NAPLEX: Alkanes, Alcohols, Phenols

Which of the following functional groups most increases a drug water’s solubility?

A. Alkane

B. Ether

C. Alcohol

D. Arene

C. Alcohol

Hydroxyl groups form hydrogen bonds with water, increasing solubility.

Drugs composed primarily of alkanes are described as:

A. Hydrophilic and rapidly excreted

B. Lipophilic and chemically stable

C. Highly polar and ionizable

D. Easily metabolized by CYP450 enzymes.

B. Lipophilic and chemically stable

Alkanes lack polar groups and undergo minimal metabolism, resulting in a long duration (“hard drugs”)

Carbamazepine undergoes which metabolic transformation?

A. O-dealkylation

B. Epoxidation of an olefinic bond

C. Hydrolysis of an ester bond

D. N-dealkylation

B. Epoxidation of an olefinic bond

CYP450 oxidizes the double bond to form an epoxide intermediate

Which metabolic pathway is primarily associated with aromatic hydrocarbons such as benzene derivatives?

A. p-Hydroxylation via CYP450

B. N-oxidation via flavin monooxygenase

C. Hydrolysis by esterases

D. Reduction by aldehyde reductase.

A. p-Hydroxylation via CYP450

Aromatic rings are metabolized mainly by para-hydroxylation to form phenolic derivatives.

Which halogenated anesthetic has the highest risk of hepatotoxicity due to free radical formation?

A. Desflurane

B. Isoflurane

C. Halothane

D. Sevoflurane

C. Halothane

Halothane metabolism forms reactive intermediates that can induce immune-mediated hepatic necrosis

Which alcohol type is most resistant to oxidation by alcohol dehydrogenase?

A. Primary alcohol

B. Secondary alcohol

C. Tertiary alcohol

D. Phenol

C. Tertiary alcohol

Tertiary alcohols lack a hydrogen on the carbon bearing the hydroxyl group, preventing oxidation

Phenols differ from alcohols mainly in that phenols?

A. Are neutral and non-ionizable

B. Undergo salt formation with weak bases

C. Are weakly acidic and can form salts with strong bases

D. Cannot undergo oxidation

C. Are weakly acidic and can form salts with strong bases

The phenolic –OH group’s acidity allows it to ionize in the presence of strong bases.

What is the main chemical instability concern for ethers in pharmaceutical formulations?

A. Hydrolysis

B. Peroxide formation

C. Esterification

D. Oxidative deamination

B. Peroxide formation

Ethers can auto-oxidize in air to explosive peroxides; antioxidants or metal inhibitors are added to prevent this.

Which of the following best describes a soft drug?

A. Chemically stable with long half-life

B. Resistant to metabolic degradation

C. Designed to undergo rapid inactivation after therapeutic action

D. Highly lipophilic with poor solubility

C. Designed to undergo rapid inactivation after therapeutic action

Soft drugs (e.g., succinylcholine) are metabolically labile, minimizing systemic toxicity.

Which of the following forces primarily stabilize alkane drug molecules?

A. Hydrogen bonding

B. Ionic bonding

C. Van der Waals forces

D. Dipole–dipole interactions

C. Van der Waals forces

Alkanes are nonpolar; their only intermolecular interaction is through weak London dispersion forces.

Ethanol is used as an antidote for methanol poisoning because:

A. It increases renal excretion of methanol

B. It competes for the same enzyme, preventing toxic metabolite formation

C. It enhances hepatic oxidation of methanol

D. It neutralizes formic acid directly

B. It competes for the same enzyme, preventing toxic metabolite formation

Explanation: Ethanol competes with methanol for alcohol dehydrogenase, preventing conversion to toxic formaldehyde and formic acid

Phenolic drugs should be stored in:

A. Clear containers at the room light

B. Amber containers under a nitrogen atmosphere

C. Open containers at low humidity

D. Alkaline solution without antioxidants

B. Amber containers under a nitrogen atmosphere

Phenols oxidize easily in air and light; protection from oxygen and light prevents quinone formation.

The main difference between phenols and alcohols is:

A. Phenols are stronger acids due to resonance stabilization of the phenoxide ion

B. Alcohols have higher acidity than phenols

C. Phenols cannot form salts with strong bases

D. Alcohols are more reactive toward electrophiles

A. Phenols are stronger acids due to resonance stabilization of the phenoxide ion

Which enzyme primarily catalyzes the metabolic O-dealkylation of ethers?

A. Monoamine oxidase

B. Cytochrome P450

C. Alcohol dehydrogenase

D. Esterase

B. Cytochrome P450

Alkanes exhibit which of the following physical properties?

A. High water solubility

B. High melting points due to hydrogen bonding

C. Non-polar and highly lipophilic nature

D. Strong dipole–dipole attraction

C. Non-polar and highly lipophilic nature

Which phase I metabolic reaction increases water solubility of aromatic compounds like benzene derivatives?

A. N-dealkylation

B. Hydrolysis

C. Aromatic hydroxylation

D. Esterification

C. Aromatic hydroxylation

Which of the following is considered a “hard drug”?

A. Succinylcholine

B. Decamethonium

C. Remifentanil

D. Propofol

B. Decamethonium

Hard drugs are chemically and metabolically stable, leading to prolonged activity and slower elimination

Which of the following characteristics best defines soft drugs?

A. Designed to resist metabolism

B. Chemically inert

C. Contain ester linkages for rapid hydrolysis

D. Poorly absorbed through biological membranes

C. Contain ester linkages for rapid hydrolysis

Example: Succinylcholine is rapidly hydrolyzed to inactive metabolites within minutes.

Which functional group is least capable of hydrogen bonding with water?

A. Alcohol

B. Carboxylic acid

C. Alkane

D. Amine

C. Alkane

The primary force responsible for alkane binding to receptor hydrophobic pockets is:

A. Hydrogen bonding

B. Ionic attraction

C. Van der Waals interactions

D. Covalent bonding

C. Van der Waals interactions

Formation of arene oxide intermediates during aromatic oxidation can cause:

A. Enhanced renal clearance

B. Toxicity via covalent binding to macromolecules

C. Increased drug potency

D. Decreased hepatic metabolism

B. Toxicity via covalent binding to macromolecules

As the hydrocarbon chain length of an alcohol increases:

A. Solubility in water increases

B. Solubility in lipids decreases

C. Solubility in water decreases

D. Melting point decreases

C. Solubility in water decreases

Metabolism of halogenated hydrocarbons such as halothane primarily involves:

A. Reduction by aldehyde reductase

B. Oxidative dehalogenation via CYP450

C. Ester hydrolysis

D. Sulfation

B. Oxidative dehalogenation via CYP450

Which oxidation product of phenol is typically colored and unstable?

A. Quinone

B. Aldehyde

C. Ether

D. Hydroquinone

A. Quinone

A salt form of a phenolic drug precipitates when pH changes. This occurs because:

A. pH change increases solubility

B. Phenolic ionization reverses, regenerating the free phenol

C. Quinone forms immediately

D. Water content increases polarity

B. Phenolic ionization reverses, regenerating the free phenol