Download Drug induced rhabdomyolysis

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, 11:1553-1561
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
1년에 2회씩 보약을 복용해온 환자로 내원 전 1개월 동안
한약을 복용하였으며, 복용 5일째부터 전심쇠약감 발생, 내원
3일전부터 양하지 무력감으로 누워 지내다 1일전부터 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 4개월간 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, 79,1031-1034
M/17
생후 3개월 – AAP투여 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