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Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases...

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Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II) 1
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Page 1: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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)

Page 2: Dr. Ahraf Abdulhaseeb Chest 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

Page 3: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 5: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 6: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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)

Page 7: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 8: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 9: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 10: Dr. Ahraf Abdulhaseeb Chest 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(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.

Page 11: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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II) Allergic and dermatological adverse reactions

Page 12: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 13: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 14: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 15: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 16: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 17: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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Page 18: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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Management

EMERGENCY• Stop all drugs• Administer aggressive hydration• Administer antihistamine and/or

corticosteroids• Refer to hospital

Page 19: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 20: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 21: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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

Page 22: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

• 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

Page 23: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

Example of desensitization protocols

Page 24: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)
Page 25: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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III. Neurological and Psychiatric adverse reactions

Page 26: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 27: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 28: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.)

Page 29: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 30: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 31: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 32: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 33: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 34: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 35: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 36: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 37: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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IV. Management of fluid and electrolyte disturbances

Page 38: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 39: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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Management of Hypokalemia, cont.

Recommended repletion protocol

Page 40: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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V. Endocrine adverse reactions

Page 41: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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

Page 42: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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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.

Page 43: Dr. Ahraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB Center, Abbassia Chest Diseases Management of Adverse Effects of Anti-TB drugs (part II)

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Thank You


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