dr. ahraf abdulhaseeb chest diseases consultant chief of dr-tb center, abbassia chest diseases
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Management of Adverse Effects of Anti-TB drugs (part II). Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases . I) Management of Gastro-intestinal intolerance. A. Gastritis Symptoms: - epigastric pain or burning sensation, - PowerPoint PPT PresentationTRANSCRIPT
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Dr. Ahraf AbdulhaseebChest Diseases Consultant
Chief of DR-TB Center, Abbassia Chest Diseases
Management of Adverse Effects of Anti-TB drugs (part II)
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I) Management of Gastro-intestinal intolerance
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A. GastritisSymptoms: - epigastric pain or burning sensation,
- bitter taste in the mouth, - less pain after eating. - Coffee ground emesis if
present means gastrointestinal hemorrhage (hematemesis)
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A. Gastritis, cont.exclude: - infections (e.g. helicobacter pylori)
- alcohol intake, - spicy diet, - other drugs e.g. NSAIDs- other diseases e.g. bile reflux, HIV, Auto-
immune diseases, renal or liver impairment Investigations: stool analysis for occult blood, maybe gastroscopy needed
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Algorithmic management of Gastritis
- Hematemesis + Emergency refer to hospital
No Hematemesis, only epigastric pain, burning sensation …etc.
Give drugs with or after food, avoid coffee, alcohol, smoking
If no improvement, give H2 blocker or proton pump inhibitor
If no improvement, give antacid e.g. Mg Hydroxide. Away from Fluoroquinolone at least 3 hours If no improvement , If receiving ethionamide, PAS, clofazimine consider reduction dose. Consider treatment for Helicobacter pylori and GIT consultation
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B. Diarrhea:Diarrhea is frequent (3-4) &/or watery bowel movements• exclude: - infections (giardia, amoebic or
bacillary dysentery, or other infectious causes)
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Algorithmic management of Diarrhea:stools frequent &watery stools frequent & loose
Encourage fluid intake, check serum electrolytes
With blood, mucous, fever
No blood, mucous, fever
• Role out infection• Treat accordingly• Avoid anti-diarrheal• Check electrolytes
• Infection rolled out• Rehydrate • Check electrolytes• Anti-diarrheal e.g.
Loperamide (2 mg orallyafter each episode of up to 10 mg total / day
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C. Nausea and vomitingAlgorithmic management
Hematemesis Urgent referral to hospitalNo hematemesis
Dehydrated • Check electrolyte• Rehydrate IV• Hospitalization to correct fluid
electrolyte disturbanceIf not and hepatitis rolled out
• Administer oral anti-emetics• Use benzodiazepines in anxiety (avoided in Co2 retention)• Administer IM/IV anti-emetics if no improvement.• Consider reducing the dose or suspending it for a short time
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D. Hepatitis: • Nausea, vomiting, jaundice, scleral icterus, tea-colored
urine, pale stool, and diminished appetite• Serum transaminases &/or Serum bilirubin exceed three
times normal level.Causes include:• Infections (e.g., viral A B C, amoebic, TB etc.), • Autoimmune disease, • Alcoholism, • Medications, including anti-tuberculosis drugs, anti-
epileptics, acetaminophen, sulfa drugs, erythromycin
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I) Management of Gastro-intestinal intolerance(SGOT) ALT (SGPT), direct or bilirubin >3 times normal values
Stop all drugs Role out other causes
TREATMENT of HEPATITIS- Hospitalization for severely ill patient- Symptomatic treatment as needed or the underlying cause if appropriate- Wait for normalization of serum liver tests prior to considering re-initiation of
Anti-tuberculosis medications- If possible, eliminate the most likely agent from the regimen- Reinitiate anti-tuberculosis medications, one by one, with serial monitoring
of serum liver tests- Introduce agents most likely to cause hepatitis first- If possible, replace the hepatotoxic medications with equally efficacious anti-
tuberculosis medications without compromising the regimen.- Follow up serum liver test every month throughout treatment.
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II) Allergic and dermatological adverse reactions
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Allergic and dermatological adverse reactions
Minor• Skin pigmentation• Photosensitivity• Dry skin
Moderate to severe adverse reactions• Hypersensitivity• Rash• Purpura• Allergic dermatitis• Exfoliative dermatitis, Steven
Johnson Syndrome• Photosensitivity• Anaphylaxis /Angiodema
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• Symptoms include:– Difficulty of breathing (often
with wheezing), – Pruritis,- Hoarseness, sensation of a
“lump” in the throat, – Urticaria (with or without
angioedema),– Nausea, Vomiting, – Cramps, – Diarrhea – Sometimes, patient also presents
with fever, arthralgia,
myalgia• Signs include:
- stridor, wheezing, swelling- of the tongue, hoarseness - Systolic blood pressure- <90mm Hg (shock)
A. AnaphylaxisFatal and appears within minutes of the administration of the offending medication.
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Management
EMERGENCY- Evaluate for airway obstruction, exclude foreign
body aspiration,- Administer epinephrine 0.2- 0.5 ml 1:1000 SC- Re-administer epinephrine if the symptoms persist
after 20 min- Administer antihistamine and corticosteroids- Intravenous fluids to expand intravascular volume - Oxygen - Consider intubation if necessary
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B. Steven Johnson syndrome • Starts as non-specific upper respiratory tract infection.
– This usually is part of a 1- to 14-day prodrome during which fever, sore throat, chills, headache, malaise may be present.
– Vomiting and diarrhea are occasionally noted as part of the prodrome.
• Muco-cutaneous lesions develop abruptly and typically non-pruritic.
• symptoms are as follows: – Cough productive of a thick purulent sputum– Headache– Malaise– Arthralgia– Fever, reported in 85% of cases.
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Signs include: – Fever– Orthostasis– Tachycardia– Hypotension– Altered level of
consciousness– Epistaxis– Conjunctivitis– Corneal ulcerations– Vulvovaginitis or
balanitis– Seizures, coma
Symptoms include: – Cough productive of a
thick purulent sputum– Headache– Malaise– Arthralgia– Fever, reported in 85%
of cases.
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Management
EMERGENCY• Stop all drugs• Administer aggressive hydration• Administer antihistamine and/or
corticosteroids• Refer to hospital
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Other allergic skin reactions
Patients may have:Skin rash, itching, dry skin, photosensitivity Management:• Consider allergic reaction• Administer antihistamine and/or corticosteroids• PRN for symptoms• Rule out other non-allergic causes e.g. scabies, insect
bites ..etc. • If associated with sun exposure, use sunscreens or avoid
exposure
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In all allergic and dermatological reactions:In addition to the specific management:
• Determine the offending substance (food, medication, insect bites)
• If an anti-tuberculosis medication is highly suspected and the reaction was life-threatening, discontinue medication and replace with equally efficacious anti-tuberculosis drug.
• When any of the severe allergic reactions are present, all anti-tuberculosis medications should be suspended.
• Desensitization should not be performed in patients with a history of Stevens-Johnson syndrome.
Desensitization,General considerations
• It is essential to determine which drug caused the reaction.
• Once the patient has improved, anti-tuberculosis therapy can be restarted as a “challenge”– a partial dose – in a serial fashion
• Start the most likely allergen administered first.
• Desensitization is only done when other therapeutic options are extremely limited.
• Challenges is done to medicines in which reactions were mild to moderate.
• Rarely agent that has caused anaphylaxis can only be introduced through a desensitization protocol under careful, hospital based observation.
Desensitization,General considerations
Example of desensitization protocols
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III. Neurological and Psychiatric adverse reactions
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Common mild adverse reactions• Dizziness• Headache• Fatigue• Somnolence• Insomnia• Confusion• Irritability• Anxiety• Behavior changes
Moderate to severe adverse reaction• Seizure• Syncope• Peripheral neuropathy• VIII nerve damage: hearing
loss, vestibular impairment• Psychosis• Suicidal ideation• Depression
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Management of HeadachesRule out meningitis: • Neck rigidity, photophobia, • fever, • confusion,• somnolence
If positive, refer to hospital
Rule out migraines:• Prior to treatment similar headaches• pulsating, with nausea, vomiting, vision
changes?• Discrete episodes • lasting hours, • relieved by darkness, sleep
• analgesics,• low-dose beta-blockers,• sumatriptan, • Supportive measures
TREATMENT• analgesics (e.g., acetaminophen, ibuprofen, etc.)• Avoid non-steroidal anti-inflammatory agents in patients with hemoptysis or gastritis• Psychosocial support • Encourage adequate fluid intake• Confirm patient on proper dose of pyridoxine• If no response, Amitriptyline 50-150 mg at night & consider lowering Cycloserine dosage
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Management of Seizures Presentations• Recurrent movement of a part of the body (e.g., finger, hand,
face, etc.) with or without loss of consciousness? • Loss of consciousness followed by rhythmic contraction of
muscles? Tongue biting? Urinary or fecal incontinence?
• Headache, confusion, drowsiness, or amnesia immediately after the event?
• Sensory disturbances (numbness, dizziness, auditory or visual hallucinations, sensations of fear or anger, etc.)?
• Psychotic changes (psychosis, hallucinations, sensations of fear or anger, etc.)
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• Rule out other causes e.g. meningitis, encephalitis, alcohol withdrawal, hypoglycemia, hyper- or hyponatremia, hyper- or hypocalcaemia, cerebrovascular accident, or space-occupying lesion.
• Consider neurology consultation
• Initiate anti-convulsant therapy (e.g. phenytoin 3-5 mg/kg/d)
• Increase pyridoxine to 300mg daily
• Lower dose or discontinue suspected agent, if this can be done without compromising regimen
Management of Seizures , cont.
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General considerations: • Anti-convulsant is generally continued until MDR-TB treatment
completed or suspected agent discontinued.
• History of prior seizure disorder is not a contraindication to the use of agents listed here if patient’s seizures are well controlled and/or patient is receiving anti-convulsant therapy.
• Patients with history of prior seizures may be at increased risk for development of seizures during MDR-TB therapy.
• Seizures not a permanent squeal of MDRTB treatment
Management of Seizures , cont.
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Management of Peripheral neuropathySymptoms: • Burning sensation,• Numbness of both feet, worse at night or when
walking• Leg weakness when walking• Leg pain
Rule out other causes, including:diabetes, alcoholism, vitamin deficiencies, HIV, hypothyroidism, uremia etc.
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Treatment • Initiate low-dose tricyclic antidepressant (e.g.,
amitriptyline 25-75 mg at bed time)• Confirm patient is on proper dose of pyrodoxine.
If no improvement • Decrease dose of responsible medication (e.g., Ethio.
to 750 mg, CS to 750 mg, aminoglycoside to 750 mg, or use CM instead etc.), then resume normal dose once pain is controlled
• Consider acetaminophen and/or NSAIDs for pain relief
Management of Peripheral neuropathy, cont.
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• Ototoxicity–Hearing loss is confirmed by audiometry.
• Patients with previous exposure to aminoglycosides may have baseline hearing loss.
• Hearing loss generally is not reversible.
• The aim is to Keep patient quality of life to be able to hear people voice
• Change parenteral to CM if patient susceptibility has documented.
• Lower dose of suspected agent, (consider administration three times a week).
• Discontinues suspected agent if this does not compromise the regimen. • Patients with renal failure has increased risk
Management of VIII cranial nerve toxicity
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Management of depression
Symptoms of major depressive disorder can include:- changes in sleep pattern,- loss of interest in usual activities, - feelings of guilt,- diminished energy, - decreased concentration, - lack of appetite, - psychomotor retardation (slowed movement and
thought), - suicidal ideation.
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Management of depression, cont.EVALUATIONMore than two weeks of persistent sadness,loss of interest, loss of appetite,weight change, insomnia, fatigue, lackof concentration, feelings of worthlessnessor guilt.
Suicidal or homicidal ideation?
EMERGENCY• Consider hospitalization• Monitor closely to ensure safety
• Rule out psychosis Delusions, hallucinations, incoherent thoughts or speech, inappropriate or catatonic behavior
• Rule out hypothyroidism.
TREATMENT• Consider psychiatric consultation• Initiate antidepressant therapy• Provide intensive psychological therapy with counseling to patient and family• Provide emotional support from the family and treatment supporter aimed at resolution of causes of stress• Organize group therapy or informal support groups
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Management of PsychosisDisintegration of personality or loss of contact with reality
EVALUATION Patient sees or hears things that others do not perceive? Unintelligible thoughts or speech? Bizarre behavior?
Suicidal or homicidal ideation?
EMERGENCY• Consider hospitalization• Monitor closely to ensure safety
TREATMENT• discontinue Cycloserine or replace suspected
agent with equally efficacious anti-tuberculosis drug
• Consider psychiatric consultation & initiate anti-psychotic medications
• Evaluate psychosocial stressors• Confirm patient is on proper dose of pyrodoxine.• Anti-psychotic medication can be continued to
the end of treatment if recurrence occur.• Cycloserine can be re-initiated in a lower dose
after remission.
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IV. Management of fluid and electrolyte disturbances
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Management of HypokalemiaPotassium level <3.5 meq/L).
Causes: • Some of the anti-tuberculosis medications–-in particular the
aminoglycosides and Capreomycin—cause renal wasting of potassium and magnesium.
• Severe vomiting or diarrhea
TREATMENT• Replete potassium orally or IV • Treat associated conditions such as vomiting or diarrhea.• Monitor potassium closely to determine when repletion may be discontinued• Empiric magnesium repletion or check Mg level and replete as needed • Discontinue any arrhythmogenic medications (e.g., digoxin, amytriptyline,)• Consider checking calcium and replete as needed.If severe consider stopping the injectable drug.
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Management of Hypokalemia, cont.
Recommended repletion protocol
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V. Endocrine adverse reactions
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Common mild adverse reactions• Poor glycemic control in
diabetics• Changes in menstrual cycle• Gynecomastia • Impotence
Moderate to severe adverse reactions• Hypothyroidism
V. Endocrine adverse reactions
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Management of HypothyroidismEVALUATIONFatigue, enlarged thyroid, lack of energy, weakness, depression, constipation, cold intolerance, lack of concentration, loss of appetite, weight gain, dry skin, coarse hair, hair loss.
Rule out depression and check TSH, Free T4 & T3 TSH >10 mIU/L
TREATMENT• Administer levo-thyroxine- Adult patients under 60 years without evidence of heart disease may be started on 50-100 mcg daily- Therapeutic dosage often between 100-200 mcg daily- Repeat TSH every month and adjust the dose of thyroxine; adjustment is made in 12.5-25 mcg increments till adjusted then TSH every 3-4 months.- Continue thyroxine and TSH estimation 2-3 months after treatment completion.
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Thank You