B5

What is the classification of GABA (Gamma Amino Butyric acid) in the brain?

Major inhibitory neurotransmitter in the brain.

What is the name of the enzyme that degrades GABA?,"

Pyridoxal-dependent enzyme, GABA transaminase (GABA-T)."

What product is GABA degraded into?,

Succinic acid semi-aldehyde.

What is the general mechanism of action for GABA agonists?,

Enhance GABA neurotransmission.

Name a drug that enhances GABA biosynthesis.,

Gabapentin or Pregabalin.

What is the mechanism of action of Vigabatrin?,

Inhibits GABA-T.

What is the mechanism of action of Tiagabine?,

Blocks GABA uptake.

Benzodiazepines are classified as what type of GABA agonist?,

GABA Receptor Modulators.

What is the specific mechanism of action of Benzodiazepines on the Cl− channel?,

Increase the frequency of Cl− channel opening.

What is the specific mechanism of action of Barbiturates on the Cl− channel?,

Increase the duration of Cl− channel opening.
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Besides increasing Cl− channel duration, what is another effect of Barbiturates?",

Barbiduration (Potentiation of GABA-A receptor action) and direct Cl− channel opening at high concentrations.

Name three examples of Benzodiazepines.,"

Chlordiazepoxide, Alprazolam, or Diazepam."

What is a potential problem with long-term use of Benzodiazepines?,

May lead to developing dependence and serious sleep problems.

What is the antidote for Benzodiazepine toxicity?,

Flumazenil.

Name two examples of long-acting Barbiturates.,

Phenobarbital or Mephobarbital.

Name two examples of intermediate-acting Barbiturates.,"

Butabarbital or Vinbarbital, or Amobarbital, or Secobarbital."

Name one example of a short-acting Barbiturate.,

Pentobarbital or Hexobarbital.

Name two examples of ultra-short-acting Barbiturates.,

Thiopental or Thiamylal.

What property is associated with greater hypnotic potency and a more rapid onset but a shorter duration of action in barbiturates?,

Increased lipid solubility.

What is Dextran used as?,

A polysaccharide used as a plasma expander.

Name four opiates/opioid analgesics derived from Opium extract.,"

Morphine, Codeine, Thebaine, Papaverine, or Noscapine."

What is the principal site of drug biotransformation?,

Liver (Enzymes).

What is the goal of drug metabolism?,

To make drugs more polar.

What are the characteristics of a drug before metabolism (LUNA)?,"

Lipophilic, Unionized, Nonpolar, Absorbed (small intestine and large surface area)."

What are the characteristics of a metabolite after metabolism (WIPE)?,"

Water Soluble, Ionized, Polar, Excreted (Kidney)."

What is a drug that is an exception to the goal of drug metabolism (making it more polar)?,

Prodrugs.

What is another term for the first-pass effect?,

Presystemic metabolism.

What effect does extensive first-pass metabolism have on oral bioavailability?,

Decrease oral bioavailability.

Name two drugs that undergo extensive first-pass effect.,"

Isoproterenol, Propanolol, Pentazocine, Propoxyphene, Meperidine, Morphine, Nitroglycerine, Salicylamide, or Lidocaine."

What are the two phases of drug metabolism?,

Phase I (Functionalization/Asynthetic) and Phase II (Conjugation/Synthetic).

What is the goal of Phase I drug metabolism?,"

Introduce small, polar functional groups (-OH, -COOH, -NH2​, -SH)."

What is the goal of Phase II drug metabolism?,

Introduce complex groups (conjugate) → more polar drug.

Name three examples of Phase I metabolism reactions.,"

Hydrolysis, Oxidation, or Reduction."

Name three examples of Phase II metabolism reactions.,"

Glucuronidation, Glutathione conjugation, Acetylation, Amino acid conjugation, Sulfation, or Methylation."

What is the most common metabolic pathway in Phase I?,

Oxidation.

What is the description/enzyme for Oxidation in Phase I?,

Oxidases → CYP450/Mixed Function Oxidase (MFO).

Give a CYP-mediated oxidation example.,

Paracetamol → NAPQI.

Give a non-CYP mediated oxidation example.,

Ethanol → Acetaldehyde → Acetic acid.

What CYP isoform is associated with metabolism in pediatrics?,

CYP3A7.

What CYP isoform is associated with metabolism in adults?,

CYP3A4.

What is the description/enzyme for Reduction in Phase I?,

Reductase.

Give two examples of functional groups that undergo reduction.,

Aldehydes → Primary alcohol or Ketones → Secondary alcohol or Azo (A2G) & Nitro → Amines.

Give an example of a drug that undergoes reduction.,

Chloral hydrate → Trichloroethanol or Prednisone → Prednisolone.

What is the description/enzyme for Hydrolysis in Phase I?,

Hydrolase.

Give two examples of functional groups that undergo hydrolysis.,

Esters → Carboxylic acid & Alcohol or Amides → Carboxylic acid & Amine.

Give an example of a drug that undergoes hydrolysis.,

Aspirin → Salicylic acid & Acetic acid or Chloramphenicol palmitate → Chloramphenicol & Palmitic acid.

What is the Mechanism of Action (MOA) of Anthracyclines and other Antitumor Antibiotics listed?,

DNA Intercalation.
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What is the source of Anthracyclines (Daunorubicin, Doxorubicin)?",

Streptomyces peucetius.
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What is the major Adverse Drug Reaction (ADR) of Anthracyclines (Daunorubicin, Doxorubicin)?",

Cardiotoxicity.

What drug is used to rescue/treat Anthracycline cardiotoxicity?,

Dexrazoxane.

What is the source of Bleomycin?,

Streptomyces verticillus.

What is the major ADR of Bleomycin?,

Pulmonary fibrosis.

What is the source of Plicamycin?,

Streptomyces plicatus.

What is the source of Dactinomycin?,

Streptomyces parvulus.

What is the MOA of Camptothecins?,

Inhibits Topoisomerase I.

What is the source of Camptothecins?,

Happy tree (Camptotheca acuminata).

Give an example of a Camptothecin.,

Irinotecan (first-line treatment for metastatic colon cancer) or Topotecan (treatment of small cell lung cancer).

What is the MOA of Podophyllotoxins?,

Inhibits Topoisomerase II.

What is the source of Podophyllotoxins?,

Mayapple (mandrake) (Podophyllum peltatum).

Give an example of a Podophyllotoxin.,

Etoposide or Teniposide.

What is the MOA of Vinca Alkaloids?,

Inhibits mitotic spindle formation/assembly.

What is the source of Vinca Alkaloids?,

Periwinkle or Chichirica (Catharanthus roseus).

Give an example of a Vinca Alkaloid.,

Vincristine or Vinblastine (treatment for Hodgkin's lymphoma).

What is the MOA of Taxanes?,

Promotes stabilization of microtubule / Inhibits disassembly.

What is the source of Taxanes?,

Pacific Yew Tree (Taxus brevifolia).

Give an example of a Taxane.,"

Paclitaxel, Docetaxel, or Cabazitaxel."

What is the MOA of the Folate Analogue Methotrexate?,

Inhibits Dihydrofolate Reductase.

What is the primary use of Methotrexate (besides as a conventional cytotoxic agent)?,

First line DMARD (Disease-Modifying Anti-Rheumatic Drug) for rheumatoid arthritis.

What is the major ADR of Methotrexate?,

Bone Suppression.
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What drug is used as a ""rescue"" for Methotrexate-induced toxicity?",

Leucovorin or Folinic Acid.

Name three examples of Purine Analogues.,"

6-Mercaptopurine, 6-Thioguanine, Fludarabine, Cladribine, or Azathioprine."

Name three examples of Pyrimidine Analogues.,"

5-Fluorouracil, Cytarabine, Capecitabine, or Gemcitabine."

What is the MOA of Hydroxyurea?,

Inhibits Ribonucleotide diphosphate reductase.

What is Hydroxyurea used to treat?,

Myelogenous leukemia and Thrombocytosis.

Name the class of Antiestrogen agents that Tamoxifen and Clomiphene belong to.,

Selective Estrogen Receptor Modulators (SERMs).

What is Tamoxifen the Drug of Choice (DOC) for?,

Breast cancer.

What is the major ADR of Tamoxifen?,

Endometrial Cancer.

What is used for the treatment of Tamoxifen-induced ADR?,

Medroxyprogesterone acetate (Depo-ProveraR◯).

What is Clomiphene used as?,

A Fertility Drug.

What is a major ADR of Clomiphene?,

Multiple Births.

Name an example of an Aromatase Inhibitor.,

Anastrozole.

What is the function of Aromatase Inhibitors?,

Block the conversion of Testosterone → Estrogen.

Name an example of an Antiandrogen.,

Flutamide or Finasteride.

What is Flutamide the DOC for?,

Prostate Cancer.

What is the MOA of Finasteride?,

5−α-reductase inhibitor.

What is Finasteride the DOC for?,

BPH (Benign Prostatic Hyperplasia).

What is a major ADR of Finasteride?,

Hypertrichosis.

What are the two major classes of sympathomimetic agents shown?,

Phenylethanolamines (α-Adrenergic Receptor Agonists) and 2-Arylimidazolines.

What is the primary action of the α1-Selective Adrenergic Agonists?,

Stimulation of vascular smooth muscle → Vasoconstriction.

What is the main clinical use of α1-Selective Adrenergic Agonists?,

Maintenance of blood pressure in hypotension or shock.

Name two examples of α1-Selective Adrenergic Agonists that are Phenylethanolamines.,"

Phenylephrine, Methoxamine, or Metaraminol."

Name two examples of 2-Arylimidazolines.,"

Naphazoline (NZ), Tetrahydrozoline (TZ), Oxymetazoline (OZ), or Xylometazoline (XZ)."

Name three examples of Angiotensin-Converting Enzyme (ACE) Inhibitors.,"

Enalapril, Captopril, or Lisinopril (generally end in -pril)."

Name four potential Adverse Effects (AEs) of ACE Inhibitors.,"

Hyperkalemia (↑K+), Hypokalemia, Agranulocytosis or neutropenia (↓WBC), Angioedema, or Dry cough."

Name three examples of Angiotensin II Receptor Blockers (ARBs).,"

Losartan, Irbesartan, or Candesartan (generally end in -sartan)."

What structural feature renders acidity to the ARBs?,

Tetrazole ring.

Which ARB has the highest bioavailability (60-80%)?,

Irbesartan.

Which ARB has the lowest bioavailability (15%)?,

Candesartan.

Name the three classes of Monoamine Oxidase Inhibitors (MAOIs) listed.,"

Nonselective MAO Inhibitors, Selective MAO-A Inhibitor, and Selective MAO-B Inhibitor."

Name two examples of Nonselective MAO Inhibitors.,"

Phenelzine, Tranylcypromine, or Isocarboxazid."