Integrated Pharmaceutical Sciences I: Pharmaceutical & Medicinal Organic Chemistry (PMOC) and Drug Discovery & Development (DDD)

Comprehensive review practice flashcards covering all aspects of Pharmaceutical and Medicinal Organic Chemistry (PMOC) and Drug Discovery and Development (DDD), including local anti-infectives, antifungals, antibacterials, antivirals, antiparasitics, antineoplastics, and the drug development pipeline.

How is medicinal chemistry defined?

The branch of science devoted to the discovery and development (including organic, analytical, and biochemical aspects) of new agents for treating diseases.

Which seven scientific disciplines converge within medicinal chemistry?

Chemistry, Biochemistry, Molecular Biology, Physiology, Pharmacology, Pharmaceutics, and Medicine.

What are the four major considerations when developing new pharmacologically active compounds?

Physicochemical properties, Mechanism of Action (MOA), Drug metabolism and metabolite activities, and Stereochemistry.

What is a pharmacophore?

The region of a molecule containing the essential organic functional groups that directly interact with the receptor active site, thereby conferring the biological activity of interest.

What major contribution did Joseph Lister introduce in 1867?

Antiseptic principles for surgical procedures and post-traumatic wound care using phenol (carbolic acid).

Who is the surgeon pictured below who introduced antiseptic principles into surgery in 1867?

Joseph Lister

What chemical compound did Joseph Lister apply as an antiseptic to reduce postsurgical infections?

Phenol (carbolic acid).

What was the clinical outcome of Joseph Lister's introduction of antiseptic techniques?

A significant decrease in the incidence of postsurgical infections.

What significant work did Paul Ehrlich initiate in 1881?

Investigations with antibacterial dyes and arsenicals, establishing the principle of selective toxicity.

Who is the scientist pictured below who developed Salvarsan and formulated the selective toxicity principle?

Paul Ehrlich

What specific anti-syphilis compound did Paul Ehrlich discover?

Salvarsan.

What historic anti-syphilis arsenical drug packaging is depicted in the photograph below?

Salvarsan (Kharsivan).

What is the selective toxicity principle pioneered by Paul Ehrlich?

The ability of a therapeutic agent to kill or inhibit a pathogen without inflicting significant injury on the host organism.

What is a germicide?

An anti-infective agent intended for local application.

How is an antiseptic distinguished from a disinfectant?

Antiseptics kill (-cidal) or prevent the growth of (-static) microbes on living tissue, whereas disinfectants destroy pathogenic microbes on inanimate objects.

What is the difference between '-cidal' and '-static' antimicrobial actions?

'-cidal' refers to killing the microorganism, while '-static' refers to inhibiting microbial replication or growth.

What eight major classes of local anti-infectives were presented in the lecture?

Alcohols and related compounds, Phenols and their derivatives, Oxidizing agents, Halogen-containing compounds, Cationic surfactants, Dyes, Mercury compounds (mercurials), and Preservatives.

What is the primary mechanism of action (MOA) of alcohols and related compounds?

Protein and carbohydrate denaturation.

Which test organism is utilized to evaluate the antibacterial potency of alcohols?

Staphylococcus aureus

According to the structure-activity relationship (SAR) of alcohols, how does molecular weight affect antibacterial potency?

Potency increases with increasing molecular weight up to an optimal chain length of 8 carbons ($8\text{C}$).

According to the SAR of alcohols, how does alkyl chain branching influence antibacterial potency?

Branching decreases antibacterial potency.

What is the order of antibacterial potency among primary, secondary, and tertiary alcohols?

Primary > Secondary > Tertiary.

What are four historical and commercial synonyms for ethanol?

Ethyl alcohol, grain alcohol, wine spirit, and spiritus vini rectificatus.

How is ethanol synthesized industrially?

Via the hydration of ethylene.

What synthetic reaction is shown in the chemical equation below?

Hydration of ethylene to produce ethanol.

What is commercial ethanol concentration by volume?

$$95\%\,\text{v/v}$$

What concentration of ethanol is safely employed for the preoperative sterilization of skin?

$$>70\%$$

What is the most common antibacterial concentration of ethanol?

$$70\%$$

What is the clinical limitation of using ethanol solutions below $60\%$?

They remain effective but require a substantially longer contact time.

What are four common uses of ethanol?

Antiseptic, preservative, mild counterirritant, and solvent.

What is denatured alcohol?

Ethanol that has been rendered unfit for human consumption by the addition of toxic or unpalatable denaturants.

What are two common chemical synonyms for isopropyl alcohol?

Isopropanol and 2-propanol.

How is isopropyl alcohol synthesized industrially?

Via the hydration of propylene.

What chemical reaction is illustrated in the reaction scheme below?

Acid-catalyzed hydration of propylene to form isopropyl alcohol (2-propanol).

What is the standard concentration of isopropyl alcohol found in commercial rubbing alcohol?

$$70\%$$

What is the chemical functional group classification of ethylene oxide?

An epoxide (oxirane).

What 3-membered cyclic ether structure is shown in the image below?

Ethylene oxide

What is the explosive concentration range of ethylene oxide when mixed with air?

$$3\% - 80\%$$

How is the flammability and explosive risk of ethylene oxide mitigated for industrial sterilization?

By mixing it with carbon dioxide ($\text{CO}_2$), commercially termed Carboxide.

What is the mechanism of action of ethylene oxide?

Alkylation of cellular macromolecules (proteins and nucleic acids).

What is the primary utility of ethylene oxide in medical care?

Sterilizing heat-sensitive medical equipment and pharmaceuticals that cannot withstand autoclaving.

What is the official compendial definition and composition of Formalin?

A solution containing not less than $37\%\,\text{w/v}$ formaldehyde together with methanol as a stabilizer.

What simple aldehyde structure is shown below?

Formaldehyde

What is the major application of formaldehyde solution?

An embalming agent.

What is glutaraldehyde disinfectant solution chemically?

A 5-carbon dialdehyde.

What 5-carbon dialdehyde sterilizing agent is shown below?

Glutaraldehyde

What is the medical use of glutaraldehyde disinfectant solution?

Sterilization of medical instruments and equipment that cannot be autoclaved.

What is the concentration-dependent MOA of phenols and their derivatives?

Protein denaturation at low concentrations and cell membrane lysis at high concentrations.

Which test organism is used as the standard in determining the phenol coefficient?

Salmonella typhi

How is the phenol coefficient defined?

The ratio of the highest dilution of a test disinfectant to the dilution of phenol that kills a standard strain of Salmonella typhi under identical conditions.

According to the SAR of phenols, what substituents at the para position enhance bactericidal activity?

Alkyl, aryl, and halogen substitutions.

According to the SAR of phenols, how does alkyl substitution geometry affect bactericidal activity?

Straight-chain alkyl substituents confer greater activity than branched-chain substituents.

How does the toxicity of alkylated phenols and resorcinols compare to parent phenol?

Alkylated phenols and resorcinols are less toxic than the parent compounds.

What are the physical appearance and odor characteristics of phenol?

Colorless to pale-pink crystalline solid with a characteristic 'medicinal odor.'

What classical toxicology term is applied to phenol?

General protoplasmic poison.

What is cresol chemically, and what is its physical description?

A mixture of three isomeric methylphenols (o-, m-, and p-cresol), appearing as a yellow to brownish-yellow liquid with a creosote odor.

What is the clinical value of cresol?

An inexpensive antiseptic and disinfectant.

What is the natural botanical source and therapeutic utility of thymol?

Thyme oil from Thymus vulgaris; possesses mild fungicidal properties used to treat tinea infections.

What substituted phenolic compound obtained from thyme oil is shown below?

Thymol

What is the botanical origin and dental application of eugenol?

Clove oil from Eugenia caryophyllata or Syzygium aromaticum; provides local anesthetic and antiseptic activity for toothache relief.

What phenylpropanoid compound derived from clove oil is shown below?

Eugenol

What are the two primary pharmacologic properties of eugenol?

Local anesthetic and antiseptic activity.

What is the phenol coefficient (PC) and primary dermatologic use of resorcinol?

Phenol coefficient of $0.4$ (weak antiseptic); used primarily as a keratolytic agent.

What m-dihydroxybenzene structure is shown in the image below?

Resorcinol

What is the general MOA of oxidizing agents?

Liberation of nascent oxygen, which oxidizes essential cellular components.

What are the two principal clinical limitations of oxidizing agents?

Poor tissue penetrability and a transient duration of effect.

What are four common inorganic oxidizing agents used as anti-infectives?

Hydrogen peroxide, metal peroxides, sodium perborate, and potassium permanganate ($\text{KMnO}_4$).

What are the dual dermatological actions and primary indication of hydrous benzoyl peroxide?

Keratolytic and keratogenic actions; indicated for the topical treatment of acne vulgaris.

What is recognized as the oldest germicide still in widespread use today?

Iodine.

What is the antimicrobial MOA of elemental iodine?

Protein inactivation via iodination of aromatic residues (such as tyrosine) and general oxidation of protein sulfhydryl groups.

What is the exact official formulation of Iodine Tincture, USP?

$2\%$ iodine in $50\%$ alcohol with sodium iodide ($\text{NaI}$).

What is the exact official formulation of Strong Iodine Solution (Lugol's Solution), USP?

$5\%$ iodine in water with potassium iodide ($\text{KI}$).

What is the exact official formulation of Iodine Solution, USP?

$2\%$ iodine in water with sodium iodide ($\text{NaI}$).

What is an iodophor?

A complex of iodine with a nonionic surfactant, typically providing $10\%$ available iodine.

What is the chemical composition of povidone-iodine?

A charge-transfer complex of elemental iodine with the nonionic polymer surfactant polyvinylpyrrolidone (PVP).

What pharmaceutical advantages does povidone-iodine have over traditional elemental iodine solutions?

It is water-soluble, non-toxic, non-volatile, non-staining, non-irritating, and releases iodine slowly.

What is the primary clinical application of povidone-iodine?

Presurgical skin preparation and wound disinfection.

What is the primary application of chlorine-containing compounds?

Disinfection of municipal and institutional water supplies.

What is the active germicidal chemical species released by chlorine in water?

Hypochlorous acid ($\text{HClO}$).

What is the MOA of chlorine-containing disinfectants?

Chlorination and oxidation of microbial proteins.

At what pH do chlorine-based disinfectants exhibit their optimal antimicrobial effect?

$$\text{pH } 7$$

What are three examples of chlorine-containing antibacterial agents?

Halazone, Chloroazodin, and Oxychlorosene sodium.

What chemical family defines cationic surfactants?

Quaternary ammonium compounds.

What are the two essential structural moieties present in a cationic surfactant molecule?

A positively charged hydrophilic quaternary nitrogen head group and a long lipophilic hydrocarbon tail.

What structural feature of a cationic surfactant is shown below?

Quaternary ammonium cationic head group with benzyl substitution.

What is the MOA of cationic surfactants?

Cell membrane destabilization and lysis.

What is the primary clinical utility of cationic surfactants?

Disinfecting surgical instruments, gloves, and operating room surfaces.

What is the major clinical disadvantage and cause of inactivation of cationic surfactants?

They are readily inactivated by soaps and other anionic detergents.

What quaternary ammonium compound serves as the active agent under the modern generic name of Merthiolate?

Benzalkonium chloride.

What is the clinical use of methylbenzethonium chloride?

Treatment and prevention of diaper rash.

What is the primary use of benzethonium chloride?

Topical skin antiseptic.

What is cetylpyridinium chloride chemically, and how is it commercially formulated?

The most active of a series of alkylpyridinium compounds; formulated as throat lozenges and antiseptic mouthwashes.

What chemical class does chlorhexidine gluconate belong to, and what are its four uses?

An antibacterial biguanide; used for preoperative skin disinfection, wound irrigation, antiseptic mouthwashes, and general sanitization.

Against what groups of microorganisms are medicinal dyes active?

Gram-positive bacteria and many species of fungi.

What are four chemical synonyms for gentian violet?

Hexamethyl-p-rosaniline chloride, crystal violet, methyl violet, and methyl-rosaniline chloride.

What are the physical appearance and metallic luster of gentian violet?

A green powder or green flakes with a metallic sheen.

What are three dosage forms and respective indications for gentian violet?

Vaginal suppositories for yeast infections, $1\% - 3\%$ topical solutions for ringworm and yeast, and oral formulations as an anthelmintic.

Which two parasitic infections are treated with oral gentian violet?

Strongyloidiasis and Oxyuriasis (pinworm infection).

What is the dye component of Castellani's paint (carbol-fuchsin solution)?

Basic fuchsin.

What are the primary dermatologic indications for basic fuchsin / Castellani's paint?

Ringworm and athlete's foot.