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Published on : Jul 20, 2021 | Views : 2821 | Downloads : 1

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Anti-infective Agents
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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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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Anti-viral and Anti-fungal drugs
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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
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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 albicans Skin fungicidal mucous membranes ketaconazole vagina miconazole nystatin
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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Antidysentery Drugs Paromomycin Tetracyclines Metronidazole Chloroquine, iodoquinol 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
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Parasitic Worm Infestation Pinworms Roundworms Tapeworms Enter the gastrointestinal tract with food or soil containing worm eggsWorms hatch with the intestines Worms are shed in the feces
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Symptoms of Worm Infestation Common symptoms Diarrhea Nausea Loss of appetite Abdominal cramping Itching (anus) Hookworms, tapeworms Perforate intestines Blood loss Anemia
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Anthelmintic Drugs Pinworms, roundworms Mebendazole, pyrantil pamoate, thiabendazole Tapeworms Praziquantel
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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
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Anthelmintic Drugs: Adverse Effects Nausea Fever Headache Cramps Diarrhea Tinnitus Hypotension
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Antiseptics and Disinfectants
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Clinical Indication Prevent or control infection of living (antiseptics) surfaces and nonliving (disinfectants) surfaces including: countertops, floors, equipment, instruments skin, mucous membranes
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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)
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Method or Route of Administration Topical application or wash-down surfaces Swab, sponge, scrub Mouthwash (occasionally)
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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) Terminology
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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 Terminology
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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
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Adverse Effects Dry skin, rash, hypersensitivity Eczamoid dermatitis (high dose long term exposure) Hypothyroidism (iodine absorption) Neurotoxicitity (hexachlorophene) From Topical Application From Internal Absorption Anorexia Vomiting Internal cramping Convulsions Death