First-line Agents to Treat Tuberculosis – Antimycobacterial Agents

by Pravin Shukle, MD

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    00:00 So isoniazid is probably the first drug you need to know.

    00:05 It's very similar to pyridoxine.

    00:07 It inhibits cell wall production in M.tuberclosis.

    00:12 So the bacteria itself is not able to make it cell wall.

    00:15 Resistance develops and it's rapidly developing if you're not using with other medications.

    00:21 It's often due to a point mutation one or two points, one of two points that code for the critical enzymes responsible for making the cell wall.

    00:30 It is not effective against a lot of dominant organisms however.

    00:35 In terms of the toxicity, the biggest thing that we are concerned about is neurotoxicity, which includes restless leg, peripheral neuritis and those thing we treat with vitamin B or pyridoxine.

    00:47 Hepatotoxicity is a concern as well.

    00:50 You can develop abnormal liver function tests.

    00:53 You can develop jaundice and you can develop hepatomegaly.

    00:57 So it's important that you monitor liver function tests regularly.

    01:01 And you do a clinical exam on these patients too.

    01:04 One of the problems that we have with isoniazid is that it interactions with other medications which include carbamazepine, phenytoin and warfarin.

    01:14 So clearly this agent is working through the cytochrome system.

    01:18 One of the other issues that we worry about is hemolysis in those patients who have gluco 6 phosphotate deficiency.

    01:25 So this is an important part of your history before you prescribe this drug.

    01:31 Another agent that we use in TB treatment is rifampin.

    01:35 So rifampin you became very familiar it with when we were talking about inducers and inhibitors of cytochrome.

    01:42 It's very bactericidal side against mycobacterium tuberculosis.

    01:47 Now remember that the drug itself is quite orange colored.

    01:50 So it may discolor urine and it may discolor the feces.

    01:53 And sometimes the patients come in and freaked out because as they are peeing out orange.

    01:57 Just reassure them that's totally normal with this pill.

    02:00 It's usually used in combination.

    02:02 Sometimes we use it individually.

    02:05 But quite frankly in the last 15 years I've never seen it used individually.

    02:09 It's given as prophylaxis to family members of TB patients on a fairly regular basis now.

    02:16 In terms of how it works, it inhibits DNA dependent RNA polymerase.

    02:21 And rifampin is the prototypical cytochrome inducers I mentioned before.

    02:26 So you'll hear a lot about this agent way out of proportion to it's level of use in the community.

    02:32 In terms of resistance to rifampin, it is due to changes in drug binding of this polymerase.

    02:39 In terms of toxicity, the toxicity is really light changed proteinuria, skin rashes and thrombocytopenia.

    02:46 You can also get nephritis and hepatic dysfunction too.

    02:50 Rifabutin is in the same class as rifampin.

    02:55 And it's equally as effective as rifampin.

    02:57 And it's actually preferred in HIV positive patients because it has fewer cytochrome inducer effects.

    03:04 Rifamixin is also another agent in the same drug class.

    03:08 And we've used this in traveler's diarrhea in the past.

    03:12 Let's move on to ethambutol or ETB.

    03:15 It is an inhibitor of arabinosyltranferases.

    03:19 Now this particular protein is a component of cell walls.

    03:26 It is well absorbed and it is excreted in the urine.

    03:29 And it is always given in combination with other antituberculosis agents.

    03:34 The toxicity of ethambutol is usually reserved to visual disturbances.

    03:40 So patients interestingly enough complain red or green color blindness.

    03:44 They may also develop an optic neuritis or retinal damage.

    03:47 So a very close evaluation of their ocular system, their visual system is really important.

    03:53 Sometimes patients may also develop headache and they can also develop confusion and hyperuricemia.

    04:00 One of the other rare complications of this medication is peripheral neuritis.

    04:05 Pyrazinamide is always given in combination with other drugs.

    04:10 It's well absorbed.

    04:11 It's excreted in the urine.

    04:13 And it's half life is increase in the liver or renal failure.

    04:16 Pyrazinamide has non-gouty polyarthalgia and that's really common up to 40% of patients develop this.

    04:24 They also often will get asymptomatic hyperucemia, myalgias, rash and hepatic dysfunction.

    04:31 Remember that you want to avoid this agent in pregnancy.

    04:34 Streptomycin is aminoglycoside, I eluded to it earlier.

    04:39 It's used in resistance strains of tuberculosis.

    04:43 And it's main concern like all aminoglycosides is renal toxicity or renal dysfunction.

    04:49 And of course we mentioned before that aminoglycosides are involved with otosclerosis and ototoxicity including some auditory as in not being able to hear toxicity.

    05:02 Amikacin is used in drug resistant TB infections.

    05:08 We also use ciprofloxacin and ofloxacin drug resistant TB.

    05:14 And we can use in combination with the other TB drugs.

    05:20 Ethionamide is a drug that is very similar to isoniazid.

    05:24 It's used in patients who have isoniazid resistant strains of TB.

    05:29 Now paraaminosalicyclic acid or PAS is also used but rarely now because the resistance is common.

    05:39 It's relatively toxic agent causes lot of GI irritation and peptic ulceration.

    05:44 You don't need to know this for your exam.

    05:46 But in case you ever come across this, you just know that is one of these agents that we use a lot but not so much anymore.

    About the Lecture

    The lecture First-line Agents to Treat Tuberculosis – Antimycobacterial Agents by Pravin Shukle, MD is from the course Antimicrobial Pharmacology. It contains the following chapters:

    • Tubercolosis Agents - First Line Drugs
    • Tubercolosis Agents - Second Line Drugs

    Included Quiz Questions

    1. Rifampin
    2. Ethambutol
    3. Streptomycin
    4. Isoniazid
    5. Dapsone
    1. Start pyridoxine and continue isoniazid.
    2. Discontinue isoniazid immediately, but maintain the other drugs in the regimen.
    3. Observe the patient only, as it is usually a self-limiting side effect.
    4. Switch to the 2nd line regimen of antituberculosis drugs.
    5. Start probenecid and decrease dose of isoniazid.
    1. Rifampin
    2. Isoniazid
    3. Streptomycin
    4. Pyrazinamide
    5. Ethambutol
    1. Rifabutin has less cytochrome induction activity.
    2. Rifabutin also has activity against the HIV virus.
    3. Rifabutin is metabolized in the liver while rifampin is metabolized in the kidney.
    4. Rifampin has a higher risk for renal failure compared to rifabutin.
    5. The HIV virus produces esterases which break down rifampin but not rifabutin.
    1. Non-gouty polyarthralgia
    2. Gout
    3. Visual disturbances
    4. Orange discoloration of urine and feces
    5. Myalgia
    1. Isoniazid
    2. Ethambutol
    3. Clarithromycin
    4. Streptomycin
    5. Rifampin

    Author of lecture First-line Agents to Treat Tuberculosis – Antimycobacterial Agents

     Pravin Shukle, MD

    Pravin Shukle, MD

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