Anti-Infective+Agents

Yelena andArlene to work on the page together(This is week #14 reading. Deadline is June1st)
 * Anti-Infective Agents **

1. **__The therapeutic andprophylactic indication of antimicrobial agents are__**: Penicillin V is most prescribedantibiotic for chemotherapy of infections of dental origin, but amoxicillin hassuperior pharmacokinetics. Penicillin G is reserved for more severe infectionsin patients where the oral route is compromised. Therapeutic uses of cephalosporins- Theyare over all used to treat infections. First generation: Treats Staph andStrep infections. Useful in surgical and endocarditis prophylaxis. Second generation: These drugs havelimited use but can work on gram- anaerobes. Third generation: Treats seriousgram- coccal and bacillary infections. Very useful in treating meningitis,pneumonia, gonorrhea, and sepsis. Fourth generation: Treat some gram-bacilli that produce B-lactamases. Cephalosporins uses in dentistry- workwell against orofacial pathogens, but have limited activity against oralanaerobes. Cephalosporins have a limited use in dentistry due to the B-lactamantibiotics that are time dependent without post. antibiotic effects. Due tothe short half-life they are unlikely to attain the high serum level for longenough to be effective. __**Macrolide Antibiotics **__ Erythromycin is used against acuteorofacial infections and in B-lactam-allergic patients. It is good in fightingagainst gram-positive aerobic/facultative cocci such as streptococci and somestaphylococci. It is not good against fighting gram-negative anaerobes such asPrevotella, Porphyromonas, Fusobacterium, and Veillonella. Azithromycin is effective against oralspirochetes and pigmented anaerobes. Also useful in the management of acuteperiapical abscesses at 500mg/day for 3 days. Clarithromycin is effective against gram-positiveanaerobes such as Actinomyces, Propionibacterium, and Lactobacillus.
 * Do we use macrolides for prophylaxispremedication for endocarditis? Amoxicillin is most popular, but yes Macrolidesare useful for endocarditis prophylaxis; especially if patient is allergic toAmoxicillin. **

Yes, However there is a 10% chancethat a person allergic to penicillin may also have an allergic reaction toClindamycin.
 * <span style="font-family: "Times New Roman","serif"; font-size: 16px;">__Lincosamides__- **<span style="font-family: "Times New Roman","serif"; font-size: 16px;">If a person is allergic to penicillin, would clindamycin bethe antibiotic of choice for him/her?

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">2. **__Superinfections are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">This is a new infection that can occurin somebody who already has a preexisting infection. Any antibiotics that isbeing used can promote an opportunistic infection. There are many differentbacterias that are present in our bodies naturally and when antibiotics areintroduced, it disrupts the microflora and a second infection can occurconcurrently.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">3. __**Antibiotics adverse reactions**__ <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotic teratology <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Studies have being published regardingability ofantibiotics to cause birth defects. Some antibiotic are able to causebirthdefects but most antibiotics those are used in United States approved byFDA asclass B or C categories, which indicates little, if any, risk. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotic induced mania <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Acute mania has been described inassociation withantibiotic therapy the primary causative agents areclarithromycin and fluoroquinolonesand isoniazid. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Long QT interval syndrome <span style="font-family: "Times New Roman","serif"; font-size: 16px;">It is a cardiac disorder caused byion channel abnormalitiesthat prolong the time interval between the beginningof QRS complex and the endof the T-wave on electrocardiogram. This syndrome canbe congenital or acquired.Acquired is caused by metabolic disorder or certaindrugs. Metabolic disorderthose reduce blood K, Ca, and Mg include heartfailure, myocardial ischemia, mitralvalve prolapse, renal and liver disorders. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotics and oral contraceptives <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotics may interfere with theaction of oral contraceptives. The action by which antibiotics reduce theeffectiveness includeincreased urinary and fecal excretions, antibiotic induceddiarrhea, increasedmicrosomal liver metabolism, reduced enterohepaticcirculations. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotic induced agranulosytosis <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Some antibiotics can reduce bloodneutrophil counts, whichcan lead to signs and symptoms of fever and septicemia. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotic induced photosensitivityand phototoxicity <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotics are the most commondrugs those induce skinreactions on exposure to the sunlight. Photosensitivitymay occur in one of twoforms: phototoxicity – chemicals of the drugs aredeposited in the skin absorbUV light and transfer the energy to local tissues,causing inflammatory response;and photoallergy – sunlight causes hapten tobecome antigen in the skin and elicitan immediate or delayed allergic reaction. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antibiotic induced diarrhea andpseudomembranous colitis <span style="font-family: "Times New Roman","serif"; font-size: 16px;">When normal flora ofgastrointestinal tract is disturbed byantibiotics the colonization of C.difficili occurs. C. difficili is a sporeforming gram positive obligateanaerobic bacillus commonly acquired bycross-infection by oral ingestion. Itreleases sitotoxins that disrupts theintestinal mucosa causing fever diarrheaand abdominal tenderness.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">4. **__Gastrointestinal complaintsassociated with anti-infective agents are__**:
 * <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Theantibiotic-induced diarrhea is basically diarrhea that occurs in response totaking an antibiotic. It can be associated with the bacteria C. difficile. Pseudomembranouscolitis is also associated with C. difficile. Any antibiotic is capable ofinducing these two adverse effects, but the most common one is amoxicillin.These two adverse effects are a type of superinfection. Symptoms can includefever, diarrhea, abdominal tenderness, profuse green watery, foul smelling,bloody diarrhea, and dehydration. **

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">5. **__The pharmacokinetics ofpenicillins are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*Absorption, fate, & excretion=orally gastric absorption with short half-lives. Excreted by the kidneys withlimited liver metabolism. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*B-lactam antibiotics producetime-dependent killing of bacteria, and frequent dosing is required to maintainrelatively constant blood levels with as little fluctuation as possible.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">6. **__The mechanism of action ofpenicillins are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Penicillin was determined to be astructural analogue of D-alanine, the final step in the formation of thebacterial rigid cell wall was a transpeptidation reaction involving enzymaticremoval of a terminal D-alanine to allow the formation of the completedpeptidoglycan cell wall. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Beta- Lactams promote the formationof cell wall-deficient microorganisms of different shapes (oval, oblong,spherical) depending on particular PBP (penicillin sensitive enzymes) affected,which cannot maintain their internal osmotic pressure and eventually burst. Themechanism of action of Beta- Lactams is a chemical that inhibits a cellularactivity only present in bacteria (a rigid cell wall) and not found inmammalian cells. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Another mecahinism of action ofBeta- Lactams is as they activate an enzyme (muramyl synthetase), responsiblefor daughter cell separation in cell division. Activation of the enzyme in theabsence of cell division produces lysis of the cell wall.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">7. **__The spectrum of penicillinsare__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Narrow spectrum- treats mainly gram +cocci, gram + bacilli, and gram – cocci.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">8. **__The resistance topenicillins are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Three mechanisms= 1.reduced drugbinding to PBPs (altered target sites), 2.hydrolysis by B-lactamase enzymes(enzymatic inactivation), 3.development of tolerance by the loss of theautolysis mechanism (penicillin becomes bacteriostatic instead ofbactericidal). <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*Principal mechanism= B-lactamaseproduction. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*Antibiotics are abused on basis ofinappropriate indications, dosages, and duration of use. They are given to patientswithout signs & symptoms of infection to prevent infections. Used asprophylaxis and due to not using culture & sensitivity tests has increasedthe use of broader spectrum antibiotics, which created a vicious cycle bydistributing the hospital microbial ecology further and fostering even greatermicrobial resistance. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*Antibiotic rx’s are a quick way toend an appointment and reduce office visits. Dentist prescribe 7-10% of all commonantibiotics (B-lactams, macrolides, tetracycline, metronidazole, clindamycin),with substantial abuse. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">*Antibiotics are underused forsymptomatic infections, overused for surgical prophylaxis and for situations inwhich they are not effective (i.e., irreversible pulpitis, necrotic pulps,after dental surgery to prevent infection that is unlikely to occur) andcommonly used at suboptimal dosing with prolonged dosing schedules and oftennot according to antibiotic prophylaxis guidelines. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">9. **__The adverse reactions topenicillins are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Bacteriostatic antibiotics, NSAIDs,and probenicid may increase the serum half-lives of penicillins by decreasingtheir renal excretion. B-adrenergic blocking drugs may have a reduced ornonexistent response to B-adrenergic receptor agonist given for the treatmentof penicillin-induced anaphylactic bronchospasm.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">10. **__The allergies andhypersensitivity to penicillins are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Penicillins areusually contraindicated in individuals allergic to the drugs. The best thing todo is to refrain if possible from penicillin if a person has had a positivehistory. May be contraindicated when taking coumarin anticoagulants becauseproblematic bleeding may occur.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">Penicillins may be the most commoncause of anaphylactic shock in the U.S. More common in people 20-49 years old.Penicillins are primarily associated with IgE mediated (type I) allergicreactions, but may also induce Cytotoxic (type II) or immune complex (type III)reactions. It is hard to determine if there is a true allergy to a penicillin. Patientsmay confuse adverse reactions with an allergy. Rarely are the suspectedallergies tested Penicillins.

<span style="font-family: "Times New Roman","serif"; font-size: 16px;">11. **__The therapeutic andprophylactic indication of antifungal agents are:__** <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Antifungal agents are used to treatfungal diseases that form superficial infestations involving the skin or mucousmembranes. Can also be systemic (deep) infections involving different internal organs. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Nystatin used to treat- Nystatin isan antibiotic and is primarily used for the treatment of candidal infections ofthe mucosa, skin, intestinal tract, and vagina. Topical nystatin is the drug ofchoice for treatment of candidal infections of the oral cavity. *Main treatmentis for Oral Candidiasis. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Imidazole used to treat- Miconazole(imidazole) – first imidazole antifungal agent approved for topical &parenteral use. For the treatment of cutaneous candidiasis (infection of theskin) & vulvovaginitis caused by C. albicans and used topically fortreatment of cutaneous dermatophyte. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Clotrimazole (imidazole) – used forvarious mucosal & cutaneous infections. For topically use only. Used to treatoral candidiasis and cutaneous candidiasis & dermatophytoses. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Econazole (imidazole) - used topicallyfor treatment cutaneous dermatophyte & Candida infections. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Oral candidiasis -Clotrimazole, OralFluconazole, and Oral itraconazole is highly effective. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Nystatin is preferred in patientswith liver disease or at greater risk of liver toxicity. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Posaconazole used for patients whoare resistant to Fluconazole, and Itraconazole. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-For advanced cases Caspofungin,micafungin, & anidulafungin is administered intravenously. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Extreme cases intravenousamphotericin B can be used. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">-Chlorhexidine oral rinses may alsobe used to treat oral candidiasis. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">12. **__The uses of antiviralagents are__**: <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Anti-influenza virus agents-Amantidine/rimantidine. Oseltamivir/zanamivir. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Influenza vaccine. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Anti-herpetic agents- Idoxuridine,vidarabine, trifluridine, acyclovir/valacyclovir, penciclovir, foscarnet,docosanol. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Anticytomegalovirus agents-Ganciclovir/valganciclovir, cidofivir, formivirsen. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Anti-varicella-zoster virus agents-Acyclovir, famciclovir. <span style="font-family: "Times New Roman","serif"; font-size: 16px;">Anti-immunodeficiency virus agents-Reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors.