Drug induced rhabdomyolysis Department of nephrology

Overview of rhabdomyolysis Definition –a syndrome resulting from destruction of skeletal muscle Classification –Pure exertional rhabdomyolysis –Genetically transmitted defect leading to rhabdomyolysis Carnitine palmitoyltrasnferase deficiency McArdle’s disease (myophophorylase deficiency) –Nonhereditary, nonexertional rhabdomyolysis

Precipitating factors leading to nonexertional rhabdomyolysis –Alcohol –Phosphate deficiency –Potassium deficiency –Bacterial and viral infections –Drugs – cocaine, amphetamines, neuroleptics, statins, protein inhibitors, fibrates –Toxins – tetanus, snake, venom, toluene, Tricholoma equestre mushrooms –Direct/ischemic injury

Clinical manifestation –Muscle weakness, pain, swelling and cramps –Compartment syndrome –Dark urine –Metabolic abnormalities –ARF Direct nephrotoxicity of ferrihemate Tubular obstruction due to protein, uric acid crystal & myoglobin cast Renal vasoconstriction

Treatment –Fluid replacement –Urine alkalization –Correction of electrolyte imbalance –DIC –Dialysis –Fasciotomy JASN 2004, 11:

Etiology of drug-induced rhabdomyolysis Current Opinion in Pediatrics 2004, 16:206–210

Mechanisms of drug induced rhabdomyolysis Primary direct toxic effect on the myocyte function Indirect secondary effect predisposing the myocyte to develop injury

Primary direct toxic effect on the myocyte function –Inhibition of calcium metabolism by the sarcoplasmic reticulum –Impairment of the production of ATP  disruption of cell membrane –Alterations in carbohydrate metabolism

Indirect secondary effect predisposing the myocyte to develop injury –Drug-induced coma  prolonged immobilization & muscle compression –Seizures –Myoclonus –Trauma, agitation, delirium

Licorice Candy, p-aminosalycylic acid, carbenoxolone sodium, boisson de coco, chewing tobacco and oriental herbal preperation Glycyrrhizin  glycyrrhetinic acid (active form)

Hypokalemia –Impaired glycogen synthesis  reduction in energy production during sustained muscle contraction –Reduced muscle cell transmembrane voltage  muscle damage –Impairment of normal increase of potassium release during contraction causing vasodilator effect on arterioles  ischemia and muscle necrosis

F/79 1 년에 2 회씩 보약을 복용해온 환자로 내원 전 1 개월 동안 한약을 복용하였으며, 복용 5 일째부터 전심쇠약감 발생, 내원 3 일전부터 양하지 무력감으로 누워 지내다 1 일전부터 자꾸 자려하는 상태로 내원.

M/78 2 년 전부터 감초, 생강 등이 포함된 한약제를 복용하였으며, 이후 고혈압 진단, 투약 중으로 내원 1 주 전부터 양측 하지 근력 약화 발생, 하루 전부터 목을 가눌 수 없을 정도로 심해져 내원.

F/55 평소 건강하던 환자로 인후염 증상 지속되어 민간요법으로 감초를 4 개월간 복용하였으며, 내원 4 일 전부터 양팔과 다리 근육이 뭉치는 증상 있었으며, 내원 당일 사지마비감을 주소로 내원.

CNS drugs General anesthetic agents and CNS drugs –Narcotics, cyclic antidepressants, benzodiazepines, antihistamines and barbiturates –Prolonged immobilization  pressure-induced ischemia LSD, sympathomimetics and phencyclidine –Derilium or agitation  prolonged involuntary muscle contraction

Mayo Clinic Proceedings 2004, 79,

M/17 생후 3 개월 – AAP 투여 후 hepatitis with agranulocytosis 10 세 – cefaclor & AAP 투여 중 desquamative dermatitis 14 세 - a febrile eruption after receiving amoxicillin and AAP, intensified after proparacetamol injection Oral challenge with paracetamol  febrile exanthema, neutropenia, and a rise of CRP & CPK-MM Allergy 1999, 54:1115