Case 3 Tuberculosis

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    Case 3: Tuberculosis

    Presented By:

    John Tinio

    Joshua Vergara

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    Patient History General Data:

    - BC, 27 years old, female

    Chief Complaint:- Several weeks of fatigue, weight loss, fevers, chills, night sweats and a

    productive cough

    Past Medical History:- Dx with HIV infection, 9/2008 with Pneumocystis Carinii Pneumonia

    - Last HIV visit clinic, 2 months ago, 5/2009

    - Depression 9/2008

    Family / Social History:

    - Heterosexual female w/ one sexual partner (also dx with HIV); currently liveswith him

    Medication History:- Nelfinavir, Zidovudine, Lamivudine, TrimethoprimSulfamethoxazole, Oral

    Contraceptive, Multi-Vitamin with Iron, Sertraline

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    Physical Exam / Lab Results

    Physical Exam:

    - General Survey: Thin female with productive cough

    - Vital Signs: BP 110/72, weight loss of 5kg in 2 months

    - HEENT: Lymphadenopathy

    - Chest Radiograph: Apical fibrocavitary infiltrates

    Lab Results:

    - Hemoglobin: 100 (120-160 g/l)

    - Leukocyte Count: 3.2x1000 (5x109 //L)

    - Mean Cell Volume (MCV): 115 fl (80-100 fl)

    - Red Blood Cell Count (RBC): 3.6 mil/mm3 (4-5 10 12/L)

    - Acid Fast Bacilli Smear: (+) Mycobacteria

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    Management In Order Of Priority

    Pulmonary Tuberculosis

    HIV Infection

    Anemia

    Pneumocystis Carinii Pneumonia

    Depression

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    Problem 1: Basis

    Pulmonary Tuberculosis

    - Malaise

    -Anorexia

    - Weight Loss

    - Fever

    - Night Sweats

    - Chills

    - Productive Cough

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    Pulmonary Tuberculosis:

    Treatment Objective

    To provide the safest, most effective therapy in theshortest period of time

    Administer multiple drugs to which organisms aresusceptible

    Add at least two new anti-tuberculous agents to a

    regimen when treatment failure is suspected

    To ensure adherence to therapy

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    Pulmonary Tuberculosis:

    Non-Pharmacologic Therapy

    Complete Blood Count

    - anemia, neutropenia and thrombocytopenia

    Absolute CD4 Lymphocyte Count

    - Predictor of HIV progression

    CD4 Lymphocyte Percentage

    - May be more reliable than the CD4 count

    HIV Viral Load Test

    - Measure the amount of activity replicating HIV virus

    - Correlate with disease progression and response toantiretroviral drugs

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    Pulmonary Tuberculosis:

    Pharmacologic Therapy

    First Line Agents Second Line Agents

    Isoniazid Amikacin

    Rifampin Aminosalicylic Acid

    Pyrazinamide Capreomycin

    Ethambutol Ciprofoxacin

    Streptomycin Clofazimine

    Cycloserine

    Ethionamide

    Levofloxacin

    Rifabutin

    Rifapentine

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    First Line Anti-Tuberculosis Agents

    The Core Of Treatment Regimens

    Isoniazid Rifampin Pyrazinamide Ethambutol Streptomycin

    Efficacy +++ +++ +++ +++ +++

    Safety ++ ++ ++ ++ ++

    Suitability +++ +++ +++ +++ +++

    Cost + ++ ++ +++ +++

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    Pulmonary Tuberculosis:

    Personal Drug

    Isoniazid

    Rifabutin

    EthambutolPyrazinamide

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    Isoniazid

    Mechanism Of Action:- Inhibits synthesis of mycolic acid, an essential component ofmycobacterial cell walls

    - Forms a covalent complex with an acyl carrier protein (AcP M) andKasA

    - Bactericidal activity agaist susceptible strians of M. Tuberculosis

    Pharmacokinetics:- Readily absorbed from the GIT

    - Average half life is 1 - 3 hours

    Adverse Effect:- Fever, skin rashes- Isoniazid-induced hepatitis is the most common major toxic effect

    - Peripheral neuropathy

    - Memory loss, psychosis, seizures

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    Rifabutin

    - Derived from Rifamycin; related to rifampin- Effective in prevention and treatment of disseminated

    aytpical mycobacterial infection in AIDS patient with

    CD4 counts

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    Rifabutin

    Mechanism Of Action:- Active against gram (+) and grm (-) cocci, enteric bacteria,

    mycobacteria and chlamydia

    - Inhibits DNA-dependent RNA polymerase; blocking production of

    RNA

    - Bactericidal actiity against susceptible bacteria and mycobacteria

    Pharmacokinetics:

    - Less cytochrome P450 induction and fewer drug interaction

    - Well absorbed in the GIT; excreted through the liver into bile- Inhibits RNA synthesis

    Adverse Effects:

    - Rash, hepatitis, uveitis

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    Ethambutol

    Mechanism Of Action:- Susceptible strains of Mycobacterium tuberculosis- Inhibits mycobacterial arabinosyl transferases; involved in the

    polymerization reaction of arabinoglycan essential component ofthe mycobacterial cell wall

    Pharmacokinetics:- Well absorbed in the gut; 20% excreted in the feces, 50% in the urine

    - Given as a single daily dose with isoniazid or rifampin

    - Ingestion of 25 mg/kg, a blood level peak of 2-5 mcg/mL is reached in2-4 hours

    Adverse Effect- Hypersensitivity is rare

    - Most common serious event is retrobulbar neuritis, resulting in loss ofvisual acuity and red-green color blindness

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    Pyrazinamide

    Mechanism Of Action:- Sterilizing agent used during first 2 months of therapy

    - Allows total duration of therapy to be shortened to 6 months

    - Bacteriostatic activity against susceptible strains of M Tuberculosis

    - Bactericidal against actively dividing organsims

    Pharmacokinetics

    - Well absorbed in the GIT; widely distributed in body tissues,

    including inflamed meninges

    - Half life is 8-11 hours

    Adverse Effect

    - hepatotoxicity, nausea, vomiting, drug fever and hyperuricemia

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    Pulmonary Tuberculosis:

    Prescription

    RxIsoniazid 300mg

    Rifabutin 450mg

    Pyrazinamide 25-30 mg/kgEthambutol 15-25 mg/kg

    Sig.2 month regimen- Isoniazid, once daily

    - Rifabutin, once daily

    - Ethambutol, once daily

    - Pyrazinamide, three times a week

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    Pulmonary Tuberculosis:

    Prescription

    RxIsoniazid 300mgRifabutin 450mg

    Sig.

    4 month regimen

    - Isoniazid, once daily

    - Rifabutin, once daily

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    HIV: Non-Pharmacologic Therapy

    Healthy lifestyle

    Mental health services

    Refer for partner notification services

    Refer to social servicesRefer to HIV prevention services

    Importance of HIV infected persons not putting others

    at risk

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    HIV: Pharmacologic Therapy

    Classification: Mechanism Of Action: Drug/s:

    Nucleoside Reverse

    Transcriptase Inhibitors

    (NRTI)

    Competitive inhibition of HIV-1reverse transcriptase

    - Zidovudine

    - Didanosine

    - Zalcitabine

    - Stavudine

    - Lamivudine

    - Emtricitabine

    - Abacavir

    Non-Nucleoside

    Reverse Transcriptase

    Inhibitors (NNRTI)

    Inhibit reverse transcriptase at a

    site different from that of the

    nucleoside and nucleotide;antiviral activity; lower pill burden

    and side effect

    - Nevirapine

    - Delaviridine

    - Efavirenz- Etravirine

    Nucleotide Reverse

    Transcriptase Inhibitors

    - Tenofovir

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    HIV: Pharmacologic Therapy

    Classification: Mechanism Of Action: Drug/s:

    Protease

    Inhibitors (PIs)

    Potently suppress HIV replication

    Dependent on metabolism through the

    cytochrome P450 system

    - Indinavir

    - Saquinavir hard gel

    - Ritonavir

    - Nelfinavir

    - Fosamprenavir

    - Lopinavir - Atazanavir

    - Tipranavir

    - Darunavir

    Fusion inhibitor it blocks the entry of HI into cells by blocking

    the fusion of the HIV envelope to the cell

    membrane

    - Enfuvirtide

    Entry Inhibitor A CCR5 co-receptor antagonist; prevents

    the virus from entering uninfected cells by

    blocking the CCR5 co-receptor

    - Marviroc

    Integrase Inhibitor Slow HIV replication by blocking the HIV

    integrase enzyme needed for the virus to

    multiply

    - Raltegravir

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    HIV: Pharmacologic Therapy

    Efavirenz Nevirapine Delavirdine Etravirine

    Efficacy +++ +++ +++ +++

    Safety +++ ++ ++ ++

    Suitability +++ ++ ++ ++

    Cost ++ ++ +++ +++

    Non-Nucleoside Reverse Transcriptase

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    HIV: Pharmacologic Therapy

    Fixed Dose Combination

    - Combivir (Zidovudine / Lamivudine)

    - Truvada (Emtricitabine / Tenofovir)

    - Epzicom (Lamivudine / Abacavir)

    - Trizivir (Zidovudine / Lamivudine / Abacavir)

    -Atripla (Emtricitabine / Tenofovir / Efavirenz)

    Other Preferred Initial Regimens

    - Truvada, A