Chemotherapy

PHARMACOLOGY
(Unit – II ) Chemotherapy &
Antibiotics – Introduction
Mr. Dipti Y. Sorte
Himalayan College of Nursing, SRHU.
Dehradun.
18/23/2018

Syllabus – (Unit II: Chemotherapy)
Pharmacology of commonly used:
• Penicillin
• Cephalosporin’s
• Aminoglycocides
• Macrolide & Broad Spectrum Antibiotics
• Sulphonamides
• Quinolones
• Ant amoebic
• Antimalarial
• Antithelmintic
• Antiscabies agents
• Antiviral & Antifungal agents
• Antitubercular drugs
• Antileprosy drugs
• Anticancer drugs
• Immune-suppressants.
Composition,
action, dosage,
route, indications,
contraindications,
drug interactions,
side effects,
adverse, effects,
toxicity & role of
nurse.
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Definition
Chemotherapy & Antibiotics:
• Chemotherapy: Chemotherapy is the treatment of
infections by substances which destroy or suppress
bacteria and other microorganism. The substances /
Agents used may natural synthetic or semi – synthetic
in nature.
• Antibiotics: An antibiotic is a chemical substance
produced by microorganism which prevents the
growth of other microorganism or kills the other
microorganism. These are natural substances
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Chemotherapy
It is a method of
therapy of infectious
disease and cancer with
chemical agents –
chemotherapeutic
medicines
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Drug
Mechanisms
of Action
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Classification of Antibiotics
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Antibiotics Classified as:
• According to the mode of action on Bacteria:
• According to the type of Bacteria:
• According to the effectiveness against
microorganism:
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According to the mode of action on Bacteria:
• Bacteriostatic: These antibiotics inhibit the growth &
multiplication of Bacteria. Eg. Tetracycline,
Chloramphenicol, Sulphonamides, Dapsone,
Erythromycin, Clindamycin.
• Bactericidal: These antibiotics destroy or kill all the
Bacteria in the process of multiplication. Eg. Penicillin,
Aminoglycosides, Cephalosporin, Fluoroquinolones,
Rifampicin, Metronidazole etc.
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According to the type of Bacteria:
• Gram Positive: Some Antibiotics are effective mainly
against Gram Positive Bacteria Eg. Penicillin.
• Gram Negative: Some Antibiotics are effective mainly
against Gram Negative Bacteria Eg. Streptomycin.
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According to the effectiveness against
microorganism:
• Broad Spectrum: The Antibiotics which acts against
wide range of microorganisms. Eg. Tetracycline.
• Narrow Spectrum: These Antibiotics are useful
against limited microorganisms. Eg. Erythromycin
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Common side effects of chemotherapeutic
Agents:
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Common side effects of chemotherapeutic
Agents:
• Toxic Effects: Gastrointestinal irritation, Nausea, Vomiting and
diarrhea may occur when given by mouth.
• Skin sensitivity may develop with Penicillin or streptomycin causing
rashes.
• Serious toxic effect may occur due to streptomycin on the vestibular
& auditory nerve causing vertigo & deafness
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• Drug Resistance: Many bacteria soon develops
resistance to particular drug after a period of
treatment, so that the bacteria will not respond to
the same drug for example tubercle bacillus develops
resistance to streptomycin quickly.
• Super infection: The antibiotics given by mouth kill
the normal bacteria inhibiting the alimentary canal
and permits the over growth of other insensitive
organisms which can cause serious complications. Eg.
Fungus cause thrush which may go to the lungs with
fatal results.
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• Hypersensitivity Reaction: Chemotherapeutic agents
can cause Hypersensitivity reactions from mild rashes
to serve anaphylactic shock. Eg. Penicillin &
Sulphonamides.
• Vitamin Deficiency: Alteration in vitamin formation
and absorption from the bowel take place . So there is
deficiency of Vitamin B complex and Vitamin K.
• Anemia: In susceptible persons chloramphenicol may
produce Aplastic anemia or agranulocytosis. (Action
must be taken through proper history about previous
drug reaction before administering penicillin
sulphonamide and cephalosporin to the patient.
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Selection of Appropriate
antimicrobial Agents
• The choice of antimicrobial agents depends on
following factors: Patient factors
1. Age.
2. History or Allergy.
3. Genetic abnormalities.
4. Pregnancy.
5. Host defence.
6. Hepatic dysfunction.
7. Renal dysfunction.
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Drug factor
1. Route of administration.
2. Spectrum of antimicrobial activity.
3. Bactericidal/Bacteriostatic effect.
4. Ability to cross blood brain barrier.
5. Cost of the AMA (American Medical Association)
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Organism related factor
1. Clinical Diagnosis.
2. Bacteriological reports.
3. Resistance to AMA drugs.
4. Cross resistance.
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Pharmacology of commonly used Drugs:
•Penicillin
•Cephalosporin’s
•Aminoglycosides
•Macrolide & Broad
Spectrum Antibiotics
•Sulphonamides
•Quinolones
•Ant amoebic
•Antimalarial
•Antithelmintic
•Antiscabies agents
•Antiviral & Antifungal
agents
•Antitubercular drugs
•Antileprosy drugs
•Anticancer drugs
•Immune-suppressants
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Penicillin
 It is an antibiotic, discovered by
Alexander Fleming (1881-1955)
in 1928.
 β-lactam antibiotics
 It was isolated from fungus
Penicillium notatum.
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Penicillin
• Introduction: Penicillins were the first antibiotics to be
isolated and used clinically in 1941. Penicillins usually are
bactericidal, they are most effective against fast growing
susceptible bacteria.
• Mechanism of Action: Penicillin inhibit the synthesis of
bacterial cell wall and causing rapid cell lysis.
• Indication & Uses:
1. Gram positive cocci infections.
2. Streptococcal, pneumococcal & meningococcal infection.
3. Venereal disease like gonorrhoea, syphilis.
4. Diphtheria, tetanus & Gas gangrene.
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Classification of Penicillins
Natural penicillins β- lactamase resistant
penicillins
Aminopenicillins Carboxypenicillins Ureidopenicillins
-Penicillin G
-Penicillin V
-Methicillin
-Nafacillin
-Isoxazolyl Penicillins
-Ampicillin
-Amoxicillin
-Ticarcillin -Piperacillin
-Mezlocillin
-Azlocillin
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Drug Examples & Doses:
S.
no.
Drugs Doses
1 Cloxacillin 250 – 500 mg orally every 6hr(Max.
4gm/day)
2 Ampicillin 0.25 to 1gm daily IM/IV every 6hr.
3 Amoxicillin 0.25 to 1gm 8hrly
4 Dicloxacillin 0.25 to 1gm orally
5 Piperacillin + Tazobactum 4-5gm and 0.5gm every day 6hr.
6 Penicillin V 0.12 to 0.5gm every 6hr.
7 Penicillin G 0.12 to 0.31gm every 4hr.8/23/2018 29

Contd
• Contraindication & Precautions: Contraindicated to the patient
who have sensitivity to penicillin drug.
• Adverse effect: Nausea, vomiting, epigastric distress, Allergic
reaction, phlebitis, diarrhoea, rash, pain at IM site.
• Drug interactions:
1) Penicillins may decrease the effect of aminoglycosides.
2) Bacterial effects of penicillin may decrease with tetracycline
drugs.
3) Use of penicillin with clavulanate or sulbactum increase
resistance against bacteria that produce beta – lactamase.
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Nursing Responsibilities.
•Before administration of drug, obtain
patients allergic history.
•After administration observe sign and
symptoms of an allergic reaction.
•Do not allow to take oral
contraceptive with this therapy.
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Cephalosporin
Cephalosporins are second major group of β-
lactam ,broad spectrum,penicillanase resistant
antibiotics
They were isolated from cultures of
Cephalosporium acremonium by italian scientist
Giuseppe Brotzu in 1945.
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Cephalosporin
• Introduction: Cephalosporin's are clinically and
pharmacologically similar to penicillin. These drugs are
bactericidal
• Mechanism of Action: as penicillin it also inhibit the synthesis
of bacterial cell wall and causing rapid cell lysis.
1. Gram positive and gram negative bacterial infection.
2. Respiratory tract infection & Septicaemia.
3. Urinary tract infection & Abdominal infections.
4. Hospital acquired infection ( 3rd Generation are preferred)
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CLASSFICATION OF CEPHALOSPORINS
First
Generation
Second
Generation
Third
Generation
Fourth
Generation
Fifth
Generation
1.Parenteral 1.Parenteral 1.Parenteral 1.Parenteral 1.Parenteral
Cephalothin Cefamycinc Cefotaxime Cefepime Ceftobiprole
Cephaloridine Cefoxitin Ceftazidime Cefpirome
Cefazolin Cefotitan Ceftriaxone
Cefmetazole
2.Oral 2.Oral 2.Oral
Cephalexin Cefachlor Cefixime
(Keflex) Cefprozil Cefdinir
Cephadroxil Ceftibuten
(Durecef)
3.Oral & Parenteral
Cephradine 348/23/2018

S.
no.
Drugs Doses
1 Cephalexin 0.25 to 1gm 6-8 hrly orally.
2 Cephalothin 1 to 2gm 6hrly IV
3 Cefuroxime 0.75 to 1.5gm I/V or I/M
4 Cefotaxime 1 to 2gm 12hrly I/V
5 Ceftriaxone 1 to 4gm daily I/V
6 Cefaclor 0.25 to 0.5gm every 8hr.
7 Cefpirome 1 to 2gm 12hrly
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Contd
• Contraindication & Precautions: Use cephalosporin cautiously in
the patient who are allergic to penicillin.
• Adverse effect: cautiously with pregnant and breast feeding
women, History of G.I. Disorders.
Cephalosporin should not used with penicillins, they should be
given separate site to prevent inactivation.
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•Before administration of drug, obtain
patients allergic history.
•After administration observe sign and
symptoms of an allergic reaction.
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Aminoglycosides
• Introduction:.
• Mechanism of Action: These drugs inhibit protein synthesis
in the bacteria, there permeability is increased and cell
contents leak out and death of cell occurs. These drugs leave
bactericidal action.
1. Gram negative infection.
2. Septicaemia.
3. Post operative UTI.
4. Tuberculosis infection.
5. Infection of bones, skin, soft tissue & Joints.
6. Pelvic inflammatory disease.8/23/2018 39

Classification of Aminoglycosides
Streptomycin
Neomycin
Gentamicin
Amikacin
Tobramycin
40
Kanamycin
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S.
no.
Drugs Doses
1 Streptomycin 1to 2gm per day divided 12 hrly (max.
2gm/day)
2 Gentamicin 1to 1.5mg/kg IV/IM 8hrly
3 Neomycin 1gm orally 4hrly.
Pediatric: 50mg/kg/day, Adult 3gm/day.
4 Kanamycin 15mg/kg/day divided 12hrly.
5 Amikacin 15mg/kg/day IM 2-3 divided doses
6 Tobramycin 3to 5 mg/kg/daily in divided dose.
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Contd
• Contraindication & Precautions: drug is contraindicated for
pregnant and breast feeding women, it is cautiously used in patient
with renal failure.
• Adverse effect:
1. Ototoxicity, Hypersensitivity reactions.
2. Nephrotoxicity, Hemolytic Anemia, Leukopenia.
3. Neuromuscular blockage, Thrombocytopenia.
4. Nausea/ vomiting, elevated liver enzyme.
5. Diarrhoea, Phlebitis.
• Drug interactions: They may cause ototoxicity use with loop
diuretic or another aminoglycosides. Inactivation occurs if penicillin
antibiotics mixed with aminoglycosides.
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• Assess adverse effect, eg. Vertigo, hear
loss.
•Monitor renal function for evidence of
nephrotoxicity.
•Make sure that patient is well hydrated
during therapy and encourage for fluid
intake 1.2 to 2lit / day.
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Macrolide & Broad Spectrum Antibiotics
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WHAT ARE MACROLIDES?
• They are antibiotics having a macrocyclic lactone ring with attached
sugars.
• THE COMMONLY USED MACROLIDES ARE:
Erythromycin
Clarithromycin
Roxithromycin
Azithromycin
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Classification of Macrolides
Erythromycin
Newer Macrolides
46
• Roxithromycin
• Clarithromycin
• Azithromycin
• Spiramycin
Older Macrolides
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ERYTHROMYCIN
• First isolated from Streptomyces erythreus in 1952
• Widely employed as an alternative to penicillin
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MECHANISM OF ACTION
• It is bacteriostatic at low concentration & bactericidal
at high concentration
• Bactericidal property depends on the concentration,
organism concerned and its rate of multiplication
• Erythromycin acts by inhibiting bacterial protein
synthesis. It combines with 50s ribosome subunits
and prevent translocation.
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ANTIMICROBIAL SPECTRUM
• It is a narrow spectrum antibiotic
• Spectrum is similar to Pencillin G. Mostly gram positive and few
gram negative bacteria.
• Str. pyogenes , Str. Pneumonia, N. gonorrhea, Clostridium, C.
Diphtheriae and Listeria
• In addition, Campylobacter, Legionella, Branhamella
catarrhalis, G. vaginalis and Mycoplasma (which are not
affected by pencillin are also highly susceptible to
erythromycin)
• Moderately sensitive to H. influenza, B. pertussis, C.
trachomatis, N. meningitidis and Rickettsiae
• Ineffective against Enterobacteriaceae, other gram negative
bacilli.
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Adverse Effects
1. Gastrointestinal – epigastric pain, diarrhea
2. Reversible hearing loss
3. Hypersensitivity – fever, rash
Interaction
• It inhibits hepatic oxidation of many drugs – it
rises plasma level of theophylline,
carbamazepine, valproate, ergotamine and
warfarin
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USES • As an alternative to penicillin
1. Streptococcal pharyngitis, tonsillitis, mastoiditis and
CAP
2. Alternative prophylaxis for RF and SABE
3. Diphtheria
4. Tetanus as an adjuvant to TT
5. Syphilis and gonorrhea
6. Leptospirosis
• As a first choice drug for
1. Atypical pneumonia caused by Mycoplasma
2. Whooping cough
3. Chancroid
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NEWER MACROLIDES
• ROXITHROMYCIN
• CLARITHROMYCIN
• AZITHROMYCIN
• SPIRAMYCIN
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Macrolides
• THE COMMONLY USED MACROLIDES ARE:
Erythromycin
Clarithromycin
Roxithromycin.
Azithromycin.
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•Mechanism of Action: It is bacteriostatic at low
concentration & bactericidal at high concentration.
Bactericidal property depends on the
concentration, organism concerned and its rate of
multiplication.
•Indication & Uses: nxt slide.
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Therapeutic Uses:
• As an alternative to penicillin.
a) Diphtheria.
b) Tetanus.
c) Leptospirosis.
d) Syphilis and gonorrhoea.
• As first choice of drug.
a) Mycoplasma pneumonia.
b) Whooping cough.
c) Cancroid
• As second choice of drug.
a) Trachomatis infection of
urogenital tract.
b) Penicillin-resistant
Staphylococcal infections
c) Legionnaires' pneumonia.
d) Campylobacter enteritis.
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S.
no.
Drugs Doses
1 Erythromycin 250-500 mg 6 hourly (max. 4 g/day), children 30-60
mg/kg/day.
2 Roxithromycin 150-300 mg BD 30 min before meals, children 2.5-5
mg/kg/day. Syp50 mg /5 ml liquid; ROXEM 50 mg kid tab.
3 Clarithromycin 250 mg BD for 7 days; severe cases 500 mg BD up to 14
days. CLARIBID 250, 500 mg tabs, 125 mg/5 ml dry syr.
4 Azithromycin Adult: 500 mg once daily 1 hour before or 2 hours after
food (food decreases bioavailability); (children above 6
month-10 mg/kg/day for 3 days is sufficient for most
infections.
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Contd
• Contraindication & Precautions:.
• Adverse effect:
1. Gastrointestinal – epigastric pain, diarrhea
2. Reversible hearing loss.
3. Hypersensitivity – fever, rash.
• Drug interactions: It inhibits hepatic oxidation of many drugs – it
rises plasma level of theophylline, carbamazepine, valproate,
ergotamine and warfarin
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• Assess I/O. Report haematuria.
•Administer I/V after diluting.
•C/S to be done before Drug therapy.
•Evaluate therapeutic response.
•Teach to take oral drug with plenty of
fluid.
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Broad Spectrum Antibiotics
•Introduction: Tetracycline & Chloramphenicol
are broad spectrum antibiotics. They are called so
because of there effectiveness against a wide
range of microorganism sucg as Gram positive &
Gram negative bacteria Eg. Rikettsia, M
pneumonia, Chlamydia, anaerobes, sirochetes, H.
pylori and some protozoa (eg. Malerial parasites
& Entamoeba)
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Tetracycline
• Introduction: Broad-Spectrum Bacteriostatic Antibiotics
• Active against many gram-positive and gram-negative bacteria, including
Anaerobes, Rickettsiae, Chlamydiae, Mycoplasmas, Protozoa, e.g. amoebas
Mechanism of Action: It inhibit bacterial protein synthesis by
binding to and interfering with ribosomes.
• Indication & Uses: Chlamydial infections, including sexually
transmitted diseases, In combination with an aminoglycoside,
indicated for plague, tularemia, and brucellosis, Treatment of acne,
Exacerbations of bronchitis, Community-acquired pneumonia, Lyme
disease, Relapsing fever, Leptospirosis Nontuberculous
mycobacterial infections (e.g., Mycobacterium marinum).
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Classification of Tetracycline's
Short-acting
(6-8 hours)
Demeclocycline and Methacycline
Long-acting
(16-18 hours)
Chlortetracycline, Tetracycline, Oxytetracycline
Intermediate-
acting (12 hours)
61
Doxycycline and Minocycline
8/23/2018

S.
no.
Drugs Doses
1 Chlortetracycline, 250 to 500mg 6hrly orally IV
2 Oxytetracycline 250 to 500mg 6hrly orally IV
3 Tetracycline 250 to 500mg 6hrly orally IV
4 Doxycycline 100 to 200mg daily/orally.
5 Minocycline 100 to 200mg daily/orally.
8/23/2018 62

Contd
• Contraindication & Precautions: Hypersensitivity to tetracycline
drugs. Take precaution in Renal disease, Hepatic disease.
• Adverse effect: Mild nausea, Anorexia, Bulky and loose stool,
Hepatotoxicity, Flatulence, pancreatitis.
Milk and dairy products, Magnesium containing laxatives, antacids,
calcium supplements, iron supplements reduce absorption of
tetracycline's.
Tetracycline's decrease the effect of penicillins & Hormonal
contraceptives drugs.
8/23/2018 63

• They should not be used during pregnancy,
lactation and childhood.
•They should not be given when renal
functions are impaired.
•Instruct the patient not to take antacids
calcium supplements, iron supplements &
Magnesium containing laxatives.
•Do not take Milk or dairy products within 2-
3hrs of taking tetracycline's.
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Chloramphenicol
Introduction:Broad spectrum (aerobic, anaerobic, gram +, gram -,
Rickettsiae) they closely resembles in the action to the tetracycline’s
 Bacteriostatic (H. influenzae, Neisseria meningitidis)
• Mechanism of Action: They inhibit protein synthesis in
susceptible bacteria, in presence of these drug, organism cannot
multiply thus it acts as bacteriostatic drug.
1. Mainly used in typhoid fever.
2. UTI, Rickettsial, Cholera, Bacterial meningitis, Eye, Ear
infections.
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• Adult & Child: PO/IV 50 to 100mg/kg/day in divided doses of Q6h not
exceed to 100mg/kg/day.
8/23/2018 66

Contd
• Contraindication & Precautions:
History of hypersensitivity or toxic reactions, Pregnancy & Lactation,
spl. precaution for renal impaired and hepatic patients.
• Adverse effect: Nausea, vomiting, diarrhea, oral/vaginal
candidiasis, Bone marrow depression, Hypersensitivity reaction.
oChemical inhibits metabolism of tobutamide chorpropamide,
warfarin, cyclophosphamide, and phenytoin.
oAs the bacteriostatic action of chloramphenicol can antagonize the
cidal action of β lactum /aminoglycosides on certain bacteria.
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• Assess signs of infection, Anemia,
C/S done before therapy.
•Administer I/V after diluting
1gm/10ml, provide oral dose with
adequate water.
•Evaluate therapeutic response.
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Sulphonamides
-Gerhard
Domagk
(1870)
8/23/2018 69

Sulphonamides
• Introduction: Sulphonamides are one of the oldest group of
antimicrobial agents. These are derivatives of the parent
compound para amino benzene, sulphonamide. They are
mainly bacteriostatic but at very high concentrations they
may have bactericidal effect. Eg. Sulfadiazine,
Sulfamethoxazole, Sulfasalazine, Co-Trimoxazole.
• Mechanism of Action: They inhibit the enzyme folic acid
synthase so folic acid is not synthesized (which is essential
bacterial growth).
UTI, Ulcerative colitis, Trachoma & Conjunctivitis, Acute
bacillary dysentery, cancroid, M. Meningitis.8/23/2018 70

S.
no.
Drugs Doses
1 Cotrimoxazole 960mg twice in a day.
2 Sulfadiazime 3g followed by 1-1.5gm every 6hrs.
3 Sulfisoxazole 4-6gm /per day in divided doses
4 Sulfasalazine 1-2gm 4time in a day or 2gm/day in divided
doses.
5 Sulmethazazole 160 – 800mg every 12 hrs.
6 Sulfamethazine 3-6gm every 6hrs.
8/23/2018 72

Contd
• Contraindication & Precautions: Children younger than 2yrs,
Pregnant and breast feeding mother, Renal and hepatic diseases,
Hypersensitivity to sulphonamides drug.
• Adverse effect: Fever, Rash, Blood Dyscrasias, Nausea/vomiting,
Aplastic Anemia.
1. Sulphonamides can increasing the blood thinning effect of
warfarin, possibly leading to abnormal bleeding.
2. Increases blood level of potassium may occur when
Sulfamethoxazole trimethoprim is combined with ACE inhibitors.
3. Sulphonamides may increase the effectiveness of oral
hypoglycemics drugs.
4. Sulphonamides may increase the effectiveness of hormonal
contraceptives drugs.
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• Assess pt. for sign & symptoms of
Urinary tract infections.
•Make sure pt. maintains fluid intake 2-3
litre/day,
•Teach pt. hygiene & measure to reduce
risk of re-infections.
•Teach pt. for good compliance of
therapy.
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Anti amoebic
• Introduction:
Amoebiasis is a protozoal
disease caused by
Entamoeba histolica
Amoeba affect liver lung
brain or other tissue and
produce hepatitis and
amoebic disease. The
drug used to treat this
kind of infection is called
Antiamoebic drug.
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AMOEBIASIS
Amebiasis (also called amebic dysentry) is
an infection of intestinal tract caused by
Entamoeba histolytica. The disease can be
acute or chronic, with the patients showing
varying degrees of illness, from no
symptoms to mild diarrhea to fulminating
dysentery (Dysentery in which the symptoms are
intensely acute, leading to prostration, collapse, and
often death).
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The diagnosis is established by isolating
E. histolytica from fresh feces.
Therapy is aimed not only at the acutely
ill patients but also at those who are
asymptomatic carriers, because dormant
E. histolytica may cause future infections
in the carrier and be a potential source of
infections for others.
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Protozoal infections are common among
the people in underdeveloped topical and
subtropical countries, where sanitary
conditions, hygienic practices and control
of vectors of transmission are inadequate.
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Life cycle of
Entamoeba histolytica
Entamoeba histolytica exists in two forms:
1. Cysts form (That can survive out side the
body).
2. Trophozoites form (That are labile and don’t
persist outside the body).
Life cycle
Life cycle consists 5 steps:
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1. Ingestion of cysts
Cysts are ingested through feces, contaminated food
or water.
2. Formation of trophozoites
Cysts are passed into the lumen of intestine, where
the
Trophozoites are liberated.
3. Penetration and multiplication of Trophozoites
Trophozoites are penetrated in intestinal wall and
multiply within colon wall. They either invade and
ulcerate the mucosa of large intestine or simply feed
on intestinal bacteria.
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4. Systemic invasion
Large numbers of Trophozoites within the
colon wall can also lead to systemic
invasion and caused liver abscess.
5. Cysts discarded
The Trophozoites within the intestine are
slowly carried toward the rectum, where
they return to cyst form and are excreted
in feces.
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Mechanism of action
• Antiamoebic requires reductive activation of nitro
group by susceptible organism. Its selective toxicity
towards anaerobic and microaerophilic pathogens such as
E. histolytica, G. lamblia, etc. These organisms contain
electron transport components such as ferredoxin, small
Fe-S proteins that have sufficiently negative redox potential
to donate electrons to metronidazole.
• The single electron transfer forms a highly reactive nitro
radical anion that kills susceptible organisms by radical-
mediated mechanisms that target DNA, resulting in cell
death.
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The single electron transfer forms a highly
reactive nitro radical anion that kills susceptible
organisms by radical-mediated mechanisms that
target DNA, resulting in cell death.
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Indication & Uses:
•Luminal amoebicides (Act on parasite in the
lumen of bowel)
• Systemic amoebicides (Against aomebias in
intestinal wall & liver)
• Mixed amoebicides ( Against both the luminal
• and systemic form of diseases).
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Classification of amoebicidal Drugs
According to the site where the drug is effective,
the amebicidal drugs are classified as:
• Luminal amebicides (Act on parasite in the
lumen of bowel)
• Systemic amebicides (Against amebas in
intestinal wall & liver)
• Mixed amebicides ( Against both the luminal
and systemic form of diseases).
8/23/2018 88

S.
no.
Drugs Doses
1 Metronidazole 400mg orally.
2 Tinidazole 500-800mg TDS
3 Secnidazole 500mg
4 Chloroquine 300mg 6-8hr
5 Antiamoebic Antibiotic
Tetracycline
0.25 mg in divided doses.
8/23/2018 89

Contd
Metronidazole's are contraindicated in neurological disorders and
blood Dyscrasias.
Cautiously used in pregnancy and alcoholism and those have hepatic
disorder.
• Adverse effect: Anorexia, headache, abd. Cramps, ECG changes, skin
rash, vertigo, nausea & vomiting, Thrombophlebitis.
Use of metronidazole with alcohol may cause the reaction like
tachycardia, flushing, sweating, vomiting.
Concurrent use with warfarin may prolonged bleeding.
Thrombophlebitis may develop if IV infusion is not done with dilution
of sterile water.
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• Assess stool for number, frequency &
character during entire treatment.
•PO dose must give after meal to avoid
G.I. disturbances.
•Teach pt. that urine dark during therapy.
•Good hygienic practices necessary.
8/23/2018 91

Antimalarial
• Introduction: These drugs are used for prophylaxis, treatment
and prevention of malaria. They acts against plasmodium ( a
protozoal parasite) which cause malaria.
• Mechanism of Action: It inhibits protein synthesis by affecting
DNA & RNA functions.
Clinical cure and prophylaxis of all kinds of malaria.
8/23/2018 93

Classification of Antimalarial
Chloroquine
Primaquin
Mefloquin
Pyrimethamine
Proguanoil
94
Artemether
8/23/2018

S.
no.
Drugs Doses
1 Chloroquine 300mg at 8hrs
2 Primaquin 15mg orally for 14 days
3 Mefloquin 25mg per kg orally single
4 Pyrimethamine 25mg weekly
5 Proguanoil 100 to 200mg daily
6 Artemether 80mg daily
8/23/2018 95

Contd
• Contraindication & Precautions: Hypersensitivity, Retinal
damage, Concurrent hepatotoxic drugs, Pregnancy & Lactation,
Renal insufficiency, Known or suspected resistant P. falciparum
infection.
• Adverse effect: Nausea & vomiting Seizures, headache, abd.
Cramps, haemolysis, Ototoxicity, G.I. upset, visual disturbances like
loss of accommodation, blurred vision.
• Drug interactions: Concurrent use of such compounds with
antiarrhythmic, tricyclic antidepressants, it may increase the risk of
cardiac conduction defects.
8/23/2018 96

•Assess the hypersensitivity reactions.
•Do not stop therapy until complete
therapy.
8/23/2018 97

Antithelmintic
• Drugs used to treat parasitic worm infections:
helminthic infections
• Drug treatment is very specific
• It is very important to identify the causative worm
• Done by finding the parasite ova or larvae in feces,
urine, blood, sputum, or tissue.
8/23/2018 98

HELMINTHS
NEMATELMINTHS (ROUND WORM)
• ROUND.W-ASCARIS.L
• HOOK W-NECATOR A
• WHIP W-TRICHURIS T
• THREAD W-STRONGYLOIDES.S
• PIN W-ENTEROBIUS V
• FILARIASIS-W BANCROFTI
• ONCHOCERCIASIS-O.VOLVULUS
• GUINEA W-DRACANCULUS M
PLATYHELMINTHS (Fluke worm)
• TREMATODES-FLUKES
• BLOOD F-SCISTOSOMIASIS
• LIVER F-CLONORCHIASIS
• INTESTINAL F-FASCIOLOPSIASIS
• LUNG F-PARAGONIMIASIS
CESTODES (Thread worm)
• BEEF TW-T.SAGINAT
• PORK TW-T.SOLIUM
• FISH TW-DIPHYLLOBOTHRIUM
• DWARF TW-HYMENOLEPIS.NANA8/23/2018 99

Classification of Antithelmintic Drugs
Against Nematodes- Albendazole, Mebendazole, Pyrantel
Pamoate, Levimasole, Piperazine, Ivermectin,
Diethylcarbamazine, Thiabendazole, Doxycycline
Against trematodes
Metrifonate, Oxamniquine, Bithionol, Triclabendazole
Against Cestodes
Niclosamide
Against trematodes and Cestodes- Praziquantel
8/23/2018 100

Worms (helminths) Drug of choice
Tapeworms (cestodes) Niclosamide or Praziquantel or Albendazole
Roundworms (nematodes)
•Enterobius vermicularis (pinworm)
•Ascaris lumbricoides
•Trichuris trichiura (whipworm)
•Trichinella spiralis (trichinellosis)
•Strongyloides stercoralis
•Necator americanus (hookworm)
•Ancylostoma duodenale
•Onchocerca volvulus (Onchocercosis)
•Wuchereria bancrofti (Elephantiasis)
Mebendazole or Pyrantel
Mebendazole or Albendazole
Mebendazole
and Thiabendazole
Thiabendazole
Mebendazole, Pyrantel, or Albendazole
Ivermectin
Diethylcarbamazine
Flukes (trematodes)
•Schistzoma (Schistozomes) Praziquantel
8/23/2018 101

Against Nematodes
PYRANTEL PAMOATE
MOA-Blocks acetylcholine at the neuromuscular junction, resulting in
paralysis of the worms, which are then expelled through the GI tract
The small amount is absorbed, so high levels are achieved in intestinal
walls luminal anthelmintic
Uses –round w, hook w, Pin w—10mg/kg
8/23/2018 102

Against Nematodes
• Benzimidazoles (ALBENDAZOLE &
MEBENDAZOLE )
It binds to beta tubulinprevents polymerisation
Break down of cytoplasmic microtubules They
inhibit uptake of glucose and other nutrients, 
Depletion of glycogen stores Decrease of ATP
Leading to autolysis and death of the parasitic worm.
8/23/2018 103

Dose: BD daily for 3 days for hookworm and roundworm infestations.
Uses:
1. Ascariasis, hook worm, pin worm infections
2. Hydatid disease-BD for 1 month
3. Neurocysticercosis- along with corticosteroids
4. Cutaneous larvae migrans-400mg for 3 days
5. Visceral larvae migrans-
6. Toxocariasis
7. Giadiasis ans tianiasis
8. Emperical treatment-Persistant eosinophilia
8/23/2018 104

Against nematodes
Thiabendazole inhibits cellular enzymes of susceptible helminths.
Inhibits the helminth-specific enzyme, fumarate reductase
8/23/2018 105

LEVAMISOLE
Anthelmintic and immunomodulator belonging to a class of synthetic
imidazothiazole derivatives. It is effective in infections with the common
round-worm as well as hook worm. It has a nicotine-like action, stimulating
and subsequently blocking the neuromuscular junctions. The paralyzed
worms are then expelled in the faeces. Ova are not killed.
Uses: To treat a variety of dermatologic conditions- skin infections, leprosy,
warts, lichen planus, and aphthus ulcers.
8/23/2018 106

Piperazine
It reversibly inhibits neuromuscular transmission in the worm It
probably by acting like GABA/GABA-gated chloride channels in
nematode muscle. The paralyzed worms are expelled alive
Uses For Ascariasis -4g * 2 days and Pin worm- 4g * 7 days
8/23/2018 107

Ivermectin
• It is highly effective broad-spectrum antiparasitic
• First choice of drug for the treatment of filarial infections and is very
effective in onchocerciasis
• It kill the worm by opening glutamate-gated chloride channels (found
only in invertebrates) and increasing Cl- conductance; by binding to a
novel allosteric site on the acetylcholine nicotinic receptor to cause an
increase in transmission, leading to motor paralysis; or by binding to
aminobutyric acid receptors.
8/23/2018 108

Ivermectin
Uses :It has also given good results against W. bancrofti, which causes
elephantiasis. A single dose kills the immature microfilariae of O.
volvulus- river blindness
The drug also has activity against infections with some roundworms:
common roundworms, whipworms, and threadworms
It works best if repeated at 6–12-month intervals.
8/23/2018 109

Diethylcarbamazine
Diethylcarbamazine is a piperazine derivtve
• It is active in filarial infections caused by W. bancrofti
• It mainly act by make opsonisation of worm that detected by our immune
system
• It immobilizes microfilariae and alters their surface structure makes them
susceptible for host defense
• The drug is absorbed by oral administration
Uses
chemoprophylaxis
Filariasis- 2-3mg/kg for 2-3 weeks
Tropical eosinophilia for 7 days, loiasis
8/23/2018 110

Against cestodes- NICLOSAMIDE
• Its action has been ascribed to inhibition of the parasite's
mitochondrial anaerobic phosphorylation of ADP which produces
usable energy
• The scolex and a proximal segment are irreversibly damaged by the
drug
• The worm separates from the intestinal wall and is expelled
• There is negligible absorption of the drug from the gastrointestinal
tract.
Uses-Taenia solium, the drug is given in a single dose after a light
meal, followed by a purgative 2 hours
8/23/2018 111

Adverse effects
Unwanted effects are few, infrequent and transient.
Drug interaction:
Enzyme inducers dexamethasone, phenytoin, and
carbamazepine increase metabolism
Cimetidine, known to inhibit cytochrome P-450
isozymes, causes increased praziquantel levels.
8/23/2018 112

Against Trematodes and Cestodes-PRAZIQUANTEL
It is the drug of choice for all forms of schistos and
for cestode infections like cysticercosis.
It make the Permeability of the cell membrane to
calcium is increased, causing contracture and
paralysis of the both adult worms and larvae.
8/23/2018 113

Against trematodes - MITRIFONATE
It is organophosphorus compound so is cholinesterase
inhibitors. It is safe and cost effective for Schistosoma
infection.
It has good oral absorption Orally active and time is 1/2 =1-5
hrs.
8/23/2018 114

Against trematodes: OXAMNIQUINE-
Used against Schistosoma mansoni. It is the drug of choice for all forms
of schistosomiasis it is given orally.
Flukes esterifies drug to produce reactive metabolite  alkylates DNA
of flukes. It intercalated with parasite DNA and inactivate it.
8/23/2018 115

Against Trematodes
BITHIONOL-orally well absorbed
For fascioliasis (sheep liver fluke) 30-50mg for 10-15 days on
alternate days.
TRICLABENDAZOLE : narrow spectrum benzimidazole
For treating human fasciola hepatica
8/23/2018 116

S.
no.
Drugs Doses
1 Albendazole 10mg/kg body wt.
2 Ivermectin 6-12mg
3 Mebendazole 100mg
4 Pyrantel 10mg/kg body wt.
5 Thiabendazole 25mg/kg body wt.
8/23/2018 117

Contd
• Contraindication & Precautions: Hepatic disease, breast feeding
women, pregnant women, use cautiously in children younger than
2yrs of age.
• Adverse effect: Abdominal pain, nausea, diarrhoea, vomiting,
drowsiness, headache, dizziness, elevated liver enzyme level.
• Nursing Responsibilities.
1. Nurse should teach the patient and family members to wash hands
well, use disposable towels to dry hands and keep hands away
from mouth.
2. Nurse should teach the patient and family members to wash
personal article including sheets and other food preparation
articles, utensils etc. Use disposable towels to dry hands and keep
hands away from mouth.
8/23/2018 118

3. Nurse should advise the patient to complete the full course of
therapy and not to discontinue the drugs when symptoms
subsides.
4. Nurse should be aware that purgative to facilitate to bowel
movements may follow the administration of these drugs.
5. Nurse should advise the patient.
8/23/2018 119

Antiscabies agents
• Sarcoptes scabiei, otherwise known as scabies, is a highly
contagious infestation of microscopic mites that affect
humans and animals alike.
• Contracting scabies is more common then one may think, and
occurs worldwide. No one is safe from an infestation of
scabies because it can affect any race or social class. Scabies
can also spread at a rapid pace, and this usually occurs in
crowded areas where there is a chance of prolonged contact.
8/23/2018 120

DEFINITION
Scabies is a contagious disease caused by the mite Sarcoptes
scabiei.
EPIDEMIOLOGY & DEMOGRAPHICS
 Mites are distributed worldwide
 affects all races and socioeconomic classes in all climates
Higher prevalence in urban areas
Greater frequency in winter than summer
8/23/2018 121

Scabies Transmission
• Direct, prolonged, skin–to-skin contact
• Sexual contact
• Exposure is most common in nursing homes, hospitals,
institutions, and daycare settings; can also be spread in
households
• Indirect transfer from clothing, towels and bedding
• Transmission occurs as long as person is infested and
untreated, including incubation period.
8/23/2018 122

Scabies Symptoms
Pimple-like rash or burrows between fingers, on wrist, elbows,
armpits, belt line, navel, abdomen, and/or back of the hip
Erythematous(red) skin
Intense itching over most of the body, especially at night
Sores on the body caused by scratching
Sores can sometimes become infected with bacteria(usually
streptococcus pyogenes or staphylococcus aureas)
Incubation period:
2-6 weeks without previous exposure
1-4 days after re-infestation (usually milder)
8/23/2018 123

LABORATORY TESTS
 Microscopic demonstration of the organism, feces, or eggs: a
drop of mineral oil may be placed over the suspected lesion
before removal; the scrapings are transferred directly to a glass
slide; a drop of potassium hydroxide is added and a cover slip
is applied.
 Skin biopsy is rarely necessary to make the diagnosis.
8/23/2018 124

Pathophysiology
The mite, S scabiei spreads disease through direct and
prolonged contact between hosts.
The mite remains viable for 2-5 days on inanimate objects;
therefore, transmission through for mites, such as infected
bedding or clothing, is possible.
Once bound to their host, 10-15 mites mate on the surface of
the skin.
8/23/2018 125

After mating, the male mite dies.
The female mite burrows into the epidermis of the
host using her jaws and front legs, where she lays up to
3 eggs per day for the duration of her 30-60 day
lifetime.
An affected host harbors approximately 11 adult
female mites during a typical infestation. The eggs
hatch in 3-4 days.
The Larvae migrate to skin surface and burrow into
the skin or hair follicles forming short burrows, called
molting pouches. Larvae have 3 pairs of legs and last
only 2 to 3 days before turning into nymphs.8/23/2018 126

Mating occurs when male mite penetrates the
molting pouch of the female mite.
Impregnated females extend their molting pouches
into burrows, laying eggs in the process; survive 1-2
months in tunnels under the skin.
A delayed type IV hypersensitivity reaction to the
mites, their eggs, or scybala (packets of feces) occurs
approximately 30 days after infestation.
This reaction is responsible for the intense
pruritus, which is the hallmark of the disease.8/23/2018 127

Scabies Treatment
•Application of scabicide over entire body below head
•Cream should be reapplied to hands after routine hand
washing, since hands are often infected
•Itching may continue for several weeks despite successful
treatment
•In ~5% of cases, 2nd treatment may be necessary after 7-
10 days.
8/23/2018 128

Sulphur
Scabies was historically treated with topical sulfur, a
treatment still in use today
10% sulphur in yellow soft paraffin is safe and
effective.
2.5% used for scabies in infants and young children.
Excessive or higher concentration may cause irritation.
8/23/2018 129

Lindane 1% (gamma benzene hexachloride)
Lindane is an organochloride.
A single application, washed off after 12-24h
6 hour application is equally effective
Adverse effects:
Neurological effect- seizure
Toxicity was usually the result of excessive topical application or
accidental ingestion.
Lindane should not be used to treat premature infants, persons with
a seizure disorder, women who are pregnant or breast-feeding,
persons who have very irritated skin or sores where the lindane will
be applied, infants, children, the elderly, and persons who weigh
less than 110 pounds.8/23/2018 130

Malathion
0.5% in aqueous base.
For one application in an adult 100ml lotion is sufficient.
Apply on cool, dry skin using clean paintbrush or cotton wool.
It should be left on the skin for 24h
If hands are washed with soap and water during the 24h, it
should be reapplied to the hands.
a second application after an interval of a week.
Skin irritation may sometimes occur.
8/23/2018 131

Ivermectin
• Ivermectin is an oral antiparasitic agent approved for the treatment
of worm infestations.
• Evidence suggests that oral ivermectin may be a safe and effective
treatment for scabies;
• Oral ivermectin has been reported effective in the treatment of
crusted scabies; its use should be considered for patients who have
failed treatment with or who cannot tolerate topical medications
for the treatment of scabies.
• The dosage of ivermectin is 200 mcg/kg orally. It should be taken
on an empty stomach with water. A total of two or more doses at
least 7 days apart may be necessary to eliminate a scabies
infestation. The safety of ivermectin in children weighing less than
15 kg and in pregnant women has not been established.8/23/2018 132

Permethrin (Elimite)
5% Dermal cream is effective.
For a single application in an adult 30-60g of cream is
needed.
Applied to the whole body and left on for 8-12h before
being washed off.
Second application after an interval of a week.
Can cause itching and reddening of the skin.
8/23/2018 133

TREATMENT OVERVIEW
5% permethrin cream: This is the most common
treatment for scabies. It is safe for children as young as
1 month old and women who are pregnant.
25% benzyl benzoate lotion.
10% sulfur ointment.
10% crotamiton cream.
1% lindane lotion.
8/23/2018 134

Other treatment
Some patients need other treatment, too.
Antihistamine: To control the itch and help you sleep.
Pramoxine lotion: To control the itch.
Antibiotic: To wipe out an infection.
Steroid cream: To ease the redness, swelling, and itch.
8/23/2018 135

Applying Prescription Creams
•Follow package insert
•Apply thin layer over whole body from neck down, paying
particular attention to folds in skin
•Trim fingernails and toenails, apply under nails
•Reapply after handwashing
•Leave on for at least 8 hours, but not longer than maximum
time recommended for product
•Wash off with warm, soapy water and dry skin
8/23/2018 136

•Educate patient about personal hygiene, including
hand washing
•Increase awareness and surveillance for scabies
•Instruct patient to bath thoroughly, scrubbing the
involved areas with a brush.
•Educate other members of the family.
•All members of the family should be treated on
the same day.
8/23/2018 137

Antiviral & Antifungal agents
8/23/2018 138

Antiviral Agents
•Introduction: These agents are used to treat
viral infections, the difficulty in treating viral
infection is that viruses live and multiply within
the cell and drug which enter the cell for not only
destroy viruses but exerts bad effects on the cell
also.
8/23/2018 139

Understanding Viruses
They are different from other Microbes
Viral replication
•A virus cannot replicate on its own
•It must attach to and enter a host cell
•It then uses the host cell’s energy to synthesize
protein, DNA, and RNA
8/23/2018 141

Understanding Viruses
Viruses are difficult to
kill because they live
inside the cells
• Any drug that kills a
virus may also kill cells
8/23/2018 142

Antivirals: Available for many viral infections
Viruses controlled by current antiviral therapy
•Cytomegalovirus (CMV)
•Hepatitis viruses
•Herpes viruses
•Human immunodeficiency virus (HIV)
•Influenza viruses (the “flu”)
•Respiratory syncytial virus (RSV)
8/23/2018 143

Anti-viral drugs
• Viruses have no cell wall and made up of nucleic acid
components
• Viruses containing envelope – antigenic in nature
• Viruses are obligate intracellular parasite
• They do not have a metabolic machinery of their own
– uses host enzymes
8/23/2018 144

Anti-viral drugs
•Certain viruses
multiply in the
cytoplasm but others
do in the nucleus
•Most multiplication
take place before
diagnosis is made
8/23/2018 145

Anti-Viral drugs
• Many antiviral drugs are Purine or Pyrimidine analogs.
• Many antiviral drugs are Prodrugs. They must be
phosphorylated by viral or cellular enzymes in order to
become active.
• Anti-viral agents inhibits active replication so the viral
growth resumes after drug removal.
8/23/2018 146

Antivirals: Mechanism of Action.
Key characteristics of antiviral drugs
Able to enter the cells infected with virus
Interfere with viral nucleic acid synthesis and/or regulation
Some drugs interfere with ability of virus to bind to cells
Some drugs stimulate the body’s immune system
Best responses to antiviral drugs are in patients with
competent immune systems
A healthy immune system works synergistically with the
drug to eliminate or suppress viral activity
8/23/2018 147

Uses: Antiviral Medications
Antiviral drugs
Used to treat infections caused by viruses other than HIV
Antiretroviral drugs
Used to treat infections caused by HIV, the virus that causes
AIDS
Herpes-Simplex Viruses
HSV-1 (oral herpes)
HSV-2 (genital herpes)
Varicella Zoster Virus
Chickenpox
Shingles8/23/2018 148

Antiviral Drugs: Non-retroviral
Mechanism of action
Inhibit viral replication
Used to treat non-HIV viral infections
Influenza viruses
HSV (herpes simplex virus), VZV (vericella zoster virus)
CMV (cytomegalovirus)
Hepatitis A, B, C (HAV, HBV, NCV)
Adverse Effects
Vary with each drug
Healthy cells are often killed also, resulting in serious toxicities
8/23/2018 149

Anti-viral drugs
• Current anti-viral agents do not eliminate non-
replicating or latent virus
• Effective host immune response remains essential for
the recovery from the viral infection
• Clinical efficacy depends on achieving inhibitory
conc. at the site of infectio.n within the infected cells.
8/23/2018 150

Anti-viral drugs
Stages of viral replication
• Cell entry – attachment
- penetration
• Uncoating
• Transcription of viral genome
• Translation
• Assembly of virion components
• Release
8/23/2018 151

• DNA polymerase inhibitors
―Purine Nucleoside Analogues:
Acyclovir, Ganciclovir Famiciclovir
Valacyclovir, Penciclovir Cidofovir
–Pyrimidine Nucleoside Analogues:
Idoxuridine
–Non nucloside
Foscarnet
Classification

• Inhibitors of viral penetration, uncoating
Amantadine, Rimantadine
• m-RNA Synthesis inhibitors
Ribvirin, Fomivirsen
• Neuraminidase Inhibitors
Zanamivir, Oseltamivir
• Immunomodulators
Immunoglobulins, Interferns, Palivizumab, Imiquimod.
8/23/2018 154

S.
no.
Drugs Doses
1 Acyclovir 5mg/kg body wt. IV 8hrly/ 200-400mg orally
4hrly
2 Amantadine 100mg BD for 5days.
3 Vidarbine 100mg/kg intravenous
4 Ganciclovir 5mg/kg every 12hrs.
5 Famciclovir 250mg tds
6 Zidovudine 600mg daily in divided doses.
8/23/2018 155

Contd
• Contraindication & Precautions: Patient who have
hypersensitivity to these drugs. Use cautiously in the patient with
renal disease, dehydration, neurologic disease.
• Adverse effect: Leucopenia, Dizziness, Headache,
Nausea/vomiting, Phlebites, sleeplessness, Thrombocytopenia,
diarrhoea, Renal failure, confusion, Hallucinations, Zidovudine may
cause anemia & bone marrow depression.
• Drug interactions: Use anticholinergic drug with may cause
additive anticholinergic effects. Use of alcohol may increases risk of
toxicity.
8/23/2018 156

• Advise the pt. to take adequate fluid during therapy.
•Monitor the pt’s neurologic status.
•Assess adverse effect.
•Mind that antiviral drugs are not much effective, so
support natural defence mechanism of patient, encourage
intake of fluid rich in immune stimulating nutrients such
as vit. A, C, & E and minerals.
•Caution the pt. with infections of skin lesions, not to use
over the counter drug because they may delay healing.
•Promote use of condoms when lesions are present.
8/23/2018 157

Antifungal Agents
• These Agents used against fungal infections ( superficial or
systemic)
• Also called antimycotic drugs.
• Used to treat two types of fungal infection:
• Superficial fungal infections
• (skin or mucous membrane)
• Systemic fungal infectons
• (lungs or central nervous system)
8/23/2018 158

Antifungal agents
• Introduction: Fungi is also known as mycoses, It is very
large and diverse group of microorganisms. It broken down
into yeasts and molds
• Yeast: Single-cell fungi, Reproduce by budding, Very useful
organisms
• Baking
• Alcoholic beverages
• Molds: Multicellular, Characterized by long, branching
filaments called hyphae.
8/23/2018 159

Fungal infections are:
Four General Types
• Cutaneous
• Subcutaneous
• Superficial
• Systemic*
*Can be life-threatening
*Usually occur in
immunocompromised
host
8/23/2018 160
Candida albicans
• Due to antibiotic therapy, antineoplastics,
or immunosuppressants it may result in
overgrowth and systemic infections.
In the mouth:
• Oral candidiasis or thrush
• Newborn infants and
immunocompromised patients
Vaginal candidiasis:
• “Yeast infection”
• Pregnancy, diabetes mellitus, oral
contraceptives

Mechanism of Action
8/23/2018 161

FLUCYTOSINE
IMIDAZOLES
TRIAZOLES
POLYENES
CANDINS
GRISEOFULVIN
OTHERS
ANTI FUNGAL DRUGS MECHANISAM

CLASSIFICATION OF ANTIFUNGAL
Con…

S.
no.
Drugs Doses
1 Amphotericin B 0.1mg/ml(1mg/10ml) IV
2 Nystatin 4-6ml four times a day
3 Clotrimazole 100mg daily (as pessary)
4 Miconazole 2% solution
5 Ketoconazole 200-400mg daily
6 Griseofulvin 0.5 to 1gm daily.
7 Fluconazole 50mg daily/150mg single in vaginal candida
or candida balanitis8/23/2018 164

Antifungal Agents: Adverse Effects
Amphotericin B: “Shake and Bake”
fever chills headache anorexia
malaise nausea hypotension tachycardia
muscle and joint pain
lowered potassium and magnesium levels
*Renal toxicity
*Reurotoxicity: seizures and paresthesias

contd
Fluconazole
• Nausea, vomiting, diarrhea, abdominal pain,
• Increased liver function studies
Flucytosine
• Nausea, vomiting, anorexia
Griseofulvin
• Rash, urticaria, headache, nausea, vomiting, anorexia

Contd
• Contraindication & Precautions: Hypersensitive patients, Pregnant
or breast feeding women.
1. Concurrent use with nephrotoxic drugs may cause additive
nephrotoxicity.
2. Ketoconazole with alcohol may increase risk of hepatotoxicity.
3. Itraconazole with antidiabetics may increase risk of
hypoglycaemia.
4. Some antifungal may increase the effect of oral anticoagulants by
increasing prothrombin times.
8/23/2018 167

• Before beginning therapy, assess for hypersensitivity, possible
contraindications, and conditions that require cautious use.
• Obtain baseline VS, CBC, liver function studies, and ECG.
• Assess for other medications used (prescribed and OTC) in order to
avoid drug interactions.
• Follow manufacturer’s directions carefully for reconstitution and
administration.
• Monitor VS of patients receiving IV infusions every 15 to 30
minutes.
• During IV infusions, monitor I & O and urinalysis findings to
identify adverse renal effects.

contd
Amphotericin B
• To reduce the severity of the infusion-related reactions, pretreatment with an
antipyretic (acetaminophen), antihistamines, and antiemetics may be given.
• A test dose of 1 mg per 20 mL 5% dextrose in water infused over 30 minutes
should be given.
• Use IV infusion pumps and the most distal veins possible.
• Tissue extravasation of fluconazole at the IV site may lead to tissue
necrosis—monitor IV site carefully.
• Oral forms of griseofulvin should be given with meals to decrease GI upset.
• Monitor carefully for side/adverse effects.

contd
Monitor for therapeutic effects:
• Easing of the symptoms of infection
• Improved energy levels
• Normal vital signs, including temperature

Pictures of Antifungals available in market
8/23/2018 171
P.T.O.

Β-3-GLUCAN SYNTHASE
INHIBITORS

Antitubercular drugs.
Introduction: Tuberculosis.
Gram positive , aerobic acid fast bacilli.
Resistant to disinfectant ,detergent & common
antibiotics.
Capable of intracellular growth.
Person to person spread is by aerosol.
Human are the only natural reservoir.
Disease is most common in south east asia, sub saharan
region, eastern europe.
8/23/2018 177

• Sites of extra-
pulmonary
tuberculosis

TUBERCULOSIS DIAGNOSIS
•Clinical (presenting symptoms, duration of
symptoms, previous TB)
•Diagnostic Imaging(X-Rays, CT Scans, MRI’s)
•Bacteriology (smears, cultures)
•Pathology of biopsy specimens
•Epidemiological Factors

Classification Of Anti T.B.
Drugs
FIRST line drugs
• F Field defects causing drug i.e. Ethambutol [E]
• I Isoniazid (INH) [H]
• R Rifampicin [R]
• S Streptomycin [S]
• T Twice a day given drug i.e. Pyrazinamide [Z]
(All other first line antituberculars are given once a day)

SECOND line drugs
• S Salicylates like Para-amino salicylate
• E Ethionamide
• C Cycloserine
• O Old drug: Thiacetazone
• N Newer Drugs: (Quinolones e.g. Ciprofloxacin, Levofloxacin,
gatifloxacin and Moxifloxacin) &( Macrolides e.g. Clarithromycin,
Azithromycin)
• D Drugs rarely used: Aminoglycosides e.g. Capreomycin,
Kanamycin, Amikacin, Rifabeutin

Mechanism of Action along with Line of
Regimen
8/23/2018 183

First –Line Drugs:
• These drugs are used in combinations of two or more agents until
bacterial conversation occurs or maximum improvement is seen.
The First-line drugs for treating tuberculosis are as follows:
• Isoniazid [INH] (Nydrazid), which affects the mycolic acid coating
of the bacterium.
• Rifampin (Rifadin, RImactane), which alters DNA and RNA activity
in the bacterium.
• Ethionamide (Trecator SC), which prevents cell division
• Rifapentine (Priftin), which alters DNA and RNA activity, causing
cell death.

Second-line drugs :
• If the patient cannot take one or more of the first-line drugs, or if the
disease continues to progress because of the emergences of a
resistance strain, the second line drugs can be used.
• These drugs are used in combination with at least one other
antituberculosis drug.
The Second-line drugs for treating tuberculosis are as
follows:
• Ethambutol (Myambutol), which inhibits cellular metabolism.
• Pyrazinamide (generic), which is both bactericidal and bacteriostatic.

Third-line drugs: If therapeutic success is still not achieved, a third-
line combination of two antituberculosis drugs can be tried.
• Using the drug in combination helps to decrease the emergence of
resistant strains and to affect the bacteria at various phases during their
long and slow life cycle.
The Third-line drugs for treating tuberculosis are as
follows:
• Capreomycin (Capastat), whose mechanism of action is not known.
• Cycloserine (Seromycin), which inhibits cell wall synthesis and leads to
cell death.

Drug name Dosage / Route Usual Indications
Capreomycin
(Capastat)
Adult: 1g/day IM for 60-120
days, followed by 1g IM 2-3
times per week for 18024
mo; reduce dosage with
renal impairment
Pediatric: 15 mg/kg/day IM
Second-line drug for
treatment of Mycobacterium
tuberculosis
Cycloserine
(Seromycin)
Adult: 250 mg PO b.i.d. for
2 wk, then 500 mg to 1
g/day PO in divided doses
Pediatric: safety not
established
tuberculosis

Ethambutol
(Myambutol)
Adult: 15 mg/kg/day PO as a
single dose
Pediatric: not recommended
for children < 13 yr.
tuberculosis
Ethionamide
(Trecator S.C.)
Adult: 15-20 mg/kg/day PO
in divided doses with
pyridoxine
Pediatric: 10-20 mg/kg/day
PO in divided doses with
pyridoxine
First-line drug for treatment
of Mycobacterium
tuberculosis
Isoniazid (INH)
(Nydrazid)
Adult: 5 mg/kg/day PO
Pediatric: 10-20 mg/kg/day
PO
of Mycobacterium
tuberculosis

Pyrazinamide (Generic) Adult and Pediatric: 15-30
mg/kg/day PO
tuberculosis
Rifabutin (Mycobutin) Adult: 300 mg PO daily
established
Treatment of Mycobacterium
avium-intracellulare (MAC)
in patients with advance HIV
infection
Rifampin (Rifadin,
Rimactane)
Adult: 600 mg 2 times per
week for 2 mo
established
of M. tuberculosis
Rifapentine (Priftin) Adult: 600 mg PO 2 times
per week for 2 mo
established
of M. tuberculosis

Contraindications and Cautions
• Antituberculosis drugs are contraindicated for patients
with any known allergy to these agents
• In those with the metabolism or excretion of the drug.
• In those with severe CNS dysfunction, which could be
exacerbated by the actions of the drug.
• In pregnancy because of possible adverse effects on the
fetus. In an antituberculosis regimen is necessary during
pregnancy, the combination of isoniazid, ethambutol and
rifampin is considered the safest.

Adverse Effects
• CNS effects: neuritis, dizziness, headache, malaise, drowsiness, and
hallucinations are often reported and are related to direct effects of the
drugs on neurons.
• GI tract: nausea, vomiting, anorexia, stomach upset and abnormal
pain.
• Rifampin, rifabutin and rifapentine cause discoloration of body fluids
from urine to sweat and tears. Patients should be alerted that in many
instances orange-tinged urine, sweat, and tears may stain clothing and
permanently stain contact lenses. This can be frightening if the patient
is not alerted that many to the possibility that it will happen.
• As with other antibiotics, there is always a possibility of
hypersensitivity reactions and the patient should be monitored on a
regular basis.

Drug Interactions
• When rifampin and INH are used in combination, the possibility
of toxic liver reactions increases. Patients should be monitored
closely.
• Increases metabolism and decreased drug effectiveness occur as a
result of administration of quinidine, metoprolol, propranolol,
corticosteroids, oral contraceptives, oral anticoagulants, oral
antidiabetic agents, digoxin, theophylline, methadone, phenytoin,
verapamil, cyclosporine or ketoconazole in combination with
rifampin or rifabutin.
• Patients who are taking these drug combinations should be
monitored closely and dosage adjustments made as needed.

• Check culture and sensitivity reports to ensure that this is the
drug of choice for this patient and arrange repeated cultures if
response is not as anticipated.
• Monitor renal and liver function test results before and
periodically during therapy to arrange for dosage reduction as
needed.
• Ensure that the patient receives the full course of the drugs to
improve effectiveness and decrease the risk of development of
resistant bacterial strains. These drugs are taken for years and
often in combination. Periodic medical evaluation and re-
teaching are often essentials to ensure compliance.
8/23/2018 193

Continuation….
• Discontinue the drug immediately if hypersensitivity
reactions occur to avert potentially serious reactions.
• Encourage the patient to eat small, frequent meals as
tolerated; perform frequent mouth care; and drink adequate
fluids to ensure adequate nutrition and hydration. Monitor
nutrition if GI effects become a problem.
• Encourage that the patient is instructed about the appropriate
dosage regimen, use of drug combinations and possible
adverse effects to enhance patient knowledge about drug
therapy and to promote compliance.

The Patient should inform:
• To drink a lot of fluids to maintain nutrition (very important)
even though nausea, vomiting and diarrhea may occur.
• To use barrier contraceptives and understand that oral
contraceptives may not be effective if antimycobacterial drugs
are being used.
• To understand that normally some of these drugs impart an
orange stain to body fluids. If this occurs, the fluids may say
stain clothing and tears may stain contact lenses.
• To report difficulty breathing, hallucinations, numbness and
tingling, worsening of condition, fever and chills or changes in
color of urine or stool to a health care provider.

Evaluation
• Monitor patient response to the drug (resolution of
mycobacterial infection).
• Monitor for adverse effects (GI effects, CNS changes and
hypersensitivity reactions).
• Evaluate the effectiveness of the teaching plan (patient can
name the drug, dosage, possible adverse effects to expect and
specific measure to help avoid adverse effects).
• Monitor the effectiveness of comfort and safety measures and
compliance with the regimen.

Antileprosy drugs
• Leprosy is a chronic
infectious disease
• characterized by lesions of
the peripheral nerve, skin,
and mucus
membrane of the URT(nasal
mucosa).
• World's oldest recorded
disease
8/23/2018 197
Every year January 27 is World Leprosy Day

Historical aspect of leprosy
• One of the Oldest and most dreaded disease known to Mankind.
• Earliest description from India in 600BC
• Kustha Roga & attributed to punishment or curse of God
• Al-Bukhari’s Muslim Hadith (volume 1, 2.443) documented Prophet Mohammed’s
apparent dread of leprosy in his statement: “Escape from the leprous the way you escape
from a lion”
• Word leper comes from Greek word “scaling”
• M. leprae was discovered by Gerhard Henrik Armauer Hansen in 1873 in Norway.
Hence referred to as Hansen’s disease.
• Leprosy control started with the use of chaulmoogra oil and for the last three decades,
MDT has been the main tool against leprosy.

What causes it?
•Mycobacterium leprae
•Rod Shaped
•First bacterium disease in humans
199

M. Leprae is discovered by Hansen from Norway in 1873
200

• Leprosy develops slowly from 6months up to 40 yrs
• Results in skin lesions and deformities, most often
affecting the cooler places on the body ( for
example: eyes, nose, earlobes, hands, feet, and
testicles) that can be very disfiguring.
201

Mode of infection
• Although human-to-human transmission is the
primary source of infection, three other species can
carry and (rarely) transfer M. leprae to humans:
chimpanzees, mangabey monkeys, and nine-
banded armadillos.
202

The nine - banded armadillo
203

Mode of transmission
The exact rout of transmission is not fully known .
The spread of leprosy is believed to be via nasal discharge
(Droplets infection).
Every 1 cc of nasal secretion contains 1- 2millions lepra
bacilli

Other modes of transmissions
1. Contact through the skin (rare).
2. Arthropod-born infection (rare).
3. Through placenta and milk.

Signs and Symptoms
Early signs and symptoms of leprosy are very
subtle and occur slowly (usually over years).
 First symptoms :
 Numbness and loss of temperature
sensation (cannot sense very hot or cold
temperatures)
 As the disease progresses :
 The sensations of touch, then pain, and
eventually deep pressure are decreased or
lost.
206

Long-term developing sequence of events :
• Relatively painless ulcers, skin lesions of
hypopigmented macules (flat, pale areas
of skin), and eye damage (dryness,
reduced blinking)
• Late stage: large ulcerations, loss of
digits, and facial disfigurement. (for
example, hands, feet, face, and knees).
207

Predisposing or risk factors
1. Residence in an endemic area.
2. Poverty (malnutrition).
3. Contact with affected armadillo.
4. Immunity
209

(cont.)
The incubation period range from 3 -5 years. Males
appear to be twice common than females.
Bimodal age (10-14years & 35-44 years).
Children are more susceptible to disease.
Genetic factors, e.g. HLA markers may determine
the type of leprosy which the patient develops .
210

Slit Skin Smear (Reporting the
smear).
(Ridley’s logarithmic
scale)Bacteriological index
0 – no bacilli in 100 fields
1+: 1-10 bacilli in 100 fields
2+: 1-10 bacilli in 10 fields
3+: 1-10 bacilli in 1 field
4+: 10-100 bacilli in 1 field
5+: 100-1000 in 1 field
6+: >1000 bacilli field (globi).

LEPROSY
Paucibacillary (PB) Multibacillary (MB)
Indeterminate Leprosy (IL)
Tuberculoid Leprosy (TL)
Borderline Tuberculoid (BT)
Borderline Borderline (BB)
Borderline Lepromatous(BL)
Lepromatous Leprosy (LL)
212

Classification & Clinical Presentation
Ridley & Jopling Classification
Based on Host Immunity
TT BL LL
BT BB BL
213

Classification & Clinical Presentation
WHO Classification
Based on Bacterial Load
Paucibacillary
1-5 skin lesions
Multibacillary
>6 skin lesions
Slit Skin Smear
PositiveNegative
214

Today, the diagnosis and treatment of leprosy is
easy and most endemic countries are striving to
fully integrate leprosy services into existing
general health services.

HISTORY OF TREATMENT
 In 1941, promin, a sulfone drug, showed efficacy but required many painful
injections.
Dapsone pills were found to be effective in the 1950s
But soon (1960s-1970s), M. leprae developed resistance to dapsone.
. In the early 1960s, Rifampicin and clofazimine, the other two components of MDT,
were discovered.
This multi-drug treatment (MDT) was recommended by the WHO in 1981 and
remains, with minor changes, the therapy of choice.
Since 1995, WHO provides free MDT for all patients in the world
 NB: MDT, however, does not alter the damage done to an individual by M. leprae
before MDT is started.

LEPROSY IS A CURABLE DISEASE
Drugs used in Leprosy treatment
What are the three commonly used drugs?
1. Dapson.
2. Rifampicine.
3. Clofazimine.
The combination of these three drugs is known as Multi Drug Therapy
(MDT)

Treatment method with dose:
1. Multibacillary – Duration(12months) It treat with combination
of three drugs:
a) Dapsone 100mg daily.
b) Rifampicin 600mg daily once a month.
c) Clofazimine initially 100mg for 14days then 50mg daily;
300mg once a month; supervised daily 50mg daily set of
administered.
2. Paucibacillary Leprosy: These are combination of two drugs
for this treatment:
a) Dapsone 100mg daily.
b) Rifampicin 600mg once a month.8/23/2018 219

ADVERVE EFFECT OF ANTI-LEPROTIC DRUGS:
DRUGS MINOR MAJOR
1. RIFAMPICIN RED URINE JAUNDICE
GIT UPSET HEPATITIS
FLU LIKE SYNDROME SHOCK
2. DAPSONE GIT UPSET DAPSONE SYNDROME
DRUG RASH AGRANULOCYTOSIS
ANAEMIA HEMOLYTIC ANAEMIA
3. CLOFAZIMINE GIT UPSET ACUTE PAIN ABDOMEN
DISCOLOURATION OF SKIN
ICHTHYOSIS 220

Antileprotic Agents
• Mechanism of Action: Bacteriostatic Dapsone is similar to
sulphonamides and has the same mechanism of action. It inhibit
PABA (Para Amino Benzoic Acid – It is precursor of folic acid
which is essential for the growth & multiplication of bacteria).
Clofazamine interfering DNA functions. It is also anti –
inflammatory property.
8/23/2018 221

S.
no.
Drugs Doses
1 Dapsone 100mg orally OD
2 Rifampicin 600mg monthly
3 Clofazimine 50 – 100mg daily.
4 Ethionamide 250mg OD
5 Ofloxacin 400mg OD
6 Clarithromycin 500mg OD
8/23/2018 222

Contd
• Dapsone should not be used for patient with Anemia and those
showing hypersensitivity reaction.
• Clofazimine avoided during early pregnancy and the patient with
kidney and liver diseases.
8/23/2018 223

• Assess immunological reaction which are
known as lepra reaction may occur due to
Multibacillary disease treatment, it is due
to release of antigen from the killed bacilli
which can be treated by corticosteroids or
Clofazimine.
•Assess side effects of multidrug therapy.
8/23/2018 224

Anticancer drugs: Introduction
• Introduction: Cancer is a disease of cells characterised by
progressive, Persistent, perverted ( abnormal) Purposeless and
uncontrolled proliferation of tissue.
• Cell cycle: Five Phases.
8/23/2018 225
CANCER: A group of
disease involving
abnormal cell growth
with the potential to
invade or spread to
other part of the body.

• CELL CYCLE
Understanding the cell cycle is necessary in cancer chemotherapy
It is a series of events that takes place in a proliferating cell (normal and
malignant ) leading to its division and duplication.
Phases of cell cycle
• G₀ Phase(resting phase)
• The cell has not started diving.
• They spend much of their lives in this phase.
• When the cell get a signal to reproduce, they move into the G₁
Phase.
• Limitation to successful eradication of many tumors by
chemotherapy. They re-enter the cycle after therapy.
8/23/2018 227

• G₁ PHASE(Pre-synthetic phase)
• The cell starts to produce proteins and enzymes necessary for DNA
synthesis.
• During this phase, RNA synthesis occurs.
• This phase last about 18 to 30 hours.
• S-PHASE(synthetic phase)
• DNA synthesis
• Cellular DNA is duplicated in preparation in preparation for
cellular division.
• Length of time S phase is approximately 18-30hrs.
• A weak link, and large number of anticancer agent act.
8/23/2018 228

• G₂ Phase (pre-mitotic phase)
• the cell checks the DNA
• Gets ready to start splitting into 2 cells.
• Here both protein, RNA, and the precursors to the mitotic
spindle apparatus are produced.
• This phase is very short 1-2hrs.
• MITOTIC PHASE
• In this phase, which last only 30-60min, the cell actually split
into 2 new cells.
8/23/2018 229

Interphase Prophase Metaphase
Anaphase Interphase Cytokinesis
STAGES OF MITOSIS:

History:
•No Treatment: Before 1940
•Surgery: before 1955
•Radiotherapy: 1955~1965
•Chemotherapy: after 1965
•Immunotherapy and Gene therapy

Goals of Therapy
• Cure or induce prolonged ‘remission’ so that all macroscopic and
microscopic features of the cancer disappear, though disease is
known to persist - Acute Lymphoblastic Leukaemia, Wilm`s tumor,
Ewing`s sarcoma etc. in children, Hodgekin`s lymphoma, testicular teratoma
and choriocarcinoma
 Palliation: Shrinkage of evident tumour, alleviation of symptoms
and prolongation of life - Breast cancer, ovarian cancer, endometrial
carcinoma, CLL, CML, small cell cancer of lung and Non-Hodgekin
lymphoma
• Insensitive or less sensitive but life may be prolonged - Cancer
esophagus, cancer stomach, sq. cell carcinoma of lung, melanoma,
pancreatic cancer, myeloma, colorectal cancer

MODALITIES OF TREATMENT
• 1-Local therapy:
• -surgery.
• -radiation therapy.
• 2-Systemic treatment:
• Chemotherapy.
• Hormonal therapy.
• Monoclonal antibodies.
• Radioactive material.
• 3-Supportive care.
• 4-Non-conventional therapy.

Cancer Chemotherapy – 5 years survival rate
Childhood Acute Lymphoblastic Leukemia 50 - 80%
Acute Adult Lymphoblastic Leukemia 20 - 60%
Childhood Acute Myeloblastic Leukemia 20 - 60%
Adult Acute Myeloblastic Leukemia 10 - 20%
Breast Cancer 5 - 20%
Hodgkin’s lymphoma 40 - 80%

Paul Ehrlich 1854 - 1915
 Father of Chemotherapy
• Initiated Treatment of Syphilis
• Nobel Prize 1908
• “Magic Bullet Concept”

HISTORICAL PERSPECTIVE
•Nitrogen mustards were a product of the secret
war gas programs in both world wars
•In World War II, an explosion at Bar Harbor
exposed seamen to mustard gas - they developed
severe marrow and lymphoid hypoplasia
•Led to the use of these agents to treat Hodgkins
and non-Hodgkins lymphomas at Yale in 1943.

HISTORICAL PERSPECTIVE
•In the 1950’s, folic acid was shown to accelerate
the progression of childhood leukemias; led to
development of folic acid antagonists
•In the 1960’s, combination chemotherapy for
childhood leukemias and Hodgkins lymphoma
began to be used.

INTRODUCTION: DEFINATIONS
•CHEMOTHERAPY: The term chemotherapy
is describe as the use of chemicals or drugs to
treat cancer.
•CYTOTOXIC DRUG: Lysis both normal and
cancer cells
8/23/2018 bbinyunus2002@gmail.com 238

CHEMOTHERAPY
•Systemic chemotherapy is the main treatment
available for disseminated malignant diseases.
•Progress in chemotherapy resulted in cure for
several tumors.
•Chemotherapy usually require multiple cycles.

MODES OF CHEMOTHERAPY
• PRIMARY CHEMOTHERAPY - chemotherapy is used as
the sole anti-cancer treatment in a highly sensitive tumor types
• Example – CHOP for Non-Hodgkins lymphoma
• ADJUVANT CHEMOTHERAPY – treatment is given after
surgery to “mop up” microscopic residual disease
• Example – Adriamycin, cyclophosphamide for breast cancer
• NEOADJUVANT CHEMOTHERAPY – treatment is given
before surgery to shrink tumor and increase chance of
successful resection
• Example – Adriamycin, ifosfamide for osteosarcoma

MODES OF CHEMOTHERAPY
•CONCURRENT CHEMOTHERAPY – treatment
is given simultaneous to radiation to increase
sensitivity of cancer cells to radiation.
•Example – Cisplatin, 5-fluourouracil, XRT for
head and neck tumors.

COMPLICATION OF CHEMOTHERAPY
•Every chemotherapeutic will have some
deleterious side effect on normal tissue .
•E.G; Myelosuppression, nausea & vomiting,
Stomatitis, and alopecia are the most frequently
observed side effects.

Mucositis
Nausea/vomiting
Diarrhea
Cystitis
Sterility
Myalgia
Neuropathy
Alopecia
Pulmonary fibrosis
Cardiotoxicity
Local reaction
Renal failure
Myelosuppression
Phlebitis
SIDE EFFECTS OF CHEMOTHERAPY

CRITERIA USED TO DESCRIBE RESPONSE
ARE:
• Complete response (complete remission)is the disappearance
of all detectable malignant disease.
• Partial response : is decrease by more than 50% in the sum of
the products of the perpendicular diameters of all measurable
lesions.
• Stable disease : no increase in size of any lesion nor the
appearance of any new lesions.
• Progressive disease : means an increase by at least 25% in the
sum of the products of the perpendicular diameters of
measurable lesion or the appearance of new lesions.

ENDOCRINE THERAPY
• Many hormonal antitumor agents are functional agonist or antagonist of
the steroid hormone family.
• Adrenocorticoids:
• Antiandrogen:
• Estrogen:
• Antiestrogen:
• Progestins
• Aromatase inhibitor:
• Gonadotropin-releasing hormone agonists:
• Somatostatin analogues:

BIOLOGIC THERAPY
•Immunotherapy:
•Cytokines:
•Cellular therapy:
•Tumor vaccine:
•Hematopoietic growth factors.

Anticancer drugs: Drugs used in Cancer
• The drugs which are used to destroy cancer cell and normal tissue is
known as antineoplastic agents. Combination therapy is usually used
to kill as many as cancer cells.
• Drug Classification: These drugs mainly classified as:
1. Alkylating Drugs: they inhibit the synthesis of DNA.
2. Antitumor Antibiotics: They act as interfere with DNA & RNA
synthesis.
3. Antimetabolites: A metabolite is a chemical substance which
takes part in cellular metabolic reaction. It blocks a metabolic
reaction.
8/23/2018 247

Mechanism of Action
 According to chemical structure and sources of drugs
• Alkylating Agents, Antimetabolite, Antibiotics, Plant Extracts,
Hormones and Others
 According to the cycle or phase specificity of the drug:
• Cell cycle nonspecific agents (CCNSA) & Cell cycle specific
agents (CCSA).

Mechanism of Anticancer Drugs
According to biochemistry mechanisms of anticancer action:
Block nucleic acid (DNA, RNA) biosynthesis
Directly destroy DNA and inhibit DNA reproduction
Interfere transcription and block RNA synthesis
Interfere protein synthesis and function
Influence hormone homeostasis.

Block nucleic acid (DNA, RNA) biosynthesis
Antimetabolites:
• Folic Acid Antagonist: inhibit dihydrofolate reductase (methotrexate)
• Pyrimidine Antagonist: inhibit thymidylate synthetase (fluorouracil) ;
inhibit DNA polymerase (cytarabine)
• Purine Antagonist: inhibit interconversion of purine nucleotide (6-
mercaptopurine and 6-Thioguanine)
• Ribonucleoside Diphosphate Reductase Antagonist: (hydroxyurea)

Influence the Structure and Function of DNA
• Alkylating Agent: mechlorethamine, cyclophosphamide,
ifosfamide, chlorambucil, Mephalan, Busulfan, Nitrosoureas and
Thio-TEPA
• Platinum: cis-platinium, carboplatin and imatinib
• Antibiotic: bleomycin and mitomycin C
• Topoismerase inhibitor: camptothecin analogues and
podophyllotoxin and antibiotics like actinomycin D,
daunorubicin and doxorubicin

Interfere Protein Synthesis
• Antitubulin: vinca alkaloids (vincristine and
vinblastin) and taxanes (paclitaxel and docetaxel)
Bind tubulin, destroy spindle to produce mitotic arrest
• Influence amino acid supply: L-asparaginase.

Influence hormone homeostasis
These drugs bind to hormone receptors to block the actions
of the sex hormones which results in inhibition of tumor
growth
• Estrogens and estrogen antagonistic drug (EE, SERM-
tamoxifene)
• Androgens and androgen antagonistic drug (flutamide and
bicalutamide)
• Progestogen drug (hydroxyprogesterone)
• Glucocorticoid drug (prednisolone and others)
• Gonadotropin-releasing hormone inhibitor: nafarelin, triptorelin
• aromatase inhibitor: Letrozole and anastrazole.

8/23/2018 bbinyunus2002@gmail.com 254
CHEMOTHERAPUETIC
AGENT
MECHANISM OF
ACTION
SIDE EFFECT
ALKYLATING AGENT
Cyclophosphamide, chlorambucil,
thiothepa, melphalan etc
Interferes with cross
linkage of DNA
Myelosupression
Hemorrhagic cystitis
Skin rash
Flu-like syndrome
ANTIMETABOLITES
• Folic acid antagonist e.g
methotraxate
• Purine antagonist e.g 6-
mercaptopurine,
• Pyrimidine antagonist e.g 5-
fluorouracil
Interfere with nucleic
acid synthesis because
they are analogues of
normal metabolites
Mucositis, Nephropathy, Hepato-
toxicity & Hand & foot syndrome
VINCAALKALOID- vincristin,
vimblastin
Cause mitotic arrest via
spindle fiber inhibition
Neuropathy, constipation,
Mucositis & myelosuppresion
ANTITUMOUR ANTIBIOTIC e.g
adramycin, daunorubicin, actinomycin
D, bleomycin
Bind to DNA to block
RNA production
cardio toxicity, pulmonary
toxicity & myelosuppresion

8/23/2018 255
CHEMOTHERA
PEUTIC AGENT
MECHANISM
OF ACTION
SIDE EFFECT
TAXANES e.g
paclitaxel,
docetaxel
Bind to tubulin.
Stop disassembly
of mitotic
spindle
neuropathy skin
rash &
myelosuppresion
MISCELLANEO
US
L-Asparaginase
Nitrosourea
Cis-platinium

8/23/2018 256
IMMUNO-
THERAPUETIC
AGENTS
MECHANISM OF
ACTION
CLINICAL USE
Levamisole
(antihelmenthic)
immunomodulator Adjuvant in colonic cancer in
combination with 5-FU
Interleukin-2(IL-2) Enhances NK-cells
and tumour specific
T-cells
Melanoma
Renal cell ca
Neuroblastoma
NHL
Interferon Enhance NK-cells
Re-expression of
HLA gene
Kaposi’s sarcoma
Multiple myeloma
Leukemia
BCG Stimulate immune
response
CIS of the bladder,

8/23/2018 257
TARGET THERAPY MECHANISM OF
ACTION
CILNICAL USES
SMALL MOLECULES
Gefitinib
Erlotinib
Inhibits EGFR
tyrosine kinase
thereby inhibiting
growth of cancer cells
Non-small cell cancer
of the lungs
MONOCLONAL
ANTIBODIES
Trastuzumab(Herceptin)
Rituximab(mabthera)
Bevacizumab
cetuximab
Selectively kill
tumour cells
expressing certain
receptors
Trastuzumab is use
Her-2 positive breast
cancer

8/23/2018 258
HORMONE CLINCAL USES
ANTI-ANDROGENS
Flutamide oestrogen
Use with gosereline in the treatment of
metastatic prostate cancer
ANTI-ESTROGEN
Tamoxifen Pure anti-oestrogen
(fasodex)
Breast cancer
SELECTIVE AROMATASE
INHIBITORS Anastrozole
2nd line in ER/PR +ve breast ca
AMINOGLUTETHIMIDE Breast and adrenal ca
PROGETINS
Medroxyprogesterone acetate
Breast and endometrial
LHRH analogue Goserelin Prostate and breast ca
CORTICOSTEROIDS
Dexamethasone
prenisolone
Breast ca as acombination, treatment of
hypercalcemia, raise ICP from brain metastesis

ADMINISTRATION OF DRUG depend on:
•Choice of agents
• Type of cancer
• The stage
• Age
• Clinical state of patient
• Co-morbidities
• Treatment in the past
• Drug interactions
8/23/2018 259

ROUTES OF DRUG ADMINISTRATION
• ROUTES OF ADMINSTRATION
• Oral
• Intravenous
• Bolus
• Infusion
• Arterial infusion
• Extracorporeal limb perfusion
• Intracavitory
• Intrathecal
• Subcutaneous
• intramuscular
• Topical
8/23/2018 260

Alkylating Drugs:
• Contraindications: Pregnant women, Blood cell suppression
patients, Renal & Liver failure, Buscofan not useful in lymphatic and
acute leukaemia.
• Adverse effect: Nausea, vomiting, Bone marrow depression,
Ototoxicity, Nephrotoxicity, Gonadal suppression, Stomatitis,
Hyperuricemia, Tinnitus, Alopecia (Cyclophosphamide),
Hepatotoxicity.
• Drug interaction:
1. Use with other nephrotoxic & ototoxic drugs may cause additive
ototoxicity.
2. Use of these drugs with anticoagulants, Asprin, NSAID’s may
increase risk of bleeding.8/23/2018 261

S.
no.
Drugs Doses
1 Cicplastin 10mg/day. IV
2 Cyclophosphamide 2-6mg/kg/ weekly in divided doses
3 Chorambucil 200mcg/kg body wt/day
4 Streptozocin 600mg/metre square/day (IV)
8/23/2018 262

• Assess the pt. for nauseas vomiting, give anti-vomiting.
• Monitor the pt. for vital signs and phlebitis because antineoplastic
irritate the veins.
• Advice the pt. to consult the physician before receiving any
vaccination.
• Teach the pt. to notify physician immediately if fever, unusual
bleeding, sore throat or S/S of infection.
• Advice to take more fluids.
• Instruct the pt. that drug may cause hair loss but that usually
returns.
• Assess side effect and complication during therapy.
8/23/2018 263

Antitumor Antibiotics:
• Contraindications: Pregnancy, Chicken pox or Herpes
infection, Use cautiously in pt with renal or liver dysfunction.
• Adverse effect: Nausea, vomiting, Anorexia, Heart failure,
Cardiomyopathy, Bladder pain, UTI, Incontinence, Gonadal
suppression, Stomatitis, Alopecia (Cyclophosphamide),
Myocardial toxicity, Phlebitis at IV site.
• Drug interaction:
1. Digoxin level may decrease with use of these drugs.
2. Concurrent use with cyclophosphamide may increase cardio
toxicity.
8/23/2018 264

S.
no.
Drugs Doses
1 Mitomycin 6-8wk internal 20mg/meter square IV single
dose.
2 Bleomycin 15,000IU once or twice a wk.
3 Dactinomycin 15mcg/kg/day.
4 Plicamycin 15-25mcg of body wt IV
5 Doxorubicin 20mg/meter square IV
8/23/2018 265

• Monitor vital signs frequently.
• Assess S/S of Myocardial toxicity, Heart failure (Dyspnoea,
Arrythmia, hypotension, wt gain.
8/23/2018 266

Antimetabolites
• Contraindications: Renal & Liver intoxicity, Bone marrow
depression, Pregnant women.
• Adverse effect: Leukopenia, Megaloblastic Anemia, Intestinal
obstruction, Stomatitis, UTI, G.I. disturbances, Hepatotoxicity,
Hyperuricemia, Alopecia due to damage of hair follicle, fever,
Hyperbilirubinemia, Thrombocytopenia, Photosensitivity,
dermatitis, Hepatotoxicity, Renal failure, Diarrhoea.
thrombophlebitis.
• Drug interaction: Methotrexate toxicity may increase if use
this drug with tetracycline, chloramphenicol, oral
hypoglycemics, phenytoin's, salicylates.
8/23/2018 267

S.
no.
Drugs Doses
1 Methotrexate 10-25mg daily
2 Pentostatin 4mg/metre square q wk IV
3 Fludarabine 40mg/metre square daily
4 Fluorouracil 15mg/kg once weekly
5 Hydroxyurea. 80mg/kg single dose q3rd day.
8/23/2018 268

• Monitor adverse effect of Antimetabolite Drugs.
• Instruct the patient to see sunscreen and wear protective
clothing to prevent photosensitivity reaction.
8/23/2018 269

Definition: New technology and drugs that allow the cancer
treatment to “target” a certain cancer cell by interfering with
the natural functions of tumor growth
How they work: They “target” specific parts of a cancer
cell or its actions.
What it means in cancer treatment: Potentially fewer side
effects
“TARGETED” THERAPIES

TARGETED THERAPIES
• Monoclonal antibodies: proteins that trigger the body’s
pathways involved in cancer growth to fight cancer more
effectively.
• EGFR: family of receptors found on surface of normal and
cancer cells that bind with an epidermal growth factor (EGF)
causing cells to divide.
• Tyrosine Kinase Inhibitors: Part of the cell that signals it to
divide and multiply; enhances cell growth. Still investigational

CONCLUSIONS
•People with cancer are living longer
•The focus is on quality of life in addition to
quantity
•People surviving cancer want to live normal lives
•New treatments of various kinds are available
and there is no need to suffer

FUTURE TRENDS
•Tumour vaccine- stimulate the body to produce
CD4 cells which suppresses tumour cells e.g
sipuleucel-T, prostate G-vax still under
investigations
•Gene therapy.
8/23/2018 274

REFERENCES
• E.A Badoe et al, “Principles and Practice of surgery including pathology in the tropics” 4th edition,
Assembly of God Literature Center ltd, 2009
• M.A.R Al-Fallouji; “Postgraduate Surgery the candidate guide”. 2nd Edition. Rced Educational and
Professional Pub. Ltd 1998
• Sriram Bhat S “SRB manual of surgery” 4th edition Jaypee Brothers Medical Publishers (P) Ltd
• Guidelines for the Safe Prescribing, Dispensing and Administration of Cancer Chemotherapy
“Clinical Oncological society of Australia” Nov. 2008
• Joseph O. Jacobson et al,” American Society of Clinical Oncology/Oncology Nursing Society
Chemotherapy Administration Safety Standards” journal of clinical oncology. volume 27 number
32 november 10 2009.
• www.slideshare .net
• www.wikepedia .org
8/23/2018 275

Immune-suppressants
•Assignment
8/23/2018 276

Immune-suppressants
• Introduction: These drugs suppress or reduce the strength of
body immune system. They are also called antirejection drugs.
One of the primary uses of immunosuppressant's drugs is to
lower the body’s ability to reject a transplanted organ such as
liver, heart or kidney.
• Mechanism of Action: Their action are different according to
the four categories:
1. Azathioprine suppress cell mediated immunity and alters
antibody formation.
2. Cyclosporine inhibit proliferation and function of T –
Lymphocytes.
8/23/2018 277

3. Monoclonal antibodies which includes basiliximab, daclizumab, and
muromonab blocks T – Cell function.
4. Corticosteroids (Prednisone) inhibit macrophage formation and
hinders migration of microphage and leukocyte to inflamed areas.
• Indication/Uses:
 Treatment of autoimmune disorders such as psoriasis, rheumatoid
arthritis, crohn’s disease, multiple sclerosis, Alopecia areata (Patchy
hair loss.
Used to prevent of organ transplantation.
Bone marrow transplantation.
Prednisone is used for its anti-inflammatory or immunosuppressive
action.
8/23/2018 278

CLASSIFICATION OF IMMUNOSUPPRESSANTS
1.PHYSICAL IMMUNOSUPRESSANTS
• Includes Total Lymphoid Irradiation, Plasmapheresis, thoracic duct drainage
• Inhibits Cell division ,cell activation, Antibody production
2.CHEMICAL IMMUNOSUPPRESSANTS:
• I. Corticosteroids
• II. Cytostatics
• III. Antibodies
• IV. Drugs acting on Immunophilins
3.BIOLOGICAL IMMUNOSUPPRESSANTS:
interferon's, interleukins, colony-stimulating factors, monoclonal antibodies

S.
no.
Drugs Doses
1 Azathioprine 1mg/kg (50-100)mg PO/IV per day in divided
dose Max. dose 2.5mg/kg PO/IV per day.
2 Cyclosporine 10-15mg per kg /day with milk
3 Daclizumab 0.1mg/kg
4 Muromonab 5mg ID OD.
5 Basiliximab 10-20 mg
6 Prednisone 5-60mg per day in divided doses
1-4times/day.
8/23/2018 280

Contd
• Contraindication & Precautions: Bone marrow depression,
Infection, cancer, Impaired liver kidney function (cautiously use),
Contraindicated in patient with hypersensitivity to poly-sorbate –
80.
• Use all immunosuppressive cautiously in pregnant and breast
feeding women.
• Adverse effect: Peptic ulcer, increase sr. glucose level,
Nausea/vomiting, Anorexia, Hepatotoxicity, Fever and chills,
electrolyte changes, tremors, weight gain, edema, mood swing,
diarrhoea, leukopenia, thrombocytopenia, G.I. disorder,
nephrotoxicity, Dyspnea, flu like symptoms.
8/23/2018 281

1. Concurrent use of cyclosporine with other nephrotoxic drugs causes
additive nephrotoxicity.
2. Ketoconazole and cimetidine increase the risk of toxicity from
cyclosporine.
3. Allopurinol increases the risk of toxicity azathioprine.
• Nursing Responsibilities:
Nurse should monitor for adverse effect, toxicity and sign &
symptoms of infection.
Nurse should monitor & maintain intake and output chart.
Nurse should instruct patient to report unusual bleeding or sign and
symptoms of transplant rejection
8/23/2018 282

• Nurse should inform the patient about potential teratogenic effects of
these drugs during pregnancies and urge the patient to use contraception.
• Nurse should teach the patient about the importance of life long
compliance with immunosuppressive therapy to prevent organ transplant
rejection.
• Assess the patient for S/S of infection, such as fever, tachycardia,
malaise, redness and inflammation.
8/23/2018 283

References
1. Dr. P.K. Panwar, Essentials of pharmacology for nurses, AITBS pub. 2017,
India, Pg no. 10 – 34.
2. Dr. Suresh k sharma, Textbook of pharmacology, pathology & genetics for
nurses, Jaypee pub. 2016 India Pg no 25 – 120.
3. Tara v. Shanbhag, Smita shenoy, Pharmacology preparation manual for
undergraduate, Elsevier pub. 2014. Pg no. 366 – 460.
4. Marilyn Herbert – Ashton, Nancy Clarkson, Pharmacology, Jones & Barlet
pub 2010 India, Pg no 2-93.
5. Govind s. mittal, Pharmacology at a glance, Paras medical book pub. 2009
India 40 – 50.
6. Madhuri Inamdar, Pharmacology in nursing, Vora medical pub. 2006 India
1st edition, Pg no 14 – 60.

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