Department of Basic Medical Sciences

517-T Pharmacology (Advanced)

ANTI-CANCER/ANTI-NEOPLASTIC DRUGS
➢ What is a Cancer?
Cancer is a type of abnormality that occurs in the genetic material of cells and generally affects the cellular growth and divisions i.e. Cell Mitosis and
can further become aggressive. Cancer cells however unable to go through a natural cell death process i.e. Apoptosis even though their genetic material
is compromised.
➢ Causes of Cancer:
Following are the causes of cancer:
1. Gender
2. Age
3. Race/ethnicity
4. Genetic predisposition (mutations in crossing-over stage)
5. Exposure to environmental carcinogens
6. Exposure to ionizing radiations
7. Chemical carcinogens:
Virus Abbreviations
a. Carcinogens present in tobacco smoke
b. Azo dyes 1) HBV= Hepatitis B Virus
c. Aflatoxin 2) HCV= Hepatitis C Virus
3) HIV= Human Immunodeficiency Virus
d. Asbestos 4) HPV= Human Papillomavirus
e. Benzene 5) EBV= Epstein – Barr virus
f. Radon 6) HHV– 4 = Human Herpesvirus 4
8. Several viruses: 7) MCV= Merkel Cell Polyoma Virus
a. HBV and HCV are associated with hepatocellular cancer
b. HIV is associated with Hodgkin’s and Non-Hodgkin’s lymphoma
c. HPV is associated with cervical, anal, penile cancers, and oropharyngeal head and neck cancers
d. EBV (also known as HHV–4) is associated with nasopharyngeal cancer, Burkitt’s lymphoma and Hodgkin’s lymphoma
e. MCV causes Merkel cell cancer (rare but aggressive form of skin cancer)
➢ Types of Cancer:
Following are the types of cancers found in humans:
1. Carcinoma (epithelial cells)
2. Sarcoma (connective tissues)
3. Leukemia (blood cells)

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
4. Lymphoma (Lymphatic system)
5. Myeloma (plasma cells)
➢ Cancer Treatment Modalities:
Following are the types of cancer therapies:
1. Primary Chemotherapy:
It is a primary treatment for advanced cancers as no other possible therapies are available. It is the main approach in treating patients with advanced
metastatic diseases.
Goal of therapy: Relieve tumor related symptoms, improve overall quality of life and prolong time to tumor progression.
2. Neoadjuvant Chemotherapy:
It is use of chemotherapy in patients who are present with localized cancer for which alternative therapies (such as surgeries) exist, but have been
clinically shown to be less effective.
Goal of therapy: To reduce the size of primary tumor for successful surgical procedures.
3. Adjuvant Chemotherapy:
It is a type of chemotherapy that is administered after surgeries to prevent and reduce the frequency of recurrence of local and systemic symptoms of
tumor/cancer, and is also used to improve the overall survival of patients. Adjuvant chemotherapy is effective in prolonging both disease – free
survival (DFS) and overall survival (OS) in breast cancer, colon cancer, gastric cancer, non – small cell lung cancer (NSCLC), Wilm’s tumor
(nephroblastoma), anaplastic astrocytoma and osteogenic sarcoma.
4. Salvage Chemotherapy:
Also known as rescue therapy, this kind of chemotherapy is given when a patient does not respond to any other standard set of chemotherapies and
when these standard modes of chemotherapies prove to be a failure in such patient case. If a patient receives salvage chemotherapy, it means that
his/her disease is already in an aggressive state and is quite less treatable.

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Sub-Class Mechanism of Action Drugs ADRs
Anti-folates:
1. Methotrexate
2. Pemetrexed
3. Pralatrexate
Fluoropyrimidines:
1. 5-fluorouracil
They interfere with the various metabolism channels of cancer 2. Capecitabine Nausea, vomiting,
Anti-metabolites cells and thus inhibit their growth and cellular divisions i.e. DNA 3. TAS-102 hepatotoxicity and
synthesis inhibition. Deoxycytidine Analogs: myelosuppression
1. Cytarabine
Cell Cycle Specific Agents
CLASSIFICATION

2. Gemcitabine
Purine Antagonist:
1. 6-Thiopurines
2. Fludarabine
3. Cladribine
Forms a complex with topoisomerase II enzyme leading to
Topoisomerase II Nausea, vomiting, and
inhibitions in normal functions of topoisomerase II causing DNA 1. Etoposide
Inhibitor hypotension
synthesis inhibition.
Topoisomerase I Also known as camptothecins, these drugs cause inhibition of 1. Irinotecan Myelosuppression,
Inhibitor topoisomerase I enzyme leading to DNA damage. 2. Topotecan diarrhea, and dehydration
Functions as a mitotic spindle poison through high-affinity 1. Albumin-bound paclitaxel
Hypersensitivity, nausea,
binding to microtubules with the enhancement of tubulin 2. Cabazitaxel
Taxanes vomiting, hypotension,
polymerization leading to inhibition of mitosis resulting in cell 3. Docetaxel
and myelosuppression.
death. 4. Paclitaxel
Inhibits the process of tubulin polymerization which causes a
1. Vinblastine
disruption in the assembly of microtubules leading to mitotic
Vinca Alkaloids 2. Vincristine Nausea and vomiting
arrest which results in inhibition of cell division causing death of
3. Vinorelbine
cell.
Myelosuppression,
Anti-microtubule Has similar MOA to taxanes and causes microtubule disruptions 1. Ixabepilone hypersensitivity
Inhibitor leading to inhibition of mitosis and cell death. 2. Eribulin reactions, and
neurotoxicity

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Binds to the DNA causing single and double strand DNA Pulmonary toxicity such
Anti-tumor
breakage due to free radical formation resulting in DNA 1. Bleomycin as pneumonitis with
Antibiotics
biosynthesis inhibition. cough, dyspnea.
1. Altretamine
2. Bendamustine
3. Busulfan
4. Carmustine
5. Chlorambucil
Binds with guanine base in the DNA molecule resulting in
6. Cyclophosphamide
Alkylating breakage of DNA strands or molecules. Both cases will result in
7. Dacarbazine Nausea and vomiting
Agents stoppage of transcription of mRNA leading to protein synthesis
8. Lomustine
Cell Cycle Non-specific Agents

inhibition and cell death.

9. Mechlorethamine
10. Melphalan
11. Temozolomide
12. Thiotepa
13. Nitrosoureas
Bind to DNA through intercalation between specific bases and
Anti-tumor 1. Dactinomycin Nausea, vomiting,
blocks the synthesis of RNA or DNA or both; causes DNA strand
Antibiotics 2. Mitomycin C thrombocytopenia,
scission and interfere with DNA cell replication
1. Cisplatin
Platinum Exact mechanism is unknown but somewhat has MOA of Nausea, vomiting and
2. Carboplatin
Analogs alkylating agents i.e. DNA synthesis inhibition. myelosuppression.
3. Oxaliplatin
They exhibit their cytotoxic action via 4 different mechanisms,
i.e. Myelosuppression with
A) Inhibition of topoisomerase II enzyme. neutropenia,
1. Daunorubicin
B) Generation of semi-quinone free radicals & oxygen free thrombocytopenia,
2. Doxorubicin
radicals through an ion-dependent, enzyme mediated reductive arrhythmias, conduction
Anthracycline 3. Epirubicin
process. abnormalities, and dilated
4. Idarubicin
cardio-myopathy
C) High-affinity binding to DNA through DNA intercalation. 5. Mitoxantrone
associated with heart
D) Cellular membrane binding resulting in alterations in fluidity failure.
and ion transportation.

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
1. Bevacizumab
2. Cetuximab
3. Daratumumab
The mechanisms of action associated with Monoclonal
4. Panitumumab
Monoclonal Antibodies (mAbs) include direct cell toxicity, immune-mediated
5. Ramucirumab Fever, Chills, Diarrhoea
Antibodies cell toxicity, vascular disruption, and modulation of the immune
6. Rituximab
system.
7. Trastuzumab
8. Panitumumab
9. Necitumumab
1. Afatinib
2. Dabrafenib
Supportive Treatments

3. Dasatinib
4. Erlotinib
5. Ibrutinib
6. Idelalisib
This class of anti-cancer drugs inhibits tyrosine kinase syntheses
Tyrosine Kinase 7. Imatinib Rash, Diarrhoea, Nausea,
that are involved in the mediation of cell growth or cellular
Inhibitors 8. Nilotinib Vomiting
division by phosphorylation of signalling proteins.
9. Osimertinib
10. Pazopanib
11. Sorafenib
12. Sunitinib
13. Trametinib
14. Vemurafenib
These anti-cancer agents work by: Thromboembolism,
1. Thalidomide
Immunomodulati A) Suppressing production of TNF – α Myelosuppression,
2. Lenalidomide
ng Agents B) Suppressing production of Interleukin – 6 Fatigue, Rash and
3. Pomalidomide
C) Inhibition of angiogenesis Constipation
These agents work by inhibiting proteasomes, which in turn
Myelosuppression,
prevents the degradation of pro-apoptotic factors leading to a 1. Bortezomib
Proteasome Diarrhoea, Nausea,
promotion in programmed cell death (apoptosis). This treatment 2. Ixazomib
Inhibitors Fatigue and Herpes
is effective because malignant cancer cells readily depend on the 3. Carfilzomib
Zoster Reactivation.
suppression of apoptotic pathway.

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Estrogen Receptor
Antagonist:
1. Tamoxifen
2. Fuvestrant
3. Raloxifene
4. Anastrozle
5. Letrozole
6. Exemestane
Steroid These drugs bind to their selective hormone receptor and
Nausea, Vomiting and
Hormones & antagonize the synthesis of their target hormones resulting in a GnRH Receptor Antagonist:
Hot flashes.
their Antagonists decline of these hormone productions. 1. Leuprolide
2. Goserelin
3. Triptorelin
Anti-androgens:
1. Flutamide
2. Nilutamide
3. Bicalutamide
4. Enzalutamide

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
ANTI-BACTERIAL DRUGS
Sub-Class Mechanism of Action Drugs ADRs
Natural Penicillins:
1. Penicillin G
2. Penicillin V
Semi-Synthetic Penicillin/Aminopenicillin/
Extended Spectrum Penicillins:
1. Ampicillin
Inhibits bacterial growth by interfering with 2. Amoxicillin
Penicillin Hypersensitivity,
transpeptidation reaction of bacterial cell-wall Anti-Pseudomonal Penicillin/ Extended
(β – Lactam Drug) Diarrhea, Nephritis
synthesis by binding with PBP Spectrum Penicillins:
Cell – wall Synthesis Inhibitors

1. Piperacillin
CLASSIFICATION

Anti-Staphylococcal Penicillins:
1. Methicillin
2. Nafcillin
3. Oxacillin
4. Dicloxacillin
Third Generation:
First Generation: 1. Cefoperazone
1. Cefazolin 2. Cefotaxime
2. Cefadroxil 3. Ceftazidime
3. Cephalexin 4. Ceftizoxime
4. Cephalothin 5. Ceftriaxone
5. Cephapirin 6. Cefixime
6. Cephradine 7. Cefpodoxime proxetil Hypersensitivity, Local
Cephalosporin
MOA similar to penicillin Second Generation: 8. Cefdinir irritation, pain at the
(β – Lactam Drug)
1. Cefaclor 9. Cefditoren pivoxil site of injection
2. Cefamandole 10. Ceftibuten
3. Cefonicid 11.Moxalactam
4. Cefuroxime Fourth Generation:
5. Cefprozil 1. Cefepime
6. Loracarbef
7. Ceforanide Fifth Generation:
1. Ceftaroline

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Cephamycin 1. Cefoxitin
MOA similar to cephalosporins (2nd generation) Diarrhea, elevated LFT
(β – Lactam Drug) 2. Cefotetan
1. Doripenem
Carbapenem 2. Ertapenem Nausea, Vomiting,
MOA similar to penicillin
(β – Lactam Drug) 3. Imipenem Diarrhea, Seizures.
4. Meropenem
Relatively a non-toxic
drug but has reported
Monobactam
MOA similar to penicillin 1. Aztreonam phlebitis, skin rash and
(β – Lactam Drug)
occasional abnormal
LFT
1. Clavulanic acid
They function by inactivating bacterial β –
2. Sulbactam
β – Lactamase Lactamase enzyme, thereby protecting the β –
3. Tazobactam –
Inhibitors Lactam category of antibiotics from degradation
4. Avibactam
and resistance.
5. Vaborbactam
Inhibits cell-wall synthesis by binding firmly to
the D-Ala-D-Ala terminus of nascent Nausea, Vomiting,
peptidoglycan pentapeptide. This inhibits the Diarrhea,
Glycopeptide 1. Vancomycin
trans-glycosylase, preventing further elongation of Irritation/Rash at the
Antibiotics 2. Teicoplanin
peptidoglycan and cross-linking resulting in site of injection,
weakened cell wall structure formation making it Phlebitis.
susceptible to lysis.
1. Telavancin
Lipoglycopeptide Nausea, Headache,
Similar to glycopeptide antibiotics 2. Dalbavancin
Antibiotics Injection site reactions.
3. Oritavancin
Bind to phospholipids on bacterial cell membrane
Polypeptide and have a detergent-like effect that disrupts cell 1. Polymyxin B Nephrotoxicity &
Antibiotics membrane integrity leading to leakage of cellular 2. Polymyxin E (Colistin) Neurotoxicity
components and cell death.

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
A) Fosfomycin: Inactivates enzyme pyruvyl
transferase which inhibits bacterial cell wall
synthesis causing death. Diarrhea, Nausea,
1. Fosfomycin Headache, Injection
B) Daptomycin: Depolarization of cell membrane
Membrane – 2. Daptomycin site reactions.
with potassium efflux and rapid cell death.
Active Agents 3. Bacitracin (Cycloserine can cause
C) Bacitracin: Interferes with dephosphorylation 4. Cycloserine serious dose-related
of lipid carrier causing cell lysis. CNS toxicities)
D) Cycloserine: Similar to vancomycin.
Bind to 30S subunit of bacterial ribosome and 1. Demeclocycline
Gastric Discomfort,
prevents addition of amino acids to growing 2. Doxycycline
Tetracyclines Hepatotoxicity,
peptide chain causing inhibition in protein 3. Minocycline
Photoxicity
synthesis. 4. Tetracycline
Significant nausea &
vomiting, acute
Protein Synthesis Inhibitors

Glycylcyclines Similar to Tetracyclines. 1. Tigecycline pancreatitis, elevations

in liver enzymes and
serum creatinine
1. Amikacin
2. Gentamicin Ototoxicity,
Bind to 30S subunit of ribosomes and cause 3. Neomycin Nephrotoxicity,
Amino-glycosides misreading of mRNA leading to breakdown of 4. Streptomycin Neuromuscular
polysomes into non-functional monosomes. 5. Tobramycin paralysis, Allergic
6. Kanamycin reactions
7. Capreomycin
1. Azithromycin
Bind to 50S subunit of ribosomes and causes 2. Clarithromycin GI distress, Cholestatic
Macrolides inhibition of translocation and may also interfere 3. Erythromycin Jaundice, Ototoxicity,
with the transpeptidation during protein synthesis Ketolides: QT prolongation
1. Telithromycin
Acts on the sigma subunit of RNA polymerase
Nausea, Vomiting,
Macrocyclic thereby disrupting bacterial transcription,
1.Fidaxomicin Abdominal pain,
Antibiotic terminating protein synthesis and causing cell
Anemia, Neutropenia
death

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Each component of this drug binds to a separate
Venous irritation,
site on the 50S subunit of ribosome. Dalfopristin
Streptogramins 1. Quinupristin/ Dalfopristin Hyperbilirubinemia,
disrupts elongation while quinupristin prevents
Arthralgia, Myalgia
elongation similar to the macrolides
Lincosamides Similar to Macrolides 1. Clindamycin Skin rash, diarrhea
GI upset, Headache,
Bind to the 23 S ribosomal RNA of the 50S Thrombocytopenia,
subunit, thereby inhibiting the formation of the 1. Linezolid Irreversible peripheral
Oxazolidinones
70S initiation complex and translation of bacterial 2. Tedizolid neuropathies, otic
proteins neuritis causing
blindness
Binds reversibly to the 50S ribosomal subunit and Anemia, Bone marrow
Others inhibits protein synthesis at the peptidyl 1. Chloramphenicol toxicity, Gray baby
transferase reaction. syndrome
1. Ciprofloxacin
Nausea, Vomiting,
Binds with DNA gyrase enzyme (for gram –ve)
Nucleic Acid Synthesis Inhibitors

2. Delafloxacin
Headache, Dizziness,
and Topoisomerase IV (for gram +ve) causing 3. Gemifloxacin
Fluoroquinolones Tendinitis, Peripheral
permanent chromosomal breakage leading to cell 4. Levofloxacin
neuropathy and CNS
death. 5. Moxifloxacin
toxicity
6. Ofloxacin
C) Topical
1. Sulfacetamide Sulfonamides:
Sulfonamides:
Sulfonamides compete with PABA (p- 2. Mafenide acetate Crystalluria,
A) Oral Absorbable
Aminobenzoic acid) to inhibit dihydropteroate 3. Silver sulfadiazine Hypersensitivity,
1. Sulfamethoxazole
synthetase and the bacterial genesis of Hematopoietic
2. Sulfadiazine DFR Inhibitors:
Folic Acid dihydrofolic acid. disturbances
3. Sulfadoxine 1. Trimethoprim
Antagonists
Trimethoprim and Pyrimethamine act by 2. Pyrimethamine DFR Inhibitors:
B) Oral; Non-
inhibiting the conversion of dihydrofolate Hematopoietic
absorbable) Combinations:
reductase (DFR) to tetrahydrofolic acid. disturbances,
1. Sulfasalazine 1. Cotrimoxazole
(Sulfamethoxazole+Tri hyperkalemia
methoprim)

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
Methenamine:
Methanamine salts hydrolyze to ammonia and
GI distress,
formaldehyde in acidic urine. Formaldehyde
Albuminuria,
denatures proteins and nucleic acid, resulting in Urinary Tract Antiseptics: Hematuria, Rashes
Anti-infectives bacterial cell death. 1. Methenamine
2. Nitrofurantoin Nitrofurantoin:
Nitrofurantoin inactivates or alters bacterial
Nausea, Vomiting,
ribosomal proteins and other macromolecules
Diarrhea, Pulmonary
leading to cell death.
fibrosis, Neuropathy

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
ANTI-MYCOBACTERIAL DRUGS
Sub-Class Mechanism of Action Drugs ADRs
After being activated from mycobacterial catalase – peroxidase Hepatitis, Vitamin B6
(KatG) and targets the enzymes acyl carrier protein reductase deficiency,
(InhA) and β-ketoacyl ACP synthase (KasA) which are essential 1. Isoniazid hypersensitivity
in the synthesis of mycolic acid. Inhibiting mycolic acid leads to reactions such as
a disruption in the bacterial cell wall. rashes and fever
Liver toxicity, uric acid
Precise mechanism is unclear 2. Pyrazinamide
First-line Therapy retention,
Inhibits arabinosyl transferase – an enzyme important for the Optic neuritis,
synthesis for mycobacterial cell wall causing disruptions in cell 3. Ethambutol decreased uric acid
wall structure and rigidity leading to cell death. excretion
Nausea, vomiting,
CLASSIFICATION

Rifamycins:
Anti-Tubercular Agents

Blocks RNA transcription leading to cell lysis and death. diarrhea, hepatitis
1. Rifampin
(rare) and death (rare)
Crystalluria, peptic
Works via folic acid inhibition. Can replace ethambutol for
1. Para-Aminosalicylic acid (PAS) ulcer, hemorrhage,
MDR-TB
hypersensitivity, etc.
QT prolongation,
It is a diarylquinoline and works as an ATP synthase inhibitor 2. Bedaquiline elevation in hepatic
enzymes
CNS disturbances,
Second-line Disrupts D-alanine incorporation into bacterial cell wall 4. Cycloserine
seizures
Therapy Nausea, vomiting,
(May be given due hepatotoxicity,
Disrupts mycolic acid synthesis 5. Ethionamide
to drug resistance hypothyroidism, CNS
of any first-line effects, etc.
treatment) Bone marrow
suppression,
Inhibits protein synthesis by preventing formation of the
6. Linezolid irreversible and
ribosome complex that initiates protein synthesis
peripheral optic
neuropathy
Pink to brownish-black
Binds to mycobacterial DNA and has redox properties. 7. Clofazimine discoloration of skin,
enteritis.

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 Department of Basic Medical Sciences
517-T Pharmacology (Advanced)
A) Aminoglycosides: Ototoxicity,
Bind to 30S subunit of ribosomes and cause misreading of 1. Streptomycin Nephrotoxicity,
mRNA leading to breakdown of polysomes into non-functional 2. Kanamycin Neuromuscular
monosomes. 3. Amikacin paralysis, Allergic
4. Capreomycin reactions
Nausea, Vomiting,
Binds with DNA gyrase enzyme (for gram –ve) and B) Fluoroquinolones: Headache, Dizziness,
Topoisomerase IV (for gram +ve) causing permanent 1. Moxifloxacin Tendinitis, Peripheral
chromosomal breakage leading to cell death. 2. Levofloxacin neuropathy and CNS
toxicity
Bind to 50S subunit of ribosomes and causes inhibition of C) Macrolides: GI distress, Cholestatic
translocation and may also interfere with the transpeptidation 1. Azithromycin Jaundice, Ototoxicity,
during protein synthesis 2. Clarithromycin QT prolongation
D) Rifamycins: Nausea, vomiting,
Blocks RNA transcription leading to cell lysis and death. 1. Rifabutin diarrhea, hepatitis
2. Rifapentine (rare) and death (rare)
Hemolysis,
Sulfones Similar to Sulfonamides 1. Dapsone methemoglobinemia,
peripheral neuropathy
Drugs for Leprosy

Teratogenesis,
peripheral neuropathy,
Inhibits TNF-α, reduces phagocytosis by neutrophils, increases
Immunomodulating constipation, rash,
production of IL-10, enhances cell-mediated immunity via 1. Thalidomide
Agents fatigue,
interactions with T-cells
hypothyroidism, deep-
venous thrombosis
Pink to brownish-black
Binds to mycobacterial DNA and has redox properties. 1. Clofazimine discoloration of skin,
Antitubercular enteritis.
Agents Nausea, vomiting,
Rifamycins:
Blocks RNA transcription leading to cell lysis and death. diarrhea, hepatitis
1. Rifampin
(rare) and death (rare)

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