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Anti-infective Agents

Anti-infective Agents. Bacterial Morphology. Bacteria are classified by bacterial shape and colony arrangement Cocci are spherical in shape and usually arranged in pairs (diplo), chains (strepto), or clusters (staphylo) Bacilli are rod-like in shape Spirilla are curved and rod-like in shape.

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Anti-infective Agents

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  1. Anti-infective Agents

  2. Bacterial Morphology • Bacteria are classified by bacterial shape and colony arrangement • Cocci are spherical in shape and usually arranged in pairs (diplo), chains (strepto), or clusters (staphylo) • Bacilli are rod-like in shape • Spirilla are curved and rod-like in shape

  3. Gram Staining • Gram staining classification is based on ability of the bacterial membrane to stain either red or blue • Bacteria that take up the red stain are classified as gram positive, Gm(+) • Bacteria that take up the blue stain are classified as gram negative, Gm(-) • Gm(-) bacteria have an additional outer lipopolysaccharide membrane layer (endotoxin) that is toxic and that can produce endotoxic shock

  4. Antibacterial Chemotherapy • Defined as the use of drugs to kill or inhibit the growth of infectious bacteria • Bactericidal drugs kill the bacteria • Bacteriostatic drugs inhibit the growth of bacteria and body defenses and immune mechanisms are required to rid the body of infecting bacteria

  5. Antibacterial Spectrum • Refers to the range of bacteria that are killed or inhibited by any antibacterial drug • Narrow spectrum drugs are effective against a limited number of different bacterial species • Broad spectrum drugs are effective against a wide range of different bacterial species

  6. Bacterial Resistance • Bacteria have the ability to produce proteins that help them resist antimicrobial drug actions • Some bacteria produce beta-lactamase enzymes that inactivate penicillins and cephalosporins • Some bacteria produce proteins that prevent drugs from penetrating the bacterial membrane or proteins that remove the drugs once they have passed through the bacterial membrane • When bacterial resistance occurs other drugs must be used to treat the infection

  7. Penicillins • Bacteriocidal drugs that inhibit cell wall synthesis • 1st generation drugs have a narrow spectrum and indicated mostly for Gm(+) infections • 2nd generation drugs have a wider spectrum that includes most common Gm(+) / Gm(-) bacterial infections • 3rd and 4th generation drugs have a broad spectrum and are effective against most Gm(-) bacteria

  8. Cephalosporins • Bacteriocidal drugs that inhibit cell wall synthesis • 1st generation drugs are effective against most common Gm(+) and Gm(-) bacteria • 2nd, 3rd, and 4th generation cephalosporins have increasing activity against Gm(-) bacteria • Cephalosporins are the drugs of choice for infections caused by Klebsiella pneumoniae • Cephalosporins are more resistant to inactivating beta-lactamase enzymes than penicillins

  9. Adverse Effects Common to Penicillins and Cephalosporins • Minor GI disturbances and diarrhea • Hypersensitivity or allergic reactions that include delayed skin reactions or immediate anaphylactic reactions • Higher dosages may cause bleeding problems • Higher dosages may cause CNS disturbances and possible seizures

  10. Aminoglycosides • Classified as broad spectrum antibiotics • Bacteriocidal drugs that inhibit bacterial protein synthesis • Administered IM or IV for systemic effects • Usually the drugs of choice for serious gram negative infections • Nephrotoxicity and ototoxicity are the most serious adverse effects

  11. Tetracyclines • Basteriostatic drugs that inhibit bacterial protein synthesis • Administered orally, but not with dairy or antacid products • Doxycycline is the most widely used tetracycline and usually taken once per day • Adverse effects include GI disturbances, rash, and photosensitivity • Tetracyclines are contraindicated during pregnancy, nursing, and in children < age 8

  12. Sulfonamides • Bacteriostatic drugs that inhibit bacterial folic acid synthesis • Sulfonamides are mainly indicated for treatment of urinary tract infections • Trimethoprim/sulfamethoxazole has a broad antibacterial spectrum and many indications • Adverse effects include rash, allergy, blood disorders, and renal tubule damage

  13. Macrolide Antibiotics • Bacteriostatic drugs that inhibit bacterial protein synthesis, effective with oral administration • Erythromycin often used in penicillin allergic patients for minor ear and throat infections • Azithromycin and clarithromycin have a broader antibacterial spectrum and clinical uses • Adverse effects include heartburn, rashes, and GI disturbances

  14. Fluroquinolones • Bactericidal drugs that inhibit an enzyme essential to the function of bacterial DNA • Administered orally • Indicated for a wide variety of urinary, soft tissue, bone, and respiratory infections • Adverse effects include GI disturbances, rash, photosensitivity, and joint pain • Contraindicated in pregnancy and young children

  15. Miscellaneous Antimicrobials • Chloramphenicol is reserved for serious infections such as typhoid fever and meningitis • Clindamycin indicated for Gm(+) and anaerobic infections • Vancomycin indicated for resistant Gm(+) staphylococcal infections • Quinupristin-dalfopristin and linezolid indicated for Gm(+) infections resistant to vancomycin

  16. Drugs Used to Treat Tuberculosis • Tuberculosis requires prolonged treatment with multiple drugs, usually 3 or 4 different drugs • The first line drug regimen includes isoniazid, rifampin, pyrazinamide, and ethambutol • After 2–4 months of treatment ethambutol and pyrazinamide are usually eliminated • Isoniazid and rifampin therapy is continued for 6–12 months • Drug resistance is a major problem

  17. Anti-viral and Anti-fungal drugs

  18. Clinical Indication Antifungal drugs Prevention or treatment of mild to severe fungal infections Antiviral drugs Prevention and treatment of viral infections, especially seriously ill and elderly patients

  19. Fungal Infections Infections Site Drug Action Systemic Blood, brain, lungs fungicidal aspergillosis amphotericin B, histoplasmosis ketaconazole candidiasis miconazole cryptococcosis nystatin Dermatophytic Hair, skin, nails fungicidal Athlete’s foot haloprogin Ringworm tolnaftate fungistatic griseofulvin Candida albicansSkin fungicidal mucous membranes ketaconazole vagina miconazole nystatin

  20. Mechanism of Antifungal Action Fungicidal: Capable of killing fungi Drugs bind to fungal membranes and increase permeability, nutrients leak out, and fungi die Drugs: amphotericin B, ketaconazole, miconazole, nystatin Fungistatic: Limits the growth of active fungi but does not eradicate the microorganisms Drug binds to keratin in the skin and hair so fungi cannot enter the tissue and undergo further growth Drug: griseofulvin

  21. Contraindications Antifungal drugs are contraindicated in patients with history of hypersensitivity Griseofulvin is contraindicated in patients with Porphyria and hepatic failure. It should not be used during pregnancy

  22. Viral Diseases Acquired immunity Protection against developing a clinical viral infection obtained by • experiencing the infectionor • vaccination with the weakened or dead virus The immune system produces proteins that recognize viruses at the next infection and inhibit viral interaction with the host cells Examples- smallpox, chicken pox, measles, polio

  23. Viral Diseases No immunity transferred with infection • Influenza • Herpes simplex • Human immunodeficiency virus (HIV) • virus goes undetected within the human cells for years • virus attacks the lymphocytes • progressive immunosuppression • opportunistic infections develop • clinical signs and symptoms characterize AIDS (acquired immunodeficiency syndrome)

  24. Propagation of Viruses • Totally dependent on the metabolic system of the human host cells • Attach to cell membranes to inject viral DNA or RNA into the cell • Enter nucleus to direct production of more viruses according to the nucleic acid blue print • Cells rupture to “shed” new viruses to infect other host cells

  25. Antiviral Drugs Influenza Amantadine, rimantadine HIV Didanosine, lamivudine, saquinavir, zidovudine Cytomegalovirus Cidofovir, foscarnet, ganciclovir Genital Herpes, Herpes zoster, chicken pox Acyclovir, famciclovir, valacyclovir Herpes simplex keratitis Idoxuridine, trifluridine, vidarabine

  26. Antiviral Drugs—Mechanisms of Action • Inhibition of cell penetration Amantadine stops Asian strain (A2) when administered prophylactically (20 hrs ahead) • Transcription of viral proteins Didanosine, lamivudine, stavudine, zalcitabine, zidovudine inhibit reverse transcriptase so HIV RNA cannot be duplicated • Inhibition of viral synthesis Acyclovir, idoxuridine, vidarabine incorporate into HIV DNA and impair protein synthesis • Protease inhibitors Indinavir, ritonavir, saguinavir inhibit HIV proteases that are essential to make HIV infectious

  27. Special Considerations HIV protease inhibitors inhibit liver metabolism centers (P450) so that other medications may accumulate in the blood because of blocked or delayed metabolism Renal impairment will cause antiviral drugs to accumulate in the blood. Dose adjustment will be required Amantadine and rimantidine doses must be reduced in the elderly where renal clearance has decreased

  28. Anti-HIV Drugs Adverse Effects • Nausea Nephrotoxicity • Gastritis Inhibition of hepatic metabolism • Vomiting anemias • Diarrhea • Headache • Confusion • Dizziness • Insomnia • Arthralgia • Allergic reactions, edema, rash • Hypertension

  29. Characteristics of Antimalarials Highly bound to plasma proteins Metabolized in the liver Produce antiinflammatory response in immuno/inflammatory conditions e.g. rheumatoid arthritis, lupus, polymositis Relax skeletal muscle Stimulate contraction of uterine muscle Depress cardioconduction (increase PR & QT intervals on the ECG)

  30. Adverse Effects of Antimalarials Adverse effects are related to the magnitude of the dose and chronic use of the drugs • Nausea • Diarrhea • Headache • Blurred vision • Vertigo • Rash • Cinchonism – sensitive individuals experience ringing in the ears (tinnitus) and headache from CNS stimulation

  31. Protozoal Dysentary Giardia lamblia and Entameba histolytica enter the gastrointestinal tract Symptoms of acute infection Irritation of intestinal tissue Inflammation and pain Spasm of anal sphincter (tenesmus) Diarrhea Fatigue and muscle weakness Loss of body water and electrolytes

  32. Chronic Entamebic Dysentary Entamebic histolytica can burrow into the wall of the liver creating an inflammation and abscess in the absence of other typical symptoms

  33. Antidysentery Drugs Antibiotics inhibit the growth of intestinal bacteria that provide critical nutrients to the protozoaAntibiotic that distributes to all tissues including bone, bile, liver abscesses and intestines to reach all protozoa. Amebicidal. Attach to protozoa DNA and impair critical protein synthesis Paromomycin Tetracyclines Metronidazole Chloroquine, iodoquinol

  34. Parasitic Worm Infestation Enter the gastrointestinal tract with food or soil containing worm eggsWorms hatch with the intestines Worms are shed in the feces • Pinworms • Roundworms • Tapeworms

  35. Symptoms of Worm Infestation Common symptoms Diarrhea Nausea Loss of appetite Abdominal cramping Itching (anus) Hookworms, tapewormsPerforate intestines Blood loss Anemia

  36. Anthelmintic Drugs • Pinworms, roundworms Mebendazole, pyrantil pamoate, thiabendazole • Tapeworms Praziquantel

  37. Anthelmintic Drugs • Remain within the intestine • Decrease worm motility by paralyzing theparasites’ muscles • Peristalsis and laxatives move the worms and eggs out of the intestines

  38. Anthelmintic Drugs: Adverse Effects • Nausea • Fever • Headache • Cramps • Diarrhea • Tinnitus • Hypotension

  39. Antiseptics and Disinfectants

  40. Clinical Indication Prevent or control infection of living (antiseptics) surfaces and nonliving (disinfectants) surfaces including: • countertops, floors, equipment, instruments • skin, mucous membranes

  41. Forms of Antiseptics & Disinfectants Chemical solutions containing • Alcohols (ethanol, isopropanol) • Aldehydes (formaldehyde) • Halogenated compounds (iodine) • Iodophors (povidone-iodine) • Phenols (hexachlorophene, triclosan) • Oxidizers (hydrogen peroxide) • Heavy metals (silver nitrate, mercurial) • Quaternary ammoniums (benzalkonium chloride)

  42. Method or Route of Administration • Topical application or wash-down surfaces • Swab, sponge, scrub • Mouthwash (occasionally)

  43. Terminology Cidal- Kills the microorganisms e.g., bacteriocidal, virucidal, germicidal Static- Inhibit or slow the growth of microorganisms but does not eradicate all organisms e.g. bacteriostatic, fungistatic Sterilization- complete eradication of all microorganisms Spectrum of activity- broad (or narrow) indicates the potency to eliminate a large variety of organism types (or limited in the type of microorganisms it affects)

  44. Terminology Nosocomial – infection acquired while staying in a hospital or institution such as nursing home Irrigation – method of washing a fluid antiseptic over the tissue(s) to remove the organisms Active vehicle – the solution used to dissolve an antiseptic has separate definite ability to destroy microorganisms Topical – applied to a surface, not swallowed or injected Systemic – reaches the blood stream (circulation) after administration

  45. Main Uses • Reduce the need for antibiotics by eliminating potential pathogenic infectious organic material on nonliving surfaces • Reduce the growth and contamination of wounds (burns, skin ulcers) • Eliminate microorganism from entering punctures encountered in procedures such as spinal, regional anesthesia, blood draws for clinical laboratory analysis

  46. Adverse Effects From Topical Application • Dry skin, rash, hypersensitivity • Eczamoid dermatitis (high dose long term exposure) • Hypothyroidism (iodine absorption) • Neurotoxicitity (hexachlorophene) From Internal Absorption • Anorexia • Vomiting • Internal cramping • Convulsions • Death

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