By the pharmacist

Ayia nazum kamal

Tuberculosis treatment

•refers to the medical treatment of the infectious disease tuberculosis(TB). Active tuberculosis will kill about 2 of every 3 people affected if left untreated. Treated tuberculosis has a mortality rate of less than 5% .

•The standard "short" course treatment for TB is isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months, then isoniazid and rifampicin alone for a further 4 months. The patient is considered cured at six months (although there is still a relapse rate of 2 to 3%).

•For latent tuberculosis ,•the standard treatment is six to• nine months of isoniazid alone.

•If the organism is known to be fully

•sensitive, then treatment is with isoniazid, rifampicin and pyrazinamide for two months, followed by isoniazid and rifampicin for four months. Ethambutol need not be used

Drugs

•First line

•Ethambutol•isoniazid

•pyrazinamide•rifampicin

•streptomycin

Drug regimens:

•2HREZ/4HR3

•means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week.

Second line•There are six classes of second-line drugs

(SLDs) used for the treatment of TB. A drug may be classed as second-line instead of first-line for one of three possible reasons:

•*it may be less effective than the first-line drugs

•(e.g., p-aminosalicylic acid)

•or•*it may have toxic side-effects (e.g.,

cycloserine)

or•*it may be unavailable in many developing

countries (e.g., fluoroquinolones)

•*aminoglycosides: e.g.amikacin, kanamycin

•*polypeptides:e.g.capreomycin, viomycin, enviomycin

•*Fluoroquinolones:e.g.ciprofloxacin, levofloxacin, moxifloxacin

•*Thioamidese:e.g.ethionamide,prothionamide

•*cycloserine•* p-aminosalicylic acid

Third line•Other drugs that may be useful, but are not on

the WHO list of SLDs:•rifabutin

•macrolides e.g.clarithromycin•linezolid

•thioacetazone•thioridazine

•arginine•These drugs may be considered "third-line drugs"

and are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive

Mode of action & Recommended dose mg/kg

Essential anti-tuberculosis drug

Mode of action

Daily dose mg/kg

3times/wk

Twice/wk

INH bactericidal

51015

Rifampicin bactericidal

101010

pyrazinamide

bactericidal

253550

streptomyicin

bactericidal

151515

Ethambutol bacteriostatic

153045

PharmacokineticDrugs name

Half-lifeMetabolismExcretion

rifampicin 6 to 7 hours Hepatic and intestinal wall

renal 15to 030%Faecal 60%

INH 0.5-1.6h (fast acetylators), 2-5h (slow acetylators)

liver urine (primarily), feces

Ethambutol 3-4 hr (increased in impaired renal function)

liver renal

pyrazinamide 9-10hr liver renal

streptomycin5-6hrWithout hepatic metabolism

renal

•

• •

Drugs names

Adverse effects

cautions contraindications

interaction Results

INH *Nausea *vomiting

*peripheral neuritis

*Convulsion

*psychotic episodes

*allergic reactions

*blood dyscrasias

*hepatic impairmet

*renal impairment

*epilepsy

*alcohol dependence

*breast-feeding

drug-induced liver disease

*Carbamazepine

&phynetoin

*Carbamazepine

*Antacids

↑toxicity of these drugs

↑INH hepatotoxicity

INH effects↓

Drugs names

Adverse effects

cautionscontraindications

interaction Results

Rifampicin

GI disturbance,

liver damage ,

influenza-like syndrome some times with thrombocytopenia, haemolytic anaemia, shock and renal failure

(particularly with intermittent therapy)

may coloure skin, urine, saliva & terars orange-red

*hepatic impairment

*pregnancy & breast-feeding,

advise patients on hormonal contraceptive to use additional means ,

*discolours soft contact lenses

jaundice

Phenytoin

Digoxin

Theophylline

Oral anticoagulant

Contraceptive

b-blockers

Sulphonylureas

↓Effects of these drugs

Drugs names

Adverse effects

cautionscontraindications

interaction

Results

Ethambutol

optic neuritis, red/green colour blindness, peripheral neuritis,

rarely rash, pruritus, urticaria, thrombocytopenia

reduce dose in renal impairment and if creatinine clearance less than 30 mL/minut

*children under 6 years

optic neuritis, poor vision

Almunium hydroxide

↓effect of

Ethambutol

Drugs names

Adverse effects

cautionscontraindications

interaction

result

pyrazinamide

Liver damage,

hyperuricemia,

*GI disturbance, arthralgia, rash

and occasionally photosensitivity

*diabetes

*gout

*renal dysfunction

Liver damage

Probenecid

Sulfinpyrazone

antagonize effects of these drugs

Drugs names

Adverse effects

cautionscontraindications

interaction

Results

streptomycin

*ototoxicity

•reversible nephrotoxicty

neuromascular blockade with apnea

↑ dose interval in renal dysfunction

*pregnan

cy

myasthenia gravis

*Cephalosprins,cycloserine,

vancomycin,

amphotericin,furosemide

*Loop diuretic

,vancomycin,

neuromascular blockers

↑nephrotoxicty

↑ototoxicity

↑skletal muscle paralysis

•

•Pregnancy and breast-feeding•The standard regimen may be used

during pregnancy and breast-feeding

•

•Streptomycin which is ototoxic to fetus should not given in pregnancy

•Liver disease• patients with established chronic

liver disease should not recived pyrazinamide

•recommended regimens are;

•2SHRE/6HR OR 2SHE/10HE

Epilepsy

•INH may be associated with an increased risk of seizures .

•Pyridoxine 10 mg daily should be given to all epileptics taking INH .

•There is no evidence that INH causes seizures in patients who are not epileptic.

• TB treatment involves numerous drug interactions with anti-epileptic drugs and serum drug levels should be closely monitored .

• There are serious interactions between rifampicin and carbamazepine, rifampicin and phenytoin, and rifampicin and

sodium valproate .

Kidney disease

•*Isoniazid ,rifampicin and pyrazinamide are either eliminated almost entierly by biliary excretion or metabolized into non toxic substance.

•*these drugs may be given in normal dosage to patients with renal dysfunction.

•*In sever renal failure patients should recived pyridoxine with isoniazid in order to prevent peripheral neuropathy.

•*Streptomycin & Ethambutol can given in reduced dose under close monitoring of renal function (since these drugs are excreted by the kidney).

•*Thiocetazone, which is partially in urine, but has a narrow margin of safety , should be avoided in patients with renal failure

•*When using 2HRZ/4HR in patients on dialysis, the drugs should be given daily

during the initial high-intensity phase .

•*In the continuation phase, the drugs should be given at the end of each haemodialysis session and no dose should be taken on non-dialysis days.