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7. Chemotherapy
Chemotherapy is the subdivision of pharmacology that,
according to the definition proposed by Paul Ehrlich, deals
with drugs that can destroy the invading organism without
destroying the host. This term is used when referring to
the use of antimicrobial agents and also to drug treatment
of malignancy.
Chemotherapy of tuberculosis, leprosy, fungal diseases,
viral diseases, AIDS, protozoal diseases, worm infections,
urinary tract infections and sexually transmitted diseases,
Chemotherapy of malignancy.
GENERAL PRINCIPLES IN CHEMOTHERAPY OF
CANCER
Bacterial metabolism differs markedly from that of a
host. While in malignant cells in fact host cell with minor
differences, therefore, selectively is limited. „ Infecting
microorganisms are amenable to immunological and
other host defense mechanisms. This is absent or minimal
with malignant cells. A single colorogenic malignant cell
is capable of producing progeny that can kill the host
therefore all malignant cells must be killed or removed,
Drugs kill cancer cells by first order kinetics
General toxicity of cytotoxic drugs
Nausea and vomiting
Alopecia
Oligozoospermia
Impotence
Amenorrhea
Abortion
Carcinogenicity
Hyperuricemia
Opportunistic infections
Cystitis
alopecia
Cardiac toxicity— doxorubicin
Pulmonary fibrosis— bleomycin and busulfan
Cisplatin— Nephrotoxicity
Methotrexate— Megaloblastic anemia and pancytopenia
Chemotherapy=chemo + therapy
In this therapy, drug is used which may be a chemical
entity or any substance derived from microorganisms that
have selective toxicity against various infections-viruses,
bacteria, protozoa, fungi and helminths are known as
chemotherapy.
When we compare chemotherapy with other types
of drugs it is clearly observable that they have narrow
therapeutic window hence, they show potential for severe
adverse effects associated with it.
Antibiotics: They are produced from microorganisms,
they may cause inhibition of microbe’s growth or have
capability to kill them at very low concentration.
Antimicrobials: They are any natural, synthetic or
semisynthetic chemical that kills or slows that growth
of germs while causing little or no host damage at low
concentration.
Bacteriostatic: They have capability to supress the
growth of Bacteria. Like sulfonamides, tetracyclines,
chloramphenicol, etc.
Bactericidal: They ultimately kill the microorganism.
Like penicillin, polypeptides, rifampin, isoniazid,
metronidazole, cotrimoxazole etc.
Resistance: when microorganism show Unresponsiveness
towards an AMA, which were they sensitive before.
Divided into two parts
Natural resistance – Some microbes show resistant to
some specific AMAs.
Acquired resistance: Development of resistance by
microorganism, due to the continued use of antibiotics
over a period of time.
Various Sources of antibiotics
From fungi like penicillin, griseofulvin, cephalosporin,
From bacteria like polymyxin B, tyrothricin, colistin
From actinomycetes like macrolides, tetracyclines,
polyenes.
History
Paul Ehrlich: Father of chemotherapy
Alexander Fleming discovered penicillin in 1928.
Gerhard Domagk in 1939 discovered sulfonamido
chrysoidine (Prontosil)
In 1944: Waksman et al., discovered streptomycin.
In 1997: Monoclonal antibody got approved for the
treatment of tumor.
In 2007: Target specific screens
Chemotherapeutic agents have various mechanisms of action
and affect cancer cells in a variety of ways. Cancer cells
have great proliferation power and actively move through
the different phases of a cell cycle those are highly chemo
sensitive, while on other hand those cells which are present
in a resting state (G0) are relatively chemo insensitive.
Common adverse effects associated with the use of
antimicrobials
Hypersensitivity reactions
Bone marrow/blood cells
Hearing impairment
Anemia
Nausea and vomiting
Hair loss
Alopecia
Peripheral neuropathy
Loss of appetite
Sexual dysfunction, reproduction, and pregnancy
Superinfection
A new infection occurs in a patient having a pre-existing
infection. Superinfections are most difficult to treat.
Section 1 Pharmacology
89
Principles of antimicrobial therapy
First step: Diagnosis
Second step: To decide whether chemotherapy is
necessary or not
Third step: If chemotherapy is required then selection
of drug is required on the basis of specificity of drug,
pharmacokinetic profile of drug, factors regarding
patient.
Fourth step: To decide the frequency and duration of
drug administration
Fifth step: To decide up to when therapy is needed
Sixth step: To test for the confirmation of cure
Classification: on the basis of chemical structure
1. Sulfonamides and related drugs: Dapsone (DDS),
Sulfadiazine, paraaminosalicylic acid (PAS)
2. Diaminopyrimidines: Trimethoprim, pyrimethamine
3. Quinolones: Nalidixic acid, norfloxacin, ciprofloxacin
4. Beta lactam antibiotics: penicillins, cephalosporins
5. Tetracyclines: Oxytetracycline, doxycycline
6. Nitrobenzene derivative: Chloramphenicol
7. Aminoglycosides: Streptomycin, gentamycin,
amikacin, neomycin
8. Macrolides antibiotics: Erythromycin, clarithromycin,
azithromycin lincosamide antibiotics: Clindamycin
9. Glycopeptide antibiotics: Vancomycin
10. Polypeptide antibiotics: Polymyxin-B, bacitracin,
tyrothricin
11. Nitrofuran derivatives: Nitrofurantoin
12. Nitroimidazoles: Metronidazole, tinidazole
13. Nicotinic acid derivatives: Isoniazid, pyrczinamide,
ethionamide
14. Polyene antibiotics: Amphotericin-B, nystatin, hamycin
15. Azole derivatives: Miconazole, clotrimazole,
ketoconazole, fluconazole
16. Others: Rifampin, ethambutol, griseofulvin
On the basis of Type of organisms
1. Antibacterial: Penicillin, aminoglycoside, erythromycin,
etc.
2. Antiviral: Acyclovir, amantadine B, zidovudine, etc.
3. Antifungal: Griseofulvin, amphotericin B, ketoconazole,
etc.
4. Antiprotozoal: Chloroquine, pyrimethamine,
Metronidazole, etc.
5. Anthelminthic: Mebendazole, niclosamide, diethyl
carbamazine, etc.
Chemotherapy of cancer
In the human body cells undergo death in a controlled
fashion called apoptosis. Some genes are responsible
for having control on cell growth and division. If any
malfunctioning occurs in these types’ genes tumor may
generate. Tumors may produce in any of basic types of cells
named Epithelial cells, Connective tissue cells, lymphoid
and Nerve tissue cells.
Carcinomas: Malignant growths of epithelial cells.
Section 1 Pharmacology
Sarcomas: Malignant growths of muscle/connective
tissue.
90
Adenocarcinoma: Malignant growth of glandular tissue
CLASSIFICATION OF ANTICANCER AGENTS
a. Alkylating agent: Nitrogen mustard, cyclophosphamide,
chlorambucil, melphalan, thiotepa and busulfan.
b. Antimetabolites—
i. Folic acid antagonist—Methotrexate.
ii. Purine antagonist: 6-mercaptopurine, 6-thioguanine.
iii. Pyrimidineantagonist—5-fluorouracil, cytarabine
and arabinoside.
c. Antibiotics—bleomycin, dactinomycin, doxorubicin,
Daunorubicin, mitomycin-C and mithramycin.
d. Plant alkaloids—vinblastine, vincristine.
e. Nitrosources—carmustine, lomustine and semustine.
f. Random synthetics—cisplatinum, dicarbazine,
hexamethyl-melamines, procarbazine and hydroxyurea.
g. Enzymes L-asparaginase.
h. Hormones:
i. Adrenocorticoids—prednisolone, dexamethasone
ii. Androgen—testosterone
iii. Estrogen—diethylstilbestrol
iv. Antiestrogen—tamoxifen
v. Progestogen—hydroxyprogestron, megestrol acetate.
β-lactum antibiotics
These are narrow spectrum antibiotics.
Includes: Penicillin and cephalosporin.
it is so called because it contains beta lactam bring it is
found in to form penicillin and cephalus.
Penicillin was originally obtained from the fungus
Penicillium notatum but present source is Penicillium
chrysogenum.
Mechanism of action
All beta-lactam antibody interferes with the synthesis of
bacterial cell wall.
Bacteria synthesise UDP n-acetyl muramic acid and UDP
n-acetyl glucosamine.
The peptidoglycan residue is linked together forming
stand and UDP split off.
The final step is the cleavage of the terminal d-alanine
of the peptide chain transpeptidase.
This crosslinking provides stability and rigidity to the
cell wall.
The beta lactam antibody inhibits the transpeptidases,
so the cross linking does not take place.
When bacteria divide in presence of beta antibodies cell
wall deficient forms are produced, therefore, the interior
of the bacteria is hyperosmotic.
Cell wall deficient
forms well and burst resulting in bacteriolysis.
The primary mechanism of acquired resistance is
production of penicillinase enzyme. This enzyme opens
the beta-lactam is inactive.
Pharmacokinetics
Penicillin G is acid labile destroyed destroyed by gastric
acid.
Only one-third of an oral dose is absorbed.
Absorption from the intramuscular site is rapid, it has
very rapid renal action.
Side effect
1) Local irritancy and direct toxicity
Pain at injected side.
Nausea on oral injection.
Thrombophlebitis of the injected vein.
Bleeding has also occurred which such high dose due to
interference with platelet function.
Intrathecal is not recommended since cause arachnoiditis
and degenerative.
Accidental intravenous injection of procaine penicillin
produces
CNS stimulation hallucination conversion due to
procaine.
2) Hypersensitivity
Hypersensitivity is highest which procaine penicillin.
Topical penicillin is highly sensitizing there for topical
preparation are banned except for use in eye in case of
gonococcal ophthalmia.
3) JARISCH -HERXHEIMER reaction
Penicillin
injected
in a syphilitic patient particularly secondary
syphilis may produce shivering, fever, Myalgia,
exacerbation of lesion, even vascular collapse.
This is due to sudden release of spirochetalytic
Products and lasts for approx. 12 hours.
It does not recur and does not need interruption
of therapy. Aspirin and sedation effort relief of symptoms.
Uses
4. Beta lactam inhibitors—clavulanic acid sulbactam,
tazobactam.
Fluoroquinolone
Classification:
First generation: Norfloxacin, ofloxacin, ciprofloxacin.
Second Generation: Lancflaxacin, levofloxacin, noropcipro.
Uses
UTI
RTI
Typhoid
Diarrhoea
Dysentery
PID (pelvic bone inflammatory disease)
Hypersensitivity reaction of most common
1. Penicillin within minute death.
2. Xylocaune. Reumatitus— fever symptom- joint pain,
red spot, fourth night,
Mechanism of action
FQ inhibit the enzyme bacterial DNA with Nick's the
double stranded DNA introduce negative supercoil and
reseal the nicked end.
DNA gyrase consists of 2A and 2B subunit a subunit
carries out nicking of DNA. B subunit introduced
negative recoil and then A reseal the strand.
FQ bind the A subunit with high negative affinity
interfere with cutting and the resealing function.
1) medical uses
DPT
Streptococcal infection: - Pharyngitis, Rheumatoid Fever,
Otitis Media.
Pneumococcal infection- cause Pneumonia.
Meningococcal infection- cause Meningitis.
Gas gangrene
Syphilis caused by is treponema pallidum.
2) Dental infection
Penicillin G is most of the common infection in dentistry.
It is also used for periodontal abscess, peri apical abscess,
pericoronitis, ulcerative gingivitis.
It can also be used profile electrical to cover the
procedure.
Semisynthetic penicillin
It is needed because penicillin G is susceptible to
penicillinase,
poor oral efficacy, narrow special activity, hypersensitivity.
Classification
1. Acid resistant alternative to penicillin G—
phenoxymethylpenicillin.
2. Penicillinase—resistant penicillins—methicillin,
cloxacillin.
3. Extended spectrum penicillin -
A. Aminopenicillin—ampicillin, bacampenicillin,
amoxicillin.
B. Carboxypenicillin—carbenicillin, ticarcillin.
C. Uridopenicillin—piperacillin, mezolocilin.
Sulphonamides
It is an antimicrobial drug effective against pyogenic
bacteria.
1. Short acting (4–8 hours)—sulfadiazine, sulfisoxazole
2. Intermediate (8–12 hours)—sulfamethoxazole
3. Long-acting (7 days)—sulfadoxine, sulfamethapyrazine
4. Special purpose—sulfacetamide sodium, silver
sulfadiazine (burn), sulfasalazine (ulcerative colitis,
RA)
Mechanism of action
Many bacteria synthesize their own folic acid of which
para aminobenzoic acid is constituted sulfonamide being
structural analogues of PABA.
It inhibits bacterial folate synthesis.
FA not formed and because of its essential metabolic
reaction suffers.
Side effect
Nausea, vomiting, abdominal pain.
Crystalline urea. It is minimised by taking plenty of fluids
and by alkalinizing the urine.
Hypersensitivity reaction (5–10%).
Topical use not recommended: Because of contact
sensitivity but ocular use is recommended.
Cause haemolysis in individual with G-6-PD deficiency
(responsible for shape and size of the RBC).
Kernicterus (jaundice in brain) precipitate in
newborn.
Section 1 Pharmacology
91
Uses: Limited because of resistance and availability of
other antibiotics.
1. RA and ulcerative colitis.
2. Urinary tract infection.
3. Streptococcal pharyngitis and gum infection.
4. Trachoma and conjunctivitis.
5. Malaria—Sulfonamide combined with pyrimethamine
for treatment of chloroquine resistant malaria.
6. Toxoplasmosis (sulfadiazine + pyrimethamine)
7. Burn.
8. Lymphogranuloma venereum (venereal infection)
characterized by formation of ulcer and genital organ.
Swelling of lymph node. Sulfonamide second drug of
choice.
9. RA and ulcerative colitis—Sulfasalozine.
Combination of trimethylprim and sulfamethoxazole
(Cotrimoxazole)
It causes sequential block of folate by metabolism.
They have nearly same t half.
Trimethoprim enters many tissue and has larger
distribution than sulfonamide so given in the ratio of 5 : 1 .
Trimethoprim crosses BBB and placenta while
sulfonamide poorer entry.
Uses
1. UTI
2. Respiratory tract infection.
3. Typhoid
4. Dysentery, diarrhoea
5. Pneumocystis carinae pneumonia
6. Chancroid- drug of choice (veneral ulcer caused by
bacillus has decreyi in the genital organs)
7. Prostatitis- trimethoprim is concentrated in prostate.
8. Sequential block in bacterial folate metabolism
Cephalosporins
These are semisynthetic antibiotics.
1. First generation: These are used because of their higher
activity against gram positive aerobic bacteria and their
good penetration into alveolar bone
z
Cefazolin
z
Cephalexin
z
Cephradine
z
Cefadroxil
2. Second generation: They are used against oral and
anaerobes.
z
Cefuroxime
z
Cefaclor
z
Cefllroxime
z
Axetil
3. Third generation:
z
Cefdinir
z
Cefotaxime
z
Ceftizoxime
z
Ceftriaxone
z
Ceftazidime
4. Fourth generation:
Section 1 Pharmacology
z
Cefepime
z
92
Cefpirome
z
This group has no side effects and no contraindication.
Mechanism of action—same as penicillin
Uses
Meningitis
Sinusitis
RTI
UTI
Pneumonia
Gonorrhoea
Dental infection (which develop rashes and other mild
allergic reactions)
First and second-generation cephalosporin is mainly
prescribed for dental infection
Aminoglycoside
1) Systemic aminoglycoside 2) Topical aminoglycoside.
z
Streptomicin
z
Gentamicin
z
Kanamycin
z
Tobramycin
z
Sisomicin
z
Amikacin
z
Netilmicin
z
Neomycin and framycetin are also antibiotics.
Framycetin
It is too toxic for systemic administration and is used
topically on the skin, eye, ear in same manner as
neomycin
For example: Soframycin.
Neomycin
It is highly toxic to the internal ear (mainly auditory) and
to kidney, so not used systemically.
It is used topically for infected wounds, ulcers, burn,
external ear injections, conjunctivitis.
Orally it is used for preparation of bowel, before surgery
and it may reduce postoperative infection ant it
Hepatic coma
Aminoglycosides is gram-negative bacteria.
Streptomycin is used in T-B patients.
Mechanism of action: They are bactericidal.
Transport of aminoglycoside through bacterial cell wall
and cytoplasmic membrane.
Binding to ribosome resulting inhibition of protein
synthesis.
It binds to 30s ribosome (streptomycin) and other
aminoglycoside bind to an additional site on 50s subunit.
After exposure to aminoglycoside bacteria becomes more
permeable, ion amino acid and even protein leak out
followed by cell death.
Side Effects
Ototoxicity
Drugs are concentrated in labyrinthine fluid and are
slowly removed from it when plasma concentration
falls.
Ototoxicity is high if the plasma concentration of the
drug is persistently high and above a threshold value.
The vestibular/ cochlear sensory cells and hairs undergo
concentration dependent destruction changes deafness
is permanent.
Aminoglycoside ear drops can cause ototoxicity
when instilled in patient with perforated eardrum.
Contraindicated in them.
Vestibular damage
Headache appears first followed by nausea, vomiting,
dizziness, myasthenia gravis, vertigo, ataxia (change
in gait)
Nephrotoxicity
Tubular damage so loss of urine concentration power,
low GFR, N
It is reversible if the drug is discontinued.
retention, albuminuria and casts.
2
Neuromuscular blockade
All aminoglycosides reduce Ach
release from motor nerve ending.
It is higher with streptomycin and neomycin.
It is partially antagonized by I/V calcium salt myasthenia
gravis weakness is increased by these drugs.
Uses
(General medical uses)
1. Gentamycin is very valuable for preventing and treating
respiratory infection in critically ill patient in those with
impaired host defence (receiving anticancer drugs or
high dose corticosteroids AIDS neutropenic). Patient
in restriction wards with tracheostomy or on respirator
post-operative. Pneumonia patient with implants and
Intensive Care Unit ICU. Patient with tracheostomy or
respirators.
2. Pseudomonas proteus or klebsiella infection ,burn,
urinary tract infection ,pneumonia ,lung abscess ,
osteomyelitis, middle ear infection, septicaemia
3. meningitis caused by gram-negative bacilli—intrathecal
injection.
4. SABE: Subacute bacterial endocarditis.
Urinary antiseptics
some AMA is oral doses attain antibacterial concentration
only in the urinary tract like many other drugs. They
have concentrated in the kidney tubule. They have been
called urinary antiseptic because this may be considered
as a form of local therapy, for example, nitrofurantoin,
methenamine.
Methanamine
It decomposes in acidic urine to release formaldehyde
which inhibits all bacterial
Most UTIs are caused by gram-negative bacteria
especially
Majority of acute infections are caused by single
organism that is self-limiting. High urine rate with
frequent voiding is sufficient
Upper UTI (kidney ureters) require more aggressive and
longer treatment.
Lower UTI (urethra bladder) bacteria do not live for
more time as with more drinking water it is flesh of
from urethra.
For upper UTI drugs
Treatment
Sulfonamide—used for cystitis
Cotrimoxazole—most commonly used
Trimethoprim—used for acute infection
Fluoroquinolone—reversed for complicated cases
Ampicillin
Beta lactam antibiotic
Cephalosporin
Gentamicin
Tetracycline—used only on sensitivity report.
Chloramphenicol
Antitubercular drugs
1. First-line drugs
These drugs have high anti TB efficacy as well as low
toxicity and are used routinely.
Isoniazid (H) / Isonicotinic acid hydrazide.
Refampin (R) /Refampicin.
Pyrazinamide (Z)
Ethambutol (E)
Streptomycin. (only intramuscular is used)
2. Second-line drugs
These drugs have low anti-TB application for high toxicity
and used in special circumstances.
Thiacetazone
Para-aminosalicylic acid
Ethionamide
Cycloserine
Kanamycin
Amikacin
3. Newer drugs
Ciprofloxacin
Ofloxacin
Clarithromycin
Azithromycin
Rifabutin
Rifampicin
Obtained from streptomyces mediterranean
It inhibits DNA dependent RNA synthesis and absorbed
orally, penetrates cavities, caseous placenta and
meninges.
Interaction
Rifampicin is a microsomal enzyme induces that
enhances its own metabolism as well as that of many
drugs oral contraceptives, corticosteroids, steroids,
HIV protease inhibitors, etc contraceptive failures
have occurred.
Contraceptive failure occurs so increased with dose of
OCP or use alternative method.
Section 1 Pharmacology
93
Side effect
1. Hepatitis
z
Especially in pre-existing liver disease.
z
Development of jaundice requires discontinuation
of therapy.
2. Respiratory syndrome
z
Breathlessness.
3. Purpura, haemolysis, shock, renal failures flushing,
Rash.
4. Cutaneous syndrome
5. Flu syndrome—with chills, fever, headache, and bone
pain.
6. Abdominal syndrome—nausea, vomiting, abdominal
cramp, diarrhoea.
7. Urine and all secretions become orange-red.
Ankle edema due to local vasoconstriction
Nausea
Anorexia
Dizziness
Uses
1. Prophylaxis of Influenza A2 during on epidemic. It does
not interfere with antibody response to vaccination both
may be given together. Influenza B remain unaffected.
2. Treatment of Influenza A2 illness—reduction in fever,
cough, congestion.
3. Parkinsonism.
Contraindication
Epilepsy and other CNS diseases.
Gastric ulcer and pregnancy
Other uses
Leprosy
Prophylaxis of meningococcal Haemophilus inuenzae
meningitis and carrier state.
Second choice drug for methicillon strepto diphtheroids
and legionella infection.
The combination of doxyciline and rifampin
is first line therapy of brucellosis.
To increase the effect of amphotericin B is system fungal
infection.
Antiviral drugs
This drug is used in viral infections.
DNA virus—chickenpox CMV (cytomegalovirus)
RNA virus—rabies, polio, mumps or papilloma,
hepatitis.
TORCH: Toxoplasma, others, rubella, cytomegalo, herpes.
Induced abortion (spontaneous abortion)
Abortion: Less than 7 months is period of viability.
Lycan fluid
Classification
1. Anti-herpes: Idoxuridine, acyclovir (5 times/day)
2. Antiretro
z
Reverse transcriptase inhibitor: Zidovudine,
stavudine, lamivudine.
z
Protease Inhibitor: Saquinavir, indinavir.
z
Non-nucleoside reverse transpeptidase inhibitor:
Nevirapine, rimantadine.
3. Anti-influenza: Amantadine, rimantadine.
4. Nonselective: Ribavirin, interferon a.
Amantadine
It inhibits the replication of Influenza a virus. The stage
of which it acts is not known.
A protein designated M2 which act on ion channel has
been identified as one of its target actions. It acts on early
stage possibly uncoating and at late stage.
Possibly assembly of viral particle, resistance developed
by mutation that cause amino acid substitution in M
protein.
Side effects
Section 1 Pharmacology
Well-tolerated Insomnia
Nightmare
94
Postural hypotension
Antifungal drugs
Mycosis is of two: (1) superficial and (2) deep.
1) Superficial
a) Candida (monilla)
z
Oral thrush
z
Vaginitis
z
Automycosis
b) Dermatophyte
z
Epidermatophyton
z
Trichophyton
z
Microsporum
*These 3 causes Tinia or ring infection.
2) Deep-candida
Crptococcosis
Histoplasma
Blastomycosis
Aspergillosis.
Classification
1. Antibiotic
z
Amphotericin B (AMB)
z
Natamycin
z
Griseofolvin
z
Nystain
2. Anti-metabolite
z
Flucytosine
3. Azoles
z
Clotrimazole
z
Micanazol
z
Ketoconazole
z
Itraconazole
z
Fluconazole.
4. Allylamine
z
Terbinafine.
5. Other topical agents
z
Benzoic acid
z
2
Quiniolones
Amphotericin (B)
It is obtained from Streptomyces nodosus. Thus, have
a high affinity for ergosterol present over fungal cell
membrane and combine with it. Get inserted into the
membrane and several molecules orient themselves
together to form micropores through which ions, amino
acids and other water-soluble substances move out.
cholesterol present in the host cell membrane closely
resembles ergosterol. ANB bind with it so it most toxic
systemic used antibiotic.
AMB can be given orally for intestinal candidiasis. It can
be administered intravenously as a suspension made
with the help of deoxycholate. It gets widely distributed
in the body used tropically for vaginitis, automycosis.
Side effect
1. Acute reaction-
z
Chills, Fever, Pain, Dyspnea, Nausea, Vomiting.
z
When these are severe dose is gradually increased.
z
Corticosteroids can be given.
2. Long-term toxicity
z
Nephrotoxicity decreases GFR
z
Hypokalaemia
z
Inability of concentrated urine.
3. Anaemia: It occurs if Amphotericin B is given in long
span due to bone marrow depression.
Uses: AMB is used in case of systemic application in case
of deep infection. it can also be used tropically in case of
vaginitis and automycosis
Antimalarial drugs
Classification
1. Sulphonamide and Sulfone—Sulfadoxine, dapsone.
2. Newer drug—Artemether, arteether.
3. Quinoline—Mefloquine.
4. Arcidine—Mepacrine.
5. 4-Aminoquinolines—chloroquine.
6. 8-Aminoquinolines—primaquine.
7. Biguanide—proguanil (chloroquanide)
8. Cinchona Alkaloid—quinine, quinidine.
9. Diaminopyrimidine—pyrimethamine.
10. Tetracyclines—tetracycline, doxicycline
Chloroquine
It is rapidly acting against erythrocytic schizontocide of
all species of plasmodium.
It does not affect on pre- and exo-erythrocytic phase of
parasite and does not prevent replaces in vivax malaria
and oval malaria.
Mechanism of action
Is not known completely.
It is actively concentrated by sensitive intraerythrocytic
plasmodia.
A higher concentration is formed in infected RBC.
It raises the vesicular pH and thereby interfere with
degradation of haemoglobin by parasitic lysosomes,
conversion of toxic to non-toxic, parasite pigment
hemozoin in inhibited by formation of chloroquine
heme complex. Heme then damage the plasmodial
membranes.
Resistance is Plasmodium falciparum is associated
with a decreased ability of the parasite to accumulate
chloroquine such cases are treated with mefloquine or
quinine along with primaquine.
Other action
It is active against Entamoeba histolytica and Giardia
lamblia also.
It has anti-inflammatory, local irritant and local
anesthetics, weak smooth muscle relaxant, antihistaminic,
antiarrhythmic properties.
Side Effects
Nausea, vomiting, anorexia, epigastric pain.
Parenteral administration causes hypertension, cardiac
depression, arrhythmia, CNS toxicity.
Prolonged use of high doses cause loss of vision due to
retinal damage as it is selectively accumulated in retina
Loss of hearing, rashes, mental disturbances discoloration
of hair, discoloration of nails.
Antileprotic drugs
Classification
1. Sulfone—dapsone
2. Phenazine derivate—clofazimine.
3. Antitubercular drug—rifampin, ethionamide.
4. Other antibiotics—ofloxacin, minocycline, clarithromycin.
Dapsone
it is diamino diphenyl sulfone.
it is chemically related to sulfonamide.
it inhibits PABA incorporation into folic acid.
it is especially concentrated in skin specially lapromatus
muscles, liver, kidney.
Side Effects: Well-tolerated at hundred milligrams per
day or less.
1. Mild hemolytic anaemia-
z
Patients with G-6-PD deficiency are more susceptible
to haemolysis and even more than 50 milligrams per
day produce haemolysis (so, this drug is not given
and high protein diet is given to that patient and then
this drug is started.)
2. Gastric intolerance—nausea, vomiting.
3. Cutaneous reaction—allergic reaction, phototoxicity
4. Hepatitis agranulocytosis
5. Lepra reaction.
Contraindication
In severe anaemia with haemoglobin less than 7-gram
percentage.
G-6-PD deficient patient.
Having hypersensitivity reaction.
Other uses
In combination with pyrimethamine for chloroquine.
Resistant malaria (qnane/artiethal, artimethal, e-mal
injection)
Lepra reaction
It occurs in lepromatous leprosy with chemotherapy or
with intercurrent injection.
Jerish Hersheimer type of reaction—due to release of
antigen from killed bacilli it may be mild, moderate,
severe or life threatening (ENL—erythema nodosum
leprosum)
Section 1 Pharmacology
95
The reaction which develops, after 4 to 6 weeks it’s
called sulfone syndrome consist fever, malase, lymph
node enlargement, desquamation of skin, generally this
syndrome is seen in the malnourished patient.
lepra reaction is of abrupt onset, existing lesion enlarged,
become red, swollen and painful even several new
lesions appear.
Dapsone is discontinued only in severe cases. Clofazimine
(200 mg/day) is highly effective and given in spite of
Dapsone and in high dose that is 200 milligram per day
MULTIPLE CHOICE QUESTIONS
due to its anti-inflammatory property and therefore,
controls the reactions.
Analgesic, antipyretic, antibiotic drugs are also used
according to need. Corticosteroids are given only in
severe cases.
Chloroquine and Thalidomide also suppress lepra
reactions.
Thalidomide is contraindicated in pregnancy. If given
result in Phacomalia (baby develops seal like body, no
proper Limbs)
1. Mechanism of cellular resistance to polyfunctional
alkylating drugs:
A. Decreased DNA repair capability
B. Reduced production of glutathione
C. Increased permeability to the drug
D. None of the above
2. Does not have direct vesicant effects:
A. Mechlorethamine (Mustargen)
B. Carmustine (BNCU,bicnu)
C. Cyclophosphamide (Cytoxan)
D. A and B
3. Piperazine antagonizes the anthelmintic action of
the following drug:
A. Pyrantel pamoate B. Mebendazole
C. Albendazole D. Niclosamide
4. The polyfunctional alkylating agent used
specically the for chronic myeloid leukaemia:
A. Cyclophosphamide B. Busulfan
C. Thiopental D. Dacarbazine
5. The principal active alkaloid of ipecac is:
A. Yohimbine B. Caffeine
C. Apomorphine D. Emetine
6. Emetine is used in the treatment of:
A. Malaria B. Tuberculosis
C. Amebiasis D. None of the above
7. Peripheral neuritis caused by isoniazide can be
prevented by pretreatment with:
A. Riboflavin B. Pyridoxine
C. Thiamine D. All of the above
8. Select the drug used in the treatment of lariasis:
A. Diethyl carbamazine citrate
B. Thiabendazole
C. Levamisole
D. Piperazine citrate
9. Zidovudine-resistant strains of HIV can be treated
with
Section 1 Pharmacology
96
A. Acyclovir B. Ribavarin
C. Dideoxycytidine D. All of the above
10. Which of the following drug is effective against
malarial parasite in the liver but not within the
erythrocyte?
A. Proguanil B. Chloroquine
C. Pyrimethamine D. Primaquine
11. Major toxicity of alkylating drugs:
A. Alopecia B. Myelosuppression
C. Renal damage D. Hepatic failure
12. In the treatment of acute inorganic arsenic
poisoning, the most likely drug to be used is:
A. Deferoxamine B. Dimercaprol
C. EDTA D. Penicillamine
13. Which of the following drugs or drug groups is not
useful in the prevention of nausea and vomiting
included by cancer chemotherapy?
A. Dexamethasone B. Dronabinol
C. Ketaserin D. Ondansetron
14. The most useful alkylating drug currently available:
A. Cyclophosphamide B. Melphalan
C. Lomustine D. Thiopental
15. Nitrosourea with minimal bone-marrow
suppression and effective in treating pancreatic,
islet cell carcinoma:
A. Lomustine B. Carmustine
C. Streptozocin D. Procarbazine
16. Which of the following antineoplastic drugs is a
mitotic inhibitor and causes metaphase arrest?
A. Busulfan B. Vincristine
C. Cytarabine D. Procarbazine
17. Vinca alkaloids exert antitumor activity by:
A. Activating topoisomerase II to cause breaks in
DNA strands
B. Crosslinking DNA strands
C. Inhibiting DNA mediated RNA synthesis
D. Inhibiting polymerization of tubulin to form
intracellular microtubules
18. Used in combination with vinblastine and
bleomycin: A major advance in treating non-
seminomatous testicular cancer:
A. Altretamine B. Cisplatin
C. Procarbazine D. Methotrexate
19. The following is true of cyclophosphamide except:
A. It is highly reactive and a vesicant on contact
B. It is a prodrug
C. It has marked immunosuppressant property
D. It frequently causes alopecia and cystitis
20. Little effect on the bone marrow: Can cause
significant renal dysfunction and sometimes
acoustic nerve dysfunction.
A. Methotrexate B. Cisplatin
C. Lomustine D. A and C
21. Combination of allopurinol with this anticancer
drug can cause an increase in toxicity:
A. 6-Thioguanine
B. Fluorouracil (5-Fu)
C. 6-Mercaptopurine
D. Azatadine (optimine)
22. A small amount of atropine is added to the
diphenoxylate tablet/syrup to
A. Suppress associated vomiting of gastroenteritis
B. Augment the antimotility action of
diphenoxylate
C. Block side effects of diphenoxylate
D. Discourage overdose and abuse of diphenoxylate
23. Recommended for treating hairy cell leukemia:
A. Methotrexate B. Cladribine
C. Vinblastine D. Cytarabine
24. The combination of trimethoprim and
sulfamethoxazole is effective against which one
of the following opportunistic infections in the
AIDS patient?
A. Disseminated herpes simplex
B. Cryptococcal meningitis
C. Toxoplasmosis
D. Oral candidiasis
25. Sulfonamide used in treatment of ulcerative colitis
is:
A. Sulfasalazine B. Sulfacetamide
C. Silver sulfadiazine D. Mafenide
26. The top four most commonly diagnosed cancers
include all of the following except:
A. Lung B. Prostate
C. Colon and rectum D. Breast
27. Which one of the following statements about the
mechanisms of action of drugs used in cancer
chemotherapy is least accurate?
A. Alkylating agents commonly attack the
nucleophilic N-7 position in guanine
B. Anthracyclines intercalate with base pairs to
block nucleic acid synthesis
C. Mercaptopurine is an irreversible inhibitor of
HGPRTase
D. Paclitaxel acts mainly in the M phase of the cell
cycle
28. The mechanism by which sulfasalazine exerts its
primary action in ulcerative colitis is inhibition of
A. Folic acid synthesis
B. The formation of leukotrienes and
prostaglandins
C. Phospholipase C
D. Proton pump activity
29. Which one of the following adverse effects is most
likely to occur with sulfonamides?
A. Neurologic effects, including headache,
dizziness, and lethargy
B. Fanconi’s aminoaciduria syndrome
C. Kernicterus in the newborn
D. Skin reaction
30. The cephalosporin that is active against
Pseudomonas aeruginosa is:
A. Ceftazidime B. Cephalexin
C. Cephalothin D. Cefuroxime
31. What is true of short course DOTS(WHO) strategy
for treatment of tuberculosis?
A. It consists of an initial intensive phase and a
later continuation phase
B. The dose of antitubercular drugs is reduced
after clinical response occurs
C. The patient himself is made responsible for
administering antitubercular drugs
D. All of the above
32 . The primary reason for the use of drug combinations
in the treatment of tuberculosis is to:
A. Ensure patient compliance with the drug
regimen
B. Reduce the incidence of adverse effects
C. Enhance activity against metabolically inactive
mycobacteria
D. Delay or prevent the emergence of resistance
33. Which one of the following drugs is most likely to
cause loss of equilibrium and auditory damage?
A. Amikacin B. Ethambutol
C. Isoniazid D. Rifabutin
34. Which one of the following statements about
uconazole is most accurate?
A. It is highly effective in treatment of aspergillosis
B. It does not penetrate the blood–brain barrier
C. Its oral bioavailability is less than that of
ketoconazole
D. It inhibits demethylation of lanosterol
35. Which one of the following drugs is least likely
to be effective in the treatment of oesophagal
candidiasis, it is used by the oral route?
A. Amphotericin B B. Fluconazole
C. Griseofulvin D. Ketoconazole
36. Which of the following viruses is most susceptible
to acyclovir?
A. Herpes simplex type I virus
B. Herpes simplex type II virus
C. Varicella-zoster virus
D. Epstein-Barr virus
Section 1 Pharmacology
97
37. How do antimetabolites exert their cytotoxic
effect?
A.
Inhibiting DNA synthesis by sliding between
DNA base pairs
B. Inhibiting RNA synthesis by sliding between
RNA base pairs
C. Acting as false metabolites in the microtubules
D. Acting as false substitutions in the production
of nucleic acid
38. The most common drug causing anaphylaxis is:
A.
Streptomycin B. Indomethacin
C. Penicillin D. Paracetamol
39. Plasmodial resistance to chloroquine is due to:
A.
Change in receptor structure
B. Decreased carrier-mediated drug transport
C. Increase in the activity of DNA repair
mechanisms
D. Induction of inactivating enzymes
40. Which one of the following drugs is most
appropriate for oral use in vaginal candidiasis?
A.
Clotrimazole B. Griseofluvin
C. Fluconazole D. Flucytosine
41. Anticancer drug that is also used to treat psoriasis
and rheumatoid arthritis:
A.
Mercaptopurine B. Methotrexate
C. Procarbazine D. Allopurinol
42. The antiviral actions of this drug include
inhibition of both RNA and DNA synthesis. The
drug is used for the treatment of severe respiratory
syncytial virus infections in neonates.
A.
Amantadine B. Amprenavir
C. Ribavirin D. Ritonavir
43. Used in the prophylaxis and treatment of infection
due to influenza viruses, this drug facilitates
clumping of mature virions and their adhesion to
infected cells.
A.
Amantadine B. Efavirenz
C. Oseltamivir D. Rimantadine
44. Which statement regarding phase-specific
chemotherapic agents is correct ? They:
A.
Are most effective in one phase of the cell cycle
B. Effective in all phases of the cell cycle
C. Are only effective in G0 phase
D. Include the antituber antibiotics
45. Infections due to gram-negative bacilli have
occurred when this agent has been used as a skin
antiseptic:
A.
Acetic acid
B. Benzalkonium chloride
C. Hexachlorophene
D. Thimerosal
46. Which one of the following antiseptics promotes
Section 1 Pharmacology
98
wound healing?
A.
Cetylpyridium B. Hexachlorophene
C. Iodine D. None of the above
47. A patient with AIDS has an extremely high viral
RNA titer. While blood is being drawn from
this patient, the syringe is accidentally dropped,
contaminating the oor, which is made of porous
material. The best way to deal with this is to:
Completely replace the contaminated part of
A.
the floor
B. Clean the floor with soap and water
C. Seal the room and decontaminate with ethylene
oxide
D. Clean the floor with a 10% solution of household
bleach
48. Tetracycline should be avoided during pregnancy
and childhood because of:
Susceptibility to superinfection
A.
B. Intolerance
C. Selectively taken up by growing bones
D. Bone marrow toxicity
49. Which of the following drugs enhances GABA
actions on the neuromuscular junctions of
nematodes and arthropods?
Glutamic acid B. Ivermectin
A.
C. Picrotoxin D. Pyrantel pamoate
50. Methotrexate:
Is useful in choriocarcinoma
A.
B. Is safe in patients with renal dysfunction
C. Induced neurotoxicity is reversed by leucovorin
D. Is not used in children
51. Auditory nerve damage is caused by:
Gentamicin
A.
B. Neomycin
C. Dihydrostreptomycin
D. All of the above
52. This drug is the preferred agent for the
treatment of nocardiosis and, in combination
with pyrimethamine, is prophylactic against
Pneumocystis carinii infections in AIDS patients.
Ampicillin B. Clindamycin
A.
C. Norfloxacin D. Sulfadiazine
53. Prolactin:
Has somatotropic activity
A.
B. If low can cause infertility in women
C. Can suppress menstrual cycle in lactating
women
D. Levels are increased by dopamine
54. In antiviral immunity, what directly recognized
and kills viral-infected cells?
Cytotoxic T cells (CTLs)
A.
B. Antiviral antibodies
C. Interferons
D. None
55. The metabolism of griseofulvin is accelerated by:
Carbamazepine B. Aspirin
A.
C. Phenobarbitone D. All of the above
56. Which one of the following enzymes is not unique
to parasites?