Relied on “serendipity” — the idea that if it worked we do it. Based only on effectiveness.
Eventually replaced by observation and experiment, however, molecular level of knowledge was lacking.
*Chemistry and *Physiology lead us to know how drugs work on the organ level.
-Accurate evaluation of therapeutic claims.
Research allowed us to:
-Gain info of drug action and receptor
-Improve understanding of molecular basis of drug action
-100MW to achieve selectivity (sufficient binding).
-1000MW to allow for proper distribution.
-If greater than 1000MW, needs to be administered at site.
-Size, shape, charge, atomic makeup
-Structure + specificity
-3 point attachment
-Specific, mimic endogenous
Noncovalent = most common = more selectivity (less reactivity)
-Hydrogen, Van der Waals’, ionic.
Many exist as chiral molecules, thus have enantiomers.
Dextro = Right = D
Levo = Left = S
E.G. Prilosec Vs. Nexium
Prilosec: Omeprazole, racemic, S has activity.
Nexium: Esomeprazole, S isomer, absorption/ half life +,
Extended patent life = + money for company.
Most start racemic but eventually produced as single isomer
-Determines appropriate therapy
-Choice and administration of drug to specific patient
-Depends on: CONCENTRATION
-Selective, and change function upon binding.
-Drugs typically look like endogenous molecule.
Bile = feces
Kidneys = urine
Inhaled, topical, transdermal,sublingual
Intramuscular, intravenous, subcutaneous
-Barriers drug is capable of passing (B/b. B/t)
-Setting in which drug will be used (Hospital vs. home)
-Urgency of situation
-First pass effect
-Vascularity. Higher = higher uptake (EG Brain/kidneys)
-Drug solubility in certain tissue
-Binding of drug to macromolecules in blood IE. Albumin
-Ability to cross special barriers IE Blood brain Blood testes
Metabolism: Enzymatic conversion of drugs to inactive derivatives, more polar, more water soluble, enzymes in GI and liver.
Excretion: Follows metabolism or unchanged
Kidneys = urine
Liver/bile = feces
-Outrageous claims of benefit and safety
-Unregulated use of addictive substances
-not for efficacy, just purity.
1912: Amended to stop false advertising claims
1938: FDCA: Label with direction for safe use / Preapproval for safety
Required efficacy in addition to safety.
Prescription and OTC included
Classifies drug schedules on basis of abuse potential.
4-8 years: Human clinical trials
8-20 years: Exclusive marketing rights
20+ years: generics form
Dose to pharmacological/therapeutic effect.
Establish safety in patients with disease, and efficacy compared to other treatments.
Patent life = 20 years. Drugs are frequently patented 5 years before marketing. After patents expire other companies can create bioequivalent generic drugs. More familiar to outpatient settings.