Tag: Ethambutol

Ethambutol

Ethambutol


ETHAMBUTOL

INTRODUCTION:

  • One of the first-line anti-tubercular drug.
  • Given in combination with Isoniazid, Rifampin & Pyrazinamide.

MECHANISM OF ACTION:

  • Selectively bacteriostatic active against Mycobacterial group including Mycobacterium avium complex (MAC).
  • Inactive against other bacterial types.
  • Inhibits mycobacterial arabinosyl transferases (Encoded by embAB gene).
  • Arabinosyl transferases essential for polymerization reaction of arabinogalactan, an essential component of mycobacterial cell wall.

RESISTANCE:

  • Due to mutations resulting in Emb gene product overexpression or within emb B structural gene.

PHARMACOKINETICS:

Absorption

  • Bioavailability: ~80%
  • Peak plasma time: 2-4 hr

Distribution

  • Widely throughout body.
  • Concentrated in kidneys, lungs, saliva, & RBC’s.

CSF:blood level ratio: 

  • 0% (normal meninges); 25% (inflamed meninges)
  • Protein binding: 20-30%

Metabolism

  • Hepatic (20%) to inactive metabolite.
  • Not a hepatotoxic antitubercular drug.

Elimination

  • Half-life elimination: 2.5-3.6 hr; 
  • In end-stage renal disease – 7-15 hr.
  • Hence, requires dose adjustment in renal conditions.
  • Excretion: ~50% urine; ~50% faeces as unchanged drug.

Pregnancy & Lactation

  • Pregnancy Category: B
  • Lactation: Enters breast milk; use with caution 

USES:

Used along with other medications to treats number of infections including:

  • Tuberculosis, 
  • Mycobacterium avium complex (MAC
  • Mycobacterium kansasii.
  • Under RNTCP, for diagnosis of MDR TB, currently, drug sensitivity testing is done for Rifampicin, Isoniazid and Ethambutol.

CONTRAINDICATIONS:

  • Optic neuritis.
  • In young children unable to report visual effects.
  • Hypersensitivity.

MONITORING PARAMETERS

  • Ophthalmologic exam
  • Platelet count
  • Serum creatinine/BUN
  • Serum uric acid

ADVERSE REACTION:

  • Acute gout/hyperuricemia.
  • Due to interference with urate excretion.
  • Abdominal pain
  • Anaphylaxis.
  • Confusion.
  • Disorientation.
  • Fever.
  • Headache.
  • LFT abnormalities.
  • Malaise & nausea.
  • Optic neuritis – Most important.
  • Is a dose & duration of therapy dependent toxicity.
  • Symptoms may include decreased acuity, colour blindness(green colour) or visual defects.
  • Usually are reversible with discontinuation.
  • Peripheral neuritis.
  • Rash.

DRUG INTERACTIONS:

  • Aluminium hydroxide  – Reduce rate or extent of ethambutol absorption. 
  • At least 4 hours should elapse between doses of aluminium hydroxide-containing antacids & ethambutol.

BCG vaccine:

  • Ethambutol may interfere with development of an immune response following Bacillus Calmette-Guerin vaccine, BCG. 
  • Vaccine is live & sensitive to commonly used antituberculosis agents (e.g., isoniazid, ethambutol, rifampin).
Exam Question
 
  • Ethambutol is not a hepatotoxic antitubercular drug.
  • Ethambutol is bacteriostatic.
  • Under the RNTCP, for diagnosis of MDR TB, currently, drug sensitivity testing is done for Rifampicin, Isoniazid and Ethambutol.
  • In ethambutol toxicity, there will be loss of ability to see green colour.
  • Retrobulbar neuritis is seen with ethambutol. 
  • Hyperuricemia is seen with ethambutol.
  • Ethambutol is avoided in children as it causes visual disturbance
  • Antitubercular drug causing gout is ethambutol.
Don’t Forget to Solve all the previous Year Question asked on Ethambutol

Ethambutol

Ethambutol

Q. 1

A 38 year old Indian origin male with known TB infection and taking medication since 1 month comes to the Eye OPD with complaint of visual disturbances including decreased visibility and slight color blindness. If these symptoms are due to his drug treatment, which one of the following drugs is most likely the cause of his symptoms?

 A Streptomycin
 B Ciprofloxacin
 C Ethambutol
 D Rifampicin
Q. 1

A 38 year old Indian origin male with known TB infection and taking medication since 1 month comes to the Eye OPD with complaint of visual disturbances including decreased visibility and slight color blindness. If these symptoms are due to his drug treatment, which one of the following drugs is most likely the cause of his symptoms?

 A Streptomycin
 B Ciprofloxacin
 C Ethambutol
 D Rifampicin
Ans. C

Explanation:

Ethambutol


Q. 2 The following is not a hepatotoxic antitubercular drug:
 A Ethambutol
 B INH
 C Rifampicin
 D Pyrazinamide
Q. 2 The following is not a hepatotoxic antitubercular drug:
 A Ethambutol
 B INH
 C Rifampicin
 D Pyrazinamide
Ans. A

Explanation:

Ethambutol


Q. 3

Which of the following is not a bactericidal agent?

 A

Rifampicin

 B

INH

 C

Pyrazinamide

 D

Ethambutol

Q. 3

Which of the following is not a bactericidal agent?

 A

Rifampicin

 B

INH

 C

Pyrazinamide

 D

Ethambutol

Ans. D

Explanation:

Rifampicin is bactericidal and effective against extracellular and intracellular bacilli.

INH is also effective against both intra and extracellular bacilli. It is more effective on rapidly multiplying bacilli.

Pyrazinamide is effective against the slow multipliers. Ethambutol is bacteriostatic.

 
Remember:
Streptomycin is bactericidal
Thiacetazone is bacteriostatic
 
Ref: Park, 21st Edition

Q. 4

Under the RNTCP, for diagnosis of MDR TB, currently drug sensitivity testing is done for:

 A

Rifampicin

 B

Rifampicin, Isoniazide

 C

Rifampicin, Isoniazide and Ethambutol

 D

Rifampicin, Isoniazide and Pyrazinamide

Q. 4

Under the RNTCP, for diagnosis of MDR TB, currently drug sensitivity testing is done for:

 A

Rifampicin

 B

Rifampicin, Isoniazide

 C

Rifampicin, Isoniazide and Ethambutol

 D

Rifampicin, Isoniazide and Pyrazinamide

Ans. C

Explanation:

Presently conventional solid egg-based Lowenstein-Jensen (LJ) media will be used for primary culture at the RNTCP accredited laboratory.

DST will be performed for streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) only.

Pyrazinamide (Z) sensitivity testing may be included at a later period of DOTS-Plus implementation.
 

Q. 5

In ethambutol toxicity there will be loss of ability to see which of the following colour?

 A

Red

 B

Green

 C

Blue

 D

Yellow

Q. 5

In ethambutol toxicity there will be loss of ability to see which of the following colour?

 A

Red

 B

Green

 C

Blue

 D

Yellow

Ans. B

Explanation:

Optic neuritis, the most serious adverse effect reported, typically presents as reduced visual acuity, central scotoma, and loss of the ability to see green (or, less commonly, red).

Ref: Harrisons Principles of Internal Medicine, 18th Edition, Page 1376.

 


Q. 6

Retrobulbar neuritis is seen with :

 A

Rifampicin

 B

Streptomycin

 C

Ethambutol

 D

Ethionamide

Q. 6

Retrobulbar neuritis is seen with :

 A

Rifampicin

 B

Streptomycin

 C

Ethambutol

 D

Ethionamide

Ans. C

Explanation:

 
The most important side effect is optic neuritis, resulting in decreased visual acuity and loss of ability to differentiate red from green. The incidence of this reaction is proportional to the dose of ethambutol and is observed in 15% of patients receiving 50 mg/kg/day, in 5% of patients receiving 25 mg/kg/day, and in <1% of patients receiving daily doses of 15 mg/kg. The intensity of the visual difficulty is related to the duration of therapy after the decreased visual acuity first becomes apparent and may be unilateral or bilateral. Tests of visual acuity and red-green discrimination prior to the start of therapy and periodically thereafter are thus recommended. Recovery usually occurs when ethambutol is withdrawn; the time required is a function of the degree of visual impairment.
 
Ref : Gumbo T. (2011). Chapter 56. Chemotherapy of Tuberculosis, Mycobacterium Avium Complex Disease, and Leprosy. In B.C. Knollmann (Ed), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

Q. 7

All of the following are examples of bactericidal drugs except –

 A

INH

 B

Rifampicin

 C

Ethambutol

 D

Pyrazinamide

Q. 7

All of the following are examples of bactericidal drugs except –

 A

INH

 B

Rifampicin

 C

Ethambutol

 D

Pyrazinamide

Ans. C

Explanation:

Ans. is ‘c’ i.e., Ethambutol

o All first line drugs are tuberculocidal except ethambutol which is tuberculostatic. Tuberculocidal –> Rifampin, INH, streptomycin, pyrazinamide.

Tuberculostatic —> Ethambutol, PAS, cycloserine, thioacetazone.


Q. 8

All are features of ethambutol toxicity, except ‑

 A

Retrobulbar neuritis

 B

Colour vision defects

 C

Hyperuricemia

 D

Hypercalcemia

Q. 8

All are features of ethambutol toxicity, except ‑

 A

Retrobulbar neuritis

 B

Colour vision defects

 C

Hyperuricemia

 D

Hypercalcemia

Ans. D

Explanation:

Ans. is ‘d’ i.e., Hypercalcemia


Q. 9

Optic neuritis is caused by –

 A

Ethambutol

 B

Pyrazinamide

 C

Rifampicin

 D

Chlormycetin

Q. 9

Optic neuritis is caused by –

 A

Ethambutol

 B

Pyrazinamide

 C

Rifampicin

 D

Chlormycetin

Ans. A

Explanation:

Ans. is ‘a’ i.e., Ethambutol


Q. 10

Ethambutol is avoided in children as it causes –

 A

Dental maldevelopment

 B

Visual disturbance

 C

Renal failur

 D

Growth retardation

Q. 10

Ethambutol is avoided in children as it causes –

 A

Dental maldevelopment

 B

Visual disturbance

 C

Renal failur

 D

Growth retardation

Ans. B

Explanation:

Ans. is ‘b’ i.e., Visual disturbance

o The main adverse effect of Ethambutol is retrobulbar optic neuritis (unilateral or B/L).

o This causes loss of visual activity, red-green colour blindness, central scotoma, peripheral vision loss. o The changes reverse, if the t/t is stopped promptly if not, the patient may go blind.

o Children below 6 years of age are not given ethambutol because children are unable to report early visual deterioration. o Ethambutol also produces hyperuricemia.


Q. 11

Which of the following is not a hepatotoxic drug ‑

 A

Ethambutol

 B

Rifampicin

 C

INH

 D

Pyrazinamide

Q. 11

Which of the following is not a hepatotoxic drug ‑

 A

Ethambutol

 B

Rifampicin

 C

INH

 D

Pyrazinamide

Ans. A

Explanation:

Ans. is ‘a’ i.e., Ethambutol


Q. 12

Which one of the following therapies would be safe in a patient with pulmonary tuberculosis having markedly abnormal liver function –

 A

Streptomycin + isoniazid

 B

Ethambutol + isoniazid

 C

Rifampicin + isoniazid

 D

Streptomycin + ethambutol

Q. 12

Which one of the following therapies would be safe in a patient with pulmonary tuberculosis having markedly abnormal liver function –

 A

Streptomycin + isoniazid

 B

Ethambutol + isoniazid

 C

Rifampicin + isoniazid

 D

Streptomycin + ethambutol

Ans. D

Explanation:

Ans. is ‘d’ i.e., Streptomycin + ethambutol

o Antitubercular drugs which do not require dose adjustment in hepatic disease.

Streptomycin          Rifabutin            Ethambutol


Q. 13

Which of the following ATT drugs is associated with visual deterioration

 A

INH

 B

Rifampicin

 C

Capreomycin

 D

Ethambutol

Q. 13

Which of the following ATT drugs is associated with visual deterioration

 A

INH

 B

Rifampicin

 C

Capreomycin

 D

Ethambutol

Ans. D

Explanation:

D i.e. Ethambutol

  • The common agents which lead to toxic amblyopia or chronic retrobulbar neuritis are – tobacco Q, methyl
    alcohol Q, ethyl alcohol, lead, arsenic, quinine Q, carbon di sulphide, cannabis indica and ethambutol Q
  • Ethambutol is contraindicated in children below 6 yearsQ because young children may be unable to report early visual impairment.
  • Ethambutol amblyopia presents with defective colour vision, reduced visual acuity and central or centrocaecal scotoma but when optic chiasma is involved a bitemporal hemianopia develops.

Q. 14

Which antitubercular drug combination is safer in a patient who develops hepatitis white on ATT:

March 2005

 A

Streptomycin+Isoniazid

 B

Streptomycin+Ethambutol

 C

Ethambutol+Isoniazid

 D

Ethambutol+Rifampicin

Q. 14

Which antitubercular drug combination is safer in a patient who develops hepatitis white on ATT:

March 2005

 A

Streptomycin+Isoniazid

 B

Streptomycin+Ethambutol

 C

Ethambutol+Isoniazid

 D

Ethambutol+Rifampicin

Ans. B

Explanation:

Ans. B: Streptomycin+Ethambutol

Hepatitis is a major side effect of isoniazid, pyrazinamide and rifampicin.

In case hepatitis develops, all these drugs should be stopped and S+E may be started or continued.

When the reaction clears, the above drug is added one by one to identify the culprit, which should never be used again, while the others found safe should be continued.

It is best to avoid Pyrazinamide in patients who once developed hepatitis.


Q. 15

Antitubercular drug causing gout is:        

March 2005

 A

Streptomycin

 B

Ethambutol

 C

Rifampicin

 D

None

Q. 15

Antitubercular drug causing gout is:        

March 2005

 A

Streptomycin

 B

Ethambutol

 C

Rifampicin

 D

None

Ans. B

Explanation:

Ans. B: Ethambutol

Drugs causing gout/hyperuricemia include

  • Diuretics
  • Low-dose salicylate
  • Cyclosporine
  • Pyrazinamide
  • Ethambutol
  • Levodopa 1
  • Nicotinic acid
  • Methoxvflurane

Q. 16

Antitubercular drug which is least hepatotoxic:

September 2010

 A

Rifampicin

 B

Pyrazinamide

 C

Ethambutol

 D

INH

Q. 16

Antitubercular drug which is least hepatotoxic:

September 2010

 A

Rifampicin

 B

Pyrazinamide

 C

Ethambutol

 D

INH

Ans. C

Explanation:

Ans. C: Ethambutol

The single biggest problem with TB treatment is drug-induced hepatitis, which has a mortality rate of around 5%. Three drugs can induce hepatitis: PZA, INH and RMP (in decreasing order of frequency). It is not possible to distinguish between these three causes based purely on signs and symptoms.


Q. 17

The antitubercular drug safe in liver disease is:

September 2011

 A

INH

 B

Rifampin

 C

Ethambutol

 D

Pyrazinamide

Q. 17

The antitubercular drug safe in liver disease is:

September 2011

 A

INH

 B

Rifampin

 C

Ethambutol

 D

Pyrazinamide

Ans. C

Explanation:

Ans. C: Ethambutol

  1. Approximately 50% of the oral dose of Ethambutol is eliminated unchanged in the urine within 24 hours; 15% of the drug is excreted in the form of 2 metabolites

Its serious toxicity is ocular

Ethambutol/ EMB/ E

  • It is a bacteriostatic antimycobacterial drug
  • Adverse effects of ethambutol are:

– Optic neuritis: Hence contraindicated in children below 6 yrs of age.

– Red-green color blindness

– Peripheral neuropathy

– Arthralgia

– Hyperuricaemia

– Vertical nystagmus

–  Milk skin reaction

  • Ethambutol is bacteriostatic against actively growing TB bacilli.
  • It works by obstructing the formation of cell wall.
  • Mycolic acids attach to the 5′-hydroxyl groups of D-arabinose residues of arabinogalactan and form mycolyl­arabinogalactan-peptidoglycan complex in the cell wall.
  • It disrupts arabinogalactan synthesis by inhibiting the enzyme arabinosyl transferase.
  • Disruption of the arabinogalactan synthesis inhibits the formation of this complex and leads to increased permeability of the cell wall
  • It is well absorbed from the gastrointestinal tract and well distributed in body tissues and fluids, 50% is excreted unchanged in urine.

Q. 18

Drug causing toxic optic neuropathy is:

March 2009

 A

Pyrazinamide

 B

Chloroquine

 C

Ethambutol

 D

Tetracycile

Q. 18

Drug causing toxic optic neuropathy is:

March 2009

 A

Pyrazinamide

 B

Chloroquine

 C

Ethambutol

 D

Tetracycile

Ans. C

Explanation:

Ans. C: Ethambutol

Causes of nutritional optic neuropathy include tobacco, ethanol, thiamine, and vitamin B-12.

  • Causes of toxic optic neuropathy include chemicals and drugs, such as methanol, ethylene glycol, ethambutol, isoniazid, digitalis, cimetidine, vincristine, cyclosporine, toluene, and amiodarone.
  • Chloroquine causes loss of vision due to retinal damage. Corneal deposits may also occur and affect vision, but are reversible on discontinuation.

Q. 19

Bacteriostatic anti TB drug ‑

 A

INH

 B

Rifampicin

 C

Ethambutol

 D

Pyrazinamide

Q. 19

Bacteriostatic anti TB drug ‑

 A

INH

 B

Rifampicin

 C

Ethambutol

 D

Pyrazinamide

Ans. C

Explanation:

Ans. is ‘c’ i.e., Ethambutol

Remember the following facts

  • All cell wall synthesis inhibitors are bactericidal.
  • All antibacterial drugs that act on cell membrane are bactericidal.
  • All first line antitubercular drugs are bactericidal except ethambutol that is bacteriostatic.
  • All protein synthesis inhibitors are bacteriostatic except aminoglycosides & streptogramins which are bactericidal.
  • All drugs affect intermediary metabolism are bacteriostatic.
  • Now, it will be very easy to remember the following table

Q. 20

Part of ethambutol in RNTCP regime ‑

 A

Bactericidal + detrimental to semidormant bacilli

 B

Bactericidal + detrimental to dormant bacilli,

 C

Bactristatic + detrimental to fast multiplying bacilli

 D

Bacteristatic + detrimental to slow multiplying bacilli

Q. 20

Part of ethambutol in RNTCP regime ‑

 A

Bactericidal + detrimental to semidormant bacilli

 B

Bactericidal + detrimental to dormant bacilli,

 C

Bactristatic + detrimental to fast multiplying bacilli

 D

Bacteristatic + detrimental to slow multiplying bacilli

Ans. C

Explanation:

Ans. is ‘c’ i.e., Bactristatic + detrimental to fast multiplying bacilli

Ethambutol

  • It is selectively bacteriostatic and is active against MAC as well as some other mycobacteria.
  • Fast multiplying bacilli are more susceptible
  • With the triple drug therapy it hastens the sputum conversion and also helps to prevent the development of resistance (primary purpose of using it).
  • It inhibits arabinosyltransferase involved in arabinogalactan synthesis, therby interfering with mycolic acid incorporationin mycobacterial cell wall.

Q. 21

All of the following are bactericidal drugs except‑

 A

Ethambutol

 B

Isoniazid

 C

Rifampicin

 D

Pyrazinamide

Q. 21

All of the following are bactericidal drugs except‑

 A

Ethambutol

 B

Isoniazid

 C

Rifampicin

 D

Pyrazinamide

Ans. A

Explanation:

Ans. is ‘a’ i.e., Ethambutol

All first line drugs are tuberculocidal except ethambutol which is tuberculostatic.

Tuberculocidal → Rifampin, INH, streptomycin, pyrazinamide.

Tuberculostatic → Ethambutol, PAS, cycloserine, thioacetazone.


Q. 22

Toxic amblyopia can be caused by ‑

 A

Ethanol

 B

Methanol

 C

Ethambutol

 D

All

Q. 22

Toxic amblyopia can be caused by ‑

 A

Ethanol

 B

Methanol

 C

Ethambutol

 D

All

Ans. D

Explanation:

Ans. is ‘d’ i.e., All 

  • Toxic amblyopia is chronic retrobulbar neuritis which results from the damage to optic nerve by the exogenous poisons.
  • It is frequently bilateral and has a chronic course with permanent visual deterioration.
  • The toxic agents involve may be : Tobacco, ethyl alcohol, methyl alcohol, ethylene glycol, lead, arsenic, cannabis
  • indica, carbon di-sulphide, various drugs like quinine, chloroquine, ethambutol, isoniazid, streptomycin, digitalis (digoxin), amiodaron, NSAIDs, vigabatrin and disulfiram.


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