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ChatBOT: Hello, I am a multilingual document assistant here to help you with any questions you
may have regarding the document you have uploaded.

The document you have uploaded covers the topic of antihistamines, specifically focusing
on histamine, its receptors, and their distribution in the human body. It discusses how
histamine is an amine derivative autacoid found in various tissues, its role in immune
responses, and its regulation of physiological functions. Additionally, the document
mentions the classification of histamine receptors into H1, H2, and H3 receptors, and
how different drugs act as antagonists.

Possible questions you can ask me about the document:

1. What are the different types of histamine receptors mentioned in the document?
2. How do antihistamines work as antagonists to histamine receptors?
3. Can you explain the role of histamine in immune responses and regulating physiolog-
ical functions?

Please feel free to ask me a question about the document!

User: 1. Write a note on proton pump inhibitors.

ChatBOT: # Proton Pump Inhibitors: Overview and Details

Proton pump inhibitors (PPIs) are a class of drugs used in the treatment of gastric ulcers
by reducing gastric acid secretion. Here is an overview of PPIs based on the extracted
information:

## Mechanism of Action
- PPIs bind to the H+K+-ATPase enzyme (proton pump) of the parietal cell, suppressing
the secretion of hydrogen ions into the gastric lumen.

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- This action inhibits the final step in the secretion of gastric acid, leading to decreased
acidity in the stomach.

## Drugs in the PPI Class

- **Omeprazole:**
- Chemical structure: 6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl
sulfinyl]-1H-benzimidazole.
- **Lansoprazole:**
- Chemical structure: 2-[[3-methyl-4-(2,2,2-trifluoro ethoxy)pyridin-2-yl]methyl
sulfinyl]-1H-benzimidazole.
- **Rabeprazole:**
- Chemical structure: 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl] methyl
sulfinyl]-1H-benzimidazole.
- **Pantoprazole:**
- Chemical structure: 6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methyl
sulfinyl]-1H-benzimidazole.

## Uses of Proton Pump Inhibitors

- Treatment of gastric ulcers.
- Zollinger-Ellison Syndrome (tumors in the stomach causing ulcers).
- Gastroesophageal reflux diseases (GERD).

## Side Effects and Other Details

- PPIs are benzimidazole derivatives.
- Common side effects include hypotension, dizziness, headache, diarrhea, and consti-
pation.
- PPIs are fully reversible competitive antagonists of histamine.
- They can completely inhibit gastric acid secretion induced by histamine or gastrin.

## SOURCES
- Page 18: Details on the drugs used for the treatment of gastric ulcers.
- Page 20: Information on the mechanism of action and uses of gastric proton pump
inhibitors.
- Page 21: Overview of the mechanism of action and uses of proton pump inhibitors in
the treatment of ulcers.

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User: 2. What are anti-histaminic? How they act? Classify them with examples.

ChatBOT: ## What are antihistamines and how do they act?

Antihistamines are drugs that diminish or antagonize the actions of histamine in the body.
They act as antagonists of the H1 receptor and are used for treating allergies and pruritus.
Antagonists of the H2 receptor are used to inhibit gastric acid secretion. Antihistamines
do not prevent the formation of histamine but counteract its effects.

## Classification of antihistamines with examples

### 1. Aminoalkyl ethers

- **Diphenhydramine Hydrochloride**: Peripheral and central H1 antagonist with seda-
tive effects. Used for allergies, insomnia, motion sickness, and Parkinsonism.

### 2. Cinnarizine
- **Properties**: Anti-Histamines, AntiAch, Antivertigo

### 3. Chlorpheniramine
- **Types**: Chlorpheniramine, Pheniramine
- **Structure**: (±) 2-[1-(p-chlorophenyl)-3-dimethylamino) propyl)]-pyridine
- **Uses**: Treatment of allergy, hay fever, and cold.

### 4. Diphenyl pyraline hydrochloride

- **MOA**: H1 antagonist with anticholinergic activity.
- **Uses**: Treatment of allergy, hay fever, rhinitis, and as an ingredient in cough
preparations.

### 5. Tripelenamine hydrochloride

- **MOA**: H1 antagonist with anticholinergic activity and weak effects on serotonin,
noradrenaline, and dopamine reuptake.
- **Uses**: Treatment of upper respiratory tract allergies, expectorants, decongestants,
and Parkinson's disease.

### 6. Mepyramine Maleate

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- **Structure**: 2-[[(2-(Dimethylamino) ethyl] (p-methoxybenzyl) amino] pyridine

maleate (1:1)

### 7. Chlorcyclizine hydrochloride

- **Use**: Treatment of allergy, hay fever, and cold.

### 8. Meclizine hydrochloride

- **Use**: Treatment of allergy, hay fever, and cold.

### 9. Buclizine hydrochloride

- **Use**: Treatment of allergy, hay fever, and cold.

### 10. Levocetirizine

- **Use**: Non-sedative antihistamine for relieving allergy symptoms.

## SOURCES
- Page 4: Information on antihistamines and their classification.
- Page 8: Details on specific antihistamines such as Diphenhydramine Hydrochloride.
- Page 12: Examples of antihistamines like Cinnarizine, Cetirizine, and Chlorpheni-
ramine.
- Page 10: Information on Diphenyl pyraline hydrochloride and Tripelenamine hy-
drochloride.

User: 3. Write a note on HMG Co-A reductase inhibitors.

ChatBOT: ## HMG Co-A Reductase Inhibitors

### Mechanism of Action:

- HMG Co-A reductase inhibitors target the enzyme HMG Co-A reductase, which plays
a key role in cholesterol synthesis in the liver.
- By inhibiting this enzyme, these drugs reduce the production of cholesterol and promote
the clearance of LDL cholesterol from the bloodstream.

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### Uses:
- Primarily used in the treatment of hypercholesterolemia to lower cholesterol levels.
- Help prevent cardiovascular events such as heart attacks and strokes by reducing LDL
cholesterol levels.

### Examples of HMG Co-A Reductase Inhibitors:

1. Simvastatin
2. Atorvastatin
3. Rosuvastatin
4. Pravastatin

### Side Effects:

- Common side effects may include muscle pain, liver enzyme abnormalities, and gas-
trointestinal symptoms.
- Rare but severe side effects include rhabdomyolysis (muscle breakdown) and liver
toxicity.

### Benefits:
- Effective in reducing LDL cholesterol levels and lowering the risk of cardiovascular
diseases.
- Have been shown to improve outcomes in patients with a history of heart disease or
stroke.

### Precautions:
- Should be used cautiously in patients with liver disease or a history of muscle disorders.
- Monitoring liver enzymes and muscle symptoms is recommended during treatment.

### Interactions:
- HMG Co-A reductase inhibitors can interact with other medications, particularly those
metabolized by the same liver enzymes.
- Grapefruit juice can also interact with these drugs and increase the risk of side effects.

### Dosage and Administration:

- Dosage varies depending on the specific drug and the patient's cholesterol levels.
- Typically taken orally, often in the evening to coincide with the body's natural choles-
terol production cycle.

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### Duration of Treatment:

- Treatment with HMG Co-A reductase inhibitors is often long-term, especially for
individuals with chronic conditions like hypercholesterolemia.

### Monitoring:
- Periodic monitoring of cholesterol levels, liver function tests, and muscle symptoms is
essential during treatment.

### Combination Therapy:

- HMG Co-A reductase inhibitors are sometimes prescribed in combination with other
cholesterol-lowering medications for enhanced efficacy.

### Adverse Reactions:

- While generally well-tolerated, adverse reactions can occur, and patients should
promptly report any concerning symptoms to their healthcare provider.

### SOURCES
- Page 21: Information on HMG Co-A reductase inhibitors.
- Page 4: Classification of Histamine Receptors mentioning H2 receptor related to gastric
acid secretions.

User: 4.Write a note on H2-antagonists.

ChatBOT: ## H2-ANTAGONISTS: A COMPREHENSIVE OVERVIEW

### Definition and Classification

- **H2-Antagonists** act on H2 receptors primarily in the stomach to inhibit gastric acid
secretion.
- They are used in the treatment of peptic ulcers by diminishing histamine-induced acid
production.
- Common H2-Antagonists include **Cimetidine, Famotidine, Piratidine, and Raniti-
dine**.

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### Mechanism of Action

- **Competitive antagonists** of histamine that are **fully reversible**.
- They **completely inhibit gastric acid secretion** induced by histamine or gastrin.

### Side Effects and Specifics

- Common side effects may include **hypotension, dizziness, headache, diarrhea, and
constipation**.
- H2-Antagonists are **highly hydrophilic** and do not cross the blood-brain barrier,
thus **do not produce sedative effects**.
- **Cimetidine** is less commonly used due to **antiandrogenic side effects**.

### Structure-Activity Relationship (SAR)

- **General structure** of H2 antagonists typically includes an **imidazole ring**
capable of **1,3-prototropic tautomerism**.
- The **NtH tautomer** is crucial for maximal H2 antagonistic activity.
- **R-group characteristics**, such as electron-donating groups like **-CH3**, influ-
ence tautomer preference and activity.

### Notable H2-Antagonists and Their Structures

1. **Cimetidine**
- Structure: *2-cyano-l-methyl-3-[2-(5-methyl imidazol-4-yl-methylthio) ethyl] guani-
dine*
- MOA: H2 Receptor Blocker, Used in gastric and duodenal ulcers.

2. **Roxatidine**
- Structure: *N-(3[3-(1-piperidinylmethyl)-phenoxy]-propyl) acetoxyacetamide*

3. **Nizatidine**
- Structure: *N-[2-[[[2-[(dimethylamino) methyl]-4-thiazolyl] methyl] thio]eth-
yl]-N’-methyl-2-nitro-l, l, ethenediamine*

### SAR Insights and Variants

- **Imidazole nucleus** not mandatory for H2 antagonist activity; compounds with
**furan or thiazole rings** can be more potent.
- **Optimal activity** requires a specific distance of the ring from the N-group in the
side chain.

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### Additional Notes

- **H2-Antagonists** are crucial for treating conditions related to **gastric acid over-
production**.
- **Understanding the SAR** of these antagonists aids in designing more **potent and
effective** drugs for related conditions.

### SOURCES
- Page 4: Details on H2-Antagonists, Mechanism, and Classification.
- Page 19: SAR of H2 Receptor Antagonists and Structural Insights.

User: 5. Enlist various histamine receptors.

ChatBOT: # Histamine Receptors

Histamine receptors play crucial roles in various physiological and pharmacological

functions in the human body. Below are the enlisted histamine receptors along with their
functions and locations:

### Enlisted Histamine Receptors:

1. **H1 Receptor (H1R):**
- Pathways: GqPCR activating IP3/DAG pathway.
- Locations: Smooth muscles in the intestine, bronchi, uterus, blood vessels, brain,
ganglia, and adrenal medulla.
- Agonists: 2-methyl histamine, 2-pyridylethylamine.
- Antagonists: Mepyramine, Chlorpheniramine.

2. **H2 Receptor (H2R):**

- Pathways: GsPCR activating cAMP/PKA pathway.
- Locations: Stomach, uterus, heart.
- Agonists: 4-methylhistamine, Dimaprit, Impromidine.
- Antagonists: Ranitidine, Cimetidine, Famotidine.

3. **H3 Receptor (H3R):**

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- Pathways: Gi/oPCR inhibiting cAMP/PKA pathway, activating K+ channels, and

inhibiting Ca2+ channels.
- Locations: Brain.
- Agonists: (R) ±-
methyl histamine, Imetit.
- Antagonists: Thioperamide, Clobenpropit.

4. **H4 Receptor (H4R):**

- Pathways: Gq/iPCR modulating IP3/DAG and cAMP/PKA pathways.
- Locations: Brain.
- Agonists: Clobenpropit, Imetit, JNJ777120.

### Additional Information:

- **Classification of Antihistamines:**
- Antihistamines are generally antagonists of the H1 receptor.
- Used for treating allergies and pruritis.
- Antagonists of the H2 receptor are used to inhibit gastric acid secretion.
- Antagonists of the H3 receptor are not used therapeutically.

With this information, you now have a clear understanding of the various histamine
receptors and their functions in the human body.

### SOURCES:
- Page 4: Histamine receptors and their distribution in the human body.
- Page 2: Details on the classification of antihistamines.
- Page 15: Usage of histamine in allergic conditions and other derivatives.

User: 5. Enlist various histamine receptors.

ChatBOT: ## Various Histamine Receptors

### Histamine Receptors Classification:

1. **H1 R**: Inflammatory and Immune Response. Location: Smooth muscles, brain,
ganglia, adrenal medulla.

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- Agonists: 2-methyl histamine, 2-pyridylethylamine.

- Antagonists: Mepyramine, Chlorpheniramine.

2. **H2 R**: Gastric Acid Secretions. Location: Stomach, uterus, heart.

- Agonists: 4-methylhistamine, Dimaprit, Impromidine.
- Antagonists: Ranitidine, Cimetidine, Famotidine.

3. **H3 R**: Auto-receptor. Location: Brain.

- Agonist: (R) ±-
methyl histamine, Imetit.
- Antagonists: Thioperamide, Clobenpropit.

4. **H4 R**: Auto-receptor. Location: Brain.

- Agonists: Clobenpropit, Imetit, JNJ777120.

### Antihistamines:
- Used to diminish or antagonize histamine actions in the body.
- Generally antagonists of H1 receptor for allergy and pruritis treatment.
- Antagonists of H2 receptor inhibit gastric acid secretion (peptic ulcer treatment).

### H1R Antagonists:

- Diphenhydramine hydrochloride, Dimenhydrinate, Doxylamine succinate, Clemastine
fumarate, Chlorpheniramine maleate, among others.

### H2 R Antagonists:
- Cimetidine, Famotidine, Ranitidine.
- Used to treat gastric ulcer by reducing gastric acid secretion.
- Common side effects include hypotension, dizziness, headache, diarrhea, and consti-
pation. They do not produce sedative effects.

### Additional Information:

- Histamine is involved in immune responses and regulates physiological functions in the
gut, vessels, smooth muscles, and acts as a neurotransmitter.
- Histamine receptors were classified into H1 R and H2 R in 1966; H3 R was located in
the brain in 1983.

### Physiological/Pharmacological Functions:

- **By H1-Receptor**: Allergic & immunogenic reaction, smooth muscle contraction,

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bronchoconstriction.
- **By H2-Receptor**: Gastric acid secretion, cardiac output increase, relaxation of
uterus muscle.
- **By H3 Receptor**: Decrease histamine release in brain and lungs, decrease acetyl-
choline release in GI, decrease noradrenaline release.

### Biosynthesis & Metabolism:

- Histamine is biosynthesized from L-histidine by L-histidine decarboxylase and stored
in mast cells and basophils.

## SOURCES
- Page 2: Detailed information on histamine, its synthesis, and physiological functions.
- Page 4: Classification of histamine receptors, antihistamines, H1R and H2 R antago-
nists, and physiological functions.

User: 6.Discuss neurochemistry of histamine.

ChatBOT: ## Neurochemistry of Histamine

### Histamine Neurotransmitter Function:

Histamine acts as a neurotransmitter in the brain, spinal cord, and uterus, playing a role
in various physiological functions such as immune responses, regulation of gut, vessel,
and smooth muscle functions.

### Histamine Receptors:

- Histamine receptors are classified into H1, H2, H3, and H4 receptors.
- H1 Receptor: Involved in inflammatory and immune responses, smooth muscle con-
traction, and bronchoconstriction.
- H2 Receptor: Primarily associated with gastric acid secretion, cardiac effects, and
uterine muscle relaxation.
- H3 Receptor: Found in the brain and regulates histamine release and neurotransmitter
levels.
- H4 Receptor: Modulates different pathways in the brain.

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### Histamine Biosynthesis & Metabolism:

Histamine is synthesized from L-histidine by L-histidine decarboxylase and stored in
mast cells and basophils. It is involved in various physiological functions and immune
responses in the body.

### Antihistamines:
Antihistamines are drugs that counteract the effects of histamine by antagonizing H1
receptors. They are commonly used to treat allergies and pruritus.

### H2 Receptor Antagonists:

- H2 receptor antagonists act on H2 receptors in the stomach and other sites to inhibit
gastric acid secretion.
- Common side effects include hypotension, dizziness, headache, diarrhea, and consti-
pation.
- Cimetidine, Famotidine, and Ranitidine are examples of H2 receptor antagonist drugs.

### Classification of Histamine Receptors:

- H1 Receptor: GqPCR pathway activation, affecting smooth muscles, brain, ganglia, and
adrenal medulla.
- H2 Receptor: GsPCR pathway activation, influencing the stomach, uterus, and heart.
- H3 Receptor: Gi/oPCR pathway activation, mainly found in the brain.
- H4 Receptor: Gq/iPCR pathway modulation in the brain.

### Structure-Activity Relationship of H1 Blockers:

- Most H1 antagonists share a general structure involving aryl groups, basic terminal
amino alkyl groups, and specific chemical groups like aminoalkyl ethers, propylamines,
ethylenediamine, and phenothiazines.

### SAR of H2 Receptor Antagonists:

- H2 antagonists possess an imidazole ring crucial for their activity, with specific struc-
tural requirements for optimal H2 antagonistic effects.

## SOURCES
- Page 2: Information on histamine, its identification, storage, and physiological func-
tions.

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- Page 3: Details on histamine receptors, biosynthesis, metabolism, and antihistamines.

- Page 4: Classification of histamine receptors and H2 receptor antagonists.

User: 7.Classify anti neoplastic alkylating agents with relevant examples.

ChatBOT: ## Classifying Anti-Neoplastic Alkylating Agents with Examples

### Alkylating Agents Classification:

1. **Nitrogen Mustards:**
- Mechlorethamine (Mustine)
- Cyclophosphamide
- Melphalan
- Chlorambucil
- Ifosfamide

2. **Nitrosoureas:**
- Carmustine
- Lomustine

3. **Alkylsulphonates:**
- Busulfan

4. **Ethylenimines:**
- Thiotepa

### Alkylating Agents Examples:

1. Mechlorethamine (Mustine): Mechlorethamine rapidly undergoes intramolecular
transformation to the active form in aqueous solution.

2. Cyclophosphamide: Activated to give aldophosphamide, then converted to phospho-

ramide mustard (cytotoxic molecule) and acrolein.

3. Melphalan: 4-bis(2-chloroethyl) amino L-phenylalanine.

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4. Carmustine: 1, 3-bis(2-chloroethyl) 1-nitrosousea.

5. Lomustine: 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea.

6. Busulfan: Has a selective effect on the bone marrow, depressing the formation of
granulocytes and platelets.

7. Thiotepa: Tris-(1-aziridinyl) phosphine sulphide.

### Antineoplastic Agents Classification (Additional Information):

- **Antimetabolites:** Include Mercaptopurine, Thioguanine, Fluorouracil, Cytarabine,
Methotrexate, Azathioprine.
- **Antibiotics:** Dactinomycin, Daunorubicin, Doxorubicin, Bleomycin.
- **Plant Products:** Etoposide, Vinblastin sulfate, Vincristin sulfate.
- **Miscellaneous:** Cisplatin, Mitotane.

These classifications provide a structured overview of alkylating agents used in cancer

treatment, highlighting specific examples and their mechanisms of action.

### SOURCES
- Page 23: Classification of anti-neoplastic alkylating agents with examples.
- Page 24-25: Detailed overview of various antineoplastic agents and additional classifi-
cations.
- Page 26: Mechanism of action of alkylating agents in cancer treatment.

User: 8.Write a note on the natural products used as antineoplastic agents.

ChatBOT: # Natural Products Used as Antineoplastic Agents

## Plant-Derived Antineoplastic Agents:

1. **Vinca Alkaloids:** Vincristine and Vinblastine are derived from plants and used in
various cancer treatments.

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2. **Podophyllotoxin:** A natural product utilized in anticancer therapy.

3. **Etoposide:** A semisynthetic derivative of podophyllotoxin, known for its effec-
tiveness against different types of tumors.
4. **Taxol (Paclitaxel):** Isolated from the Pacific Yew tree bark, Taxol is an important
antimitotic agent.

## Antibiotics with Antineoplastic Properties:

5. **Actinomycin-D (Dactinomycin):** A natural product produced by Streptomyces
species, commonly used for treating several cancers.
6. **Doxorubicin and Daunorubicin:** Antibiotics with antitumor properties, employed
in various cancer therapies.
7. **Bleomycin:** Another antibiotic with antineoplastic effects, contributing to cancer
treatment regimens.
8. **Mithramycin and Mitomycin-C:** Additional antibiotics used as antineoplastic
agents in cancer therapy.

## Miscellaneous Natural Agents with Anticancer Activity:

9. **Cisplatin:** A platinum-containing compound used in treating metastatic testicular
and ovarian tumors, as well as bladder cancer.
10. **Mitotane:** Employed in specific cancer treatments, Mitotane is a notable natural
product with antineoplastic properties.

## **SOURCES**
- Page 38: Information on Vinca alkaloids, Podophyllotoxin, Etoposide, and Taxol.
- Page 35: Details on Actinomycin-D, Doxorubicin, Daunorubicin, Bleomycin,
Mithramycin, and Mitomycin-C.
- Page 25: Overview of natural products used as antineoplastic agents, including plant-de-
rived compounds, antibiotics, and miscellaneous agents.

User: 9.Write a note on antimetabolites.

ChatBOT: # Antimetabolites: Overview and Mechanism of Action

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Antimetabolites are a class of drugs that block vital cellular metabolic reactions by mim-
icking normal cellular metabolites. These drugs prevent the biosynthesis or utilization of
essential cellular metabolites, leading to inhibition of DNA synthesis and cell replication.
Antimetabolites can be categorized into different subgroups based on their mechanisms
of action and structural similarities to specific metabolites.

## Folate Antagonists
- **Methotrexate:** N-{4-[(2,4-diaminopteridin-6 yl methyl) methylamino] benzoyl}
L-glutamic acid
- Mechanism: Blocks folate reductase irreversibly, inhibiting the production of tetrahy-
drofolic acid necessary for DNA synthesis.
- Uses: Treatment of various cancers, including leukemia.

- **Azathioprine:** 6-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-7H-purine
- Mechanism: Purine synthesis inhibitor
- Uses: Immunopressant for organ and tissue transplantation survival facilitation.

## Pyrimidine Analogues
- **5-fluorouracil (5-FU):** 5-fluoropyrimidine-2, 4(1H, 3H) dione
- Mechanism: Converted to FdUMP, inhibiting thymidylate synthetase, leading to
"thymineless death" of cells.
- Uses: Treatment of various cancers like stomach, colon, rectum, breast, ovaries, and
ocular surface neoplasia.

- **Floxuridine:**
- MOA: Similar to 5-fluorouracil (thymidylate synthetase inhibitor)
- Uses: Treatment of malignant neoplasms of the liver and GIT, mainly colon cancer.

- **Cytarabine (Cytosine arabinoside, Ara C):** 4-amino-1 b-D-arabinofuranosyl pyrim-

idin-2(1H)-one
- MOA: Competitively inhibits DNA polymerase, blocking DNA synthesis.
- Uses: Treatment of acute non-lymphoblastic leukemia and antiviral agent for Herpes
infections.

## Miscellaneous Agents
- **Dacarbazine:** 5-(3, 3-dimethyl-1-triazeno)-imidazole-4-carboxamide
- Uses: Treatment of malignant melanoma, Hodgkin's disease, and sarcomas.

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These antimetabolites play a crucial role in cancer treatment by interfering with key
metabolic pathways essential for cancer cell growth and proliferation.

## SOURCES
- Page 25: List of antimetabolites and their respective mechanisms of action.
- Page 32-33: Detailed information on folate antagonists, pyrimidine analogues, and
miscellaneous antimetabolites.

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