Chemotherapy

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CHEMOTHERAPY

• By Mrs. Kalaivani Sathish M. Pharm
• Assistant Professor,
• PIMS - Panipat

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Definition

• The treatment of disease by the use of chemical
  substances, especially the treatment of cancer by
  cytotoxic and other drugs.

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UNIT OVERVIEW

• Penicillin and Sulphonamides
• Broad Spectrum Antibiotics
• Aminoglycosides and Treatment of UTI
• Macrolides and Misc. AMA
• Quinolones
• Anti TB, HIV AIDS Drugs Treatment of AIDS.
• Anti Leprosy Drugs Treatment of Anaerobic
  Infections

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UNIT OVERVIEW (Cont)

• Anti Cancer Drugs
• Treatment of Amoebiasis, Helminthic Infections
• Antifungal Drugs
• Anti Septics and Disinfectants

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PENICILLIN

• Alexander Fleming
• Pencillin was discovered by chance in 1928.
• It was the first antibiotic to be used clinically
  in 1941.
• It was originally obtained from the fungus
  Penicillium notatum, but the present source is P.
  Chrysogenum

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CLASSIFICATION

• A. Natural Penicillin G
• B. Semi Synthetic
• 1. Acid Resistant Alternative To Pencillin G
  Phenoxy Methyl Penicillin Penicillin V
• 2. Penicillinase Resistant Penicillin
  Methicillin, Cloxacillin

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CLASSIFICATION (Cont..)

• 3. Extended Spectrum Penicillin 3 Types
• A. Aminopenicillin. E.g., Ampicillin, Bac
  Ampicillin, Amoxicillin
• B. Carboxypenicillin, E.g., Carbenicillin,
  Ticarcillin
• C. Ureidopenicillin, E.g., Pipercillin,
  Mezlocillin.
• ? - Lactamase Inhibitors Clavulanic acid,
  Sulbactam, Tazobactam

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NATURAL PENICILLIN

• Penicillin G has a narrow antibacterial spectrum
  and is effective against gram positive cocci and
  bacilli and a few gram negative cocci.
• Resistance
• Many organisms like staphylococci produce a
  penicillinase which is a ? - Lactamat.
• It opens the ? - Lactam ring and inactivate
  penicillin

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• Penicillin may not bind to the bacteria, because
  of changes in the target protein, this leads to
  resistance.

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PHARMACOKINETICS OF PENICILLIN G

• Penicillin G is destroyed by gastric juice. It
  could interfere with its absorption hence it is
  to be given 2 hours after food.
• It does not readily cross the BBB in the presence
  of inflammation, therapeutic concentration is
  attained in the CSF.
• It is excreted by the kidney.

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PREPARATION DOSE

• Penicillin G is mainly given parentally, Oral
  Penicillin is used only in minor infections.
• Procaine Penicillin G (0.5 to 1 MU) 12 24 Hrs.
  IM Route.
• Benzaphine Penicillin G (1.2 to 2.4 MU) Every 3
  4 weeks, Deep IM.

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ADVERSE EFFECTS

• Hypersensitivity
• Other adverse effects includes
• Pain at the site of infection, thrombophelebitis
  on IV injections.
• On CNS Large dose may produce confusion, muscle
  twitching, convulsions and coma, supra
  infections.

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USES

• Pneumococcal infections Pneumonia, Meningitis,
  Osteomyelitis.
• Streptococcal infections pharygitis, sinusitis,
  pneumonia, meningitis and endocarditis.
• Meningococcal infection
• Staphylococcal infection
• Syphillis
• Diptheria
• Anerobic infections pulmonary, dental and brain
  abscess.

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USES

• Actinomycosis
• Tetanus and Gas Gngrene
• Other infections Anthrax, trench mouth, rat
  bite fever and listeria infections.
• Prophylactic Uses Includes
• Rheumatic Fever, Gonorrhea and syphillis
• Valvular heart diseases.

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DISADVANTAGE OF NATURAL PENICILLIN

• Narrow spectrum of activity
• Not effective orally
• Susceptible to pencillinases
• Risk of hypersensitivity.

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SEMI SYNTHETIC PENICILLIN

• These are produced by chemically combining
  specific side chain or by incorporating specific
  precursors in the mould cultures.
• It has overcome the short comings of the
  Penicillin G, which are as below
• Poor Oral Efficacy
• Susceptibility to Penicillinase
• Narow Spectrum activity
• Hypersensitivity reactions.

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. Acid Resistant Alternative To Pencillin G

• Phenoxy Methyl Penicillin Penicillin V
• It differs from PnG. Only in that it is acid
  stable and oral absorption is better , Peak blood
  level is reached in 1 Hr Plasma T ½ is 30 to
  60 minutes.
• The antibacterial spectrum of PnV is identical to
  PnG.
• It is used only for streptococcal Pharyngitis,
  Sinusitis, Ottitis media.

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. Acid Resistant Alternative To Pencillin G

• Prophylaxis of Rheumatic fever, less serious
  Pneumococcal infections and Trench Mouth.
• Dose 250 500 mg for adults and for infants 60
  mg, children 125 250 mg given 6th Hourly.

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Penicillinase Resistant Penicillin Methicillin,
Cloxacillin

• They are resistant to hydrolysis by penicillinase
  produced by bacteria.
• They are less effective than PnG.
• Methicillin
• It is highly penicillinase resistant but not acid
  resistant.
• It is also an inducer of penicillinase
  production.
• MRSA (Methicillin Resistant Staph Aureus ) also
  called as Super Bug Bacteria.

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• MRSA have altered PBPs (Penicillin-binding
  proteins)
• Adverse Effects Hematuria, Albuminuria,
  Reversible interstitial Nephritis.
• Adverse effects has been replaced by Cloxacillin.
• Cloxacillin
• It is less active against PnG sensitive
  organisms, should not been used as its
  substitute. It is more active than Methicillin
  against penicillinase producing Staph, but not
  against MRSA.

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• Cloxacilline is incompletely but dependably
  absorbed from oral route especially when taken in
  empty stomach.
• It is gt 90 plasma protein bound.
• It is eliminated by kidney primarily and also
  partially by liver.
• Plasma T ½ is about 1 Hour.
• Dose 0.25 0.5 gram orally every 6 Hrs for
  severe infection 0.25 to 1 gram may be injected.

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Extended Spectrum Penicillin

• Aminopenicillin
• These agents cover a wider antibacterial spectrum
  including many gram ve bacilli. They are orally
  effective.
• 1. Ampicillin
• It is active against all organisms sensitive to
  PnG for Strepto. Viridens and Enterococci,
  equally active for Pneumococci, Gonococci and
  Meningococci.

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• But less active against other gram positive
  cocci.
• Pharmacokinetics
• Ampicillin is not degraded by gastric acid.
• Oral absorption is incomplete but adequate.
• It is partially excreted in bile and reabsorbed
  in entero hepatic circulation .
• Primarily excreted through kidney
• T ½ Period is 1 Hour
• Dose 0.5 to 2 gram Oral / IM IV every 6th
  Hour.

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• Children Dose is 25 to 50 mg / Kg / Day.
• Uses
• Drug of choice for Acute UTI.
• RTI including broncitis, Sinusitis, Otitis.
• Meningitis
• Gonorrhoea First line drug of choice for oral
  treatment of non penicillinase producing
  Gonococcal infection.
• Typhoid Fever

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• Bacillary dysentery
• Cholecystitis (Inflammation of Gall bladder)
• Sub acute bacterial endocarditis
• Septicemia
• Adverse Effects
• Diarrhoea is frequently common after oral
  administration.
• Rashes especially in AIDS, EB infected Patients.

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• Drug Interactions Hydrocortisone inactivates
  ampicillin if mixed with IV Solution.
• It interferes with oral contraceptives, failure
  of oral contraception.
• Bac Ampicillin
• It is an ester of ampicillin.
• It is a pro drug i.e., better absorbed and longer
  acting than ampicillin.
• Dose 400 800 mg bd.

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• AMOXICILLIN
• It differs from ampicillin in the following
• Amoxicillin is better absorbed orally
• Food does not interfere with its absorption
• Diarrhoea is rare
• Amoxicillin is given thrice daily but ampicillin
  is given 4 times a day.
• USES
• It is used in respiratory infection, UTI,
  Salmonella gastroenteritis

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• Doses
• 0.25 to 1 gram Tds. Oral IM
• Carboxypenicillin
• In adittion to activity against gram ve and gram
  ve organism is also effective against P.
  Aeruginosa and Proteas Infections.
• DOSE 1 5 gram IV every 4 to 5th Hour.

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• Ticarcillin
• It is more potent than carbencillin but
  properties are similar to each.
• Ureidopenicillins
• Piperapacillin this anti pseudomonal penicillin
  is about 8 times more active than carbenicillin
• It has good activity against klebsiella and used
  mainly in neutropenic.
• T ½ IS 1 Hour. Dose 100 150 mg / kg/ day

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• Meziotilline
• It has activity similar to Ticarcilline.
• It is given parentally primarily for infections
  caused by Enteric bacilli.

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? - Lactamase Inhibitors

• ? - Lactamase are enzyme produced by bacteria,
  that open up the ? - Lactam ring and inactive the
  ? - Lactam antibiotics.
• ? - Lactamase Inhibitors bind to inactivate ? -
  Lactamase, thus preventing the destruction of ? -
  Lactam antibiotics.

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CLAVULANIC ACID INHIBITORS

• ? - Lactamases and is combined with Amoxycillin
  for both oral and parentral administration.
• The combination of Amoxycillin and Clavulanic
  acid used for mixed aerobic, anaerobic and
  Nosocomical infections.
• Clavulanic acid is also combined with
  Ticarcilline for Parentral use,

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PHARMACOKINETICS OF CLAVULANIC ACID

• It has rapid oral absorption and bio availability
  of 60 can also be injected.
• T ½ is One Hour. It is eliminated mainly
  glomerular filteration.

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USES

• Skin and Soft tissue infection.
• Intra abdominal and gynaecological sepsis.
• Urinary and RTI
• Nosocomical Infections (Hospital Acquired
  Infections)
• Gonnorrhea Single dose Amoxycilline 3 g.
  Clavulanic acid 0.5 g Probenecid 1 g.

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ADVERSE EFFECTS

• Tolerance is poor especially in children.
• Other side effects are Candida stomatitis.
• Vaginitis and Rashes
• Hepatic Injury causes in combinations of
  Clavulanic acids.

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SULBACTAM

• It is a semi synthetic ? - Lactamase Inhibitors.
• Related chemically and as well as in activity to
  clavulanic acid.
• It is 2 3 times less potent time than
  clavulanic acid.
• It does not induce chromosomal ? - Lactamases.
• Preferably administered Parenterally

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SULBACTAM INDICATIONS

• Penicillinase-producing Neisseria gonorrhoeae
  (PPNG).
• N. Gonorrhoeae.
• Mixed aerobic and anaerobic infections.
• Intra abdominal Gynaecological , surgical and
  skin soft tissue infections, especially those
  acquired in hospitals.

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SULBACTAM ADVERSE EFFECTS

• Pain at site of injections
• Thrombophlebitis
• Rashes and Diarrhoea.

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TAZOBACTUM

• It is another ? - Lactamase inhibitor similar to
  sulbactam.
• Its pharmacokinetics mataches with Piperacillin.
• It is used in severe infections like Peritonits,
  Pelvic, Urinary, RI caused by ? - Lactamase
  producing bacilli

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TAZOBACTUM (Cont)

• Dose 0.5 combined with Piperacilline, 4 g IV,
  30 Minutes for 8th Hourly.

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