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INH

Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. It is often prescribed under the name INH. The chemical name is isonicotinyl hydrazine or isonicotinic acid hydrazide. more...

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It is available in tablet, syrup, and injectable forms (given via intramuscular injection), available world-wide, inexpensive to produce, and is generally well tolerated.

Mechanism of action

Isoniazid is a prodrug and must be activated by bacterial catalase. The active form inhibits the synthesis of mycolic acid in the mycobacterial cell wall.

Isoniazid reaches therapeutic concentrations in serum, cerebrospinal fluid (CSF), and within caseous granulomas. Isoniazid is metabolized in the liver via acetylation. There are two forms of the enzyme responsible for acetylation, so that some patients metabolize the drug quicker than others. Hence, the half-life is bimodal with peaks at 1 hour and 3 hours in the US population. The metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of renal failure.

Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.

Side effects

Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects, and drug interactions resulting in increased phenytoin (Dilantin) or disulfiram (Antabuse) levels.

Peripheral neuropathy and CNS effects are associated with the use of isoniazid and is due to pyridoxine (vitamin B6) depletion, but is uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10-50 mg/day) with isoniazid.

Reference

  • Core Curriculum on Tuberculosis (2000) Division of Tuberculosis Elimination, Centers for Disease Control and Prevention

See Chapter 6, Treatment of LTBI Regimens - Isoniazid
See Chapter 7 - Treatment of TB Disease Monitoring - Adverse Reactions to First-Line TB Drugs - Isoniazid
See Table 5 First-Line Anti-TB Medications

  • Isoniazid Overdose: Recognition and Management American Family Physician 1998 Feb 15

Read more at Wikipedia.org


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Diary: from a week in practice
From American Family Physician, 11/1/05 by Tony Miksanek

Monday

There are going to be occasions when doctors and patients butt heads. Mr. Zetes disappeared from my practice two years ago. I assumed he was avoiding me--not an easy thing to do when you live in a small town. I last saw him when he came for a routine checkup, and I recommended a colonoscopy to the 60-year-old man. He had never had one before. "No way," he roared. "No one's sticking a camera up my behind." His mind was made up. Mr. Zetes unexpectedly returned to my office this week. He handed me a copy of recent blood tests. All the results were normal except an elevated carcinoembryonic antigen (CEA) level of 24.6 ng per mL (24.6 mcg per L). He had changed doctors but not transferred his medical records. His new physician also had recommended a colonoscopy, but once again Mr. Zetes remained steadfastly opposed. I guess the two of them compromised on fecal occult blood testing and some laboratory tests. I made it clear to Mr. Zetes that the CEA is not a screening test for colon cancer. I mentioned some factors that might contribute to an abnormal CEA level, such as his habit of smoking cigarettes. He knew what was coming next, but still wiggled like a fish on a hook. "Maybe the lab made a mistake. Can't we recheck it? he pleaded. The repeat CEA level was 24.1 ng per mL (24.1 mcg per L). Two years and two opinions later, Mr. Zetes is finally getting a colonoscopy and maybe some extra tests, too.

Tuesday

Eleanor's blood pressure--156/94 mm Hg--has not budged since I checked it two weeks ago. The middle-aged woman had purchased her own sphygmomanometer. Her home systolic and diastolic readings averaged 4 to 6 mm Hg lower than the values obtained in my office. Her Stage 1 hypertension had been diagnosed four months earlier, and we opted to monitor it closely and try lifestyle changes. As it turned out, there really slim woman who already follows a healthy diet and exercises 60 minutes daily. She was willing to begin antihypertensive medication but only as a last resort. "I don't want to become dependent on a drug for the rest of my life," she told me after the hypertension was initially diagnosed, "but I don't want to have a stroke or heart attack either." This morning, I noticed the unmistakable scent of garlic in the room. Eleanor admitted she had been eating two or three cloves of fresh garlic every day and had upped her consumption of onions. "They're supposed to help lower blood pressure naturally," she reported. Eleanor then removed the lid of a shoe box she had brought with her. Inside the box were bottles containing supplements such as vitamin E, calcium, potassium, magnesium, and coenzyme Q10. "I reckon none of this stuff has done me much good," she said dejectedly. "It was worth a try," I consoled her. Eleanor was now ready to accept a prescription for hydrochlorothiazide (Hydrodiuril) 12.5 mg once daily. I don't know as much as I'd like to about complementary medicine, but I do know that I respect patients who are open to alternatives.

Wednesday

"Help," Annie begged. "I'm running out of doctors." The 32-year-old woman was a new patient with a rash that wouldn't stop itching. She had already seen another physician for the problem and had been to an urgent care clinic. Her rash had been diagnosed as contact dermatitis by one doctor and a possible bacterial skin infection by the other. Treatment with a methylprednisolone (Medrol) dose pack and later a course of dicloxacillin (Pathocil) didn't help at all. Her intense itching was especially bad at night. The rash appeared pimply and irritated. The papules were present primarily on the finger webs and wrists, but a few lesions had appeared on her chest. The two failed treatments and further spread of the rash helped establish the diagnosis. "Scabies," I said matter-of-factly. Annie was appalled. I think she was insulted because of her misconception that scabies is associated with poor personal hygiene or low social status. After two previous and unsuccessful medical encounters, she was skeptical of the diagnosis. "Is there a test to prove it?" she asked. A skin scraping was done and examined under the microscope to look for the presence of mites, eggs, or fecal matter. It was positive. I prescribed permethrin 5 percent cream (Elimite) and recommended a reapplication in one week. All household contacts had to be treated. I warned her that the pruritus might persist for another two to three weeks. Sarcoptes scabiei is a mischievous mite that can mimic other skin conditions and make many physicians scratch their heads.

Thursday

"A coal miner with a cough," Lucas chuckled. "I bet a dime a dozen." He had worked underground for more than 15 years. Unlike many of his coworkers, Lucas had never been a cigarette smoker. He had been coughing for several months but denied any shortness of breath, night sweats, hemoptysis, weight loss, or fever. He remembered that as a child he once had a skin test done after his uncle was diagnosed with tuberculosis (TB). "It was okay," he recalled. "I never had to take any medicine. I never had any more TB tests done after that." His physical examination was normal. Spirometry showed a forced vital capacity of 5.03 liters and forced expiratory volume of 4.05 liters. A purified protein derivative skin test was applied to his right forearm. Lucas developed 16 millimeters of induration at the site with considerable erythema and ulceration. Some calcified right hilar and paratra-cheal lymph nodes were present on his chest radiograph. A complete blood count and hepatic profile were normal. Three sputum samples for acid-fast bacillus smear and culture were negative. Lucas requires isoniazid (INH) and pyridoxine (vitamin [B.sub.6]) for six to nine months. "Let me get this straight," he said. "I but I still have to take medicine for six months, and the medicine puzzled look and then asked, "Am I missing something here?" I put my hand on his shoulder and owned up to my lack of an explanation for his cough. "Evidently, we both are," I admitted.

Friday

Gabriel was no angel. In fact, he was more like a monster when it came to playing high school football. The manner in which he recklessly threw his body around during games led me to believe that the teenage boy had absolutely no sense of self-preservation. "Play smart. Use your head out there," his mother yelled from her seat in the bleachers on one humid Friday night. I doubt Gabriel heard her advice down on the field, and if he did, surely it wasn't Gabriel was pulled out of the game after he absorbed a jarring hit to the head and sustained a concussion. Although he never lost consciousness, Gabriel was unable to recall anything immediately before and after the collision. He was unsteady on his feet and slightly confused. A few weeks later, I still refused to release Gabriel to return to playing football even though he swore that he felt fine. "Don't-hea o concentration also was worse than usual. Gabriel had postconcussion syndrome. He pleaded for clearance to return to practice, but my decision was firm. Besides, I had an ally. we're you," Gabriel's final." Doctors, parents, and coaches need a game plan h

Saturday/Sunday

Although he had lost most of his carrot-colored hair years ago, Rusty never had to worry about forfeiting his nickname. Now, the 63-year-old former cigarette smoker with type 2 diabetes and chronic obstructive pulmonary disease had much bigger concerns. Rusty had a resection of a Stage 1 carcinoma of the right lung but developed a postoperative empyema necessitating a repeat thoracotomy. Later, an abscess of the posterior chest wall occurred. Incision and drainage were performed and followed by a prolonged course of antibiotics. Rusty was allergic to penicillin and ciprofloxacin (Cipro). Just when things seemed to quiet down, he was back at my office with a lump the size of a lemon at the edge of his right thoracotomy incision. "More trouble," he muttered. It was a recurrent chest wall abscess. Aspiration yielded pus containing methicillin-resistanthave active TB, Staphylococcus aureus. In the hospital, Rusty was treated with intravenous antibiotics. The abscess was drainedgoing to help my cough." He shot me a and packed. A peripherally inserted central catheter was placed, and Rusty was discharged home on intravenous vancomycin (Vancocin) and oral rifampin (Rifadin). His erythrocyte sedimentation rate went from 87 to 62 to 37 mm per hour. Throughout this ordeal, Rusty demonstrated the patience of Job. "Why do these darn germs like me so much?" he asked. "Probably because you're such a sweet guy," his wife said, putting forward her own "germ theory." Rusty is unflappable. Let's hope he's soon "unstaphable."

TONY MIKSANEK, M.D., Benton, Illinois

Tony Miksanek, M.D., has been a family physician for more than 20 years. Most of that time he has been in solo private practice in Benton, a town with a population of about 7,000 in rural southern Illinois.

Address correspondence to Tony Miksanek, M.D., 712 Old Orchard Dr., Benton, IL 62812.

To preserve patient confidentiality, the names and identifying characteristics have been changed in each scenario. Any resemblance to actual persons is coincidental.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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