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DRUG
METABOLISM
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Metabolism

 Liver = main organ for metabolism

 “First pass effect”
 Portion of drugs are transported into
hepatocytes  metabolized by
hepatic enzymes to inactive chemicals
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 Lidocaine = drug that is extensively

metabolized by the liver
 A local anesthetic antiarrhythmic agent

 60% of this drug is metabolized during its initial

passage through the liver
 Impractical to be used for oral administration

 T ½ = less than 2hrs

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 TOCAINIDE
 Primary Amine analog of Lidocaine
 T1/2 = 15hrs
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 Some metabolites are Also Active, pharmacologically active substance

 Lead to additional potential New Product

 Ex. Of Inactive Drug  Active Drug

 SULINDAC = NSAIDs
 Active metabolite: Sulfide metabolite

 Azathioprine = Immunosuppressant agent/Antimetabolite

 Active metabolite: 6-Mercaptopurine

 Acyclovir = Antiviral
 AM: Acyclovir triphosphate
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Sometimes, Both the parent drug and its
metabolites are ACTIVE
 Ex.

 PHENACETIN = Analgesic agent

 AM: Acetaminophen

 IMIPRAMINE = Tricyclic antidepressant

 AM: Desipramine (via N-demethylation)

 AMITRIPTYLINE = Tricyclic antidepressant

 AM: Nortriptyline
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It is fortunate that the body can metabolized
foreign molecules (xenobiotics)
 If not, this xenobiotic could remian in the body for years.

 Ex.

 DICHLORODIPHENYLTRICHLOROETHANE (DDT)

 Lipophilic chemical pollutants

 After entering the body, these chemicals reside in body tissues,

slowly diffusing out of the depots and potentially harming the
individual on a chronic basis for several years  can occur in a
commercial food animals that have been slaughtered before the
drug has washed out of the body
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EXCRETION

 Kidney:
 This is where the main route of
excretion of drug and its
metabolites occur.
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RECEPTORS

 Drug binding to a specific receptor 

Pharmacological Effect
 Many drug receptors are the same as
those used by endogenously produced
ligands.
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Receptor
 Cholinergic agents  bind to same receptor as the Neurotransmitter Acetylcholine

 Synthetic corticosteroid  bind to same receptor as Cortisone and Hydrocortisone

 ***ligands are found in various tissues throughout the body

 Ex. NSAIDS = inhibits the prostaglandin-forming enzymes CYCLOOXYGENASE

 COX = found in nearly every tissue

 2ND Gen Antihistamine : FEXOFENADINE = less sedation because it does not readily
penetrate the BBB
 Less of the drug enters the receptor in the CNS

 1st Gen Antihistamine: Chlorpheniramine

 Can penetrate BBB  Enters the CNS  sedation
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Undesirable effect can lead to Beneficial
and New Product

 Sulfonamide
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Same PCOL class have certain structural features in
common

 Barbiturates = Act on specific CNS

receptor  Depressant effect
 Hydantoins = Act on CNS receptor
 Anticonvulsant effect
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 Benzodiazepine = combine with the

y-aminobutyric acid (GABA)
receptor  Anxiolytic effect