Roselyn A. Naranjo

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Physicochemical Properties of Drugs in relation
to Drug Action

• Roselyn A. Naranjo
• USPF, College of Pharmacy
• www.roselynnaranjo.vze.com
• roselean_at_gmail.com

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DRUG-RECEPTOR INTERACTIONS
ORAL
Systemic Circulation
Intramuscular Subcutaneous Intravenous
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DRUG-RECEPTOR INTERACTIONS
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DRUG-RECEPTOR INTERACTIONS


drug
good fit

• more drug molecules are bounded

• Favors irreversible reaction

• Desired pharmacologic response

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DRUG-RECEPTOR INTERACTIONS


drug
receptor
poor fit

• Small amount of drug molecules are bounded

• Favors reversible reaction

• No response

• Ineffective drug

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DRUG-RECEPTOR INTERACTIONS

• Variables that affects drug binding

- OH O \ / C -
OH - ll C / \

• Structural class

• 3D shape of molecule

• Type of chemical bonds

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DRUG-RECEPTOR INTERACTIONS
Drugs with the same Pharmacologic class
structural features






DRUGS
RECEPTOR SITE
EFFECT

• Barbiturates

• Depressant effects

• Specific CNS receptors

• Hydantoin

• Anticonvulsant response

• Specific CNS receptors

• Benzodiazepines

• Anxiolytic activity

• GABA receptors

• Penicillin

• Inhibit bacterial cell wall construction

• Specific enzymes

• Cephalosporins

• Tetracyclines

• Bacterial wall ribosomes

• Inhibit bacterial cell wall construction

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DRUG-RECEPTOR INTERACTIONS

• RECEPTORS

First Receptor Model Enzymes

• Acetylcholinesterase

• Dihydrofolate reductase

• Angiotensin

• HIV protease-converting enzymes

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DRUG-RECEPTOR INTERACTIONS

• RECEPTORS

Proteins
()
(-)
H
- receptors are not distributed equally
Acid group
Amine group
Amine group
Alkyl group
- behave differently
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DRUG-RECEPTOR INTERACTIONS

• RECEPTORS

Proteins
Drug therapy
Produce 2 effects

• Pharmacologic response

• Adverse reactions

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DRUG-RECEPTOR INTERACTIONS

• RECEPTORS

Proteins
Example
Paste tamoxifen Structure here
ANTAGONIST in the Mammary Gland
Pharmacologic response
Adverse effect

• Prolonged treatment results to endometrial cancer
  due to the response of estrogen
• uterine receptors

• For estrogen-sensitive breast cancer

AGONIST in the Uterus Bone

• For reducing bone loss from osteoporosis

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DRUG-RECEPTOR INTERACTIONS

• RECEPTORS

Proteins
Example
Paste sildenafil Structure here
NO EFFECT in Angina
Expected effect
Unexpected Results

• Effective inhibitor of an enzyme found in the
  corpus cavernosum

• Inhibit phosphodiesterase that would treat angina

EFFECTIVE in erectile dysfunction

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

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DRUG-RECEPTOR INTERACTIONS

• FORCES INVOLVED

Biological response
Biological receptor site
Bonding force
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DRUG-RECEPTOR INTERACTIONS

• FORCES INVOLVED

Biological response
Ionic bond/weaker

• short-acting
• reversile

Bonding force
Covalent bond/stronger

• long-lasting effect
• irreversible

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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
()---(-)
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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
l O C ....NR3 l
d- d
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DRUG-RECEPTOR INTERACTIONS

• FORCES INVOLVED

• Cis trans structure formation