteins

Amine group

Acid group

Alkyl group

(-)(+)H

Amine group

- receptors are not distributed equally

- behave differently

DRUG-RECEPTOR INTERACTIONS

RECEPTORS ProteinsDrug therapy

Produce 2 effects

Pharmacologic response

Adverse reactions

DRUG-RECEPTOR INTERACTIONS

RECEPTORS ProteinsExample

Paste tamoxifen Structure

here

For estrogen-sensitive breast cancer

For reducing bone loss from osteoporosis

Pharmacologic response Prolonged treatment results to

endometrial cancer due to the response of estrogen

uterine receptors

Adverse effect

ANTAGONIST in the

Mammary Gland

AGONIST in the Uterus &

Bone

DRUG-RECEPTOR INTERACTIONS

RECEPTORS ProteinsExample

Paste sildenafil Structure

here

Inhibit phosphodiesterase that would treat angina

Expected effect Effective inhibitor of an enzyme

found in the corpus cavernosum

Unexpected Results

NO EFFECT in Angina

EFFECTIVE in erectile

dysfunction Vasodilate the blood vessels in the male organ that leads to penile erection

DRUG-RECEPTOR INTERACTIONS

Biological response

Biological receptor site

Bonding forceBonding force

FORCES INVOLVED

DRUG-RECEPTOR INTERACTIONS

Biological response

Bonding forceBonding force

Ionic bond/weaker

Covalent bond/stronger

-short-acting-reversile

-long-lasting effect-irreversible

FORCES INVOLVED

DRUG-RECEPTOR INTERACTIONS

Types of Chemical Bonds

Bond Type Bond Strength example

Covalent 40 – 140 CH3 – OH

Reinforced Ionic 10

Ionic 5 R4 N ---- I

H lR-N-H-O l C - R’ H O

(+)---(-)

(+)---(-)

DRUG-RECEPTOR INTERACTIONS

Types of Chemical Bonds

Bond Type Bond Strength example

Hydrogen 1 – 7

Ion-dipole 1 - 7 R4 N ----:NR3

Dipole-dipole 1 - 7

- OH – O = \ / C - OH - ll C / \

lO = C ....:NR3

lδ- δ+

DRUG-RECEPTOR INTERACTIONS

Cis & trans structure formation

FORCES INVOLVED