PRESENTED BY :ARIF KAHN

PAS (Para-aminosalicylic acid or PASER);

PAS-sodium (Para-aminosalicylic acid

sodium)

PAS was discovered in 1944. Initially, PAS was

used to treat TB, but with the discovery of

other more potent drugs including

rifampicin, its use in first line regimens was

discontinued.

Trade Names=Paser

Competitively antagonizes metabolism of

para-aminobenzoic acid, resulting in

bacteriostatic activity against Mycobacterium

tuberculosis .

Absorption

T max is about 6 h; C max is about 20 mcg/mL.

Distribution

About 50% to 60% is protein bound.

Elimination

80% is excreted in the urine with at least 50%

excreted in acetylated form. The t 1/2 of free

aminosalicylic acid is 26.4 min.

Adults:150 mg/kg daily (max dose 12 g)

Take PAS twice daily, generally 4g per dose PASER granules should be taken with an acidic liquid such as fruit juice

Adults with liver damage -creatine clearance < 30 ml/min:150 mg/kg daily (max dose 12 g) No change to dosage. PAS-sodium should be avoided.

Children:

150 mg/kg daily (max dose 8 g)

PAS is a chemotherapeutic agent. The precise

mechanisms of action are unknown.

The most common side effects of PAS are persistent nausea, vomiting and diarrhoea. If the patient experiences fatigue, it may be due to hypothyroidism (when the thyroid gland produces insufficient thyroid hormone) caused by PAS.

PAS may cause hepatitis (inflammation of the liver), usually preceded by a rash or a fever. Other occasional side effects include increased prothrombin time (time for blood to clot) and malabsorption syndrome (disorders in the intestines' ability to absorb nutrients).

While there is no dose adjustment for patients with liver disease, PAS should be avoided in patients with severe liver disease as it may cause crystalluria (crystals in the urine). PAS should not be taken by patients that are allergic to aspirin.

Cycloserine is part of a group of drugs used in

the treatment of drug resistant TB called oral

bacteriostatic second-line agents. It is used as

part of treatment regimens, generally involving

5 medicines, to treat MDR and XDR TB. It was

originally discovered in 1952.

Cycloserine is also sometimes used to treat

urinary tract and other types of infections that

have not responded to other treatments.

Cycloserine may also be used for purposes other

than those listed in this medication guide.

Cycloserine works as an antibiotic by

inhibiting cell-wall biosynthesis in

bacteria. As a cyclic analogue of D-alanine,

cycloserine acts against two crucial enzymes

important in the cytosolic stages

of peptidoglycan synthesis: alanine

racemase (Alr) and D-alanine:D-alanine ligase

Adults:15 – 20 mg/kg daily (max dose 1000

mg)

Adults with liver damage -creatine clearance

< 30 ml/min:250 mg once daily or 500 mg

three times a week

Children:10 – 20 mg/kg daily (max dose 1000

mg)

Cycloserine is associated with neurologic and

psychiatric disturbances. Side-effects include

chronic headaches, dizziness, nightmares,

depression, anxiety, hearing voices or seeing

things that do not exist, confusion, sleep

disturbances and coma.

Cycloserine may also cause rashes,

peripheral neuropathy (burning/tingling

sensation in the hands and feet), jaundice

(yellowing of the eyes and skin) and vision

disturbances.

Cycloserine should not be given to patients with

epilepsy, severe depression or psychosis, severe

kidney failure or patients that excessively abuse

alcohol.

Cycloserine is in the FDA pregnancy category C.

This means that it is not known whether

cycloserine will harm an unborn baby. Do not take

this medication without first talking to your doctor

if you are pregnant

Cycloserine passes into breast milk, and it is not

known whether cycloserine will harm a nursing

baby. Do not take this medication without first

talking to your doctor if you are breast-feeding a

baby.

Terizidone is part of a group of drugs used in

the treatment of drug resistant TB called

oral bacteriostatic second-line agents. It is

used as part of treatment regimens,

generally involving 5 medicines, to treat MDR

and XDR TB. Terizidone is obtained by

combining tw o molecules of cycloserine.

Terizidone acts by preventing cell wall

synthesis by inhibiting two necessary

enzymes.

Adults:15 – 20 mg/kg daily (max dose 1000

mg)

Children:10 – 20 mg/kg daily (max dose 1000

mg)

All patients receiving terizidone should be

given 50 mg of pyridoxine for every 250 mg

of terizidone.

Terizidone is associated with neurologic and psychiatric disturbances. Symptoms can include severe depression, anxiety, panic attacks, psychosis, seeing and hearing things that do not exist, paranoia, dizziness, slurred speech and convulsions. Terizidone should be immediately halted if the patient is suicidal or psychotic. Terizidone should not be given to patients with epilepsy, severe depression or psychosis.

Terizidone may also cause nausea, vomiting and skin allergies.

Ethionamide (Eto)

Ethionamide is part of a group of drugs used

in the treatment of drug resistant TB called

thioamides. It is used as part of treatment

regimens, generally involving 5 medicines, to

treat MDR and XDR TB. It was discovered in

1956.

It has been proposed for use in combination

with gatifloxacin

Ethionamide is an antibiotic used in the

treatment of tuberculosis. The action may be

through disruption of mycolic acid.

Adults:15 – 20 mg/kg daily (max 1000 mg)

Adults with liver damage -creatine clearance < 30 ml/min:250 – 500 mg daily

Children:15 – 20 mg/kg daily (max 1000 mg)

Ethionamide is taken twice daily, generally one tablet (250 mg) in the daytime and 2 tablets (500 mg) at night.

Ethionamide is taken during the intensive and continuation phases of treatment.

Ethionamide can cause persistent nausea and vomiting. Decreasing the dosage will decrease the symptoms, which is why ethionamide is taken twice a day. Ethionamide may also cause dizziness and fatigue. Occasionally ethionamide may cause jaundice (yellowing of the skin and eyes) or changes in mood (depression) and allergic reactions. Rarely, ethionamidewill cause peripheral neuritis (tingling in the hands and feet) as well as vision disturbances.

It is recommended that ethionamide is avoided during pregnancy as it may increase nausea and vomiting. Ethionamide was shown to be teratogenic in animal studies.

Ethionamide should not be used in patients with severe liver disease or porphyria (a rare, inherited disease affecting the skin and nervous system). Blood sugar levels should be monitored in diabetic patients.