CNS, neoplastic

Increase the FREQUENCY of GABA-mediated chloride ion channel opening

What is the MOA of benzodiazepines

Triazolobenzodiazepines

Benzodiazepines fused with a triazolo ring, examples include Triazolam and Alprazolam.

Imidazobenzodiazepines

Benzodiazepines fused with an imidazole ring, example includes Midazolam.

Barbiturates

Extensively used as sedative hypnotics, they increase the duration of GABA-mediated chloride ion channel opening.

At 5

+alkyl/aryl groups confer activity in Barbiturates.

At 2

If S replaces O, it leads to Thiobarbiturates, which are more lipid-soluble.

Short acting

Characteristic of both Triazolobenzodiazepines and Imidazobenzodiazepines.

Phenothiazines

A class of antipsychotics divided into categories such as Aliphatic, Piperidine, Piperazine, and Butyrophenone.

Aliphatic

A subtype of Phenothiazines including Chlorpromazine, Promazine, and Trifluoperazine.

Piperidine

A subtype of Phenothiazines including Thioridazine, Mesoridazine, and Piperacetazine.

Piperazine

A subtype of Phenothiazines including Fluphenazine, Perphenazine, and Trifluoperazine.

Butyrophenone

A class of antipsychotics including Haloperidol and Droperidol.

Thioxanthene

A class of antipsychotics including Thiothixene, Chlorprothixene, and Flupenthixol.

Butyrophenones > Piperazine > Piperidine ≥ Thioxanthenes >>> Aliphatic.

Potency ranking of typical anti-psychotics

Atypical Antipsychotics

A class of antipsychotic drugs that includes Dibenzodiazepines, Dibenzothiazepines, Benzoxazole, Thienobenzodiazepines, Dihydroindolone, and Benzamide.

Phenothiazines

A class of antipsychotics characterized by a 6-6-6 system with linkages between benzene rings via sulfur and nitrogen.

SAR for Phenothiazines

Key structural characteristics include: 6-6-6 system, two benzenes linked by sulfur and nitrogen, EWG substituent at position 2, amino nitrogen must be separated from the substituent by a 3-carbon chain.

Promethazine

An example of a phenothiazine showing antihistaminic and anticholinergic effects.

Butyrophenones

A class of antipsychotics with a distinct structure that includes a tertiary amino group essential for neuroleptic activity.

Activity of Butyrophenones

Highest activity is observed if the cyclic form p-fluoro aids in potency, with modification to the 3-carbon propyl chain decreasing neuroleptic activity.

Insulin Lispro (Humalog)

Lysine and Proline exchanged at positions B28 and B29 stabilized by cresol preservative into hexamers.

Insulin Aspart (Novolog)

Formed by replacement of Proline at B28 with Aspartic acid.

Insulin Glulisine (Apidra)

Glutamic acid replaces lysine at B29 and lysine replaces asparagine at B3.

Regular Insulin

Soluble crystalline Zn insulin, administered only IV.

Neutral Protamine Hagedorn/ NPH/ Isophane Insulin

Suspension of insulin in a complex with Zn and protamine in PO4- buffer.

Insulin Glargine (Lantus)

Asparagine at A21 is replaced with Glycine.

Insulin Detemir (Levemir)

Terminal threonine is dropped and myristic acid is attached to the B29 lysine.

Insulin Degludec (Tresiba)

Threonine at B30 is removed and the lysine at B29 is conjugated to hexadecanoic acid.

Insulin Zn suspension

An insulin formulation that maintains stability in suspension.

Mixture of crystallized and amorphous form of insulin in acetate buffer

A formulation that includes both crystallized and non-crystallized insulin for better absorption.

prevent, inhibit or halt the development of a neoplasm or tumor.

What is the purpose of antineoplastic agents?

collection of abnormally proliferating cells.

What is a tumor/neoplasm?

does not invade surrounding tissues.

What characterizes a benign neoplasm?

invade and metastasize to all parts of the body.

What characterizes a malignant neoplasm?

the cell is not committed to division.

What is the G0 phase of the cell cycle?

RNA and proteins are synthesized; cells grow larger.

What occurs in the G1 phase of the cell cycle?

DNA synthesis and replication occurs.

What occurs in the S phase of the cell cycle?

DNA synthesis ceases; RNA and other enzymes are produced to prepare for cell duplication.

What happens in the G2 phase of the cell cycle?

the cell divides into 2 daughter cells.

What happens during the M phase or mitosis?

are not dependent on the cell being in a particular phase of the cell cycle for them to work; they affect cells in all phases of the cell cycle.

What are cell cycle non-specific agents?

act on the cells in a specific phase.

What are cell cycle specific agents?

Vinca alkaloids, Asparaginase, Prednisone, Antimetabolites.

Examples of cell cycle specific agents?

alkylation of reactive species on DNA

What is the MOA of alkylating agents?

Nitrogen mustards

A subtype of alkylating agents that include Mechlorethamine, Melphalan, Chlorambucil, Bendamustine, Ifosfamide, and Cyclophosphamide.

Cyclophosphamide/Ifosfamide

Alkylating agents associated with hemorrhagic cystitis due to the toxic metabolite Acrolein.

AD: MESNA

What is administered as a protective agent against hemorrhagic cystitis caused by Cyclophosphamide/Ifosfamide?

Thiote pa and Altretamine.

What are Ethyleneimine and Methylmelamines?

Busulfan.

What is the Alkyl sulfonate drug?

Carmustine and Streptozocin.

What are the Nitrosoureas?

Dacarbazine and Temozolomide.

What are the Triazene drugs?

Procarbazine.

What does Methylhydrazine refer to?

Cisplatin, Carboplatin, and Oxaliplatin.

What are the Platinum coordination complexes?

It is associated with nephro- and ototoxicity.

What is notable about Cisplatin?

Anthracyclines and Anthracenedione.

What are the Antibiotics mentioned?

Doxorubicin, Daunorubicin, Epirubicin, and Idarubicin.

What are the Anthracyclines?

Mitoxantrone.

What is the Anthracenedione drug?

It inhibits topoisomerase II and intercalates DNA.

What is the MOA of Anthracenedione?

Cardiotoxicity.

What is a side effect of Anthracyclines?

Dexrazoxane.

What is administered as an antidote for Cardiotoxicity?

Dactinomycin/Actinomycin D and Plicamycin.

What other antibiotics are mentioned?

Intercalates between GC base pairs of DNAs.

What is the MOA of Dactinomycin?

From Streptomyces spp.

What is Mitomycin C?

E. coli.

What is the source of L-asparaginase?

Hydrolyzes asparagine to aspartic acid and ammonia, thus depriving the tumor cells of asparagine, which is needed for protein synthesis.

What is the MOA of L-asparaginase?

Corticosteroid.

What type of agent is Prednisone?

Ribo-nucleotide reductase (RNR) - conversion of ribo- to deoxyribonucleotides.

What does Hydroxyurea inhibit?

Inhibit enzymes necessary for nucleic acid, DNA or RNA synthesis.

What is the MOA of antimetabolites?

Methotrexate and Pemetrexed.

What are the two Folic acid analogues mentioned?

Myelosuppression.

What is the toxicity associated with Methotrexate?

5-Fluorouracil, Capecitabine, Cytarabine, Gemcitabine, and 5-Azacytidine.

What are the two drugs associated with pyrimidine analogues?

6-mercaptopurine, Fludarabine, Cladribine, Pentostatin.

What is the purine analogue mentioned?

Inhibit Topoisomerase I.

What is the MOA of Camptothecin derivatives?

Topotecan, Irinotecan.

What drugs are included under Camptothecin derivatives?

Cholinergic diarrhea (managed with Atropine or Loperamide).

What side effect is associated with Irinotecan?

S. verticillus.

What is the source of Bleomycin?

Binds to DNA, generates free radicals.

What is the MOA of Bleomycin?

Pulmonary toxicity (pulmonary fibrosis).

What is a toxicity associated with Bleomycin?

Semisynthetic derivatives of podophyllotoxin, isolated from mayapple root.

What are Epipodophyllotoxins?

Inhibits Topoisomerase II.

What is the MOA of Epipodophyllotoxins?

Etoposide, Teniposide.

Which drugs are classified as Epipodophyllotoxins?

Isolated from the bark of the pacific yew tree (Taxus brevifolia).

What are Taxanes?

Stabilize microtubules, inhibit depolymerization.

What is the MOA of Taxanes?

Paclitaxel, Docetaxel.

Which drugs are classified as Taxanes?

Catharanthus roseus leaves.

What is the source of Vinca alkaloids?

Inhibit tubulin polymerization and microtubule formation.

What is the MOA of Vinca alkaloids?

Vincristine, Vinblastine, Vinorelbine.

Which drugs are classified as Vinca alkaloids?

Glucocorticoid receptor agonist.

What type of agent is Prednisone?

Selective Estrogen Receptor Modulator.

What is Tamoxifen classified as?

For premenopausal patients with HR (+) breast cancer.

What is the indication for Tamoxifen?

Selective Estrogen Receptor Down regulator.

What is Fulvestrant classified as?

Aromatase inhibitors.

What are Anastrozole, Letrozole, and Exemestane categorized as?

Inhibit growth factor receptors and inhibit cell growth.

What do Monoclonal antibodies do?

Trastuzumab (HER-2/neu inhibitor), Bevacizumab (VEGF inhibitor).

What are example drugs of Monoclonal antibodies?

Inhibit tyrosine kinases and prevent phosphorylation of substrate.

What do Tyrosine kinase inhibitors do?

Erlotinib (EGFR inhibitor), Imatinib (BCR-ABL kinase inhibitor).

What are example drugs of Tyrosine kinase inhibitors?