Microbiology pharm – TB drugs

MOA is inhibition of DNA-dependent RNA polymerase.

USMLE will simultaneously list the wrong answer choice RNA-dependent DNA polymerase. Way to remember the MOA is:

RDR –> Rifampin is a DNA-dependent RNA polymerase.

Inhibition of arabinosyl transferase = ethambutol.

Inhibition of fatty acid synthase I = pyrazinamide.

Inhibition of mycolic acid synthesis = isoniazid (INH).

MOA is inhibition of mycolic acid synthesis.

Inhibition of arabinosyl transferase = ethambutol.

Inhibition of fatty acid synthase I = pyrazinamide.

Inhibition of DNA-dependent RNA polymerase = rifampin.

MOA is inhibition of fatty acid synthase I.

Inhibition of arabinosyl transferase = ethambutol.

Inhibition of mycolic acid synthesis = isoniazid (INH).

Inhibition of DNA-dependent RNA polymerase = rifampin.

MOA is inhibition of arabinosyl transferase

Inhibition of fatty acid synthase I = pyrazinamide.

Inhibition of mycolic acid synthesis = isoniazid (INH).

Inhibition of DNA-dependent RNA polymerase = rifampin.

Orange bodily secretions.

• Tears, sweat, and urine can all turn an orange or rusty tinge.
• This is a normal finding. USMLE can turn this into a pharm-behavioral science type Q, where the patient is concerned that, e.g., his contact lenses turn an orange color, and the correct physician response is: “this is a benign and normal finding of your medication.”

Upregulation of P-450.

• • If patient has TB and is simultaneously on HAART therapy for HIV, rifampin is avoided because it increases metabolism of the anti-retroviral meds. Rifampin may be replaced with rifapentine (does not upregulate P-450).
  • If patient is on anti-epileptic meds (i.e., phenytoin, carbamazepine, valproic acid, etc.), giving rifampin might precipitate seizures –> i.e., increased metabolism of the anti-epileptics.

Hepatotoxicity.

• Increased LFTs; patient’s LFTs should be checked before commencement.
• Mild transaminitis is a normal finding in patients commencing hepatotoxic agents. For instance: patient commences rifampin (or a statin, or lithium, etc.) + LFTs increase slightly –> answer = “maintain dose of the drug”; discontinuation of the drug or decreasing the dose is the wrong answer; once again, mild elevation in LFTs is normal.
• RIP –> mnemonic for TB drugs that are hepatotoxic –> Rifampin, Isoniazid, Pyrazinamide.

a)

Empiric treatment for bacterial meningitis (before culture results are known but CSF suggests bacterial): ceftriaxone + vancomycin.

Treatment for confirmed Neisseria meningitides meningitis = ceftriaxone.

b)

Prophylaxis given to close-contacts of someone with confirmed Neisseria meningitides meningitis (i.e., roommates + those living on the same floor in the dormitory) = rifampin.

Patients with H. influenzae type B epiglottitis receive ceftriaxone as the treatment; but close contacts get rifampin.

Same is true for confirmed Niesseria meningitides meningitis: ceftriaxone as Tx, but close contacts get rifampin.

Added to endocarditis treatment when the patient has prosthetic material in the heart.

For instance, empiric Tx for endocarditis (i.e., when we don’t yet know the organism) is gentamicin PLUS either vancomycin or ampicillin/sulbactam.

If the patient has a prosthetic valve, we add rifampin, so empiric becomes: gent + vanc + rifampin, OR gent + ampicillin/sulbactam + rifampin.

Isoniazid (INH) can cause vitamin B6 (pyridoxine) deficiency –> presents as miscellaneous neuropathy and/or seizures –> i.e., paresthesias, numbness, seizures.

• • Do not confuse pyridoxine, which is the medical term for vitamin B 6, with the TB drug pyrazinamide.

Isoniazid inhibits P-450.

RIP –> mnemonic for TB drugs that are hepatotoxic –> Rifampin, Isoniazid, Pyrazinamide.

Isoniazid (INH) can cause a high anion-gap metabolic acidosis.

• It is part of MUDPILES –> Methanol, Uremia, DKA, Phenformin, Iron supplements / INH, Lactic acidosis, Ethylene glycol, Salicylates.

Anion gap is elevated if 13 or greater.

It is calculated as Na – (Cl + HCO3).

In this case: 140 – (104 + 20) = 140 – 124 = 16.

Isoniazid (INH) can cause drug-induced lupus erythematosus (DILE).

• Anti-histone antibodies + arthritis + many other findings such as erythema nodosum, pleuritis, mediastinitis, pericarditis, anti-hematologic cell line antibodies causing thrombocytopenia, erythropenia, and/or leukopenia.
• Malar rash and renal phenomena are rare in DILE. These are common in systemic lupus erythematosus (SLE).

USMLE answer for monoprophylaxis of TB is 9 months INH + vitamin B6.

• That is, when the patient has a (+) PPD test but negative CXR, the answer is “treat for latent TB” or “TB prophylaxis” (same thing, and both are answers). But the Q can also just ask for “9 months INH + pyridoxine” (once again, don’t confuse with pyrazinamide).
• Preferred over rifampin as monoprophylaxis because it’s not as hepatotoxic.
• When the patient has a (+) PPD and then also has a (+) CXR, the answer is “treat for active TB” –> RIPE for 2 months, then just RI for 4 more months (6 months total of Tx for most patients).
• For a detailed post on the TB treatment algorithm/protocol, see here (open as separate tab or you’ll leave this page).

When the patient has a (+) PPD test but negative CXR, the answer is “treat for latent TB” or “TB prophylaxis” (same thing, and both are answers) –> 9 months INH + pyridoxine (medical term for vitamin B6, don’t confuse with pyrazinamide).

Pyrazinamide.

In other words, pyrazinamide is the answer if they ask which TB drug is most effective against Mycobacteria that have already been phagocytosed.

Hepatotoxicity.

• RIP –> mnemonic for TB drugs that are hepatotoxic –> Rifampin, Isoniazid, Pyrazinamide.

Hyperuricemia –> causes gout.

1) Ocular toxic –> central scotoma; red-green color-blindness; blurry vision.