(P) INTRODUCTION Flashcards
the practice of medicinal chemistry that is devoted to the discovery and development of new drugs
Organic Medicinal Chemistry
an agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or in other animals
Drug
(6) Key Concepts in Drug Action
- Receptor
- Affinity
- Intrinsic Activity
- Agonist
- Antagonist
- Allosteric Site
• A substance with which a drug interacts to produce a pharmacological response.
• 90% are primarily proteins
• also contain nucleic acids and lipids
Receptor
The drug’s ability to bind to a receptor
Affinity
The drug’s ability to elicit a pharmacologic action upon binding.
Intrinsic Activity
Combines affinity and intrinsic activity.
Agonist
Only possesses affinity without intrinsic activity.
Antagonist
A site on the receptor other than the main binding site.
Allosteric Site
4 Fundamental Pathways of Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
the transfer of a drug from its site of administration to the systemic circulation (or to the bloodstream)
Absorption
(8) Factors that influence the absorption/ Transport Mechanism
• Chemical structure
• Variation in particle size
• Nature of the crystal form (Amorphous > Crystalline)
• Type of tablet coating
• Blood flow to the absorption site
• Total surface area available for absorption
• Contact time at the absorption surface
Nature of Crystal Form:
• 100% crystalline (long-acting)
Ultra-lente
Nature of Crystal Form:
• 70% crystalline, 30% amorphous (intermediate)
Lente insulin
Nature of Crystal Form:
• 100% amorphous (short-acting)
Semi-lente
• The fraction of the drug that enters systemic circulation unchanged
Bioavailability
• 100% bioavailability
• Immediate effect and rapid drug action
• But higher risk of toxicity and side effects
Intravenous
• The reversible transfer of drugs from the bloodstream to tissues or interstitial fluid.
Distribution
The reversible transfer of drugs from the bloodstream to tissues or interstitial fluid (small intestine)
Distribution
• serves as reservoir
• it magnets the drug and slowly releases the drug overtime
• may limit access to certain body compartments
• Prolongs drug duration of action
Plasma Protein Binding
Protein that binds acidic drugs
Albumin
Protein that binds basic drugs
α-1-acid-glycoprotein
• converts drugs into polar form, water-soluble products that are readily excretable
• detoxification process but not all the time
Metabolism
Main site of metabolism
Liver
• compounds that are inactive in their native form, but are easily metabolized to the active agent
Prodrugs
Examples of Prodrugs
• Enalapril to Enalaprilat
• Chloramphenicol palmitate to Chloramphenicol
• Primidone to Phenobarbital
• Phenacetin to Paracetamol
• when a drug is partially broken down by the liver before it reaches the bloodstream.
• This reduces the amount of active drug available to the body, making some oral/rectal medications less effective
• applies to oral/rectal drugs (CYP 450)
• Ex: Nitroglycerin
First-pass effect
• Primary route is via the kidney
(for Low Molecular Weight and Polar drugs).
• Other routes include biliary/fecal excretion, breastmilk, and sweat.
(for High Molecular Weight and Lipophilic Drugs)
Excretion
Water-soluble, easily filtered from blood by the kidney
Low Molecular Weight and Polar drugs
Dissolves in fats, oils, and lipids
High Molecular Weight and Lipophilic Drugs
Drugs excreted via the bile can be reabsorbed in the intestines.
Enterohepatic Recirculation
