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PHARMACOLOGY

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Title: PHARMACOLOGY


1
PHARMACOLOGY
  • Anti-infective drugs

2
OBJECTIVES
  • Identify the classes of drugs that act as
    anti-infectives.
  • Identify the uses and varying actions of these
    drugs.
  • Identify how these drugs are absorbed,
    distributed, metabolized and excreted.

3
OBJECTIVES
  • Identify drug interactions and adverse reactions
    to these drugs.

4
ANTI-INFECTIVE DRUGS
  • Important factors affecting choice of
    anti-infective drugs
  • Identification of microorganism through culture.
  • Determination of susceptibility of organism to
    anti-infective drugs through sensitivity.

5
ANTI-INFECTIVE DRUGS
  • Location of infection.
  • Cost of drug.
  • Wise use to prevent resistance.

6
ANTI-INFECTIVE DRUGS
  • Include the following classifications
  • Antibacterial
  • Antiviral
  • Antitubercular
  • Antimycotic
  • Antimalarial and antiprotozal

7
ANTIBACTERIAL DRUGS
  • Used mainly to treat systemic bacterial
    infections.
  • Classes include
  • aminoglycosides
  • cephalosporins
  • tetracyclines
  • clindamycin and lincomycin

8
ANTIBACTERIAL DRUGS
  • macrolides
  • vancomycin
  • carbapenems
  • monobactams
  • flouroquinolones
  • sulfonamides
  • nitrofurantoin

9
AMINOGLYCOSIDES
  • Provide effective bactericidal activity against
    aerobic gram-negative bacilli some aerobic
    gram-positive bacteria mycobacteria and some
    protozoa.

10
AMINOGLYCOSIDES
  • Aminoglycosides currently in use include
    amikacin sulfate gentamycin sulfate kanamycin
    sulfate neomycin sulfate netilmicin sulfate
    paromomycin sulfate streptomycin sulfate and
    tobramycin sulfate.

11
AMINOGLYCOSIDES
  • Pharmacokinetics
  • Given IM or IV absorbed poorly from the GI
    tract.
  • Distributed widely cross the placental barrier
    but not the blood-brain barrier.
  • Not metabolized excreted primarily by the
    kidneys.

12
AMINOGLYCOSIDES
  • Pharmacodynamics
  • Act as a bactericidal agents by interrupting
    protein synthesis in the microorganism.

13
AMINOGLYCOSIDES
  • Pharmacotherapeutics
  • Most useful in treating aerobic gram-negative
    bacilli infections serious nosocomial infections
    such as bacteremia, peritonitis, and pneumonia
    UTIs caused by enteric bacilli CNS and eye
    infections.

14
AMINOGLYCOSIDES
  • Drug interactions
  • Interactions with a variety of drugs can cause
    neuromuscular reactions, ototoxicity, and kidney
    toxicity.

15
PENICILLINS
  • One of the most important and useful
    antibacterials.
  • Divided into four groups natural penicillins
    penicillinase-resistant penicillins
    aminopenicillins and extended-spectrum
    penicillins.

16
PENICILLINS
  • Pharmacokinetics
  • Absorbed mainly in the duodenum and upper
    jejunum rate depends on particular penicillin,
    pH of GI tract, food in GI tract.
  • Distributed widely, even in the urine.

17
PENICILLINS
  • Pharmacokinetics (cont.)
  • Metabolized to a limited extent in the liver to
    inactive metabolites and excreted 60 unchanged
    by the kidneys.

18
PENICILLINS
  • Pharmacodynamics
  • Bind to enzymes outside the bacterial cytoplasmic
    membrane called penicillin-binding proteins
    inhibiting cell wall synthesis and cell division.

19
PENICILLINS
  • Pharmacotherapeutics
  • No other class of antibacterial drugs provides as
    wide a spectrum of antimicrobial activity as the
    penicillins.
  • Can be given IM when oral administration is not
    an option.

20
PENICILLINS
  • Drug interactions
  • May interact with various drugs.
  • The effectiveness of oral contraceptives is
    reduced when they are taken with penicillin V and
    ampicillin.

21
CEPHALOSPORINS
  • Introduced in recent years for clinical use.
  • Grouped into generations according to their
    effectiveness against different organisms, their
    characteristics, and their development (first
    through fourth generation).

22
CEPHALOSPORINS
  • Loracarbef (Lorabid) is a synthetic beta-lactum
    antibiotic that belongs to a new class of drugs
    called the carbacephen antibiotics.
  • It is similar to the second generation
    cephalosporins, and therefore is classified as
    such.

23
CEPHALOSPORINS
  • A person who has a reaction to penicillin may
    also have a reaction to cephalosporins.

24
CEPHALOSPORINS
  • Pharmacokinetics
  • Many cephalosporins are administered parenterally
    but some can be absorbed from the GI tract.
  • Distributed widely throughout the body but
    limited to the CNS.

25
CEPHALOSPORINS
  • Pharmacokinetics (cont.)
  • Many are not metabolized at all.
  • Excreted primarily unchanged by the kidneys.

26
CEPHALOSPORINS
  • Pharmacodynamics
  • Inhibit cell wall synthesis by binding to the
    bacterial enzymes (PBPs).

27
CEPHALOSPORINS
  • Pharmacotherapeutics
  • First-generation - act primarily against
    gram-positive organisms and used as an
    alternative to penicillin.
  • Second-generation - act primarily against
    gram-negative bacteria.

28
CEPHALOSPORINS
  • Pharmacotherapeutics (cont.)
  • Third-generation - act primarily against
    gram-negative organisms and are the drug of
    choice for anaerobic organisms.
  • Fourth-generation - active against a wide range
    of gram-positive and negative bacteria.

29
CEPHALOSPORINS
  • Drug interactions
  • Mixing cefamaodole, cefoperazone, or moxalactam
    with alcohol (up to 72 hours after taking a dose)
    may lead to acute alcohol intolerance.
  • Taking with uricosurics may reduce kidney
    excretion.

30
TETRACYCLINES
  • Broad spectrum antibiotics.
  • Classified as short-acting, intermediate-acting,
    and long-acting.

31
TETRACYCLINES
  • Pharmacokinetics
  • Absorbed from the duodenum when taken orally.
  • Distributed widely excreted primarily by the
    kidneys.

32
TETRACYCLINES
  • Pharmacodynamics
  • Inhibit the growth or multiplication of bacteria
    by penetrating the cell and binding to the
    ribosome inhibiting protein synthesis required
    for maintaining the cell.

33
TETRACYCLINES
  • Pharmacotherapeutics
  • Provide a broad spectrum of activity against
    gram-positive and negative aerobic and anaerobic
    bacteria spirochetes mycoplasmas rickettsiae
    chlamydiae and some protozoa.

34
TETRACYCLINES
  • Pharmacotherapeutics (cont.)
  • Doxycycline and minocycline provide more action
    against various organisms than other
    tetracyclines.
  • Used to treat Rocky Mountain Spotted Fever, Lyme
    Disease, and acne.

35
TETRACYCLINES
  • Drug interactions
  • Can reduce the effectiveness of oral
    contraceptives.
  • Aluminum, calcium, and magnesium antacids reduce
    absorption.
  • May bind with milk and milk products preventing
    absorption.

36
CLINDAMYCIN
  • Due to adverse effects, only prescribed when
    there is no alternative.

37
CLINDAMYCIN
  • Pharmacokinetics
  • Absorbed well distributed throughout the body
    metabolized by the liver excreted by the kidneys.

38
CLINDAMYCIN
  • Pharmacodynamics
  • Inhibits bacterial protein synthesis.
  • Primarily bacteriostatic against most organisms.

39
CLINDAMYCIN
  • Pharmacotherapeutics
  • Because of its potential for serious toxicity and
    pseudomembrane colitis, it is limited to a few
    clinical situations in which safer alternative
    antibacterials are not available.

40
CLINDAMYCIN
  • Drug interactions
  • May block neuromuscular transmission and may
    enhance the action of neuromuscular blockers.

41
MACROLIDES
  • Used to treat a number of common infections.
  • Include erythromycin derivatives, azithromycin,
    and clarithromycin.

42
MACROLIDES
  • Pharmacokinetics
  • Must be buffered or have an enteric coating since
    it is acid-sensitive.
  • Absorbed in the duodenum distributed to most
    tissues (except for CSF) metabolized by the
    liver excreted in bile.

43
MACROLIDES
  • Pharmacokinetics (cont.)
  • Crosses the placental barrier and is excreted in
    breast milk.

44
MACROLIDES
  • Pharmacodynamics
  • Inhibit RNA-dependent protein synthesis by acting
    on the ribosome.

45
MACROLIDES
  • Pharmacotherapeutics
  • Erythromycin is the drug of choice for treating
    mycoplasma pneumonaie infections as well as
    legionella pneumophila pneumonia.
  • Used to treat a number of common infections.

46
MACROLIDES
  • Drug interactions
  • Can increase theophylline levels increasing
    toxicity risk.

47
VANCOMYCIN
  • Used increasingly to treat methicillin-resistant
    s. aureus (MRSA).
  • Because of vancomycin-resistant enterococci
    (VRE), vancomycin must be used judiciously.

48
VANCOMYCIN
  • Pharmacokinetics
  • Must be given IV because of its poor absorption
    in the GI tract.
  • Metabolism unknown 85 is excreted in the urine
    unchanged.

49
VANCOMYCIN
  • Pharmacodynamics
  • Inhibits bacterial cell wall synthesis allowing
    the bodys natural defenses to attack the
    organism.

50
VANCOMYCIN
  • Pharmacotherapeutics
  • Active against gram-positive organisms.
  • The therapy of choice for patients with serious
    resistant staphylococcal infections who are
    hypersensitive to penicillins.

51
VANCOMYCIN
  • Drug interactions
  • May increase the risk of toxicity when
    administered with other drugs toxic to the
    kidneys and organs of hearing.

52
CARBAPENEMS
  • A class of beta-lactum antibacterials that
    includes imipenem-cilastatin sodium (Primaxin)
    and meropenem (Merrem).
  • Their antibacterial spectrum of activity is
    broader than any other antibacterial to date.

53
CARBAPENEMS
  • Pharmacokinetics
  • Pharmacokinetic properties slightly vary.
  • Distributed widely metabolized by several
    mechanisms excreted in the urine.

54
CARBAPENEMS
  • Pharmacodynamics
  • Inhibit bacterial cell wall synthesis.

55
CARBAPENEMS
  • Pharmacotherapeutics
  • Used alone for mixed aerobic and anaerobic
    infections, as therapy for serious nosocomial
    infections, or infections in immunocompromised
    hosts.

56
CARBAPENEMS
  • Drug interactions
  • May interact with other drugs.

57
MONOBACTAMS
  • Aztreonam (Azactum) is the first member in the
    class.
  • Has a narrow spectrum of activity that includes
    many gram-negative aerobic bacteria.

58
MONOBACTAMS
  • Pharmacokinetics
  • After administered IV completely absorbed
    distributed widely partially metabolized
    excreted primarily unchanged in the urine.

59
MONOBACTAMS
  • Pharmacodynamics
  • Inhibits cell wall synthesis preventing cell wall
    division.

60
MONOBACTAMS
  • Pharmacotherapeutics
  • Is indicated in a range of therapeutic
    situations.
  • Should not be used alone in seriously ill
    patients if the infection may be caused by a
    gram-positive or a mixed aerobic-anaerobic
    bacteria.

61
MONOBACTAMS
  • Drug interactions
  • Synergistic or additive effects occur when used
    with a variety of other antibiotics.

62
FLUOROQUINOLONES
  • Structurally similar synthetic antibiotics.
  • Used to treat UTIs, URIs, pneumonia, and
    gonorrhea.
  • Drugs include
  • (suffix - floxacin oxacin)

63
FLUOROQUINOLONES
  • Pharmacokinetics
  • Absorbed well metabolism and excretion vary
    depending on the drug.

64
FLUOROQUINOLONES
  • Pharmacodynamics
  • Interrupt DNA synthesis during bacterial
    replication.

65
FLUOROQUINOLONES
  • Pharmacotherapeutics
  • Used to treat a variety of UTIs.

66
FLUOROQUINOLONES
  • Drug interactions
  • Several interactions may occur.

67
SULFONAMIDES
  • Were the first effective systemic antibacterial
    drugs.
  • Drugs include
  • (prefix - sulf suffix - azole)

68
SULFONAMIDES
  • Pharmacokinetics
  • Absorbed well distributed widely metabolized in
    the liver into inactive metabolites excreted by
    the kidneys.

69
SULFONAMIDES
  • Pharmacodynamics
  • Prevent the growth of microorganisms by
    inhibiting folic acid production which decreases
    the number of bacterial nucleotides and inhibits
    bacterial growth.

70
SULFONAMIDES
  • Pharmacotherapeutics
  • Frequently used to treat acute UTIs.

71
SULFONAMIDES
  • Drug interactions
  • Have few significant interactions.
  • Increase the hypoglycemic affects of oral
    diabetic agents.

72
NITROFURANTOIN
  • Used primarily to treat acute and chronic UTIs.

73
NITROFURANTOIN
  • Pharmacokinetics
  • Absorbed well taking drug with food increases
    bioavailability 20 - 60 protein-bound crosses
    the placental barrier partially metabolized by
    the liver 30 - 50 excreted unchanged in the
    urine also excreted in breast milk.

74
NITROFURANTOIN
  • Pharmacodynamics
  • Inhibits formation of acetyl coenzyme A from
    pyruvic acid inhibiting the energy production of
    the infecting organism.

75
NITROFURANTOIN
  • Pharmacotherapeutics
  • Used to treat UTIs.

76
NITROFURANTOIN
  • Drug interactions
  • Has few significant drug interactions.

77
ANTIVIRAL DRUGS
  • Used to prevent or treat viral infections.
  • Drugs include acyclovir, ganciclovir,
    famciclovir, foscarnet, amantadine hydrochloride,
    nelfinavir, zidovudine, didanosine, and
    zalcitabine.

78
ANTIVIRAL DRUGS
  • Antiherpes drug, acyclovir, is used to treat
    infections caused by herpes viruses and
    varicella-zoster virus by disrupting viral
    replication.
  • Foscarnet is used to treat cytomegelovirus (CMV)
    retinitis in patients with AIDS.

79
ANTIVIRAL DRUGS
  • Amantadine and rimantadine hydrochoride are used
    to prevent or treat influenza A respiratory
    infections by inhibiting the early stage of viral
    replication.

80
ANTIVIRAL DRUGS
  • Ribovirin, administered by nasal or oral
    inhalation, is used to treat respiratory
    syncytial virus (RSV) infections in children.
  • Nucleoside reverse transcriptase inhibitors are
    used in the treatment of HIV/AIDS infections.

81
ANTIVIRAL DRUGS
  • Protease inhibitors act against an enzyme, HIV
    protease, preventing the enzyme from dividing a
    larger viral precursor protein into the active
    smaller enzymes the virus needs to fully mature.
    The result is an immature, noninfectious cell.

82
ANTITUBERCULAR DRUGS
  • Used to treat tuberculosis which is caused by
    mycobacterium tuberculosis.
  • These drugs can halt the progression of an
    infection but are not always curative.
  • Need to be administered over many months.

83
ANTITUBERCULAR DRUGS
  • Because of drug-resistant TB strains, a four-drug
    regimen is recommended that includes isoniazid,
    rifampin, pyrazinamide, and streptomycin or
    ethambutol.

84
ANTIMYCOTIC DRUGS
  • Also known as antifungal drugs.
  • Are used to treat fungal infections by binding to
    sterols in fungal cell membranes and altering the
    permeability of the membranes.

85
ANTIMYCOTIC DRUGS
  • These drugs include
  • Amphoceterin B - the most widely used antimycotic
    drug for severe systemic fungal infections.
  • Nystatin - Used only topically or orally to treat
    local fungal infections.

86
ANTIMYCOTIC DRUGS
  • Flucytosine - the only metabolite that acts as an
    antimycotic.
  • Ketoconazole - an effective oral antimycotic drug
    with a broad spectrum of activity.

87
ANTIMYCOTIC DRUGS
  • Fluconazole - used to treat mouth, throat, and
    esophageal candidiasis, serious systemic candidal
    infections, and cryptococcal meningitis.
  • Itraconazole - inhibits synthesis of ergosterol,
    a vital component of fungal cell membranes.

88
ANTIMALARIAL/PROTOZOAL DRUGS
  • One of the major drugs used to prevent and treat
    malaria is chloroquine.
  • Action results from its incorporation into the
    DNA of the parasite, rendering it ineffective.

89
ANTIMALARIAL/PROTOZOAL DRUGS
  • Antiprotozoal drugs are used for a variety of
    disorders including pneumocystis carinii
    infections, giardiasis, trichomoniasis, and
    toxoplasmosis.
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