PHARMACOLOGY

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PHARMACOLOGY

• Anti-infective drugs

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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.

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OBJECTIVES

• Identify drug interactions and adverse reactions
  to these drugs.

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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.

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ANTI-INFECTIVE DRUGS

• Location of infection.
• Cost of drug.
• Wise use to prevent resistance.

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ANTI-INFECTIVE DRUGS

• Include the following classifications
• Antibacterial
• Antiviral
• Antitubercular
• Antimycotic
• Antimalarial and antiprotozal

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ANTIBACTERIAL DRUGS

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

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ANTIBACTERIAL DRUGS

• macrolides
• vancomycin
• carbapenems
• monobactams
• flouroquinolones
• sulfonamides
• nitrofurantoin

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AMINOGLYCOSIDES

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

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AMINOGLYCOSIDES

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

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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.

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AMINOGLYCOSIDES

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

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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.

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AMINOGLYCOSIDES

• Drug interactions
• Interactions with a variety of drugs can cause
  neuromuscular reactions, ototoxicity, and kidney
  toxicity.
• Adverse reactions ototoxicity, nephrotoxicity,
  N,V,D.

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PENICILLINS

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

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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.

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PENICILLINS

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

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PENICILLINS

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

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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.

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PENICILLINS

• Drug interactions
• May interact with various drugs.
• The effectiveness of oral contraceptives is
  reduced when they are taken with penicillin V and
  ampicillin.
• Adverse reactions anaphylaxis, rashes, N,V,D.

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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).

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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.

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CEPHALOSPORINS

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

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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.

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CEPHALOSPORINS

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

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CEPHALOSPORINS

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

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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.

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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.

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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.

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CEPHALOSPORINS

• Adverse reactions hypersensitivity (hives,
  itching, rashes), N,V,D.

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TETRACYCLINES

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

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TETRACYCLINES

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

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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.

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TETRACYCLINES

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

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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.

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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.

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TETRACYCLINES

• Adverse reactions superinfection,
  photosensitivity, N,V,D.

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CLINDAMYCIN

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

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CLINDAMYCIN

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

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CLINDAMYCIN

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

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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.

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CLINDAMYCIN

• Drug interactions
• May block neuromuscular transmission and may
  enhance the action of neuromuscular blockers.
• Adverse reactions pseudomembranous colitis,
  N,V,D.

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MACROLIDES

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

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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.

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MACROLIDES

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

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MACROLIDES

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

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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.

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MACROLIDES

• Drug interactions
• Can increase theophylline levels increasing
  toxicity risk.
• Adverse reactions few but can include N,V,D.

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VANCOMYCIN

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

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VANCOMYCIN

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

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VANCOMYCIN

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

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VANCOMYCIN

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

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VANCOMYCIN

• Drug interactions
• May increase the risk of toxicity when
  administered with other drugs toxic to the
  kidneys and organs of hearing.
• Adverse reactions rare but can include
  hypersensitivity and anaphylactic reactions.

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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.

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CARBAPENEMS

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

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CARBAPENEMS

• Pharmacodynamics
• Inhibit bacterial cell wall synthesis.

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CARBAPENEMS

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

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CARBAPENEMS

• Drug interactions
• May interact with other drugs.
• Adverse reactions N,V,D.

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MONOBACTAMS

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

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MONOBACTAMS

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

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MONOBACTAMS

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

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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.

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MONOBACTAMS

• Drug interactions
• Synergistic or additive effects occur when used
  with a variety of other antibiotics.
• Adverse reactions N,V,D, hypersensitivity,
  hypotension.

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FLUOROQUINOLONES

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

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FLUOROQUINOLONES

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

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FLUOROQUINOLONES

• Pharmacodynamics
• Interrupt DNA synthesis during bacterial
  replication.

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FLUOROQUINOLONES

• Pharmacotherapeutics
• Used to treat a variety of UTIs.

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FLUOROQUINOLONES

• Drug interactions
• Several interactions may occur.
• Adverse reactions few but may include N,V,D.

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SULFONAMIDES

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

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SULFONAMIDES

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

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SULFONAMIDES

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

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SULFONAMIDES

• Pharmacotherapeutics
• Frequently used to treat acute UTIs.

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SULFONAMIDES

• Drug interactions
• Have few significant interactions.
• Increase the hypoglycemic affects of oral
  diabetic agents.
• Adverse reactions urinary crystals,
  hypersensitivity.

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NITROFURANTOIN

• Used primarily to treat acute and chronic UTIs.

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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.

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NITROFURANTOIN

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

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NITROFURANTOIN

• Pharmacotherapeutics
• Used to treat UTIs.

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NITROFURANTOIN

• Drug interactions
• Has few significant drug interactions.
• Adverse reactions GI irritation, N,V,D, dark
  yellow or brown urine.

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ANTIVIRAL DRUGS

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

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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.

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ANTIVIRAL DRUGS

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

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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.

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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.

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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.

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ANTITUBERCULAR DRUGS

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

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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.

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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.

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ANTIMYCOTIC DRUGS

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

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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.

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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.

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ANTIMALARIAL/PROTOZOAL DRUGS

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