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ANTIMICROBIAL AGENTS NAPLEX. Empiric therapy Identify the causative organism Test the sensitivity of the organism to antimicrobial drugs Identify important.

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Presentation on theme: "ANTIMICROBIAL AGENTS NAPLEX. Empiric therapy Identify the causative organism Test the sensitivity of the organism to antimicrobial drugs Identify important."— Presentation transcript:

1 ANTIMICROBIAL AGENTS NAPLEX

2 Empiric therapy Identify the causative organism Test the sensitivity of the organism to antimicrobial drugs Identify important host factors: Site of infection-CNS, bone, prostate, UTI Susceptibility to toxicity Patient allergies Empiric therapy Identify the causative organism Test the sensitivity of the organism to antimicrobial drugs Identify important host factors: Site of infection-CNS, bone, prostate, UTI Susceptibility to toxicity Patient allergies Selecting Appropriate Antimicrobial Agents PG 52

3 Interference with cell wall synthesis penicillins, cephalosporins Inhibition of protein synthesis macrolides, clindamycin, tetracyclines, quinolones Interference with enzyme unique to bacterial cell sulfonamides Interference with the permeability of microbial cell membranes amphotericin B Interference with cell wall synthesis penicillins, cephalosporins Inhibition of protein synthesis macrolides, clindamycin, tetracyclines, quinolones Interference with enzyme unique to bacterial cell sulfonamides Interference with the permeability of microbial cell membranes amphotericin B Mechanisms of Action of Antimicrobial Agents PG 52

4 PABA dihydrofolic acid (DHFA) tetrahydrolfolic acid (THFA) Sulfonamides PG 53 Sulfa

5 Mechanism of action : competitive antagonism of PABA in enzyme system essential for bacteria growth. For ophthalmic use, sulfa sodium salt solutions are very alkaline (i.e., pH 10 + ). The only sodium salt suitable for ophthalmic use is sulfacetamide sodium (solutions have pH of about 7.4). Sulfas are eliminated renally unchanged. Makes them good for UTIs. Sulfas are less soluble in acid urine. This is one cause of crystalluria. Stevens-Johnson syndrome is associated with sulfa use. Mechanism of action : competitive antagonism of PABA in enzyme system essential for bacteria growth. For ophthalmic use, sulfa sodium salt solutions are very alkaline (i.e., pH 10 + ). The only sodium salt suitable for ophthalmic use is sulfacetamide sodium (solutions have pH of about 7.4). Sulfas are eliminated renally unchanged. Makes them good for UTIs. Sulfas are less soluble in acid urine. This is one cause of crystalluria. Stevens-Johnson syndrome is associated with sulfa use. PG 53 General considerations - Sulfonamides

6 Combinations of sulfamethoxazole and trimethoprim (Bactrim, Septra, etc.) are less likely to result in bacterial resistance. Sulfasalazine (Azulfidine) is used in treating inflammatory bowel disease and RA. Watch for sulfa allergy, salicylate allergy, and urine discoloration. - GI side effects, dose is titrated upward slowly, monitor blood counts – dyscrasias If a patient cannot use sulfasalazine because of sulfa sensitivity, use mesalamine products, i.e., Asacol, Pentasa, Rowasa. – various dosage forms Remember that silver sulfadiazine (Silvadene) and mafenide (Sulfamylon) are used topically for treatment of serious burns. Combinations of sulfamethoxazole and trimethoprim (Bactrim, Septra, etc.) are less likely to result in bacterial resistance. Sulfasalazine (Azulfidine) is used in treating inflammatory bowel disease and RA. Watch for sulfa allergy, salicylate allergy, and urine discoloration. - GI side effects, dose is titrated upward slowly, monitor blood counts – dyscrasias If a patient cannot use sulfasalazine because of sulfa sensitivity, use mesalamine products, i.e., Asacol, Pentasa, Rowasa. – various dosage forms Remember that silver sulfadiazine (Silvadene) and mafenide (Sulfamylon) are used topically for treatment of serious burns. PG 53 General considerations – Sulfonamides (contd)

7 PG 54 Penicillins

8 Mechanism of action: interfere with bacterial cell-wall synthesis (bactericidal) Note that all penicillins have a beta lactam ring and thiazolidine ring. Possible cross-sensitivity with other beta lactam antimicrobials (e.g., cephalosporins). - percent cross-sensitive ranges from 5-7% Mechanism of action: interfere with bacterial cell-wall synthesis (bactericidal) Note that all penicillins have a beta lactam ring and thiazolidine ring. Possible cross-sensitivity with other beta lactam antimicrobials (e.g., cephalosporins). - percent cross-sensitive ranges from 5-7% PG 54 General Considerations – Penicillins

9 PG 55 Structure Activity Relationships: AMino penicillins – AMpicillin, AMoxicillin, bacAMpicillin NOX penicillins – penicillinase (beta lactamase) resistant penicillins: Nafcillin, OXacillin, clOXacillin (PO), diclOXacillin(PO)----MSSA (vanco alternative) MEZPCT penicillins – antipseudomonal penicillins: MEZlocillin, Piperacillin, Carbenicillin, Ticarcillin (combo with aminoglycosides, not in the same IV) Therapy problems with penicillins: Acid Resistance Beta-lactamase (penicillinase) resistance (combo products; Zosyn, Timentin, Augmentin) Hypersensitivity Hypersensitivity AMino penicillins – AMpicillin, AMoxicillin, bacAMpicillin NOX penicillins – penicillinase (beta lactamase) resistant penicillins: Nafcillin, OXacillin, clOXacillin (PO), diclOXacillin(PO)----MSSA (vanco alternative) MEZPCT penicillins – antipseudomonal penicillins: MEZlocillin, Piperacillin, Carbenicillin, Ticarcillin (combo with aminoglycosides, not in the same IV) Therapy problems with penicillins: Acid Resistance Beta-lactamase (penicillinase) resistance (combo products; Zosyn, Timentin, Augmentin) Hypersensitivity Hypersensitivity

10 Which of the following is an adverse effect associated with use of aminopenicillins? a. polydipsia b. hemolytic anemia c. cholelithiasis d. tardive dyskinesia e. angina Which of the following is an adverse effect associated with use of aminopenicillins? a. polydipsia b. hemolytic anemia c. cholelithiasis d. tardive dyskinesia e. angina

11 Which of the following is an adverse effect associated with use of aminopenicillins? a. polydipsia b. hemolytic anemia c. cholelithiasis d. tardive dyskinesia e. angina Which of the following is an adverse effect associated with use of aminopenicillins? a. polydipsia b. hemolytic anemia c. cholelithiasis d. tardive dyskinesia e. angina

12 PG 56 Cephalosporins

13 Contains beta-lactam ring. Therefore, may have cross-sensitivity with penicillins. As you go from 1 st generation to 4 th generation, you get: increased gram-negative activity decreased gram-positive activity increased resistance to beta-lactamase destruction increased ability to enter cerebrospinal fluid Contains beta-lactam ring. Therefore, may have cross-sensitivity with penicillins. As you go from 1 st generation to 4 th generation, you get: increased gram-negative activity decreased gram-positive activity increased resistance to beta-lactamase destruction increased ability to enter cerebrospinal fluid PG 56 General considerations

14 Which of the following antimicrobial agents has effective coverage of streptococcus pneumoniae? I. amoxicillin II. doxycycline III. gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following antimicrobial agents has effective coverage of streptococcus pneumoniae? I. amoxicillin II. doxycycline III. gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III

15 Which of the following antimicrobial agents has effective coverage of streptococcus pneumoniae? I. amoxicillin II. doxycycline III. gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following antimicrobial agents has effective coverage of streptococcus pneumoniae? I. amoxicillin II. doxycycline III. gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Gram + Non-DRSP

16 First generation (generally start with CEPH): Good for surgical prophylaxis Second generation (generally start with CEF): Good for otitis, sinusitis and respiratory tract infections Third generation (generally end with IME or ONE): Good for meningitis, CAP, gram-negative bacilli, gonorrhea, Proteus, Salmonella, Klebsiella Cefixime (suprax), cefotaxime (claforan), ceftriaxone (rocephin) Fourth generation (cefepime) Maxipime: Good antipseudomonal activity First generation (generally start with CEPH): Good for surgical prophylaxis Second generation (generally start with CEF): Good for otitis, sinusitis and respiratory tract infections Third generation (generally end with IME or ONE): Good for meningitis, CAP, gram-negative bacilli, gonorrhea, Proteus, Salmonella, Klebsiella Cefixime (suprax), cefotaxime (claforan), ceftriaxone (rocephin) Fourth generation (cefepime) Maxipime: Good antipseudomonal activity PG 57 General considerations (contd)

17 Tetracyclines PG 58

18 Products: Tetracycline HCI (Achromycin V, Sumycin, Robitet, Panmycin) Minocycline (Minocin) Doxycycline (Vibramycin, Doxy 100, Doxychel, Vibra-Tabs) These are bacteriostatic antimicrobials. They interfere with protein synthesis. Broad spectrum antimicrobials. Work against many gram-positive and gram-negative organisms. coverage - also effective against atypical organisms mycoplasma and chlamydia pneumoniae, useful for patients allergic to penicillin b/c gram + coverage Products: Tetracycline HCI (Achromycin V, Sumycin, Robitet, Panmycin) Minocycline (Minocin) Doxycycline (Vibramycin, Doxy 100, Doxychel, Vibra-Tabs) These are bacteriostatic antimicrobials. They interfere with protein synthesis. Broad spectrum antimicrobials. Work against many gram-positive and gram-negative organisms. coverage - also effective against atypical organisms mycoplasma and chlamydia pneumoniae, useful for patients allergic to penicillin b/c gram + coverage PG 58 General Considerations

19 PG 58 Not for use in children under age 8. May cause discoloration of developing tooth enamel. Not for pregnant women. May adversely affect fetal development. Most have the potential for causing phototoxicity. Drug interaction with divalent (Mg, Ca, Fe) or trivalent (Al) compounds and tetracyclines may result in complexation and impaired absorption. Do not use together. Broad spectrum activity can lead to thrush or vaginal candidias Not for use in children under age 8. May cause discoloration of developing tooth enamel. Not for pregnant women. May adversely affect fetal development. Most have the potential for causing phototoxicity. Drug interaction with divalent (Mg, Ca, Fe) or trivalent (Al) compounds and tetracyclines may result in complexation and impaired absorption. Do not use together. Broad spectrum activity can lead to thrush or vaginal candidias General Considerations

20 PG 59 Macrolides General Considerations: Bacteriostatic – inhibit protein synthesis Bacteriostatic – inhibit protein synthesis May be good for patients who are May be good for patients who are hypersensitive to beta-lactam hypersensitive to beta-lactam antimicrobials. antimicrobials. Good respiratory coverage. Good respiratory coverage. CAP caused by S.pneumo, M.cat, H.flu or atypicals (mycoplasma, legionella, and chlamydia) CAP caused by S.pneumo, M.cat, H.flu or atypicals (mycoplasma, legionella, and chlamydia)

21 PG 59 Erythromycin Oral Products Erythromycin base (E-Mycin, Ery-Tab, PCE, Eryc) Coating used on most products Coating used on most products Administer on an empty stomach Administer on an empty stomach Erythromycin stearate (Erythromycin Stearate, Wyamycin S) Better absorbed than erythromycin base Better absorbed than erythromycin base

22 PG 59 Erythromycin esolate (Ilosone) Associated with cholestatic hepatitis Associated with cholestatic hepatitis Better absorbed than erythromycin base Better absorbed than erythromycin base Erythromycin ethylsuccinate (eryPed, E.E.S.) Most well absrobed Most well absrobed Available in liquid form Available in liquid form 400 mg of EES = 250 mg of erythromycin base 400 mg of EES = 250 mg of erythromycin base Parenteral Products Erythromycin lactobionate Erythromycin glucepate Drug Interactions: Mainly due to enzyme inhibition of erythromycin – (3A4) Erythromycin (contd)

23 PG 60 Clarithromycin (Biaxin) Usually used BID. XL form used once daily. Prodrug: May be given with or without meals Used in combination with a proton pump inhibitor for H. pylori treatment. Metallic taste

24 PG 60 Azithromycin (Zithromax) More gram-negative activity than erythromycin or clarithromycin Once-daily dosing, usually for five days after otitis media (e.g., Z-Pack) Available as suspension, tablets, IV Suspension should not be taken with food or antacids. Dirithromycin (Dynabac) Prodrug Once-daily dosing

25 PG 61 Lincosamides General considerations Watch for pseudomembranous enterocolitis (Clostridium difficile). Treat clostridium with metronidazole (Flagyl) or oral vancomycin.Treat clostridium with metronidazole (Flagyl) or oral vancomycin. Good in gram positive (staph) and gram-negative infections, particularly anaerobes Lincomycin (Lincocin, Lincorex) Morbilliform rash possible; DC drug if it happens Clindamycin (Cleocin) Available in topical form for acne

26 Which of the following antibiotics has bacteriostatic activity? a. amoxicillin b. ciprofloxacin c. erythromycin d. penicillin e. cephalexin Which of the following antibiotics has bacteriostatic activity? a. amoxicillin b. ciprofloxacin c. erythromycin d. penicillin e. cephalexin

27 Which of the following antibiotics has bacteriostatic activity? a. amoxicillin (cell wall) b. ciprofloxacin (inhibits DNA gyrase) c. erythromycin (protein synthesis) d. penicillin (cell wall) e. cephalexin (cell wall) Which of the following antibiotics has bacteriostatic activity? a. amoxicillin (cell wall) b. ciprofloxacin (inhibits DNA gyrase) c. erythromycin (protein synthesis) d. penicillin (cell wall) e. cephalexin (cell wall)

28 PG 61 Aminoglycosides General Considerations Glycosides – poorly absorbed from the GI tract Bactericidal Good for serious gram-negative pathogens (pseudomonas, proteus, etc.) Frequently administered with extended-action penicillin (IV incompatible) - dosed q8h or q24h (conc. dependant kill) Eliminated by glomerular filtration; Watch for ototoxicity Monitor peaks and troughs – peaks 30 min after infusion, trough 30 minutes before next dose. peak = 4-10ug/ml trough = 0.5-2, adjust dose if CrCl < 60ml/min. hearing test if prolonged therapy

29 Which of the following antimicrobial agents is available for parenteral use only? I. cefaclor II. tobramycin III. ticarcillin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following antimicrobial agents is available for parenteral use only? I. cefaclor II. tobramycin III. ticarcillin a. I only b. III only c. I and II only d. II and III only e. I, II, and III

30 Which of the following antimicrobial agents is available for parenteral use only? I. cefaclor II. tobramycin III. ticarcillin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following antimicrobial agents is available for parenteral use only? I. cefaclor II. tobramycin III. ticarcillin a. I only b. III only c. I and II only d. II and III only e. I, II, and III

31 PG 61 Parenteral use Streptomycin sulfate Kanamycin sulfate (Kantrex) Gentamicin sulfate (Garamycin (4mcg-10mcg/ml) Tobramycin sulfate (Nebcin) (4mcg-10mcg/ml) Amikacin sulfate (Amikin) (15mcg-25mcg/ml) Netilmicin sulfate (Netromycin) Reference Peak Range

32 Which of the following antibiotics requires monitoring of serum levels? a. penicillin b. ceftazidime c. azithromycin d. gentamicin e. cephalexin Which of the following antibiotics requires monitoring of serum levels? a. penicillin b. ceftazidime c. azithromycin d. gentamicin e. cephalexin

33 Which of the following antibiotics requires monitoring of serum levels? a. penicillin b. ceftazidime c. azithromycin d. gentamicin e. cephalexin Which of the following antibiotics requires monitoring of serum levels? a. penicillin b. ceftazidime c. azithromycin d. gentamicin e. cephalexin

34 PG 62 Oral use Not for systemic action Neomycin sulfate (Mycifradin) - Used for bowel prep prior to surgery, treat diarrhea caused by e.coli, neomycin also binds ammonia, use in patients w/hepatic encephalopathy, watch for absorption interactions Tobramycin (TOBI) –inhaled product for CF patients Tobramycin (TOBI) – inhaled product for CF patients

35 PG 62 Fluoroquinolones General Considerations - Inhibits DNA-Gyrase May cause phototoxicity Not for patients under 18 – affects growth Do not use within 2-4 hours of antacids; iron – also inhibits CYP1A2 (increased levels of theophylline and caffeine) Generally useful for UTI, lower respiratory infections, gonorrhea, prostatitis – older agents have more gram -, less gram + coverage, newer agents have broader gram + [moxifloxacin, gatifloxacin] All end in -oxacin

36 PG 62 Names Second generation Norfloxacin (Noroxin) – high urine levels - UTIs Ciprofloxacin (Cipro)- renal elimination: reduce dose Ofloxacin (Floxin) Third generation Levofloxacin (Levaquin) – renal elimination: reduce dose Sparfloxacin (Zagam) – reports of prolongation of QT interval (D/C) Gemifloxacin (Factive) – renal elimination: reduce dose, skin rash Fourth generation Moxifloxacin (Avelox) – Multi-drug resistant Streptococcus pneumonia (MDRSP)

37 PG 63 MISCELLANEOUS ANTIMICROBIAL AGENTS Antibacterials Mupirocin (Bactroban) – topical use for impetigo, intranasal for staph Vancomycin (Vancocin) – associated with red man syndrome (must be infused slowly, over min of 30 minutes); reserved for serious/resistant gram + infections (MRSA, enterococcus) – rapid drop in BP accompanied by rash in neck or chest area - Monitoring – 1 hour before and 1 hour after - Peak – 25-40mcg/dl & Trough 5-12mcg/dl Metronidazole (Flagyl) – active against gram-negative organisms and protozoa, (anaerobes) Avoid alcohol. May darken urine.

38 PG 63 MISCELLANEOUS ANTIMICROBIAL AGENTS (contd) Carbapenems broad spectrum; used for resistant gram +/– organisms, pseudomonas, MRSA, enterococcus, anaerobesbroad spectrum; used for resistant gram +/– organisms, pseudomonas, MRSA, enterococcus, anaerobes similar to penicillins (cross-sensitivity) but b-lactamase resistantsimilar to penicillins (cross-sensitivity) but b-lactamase resistant Risk of seizures and renal adjustmentRisk of seizures and renal adjustment Imipenem/cilastatin (Primaxin) – cilastatin is a renal dipeptidase inhibitor Meropenem (Merrem)---lacks good pseudomonas coverage Doripenem (Doribax) Ertapenem (Invanz) ----Aztreonam (Azactam)---monobactam, ok with PCN allergy

39 Which of the following antibiotic is classified as a macrolide? a. telithromycin b. tobramycin c. azithromycin d. doxycycline e. kanamycin Which of the following antibiotic is classified as a macrolide? a. telithromycin b. tobramycin c. azithromycin d. doxycycline e. kanamycin

40 Which of the following antibiotic is classified as a macrolide? a. telithromycin b. tobramycin c. azithromycin d. doxycycline e. kanamycin Which of the following antibiotic is classified as a macrolide? a. telithromycin b. tobramycin c. azithromycin d. doxycycline e. kanamycin

41 PG MISCELLANEOUS ANTIMICROBIAL AGENTS (contd) VRE and MRSA drugs Quinupristin / dalfopristin (Synercid) – Linezolid (Zyvox) –……oral dosing available Tigecycline (Tygacil) – Chloramphenicol (Chloromycetin) – for typhoid fever; may cause aplastic anemia and gray baby syndrome

42 Pneumonia Organisms: Treatment: Organisms: Treatment: --Comorbidities: Chronic obstructive pulmonary disease (COPD), diabetes, chronic renal failure, chronic liver failure, heart failure (HF), cancer, asplenia, immunosuppressed

43 Pneumonia Treatment: --Risk factors for MDR organisms: recent antibiotic therapy (in last 90 days), hospitalized 5 days, resistance in environment, nursing home resident, chronic dialysis, home infusion therapy, immunosuppressed

44 Meningitis Organisms: Treatment: Organisms: Treatment:

45 Urinary Tract Infection Organisms: Treatment: Organisms: Treatment:

46 STDs Organisms: Treatment: Organisms: Treatment:

47 Antitubercular Drugs Rrifampin I isoniazid P pyrazinamide E ethambutol S streptomycin Rrifampin I isoniazid P pyrazinamide E ethambutol S streptomycin PG 64

48 Antitubercular Drugs Isoniazid (Nydrazid, Laniazid) May cause B 6 deficiency – supplement malnourished, alcoholics, kids May cause B 6 deficiency – supplement malnourished, alcoholics, kids Used for prophylaxis or in combo with other drugs for active disease Used for prophylaxis or in combo with other drugs for active disease 6 months of prophylaxis if +PPD; For treatment used in combo with 6 months of prophylaxis if +PPD; For treatment used in combo with rifampin for at least 6 months rifampin for at least 6 months Metabolized by acetylation (slow versus rapid acetylators) Metabolized by acetylation (slow versus rapid acetylators) monitor for hepatoxicity monitor for hepatoxicity Rifampin (Rifadin, Rimactane) Potent enzyme inducer (potential drug interactions with many drugs) Potent enzyme inducer (potential drug interactions with many drugs) Potentially hepatotoxic; Potentially hepatotoxic; Use may result in discoloration of virtually all body fluids (urine and tears----watch contact lenses) Use may result in discoloration of virtually all body fluids (urine and tears----watch contact lenses)

49 PG 65 Antitubercular Drugs (cont.) Ethambutol (Myambutal) – for treatment of MAC and drug-resistant Tb as part of combination therapy - optic neuritis is a rare but serious side effect - monitor with eye exams Pyrazinamide – used in combination therapy; potentially hepatotoxic - may increase uric acid levels Steptomycin- can be used as fourth drug in regimen instead of pyrazinamide

50 PG 65 Antimalarials Quinine sulfate (Quinamm) – also used for muscle cramps; no longer used due to hematologic adverse effects Doxycycline – tetracycline; possible phototoxicity and binding interactions Melfoquine HCl (Lariam) – may cause neuropsychiatric adverse effects; once- weekly dosing Atovaquone/proguanil (Malarone) – newer product; once daily; do not use if renally impaired

51 PG 66 Antimalarials Chloroquine (Aralen) – may worsen psoriasis symptoms Hydroxychloroquine sulfate (Plaquenil Sulfate) – may worsen psoriasis symptoms - also used as a DMARD for RA; phototoxicity, hematological side effects, ocular and ototoxicity hematological side effects, ocular and ototoxicity Primaquine phosphate – take with food to reduce GI upset; may be used for PCP

52 HIV Antiretroviral Therapy Therapy initiated based on CD4 count, viral load and presence of symptoms Initial regimen in treatment naive patients: NNRTI + 2 NRTIs PI + 2 NRTIs Learn drug class representatives and major toxicities Therapy initiated based on CD4 count, viral load and presence of symptoms Initial regimen in treatment naive patients: NNRTI + 2 NRTIs PI + 2 NRTIs Learn drug class representatives and major toxicities PG 69

53 Which HIV drug is correctly matched with its mechanism of action? a. Lamivudine - nucleoside reverse transcriptase inhibitor b. Enfuvirtide - protease inhibitor c. Stavudine - binds to human CCR5 receptor d. Didanosine – protease inhibitor e. Indinavir – blocks virus entry into human cells and subsequent viral replication a. Lamivudine - nucleoside reverse transcriptase inhibitor b. Enfuvirtide - protease inhibitor c. Stavudine - binds to human CCR5 receptor d. Didanosine – protease inhibitor e. Indinavir – blocks virus entry into human cells and subsequent viral replication

54 Which HIV drug is correctly matched with its mechanism of action? a. Lamivudine - nucleoside reverse transcriptase inhibitor b. Enfuvirtide - protease inhibitor c. Stavudine - binds to human CCR5 receptor d. Didanosine – protease inhibitor e. Indinavir – blocks virus entry into human cells and subsequent viral replication a. Lamivudine - nucleoside reverse transcriptase inhibitor b. Enfuvirtide - protease inhibitor c. Stavudine - binds to human CCR5 receptor d. Didanosine – protease inhibitor e. Indinavir – blocks virus entry into human cells and subsequent viral replication

55 non-nucleoside reverse transcriptase inhibitors NNRTIs non-nucleoside reverse transcriptase inhibitors (vir in the middle) Delavirdine (rescriptor) (rash, LFTs) Efavirenz (Sustiva) Drug of choice Category X, vivid dreams Nevirapine (Viramune) Rash (Steven Johnson Syndrom) Liver metabolism Delavirdine (rescriptor) (rash, LFTs) Efavirenz (Sustiva) Drug of choice Category X, vivid dreams Nevirapine (Viramune) Rash (Steven Johnson Syndrom) Liver metabolism

56 PG 72 Exception – darunavir, tenofovir, raltegravir, abacavir Metabolized through the liver (commonly 3A4) potential for significant drug interactionspotential for significant drug interactions Low dose of ritonavir frequently used to enhance the concentrations of coadministered PIs Adverse effects: GI intolerance, hyperglycemia, dyslipidemia, lipodystrophy, LFT alterations PIs Protease inhibitors (vir at the end)

57 PG 69 Exception – maraviroc All NRTIs (except abacavir) are excreted renally; require dose adjustment but few drug interactions Most common ADRs – GI intolerance, typically subsides in first couple of weeks - High risk for perpheral neuropathy Black Box warning: Risk of lactic acidosis with hepatic steatosis nucleoside reverse transcriptase inhibitors NRTIs nucleoside reverse transcriptase inhibitors (all the others)

58 AIDS – Opportunistic Infections PCP / PJP (pneumocystis carninii pneumonia) trimethoprim-sulfamethoxazole CMV retinitis Ganciclovir MAC / MAI (mycobacterium avium complex) Macrolide + ethambutol Cryptococcus neuformans meningitis Amphotericin B +/- flucytosine Fluconazole used for maintenance PCP / PJP (pneumocystis carninii pneumonia) trimethoprim-sulfamethoxazole CMV retinitis Ganciclovir MAC / MAI (mycobacterium avium complex) Macrolide + ethambutol Cryptococcus neuformans meningitis Amphotericin B +/- flucytosine Fluconazole used for maintenance PG 74

59 Drugs for influenza M2 inhibitors Amantadine, rimantidine Effective for influenza A virus only Begin within 48h of symptom onset; continue 2-5 days Neuroaminidase inhibitors Oseltamivir (Tamiflu) Zanamivir (Relenza) Effective for influenza A and B viruses Begin with 48h of symptoms onset; continue 5 days

60 PG 75 Drugs for herpes simplex and herpes zoster (shingles) Acyclovir (Zovirax) – for herpes simplex types 1 and 2 - dosed 5x/day for 10 days, 5 days if recurrence Penciclovir (Denavir) – topical treatment for herpes labialis (cold sores) Valacyclovir HCl (Valtrex) – for herpes simplex and herpes zoster; acyclovir prodrug Famcyclovir (Famvir) for herpes simplex and herpes zoster (shingles); penciclovir prodrug - begin therapy as soon as first sign of lesion Docosanol (OTC-Abreva) topical cream

61 PG 75 Anthelmintic drugs of choice Nematodes (roundworm) Mebendazole (Vermox) do not use in pregnancy – blocks glucose uptake Mebendazole (Vermox) do not use in pregnancy – blocks glucose uptake Albendazole (Albenza) – degeneration of cytoplasmic microtubules intestinal cells of helminths Albendazole (Albenza) – degeneration of cytoplasmic microtubules intestinal cells of helminths Piperazine citrate Preg B – blocks affect of ACH Piperazine citrate Preg B – blocks affect of ACH Pyrantel pamoate (Antiminth) Pyrantel pamoate (Antiminth) Trichuriasis (whipworm) Mebendazole (do not use in pregnancy) Mebendazole (do not use in pregnancy) Hookworm – mebendazole (do not use in pregnancy)

62 Which of the following medication(s) can cause nephrotoxicity? I. Ganciclovir II. Foscarnet III. Gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following medication(s) can cause nephrotoxicity? I. Ganciclovir II. Foscarnet III. Gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III

63 Which of the following medication(s) can cause nephrotoxicity? I. Ganciclovir II. Foscarnet III. Gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following medication(s) can cause nephrotoxicity? I. Ganciclovir II. Foscarnet III. Gentamicin a. I only b. III only c. I and II only d. II and III only e. I, II, and III

64 Which of the following agents inhibits the HIV enzyme reverse transcriptase? I. zanamivir II. ritonivir III. didanosine a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following agents inhibits the HIV enzyme reverse transcriptase? I. zanamivir II. ritonivir III. didanosine a. I only b. III only c. I and II only d. II and III only e. I, II, and III

65 Which of the following agents inhibits the HIV enzyme reverse transcriptase? Neuroaminidase inhibitors) I. zanamivir ( Neuroaminidase inhibitors) II. ritonivir (protease inhibitor) ( nucleoside reverse transcriptase inhibitors) III. didanosine ( nucleoside reverse transcriptase inhibitors) a. I only b. III only c. I and II only d. II and III only e. I, II, and III Which of the following agents inhibits the HIV enzyme reverse transcriptase? Neuroaminidase inhibitors) I. zanamivir ( Neuroaminidase inhibitors) II. ritonivir (protease inhibitor) ( nucleoside reverse transcriptase inhibitors) III. didanosine ( nucleoside reverse transcriptase inhibitors) a. I only b. III only c. I and II only d. II and III only e. I, II, and III

66 PG 146 DERMATOLOGIC STUDY OUTLINE Acne Pathophysiology abnormal keratinization leads to obstruction of the follicle and accumulation of sebum to form a closed comedo or white-head Goal of therapy is to unblock follicles

67

68 Normal Pore Inflamed Pore

69 PG 146 Dermatologic Study Outline

70 PG 146 Dermatologic Study Outline Isotretinoin (Accutane) Isotretinoin (Accutane) Effective therapy option for the treatment of severe, inflammatory acne, or more moderate forms that have been refractory to other treatment options Effective therapy option for the treatment of severe, inflammatory acne, or more moderate forms that have been refractory to other treatment options pregnancy category X pregnancy category X two forms of contrception, iPLEDGE program two forms of contrception, iPLEDGE program Oral Antimicrobials Oral Antimicrobials Tetracycline Tetracycline Erythromycin Erythromycin Clindamycin Clindamycin

71 PG 146 Psoriasis Pathophysiology exact mechanism unknown. May be due to defects in epidermal cell cycle, AA metabolism, immunologic mechanisms, environmental triggers Treatment modalities Emollients (e.g., petrolatum) Emollients (e.g., petrolatum) Ultraviolet light Ultraviolet light Coal tars (typically compounded) Coal tars (typically compounded) Topical corticosteroids Topical corticosteroids Systemic corticosteroids (pulse dosing) Systemic corticosteroids (pulse dosing) Antineoplastic agents (methotrexate, hydroxyurea) Antineoplastic agents (methotrexate, hydroxyurea) Psoralens (pulse dosing) Psoralens (pulse dosing) Immunosuppressant agents (Etanercept, Efalizumab) Immunosuppressant agents (Etanercept, Efalizumab) Retinoids (pulse dosing) Retinoids (pulse dosing)

72 Which of the following psoriasis medications is not pregnancy category X? I. Dovonex II. Methotrexate III. Soriatane A. I only B. III only C. I and II only D. II and III only E. I, II and III I. Dovonex II. Methotrexate III. Soriatane A. I only B. III only C. I and II only D. II and III only E. I, II and III

73 Which of the following psoriasis medications is not pregnancy category X? I. Dovonex II. Methotrexate III. Soriatane A. I only B. III only C. I and II only D. II and III only E. I, II and III I. Dovonex II. Methotrexate III. Soriatane A. I only B. III only C. I and II only D. II and III only E. I, II and III

74 A patient presents to the pharmacy with obvious mild acne, which of the following cannot be recommended without a prescription? a. Benzoyl peroxide 2.5% cream b. Sulfur soap c. Benzamycin gel d. Salicylic acid wash e. Benzoyl peroxide 10% lotion a. Benzoyl peroxide 2.5% cream b. Sulfur soap c. Benzamycin gel d. Salicylic acid wash e. Benzoyl peroxide 10% lotion

75 A patient presents to the pharmacy with obvious mild acne, which of the following cannot be recommended without a prescription? a. Benzoyl peroxide 2.5% cream b. Sulfur soap c. Benzamycin gel d. Salicylic acid wash e. Benzoyl peroxide 10% lotion a. Benzoyl peroxide 2.5% cream b. Sulfur soap c. Benzamycin gel d. Salicylic acid wash e. Benzoyl peroxide 10% lotion

76 Fungal Infections Tinea corporis – body surface Tinea capitis – scalp Tinea cruris – groin (jock itch) Tinea pedis – feet (athletes foot) Onychomycosis – nails Tinea corporis – body surface Tinea capitis – scalp Tinea cruris – groin (jock itch) Tinea pedis – feet (athletes foot) Onychomycosis – nails PG and 147

77 PG 147 Therapy Prophylaxis. Keep skin dry; frequent changes and thorough cleaning of clothing; and avoid likely areas of contamination. Active: Dusting powders (medicated versus nonmedicated), wet compresses Topical drug therapy Fatty acids (undecylenic acid) Tolnaftate (Tinactin, Aftate) Fatty acids (undecylenic acid) Tolnaftate (Tinactin, Aftate) Haloprogin (Halotex) Miconazole (Micatin,Monistat) Haloprogin (Halotex) Miconazole (Micatin,Monistat) Clotrimazole (Lotrimin) Oxiconazole (Oxistat) Clotrimazole (Lotrimin) Oxiconazole (Oxistat) Sulconazole (Exelderm) Butenafine (Mentax) Sulconazole (Exelderm) Butenafine (Mentax) Nystatin (Mycostatin, Nilstat) – good for superficial candida (thrush) Systemic drug therapy for topical fungal disorders Griseofulvin (microsized versus ultramicrosized) Griseofulvin (microsized versus ultramicrosized) Terbinafine (Lamisil) Terbinafine (Lamisil) Avoid corticosteroids Avoid corticosteroids

78 PG 67 Antifungal Drugs (contd) Miconazole (Monistat, Micatin) – broad-spectrum antifungal agent available as powder, aerosol, cream, and suppository; may be used topically or vaginally Clotrimazole (Lotrimin, Mycelex) – broad-spectrum antifungal available as cream, lotion, suppositories, and troches (OTC use for 2 weeks after infection clears) Ketoconazole (Nizoral) – for superficial and systemic fungal infections; also available as OTC shampoo for dandruff; enzyme inhibitor Itraconazole (Sporanox) – for oral or topical treatment of superficial or systemic fungal disorders; enzyme inhibitor. - hepatotoxicity; take w/ food and avoid antacids

79 Antifungal Drugs (contd) Terbinafine (Lamisil) – used orally for onychomycosis of fingernail or toenail. Used topically for superficial tinea infections (OTC use for 1 week). Monitor for hepatoxicity with oral use. Terbinafine (Lamisil) – used orally for onychomycosis of fingernail or toenail. Used topically for superficial tinea infections (OTC use for 1 week). Monitor for hepatoxicity with oral use. Ciclopriox (Penlac) – applied topically once daily for treatment of onychomycosis. – requires long-term therapy Ciclopriox (Penlac) – applied topically once daily for treatment of onychomycosis. – requires long-term therapy Terbinafine (Lamisil) – used orally for onychomycosis of fingernail or toenail. Used topically for superficial tinea infections (OTC use for 1 week). Monitor for hepatoxicity with oral use. Terbinafine (Lamisil) – used orally for onychomycosis of fingernail or toenail. Used topically for superficial tinea infections (OTC use for 1 week). Monitor for hepatoxicity with oral use. Ciclopriox (Penlac) – applied topically once daily for treatment of onychomycosis. – requires long-term therapy Ciclopriox (Penlac) – applied topically once daily for treatment of onychomycosis. – requires long-term therapy PG 67

80 Antifungal Drugs (contd) Griseofulvin (Grisactin, Grifulvin V, Fulvicin) Griseofulvin (Grisactin, Grifulvin V, Fulvicin) For tinea only For tinea only Duration of therapy Duration of therapy depends on type: corporis: 2-4 wks.; capitis: 4-6 wks., pedis: 4-8 wk depends on type: corporis: 2-4 wks.; capitis: 4-6 wks., pedis: 4-8 wk Regular versus microsized versus ultramicrosized Regular versus microsized versus ultramicrosized ultra is better absorbed; take w/ fatty meal ultra is better absorbed; take w/ fatty meal causes induction interactions causes induction interactions Griseofulvin (Grisactin, Grifulvin V, Fulvicin) Griseofulvin (Grisactin, Grifulvin V, Fulvicin) For tinea only For tinea only Duration of therapy Duration of therapy depends on type: corporis: 2-4 wks.; capitis: 4-6 wks., pedis: 4-8 wk depends on type: corporis: 2-4 wks.; capitis: 4-6 wks., pedis: 4-8 wk Regular versus microsized versus ultramicrosized Regular versus microsized versus ultramicrosized ultra is better absorbed; take w/ fatty meal ultra is better absorbed; take w/ fatty meal causes induction interactions causes induction interactions PG 67

81 Antifungal Drugs (contd) Other Azoles Posaconazole (Noxafil) Voriconazole (Vfend) Reserved for severe invasive fungal infections (asperigillosis) Echinocandins (less DI, but monitor LFTs) Anidulafungin (Eraxis) Caspofungin (Cancidas) Micafungin (Mycamine) Ampho B and related Lipid products nephrotoxicity Other Azoles Posaconazole (Noxafil) Voriconazole (Vfend) Reserved for severe invasive fungal infections (asperigillosis) Echinocandins (less DI, but monitor LFTs) Anidulafungin (Eraxis) Caspofungin (Cancidas) Micafungin (Mycamine) Ampho B and related Lipid products nephrotoxicity PG 68

82 Sample Questions NAPLEX

83 Which of the following antibiotics does not have a significant drug interaction with warfarin? A. ciprofloxacin B. azithromycin C. TMP-SMZ D. Metronidazole E. Nafcillin A. ciprofloxacin B. azithromycin C. TMP-SMZ D. Metronidazole E. Nafcillin

84 Which of the following antibiotics does not have a significant drug interaction with warfarin? A. ciprofloxacin B. azithromycin C. TMP-SMZ D. Metronidazole E. Nafcillin A. ciprofloxacin B. azithromycin C. TMP-SMZ D. Metronidazole E. Nafcillin

85 Which of the following medications is the best treatment option for an uncomplicated urinary tract infection? A. penicillin B. cefuroxime C. levofloxacin D. gentamicin E. clarithromycin A. penicillin B. cefuroxime C. levofloxacin D. gentamicin E. clarithromycin

86 Which of the following medications is the best treatment option for an uncomplicated urinary tract infection? A. penicillin B. cefuroxime C. levofloxacin D. gentamicin E. clarithromycin A. penicillin B. cefuroxime C. levofloxacin D. gentamicin E. clarithromycin

87 Which of the following antimicrobial agents is available for parenteral use only? I. piperacillin II. aztreonam III. rifampin A. I only B. III only C. I and II only D. II and III only E. I, II and III I. piperacillin II. aztreonam III. rifampin A. I only B. III only C. I and II only D. II and III only E. I, II and III

88 Which of the following antimicrobial agents is available for parenteral use only? I. piperacillin II. aztreonam III. rifampin A. I only B. III only C. I and II only D. II and III only E. I, II and III I. piperacillin II. aztreonam III. rifampin A. I only B. III only C. I and II only D. II and III only E. I, II and III

89 Which of the following agents is a non-nucleoside reverse transcriptase inhibitor? A. didanosine B. delavirdine C. stavudine D. zidovudine E. lamivudine A. didanosine B. delavirdine C. stavudine D. zidovudine E. lamivudine

90 Which of the following agents is a non-nucleoside reverse transcriptase inhibitor? A. didanosine B. delavirdine C. stavudine D. zidovudine E. lamivudine A. didanosine B. delavirdine C. stavudine D. zidovudine E. lamivudine

91 Which of the following agents may be utilized in combination with other medications for H. pylori eradication? A. tetracycline B. azithromycin C. penicillin D. fluconazole E. cefuroxime A. tetracycline B. azithromycin C. penicillin D. fluconazole E. cefuroxime

92 Which of the following agents may be utilized in combination with other medications for H. pylori eradication? A. tetracycline B. azithromycin C. penicillin D. fluconazole E. cefuroxime A. tetracycline B. azithromycin C. penicillin D. fluconazole E. cefuroxime

93 Peripheral neuropathy is associated with which one of the following agents: A. nevirapine B. delavirdine C. Saquinavir D. Stavudine E. tenofovir A. nevirapine B. delavirdine C. Saquinavir D. Stavudine E. tenofovir

94 Peripheral neuropathy is associated with which one of the following agents: A. Nevirapine (NNRTI) B. Delavirdine (NNRTI) C. Saquinavir (PI) D. Stavudine (NRTI) do not use with AZT (zidovudine) E. Tenofovir (NRTI) A. Nevirapine (NNRTI) B. Delavirdine (NNRTI) C. Saquinavir (PI) D. Stavudine (NRTI) do not use with AZT (zidovudine) E. Tenofovir (NRTI)

95 Administration of calcium or iron must be separated by at least 2 hours if antibiotics in this category are prescribed: I. Macrolides II. Tetracyclines III. Fluroquinolones A. I only B. III only C. I and II only D. II and III only E. I, II and III I. Macrolides II. Tetracyclines III. Fluroquinolones A. I only B. III only C. I and II only D. II and III only E. I, II and III

96 Administration of calcium or iron must be separated by at least 2 hours if antibiotics in this category are prescribed: I. Macrolides II. Tetracyclines III. Fluroquinolones A. I only B. III only C. I and II only D. II and III only E. I, II and III I. Macrolides II. Tetracyclines III. Fluroquinolones A. I only B. III only C. I and II only D. II and III only E. I, II and III

97 Which of the following antimicrobial agents has effective coverage for M. pneumoniae? A. amoxicillin B. erythromycin C. metronidazole D. cefotriaxone E. clindamycin A. amoxicillin B. erythromycin C. metronidazole D. cefotriaxone E. clindamycin

98 Which of the following antimicrobial agents has effective coverage for M. pneumoniae? A. amoxicillin B. erythromycin C. metronidazole D. cefotriaxone E. clindamycin A. amoxicillin B. erythromycin C. metronidazole D. cefotriaxone E. clindamycin

99 Which of the following regimens is most appropriate for C. difficile eradication? A. Clarithromycin 500 mg PO q 12 hours B. Clindamycin 300 mg IV q 6 hours C. Vancomycin 125 mg PO q 6 hours D. Doxycycline 100 mg PO q 12 hours E. Vancomycin 1000 mg IV q 12 hours A. Clarithromycin 500 mg PO q 12 hours B. Clindamycin 300 mg IV q 6 hours C. Vancomycin 125 mg PO q 6 hours D. Doxycycline 100 mg PO q 12 hours E. Vancomycin 1000 mg IV q 12 hours

100 Which of the following regimens is most appropriate for C. difficile eradication? A. Clarithromycin 500 mg PO q 12 hours B. Clindamycin 300 mg IV q 6 hours C. Vancomycin 125 mg PO q 6 hours D. Doxycycline 100 mg PO q 12 hours E. Vancomycin 1000 mg IV q 12 hours A. Clarithromycin 500 mg PO q 12 hours B. Clindamycin 300 mg IV q 6 hours C. Vancomycin 125 mg PO q 6 hours D. Doxycycline 100 mg PO q 12 hours E. Vancomycin 1000 mg IV q 12 hours

101 Which agent is available in both a topical and an oral product for the treatment of acne? I. clindamycin II. erythromycin III. doxycycline A. I only B. III only C. I and II only D. II and III only E. I, II and III I. clindamycin II. erythromycin III. doxycycline A. I only B. III only C. I and II only D. II and III only E. I, II and III

102 Which agent is available in both a topical and an oral product for the treatment of acne? I. clindamycin II. erythromycin III. doxycycline A. I only B. III only C. I and II only D. II and III only E. I, II and III I. clindamycin II. erythromycin III. doxycycline A. I only B. III only C. I and II only D. II and III only E. I, II and III

103 Which of the following drugs represents first (primary) agents in the treatment of TB? A. Ethambutol + PASA B. Ciprofloxacin + PASA C. Isoniazid + rifampin D. Cycloserine + streptomycin E. Penicillin + Benemid A. Ethambutol + PASA B. Ciprofloxacin + PASA C. Isoniazid + rifampin D. Cycloserine + streptomycin E. Penicillin + Benemid

104 Which of the following drugs represents first (primary) agents in the treatment of TB? A. Ethambutol + PASA B. Ciprofloxacin + PASA C. Isoniazid + rifampin D. Cycloserine + streptomycin E. Penicillin + Benemid A. Ethambutol + PASA B. Ciprofloxacin + PASA C. Isoniazid + rifampin D. Cycloserine + streptomycin E. Penicillin + Benemid

105 Which of the following antibiotics is considered first line treatment for a gonorrhea infection? A. Ampicillin B. Ciprofloxacin C. Doxycycline D. Penicillin E. Tetracycline A. Ampicillin B. Ciprofloxacin C. Doxycycline D. Penicillin E. Tetracycline

106 Which of the following antibiotics is considered first line treatment for a gonorrhea infection? A. Ampicillin B. Ciprofloxacin (also..ceftriaxone, cefixime) C. Doxycycline (chlamydia) D. Penicillin E. Tetracycline A. Ampicillin B. Ciprofloxacin (also..ceftriaxone, cefixime) C. Doxycycline (chlamydia) D. Penicillin E. Tetracycline

107 Which of the following groups of antibiotics may be prescribed for a gravid patient with gonorrhea? I. cephalosporins II. fluoroquinolones III. tetracyclines A. I only B. III only C. I and II only D. II and III only E. I, II and III I. cephalosporins II. fluoroquinolones III. tetracyclines A. I only B. III only C. I and II only D. II and III only E. I, II and III

108 Which of the following groups of antibiotics may be prescribed for a gravid patient with gonorrhea? I. cephalosporins II. fluoroquinolones III. tetracyclines A. I only B. III only C. I and II only D. II and III only E. I, II and III I. cephalosporins II. fluoroquinolones III. tetracyclines A. I only B. III only C. I and II only D. II and III only E. I, II and III

109 A gravid patient with a Chlamydia infection is likely to be prescribed which of the following antibiotics? A. Ampicillin B. Levofloxacin C. Doxycycline D. Erythromycin E. Penicillin A. Ampicillin B. Levofloxacin C. Doxycycline D. Erythromycin E. Penicillin

110 A gravid patient with a Chlamydia infection is likely to be prescribed which of the following antibiotics? A. Ampicillin B. Levofloxacin C. Doxycycline D. Erythromycin E. Penicillin A. Ampicillin B. Levofloxacin C. Doxycycline D. Erythromycin E. Penicillin

111 Which of the following is the BEST treatment for a patient with herpes zoster? A. Cidofovir B. Famciclovir C. Ganciclovir D. Penciclovir E. Tenofovir A. Cidofovir B. Famciclovir C. Ganciclovir D. Penciclovir E. Tenofovir

112 Which of the following is the BEST treatment for a patient with herpes zoster? A. Cidofovir B. Famciclovir C. Ganciclovir D. Penciclovir E. Tenofovir A. Cidofovir B. Famciclovir C. Ganciclovir D. Penciclovir E. Tenofovir

113 Which of the following medications would be appropriate for the treatment of Pseudomonas aeruginosa? a. Ampicillin b. Cefepime c. Ceftriaxone d. Erythromycin e. Clindamycin a. Ampicillin b. Cefepime c. Ceftriaxone d. Erythromycin e. Clindamycin

114 Which of the following medications would be appropriate for the treatment of Pseudomonas aeruginosa? a. Ampicillin b. Cefepime c. Ceftriaxone d. Erythromycin e. Clindamycin a. Ampicillin b. Cefepime c. Ceftriaxone d. Erythromycin e. Clindamycin


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