PHARM CHEM 2: Organic Medicinal Chemistry

Complete set of vocabulary flashcards for Organic Medicinal Chemistry Module 1, covering metabolism, anti-infectives, autonomic nervous system drugs, CNS agents, and antineoplastics.

Medicinal Chemistry

The practice of chemistry devoted to the discovery and development of new drugs, described as a higher form of chemistry.

Metabolism

The biotransformation of drugs in the body, primarily in the liver, converting drugs to hydrophilic, inactive, and nontoxic forms for elimination.

Phase I Metabolism (Functionalization)

The introduction of a polar functional group ($-OH$, $-COOH$, $-NH_2$, or $-SH$) by direct introduction or modifying/unmasking existing functionalities via oxidation, reduction, or hydrolysis.

Oxidation

The most common Phase I reaction, undergone by olefins, alcohols, aldehydes, and aromatic moieties; for example, phenylbutazone undergoes aromatic hydroxylation to form oxybutazone.

Reduction

A Phase I reaction converting carbonyl compounds to alcohol derivatives and nitro/azo compounds to amine derivatives (e.g., chloral hydrate to trichloroethanol).

Hydrolysis

A Phase I reaction commonly undergone by lactams, esters, and amides, such as Aspirin converting to salicylic acid and acetic acid.

Phase II Metabolism (Conjugation)

The attachment of small, ionizable, endogenous compounds to functional handles to form excretable and inactive metabolites and detoxify molecules.

Glucuronidation

The most common Phase II reaction using the coenzyme Uridine-$5’$-diphospho-$\alpha$-D-glucuronic acid (UDPGA) and the enzyme glucuronyltransferase; this process is not yet developed in neonates.

Sulfation

A Phase II process using the coenzyme $3$-phosphoadenosine-$5$-phosphosulfate (PAPS) and sulfotransferase; it is the major metabolic process in neonates.

Glutathione

A tripeptide (Cysteine, Glycine, Glutamine) used for detoxifying chemically reactive electrophilic compounds; the sulfhydryl ($-SH$) group of Cysteine is responsible for detoxification.

Acetylation Polymorphism

Variation in acetylating activity where Europeans/Caucasians are slow acetylators (requiring low doses) and Eskimos/Asians are fast acetylators (requiring high doses).

Methylation

A minor Phase II pathway using S-Adenosylmethionine (SAM) that leads to non-polar inactivated compounds; it is involved in the biosynthesis of epinephrine and melatonin.

First-Pass Metabolism

Also known as pre-systemic metabolism, it occurs when orally administered drugs (e.g., Lidocaine, Nitroglycerin, Propranolol) are extensively metabolized before reaching systemic circulation.

Enzyme Inducers

Substances like Phenobarbital, Rifampicin, and chronic Alcohol intake that increase enzyme activity, leading to increased drug metabolism and decreased drug effects.

Enzyme Inhibitors

Substances like Cimetidine, Ketoconazole, and Erythromycin that decrease enzyme activity, leading to decreased drug metabolism and increased drug effects.

Antisepsis

The application of a chemical agent to living tissue to prevent infection.

Sterilization

The process of killing or removing all types of microorganisms.

Alcohol, USP

Commercial ethanol ($95\%$) manufactured by fermentation of grains or hydration of ethene; it is metabolized by alcohol dehydrogenase to acetaldehyde and then by aldehyde dehydrogenase to acetic acid.

Disulfiram

A deterrent for alcohol addiction that inhibits aldehyde dehydrogenase, causing aldehyde accumulation and symptoms like nausea, vomiting, and vasodilatory flushing.

Isopropyl Alcohol

Also known as $2$-propanol, it is a substitute for ethanol prepared by sulfuric acid catalyzed hydration of propylene; it is more potent and less toxic than ethanol.

Formaldehyde

Also known as Methanal ($HCHO$), it acts by direct and nonspecific alkylation of nucleophilic functional groups of proteins; used as embalming fluid.

Phenol COEFFICIENT

The ratio of the dilution of a disinfectant to the dilution of phenol required to kill a strain of Salmonella typhi, used as a germicidal standard.

Iodophors

Complexes of iodine and non-ionic surfactants (e.g., Povidone-Iodine/Betadine) that retain germicidal properties while reducing volatility and irritation.

Benzalkonium Chloride

A quaternary ammonium cationic surfactant (Zephiran) used as an anti-infective; it is inactivated by soaps and other anionic detergents.

Parabens

Esters of $p$-hydroxybenzoic acid with antifungal properties; methylparaben is effective against molds while propylparaben is effective against yeast.

Gentian Violet

A triphenylmethane dye used as a pessary for yeast infections and as an anthelmintic for strongyloides.

Methylene Blue

A thiazine dye used as an antidote for cyanide poisoning and as an antiseptic for cystitis; it may cause blue-green color of stool.

Piperazine

An anthelmintic that blocks the response of ascaris muscle to ACh, leading to flaccid paralysis; used for pinworms and roundworms.

Praziquantel

The agent of choice for blood flukes (schistosomes), acting by increasing $Ca^{2+}$ membrane permeability, leading to contraction, paralysis, and death.

Metronidazole

A 5-nitroimidazole (Flagyl) that treats amoeba and anaerobic infections; it causes a disulfiram-like effect if taken with alcohol.

Permethrin

A synthetic pyrethrin that disrupts $Na^+$ channel conductance on nerve membranes; a $1\%$ lotion is used for lice and a $5\%$ cream is used for scabies.

6-Aminopenicillanic acid (6-APA)

The core nucleus of penicillins, consisting of a beta-lactam ring fused to a thiazolidine ring; precursors are Cysteine and Valine.

Penicillin G

Also known as Benzyl penicillin, it is the Drug of Choice (DOC) for Syphilis and is typically administered IV.

7-Aminocephalosporanic acid (7-ACA)

The core nucleus of cephalosporins, consisting of a beta-lactam ring fused to a dihydrothiazine ring.

Vancomycin

A glycopeptide from Streptomyces orientalis that inhibits transglycosidation; it is the DOC for MRSA (IV) and can cause red-man syndrome.

Aminoglycosides

Antibiotics that bind to the $30s$ ribosomal subunit; examples include Gentamicin and Streptomycin (the first effective agent against TB).

Tetracyclines

Broad-spectrum antibiotics consisting of $4$ fused rings that bind to the $30s$ subunit; they can cause tooth discoloration and are contraindicated in pregnancy.

Macrolides

Antibiotics like Erythromycin that contain a $14$-membered lactone ring and bind to the $50s$ ribosomal subunit to inhibit translocation.

Chloramphenicol

A protein synthesis inhibitor ($50s$ subunit) that can cause Gray baby syndrome and Aplastic anemia; its toxicophore is the nitro group.

Quinolones

Synthetic antibacterials patterned after Nalidixic acid that inhibit DNA Gyrase (Topoisomerase); addition of fluorine at position $6$ increases activity.

Sulfonamides

Antibacterials that inhibit dihydropteroate synthetase to prevent folic acid synthesis; they require a para-amino group for activity.

Rifampicin

An anti-TB drug that inhibits RNA polymerase; side effects include red-orange secretions and hepatotoxicity.

Isoniazid (INH)

A first-line anti-TB drug that inhibits mycolic acid synthesis; Pyridoxine (Vitamin $B_6$) is administered with it to prevent peripheral neuropathy.

Ethambutol

An anti-TB drug that inhibits arabinosyl transferase; a notable side effect is optic neuritis resulting in blue-green vision.

Amphotericin B

A polyene antifungal from Streptomyces nodosus that forms pores in the cell membrane by binding to ergosterol.

Azoles

Antifungals that inhibit the enzyme $C-14$ $\alpha$-demethylase, blocking the conversion of lanosterol to ergosterol.

Griseofulvin

A microtubule poison derived from Penicillium griseofulvum; it is the DOC for refractory ringworm and should be taken with fatty food.

Benzodiazepines

Anxiolytics that act by increasing the FREQUENCY of GABA-mediated chloride ion channel opening.

Barbiturates

Sedative-hypnotics that act by increasing the DURATION of GABA-mediated chloride ion channel opening.

Phenothiazines

Typical antipsychotics where a $3$-carbon chain between position $10$ and the amino nitrogen is essential for antipsychotic potency.

Insulin Lispro (Humalog)

A rapid-acting insulin where Lysine and Proline are exchanged at positions $B28$ and $B29$.

Cyclophosphamide

An alkylating agent that can cause hemorrhagic cystitis due to the metabolite Acrolein; MESNA is the antidote used to manage this toxicity.

Methotrexate

A folic acid analogue that inhibits enzymes for DNA synthesis; its toxicity (myelosuppression) is managed with Leucovorin (Folinic acid).

Taxanes

M-phase specific antineoplastics (e.g., Paclitaxel) isolated from the Pacific yew tree that stabilize microtubules and inhibit depolymerization.