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Chemotherapy

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Title: Chemotherapy


1
CHEMOTHERAPY
  • By Mrs. Kalaivani Sathish M. Pharm
  • Assistant Professor,
  • PIMS - Panipat

2
Definition
  • The treatment of disease by the use of chemical
    substances, especially the treatment of cancer by
    cytotoxic and other drugs.

3
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

4
UNIT OVERVIEW (Cont)
  • Anti Cancer Drugs
  • Treatment of Amoebiasis, Helminthic Infections
  • Antifungal Drugs
  • Anti Septics and Disinfectants

5
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

6
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

7
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

8

9
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

10
  • Penicillin may not bind to the bacteria, because
    of changes in the target protein, this leads to
    resistance.

11
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.

12
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.

13
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.

14
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.

15
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.

16
DISADVANTAGE OF NATURAL PENICILLIN
  • Narrow spectrum of activity
  • Not effective orally
  • Susceptible to pencillinases
  • Risk of hypersensitivity.

17
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.

18
. 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.

19
. 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.

20
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.

21
  • 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.

22
  • 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.

23
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.

24
  • 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.

25
  • 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

26
  • 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.

27
  • 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.

28
  • 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

29
  • 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.

30
  • 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

31
  • Meziotilline
  • It has activity similar to Ticarcilline.
  • It is given parentally primarily for infections
    caused by Enteric bacilli.

32
? - 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.

33
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,

34
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.

35
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.

36
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.

37
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

38
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.

39
SULBACTAM ADVERSE EFFECTS
  • Pain at site of injections
  • Thrombophlebitis
  • Rashes and Diarrhoea.

40
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

41
TAZOBACTUM (Cont)
  • Dose 0.5 combined with Piperacilline, 4 g IV,
    30 Minutes for 8th Hourly.

42
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