Chapter 1 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
•a substance to which a drug needs to interact with to elicit a pharmacological response
•90% proteins, some are nucleic acids and lipids
RECEPTOR
•ability of drug to bind to the receptor
AFFINITY
Is Receptor a macromolecules? Yes or no and why?
Yes! 90% proteins, some are nucleic acids and lipids
•ability of a drug to exert a pharmacologic action
INTRINSIC ACTIVITY
•Affinity + Intrinsic activity
AGONIST
•Affinity only
ANTAGONIST
•site other than the binding site
ALLOSTERIC SITE
FACTORS THAT INFLUENCE THE ABSORPTION:
•Chemical structure
•Variation in particle size
•Nature of the crystal form (Amorphous > Crystalline)
–Example:
- Ultra-lente = 100% crystalline (long-acting)
- Lente insulin = 70% crystalline, 30% amorphous (intermediate)
- Semi lente = 100% amorphous (short-acting)
•Type of tablet coating
•Blood flow to the absorption site
•Total surface area available for absorption
•Contact time at the absorption surface
…
FOUR FUNDAMENTAL PATHWAYS OF DRUG PHARMACOKINETICS
Absorbtion
Distributiom
Metabolism
Excretion
the transfer of a drug from its site of administration to the systemic circulation (or to the bloodstream)
Absorption
————= 100% crystalline (long-acting)
Ultra-lente
—————= 70% crystalline, 30% amorphous (intermediate)
Lente insulin
————-= 100% amorphous (short-acting)
Semi lente
Major site of Absorption
Small intestine
Small intestine was consider major site of absorption specifically due to two parts found in small intestine which is the —— and —-
Villi and microvilli
Major site of metabolism
Liver
Major site of excretion
Kidney
Filtering unit of kidney
Nephron
Drug for prevention is called ——
Prophylaxis
•the fraction of administered drug that reaches the systemic circulation in a chemically unchanged form (f)
BIOAVAILABILITY
Bioavalability Equation
F= AUC(oral)/AUC(IV) X AUC(IV) /AUC(Oral)
AUC Means
Area Under the Curve
————is used to calculate the extent of absorption of a drug. A higher ———— indicates greater bioavailability.
AUC
Bioavailability is from Pharmacokinetic or Pharmacodynamic
Pharmacokinetic
the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues
Distribution
•serves as a reservoir
•Albumin - binds acidic drugs
•α-1-acid-glycoprotein - binds basic drugs
•may limit access to certain body compartments
•Prolongs drug duration of action
PLASMA PROTEIN BINDING
binds acidic drugs
Albumin
binds basic drugs
α-1-acid-glycoprotein
Prolongs drug duration of action
PLASMA PROTEIN BINDING
serves as a reservoir
PLASMA PROTEIN BINDING
converts drugs into polar form, water-soluble products that are readily excretable
METABOLISM
detoxification process but not all the time
METABOLISM
compounds that are inactive in their native form, but are easily metabolized to the active agent
Prodrugs
•an inactive precursor chemical that is readily absorbed and distributed and then converted to the active drug by biologic processes inside the body
Ex:
–Enalapril to Enalaprilat
–Chloramphenicol palmitate to Chloramphenicol
–Primidone to Phenobarbital
–Phenacetin to Paracetamol
Prodrug
All ACE’s that end with “Pril” are Prodrug except——
Captopril(already active)
•drugs may be metabolized by hepatic enzymes to inactive chemicals (drug is metabolized prior to absorption)
•only drugs administered orally and rectally undergo first pass metabolism (CYP 450)
•Ex: Nitroglycerin
FIRST PASS EFFECT
only drugs administered——and ———- undergo first pass metabolism (CYP 450)
orally and rectally
•the main route of excretion of a drug and its metabolite is through the kidney (for LMW & polar drugs)
•Other types: Biliary/Fecal, Breastmilk, Sweat (for HMW & lipophilic drugs)
EXCRETION
•drugs emptied via the bile duct into the small intestine can be reabsorbed in the intestinal lumen back to systemic circulation
ENTEROHEPATIC RECIRCULATION
