Antitussive

I- central antitussive
Mech: suppress cough center

1- Narcotic antitussive :
a- High addictive e.g morphine , heroin , methadone ( not used)

b- Mild addictive e.g Codeine phosphate , dihydrocodeinone

Pholcodeine ( less addiction , less constipation )

2- Non Narcotic antitussive :

a- Opiate dvs e.g
- Dextromethorphan ( no , no )
- Narcotine ( noscapine) : alkaloid of benzylisoquinoline

b- Non opiate dvs: e.g benzonatate , cramiphen ,diphenhydramine

II- Peripheral antitussive

Mech: suppress afferent pathway

1- Demulcent : e.g Liqurice lozenges

2- Steam inhalation e.g tincure benzoin CO or menthol

3- Local anaesthetic e.g benzonatate

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Mucolytics

1- Acetylcysteine
Contain SH group that dissolve disulphide bond in mucus
SO, reduce its viscosity ( easy expulsion )

2- Carboxymethyl-cysteine

3- Bromhexine , Ambroxol :
Act by depolymerization of mucopolysaccharides of mucus

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 HEPARIN ORAL ANTICOAGULANT
SOURCE -
-

KINETIC

MECH
-
-

1- Prevent propagation & recurrence of thrombosis in

USES
2- Prophylaxis against thrombosis in

S.E

Antidote

Control

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dose

CI

Drugs used in cancer chemotherapy

general toxic effects:
1- Bone marrow toxicity (myelosuppression) with decreased leucocyte production and thus
decreased resistance to infection.

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 2- Impaired wound healing.
3- Loss of hair (alopecia).
4- Damage to gastrointestinal epithelium.
5- Depression of growth in children.
6- Sterility.
7- Teratogenicity.
8- carcinogenic.
9- Rapid cell destruction also entails extensive purine catabolism, and urates may precipitate
in the renal tubules and cause kidney damage.
10- All cytotoxic drugs produce severe nausea and vomiting

A) Alkylating agents

Mech:
- Cross linking leading to interference with transcription and replication.
- Alkyl groups attach to DNA bases, which results in fragmentation o the DNA by repair
enzymes.
- Attachment of alkyl groups to DNA base pairs results in mismatched pairing of nucleotides,
leading to DNA mutations (cell cycle non-specific).

Uses:
- They are effective in tumors of the brain, breast, lymphomas and leukaemias.

e.g.:
- Busulfan, Cyclophosphamide,
- Dacarbazine, estramustine.

Unwanted effects:
- Bone marrow depression.
- Gastrointestinal disturbances.
- Depression of gametogenesis (particularly in men), leading to sterility.
- Increased risk of acute non – lymphocytic leukaemia and other malignancies.

Cyclophosphamide

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  It is inactive until metabolized in the liver by the P450 mixed function oxidases.

 Unwanted effects:
 - Nausea and vomiting.
 - Bone marrow depression.
 - Haemorrhagic cystititis caused by the metabolite acrolein and can be ameliorated by
increasing fluid intake and administering sulfhydryl donors as N-acetylcysteine or mesna
(sodium -2-mercaptoethane sulfonate).

B) Platinum compounds
Cisplatin
- It acts similar to alkylating agents.
- When it enters the cell, forming a reactive complex that reacts with water and then interacts
with DNA.
- It causes intrastrand crosslinking, which results in local denaturation of DNA.

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Uses:
- Cisplatin is used for the treatment of solid tumors of germ cell, ovary, bladder, colorectal ,
lung, head and neck.

Unwanted effects:
- Nephrotoxicity.
- Low myelotoxicity.
- Severe nausea and vomiting (the 5- HT3 receptor antagonists as ondansetron are very
effective in preventing that).
- Tinnitus and hearing loss.
- Peripheral neuropathies
- Hyperuricaemia.
- Anaphylactic reactions.

Carboplatin
- It is a derivative of cisplatin that causes less :
nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting (although more myelotoxic)
than cisplatin.

C) Antimetabolites
Folate antagonists (Methotrexate)

- Folates are essential for the synthesis of purine nucleotides and thymidylate, which in turn are
essential for DNA synthesis and cell division.
- Dihydrofolate reductase converts folate to dihydrofolate (FH2), then to tetrahydrofolate (FH4).
- FH4 functions as an essential cofactor necessary for the synthesis of DNA and purines.
- Methotrexate Has a higher affinity than FH2 for dihydrofolae redutase and thus inhibits the
enzyme, depleting intracellular FH4.
Unwanted effects:
-Bone marrow depression. - Damage to Gl epithelium.
- Pneumonitis, - Nephrotoxicity.

Pyrimidine analogues
Fluorouracil, Cytarabine (cytosine arabinoside), Gemcitabine.

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 Purine analogues
Fludarabine, Pentostatin, Mercaptopurine.

D) Cytotoxic antibiotics
- It intercalates in the DNA (stabilize the DNA – topoisomerase II complex thus halting the
process of replication).
- Affect RNA polymerase activity, stopping transcription.
- Regulate gene expression and involved in the production of free radical that may damage DNA
(Non-cell-cycle specific).
Uses:
- Germ cell, Breast, Colorectal, Prostate cancer.

The anthracyclines (Doxorubicin)

- It binds to DNA and inhibits both DNA and RNA synthesis.
- It Inhibits topoisomerase II required for mitosis.

Unwanted effects:
- Local necrosis during IV infusion.
- Cardiac damage (dysrhythmias and heart failure). - Hair loss.
Dactinomycin
- Interfering with RNA polymerase.
- It inhibit topoisomerase II
- Produces similar toxic effects (except cardiotoxicity).
- It is mainly used for treating paediatric cancer.

Bleomycins
- They degrade preformed DNA, causing chain fragmentation and release of free bases.
- Belomycin is most effective in the G2 phase of the cell cycle and mitosis, but it is also active
against non – dividing cells (G0 phase).
- It is often used to treat germline cancer.
Unwanted effects:
- Little myelosuppression.
- Pulmonary fibrosis.

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- Allergic reactions.

E) Plant derivatives
Vinca alkaloids
- Vincristine, vinblastine, vindesine.
- They bind to microtubules, preventing spindle formation in dividing cells and causing arrest
during mitosis.
- The vinca alkaloids are relatively non – toxic and cause reversible alopecia.
Uses: brain, breast, lymphomas, lung cancers.

Taxanes
- e.g. Paciltaxel and docetaxel
- They act on microtubules, similar end effect to that of the vinca alkaloids.
-Also induce programmed cell death by binding to Bcl-2, an apoptosis stopping protein (arresting
its function).
- Used for treatment of breast, germ cell, head and neck, lung & ovarian cancer.
Unwanted effects:
- Bone marrow suppression.
- Neurotoxicity.
- Fluid retention (leg oedema).
- Hypersensitivity
Campothecins
- Irinotecan and topotecan.
- Derived from a natural plant source, they bind to and inhibit topoisomerase.
Uses: Colorectal, lung & ovarian cancer.

F) Hormones
- Tumors derived from hormone – sensitive tissues may be hormone – dependent (due to the
presence of steroid receptors).

Their growth can be inhibited by :

- Hormones with opposing actions.

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- Hormone antagonists.
- Agents that inhibit endogenous hormone synthesis.

A) Glucocorticoids
- Prednisolone.
- They have marked inhibitory effects on lymphocyte proliferation and are used in the treatment of
leukaemias and lymphomas.
- useful as supportive therapy in cancer ( S.E of anticancer).

B) Oestrogens
- Diethylstilbestrol
- Used in palliative treatment of androgen – dependent prostatic tumors.
- Oestrogens can be used to recruit resting mammary cancer cells (cells in compartment B) into the
proliferating pool of cells (compartment A), thus facilitating killing by other cytotoxic drugs.

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 C) Progestogens
- Megestrol & medroxyprogesterone
- Used in endometrial neoplasms and in renal tumors.
D) Gonadotrophin – releasing hormone analogues
- Goserelin and triptorelin
- They can inhibit gonadotrophin release and are used to treat advanced breast cancer in
premenopausal women and prostate cancer.

G) Hormone antagonists
A) Antioestrogens
e.g. tamoxfien
- Effective in hormone – dependent breast cancer, it competes with endogenous oestrogens for
the oestrogen receptors and therefore inhibits the transcription of oestrogen – responsive
genes.
Unwanted effects:
- Hyperplastic endometrium (may progress to malignant changes).
- Risk of thromboembolism.

B) Aromatase inhibitors
e.g. anastrozole and exemestane
- Suppress the synthesis of estrogen from androgens.
- Effective in the treatment of breast cancer.
C) Aminoglutethimide
- Blocks the generation of all steroids
- Replaced by the aromatase inhibitors.
D) Antiandrogens
- Flutamide, cyproterone and bicalutamide
- Used either alone or in combination with other to treat tumors of the prostate.

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 E) Adrenal hormone synthesis inhibitors
e.g., Trilostane and aminoglutethimide
- Inhibit the early stages of sex hormone synthesis and may have effects in postmenopausal breast
cancer.

H) Radioactive isotopes
- Radioactive iodine (131I) is used in treating thyroid tumors.

I) Miscellaneous agents
Non-cytotoxic cancer agents: Not directly interfere with DNA.
Tyrosine Kinase Inhibitors
e.g. Erlotinib, imatinib.
- Tyrosine kinase enzymes act as receptors for many signaling proteins.
- Once activated, tyrosine kinase triggers a chemical signal that may lead to cell growth and
division.
Uses: leukemias, lung cancer

Imatinib mesylate:
It inhibits:
- Platelet – derived growth factor (a receptor tyrosine kinase)
- Cytoplasmic kinase (Bcr/Abl kinase) which is considered to be a unique factor in the
pathogenesis of chronic myeloid leukaemia.
Unwanted effects:
- Gl symptoms (pain, diarrhea, nausea).
- Fatigue, headache, rashes.
Crisantaspase
- Preparation of the enzyme asparaginase, It breaks asparagines to aspartic acid and ammonia.
- It is active against leukaemia cells that have lost the capacity to synthesize asparagines and
require an exogenous source.
- Normal cells can synthesize asparagines, so the drug is very selective and has very little
suppressive effect on the bone marrow, the mucosa of the gastrointestinal tract or hair
follicles.

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 S.E. :
- Nausea and vomiting, - CNS depression
- Analphylactic reactions - liver damage.
Monoclonal antibodies
e.g.: Alemtuzumab, Rituximab.
- React with defined target proteins expressed on cancer cells leading to:
o Activation of the immune mechanisms and the cancer cell is killed.
o Inactivation of growth factor receptors.
o Inhibition of the survival pathway.
o Promoting apoptosis.

Uses:
- Breast, colorectal, head and neck tumors & leukaemias.

Rituximab:
- Monoclonal antibody that is used for treatment of certain types of lymphoma.
- It lyses B lymphocytes by:
o Binding to the calcium channel – forming protein.
o Activating complement.
- Also sensitizes resistant cells to other chemotherapeutic drugs.
- May be combined with standard chemotherapy.
Unwanted effects:
- Hypotension, - Chills and fever.
- Hypersensitivity reactions.
- Cytokine release reaction (fatal).

Biological response modifiers

- Enhance the host's response.
E.g.- Interferon – α: used in treating solid tumors and lymphomas.
- Aldesleukin (recombinant interleukin -2) used in some cases of renal tumors.
- Tretinoin (a form of vitamin A) a powerful inducer of differentiation in leukaemic cells and
is used as an adjunct to chemotherapy to induce remission.

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