Question-7: A 65-year-old male hepatic cirrhosis patient was admitted to the hospital for treatment of
gross ascites. He was administered inj. furosemide 40 mg i.m. three times a day to excrete the
ascitic fluid. He responded with brisk diuresis, but on the 3rd day he was found to be talking
irrelevant, was weak and partly disoriented. He had a fainting episode on getting up from the
bed. His serum K+ was 2.8 mEq/L (low) and blood pH was 7.6 (raised).
(a) What is the likely cause of his condition on the 3rd day?
(b) What should be the principles of management of this complication?
Solution:(a) The most likely pathogenesis of the symptoms on the 3rd day of brisk diuretic therapy in this patient is occurrence of hypokalaemic alkalosis, which precipitated encephalopathy. In cirrhotics with moderate to severe hepatic dysfunction, ammonia produced by gut bacteria is not completely detoxified in the liver. Ammonia level in blood tends to rise. This ionizes partly to NH4+ and is exvreted in urine as NH4Cl. The NH4+ ions do not cross the blood brain barrier. During alkalosis, NH3 ionizes to a lesser extent, raising blood NH3 level which enters brain to cause encephalopathy. Weakness and postural hypotension are the other manifestations of hypokalaemic alkalosis.
(b) The diuretic should be withheld till the fluid electrolyte and acid-base balance is restored. Intravenous infusion of KCl along with normal saline can hasten recovery from hypokalemia and alkalosis. Oral lactulose helps in reducing blood NH3 level by producing acidic degradation products in the gut which convert NH3 into poorly absorbed NH4+ ions. Moreover, lowering of stool pH by lactulose has a suppressant effect on NH3 producing gut bacteria.
Question-8: A 40-year-man weighing 60 kg suffering from chronic cough with expectoration and fever was diagnosed to have cavitary pulmonary tuberculosis. He was put on the standard 1st line antitubercular regimen consisting of isoniazid (H) + rifampin (R) + pyrazinamide (Z) + ethambutol (E). His condition improved, but in the 4th week he developed jaundice with enlarged tender liver and rise in serum bilirubin as well as serum transaminase levels. He was suspected to have developed antitubercular drug induced hepatitis.
(a) Should his antitubercular treatment be stopped or continued?
(b) How would you proceed to confirm and identify the causative drug, and then select the alternative regimen?
Solution:(a) The patient has a serious disease for which many effective drugs are available. As such, antitubercular treatment should be continued, albeit with non-hepatotoxic drugs.
(b) The patient should be checked very carefully, a full casuality assessment must be done, to identify the causative drug. Here, the reaction occured in the 4th week of drug therapy which is consistent with the time-sequencing of drug-induced hepatitis.
The reaction can be confirmed and the actual causative drug identified by dechallange and rechallange.
1. Stop all suspected drugs (H, R and Z); treat the patient with E and two other nonhepatotoxic drugs, preferably streptomycin (i.m.) and a fluoroquinolone (e.g. levofloxacin). If the jaundice clears in the subsequent weeks, dechallenge is positive (one or more of the 3 stopped drugs had caused hepatitis).
2. Rechallenge by reintroducing the stopped drugs, one at a time, and repeatedly monitor liver function tests.
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3. Generally, R is started first followed by H after 7–10 days. If both are tolerated, Z could have been the causative drug. In any case, after completing the intensive phase with H+R+E, the continuation phase with H+R should be extended to 9 months.
4. If R is implicated, it should be stopped as soon as the liver function tests become abnormal. Start H and continue H+E+S for 2 months followed by H+E for 10 months.
5. If H is implicated, it should be stopped immediately, and R+E+Z may be given for 9 months. In this way, the implicated drug can be identified and antitubercular therapy completed with minimal use of parenteral/2nd line drugs.
Question-9: A man aged 45 years presented with gradual onset complaints of double vision, drooping eyelids, difficulty in chewing food and weakness of limbs which is accentuated by exercise. The symptoms fluctuate in intensity over time. A provisional diagnosis of myasthenia gravis is made.
(a) Can a pharmacological test be performed to confirm/refute the diagnosis?
(b) In case the diagnosis is confirmed, can this disease be cured by medication?
(c) Is there a surgical solution for this illness?
Solution:(a) The diagnosis of myasthenia gravis can be confirmed by the ‘edrophonium test’. Edrophonium
is injected i.v. (2 mg initially which if tolerated; followed by 8 mg after 30–60 sec). Reversal
of ptosis, diplopia and increase in the strength of affected muscles lasting 5–10 min constitutes
a positive result.
In case edrophonium is not available, the test can be performed with neostigmine 1.5 mg
i.v. Atropine 0.6 mg may be given i.m./i.v. to block the muscarinic side effects of edrophonium/
neostigmine.
(b) Myasthenia gravis is an autoimmune disorder due to production of antibodies against the nicotinic receptor at the muscle end-plate. No drug is curative. Both anticholinesterases (neostigmine, etc.) and corticosteroids (other immunosuppressants as well) afford only symptomatic relief till administered. The former preserve ACh and improve neuromuscular transmission, while the latter inhibit the immunological reaction, without removing the cause of the illness.
(c) In many cases (especially older men), thymus is the source of the nicotinic receptor antigen. As such, thymectomy has been found to lower disease activity and even induce long-lasting remission.
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(a) What is the likely cause of his condition on the 3rd day?
(b) What should be the principles of management of this complication?
Solution:(a) The most likely pathogenesis of the symptoms on the 3rd day of brisk diuretic therapy in this patient is occurrence of hypokalaemic alkalosis, which precipitated encephalopathy. In cirrhotics with moderate to severe hepatic dysfunction, ammonia produced by gut bacteria is not completely detoxified in the liver. Ammonia level in blood tends to rise. This ionizes partly to NH4+ and is exvreted in urine as NH4Cl. The NH4+ ions do not cross the blood brain barrier. During alkalosis, NH3 ionizes to a lesser extent, raising blood NH3 level which enters brain to cause encephalopathy. Weakness and postural hypotension are the other manifestations of hypokalaemic alkalosis.
(b) The diuretic should be withheld till the fluid electrolyte and acid-base balance is restored. Intravenous infusion of KCl along with normal saline can hasten recovery from hypokalemia and alkalosis. Oral lactulose helps in reducing blood NH3 level by producing acidic degradation products in the gut which convert NH3 into poorly absorbed NH4+ ions. Moreover, lowering of stool pH by lactulose has a suppressant effect on NH3 producing gut bacteria.
Question-8: A 40-year-man weighing 60 kg suffering from chronic cough with expectoration and fever was diagnosed to have cavitary pulmonary tuberculosis. He was put on the standard 1st line antitubercular regimen consisting of isoniazid (H) + rifampin (R) + pyrazinamide (Z) + ethambutol (E). His condition improved, but in the 4th week he developed jaundice with enlarged tender liver and rise in serum bilirubin as well as serum transaminase levels. He was suspected to have developed antitubercular drug induced hepatitis.
(a) Should his antitubercular treatment be stopped or continued?
(b) How would you proceed to confirm and identify the causative drug, and then select the alternative regimen?
Solution:(a) The patient has a serious disease for which many effective drugs are available. As such, antitubercular treatment should be continued, albeit with non-hepatotoxic drugs.
(b) The patient should be checked very carefully, a full casuality assessment must be done, to identify the causative drug. Here, the reaction occured in the 4th week of drug therapy which is consistent with the time-sequencing of drug-induced hepatitis.
The reaction can be confirmed and the actual causative drug identified by dechallange and rechallange.
1. Stop all suspected drugs (H, R and Z); treat the patient with E and two other nonhepatotoxic drugs, preferably streptomycin (i.m.) and a fluoroquinolone (e.g. levofloxacin). If the jaundice clears in the subsequent weeks, dechallenge is positive (one or more of the 3 stopped drugs had caused hepatitis).
2. Rechallenge by reintroducing the stopped drugs, one at a time, and repeatedly monitor liver function tests.
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3. Generally, R is started first followed by H after 7–10 days. If both are tolerated, Z could have been the causative drug. In any case, after completing the intensive phase with H+R+E, the continuation phase with H+R should be extended to 9 months.
4. If R is implicated, it should be stopped as soon as the liver function tests become abnormal. Start H and continue H+E+S for 2 months followed by H+E for 10 months.
5. If H is implicated, it should be stopped immediately, and R+E+Z may be given for 9 months. In this way, the implicated drug can be identified and antitubercular therapy completed with minimal use of parenteral/2nd line drugs.
Question-9: A man aged 45 years presented with gradual onset complaints of double vision, drooping eyelids, difficulty in chewing food and weakness of limbs which is accentuated by exercise. The symptoms fluctuate in intensity over time. A provisional diagnosis of myasthenia gravis is made.
(a) Can a pharmacological test be performed to confirm/refute the diagnosis?
(b) In case the diagnosis is confirmed, can this disease be cured by medication?
(c) Is there a surgical solution for this illness?
(b) Myasthenia gravis is an autoimmune disorder due to production of antibodies against the nicotinic receptor at the muscle end-plate. No drug is curative. Both anticholinesterases (neostigmine, etc.) and corticosteroids (other immunosuppressants as well) afford only symptomatic relief till administered. The former preserve ACh and improve neuromuscular transmission, while the latter inhibit the immunological reaction, without removing the cause of the illness.
(c) In many cases (especially older men), thymus is the source of the nicotinic receptor antigen. As such, thymectomy has been found to lower disease activity and even induce long-lasting remission.
**For more visit and like our facebook page**
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