Download - Case 3 Tuberculosis

7/28/2019 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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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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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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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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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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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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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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Efavirenz Nevirapine Delavirdine Etravirine

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

Safety +++ ++ ++ ++

Suitability +++ ++ ++ ++

Cost ++ ++ +++ +++

Non-Nucleoside Reverse Transcriptase


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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, Atazanavir, Ritonavir

- Truvada, Darunavir, Ritonavir

- Truvada, Raltegravir


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HIV: Personal Drug

Drug Mechanism Of Action Adverse Effect

Ziduvidine

Inhibit the activity of reverse

transcriptase, a viral DNA

polymerase enzyme thatretroviruses need to produce

Anemia, Neutropenia,

nausea, malaise,

headache, insomnia,

myopathyLamivudine No significant side

effects

Efavirenz Inhibit reverse transcriptase at a

site different from that of the

nucleoside and nucleotide agents

Neurologic, lack of

concentration, strange

dreams, delusions,mania; administration

with fatty food may

increase serum levels

& consequent

neurotoxicity


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Ziduvidine

- Co-administered with Lamivudine- First antiretroviral agent to be approved; has been well studied

- Decreases the rate of clinical disease progression

- Prolong survival in HIV infected individuals

Pharmacokinetics:- Well absorbed (63%) and distributed in the body tissues and fluids

- Half life averages 1.1 hours

- Eliminated by renal excretion

Adverse Effect

- Myelosuppression macrocytic anemia or neutropenia- Gastrointestinal intolerance

- Headaches, insomnia

- Thrombocytopenia, hyperpigmentation of the nails and myopathy


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Lamivudine

- Cytosine analog with in vitro activity against HIV-1 that issynergistic with Zidovudine

Pharmacokinetics:

- Oral bioavailability >80%, not food dependent

- Half life averages 2.5 hours

- Eliminated in the urine

Adverse Effect

- Headache, dizziness, insomnia, fatigue, gastrointestinal

discomfort


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Efavirenz

Mechanism Of Action:- Bind directly to HIV-1 reverse transcriptase allosteric

inhibition of RNA and DNA dependent DNA polymerase

Pharmacokinetics:

- Well absorbed (63%) and distributed in the body tissues andfluids

- Long half life (40-55 hours)

- Should be taken in an empty stomach; increased bioavailability

after a high fat meal

Adverse Effect

- Skin rash, dizziness, drowsiness, insomnia, headache

- Depression, mania, psychosis


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HIV: Prescription

RxZidovudine 300mg

Lamivudine 150mg

Efavirenz 600mg

Sig.Take one tab B.I.D of Zidovudine & Lamivudine

Efavirenz one tab daily on an empty stomach


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Problem 3: Anemia

Basis:

- Decreased Hemoglobin

- Decreased RBC

- Increased MCV

-Adverse effect of Zidovudine

-Adverse effect of Trimethoprim-Sulfamethoxazole

Treatment Objective:

- By evaluating the response to a therapeutic trial of iron

replacement

- The most important part of treatment is identification of the

cause of occult blood loss


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Anemia


Drug Adverse Effects

Iron Supplement -Bright red blood in stools

-Constipation, diarrhea

-Nausea, heartburn-Vomiting

Erythropoietin(Procrit) -Seizures

-Hypertension

-Allergic Reactions-Fatigue


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Anemia: Pharmacologic Therapy

Procrit (Erythropoietin)

Was just approved to be used with HIV patients with anemia

Also used for patients that were/are taking zidovudine

MOA

Is a glycoprotein growth factor produced by the peritubular endothelial

cells

Regulated by renal oxygen

Pharmacodynamics

Mainly increases the number of progenitor cells with the ability to

differentiate into mature erythroblasts Augment hemoglobin synthesis

Enhance the release of reticulocytes from the bone marrow

Most common adverse effect is hypertension


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Anemia: Drug Interaction

Efavirenz vs. Oral contraceptives

- Decrease in progestin levels: risk of contraceptive

failure

Plan B: including failure of emergency

contraception

Treatment:

- Use alternative or additional method of contraception


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Anemia: Prescription

RxMulti-vitamin with Iron supplement

Vitamin B12Folic Acid

Sig.Take one tab daily

A i


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Anemia:

Alternative Prescription

RxProcrit 8000 units

Sig.3 times a weekSubcutaneously

P bl 4


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Problem 4:


Basis:

- The most common cause of pneumonia in

immunosuppressed patients

Treatment Objective:

- Prophylaxis, decrease the likelihood of adherence to more

complex antiretroviral regimen

- Complete suppression of viral replication

- Therapy that achieves a plasma viral load of


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Pneumocystis Carinii Pneumonia:

Non-Pharmacologic Therapy

Proper diet

Hydration

Rest

Exercise

Medication

Check-up

Reaction of drugs

C


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Trimethoprim-

Sulfamethoxazole Dapsone AtovaquoneAerosolized

Penamidine

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

Safety +++ ++ ++ ++

Suitability +++ ++ ++ ++

Cost ++ ++ +++ +++


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Personal Drug:

Trimethoprim Sulfamethoxazole

Mechanism Of Action:

- Inhibit successive steps in the folate synthesis pathway

- Sulfamethoxazole acts as a false-substrate inhibitor ofdihydropteroate synthetase inhibiting the production ofdihydropteroic acid

- Trimethoprim acts by interfering with the action of bacterialdihydrofolate reductase, inhibiting synthesis of tetrahydrofolic

acid

Adverse Effects:- Hypersensitivity, nausea, neutropenia, anemia, hepatitis, drug rash,

Stevens-Johnson Syndrome

P ti C i ii P i


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Prescription

RxTrimethoprim Sulfamethoxazole 15mg/kg/d

Sig.Take one double-strength tablet three times a

week for 21 days

Take one tablet daily thereafter


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Problem 5: Depression

Basis:

- History of depression, September 2008

- Currently on anti-depressant medication, Sertraline

Treatment Objective:- To pick a drug that will most effectively help the patient

- To assess the responses of the drug

- If patient shows signs of improvement treatment will continuefor 6 weeks

- Complete remission?

- Yes

- Continued medication for 4-9 months

- No

- Change treatment


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Depression:


Drug Adverse effects

SSRIs -Headache, Tinnitus, insomnia and

nervousnes

-Abnormal bleeding

Tricyclic antidepressants (TCAs) -Loss of libido

-Anti-cholinergic side effects

Monoamine oxidase inhibitors (MAO

inhibitors)

-Tachycardia, sweating and tremors

-Nausea, insomnia and sexual

dysfunction


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Depression:

Non-pharmacologic

Lifestyle changes can improve depression for

some people

- Regular exercise

- Increased exposure to sunlight

- Stress management

- Counseling

- Improve sleep habits


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Depression: Personal Drug

Patient will continue on SSRI drug therapy- This did not change because SSRIs have less side effects than TCAs

- MAOs should only be picked if the SSRI is not effective

- MAOs have a high blood pressure side effect

Setraline MOA:

- Highly selective reaction on the serotonin transporter

- Inhibit the transporter binding site

- Have no effects on NE transporter

- No blocking actions on adrenergic and cholinergic receptors

Toxicity- Nausea, headache, anxiety, agitation, insomnia and sexual

dysfunction


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Depression: Prescription

RxSetraline (50mg)

Sig.Take one tab daily with food taken with breakfast

or dinner


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Thank You