7/28/2019 Case 3 Tuberculosis
1/47
Case 3: Tuberculosis
Presented By:
John Tinio
Joshua Vergara
7/28/2019 Case 3 Tuberculosis
2/47
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
7/28/2019 Case 3 Tuberculosis
3/47
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
7/28/2019 Case 3 Tuberculosis
4/47
Management In Order Of Priority
Pulmonary Tuberculosis
HIV Infection
Anemia
Pneumocystis Carinii Pneumonia
Depression
7/28/2019 Case 3 Tuberculosis
5/47
Problem 1: Basis
Pulmonary Tuberculosis
- Malaise
-Anorexia
- Weight Loss
- Fever
- Night Sweats
- Chills
- Productive Cough
7/28/2019 Case 3 Tuberculosis
6/47
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
7/28/2019 Case 3 Tuberculosis
7/47
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
7/28/2019 Case 3 Tuberculosis
8/47
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
7/28/2019 Case 3 Tuberculosis
9/47
First Line Anti-Tuberculosis Agents
The Core Of Treatment Regimens
Isoniazid Rifampin Pyrazinamide Ethambutol Streptomycin
Efficacy +++ +++ +++ +++ +++
Safety ++ ++ ++ ++ ++
Suitability +++ +++ +++ +++ +++
Cost + ++ ++ +++ +++
7/28/2019 Case 3 Tuberculosis
10/47
Pulmonary Tuberculosis:
Personal Drug
Isoniazid
Rifabutin
EthambutolPyrazinamide
7/28/2019 Case 3 Tuberculosis
11/47
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
7/28/2019 Case 3 Tuberculosis
12/47
Rifabutin
- Derived from Rifamycin; related to rifampin- Effective in prevention and treatment of disseminated
aytpical mycobacterial infection in AIDS patient with
CD4 counts
7/28/2019 Case 3 Tuberculosis
13/47
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
7/28/2019 Case 3 Tuberculosis
14/47
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
7/28/2019 Case 3 Tuberculosis
15/47
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
7/28/2019 Case 3 Tuberculosis
16/47
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
7/28/2019 Case 3 Tuberculosis
17/47
Pulmonary Tuberculosis:
Prescription
RxIsoniazid 300mgRifabutin 450mg
Sig.
4 month regimen
- Isoniazid, once daily
- Rifabutin, once daily
7/28/2019 Case 3 Tuberculosis
18/47
7/28/2019 Case 3 Tuberculosis
19/47
7/28/2019 Case 3 Tuberculosis
20/47
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
7/28/2019 Case 3 Tuberculosis
21/47
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
7/28/2019 Case 3 Tuberculosis
22/47
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
7/28/2019 Case 3 Tuberculosis
23/47
HIV: Pharmacologic Therapy
Efavirenz Nevirapine Delavirdine Etravirine
Efficacy +++ +++ +++ +++
Safety +++ ++ ++ ++
Suitability +++ ++ ++ ++
Cost ++ ++ +++ +++
Non-Nucleoside Reverse Transcriptase
7/28/2019 Case 3 Tuberculosis
24/47
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, Atazanavir, Ritonavir
- Truvada, Darunavir, Ritonavir
- Truvada, Raltegravir
7/28/2019 Case 3 Tuberculosis
25/47
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
7/28/2019 Case 3 Tuberculosis
26/47
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
7/28/2019 Case 3 Tuberculosis
27/47
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
7/28/2019 Case 3 Tuberculosis
28/47
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
7/28/2019 Case 3 Tuberculosis
29/47
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
7/28/2019 Case 3 Tuberculosis
30/47
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
7/28/2019 Case 3 Tuberculosis
31/47
7/28/2019 Case 3 Tuberculosis
32/47
Anemia
Pharmacologic Therapy
Drug Adverse Effects
Iron Supplement -Bright red blood in stools
-Constipation, diarrhea
-Nausea, heartburn-Vomiting
Erythropoietin(Procrit) -Seizures
-Hypertension
-Allergic Reactions-Fatigue
7/28/2019 Case 3 Tuberculosis
33/47
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
7/28/2019 Case 3 Tuberculosis
34/47
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
7/28/2019 Case 3 Tuberculosis
35/47
Anemia: Prescription
RxMulti-vitamin with Iron supplement
Vitamin B12Folic Acid
Sig.Take one tab daily
A i
7/28/2019 Case 3 Tuberculosis
36/47
Anemia:
Alternative Prescription
RxProcrit 8000 units
Sig.3 times a weekSubcutaneously
P bl 4
7/28/2019 Case 3 Tuberculosis
37/47
Problem 4:
Pneumocystis Carinii Pneumonia
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
7/28/2019 Case 3 Tuberculosis
38/47
Pneumocystis Carinii Pneumonia:
Non-Pharmacologic Therapy
Proper diet
Hydration
Rest
Exercise
Medication
Check-up
Reaction of drugs
C
7/28/2019 Case 3 Tuberculosis
39/47
Pneumocystis Carinii Pneumonia:
Pharmacologic Therapy
Trimethoprim-
Sulfamethoxazole Dapsone AtovaquoneAerosolized
Penamidine
Efficacy +++ +++ +++ +++
Safety +++ ++ ++ ++
Suitability +++ ++ ++ ++
Cost ++ ++ +++ +++
7/28/2019 Case 3 Tuberculosis
40/47
Pneumocystis Carinii Pneumonia
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
7/28/2019 Case 3 Tuberculosis
41/47
Pneumocystis Carinii Pneumonia:
Prescription
RxTrimethoprim Sulfamethoxazole 15mg/kg/d
Sig.Take one double-strength tablet three times a
week for 21 days
Take one tablet daily thereafter
7/28/2019 Case 3 Tuberculosis
42/47
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
7/28/2019 Case 3 Tuberculosis
43/47
Depression:
Pharmacologic Therapy
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
7/28/2019 Case 3 Tuberculosis
44/47
Depression:
Non-pharmacologic
Lifestyle changes can improve depression for
some people
- Regular exercise
- Increased exposure to sunlight
- Stress management
- Counseling
- Improve sleep habits
7/28/2019 Case 3 Tuberculosis
45/47
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
7/28/2019 Case 3 Tuberculosis
46/47
Depression: Prescription
RxSetraline (50mg)
Sig.Take one tab daily with food taken with breakfast
or dinner
7/28/2019 Case 3 Tuberculosis
47/47
Thank You