This is a slide on drugs used in treatment of tuberculosis and leprosy

1. DRUGS USED IN THE TREATMENT OF
TUBERCULOSIS AND LEPROSY
DR UMARUDEEN AJIBOLA M.
DEPT. OF PHARMACOLOGY & THERAPEUTICS, CHS,
UNIABUJA

2. DRUGS USED IN THE TREATMENT OF TUBERCULOSIS
AND LEPROSY: INTRODUCTION
• 5 closely related mycobacteria responsible for TB: M. tuberculosis, M. bovis, M.
africanum, M. microti and M. canetti.
• M. tuberculosis, by far the commonest: transmitted btw. humans via airborne
droplets through the respiratory airway
• No known animal reservoirs of M. tuberculosis.
• M. bovis may penetrate GIT mucosa or invade the lymphatic tissue of the
oropharynx when ingested in milk from diseased cows
• M. bovis human infection has decreased significantly in developed countries as a
result of the pasteurization of milk and effective tuberculosis control amongst
cattle
• Infection with the other Mycobacteria is relatively rare

3. DRUGS USED IN THE TREATMENT OF
TUBERCULOSIS AND LEPROSY: INTRODUCTION
• Transmission generally occurs indoors, in dark, poorly ventilated spaces
where droplet nuclei stay airborne for a long time
• Direct sunlight quickly kills tubercle bacilli, but they can survive in the
dark for several hours. Close contact and prolonged exposure increases
the risk of transmission
• Once infected, the progression to active disease is dependent on the
immune status of the individual
• In those with normal immunity, 90% will not progress and only 10%
will develop active disease (half of these now and half later on in life)
• The risk is highest in the first two years after infection, when half the
cases will occur

4. Risk factors to pulmonary tuberculosis include:
• Early childhood
• Old age
• Cigarette smoking
• Heavy alcohol intake
• Diabetes mellitus
• Silicosis (cement factory, quarry workers)
• HIV/AIDS

5. Types of Clinical Tuberculosis
•Pulmonary
•Extra-pulmonary
• TB lymphadenitis
• Tuberculous pleural effusion (usually single-sided)
• TB of the bones and joints
• Tuberculous pericardial effusion
• TB meningitis
• Disseminated / miliary tuberculosis
• Tuberculous empyema
• TB peritoneal effusion

6. Pulmonary Tuberculosis: Symptoms/Signs
• Persistent cough of 2 weeks or more or any duration if HIV positive
• Fever for more than 2 weeks
• Cough of any duration with heamoptysis
• Drenching night sweats
• Unexplained weight loss (more than 1.5 kg in a month)
• Body temperature may be high or irregular (greater than 38.5 degrees Celsius)
• The pulse rate may be raised because of fever
• Chest may have no abnormal signs or there may be lung apical crepitations
more pronounced on deep
• Localised wheeze in local obstruction or pressure; dullness where there is
effusion and in chronic disease there may be extensive fibrosis with the trachea
pulled to one side

7. Extra-pulmonary Tuberculosis
• Symptoms/Signs
• Extra-pulmonary TB can present with non-specific symptoms
such as
• unintentional weight loss (more than 1.5 kg in a month),
• night sweats and fever for more than 2 weeks.
• Other symptoms depend on the site or organ affected.
• Disseminated / miliary tuberculosis may present with acute
on chronic symptoms and signs
• Tuberculous meningitis may present with headache, malaise,
confusion, neck stiffness

8. ROLE OF CHEMOTHERAPY IN TB
MANAGEMENT
•Chemotherapy plays a pivotal role in the control of tuberculosis
as it is as at today the surest and quickest means of elimination
of live active TB bacilli from the patients

9. PRINCIPLES OF TB TREATMENT
• TB chemotherapy is to be carried on the principle of DOTS
• Prompt diagnosis and chemotherapy
• Correct drugs are given for the correct period of time
• PTB and EPTB are both treated with the same sets of drugs
• Provide safest and most effective therapy in shortest time possible to minimize
morbidity and mortality
• Prevent the development of acquired drug resistance and possible relapse by
prescribing multiple drugs to which the organisms are susceptible
• Never prescribe a single drug or add a single drug to a failing drug regime
• Ensure patient’s adherence and completion of therapy
• Ensure concurrent treatment of co-morbid clinical conditions e.g. HIV/AIDS,
Diabetes mellitus, malnutrition, Anemia etc

10. INDIVIDUAL ANTI-TB DRUGS
• TB drugs have different properties: while some are bactericidal, others
are bacteriostatic (sterilizing) or have the ability to prevent resistance
• They also gave varying capacities to act against the various populations
of bacilli found in a tuberculosis lesion such as metabolically active
bacilli, intermediately active bacilli, semi-dormant bacilli (persisters),
which undergo occasional spurts of metabolism and dormant bacilli
(that may become active).
• Again some TB drugs act best in an acid environment while others
better at a more alkaline pH.
• Meanwhile TB bacilli occur both in extracellular spaces where the pH is
usually neutral or alkaline and in intracellular spaces where it is acid

11. RIFAMPICIN
•Rifampin is a semisynthetic derivative of the rifamycins
- a group of antibiotics produced from Streptomyces
mediterranei
•Has a broad antibacterial spectrum, including activity
against several forms of Mycobacterium
•It is bactericidal for both intracellular and extracellular
mycobacterium and also active against Mycobacterium
leprae, Staphyloccus aureus, Nesseria meningittidis, H.
influenza, Brucella, Clamydia and Legionella

12. Pharmacokinetics of Rifampicin
•It is well absorbed ff. oral administration and penetrates
all tissues including tubercular cavities, placenta and is
highly bound to plasma protein
•It is metabolized in the liver and excreted mainly
through bile into the biliary tree where it undergoes
extensive enterohepatic circulation. The de-acetylated
products are eventually excreted in the faeces

13. Mechanisms of Action of Rifampicin
•In susceptible organisms rifampicin inhibits DNA-dependent
RNA polymerase activity by forming a stable complex with the
enzyme. It thus suppresses the initiation of RNA synthesis
•It is bactericidal on both intra/ and extracellular organisms
•It has high sterilizing and resistance preventing action on TB
bacilli
•Resistance to its activity derives from point mutations in rpo
gene
•Rifampicin is a potent inducer of liver metabolizing enzymes

14. Therapeutic Indications of rifampicin
•Treatment of all forms of PTB and EPTB in combination with
other first-line TB drugs.
•Dose is 600mg or 10mg/kg daily
•Treatment of leprosy
•Prophylaxis of meningococcal & H influenza meningitis and
carrier state
•Prophylaxis of MRSA infection, legionella, brucellosis (with
doxycycline)

15. Adverse effects of Rifampicin
•Hepatitis is a major toxicity of rifampicin. It is dose dependent
and reversible
•Generalised body rash
•Dizziness
•‘’Flu –like syndrome”
•Red orange colouration of urine

16. Adverse drug-drug interactions of rifampicin
•Due to liver enzyme (CYP450)-inducing property of
rifampicin, co-administration with rifampicin can
result in increased metabolism of oral
contraceptive pills, warfarrin and protease
inhibitors

17. ISONIAZID
•Isoniazid is a structural analogue of pyridoxine. Isoniazid is
chemically known as isonicotinyl hydrazine or isonicotinic acid
hydrazide. It has an empirical formula of C6H7N3O and a
molecular weight of 137.14. It has the following structure
•Isoniazid is a potent anti-TB agent: it is bactericidal against
actively dividing intra- and extra-cellular TB bacilli in both acidic
and alkaline mediums.

18. Isoniazid Pharmacokinetics
•It has good oral absorption and bio-availability
•Isoniazid has wide distribution in the body despite the fact it is
not protein-bound
•It is metabolized in the liver through N-acetylation by nicotinic
acetyl transferase into acetyl hydrazine, hydrazine and acetyl
isoniazid which are responsible for isoniazid liver toxicity
•The rate of N-acetylation of isoniazid determines INH toxicity in
different patients. There is genetic variation in N-acetylation
with fast acetylators more prone to toxicity

19. Mechanism(s) of action of Isoniazid
• Isoniazid is a prodrug and must be activated by bacterial catalase in the liver.
• Specficially, activation is associated with reduction of the mycobacterial ferric Kat
G catalase-peroxidase by hydrazine and reaction with oxygen to form an
oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of
mycoloic acids, an essential component of the bacterial cell wall.
• At therapeutic levels isoniazid is bactericidal against actively growing intracellular
and extracellular M. tuberculosis organisms. Specifically isoniazid inhibits the
enoyl reductase from M. tuberculosis, by forming a covalent adduct with the NAD
cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive
inhibitor of enoyl reductase
• Resistance to anti-TB activity of INH is achieved by point mutation of kat G gene
of target site involved in mycobacterial enol reductase mycolic acid synthesis.

20. Therapeutic indicators for Isoniazid
•Treatment of susceptible TB
•Prophylaxis of susceptible TB
•Dose: 300mg OD daily or 5mg /kg/day
•If given thrice weekly: 10mg/kg/day or 600mg

21. Adverse effects of Isoniazid
•Lethal dose (LD50)100 mg/kg (Human, oral)
•Rash
•Hepatitis (dose-dependent)
•Peripheral neuropathy (dose-dependent)
•Mild central nervous system (CNS) effects (confusion, seizures)
•Systemic Lupus Erythromatosis
•Xerostomia

22. Contra-indications to Isoniazid use
•Drug-induced hepatitis
•Previous isoniazid-associated hepatic injury
•Severe adverse reactions to isoniazid (eg, drug fever, chills,
arthritis)
•Acute liver disease of any etiology

23. Adverse drug-drug & drug-food interactions of Isoniazid
• In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of
pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere
with the coenzyme function of the latter.
• Aluminium hydroxide ( antacids ) inhibits absorption of isoniazid
• Isoniazid inhibits metabolism of phenytoin and carbamazepine
• Avoid aged foods (cheese, red wine), pickled foods, cured foods (bacon/ham), chocolate, fava
beans, beer, unless approved by your physician.
• Avoid alcohol.
• Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this
medication.
• Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a
multivitamin.
• Take on empty stomach: 1 hour before or 2 hours after meals.
• Take with a full glass of water.

24. ETHAMBUTOL
•Ethambutol hydrochloride also known as myambutol is a
synthetic oral TB chemotherapeutic agent that is bacteriostatic
and of low potency though against actively growing
microorganisms of the genus Mycobacterium,
including M. tuberculosis
•Ethambutol is largely bacteriostatic: It inhibits RNA synthesis
and decreases tubercle bacilli replication
•Nearly all strains of M. tuberculosis and M. kansasii as well as a
number of strains of MAC are sensitive to ethambutol

25. •Pharmacokinetics of Ethambutol
• About 75% to 80% of an orally administered dose of ethambutol is absorbed
from the gastrointestinal tract.
Up to 15% of administered drug is metabolized to inactive metabolites. The main
path of metabolism appears to be an initial oxidation of the alcohol to an
aldehydic intermediate, followed by conversion to a dicarboxylic acid. Most
administered drug is excreted unchanged in urine.
Mechanism of action
• Ethambutol inhibits arabinosyl transferases which are involved in cell wall
biosynthesis. By inhibiting this enzyme, the bacterial cell wall complex
production is inhibited. This leads to an increase in cell wall permeability
• Resistance to ethambutol is due to point mutation in Emb gene that encodes
arabibinosyl transferases

26. Mechanism of action of Ethambutol
• Ethambutol inhibits arabinosyl transferases which are involved
in cell wall biosynthesis. By inhibiting this enzyme, the bacterial
cell wall complex production is inhibited. This leads to an
increase in cell wall permeability
•Resistance to ethambutol is due to point mutation in Emb gene
that encodes arabinosyl transferases

27. Therapeutic Indications of Ethambutol
•Rx of pulmonary TB in combination with other 1st line
anti-TB drugs
•Mycobacterium avium complex in AIDs in combination
with clarithromycin and rifabutin
•Dose 800-1000 mg PO (15mg/kg/day) or
1600mg/day(30mg/kg/day) thrice a week

28. Adverse effects of ethambutol
• Most prominent: optic neuropathy (uncommon & reversible)
• Reduced visual acuity due to above reason
• Loss of red-green colour vision
• Pruritus
• Arthritis
• GIT upset
• Abdominal cramps
• Malaise
• Dizziness
• Headache
• Mental confusion/Disorietation/Hallucinations

29. Contra-indications to ethambutol
•Childhood < 5years
•Previous allergy

30. Adverse drug-drug interactions
•Aluminum hydroxide can cause a decrease in the absorption of
ethambutol resulting in a reduced serum concentration and
potentially, a decrease in efficacy
•Efficacy of BCG vaccine can be reduced by con-current
administration of ethambutol

31. PYRAZINAMIDE
•Pyrazinamide is a synthetic derivative of nicotinamide
that exhibits potent anti-TB activity following its
intracellular conversion to pyrazinoic acid by the
mycobacterial pyrazinamidase

32. Pharmacokinetics of Pyrazinamide
•It is rapidly and well absorbed from the gastrointestinal tract
and widely distributed in tissues, macrophages and tubercular
cavities and meninges
•It is about 10% plasma protein bound. Metabolism is mainly in
the liver and the by products are excreted largely in the kidneys

33. Mechanism of action of Pyrazinamide
• Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts
pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic
acid that slowly leaks out converts to the protonated conjugate acid, which is thought
to diffuse easily back into the bacilli and accumulate. The net effect is that more
pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH.
• Pyrazinoic acid and pyrazinamide inhibit the enzyme fatty acid synthase (FAS) I, which is
required by the bacterium to synthesise fatty acids
• It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane
potential and interferes with energy production, necessary for survival of M.
tuberculosis at an acidic site of infection.
• Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and
inhibit trans-translation. This may explain the ability of the drug to kill dormant
mycobacteria
• Pyrazinamide is bactericidal and highly potent against intracellular and dormant TB
bacilli.
• Resistance to its activity is due to point mutation in pcnA gene of the TB bacilli.

34. Therapeutic indications of Pyrazinamide
•Initial Rx of active tuberculosis when combined with other
anti-TB agents
•Dose 1500mg (25mg/kg/day) or 2000mg(35mg/kg/day) thrice
a week

35. Adverse effects of Pyrazinamide
• Hepatopathy
• Arthralgias
• Anorexia/nausea /vomiting
• Dysuria, malaise and fever
• Sideroblastic anemia
• Anomaly of blood clotting mechanism or vascular integrity
• Hypersensitivity reactions such as urticaria, pruritis and skin rashes
• Increased teratogenic risk

36. Adverse drug-drug interactions of pyrazinamide
• Metabolism of Pyrazinamide can be deceased when con-currently
administered with amiadarone, acetyl sulfisoxazole and azithromycin
• BCG vaccine efficacy can be reduced by Pyrazinamide

37. STREPTOMYCIN
• Streptomycin is an aminoglycoside antibiotic produced by the soil
actinomycete Streptomyces griseus.
• It was the first drug found to be active against mycobacterium
tuberculosis.
• It is of low potency and active only against extracellular TB bacilli

38. Pharmacokinetics of streptomycin
• Rapidly absorbed after intramuscular injection with peak serum concentrations
attained after 1 - 2 hours
• Not absorbed in the GI tract
• Small amounts are excreted in milk, saliva, and sweat
• Streptomycin is excreted by glomerular filtration. 5 - 6 hours in adults with
normal renal function

39. Mechanism of Action of streptomycin
•It acts by binding to the 30S ribosomal subunit of susceptible
organisms and disrupting the initiation and elongation steps in
protein synthesis
•It is bactericidal due to effects that are not fully understood

40. Therapeutic indications of Streptomycin
• Treatment of TB – as a reserve first line drug – in combination with other drugs.
Dose ;adults 15mg/kg/day in 2 dd, max 1gm/day,
• May also be used in combination with other drugs to treat:
• Tularemia (Francisella tularensis)
• Plague (Yersinia pestis)
• Severe M. avium complex, brucellosis, and
• Enterococcal endocarditis (e.g. E. faecalis, E. faecium)

41. Adverse drug effects of streptomycin
• Nephrotoxicity
• Othotoxicity
• Nausea/vomiting,
• Vertigo
• Paresthesia of face
• Allergic Rash, fever, urticaria, angioneurotic edema, and eosinophilia
• Teratogenic risks to the fetus/newborn

42. RIFABUTIN
• Rifabutin is a relatively new drug and a structural analogue of rifampicin with
which it shares:
• common mechanism of action
• common antimicrobial activity spectrum
• common molecular basis of antimicrobial resistance, and,
• similar pharmacokinetics

43. Rifabutin comparative advantages over rifampicin
• Rifabutin induces hepatic enzymes to a lesser extent than rifampicin
• Rifabutin had fewer adverse drug-drug interaction
• Rifabutin is more active against mycobacterium avium complex
• Rifabutin has longer half-life

44. Therapeutic Indications of Rifabutin
• And for these advantages, rifabutin enjoys some comparative advantages over
rifampicin for certain therapeutic indications:
• Treatment of TB in HIV patient
• Prevention and treatment of MAC in HIV patients
• Dose is 300mg/d in adults

45. Adverse effects of rifabutin
• Skin rash
• GIT upset
• Hepatitis
• Neutropenia

46. SECOND LINE ANTI-TB DRUGS
•The second line drugs are only used to treat disease that is
resistant to first line therapy such as:
• extensively drug-resistant tuberculosis (XDR-TB), or,
• multidrug-resistant tuberculosis (MDRTB).

47. Criteria for classifying an anti-TB drug as 2nd-line
instead of 1st-line drug
• Less anti-TB efficacy than the first-line drugs (e.g., p-aminosalicylic acid)
• Greater toxicity than 1st-line drugs (e.g., cycloserine)
• It may be effective, but unavailable and/or unaffordable in many developing
countries (e.g., fluoroquinolones)
• Poor pharmacokinetics/Bioavailability

48. Drug classes and their class examples
• Aminoglycosides e.g., amikacin, kanamycin
• Polypeptides e.g. capreomycin, viomycin, enviomycin
• Fluoroquinolones e.g., ciprofloxacin, levofloxacin, moxifloxacin
• Thioamides e.g. ethionamide, prothionamide
• Cycloserine
• Terizidone

49. PARA-AMINOSALYSILIC ACID (PAS)
• PAS is a bacteriostatic structural analogue of PABA
• Like sulphonamides it inhibits folate synthesis of mycobacteria only
• Readily absorbed ff. oral adminis. with wide distribution excepting the CSF due to
BBB
• It is metabolized in liver by acetylation and about 80% of the metabolic products
excreted through the kidneys
Therapeutic Indications of PAS
• 2nd line drug in TB Rx in combination with other antituberculotics
• Dose 10-12 g orally daily in 2-4 divided doses (gastric irritant, used rarely)

50. Adverse effects of PAS
• GIT intolerance- poor compliance
• Hypersensitivity reactions
• Arthritis
• Malaise
• Fever
• Skin eruptions
• Leukopenia
• Agranulocytosis
• Acute hemorrhagic anemia
Contra-indication
• Chronic renal failure

51. CYCLOSERINE
• It is an antibiotic substance produced by Streptomyces garyphalus
• It is broad spectrum bacteriostatic agent against M. tuberculosis, E coli,
enterococcus, nocardia, chlamydia and Staphyllococcus aureus. It acts by
bacterial cell wall synthesis inhibition
• It is well absorbed and widely distributed in the body including the cerebrospinal
fluid
• Cycloserine is mainly excreted unchanged in urine
Therapeutic indications
• TB
• MAC in HIV patients
• Dose 250-500mg BID for both indications and in combinations with up to 5 drugs
sometimes

52. Adverse effects of cycloserine
Mainly in the CNS:
• Tremor
• Dysarthria
• Vertigo
• Confusion
• Irritability
• Psychotic state with suicidal tendencies
• Seizures
Contra-indications to cycloserine
• Epilepsy
• Chronic renal failure

53. ETHIONAMIDE
• Ethionamide is bacteriostatic agent belonging to the thioamide class
• Has good oral absorption with rapid and extensive tissue distribution including
the CSF
• It undergoes extensive hepatic metabolism
Therapeutic Indications
• Used only as 2nd line, given orally as 250mg BID initial dose to a max 1gm /day

54. Adverse effects of ethionamide
• Intense GI irritation
• Metallic taste
• Postural hypotension
• Depression
• Asthenia
• Convulsions
• Allergic reactions
• Hepatitis
• Note that liver function must be monitored and concurrent pyridoxine must be
given

55. CAPREOMYCIN
• It is polypeptide derivative found to exhibit effective bacteriocidal action against
M.tuber, M.kansasi, M.avium.
• It is only given parenterally at 1g IM daily due to its poor oral absorption and
bioavailability.
Mechanism of action
• Little is known about capreomycin's exact mechanism of action
• But thought to inhibit protein synthesis by binding to the 70S ribosomal unit
• Capreomycin also binds to components in the bacterial cell which result in the
production of abnormal proteins. These proteins are necessary for the bacteria's
survival. Therefore the production of these abnormal proteins is ultimately fatal
to the bacteria

56. Therapeutic Indications of capreomycin
•2nd line drug in TB Rx especially important for MDR-TB
Adverse effects
•Ototoxicity
•Nephrotoxicity
•Hypokalemia/ hypocalcemia/hypomagnesemia,

57. KANAMMYCIN AND AMIKACIN
• They are aminoglycoside derivatives and are such are used only
parenterally due to poor oral bio-availability
• Kanamycin is no longer in use due to its intolerable toxicity
• Amikacin on its part is still used for MDR TB & MAC in AIDS patients
• Dose is 15mg/kg/day IM/IV
Adverse Effects
• Nephrotoxicity
• Ototoxicity

58. Fluoroquinolones
• Vital recent addition to anti-TB drugs especially for MDR strains
• Also effective as part of regimen in HIV infected patients
• E.g. ciprofloxacine, ofloxacine, levofloxacine and moxifloxacine
• Inhibit 80-90% of susceptible Mycobacterium strains including MAC &
M.fortuitum
Pharmacokinetics of the fluoroquinolones
• They exhibit good intracellular penetrating capacity and convenient dosage
schdedule
• They are well tolerated orally with little or no hepatic injury.
• Dosage: Ciprofloxacine 750 mg BID or 500mg TDS, Ofloxacine 400mg BD,
Levofloxacine 500mg OD,and moxifloxacine 400mg OD , all PO

59. MACROLIDES
•Clarithromycin 500mg BID PO, and Azithromycin 500mg OD are
active against M kansasii, M fortuitum, M marinum & MAC
•But they have limited activity against M. tuberculosis
•They are therefore only useful for prevention & treatment of
MAC in AIDS patients

60. CHEMOTHERAPY OF TUBERCULOSIS
• Pulmonary and extra-pulmonary TB
• All diagnoses cases are treated under DOTS regime for a total of 6-9 months.
• DOT-S means directly observed therapy-short course.
• It means a treatment modality whereby Tuberculosis patients are given anti-
Tuberculosis treatment drugs under the direct observation of the health professionals
for at least the first 2 months.
• Five components of DOTS include the following:
• Government commitment to establish and prioritise a central TB monitoring, recording
and training system
• TB Case detection by sputum smear microscopy
• Standardised treatment regimen of six to nine months of anti-TB therapy directly
observed by a healthcare personnel for at least the first two months of treatment
• Consistent and reliable quality drug supply
• A standardised TB treatment outcome recording, reporting and assessment

61. CHEMOTHERAPY OF TUBERCULOSIS: DOTS
•Patients are placed on a combination of rifampicin(R) or
rifabutin(R), isoniazid (H), Ethambutol (E) or Streptomycin (S)
and pyrazinamide (Z) for the 1st 2 months of intensive therapy
•Rifabutin is an alternative drug to rifampicin, streptomycin is a
reserve drug to replace ethambutol in case it cannot be used
due to any reason
•For the remaining 4-7 months of continuation stage patients
are placed on a combination of rifampicin and isoniazid only
•Adjunctive drugs like pyridoxine, analgesics and corticosteroids
may be used along with the anti-TB drugs when necessary

62. CHEMOTHERAPY OF MULTIDRUG RESISTANT(MDR TB) &
EXTENSIVELY RESISITANT (XDR TB) TUBERCULOSIS
• For multidrug resistant TB (MDR TB): i.e. TB that is resistant to ISONIAZID &
RIFAMPICIN, 2nd line drugs are used for longer duration
• Extensively drug resistant (XDR TB) i.e. MDR TB that is also resistant to any
fluoroquinolone and to one of the three injectabe 2nd line drugs (amikacin,
capreonine)
• XDR TB Rx is very difficult and takes 18-24 months of 4-6 2nd line drugs

63. TB chemoprophylaxis
• TB chemoprophylaxis: give isoaniazid 300mg/day 6-12mths in normal adults.
• Rifampicin and pyrazinamide for 2 months is effective in HIV patients.

64. Chemotherapy of TB in pregnant mothers
• A combination of rifampicin, isoniazid and ethambutol is safe in all trimesters but
• pyrazinamide may be safe only in last trimester.
• Streptomycin and amikacin have increased teratogenic risk.

65. Chemotherapy of TB in nursing mothers
• Full course of intensive and continuation regimens are given
• Infants are given isoniazid prophylaxis

66. Chemotherapy of MAC TB infection
•Rx of MAC TB infection in HIV is more severe. Drug regimen
same as for PTB patients above but continuation phase last 7
mths i.e. total duration of 9 months
•MAC infection is common in HIV patients, causes disseminated
disease in later stages of AIDS: Common regimens are :
• clarithromycin 500mg BID + Etambutol 15mg/kg/d,
• Azithromycin 500mg OD + Ethambutol 15mg/kg/d,
• Azithromycin 500mg OD + Ethambutol 15mg/kg/d+ Ciprofloxacine
750 mg BID or Rifabutin 300mg OD

67. Chemotherapy of TB spine
•TB spine is treated 2 months intensively and 22 months
of continuation treatment, making a total of 24 months

68. CHEMOTHERAPY OF LEPROSY: INTRODUCTION
• Leprosy is a chronic, infectious disease that mainly affects the skin,
peripheral nerves and mucous membrane of the upper respiratory
tract
• It is caused by a bacterium called Mycobacterium Leprae
• Transmission is through droplets (coughing and sneezing): most
important route of exit is through the nasal discharges
• Average incubation period is between 2 and 5 years
• Only 5% of people exposed to infections progress to develop clinical
leprosy
• Leprosy is a highly curable disease when correct treatment is
commenced early

69. DIAGNOSIS OF LEPROSY
•Leprosy is diagnosed by finding at least one of the following
cardinal signs:
• Definite loss of sensation in a pale (hypo-pigmented) or reddish skin
patch
• A thickened or enlarged peripheral nerve, with loss of sensation and
/ or weakness of muscles supplied by that nerve
• The presence of acid-fast bacilli in a slit skin smear (SSS)

70. Differential Diagnosis of suspected leprosy Skin Lesions
• Pityriasis versicolor: Lesions are hypopigmented but without loss of sensation
and often itch. Give an anti-fungal ointment for 6 weeks
• Ringworm (Tineasis): Lesions are well defined areas of hypopigmentation with
white scales but without loss of sensation. There is itching. Give an anti-fungal
ointment for 6 weeks
• Vitiligo (Leucoderma): Completely depigmented areas of skin with clear, flat
edges without loss of sensation, refer to a medical officer
• Birthmarks: Lightly or deeply pigmented areas of different sizes that are present
from birth without loss of sensation. Reassure the patient.
• Granuloma Multiforme (Mkar Disease): Initially there is itch in a patch, which
gradually develops into a hypo-pigmented, fine papular ring, with central de-
pigmentation, without loss of sensation.

71. Differential Diagnosis of suspected leprosy Skin Lesions
• Onchocerciacis (River Blindness): Thickened skin, very itchy nodules, areas of scratch
marks, and hypo-pigmentation. Slit skin smears for acid fast bacilli are negative.
Nodules usually on bony prominences. Skin snip for microfilaria may be positive. Treat
or refer
• Neurofibromatosis: Multiple nodular lesions, which are soft and may be pendulant
(hanging). The peripheral nerves are not involved. Skin smears are negative. Sometimes
the disease manifests itself as scattered coffee brown (café au lait) spots and patches
• Psoriasis: Hypo-pigmented plaques with silvery scales. Slight scratching on the surface
reveals micro bleeding. Pityriasis (in children) Alba Present over the face and upper
neck. Asymptomatic, hypo-pigmented rounded or oval patches variable in size with the
margins sharply demarcated covered with fine adherent scales. Sometimes the patches
are erythromatous and elevated. Responds well to tar ointments or refer
• Nutritional deficiencies (in children). These deficiencies cause hypopigmentation usually
on the cheek; single or multiple, ill-defined, hypopigmented patches together with
other features of avitaminosis such as glossitis, angular stomatitis and pharynoderma.
These patches will clear with administration of vitamins. Give dietary advice

72. Classification of leprosy
• There are two types of leprosy namely –
• paucibacillary (PB) and
• multibacillary (MB) leprosy
• Type of leprosy in an individual can be determined on the basis of counting
number of skin lesions and nerves affected

73. Classification of leprosy
Pathology Paucibacillary Multibacillary
No of skin lesions with
sensory loss
1-5 lesions 6 or more lesions
No. of nerve involvement
(demonstrated by either thickness,
loss of sensation and muscle
weakness)
Only 1 nerve involved 2 or more lesions involved
It should be noted that:
1. Where slit skin smear (SSS) is done, if positive patient is classified as MB
2. If there is doubt about the classification, the patient should be classified as MB and treated
with MB- MDT
3. Any patient with more than one nerve involvement but less than 5 five skin patches should be
classified as MB

74. Case Categorisation for Leprosy Patients
• New Case: A person who has never taken any leprosy treatment before (DDS or
MDT)
• Relapse After PB: A person who has completed a six-month course of PB-MDT
but is now reporting back with active leprosy that has been confirmed by the
STBLCO/MO designated
• Relapse After MB: A person who has completed a twelve-month course of MB-
MDT but is now reporting back with active leprosy that has been confirmed.
• Re-Admission After DDS: A person who was treated with DDS monotherapy and
is now reporting with signs of active leprosy
• Transfer-in: A person on MDT transferred from one LGA/State to another
• Treatment After Default: A person who started MDT (PB or MB) but did not
complete the course within the stipulated period of time who is now reporting
with signs of active leprosy.

75. TREATMENT OF LEPROSY
•It is the policy of the Federal Ministry of Health to treat leprosy
patients with Multi Drug Therapy (MDT) as recommended by
WHO. The effectiveness of MDT is well known and relapses are
very few. MDT cures the patient within a short period of time
and interrupts the transmission of the disease rapidly. PB-MDT
consists of rifampicin 600 mg once a month and dapsone 100
mg daily while MD-MDT consists of rifampicin 600 mg once a
month, dapsone 100 mg daily and clofazimine 300mg once a
month

76. WHO RECOMMENDED MDT REGIMENS
• The experience of the WHO MDT regimens has been positive. Since the start of
implementation in 1983, more than eight million patients have been treated
throughout the world and few side effects of MDT have occurred.
• PB patients should receive one blister pack of PB MDT every 28 days for a period of 6
months (TOTAL 6 BLISTERS). The intake of drugs on every day of collection must be
supervised.
• These 6 Blisters should be completed within a maximum period of 9 months. After
completing 6 Blisters the patient should be released from treatment (RFT)
• MB patients should receive one Blister of MB MDT every 28 days for a period of 12
months (TOTAL 12 DOSES), intake of drugs on every day of collection must be
supervised. These 12 Blisters should be completed within a maximum period of 18
months
• Note: leprosy Rx is simple. It is available free, and the drugs are supplied in special
packs that contain the correct dose for one person for four weeks. All that is needed is
to decide which course of treatment the patient needs and to make sure that they take
it regularly.

77. Stopping MDT
• MDT is a fixed duration therapy
• When 6 doses of PB-MDT have been completed stop the treatment,
and remove the patient from the Register as treatment completed
• When 12 doses of MB-MDT have been completed stop the treatment,
and remove the patient from the Register as treatment completed
• Prior to release from MDT the health worker should examine the
patient and record all clinical findings on the back page of the Patient
Record Card

78. Common side effects of anti-leprosy
drugs and their managements
SIDE EFFECTS/COMPLAINTS Possible cause
Action
The urine may stain slightly reddish for a few hours after taking the
supervised dose.
Rifampicin This is harmless and should be explained to the patient at the start of
MDT.
The skin may in the course of months gradually turn brownish-black
and show dryness.
Daily Clofazimine for (MB patient) It will disappear within a few months after completing MDT, but the
patient should be informed when starting MDT.
Itching and skin rashes, even the skin may start to peel off and the
patient will feel very ill.
Typical for a (serious) allergic reaction due to Dapsone. Pt to stop taking the dapsone and come to the (LGA) TBL clinic if he
has rash only or go immediately to the TBL hospital if more severely ill.
The PB pts should receive daily 50 mg
Clofazimine and a monthly dose of 300mg as a substitute for Dapsone
MB pts continue with Rifampicin and Clofazimine in the usual dosage.
Jamndice often accompanied by lack of appetite, nausea and
vomiting.
Either Rifampicin or Dapsone Stop MDT and refer to the TBL referral hospital.
The patient may experience nausea vomiting and diarrhoea.
Clofazimine Abdominal complaints may spontaneously disappear, but if they
continue, the patient needs to be referred for further examination
and management at the TBL referral hospital.
A patient may quite suddenly develop chills, fever, headache and
bone pains, in a few hours followed by a weak, quick pulse (shock) and
renal failure.
Rifampicin This flu-like syndrome needs urgent hospital treatment. Stop
Rifampicin.
Tiredness and shortness of breath. Anaemia, a known side-effect of Dapsone This is often a dose related effect and treatment with Dapsone can be
continued with half or a quarter of the daily dose.
Exceptionally a patient may become very excited or frightened, even
psychotic.
Dapsone Stop the drug and refer to the TBL referral hospital.

79. Leprosy Reaction
• Leprosy is not usually a painful disease. But sometimes a person with leprosy will
experience pain and discomfort. This happens because the body reacts against
the presence of the leprosy bacilli. These reactions are the main cause of nerve
damage and disability in leprosy.
• Leprosy reactions can happen at any time during the illness: before, during or
even after release from treatment.
• Recognising Lepra-reaction
• Lepra-reaction is an acute inflammatory process, therefore, look for the
following signs:
• Redness
• Swelling
• Heat
• Pain / tenderness
• Loss of function

80. Lepra reactions on different body parts
Body part Look/Feel for
Skin Red patches
Raised / swollen patches
Tender patches and new skin patches may re-appear
Nerves Pain or tenderness in a nerve
New loss of sensation
New muscle weakness
Eye Pain or redness in the eye
New loss of sensation (loss of ability to blink)
New weakness of eye closure

81. How to different the 2 types of leprosy reactions: Type 1 leprosy reaction
Body part Mild Severe
Skin Red, raised and tender skin lesions (except on
the eye)
Ulcerating skin lesions
Red, raised facial lesion
Nerves No nerve tenderness Painful/ tender & enlarged nerves on palpation
Red, raised patch on or around any peripheral nerve
Muscle test No change Recent change in VMT (< 6/12)
Muscle weakness
in eyes, hands, feet
Sensation test No change Recent change in ST
(<6/12). Change in sensation in one or more points in any one hand or foot
Eyes Not affected Sudden lagophthalmos (inability to close the eye)
Sudden loss of corneal sensation (loss of automatic blink)
General body condition Good fever and malaise can occur in the acute phase only
Systemic effects No effect joint pain due to enlarged nerves.

82. How to different the 2 types of leprosy reactions: Type 2 leprosy reaction
Body part Mild Severe
Skin Appearance of red, raised sub-cutaneous nodules (and
patches). Few crops of nodules
Ulcerating sub-cutaneous lesions
Nerve No nerve tenderness Painful or tender and enlarged nerves on palpation
Muscle test No change Recent change in VMT (< 6 /12). Muscle weakness
in eyes, hands, feet
Sensation test No change Recent change in ST
(less than 6 months duration)
Change in sensation in one or more points in any one hand or
foot
Eyes No effect Painful eyes with redness around the cornea, fear of
light, excessive tearing and diminished vision
General body condition Good Fever and malaise common and prolonged
Systemic effects Nil Orchitis - painful, testicular swelling
Dactylitis - painful, swollen joints, hands and feet.
Renal involvement (blood in the urine)

83. Treating leprosy reactions
• Treatment of Mild Reaction (Type I or Type II)
• Mild reaction should be treated by general health care workers in the field as
follows:
• Aspirin 600mg (2 tablets of 300mg) 4 times daily x 1 week
• Chloroquine 150mg base (1 tablet) twice daily for 1 week
• If the patient cannot tolerate Aspirin, replace with paracetamol 1g (2 tablets) 3
times daily for 1 week
• Re-examine the whole body after 1 week and record findings in the leprosy
treatment form. If there are still signs of reaction, repeat for another week. Re-
examine the whole body after another week and record findings in the leprosy
treatment form, if no improvement or if there is deterioration treat as severe
reaction.

84. Treatment of Severe Type I Reaction
• Treatment of severe type 1 reaction without conditions for referral
should be by general health care workers in the field, however
diagnosis and monitoring should be supported by TBLS
• Any person with severe type I reaction, without any of the criteria
needing referral can be treated in the field with a standard course of
Prednisolone
• Prednisolone is a potent corticosteroid drug. As the drug may also
worsen various other conditions, treatment of these conditions should
be started immediately, but need not be finalised before the start of
treatment with Prednisolone
• Refer patients with corneal ulcer should be referred to a leprosy
hospital.
• Patients with peptic ulceration should not be placed on prednisolone

85. Treating other sundry diagnoses
Diagnosis Treatment
Worm infestation Mebendazole 100mg BD x 3 days
Diarrhoea with blood / mucus suggestive of dysentery Metronidazole 400mg TDS x 7 days
Conjunctivitis Chloramphenicol eye drops 1-2 drops QID x 5 days
Scabies Benzyl Benzoate applied after bath x 3 nights