• I

'
Chapter 15
Cancer chemothera y & Gene thera
Cancer chemotherapy
Defini tion of cancer: Cancer is a di sease characterized by uncontro lled mu ltiplication and spread of abnormal
forms of th e body's own ce ll s. The terms cancer, malignant neoplasm (neoplasm simply means 'new growth') and
malignant tumo ur are synonymous.
(Ref Rang & Dale's-8th)
Cancer cells have fo ur characteristics that distingui sh them from normal cell s:
1. uncontrolled pro liferati on
2. loss of function because of lack of capacity to differentiate
3. invas iveness
4. the abi lity to metastasise.
(Ref Rang & Dale's-8th)
Treatment of cancer: There are three main approaches to treating established cancer- surgical excision ,
irradiation (radiothera py) and chemoth erapy- and the ro le of each of these depend s on the type of tumour and
the stage of its deve lopment.
(Ref Rang & Dale 's-8th)
Pri nciples of Cancer Chemotherapy: Cancer chemotherapy st rives to cause a lethal cytotoxic eve nt or apoptos is
in the cancer cell that can arrest a tumor's progression. The attack is genera lly directed toward DNA or against
metabolic sites essential to ce ll replication- for exam ple, the ava ilabil ity of purines and pyrimid ines that are the
build ing bloc ks fo r DNA or RNA syn thes is. Ideally, these anticanc er drugs shou ld interfere only with cel lul ar
processes that are unique to malignan t cel ls. Unfortunatel y, most curren tly available anticancer drugs do not
spec ifically recogni ze neoplastic cel ls but, rather, affec t all ki nd s of pro life rating ce lls- both normal and abnormal.
Therefore, al most all antitumor agents have a steep dose- response curve fo r both tox ic and therapeutic effects.
(Ref Lippincott 's-6th)
Goa l of treatment : The ul timate goal of chemotherapy is a cure (that is, long-term , disease-free survi val). A true
cure requ ires th e eradication of every neo plastic cell. If a cure is not attai nable, then th e goal becomes control of
the disease (stop the cancer from enlarging and spreading) to extend survi val and maintain the best quality of life.
In advanced stages of cancer, the like lihood of controll ing the cancer is far from reality and the goal is palliation
(that is, all ev iation of symptoms and avo idance of life-th reatening toxicity). This means that chemotherapeutic
drugs may be used to rel ieve symptoms cau sed by the cancer and improve the qual ity of life, even though the
drugs may not lengthe n life.
(Ref' Lippincott 's-6th)
Indications fo r treatment: Chemotherapy is in dicated when neop lasms are di sseminated and are not amenable to
surgery. Chemothera py is also used as a supp lemental treatment , to attack micrometastases fol lowin g surgery and
rad iation treatment in whi ch case it is ca lled adj uva nt chemotherapy. Chemotherapy give n prior to the surgi cal
procedure in an attempt to shrink the cancer is referred as neoadj uvant chemotherapy, and chemotherapy given in
lower doses to assist in pro long in g a remission is known as main tenance chemotherapy.
(Ref Lippincott 's-6th)

Plrnrmacology-98
~~~!!!!:!!~~---~---------------
Blueprintn • Pharmacology 766
CeII cycle and action of anticancer drugs on the cells:
Mitosis · 1·,on
~ Different,a
Synthesis 2% /
_e:.-: ___
I
of cellular
components __.-!~,,...-
for mitosis

Synthesis
of cellular
components
needed for
ONA synthesis

Figure: The cell cycle and cancer. A conceptual depiction of the cell cycle phases that all cells- normal and neoplastic-
must traverse before and during cell division. Th e percentages given represent the approximate percentage of time spent in
each phase by a typical malignant cell; the duration of G 1, however, can vary markedly.

On the basis of cell cycle, anticancer drugs are group into -

1. Cell cycle specific (CCS) drugs &
2. Cell cycle nonspecifi c (CCNS) drugs.

Cell cycle specific drugs: Anticancer drugs which exert their action on cells by traversing the cell cycle are called
cycle specific drugs. In general, CCS drugs arc most effective in hematologic malignanc ies and in solid tumors in
which a relatively large proportion of the cells are proliferating or are in the growth fraction.

Cell cycle nonspecific drugs: Anticancer drugs wh ich can sterilize or kill tumour cells both resting in the GO
phase & cyc ling are called cell cycle nonspecific drugs. CCNS drugs (many of which bind to ce llular DNA and
damage these macromolecules) are particularly useful in low growth fraction s lid tumors as well as in high
growth fraction tumors .
(Ref Katzung-l 3th)
 767 Cancer chemoth erapy & Gene thera py
Q. Classify anticancer drugs. (DU- l 7M)
Q. Classify the drugs used in cancer chemotherapy. (RU-06M)
Q. Name the structural analogs used in cancer chemotherapy. (SU-99M, CU-99M)
Ans.
Classification of anticancer drugs:
Cell C~'Cle-Specific (CCS) A~ents I Cell C)·cle-Nonspecific (CCNS) A~ents
Antimetabolites (S phase) Alkylating agents
• Capecitabine • Altretamine
• Cladri bine • Bendamustine
• Clofarabine • Busulfan
• Cytarabine (ara-C) • Carmustine
• Fl udarabine • Chlorambuci l
• 5-Fluorouracil (5-FU) • Cyc lophospham ide
• Gemcitabine • Dacarbazine
• 6-Mercaptopurine (6-MP) • Lomustine
• Methotrexate (MTX) • Mechlorethamine
• 6-Thioguanine (6-TG) • Melphalan
• Temozolomide
• Thiotepa
Epipodophyllotoxin (topoisomerase II inhibitor) Anthracyclines
(G 1-S phase) • Daunoru bicin
• Etoposide • Doxorubicin
• Epirubicin
• ldaru bicin
• Mitoxantrone
Taxanes (M phase) Antitumor antibiotics
• Album in-bound paclitaxel • Dactinomycin
• Docetaxel • Mitomycin
• Paclitaxel
Vinca alkaloids (M phase) Camptothecins (topoisomerase I inhibitors)
• Vinblastine • Irinotecan
• Vincristine • Topotecan
• Vinorelbine
Antimicrotubule inhibitor (M phase) Platinum analogs
• Ixabepilone • Carboplatin
• Cisplatin
• Oxaliplatin
Antitumor anti biotics (Gr M phase)
• Bleomyc in
(Ref Katzung-l 3th)

Q. Outli ne the principles of combining cytotoxic drugs in the treatment of malignancy. (RU- l 6Ju)
Ans.
Principles of combining cytotoxic drugs in the treatment of malignancy: The selection of drugs m
combination chemotherapy is influenced by:
1. Choosing drugs that act at different biochemical sites in the cell.
2. Using drugs that attack cells at different phases of the growth cycle. 'CHOP' is a standard
combination chemotherapy regimen for non-Hodgk in's lymphoma. The acronym stands for
cyclophospham ide, doxorubicin (previously known as hydroxydoxyru bicin), vincristine (previously
 T:\I
Blueprint ' Pharmacology 768
called oncovin) and prednisolone. The first three cytotoxic drugs exert their antitumour effect on different
aspects of cell proliferation. The antitumour effect of corticosteroid remains unclear.
3. The desirability of attaining synchronisation of cell cycling to achieve maximum cell kill. Cells are
killed or are arrested in mitosis by vincristine, which is then withdrawn. Cells then enter a new
reproductive cycle more or less synchronously, and when most are judged to be in a phase sensitive to a
particular phase-specific drug, e.g. methotrexate or cytarabine, it is given.
4. Avoidance of cross-resistance between drugs. In some instances, us~ of one dru~ regimen fol~owed by
another rather than using them simultaneously in combination avoids drug resistance and improves
therapeutic efficacy. For example, epirubicin given for four cycles fol lowed by CMF (concomitant
cyclophosphamide, methotrexate and 5-fluorouracil) for four cycles has largely replaced CM F alone as
standard adjuvant chemotherapy for breast cancer, because the outcome is better.
5. Non-overlapping toxicity profiles. Before establishing a combination regimen, phase I trials are
undertaken, frequently fixing the dose of one drug while escalating the dose of another, in small cohorts
of carefully monitored patients, so that toxicity and patient safety can be monitored .
6. Empirical evidence of efficacy against a particular tumour type. The antitumour activity of platinum
complex s was a chance finding.
7. Enhanced cell killing in preclinical models when drugs are combined. Oxa liplatin on its own has
limited cytotox icity against colorectal cancer cell lines in vitro and in mouse xenograft models, but its
combination with SFU confers a more than additive, i.e. synergistic, killing effect on tumour cells.
Considerations of pharmacokinetics in relation to cell kinetics are of great importance, as drug treatment alters the
behaviour of both malignant and normal cel ls.
(Ref Bennet & Brown-J 2°1151 6)

Q. Lists the common adverse effects of anticancer drugs. (DU-l 7M,07Ju; RU-I 0/07J,06M)
Q. Mention the general hazards of cancer chemotherapy. (RU-I 6Ju)
Q. Discuss the common adverse effects of cancer chemotherapy. (RU-08J)
Ans.
Common adverse effects of anticancer drugs: Because their main effect is on cell division, anticancer drugs
will affect all rapidly dividing normal tissues and thus they are likely to produce, to a greater or lesser extent, the
fol lowing general toxic effects:
I. Nausea and vomiting
2. Bone marrow toxicity (mye losuppression) with decreased leukocyte production and thus decreased
resistance to infection
3. Impaired wound healing
4. Loss of hair (alopecia)
5. Damage to gastro intestinal epithelium
6. Depression of growth in chi ldren
7. Sterility
8. Teratogenicity.
(Ref Rang & Dale's-8th)

Q. Short note: Anti-cancer induced nausea and vomiti ng (emesis).

Q. How will you manage anti-cancer induced nausea and vomiting (emesis)?
Q. Discuss the management of drug induced vomiting. (DU-17M)
Ans.
Anti-cancer induced emesis: Nausea and vomiting is the principle side effects of anti-cancer chemotherapy.
Chemoreceptor trigger zone (CTZ) is directly stimulated by toxins or drugs. Neurotra nsm itters (e.g. dopamine)
al so sti mul ate the vomiting center. There is variation of emetic effect among chemotherapeutic drugs-
 769 C rnccr chemotherapy & Ccnc therapy
Mild emetics • Methotrexate ' I

• Fluorouracil
Severe emetics • Doxorubicin (adria myc in)
• Dacarbazine
• Mechl orethamin e
Very severe emetics • Cisp lati n

Prevention of an ti-cancer induced emesis: Use of antiemetics as a compone nt of regular chemotherapeu tic
regimen. The drugs are -
I. Serotonin antagonists : Ondansetron, gran isetron.
2. Dopamine antagonists: Metoclopramide.
3. Major tranquilizers : Phenothiazines.
4. Cannabinoids: Dronabinol.
5. Others: High dose glucocorticoids (dexamethasone), benzodiazepines (sedatives) and antihistam ines.

Q. Why SHT3 receptor blockade is so importan t in cancer chemotherapy induced vomiting? (CU-I 7M)
Ans.
SHT3 receptor blockade is important in cancer chemotherapy induced vomiting: 5-HT3 receptor antagonists
Granisetron, ondansetron and palonosetron are of particular value in preventing and treating the vomiting and, to
a lesser extent the nausea, commonly encountered during administration of cytotoxic drugs such as cisplatin. The
primary site of action of these drugs is the CTZ.
(Ref Rang & Dales-81hl375)

Nice to know:
Mechanism of action of alkylating anticancer drugs:
Alkylating anticancer drugs
l
Transfe r alky l group to DNA
l
Alkylati on of DNA
l
fntra-strand linking and cross linking of DNA stran ds
l
Blocks replication and transcription of DNA
l
Blocks production of undifferent iated cells
l
Anticancer effect.
(Ref Katzung-1 Jth)

Mechanism of action of 5- fl uorou racil (5-FU): 5-Fluorourac il (5-FU) is a prodrug requiring activation via a
complex seri es of biotransformation reacti ons to ribosyl and deoxyribosyl nucleotide metabolites.
I. 5-FU is converted to 5-fluoro-2'-deoxyuridi ne-5'-monophosphate (FdUMP) ._ FdUMP inhibits the
enzyme thymidy late synthase ._ inhi bits synthesis of thymidylate - inhibition of DNA synthesis
th rough "thym ineless d ath."
2. 5-FU is converted to 5-fluorouridine-5'-tri phosphate (FU TP) ._ FUTP is then incorporated into RNA -
interferes with R A processing and mRNA translation.
J . In addition, 5-FU is converted to 5-fluorodeoxyuridine-5'-triphosphate (FdUTP ) ._ FdUTP can be
incorporated into ce ll ular D 1A, resultin g in inhi bition of D A synthesis and function.
Thus, the cytotoxicity of 5-FU is thought to be the result of the combined effects on both DNA- and RNA -
mediated events.
(Ref Katzung-13th)
 TI\I
Blueprint Pharmacology 770
Mechanism of action of vincristine: Vincristine ---. Tubulin inhibitor ---. Inhibits polymerization of the
microtubules of the cytoskeleton and mitotic spindle---. Mitotic arrest at metaphase ___. Dissolution of the mitotic
spindle---. Inhibits chromosomal segregation at the pole of dividing cell ---. Blocks uncontrolled cell division ~
Anticancer effect.
(Ref Katzung-l 3th)
Malignancies responsive to chemotherapy:
I. Acute lymphocytic leukemia (ALL)
2. Acute myelocytic & myelomonocytic leukemia
3. Chronic lymphocytic leukemia (CLL)
4. Chronic myelogenous leukemia (CML)
5. Hodgkin 's disease (stages III & IV)
6. Non-Hodgkin 's lymphoma
7. Multiple myeloma
8. Macroglobulinemia
9. Polycythaemia vera
I 0. Carcinoma of diffe rent organs: Adrenal, breast, cervix, colon, endometrium, lung, ovary, pancreas,
prostate, stomach, testi s, thyroid, head & neck, choriocarcinoma (trophoblastic neoplasm).
I 1. Wilm 's tumor
12. Neuroblastoma
13. Carcinoid
14. lnsulinoma
15 . Estrogen ic sarcoma
16. Miscellaneous sarcomas
17. Melanoma

Gene therapy
Gene therapy: Gene therapy is the genetic modificat ion of cells to prevent, alleviate or cure disease.
(Ref Rang & Dale 's-Bth)
Potential applications :
I. radical cure of monogenic diseases (e.g. cystic fibrosi , haemoglobinopathies)
2. amelioration of diseases with or without a genetic component, including many mal ignant,
neurodegenerative and infectious diseases.
(Ref Rang & Dale 's-8th)
Steps of gene therapy: Two steps -
I. Gene identification and cloning
2. Gene transfer and expression
(Ref- Misbahuddin-5thl l98,1 99)
Transfer of recom binant gene into target cells: The transfer of recombinant nucleic acid into target cells is
critical to the success of gene therapy. Target genes must cross the plasma and nuclear membranes, and it must
then bind to the chromosomes of target cells.

There are two main strategies fo r delivering genes into patients: the in vivo and ex vivo approach.
I. In vivo strategy: The vector containing the therapeutic gene is injected into the patient, either
intravenous ly or directly into the target tis ue (e.g. a mal ignant tumour).
2. Ex vivo strategy: The ex vivo strategy is to remove cells fro m the patient (e.g. stem cells from marrow or
circulati ng blood, or myob lasts fro m a biopsy of striated muscle), treat them with the vector and inject the
genetically altered cel ls back into the patient.

Criteria of an ideal vector

1. Safe
2. Highly efficient (i.e. insert the therapeutic gene into a high proportion of target cells.)
 771 Cancer chemotherapy & Gene therapy
3. Selective (i .e. it wou ld lead to expression of the therapeutic protein in the target cell s but not 10 lli<.:
expression of viral proteins.)
(Ref- Rang & Dale 's-8/h)
Table: Delivery systems for gene therapy
Vector
AdvantaJ?;es Disadvantages
1. Liposomes Virus-free Low efficiency, sometimes cytotox ic
2. DNA cassettes Virus-free Low efficiency, expression tem porary
3. Herpes simplex Highly infective, persistent No integration with host DN A, cytotox ic, diffi cul t to
virus type I expression handle
4. Adenovirus Highly infective in epithelia Immunogenic and temporary
5. Adeno-associated Stable Low capacity, requires a helper virus
virus
6. Retrovirus Efficient, permanent Low capacity, unstabl e, must integrate into host
DN A
(Ref Rang & Dale s-8th)

MCQ
Q. Following medications would be effective to cou nteract the emesis in patient with ovarian cancer taki ng
cisplatin: (CU-l4Ju)
a) Droperidol.
b) dolasetron
c) prochlorperazi ne.
d) Dronabinol
e) Ondansetron
a. T. b. T, c. T. d. T. e. T
 : t , I I !
=-----

Chapter 16
Dermatology
Topical Antibacterial Preparations
Indications: Topica l antibacterial agents may be usefu l in
1. Preventing in fections in clean wounds
2. early treatment of infected dermatoses and wounds
3. reduci ng coloni zation of the nares by staphylococci
4. Axillary deodori zation, and
5. the management of acnevulgari s.
(Ref Katzung-1 J'h edition)

Anti biotic-co rticosteroid combinations: Some top ical anti-i nfecti ves conta in corticostero ids in addition to
anti biotics. There is no conv incing ev idence that to pical co1ticosteroids inhibi t the antibacterial effect of
antib iotics when the two are incorporated in the same preparation. In the treatment of secondari ly infected
dermatoses, which are usually coloni zed with streptococci, staphy lococc i, or both, comb inati on therapy may
prove superior to corti costero id therapy alone. Antib iotic-corticosteroid combi nations may be usefu l in treating
diaper dermatiti s, otitis externa, and impetiginized eczema.
(Ref Katzung-1 3'" edition)

Topical Antibacterial Indication

Bacitracin
(Ointment base alone or in
com bination with neomyc in,
po lymyxin B, or both.)
Mupirocin
(o intment)
Retapa mulin
Polymyxin B
(so lution or oi nt men t)
Neo mycin & Genta mic in
(Powder, ointment or cream)
Clindamycin
(water-based ge l and lotion)
Erythromyci n (water-based gel)
Metro nidazole (water-based gel)
• Gra m-positive organi sms such as streptococci. pneumococci, and
staphylococci.
• Most anaerob ic cocc i, neisseri ae, tetanus bacill i, and diphtheria
baci lli are sensit ive.
• Most gram-positive aerobic bacteria, including methici lli n-resistant S
aureus (MRS/\).
• Impetigo caused by S aureus and gro up A ~-hemolytic streptococci .
• Gro up A ~-hemolytic st reptococci and S aureus, excluding MRS A.
• Gram-negative organi sms, includ ing Psrudomonas aeruginosa,
Escherichiu coli, enterobacter, and kl ebsiell a.
• Gram-n egative organisms, including E coli, proteus, klebsiel la, P
aeruginosu and cnterobac tcr.
• Staphylococci and gro up/\ ~-he molytic streptococc i.
• Acne
• Acne
• Rosacea

Sodium Sulfacetamide
( 10% lotion and as a I 0% wash)
Topical Antifungal Preparations
Topical Antifungal Agents
Topical Azole Derivatives :
Clotrimazole, econazole,
ketoconazole, miconazole,
oxiconazole, sulconazole, and
sertaconazole
Ciclopirox olamine
Allylamines: Naftifine &
Terbinafine
Butenafine
Tolnaftate
Nystatin
Amphotericin B
Topical antiviral agents
I . Acyclovir (Zovirax) (5% ointment)
2. Penciclovir (1 % cream)
3. Valacycl ovi r
4. Famciclovir
Adverse effects: Adverse loca l reactions to acyclovir and penciclovi r may include pru ritu s and mild pain with
transient stinging or burning.
Pharmacology-99
773 Dermatology
-- J
• Acnevu Igaris and acne rosacea
(Ref. 1-:otzw 17,- I _t' f!dit ion;
Topical formulation Indications/ Antifungal spectrum
Cream or lotion and • Dennatophytes (ep iderm ophyton. microsporu m,
as vaginal cream or and trichophyton)
su ppos itories • Yeasts (Candida albicans and Pityrosporwn
orbicu/are)
I% cream and lotion • Inhibitory acti vity agai nst derrn ato phytes,
candida species, and P orb iculare.
1% creams and other • Highly active agai nst dermatophytes but less
forms active against yeasts.
1% cream • superficial dermatophytos is
Cream, solution, • Dermatophyte infections caused by
powder, or powder epidermophyton, microsporum, and
aeroso l tri chophyton. It is also active against P
orbiculare but not against cand ida.
Oral suspension, • Effective against C albicans infections but
vaginal tablet, ineffective against derm atophytes .
Cream and lotion • Effective against C albicans infections but
form ineffective against dermatophytes.
. .
(Ref Katzung- 13 Iii edztwn)
Topical Antiviral Agents
Indication
Herpes virus famil y, including herpes sim plex types I and 2
(Ref Katzung- I 31h edition)
 · r:H l'I rnnnaco Iog)'
Blm·pnnt 774

Ecto parasi ti ci des

-
I.
Ectoparas iticidcs
Permethrin (Cream) • Pediculosis (I % cream)
Indications
-
• Scabies (5% cream)
2. Lindanc (Hexachlorocyclo hexane) • Pediculos is capi ti s or pubis -
(shampoo or loti on)
3. Crotamiton (cream or lotion) • Scabies -
• Anti pruritic
-t Sulfur • Scabies
Alrho11gh ir is nonirritating, ii has an unpleasant odor, is staining,
and is tltus disagreeah/e to use. Ir has been replaced by more
aesthetic and ef(ective scabicides i11 recent years, bur it remains a
possible olrernativ<! dnt P, for use in in/ants and prer;nam women.
5. Ma lathion (0.5% lotion) • Pecli cul os is
..th
(Ref Katzung-13 edu1on)

Treabnent of Scabies
Scabies: Scabies is an infectious disease of the skin caused by the itch mi te characterized by pruritic papular
les ions along th e burrows containing the mites and their eggs.
(Rel Rashid, Khab ir, Hyder-4°'1264)
Causative agent: Female Sarcoptes scahiei homi11is.
Site of lesion:
I . Aro und the finger webs, wri sts, extensor aspect of el bows and axiIla
2. Nipples in women & ge nit als in rn en
3. Around the umbili cus, lower abdomen, th ighs and buttock
4. Feet and ankles
5. Palms in infa nts

Q. Outline the pharmacothcrapy of sca bies. (RU-I 5Ju)

An s.
Treatment of scabies:
a. Children should be excl uded fro m the school until the day after treatment.
b. All affected persons of a family shou ld be treated si multan ously.
c. Before treatment, al l patients shou ld have a good soap and warm water bath.
d. Scabicides : The drug used are-
1. , Permethrin (Cream): Single application of' 5% cream is applied to the body fro m the neck down,
left on fo r 8- 14 hours, and then washed off
· 2. Benzyl benzoate (25%) emulsion .
3. Tetra ethyl Monosulfiram (Tetmosol)
4. Lindane (Hexachlorecyclohexane) (sham poo or lotion): Sin gle appl ication to the entire body
from th e neck down, left on for 8- 12 hour , and then washed off.
5. Crotamiton (10%) cream or lotion: Two ap plications to the ent ire body fro m the chin down at
24- hour interva ls, with a cleans ing bath 48 hours after the last appl icati on.
6. Sulfur ointment (0. 5 - I %) in vase line
e. Antipruritic agent: Antihistamine
f. A clea ning bath i taken two days after th e last applicati on, and changed to fresh cloth .
(Ref Rashid. Khabir, Hyder-l'/264,265)
Chapter 17
Immuno harmacolo y
Immunization: It is defined as a technique by which immunizing agents are introduced into the body for the
production of antibody to prevent disease.
Active Immunization: Active immunization consists of the administration of antigen to the host to induce
fo rmation of anti bodies and cell-mediated immunity. Immunization is practiced to induce protecti on against many
in fectious agents and may utilize either inactivated (k illed) materials or live attenuated agents.
(Ref Kat?.ung-1 f' edition)
Q. Active immunization is generally preferable to passive immunization- Explain.
Ans.
Active immunization is generally preferable to passive immun ization-in most cases because higher antibody
levels are sustained fo r longer periods of time, requiring less frequent immu nizati on, and in some cases beca use of
the development of concurrent cell-med iated im munity. However, acti ve immunizat ion req uires ti me to devel op
and is therefo re generally inactive at the time of a specific exposure (eg, fo r parenteral exposure to hepa titis B,
concurrent hepatitis B IgG [passi ve antibodies] and acti ve im munizat ion are given to preven t illness). ·
(Ref Katzung- 1i ' edition)
Vaccine: Vaccine is an immune-biological substance designed to produce specific protection aga inst a given
disease.
(Ref Park-20'"! 98)
Vaccines may be prepared from-
! . Live mod ified organisms
2. Inactivated or ki lled organisms
3. Extracted cellu lar fractions
4. Toxoids or
5. Com bi nat ion of these
More recent preparations are-
! . Sub-un it vaccines
2. Recombi nant vaccines.
(Ref Park-2t'l 98)
Types of vaccines:
Live attenuated Inactivated or Toxoids Cellula r fractions Combinatio1ns
vaccines killed vaccines
Bacterial: Bacterial: Bacterial: • Men ingococcal • Pentava lent vaccine (Diphthe ri a-
• BCG • Typhoid • Diph theria vacc me pertussis-tetanus-hepatitis 8 -
• Typhoid oral • Cho lera • Tetanus • Pneumococcal haemophilus influe nza type b)
• Plague • Pertuss is vaccine • OT (Diphther ia- tetan u )
Viral: • C.S. men ingitis • DP (Diph the ria- peri ussi s)
• Oral poli o • Plague • DPT and typhoid vaccine
• Yellow fe ver Viral: • MR (Measles and rubella)
• Meas les • Rabies • DPTP (DPT pl us inact ivated
• Rubella • Salk (po li o) polio)
• Mumps • InCTuenza
• Influenza • Hepatitis B
Rickettsial: • Japanese
• Epi. typhus encephaliti s
• KFD
'"
(Ref Park/ JO /98, 99)
 Ti\l
Blueprint · Pharmacology 776
Q. Define toxoid with example.
Ans.
Toxoid: These are vacc ines prepared from toxin by inactivation (combining formaldehyde with toxin) which have
no toxigenicity but retain antigenicity.
Example: Tetanus toxoid (TT), Diphtheria toxo id (OT).
(Ref Park/2 (/"; I 00)

Q. Discuss about EPI in Bangladesh.

Ans.
EPI: It means Expanded Programme of Immunization. It is a global programme on immunization launched in
May 1974, by the WHO to protect all children of the World aga inst six vaccine preventable diseases namely-
Tuberculosis, Diphtheria, Whooping cough, Tetanus, Poliomyelitis & Meas les. EPI in Bangladesh was formall y
launched on 7th April , 1979.
Now, hepatitis B vacc ine to prevent hepatitis B, and haemophylus influenza type b (Hib) vaccine to prevent
childhood menin gitis and pneumonia have been added in EPI.
(Ref Rashid, Khabir. Hyder-4'"1408)

Vaccines used in F:PI:

I. BCG vaccine
2. Pentava lcnt vaccine (Diphtheria-pertussis-tetanus-hepatitis 8-haemophylus influenzae type b (Hib))
3. Oral polio vaccine (OPV)
4. Measles vacci ne

EPI schedule in Bangladesh:

..
Vaccine
I IDose '.·, IAge of INo. f IInterval ISite of IRoute of
Administration
,I Starting Dos between Vaccination
l I
I doses
BCG 0.05 ml After birth I - Upper & outer part of Intradermal
left arm (Deltoid
region)
-
Pentavalent vaccine 0.5 ml 6 weeks 3 4 weeks Antero- Intramuscu lar
(Diphtheria-Pertussis- lateral part of (IM)
Tetanus-Hepatitis B- mid th igh
Haemophylus injluenwe
type b (Hib)J
Oral polio vaccine (OPV) 2-3 drops 6 weeks 4 4 weeks Oral Ora l
MR (Measles-rubella) 0.5 ml 9 months I - Antero-lateral Su bcutaneous
part of mid thigh
Measles 0.5 ml 15 months I - Antero- lateral Subcutaneous
part of mid thigh

Passive Immun ization : Passive immunization c.onsi sts of transfer of immunity to a host using preformed
immunoglobulins . Passive immun ization is useful fo r-
! . individuals unable to form antibodies (eg, con genital agammaglobul inem ia);
2. prevention of disease when time does not permit acti ve immun ization (eg, postexposure);
3. for treatment of certain diseases normally prevented by immuni zati on (eg, tetan us); and
4. for treatment of conditions for whi ch active immun ization is unavailable or impracti cal (eg, snakebite).
(Ref Katzung- 13'" edition)
 777 f mmunopharmaco logy
Examples of passive immunization
Indication
Product
Botulism
Botuli sm antitox in, eq uine
Cytomegalovirus (CMV )
Cytomegalovirus immune globulin (IV )
Di phtheria
Diphtheria antitox in, eq uine
Hepatitis A
Immune globulin (intramusc ular, IM )
Hepatitis B
Hepatitis B immune globulin (HBI G)
HIV-infected children
Imm une globulin (IV)
Meas les
Immune globulin (IM )
Idi_opathi_c thrombocytopenic purpura (ITP) Immune globulin (IV)
Pnmary 11nmunodefi ciency disorders Immune globulin (I V)
Rabies
Rabies immune globulin
Respiratory syncytial virus (RS V) Palivizumab
Rubella Immune globulin (IM )
Snake bite (coral snake) Antiveni n (Micrurus fulvius), eq uine
Snake bite (pit vipers) Antivenin (Crotalidae) pol yvalent, eq uine
Antiven in (Crotal idae) polyvalent immune Fab, ovi ne
Tetanus Tetanus immune globulin (TIG)
Varice lla Varice lla-zoster imm une globu lin
111 . .
(Ref Katzung- 13 echtwn)

Aotisera / antitoxins: Antisera is the human or animal (eg, horse) serum containing one or more antibodies that
are specific fo r one or more antigens and are admini stered to confer immunity. The antibodies in an antiseru m
result from previous immunization or exposure to an agent of disease.

Examples of antisera:
1. ATS : Anti-tetanus serum
2. ADS: Anti-diphtheria serum
3. ARS : Anti-rabies serum
4. AGS : Anti-gas gangrene serum

Adverse effects of antisera: Hypersens itivity reactions ranging from anaphy laxis to seru m sickness may occur.