פרק 41 Chapter 41 Disorders of the Nervous System Caused by Alcohol, Drugs, Toxins, and Chemical Agents Flashcards
איזו מן התרופות הבאות עלול לגרום ל-
cerebral venous thrombosis?
1. vincristine
2. L-asparginase
3. Methotrexate
4. Fluorouracyl- 5
L- asparginase
This enzymatic inhibitor of protein synthesis is used in the treatment of acute lymphoblastic leukemia. Drowsiness, confusion, delirium, stupor, coma, and diffuse EEG slowing are the common neurologic effects and are dose related and cumulative. They may occur within a day of onset of treatment and clear quickly when the drug is withdrawn, or they may be delayed in onset, in which case they persist for several weeks. These abnormalities are at least in part attributable to the systemic metabolic derangements induced by l-asparaginase, including liver dysfunction.
In recent years, increasing attention has been drawn to cerebrovascular complications of l-asparaginase therapy, including ischemic and hemorrhagic infarction and cerebral venous and dural sinus thrombosis. These cerebrovascular complications are attributable to
transient deficiencies in plasma proteins that are important in coagulation and fibrinolysis.
כמה מילים על התרופות האחרות:
-
5-Fluorouracil
secondary treatment of cancer of the breast, ovary, and gastrointestinal tract. dizziness, cerebellar ataxia of the trunk and the extremities, dysarthria, and nystagmus—symptoms that are much the same as those produced by cytarabine(ara-C). These abnormalities must be distinguished from metastatic involvement of the cerebellum and paraneoplastic cerebellar degeneration. The drug effects are usually mild and subside within 1 to 6 weeks after discontinuation of therapy. -
Methotrexate -Administered in conventional oral or intravenous doses, methotrexate (MTX) is not usually neurotoxic. However, given intrathecally to treat meningeal leukemia or carcinomatosis, MTX commonly causes aseptic meningitis, with headache, nausea and vomiting, stiff neck, fever, and cells in the spinal fluid. Very rarely, probably as an idiosyncratic response to the drug, intrathecal administration results in an acute paraplegia that may be permanent.
The most serious and more common of the neurologic problems associated with systemic MTX chemotherapy is leukoencephalopathy or leukomyelopathy, especially when it is given in combination with cranial or neuraxis radiation therapy. This develops several months after repeated intrathecal or high systemic doses of the drug, and a few milder cases are known to have occurred without radiation treatments, that is, with oral or intravenous MTX alone. The full-blown syndrome consists of the insidious evolution of dementia, pseudobulbar palsy, ataxia, focal cerebral cortical deficits, or paraplegia. Milder cases show only radiographic evidence of a change in signal intensity in the posterior cerebral white matter (“posterior leukoencephalopathy”) that is similar to the imaging findings that follow cyclosporine use and hypertensive encephalopathy. In severe cases, the brain shows disseminated foci of coagulation necrosis of white matter, usually periventricular, which can be detected with CT and MRI. Mineralizing microangiopathy(fibrosis and calcification of small vessels, mainly in the basal ganglia) is yet another complication of MTX therapy. It may occur with MTX treatment or with cranial irradiation but is particularly common when both forms of treatment are combined. -
Vincristine
treatment of acute lymphoblastic leukemia, lymphomas, and some solid tumors. Its most important toxic side effect, and the one that limits its use as a chemotherapeutic agent, is a peripheral neuropathy. Paresthesias of the feet, hands, or both may occur within a few weeks of the beginning of treatment; with continued use of the drug, a progressive symmetrical neuropathy evolves (mainly sensory with reflex loss). Cranial nerves are affected less frequently, but ptosis and lateral rectus, facial, and vocal cord palsies have been observed. Autonomic nervous system function may also be affected: constipation and impotence are frequent complications; orthostatic hypotension, atonicity of the bladder, and adynamic ileus are less frequent. Inappropriate antidiuretic hormone secretion and seizures have been reported but are uncommon.
Although rarely noted in the literature, the authors have seen an instance of reversible posterior leukoencephalopathy with cortical blindness and headache after a single dose of vincristine, identical to the syndrome reported with the use of calcineurin inhibitors.
The neural complications of vinblastine are similar to those of vincristine but are usually avoided because bone marrow suppression limits the dose of the drug that can safely be employed. Vinorelbine is a more recently introduced semisynthetic vinca alkaloid. It has much the same antitumor activity as vincristine but is supposedly less toxic.
Table 41-1
NON-VASCULAR CAUSES OF REVERSIBLE POSTERIOR
LEUKOENCEPHALOPATHY (19)
Figure 41-1. Relation of acute neurologic disturbances to cessation of drinking
בת 19, עולה מסיביר. לפני שבועיים כאב גרון . לפני שבוע צרידות וקושי בבליעה. כעת מתייצגת עם חולשת גפיים שמתקדמת בהדרגה . מה החיידק האחראי?
1. Clostridium botulinium
2. Corynebacterium diphteriae
3. Tetanus
4. Treponema whipplie
Corynebacterium diphteriae
צעירה שנוטלת תרופות נגד חרדה ממשפחת ה
SSRI
מתקבלת בדליריום, חום, טכיקרדיה, שלשולים לאחר שקיבלה תרופה נוספת. מהי התרופה?
1. Phenelzine
2. Olanzapine
3. benzodiazapine
4. Cyproheptadine
Phenelzine-= MAOi
מדובר בסרוטונין סינדרום
The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
.
תיאור של חולה עם סינדרום סרוטונרגי ושאלו מה הטיפול?
1. ברומוקריפטין
2. ציפרוהפטדין
3. תמיכה נשימתית
4. בטא בלוקר
ציפרוהפטדין.
The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
שאלה על סנדרום סרוטונין. במה לא נטפל?
1. cyproheptadine
2. לורזפם
3. אולנזפין
4. buproprion
לא נטפל ב
bupropion
* The selective serotonin reuptake inhibitors (SSRIs) constitute a newer class of antidepressants; paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) are common examples but they continue to be developed at a rapid pace. Of the several related drugs such as venlafaxine (Effexor), nefazodone (Serzone), mirtazapine (Remeron), citalopram (Celexa), trazodone (Desyrel), and bupropion (Wellbutrin),
- The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
חולה מאושפז במחלקה פנימית עקב דליריום, הוא מזיע ומשלשל. בבדיקתו החזרים גידיים מוגברים.
מינון יתר של איזו תרופה עשוי להסביר את התסמינים?
א. amitriptyline
ב. citalopram
ג. clonazepam
ד. levodopa
Citalopram
- The selective serotonin reuptake inhibitors (SSRIs) constitute a newer class of antidepressants; paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) are common examples but they continue to be developed at a rapid pace. Of the several related drugs such as venlafaxine (Effexor), nefazodone (Serzone), mirtazapine (Remeron), citalopram (Celexa), trazodone (Desyrel), and bupropion (Wellbutrin),
- The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
תיאור של
neuroleptic malignant syndrome
מה הגורם האפשרי?
1. הלידול
2. אופיטאים
3. נוגדי דכאון
4. בטא בלוקר
הלידול
NMS-
* Associated with phenothiazines, haloperidol, l-Dopa,
Dopaminergic agents, Antipsychotic, promethazine, olanzapine.
* Its incidence has been calculated to be only 0.2 percent of all patients receiving neuroleptics.
* mortality rate of 15 to 30 percent if not recognized and treated promptly.
* May occur days, weeks, or months after neuroleptic treatment is begun.
* The syndrome consists of hyperthermia, rigidity, stupor, unstable blood pressure, diaphoresis, and other signs of sympathetic overactivity, high serum creatine kinase (CK) values (up to 60,000 units), and, in some cases, renal failure because of myoglobinuria.
* If treatment of the neuroleptic malignant syndrome is started early, when consciousness is first altered and the temperature is rising, bromocriptine in oral doses of 5 mg tid (up to 20 mg tid) will terminate the condition in a few hours. If oral medication can no longer be taken because of the patient’s condition, dantrolene, 0.25 to 3.0 mg intravenously, may be lifesaving.
* Once coma has supervened, shock and anuria may prove fatal or leave the patient in a vegetative state. The rigors during high fever may cause muscle damage and myoglobinuria, and shock may lead to hypoxic-ischemic brain injury.
* One pitfall is to mistake neuroleptic malignant syndrome for worsening of the psychosis and inadvisably administer more antipsychosis medication.
* Meningitis, heat stroke, lithium intoxication, catatonia, malignant hyperthermia, and acute dystonic reactions figure in the differential diagnosis.
* Of course, neuroleptic medication must be discontinued as soon as any of the severe extrapyramidal reactions are recognized.
The neuroleptic malignant syndrome bears an
uncertain relationship to malignant hyperthermia by way of its clinical aspects but also in its response to bromocriptine and dantrolene
תופעה שאינה מתאימה ל
serotonin syndrome
1. ריור יתר
2. שלשולים
3. טכיקרדיה
4. הזעה
5. מיוקלונוס
ריור יתר לא מתאים לסרוטונין סינדרום
- The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine)..
מה גורם ל-
neuroleptic malignant syndrome
1. discontinuation of treatment with DOPA
2. discontinuation of treatment with benzodiazapine
3. discontinuation of treatment with TCA
4. treatment with anti-cholinergic medication
discontinuation of treatment with DOPA
NMS-
* Associated with phenothiazines, haloperidol, l-Dopa,
Dopaminergic agents, Antipsychotic, promethazine, olanzapine.
* Its incidence has been calculated to be only 0.2 percent of all patients receiving neuroleptics.
* mortality rate of 15 to 30 percent if not recognized and treated promptly.
* May occur days, weeks, or months after neuroleptic treatment is begun.
* The syndrome consists of hyperthermia, rigidity, stupor, unstable blood pressure, diaphoresis, and other signs of sympathetic overactivity, high serum creatine kinase (CK) values (up to 60,000 units), and, in some cases, renal failure because of myoglobinuria.
* If treatment of the neuroleptic malignant syndrome is started early, when consciousness is first altered and the temperature is rising, bromocriptine in oral doses of 5 mg tid (up to 20 mg tid) will terminate the condition in a few hours. If oral medication can no longer be taken because of the patient’s condition, dantrolene, 0.25 to 3.0 mg intravenously, may be lifesaving.
* Once coma has supervened, shock and anuria may prove fatal or leave the patient in a vegetative state. The rigors during high fever may cause muscle damage and myoglobinuria, and shock may lead to hypoxic-ischemic brain injury.
* One pitfall is to mistake neuroleptic malignant syndrome for worsening of the psychosis and inadvisably administer more antipsychosis medication.
* Meningitis, heat stroke, lithium intoxication, catatonia, malignant hyperthermia, and acute dystonic reactions figure in the differential diagnosis.
* Of course, neuroleptic medication must be discontinued as soon as any of the severe extrapyramidal reactions are recognized.
The neuroleptic malignant syndrome bears an
uncertain relationship to malignant hyperthermia by way of its clinical aspects but also in its response to bromocriptine and dantrolene
בחורה צעירה עם רקע של דכאון מגיעה למיון בחוסר שקט, טכיקרדיה, שלשולים, החזרים ערים וכו’. מה הסיבה?
1. גמילה מבנזודיאזפינים
2. אלכוהול
3. שימוש יתר בSSRI
SSRI
- The selective serotonin reuptake inhibitors (SSRIs) constitute a newer class of antidepressants; paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) are common examples but they continue to be developed at a rapid pace. Of the several related drugs such as venlafaxine (Effexor), nefazodone (Serzone), mirtazapine (Remeron), citalopram (Celexa), trazodone (Desyrel), and bupropion (Wellbutrin),
- The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRis can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is by discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT 2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
רופא מרדים משתמש באופיאטים , מפתח התקף אפילפטי כללי ראשון לחייו. באיזה מהתכשירים השתמש:
1. Fentanyl
2. Morphine
3. Methadone
4. Meperidine
5. Pentatozine
Meperidine.
meperidine addiction is of particular importance because of its high incidence among physicians and nurses. Tolerance to the drug’s toxic effects is not complete, so that the addict may show tremors, twitching of muscles, confusion, hallucinations, and sometimes convulsions. Signs of abstinence appear 3 to 4 h after the last dose and reach their maximum intensity in 8 to 12 h, at which time they may be worse than those of morphine abstinence.
רופא מרדים סובל מכאבים כרוניים, נוטל אופייטים ומפתח פרכוסים. איזור תרופה?
1. פנטניל
2. טרמדקס
3. מורפיום
טרמדקס
Medications as a Cause of Seizures
A large number of medications are capable of causing
seizures, usually when toxic blood levels are attained.
The antibiotic imipenem and excessive doses of other penicillin congeners and linezolid may be responsible, particularly if renal failure leads to drug accumulation.
Cefepime, a fourth-generation cephalosporin, widely used for the treatment of gram-negative sepsis, can result in status epilepticus, if given in excessive dosage (Dixit et al). The tricyclic antidepressants, bupropion, and lithium may cause seizures, particularly in the presence of a structural brain lesion. Lidocaine and aminophylline are known to induce an unheralded single convulsion if administered too quickly or in excessive doses. The use of the analgesic tramadol has also been associated with seizures. Curiously, the anesthetic propofol, which is discussed further on as a potent anticonvulsant in the treatment of status epilepticus, has caused marked myoclonic phenomena in some patients and, rarely, seizures. These may occur during induction or emergence from anesthesia or as a delayed effect
בת 74, סרטן שד. כימותרפיה ממושכת. עם תום הטיפול פיתחה הפרעת תחושה דיסטלית, ללא הפרעת מוטורית. החזרים בידיים לא הופקו.
PET CT תקין.
מה גורם לזה:
- Methotrexate
- Paclitaxel (Taxol)
- Adriamycin
- Avastin
- Cyclophosphamide
Paclitaxel (Taxol)
Taxol (paclitaxel) and Taxotere (docetaxel) are anticancer drugs derived from the bark of the western yew. Both are particularly useful in the treatment
of ovarian and breast cancer, but they have a wide range of antineoplastic activities. A purely or predominantly sensory neuropathy is a common complication. These drugs are thought to cause neuropathy by their action as inhibitors of the depolymerization of tubulin, thereby promoting
excessive microtubule assembly within the axon. The neuropathy is dose-dependent, occurring with doses greater than 200 mg/m2 of paclitaxel and at
a wide range of dose levels for docetaxel (generally greater than 600 mg/m2). Symptoms may begin 1 to 3 days following the first dose and affect the
feet and hands simultaneously. Autonomic neuropathy (orthostatic hypotension) may occur as well. The neuropathy is axonal in type, with secondary demyelination, and is at least partially reversible after discontinuation of the drug.
—–
קצת על המסיחים האחרים-
* adriamycin, avastin- aren’t mentioned in ADAMS
- Cyclophpsphamide- may cause PRES
- methotrexate- Administered in conventional oral or intravenous doses, methotrexate (MTX) is not usually neurotoxic (See Also Chap. 30). However, given intrathecally to treat meningeal leukemia or carcinomatosis, MTX commonly causes aseptic meningitis, with headache, nausea and vomiting, stiff neck, fever, and cells in the spinal fluid. Very rarely, probably as an idiosyncratic response to the drug, intrathecal administration results in an acute paraplegia that may be permanent. The pathology of this condition has not been studied.
The most serious and more common of the neurologic problems associated with systemic MTX chemotherapy is leukoencephalopathy or
leukomyelopathy, especially when it is given in combination with cranial or neuraxis radiation therapy. This develops several months after repeated intrathecal or high systemic doses of the drug, and a few milder cases are known to have occurred without radiation treatments, that is, with oral or intravenous MTX alone, such as the case reported by Worthley and McNeil. We have seen one such instance in a woman receiving oral MTX for a systemic vasculitis; no alternative explanation for widespread white matter changes and mild dementia could be discerned. Nonetheless, this must be quite uncommon. The fullblown syndrome consists of the insidious evolution of dementia, pseudobulbar palsy, ataxia, focal cerebral cortical deficits, or paraplegia. Milder cases show only radiographic evidence of a change in signal intensity in the posterior cerebral white matter (“posterior leukoencephalopathy”) that is similar to the imaging findings that follow cyclosporine use (see further on) and hypertensive encephalopathy (Fig. 412).
In severe cases, the brain shows disseminated foci of coagulation necrosis of white matter, usually periventricular, which can be detected with CT and MRI.
Mineralizing microangiopathy (fibrosis and calcification of small vessels, mainly in the basal ganglia) is yet another complication of MTX therapy. It may occur with MTX treatment or with cranial irradiation but is particularly common when both forms of treatment are combined. The present authors
have the impression that the severe necrotic lesions possess features comparable to (and therefore may be the result of) the coagulative necrosis of radiation encephalopathy.
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
מה לא עושה נוירופתיה סנסורית מוטורית תת חריפה?
1. אמיודורון
2. וינקריסטין
3. גרמיצין
גרמיצין
- Amiodarone, a drug used for treating recalcitrant ventricular tachyarrhythmias, induces a motorsensory
neuropathy in about 5 percent of patients
after several months of treatment. It may also cause a toxic myopathy. - VINCRISTINE This drug is used in the treatment of acute lymphoblastic leukemia, lymphomas, and some solid tumors. Its most important toxic side effect, and the one that limits its use as a chemotherapeutic agent, is a peripheral neuropathy- . Paresthesias of the feet, hands, or both may occur within a few weeks of the beginning of treatment; with continued use of the drug, a progressive symmetrical neuropathy evolves (mainly sensory with reflex loss). Cranial nerves are affected less frequently, but ptosis and lateral rectus, facial, and vocal cord palsies have been observed. Autonomic nervous system function may also be affected: constipation and impotence are frequent complications; orthostatic hypotension, atonicity of the bladder, and adynamic ileus are less frequent.
- The polyneuropathy caused by vincristine - Paresthesias are the most common early symptom, and loss of ankle jerks is an early sign. Some degree of weakness usually precedes objective sensory loss; the extensor muscles of the fingers and wrists are affected; later the dorsiflexors of the toes and feet causing footdrop become involved either early or late in the clinical course. With the dose regimens currently used, the weakness is usually mild, but in the past, some patients became quadriparetic and bedbound. Adults are more severely affected than are children, as are persons with preexisting polyneuropathies. The neuropathy is strictly doserelated and reduction in dosage is followed by improvement of neuropathic symptoms although this may take several months. Many patients are then able to tolerate vincristine in low dosage, such as 1 mg every 2 weeks, for many months.
- Inappropriate antidiuretic hormone secretion and seizures have been reported but are uncommon. Although rarely noted in the literature, the authors have seen an instance of reversible posterior leukoencephalopathy with cortical blindness and headache after a single dose of vincristine, identical to the syndrome reported with the use of calcineurin inhibitors.
- The neural complications of vinblastine are similar to those of vincristine but are usually avoided because bone marrow suppression limits the dose of the drug that can safely be employed. Vinorelbine is a more recently introduced semisynthetic vinca alkaloid. It has much the same antitumor activity as vincristine but is supposedly less toxic.
לא מצאתי מידע על גרמיצין ולכן זו התשובה
מי מהבאים עושה נוירופתיה?
1. ציטרבין
2. מטוטרקסט
3. ציספלטין
ציספלטין- טיניטוס, נוירופתיה, נפרוטוקסי, בחילות והקאות.
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
בן 56 עם
non hodgkin lymphoma
מקבל טיפול כימי לתוך הוריד. תוך כדי קבלת טיפול, החולה פיתח כאב ראש, הפרעה בשיווי משקל, חוסר קואורדינציה בגפיים ודיבור מקוטע. מה הסיבה הסבירה ביותר מהבאות שגרמה לתופעות אלה?
1. תגובה טוקסית לתרופה אנטיאפילפטית אשר רמתה בדם עלתה כתוצאה מאינטגרציה עם התרופה הכימית
2. פגיעה מוחית וסקולרית באיזור גזע המוח
3. תגובה טוקסית לציטרבין
4. תגובה טוקסית למטוטרקסט
5. אנצפליטיס
לאור האקוטיות בשאלה של “תוך כדי טיפול” התשובה היא פגיעה מוחית וסקולרית באזור גזע המוח.
Cytarabine (AraC)
This drug, long used in the treatment of acute nonlymphocytic leukemia, is not neurotoxic when given in the usual systemic daily doses of 100 to 200
mg/m2. The administration of very high doses (up to 30 times the usual dose) induces remissions in patients’ refractory to conventional treatments. It also may produce, however, a severe degree of cerebellar degeneration in a considerable proportion of cases (4 of 24 reported by Winkelman and
Hines). Ataxia of gait and limbs, dysarthria, and nystagmus develop as early as 5 to 7 days after the beginning of highdose treatment and worsen rapidly. Postmortem examination has disclosed a diffuse degeneration of Purkinje cells, most marked in the depths of the folia, as well as a patchy degeneration of other elements of the cerebellar cortex. Other patients receiving highdose
araC have developed a mild, reversible cerebellar
syndrome with the same clinical features. Because patients older than 50 years of age are said to be far more likely to develop cerebellar degeneration than those younger than 50 years of age, the former should be treated with a lower dosage.
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
חולה אונקולוגית מקבלת טיפול כימותרפיה. מספר ימים לאחר תחילת הטיפול מפתחת דיסארתריה, כאב ראש, חוסר יציבות, סחרחורת ודיסמטריה. מה הסיבה הסבירה?
1. טיפול במטוטרקסט
2. טיפול בציטרבין
3. אינטרקציה של תרופה אנטיאפילפטית שמקבלת עם טיפול כימותרפי גרמה לרמות טוקסיות של התרופה האנטי אפילפטית.
טיפול בציטרבין
Cytarabine (AraC)
This drug, long used in the treatment of acute nonlymphocytic leukemia, is not neurotoxic when given in the usual systemic daily doses of 100 to 200
mg/m2. The administration of very high doses (up to 30 times the usual dose) induces remissions in patients’ refractory to conventional treatments. It also may produce, however, a severe degree of cerebellar degeneration in a considerable proportion of cases (4 of 24 reported by Winkelman and
Hines). Ataxia of gait and limbs, dysarthria, and nystagmus develop as early as 5 to 7 days after the beginning of highdose treatment and worsen rapidly. Postmortem examination has disclosed a diffuse degeneration of Purkinje cells, most marked in the depths of the folia, as well as a patchy degeneration of other elements of the cerebellar cortex. Other patients receiving highdose
araC have developed a mild, reversible cerebellar
syndrome with the same clinical features. Because patients older than 50 years of age are said to be far more likely to develop cerebellar degeneration than those younger than 50 years of age, the former should be treated with a lower dosage.
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
בן 64 מאושפז במחלקה המטואונקולוגית עקב חשד לפיזור לפטומנינגיאלי של לויקמיה.
מספר שעות לאחר דיקור מותני ומתן טיפול אינטרה-תקלי של מתוטרקסט , הוא מפתח חום, כאב
ראש קשה, קישיון עורף, בחילות והקאות.
הסיבה הסבירה לתסמינים אלה היא:
א. מנינגיטיס כימית משנית לתרופה.
ב. מנינגיטיס חיידקית עקב אי הקפדה על סטריליות.
ג. דימום אפידורלי בעקבות הדיקור.
ד. פיזור לויקמי נרחב יותר בקרומי המוח משני לפרוצדורה.
מנינגיטיס כימית משנית לתרופה
methotrexate- Administered in conventional oral or intravenous doses, methotrexate (MTX) is not usually neurotoxic (See Also Chap. 30). However, given intrathecally to treat meningeal leukemia or carcinomatosis, MTX commonly causes aseptic meningitis, with headache, nausea and vomiting, stiff neck, fever, and cells in the spinal fluid. Very rarely, probably as an idiosyncratic response to the drug, intrathecal administration results in an acute paraplegia that may be permanent. The pathology of this condition has not been studied.
The most serious and more common of the neurologic problems associated with systemic MTX chemotherapy is leukoencephalopathy or
leukomyelopathy, especially when it is given in combination with cranial or neuraxis radiation therapy. This develops several months after repeated intrathecal or high systemic doses of the drug, and a few milder cases are known to have occurred without radiation treatments, that is, with oral or intravenous MTX alone, such as the case reported by Worthley and McNeil. We have seen one such instance in a woman receiving oral MTX for a systemic vasculitis; no alternative explanation for widespread white matter changes and mild dementia could be discerned. Nonetheless, this must be quite uncommon. The fullblown syndrome consists of the insidious evolution of dementia, pseudobulbar palsy, ataxia, focal cerebral cortical deficits, or paraplegia. Milder cases show only radiographic evidence of a change in signal intensity in the posterior cerebral white matter (“posterior leukoencephalopathy”) that is similar to the imaging findings that follow cyclosporine use (see further on) and hypertensive encephalopathy (Fig. 412).
In severe cases, the brain shows disseminated foci of coagulation necrosis of white matter, usually periventricular, which can be detected with CT and MRI.
Mineralizing microangiopathy (fibrosis and calcification of small vessels, mainly in the basal ganglia) is yet another complication of MTX therapy. It may occur with MTX treatment or with cranial irradiation but is particularly common when both forms of treatment are combined. The present authors
have the impression that the severe necrotic lesions possess features comparable to (and therefore may be the result of) the coagulative necrosis of radiation encephalopathy.
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
מהם תופעות הלוואי העיקריות של
* Procarbazine
* L-Asperginase
* Nitrosoureas
* Calcineurin inhibitors
* Thalidomide
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
בן 30 מגיע למיון עם בלבול וחוסר שיווי משקל שהופיעו בהדרגה ביממה האחרונה. בבדיקתו –דליריום,
ניסטגמוס הוריזונטלי לכל כיווני המבט, תנועות עיניים מלאות, אטקסיה בארבע גפיים ואטקסיה בהליכה.
איזו תוצאה של בדיקה מסבירה את הקליניקה ?
א. רמת גבוהה של ליתיום בדם
ב. אוטם בפיזור של העורק
posterior inferior cerebellar artery
ג. נוגדנים חיוביים בדם כנגד
anti-GAD
ד. חוסר של ויטאמין
B12
רמה גבוהה של ליתיום בדם.
סעיף ב נשלל כי סיפור המקרה מתאר התייצגות הדרגתית המחמירה על פני יממה.
סעיף ג נשלל כי חסר עקב אנטי גאד יתפתח על פני ימים שבועות…
סעיף ד נשלל כי בי 12 לא יעשה ניסטגמוס לכל כיווני התנועה.
מה לא תופעת לוואי של ליתיום?
1. פרכוסים
2. גויטר
3. nephrogenic DI
4. Down beat nystagmus
5. פרקינסוניזם
פרקינסוניזם אינה תופעת לוואי של ליתיום
* The side effects of lithium are nausea and vomiting, diarrhea (especially if the dose is increased too rapidly), a feeling of mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, nystagmus (especially vertical or down beating), stupor, and coma. A confusional psychosis with polymyoclonus and ataxia-simulating Creutzfeldt-Jakob disease (including periodic sharp waves in the electroencephalogram) may occur at toxic levels.
- With blood levels of lithium in the upper therapeutic range (therapeutic 0.6 to 1.2 mEq/L), it is not uncommon to observe a fast-frequency action tremor or asterixis, together with nausea, loose stools, fatigue, polydipsia, and polyuria. These symptoms usually subside with time.
- Above a level of 1 .5 to 2 mEq/L, particularly in patients with impaired renal function or in those taking a thiazide diuretic, serious intoxication becomes manifest clouding of consciousness, confusion, delirium, dizziness, nystagmus, ataxia, stammering, diffuse myoclonic twitching, and nephrogenic diabetes insipidus. Vertical (downbeating) nystagmus and opsoclonus may also be prominent. A variety of skin problems is common including worsening of acne vulgaris. An uncommon toxic effect is the development of goiter but most patients remain euthyroid although the thyroid-stimulating hormone (TSH) levels may increase slightly. The goiter usually requires no treatment but it is possible to administer thyroid hormone so as to cause the thyroid enlargement to regress. The myoclonic state, particularly when combined with confusion and sharp waves in the EEG, may mimic Creutzfeldt-Jakob disease (see Chap. 33) but there should be no problem in diagnosis if the setting of the illness and the administration of lithium are known.
- At blood lithium concentrations above 3.5 mEq/L, these symptoms are replaced by stupor and coma, sometimes with convulsions, and may prove fatal.
- Discontinuing lithium in the intoxicated patient, which is the initial step in therapy, does not result in immediate disappearance of toxic symptoms. This may be delayed by a week or two, and the diabetes insipidus may persist even longer. Fluids, sodium chloride, aminophylline, and acetazolamide promote the excretion of lithium. lithium coma may require hemodialysis, which has proved to be the most rapid means of reducing the blood lithium concentration.
חולה פסיכיאטרית מובאת למיון על ידי שכנתה במצב של בלבול ומיוקלוניות. היא יודעת שהיא מטופלת בליתיום. מה הכי פחות חשוב על מנת להתקדם באבחנה
1. רמת נתרן בדם
2. האם מקבלת משתנים
3. האם בדקה תפקודי תריס לאחרונה
4. האם ממוצא לובי
5. רמת ליתיום בדם
הכי פחות חשוב לברר אם בדקה תפקודי תריס לאחרונה
מה הטיפול בטטנוס?
1. אנטיביוטיקה
2. אנטיטוקסין
3. אנטיביוטיקה ואנטי טוקסין
4. פלזמה פרזיס ואנטי טוקסין
5. ivig אנטיטוקסין ו
אנטיביוטיקה ואנטיטוקסין!
Treatment of Tetanus
This is directed along several lines. At the outset, a single dose of antitoxin (3,000 to 6,000 U of tetanus immune human globulin) should be given along with a 10-day course of penicillin (1.2 million U of procaine penicillin daily), metronidazole (500 mg q6h intravenously or
400 mg rectally), or tetracycline (2 g daily). These drugs are effective against the vegetative forms of C. tetani. Immediate surgical treatment of the wound (excision or debridement) is imperative, and the tissue around the wound should be infiltrated with antitoxin.
מה נכון לגבי ה
EMG
של שריר המסטר במחלת הטטנוס?
1. loss of the “silent period” with preservation of normal motor units
2. normal EMG
3. small motor units with preservation of the “silent period”
loss of the silent period with preservation of normal motor units
The tetanus toxin interferes with the function of the reflex arc by the blockade of inhibitory transmitters, mainly GABA, at presynaptic sites in the spinal cord and brainstem.
The Renshaw cell, the source of recurrent inhibition of spinal and brainstem motor neurons, is preferentially affected.
Elicitation of the jaw jerk, for example, is normally followed by the abrupt suppression of motor neuron activity, manifested in the electromyogram (EMG) as a “silent period” (see further on). In the patient with tetanus, there is a failure of this inhibitory mechanism, with a resulting increase in activation of the neurons that innervate the masseter muscles (trismus, or lockjaw). Of all neuromuscular systems, the masseter innervation seems to be the most sensitive to the toxin. Not only do afferent stimuli produce an exaggerated effect, but they also abolish reciprocal innervation, allowing both agonists and antagonists to contract, giving rise to the characteristic muscular spasm of tetanus.
בחור צעיר שמתקבל עם הופעה אקוטית של בחילות, הקאות, אופתלמופלגיה עם מעורבות אישון ולאחר כיממה חולשת שרירי גפיים והפרעת בליעה. מה הטיפול?
1. פלסמה פרזיס
2. טיפול בIVIG
3. גואנידין
גואנידין- הרעלת בוטוקס
מה לא נגרם עקב שימוש ממושך במריחואנה?
1. ישנוניות
2. ירידה קוגניטיבית
3. אפילפסיה
4. אופוריה
אפילפסיה לא נגרמת עקב שימוש במריחואנה.
With low doses, the symptoms are like those of mild alcohol intoxication (drowsiness, euphoria, dulling of the senses, and perceptual distortions). With increasing amounts, the effects are similar to those of LSD, mescaline, and psilocybin; they may be quite disabling for many hours. With even larger doses, severe depression and stupor may occur, but death is rare. No damage to the nervous system has been found after chronic use
this agent activates the CB1 receptor, mainly on gabanergic neurons in the hippocampus, amygdala, and cortex. Activation of the receptor inhibits the release of oligopeptide neurotransmitters and monoamines. They also have complex electrophysiologic effects on neurons.
Chronic intoxicated users demonstrate reduced cognitive Performance – though not definitevely
עובד במפעל סוללות, הגיע עם חולשה ביד. בבדיקה יש פס שחור על החניכיים וכן :
wrist drop
מה הטיפול?
1. EDTA + Dimercaprol
2. plasma exchange
3. anti dipteria toxin
EDTA + dimercaprol
Lead intoxication in adults is much less common than in children. The hazards to adults are the result of inhaling the dust of inorganic lead salts and the fumes from the burning of objects containing lead or involvement in processes that require the remelting of lead. Painting, printing, pottery glazing, lead smelting, welding, and storage battery manufacturing are the industries in which these hazards are likeliest to occur.
The usual manifestations of lead poisoning in
adults are colic, anemia, and peripheral neuropathy.
Encephalopathy of the type described above is decidedly rare. Lead colic, frequently precipitated by an intercurrent infection or by alcohol intoxication, is characterized by severe, poorly localized abdominal pain, often with rigidity of abdominal muscles but without fever or Leukocytosis. The pain responds to the intravenous injection of calcium salts, at least temporarily, but responds poorly to morphine. Mild anemia is common. A black line of lead sulfide may develop along the gingival margins. Peripheral neuropathy, usually a bilateral wrist drop, is a rare manifestation
Treatment- chelation therapy with 2,3-dimercaptopropanol (British anti-Lewisite [BAL]; 12 to 24 mg/kg) and CaNa2 EDTA (0.5 to 1 .5 g/m2 body surface area) for 5 to 7 days. This is followed by a course of oral penicillamine.
פולינוירופתיה תחושתית טהורה אינה מופיע ב:
1. פארא-נאופלסטית
2. נורופתיה תורשתית
3. לאחר טיפול בציספלטינום
4. כתוצאה מהרעלת עופרת
5. מטופלים הסובלים מפרידריך אטקסיה
הרעלת עופרת עושה
bilateral wrist drop
-
Vincristine: 1) peripheral neuropathy – sensory,
2) CN involvement – motor as well. 3) Autonomic involvement – constipatin, impotence, hypotension 4) Reversible PRES - Cisplatin: Nephrotoxicity, peripheral neuropathy – predominantly sensory – someties painful. Tinnitus, hearing loss – ototoxicity.
- Pacliteaxel – Taxol: Purely sensory neuropathy, may be associated with autonomic neuropathy – axonal
- Procarbazine: somnolence, confusion, agitation, depression, reversible ataxia, proximal muscle aching.
- L-Asparginase: drowsiness, coma, diffuse EEG slowing. Vacular effect – ischaemic and haemorrhagic, SVT
- 5-FU: dysarthria, cerebellar ataxia, nystagmus (similar to cytarabine)
-
Methotrexate:
Intrathecal – leukoencephalopathy, leukomyelopathy.
PRES
Mineraising microangiopathy – fibrosis and calcification of small vessels. - Carmustine – diffuse vasculopathy – microthrombi – orbital pain, focal seizures, confusion.
- Cytarabine: Cerebellar degeneration as early as 5-7 days from start of treatment
- Cyclosporin, tacrolimus – tremor, myoclonus, headache, insomnia, seizures, PRES
מה ההסתמנות שכיחה של הרעלת עופרת במבוגרים?
1. אנצפלופתיה
2. נוירופתיה
3. SIADH
נוירופתיה
בחור צעיר הגיע למיון לאחר שאכל פטריה. על מה יתלונן?
1. שלשול
2. טכיקרדיה
3. מידריאזיס
4. לחץ דם גבוה
5. עור יבש
שלשול.
The gathering of wild mushrooms, a popular pastime in late summer and early fall, always carries with it the danger of poisoning. As many as 100 species of mushrooms are poisonous. Most of them cause only transient gastrointestinal symptoms but some elaborate toxins that can be fatal. The most important of these toxins are the cyclopeptides, which are contained in several species of Amanita phalloides and muscaria and account for more than 90 percent of fatal mushroom poisonings. These toxins disrupt RNA metabolism, causing hepatic and renal Necrosis. Symptoms of poisoning with Amanita usually appear between 10 and 14 h after ingestion and consist of nausea, vomiting, colicky pain, and diarrhea, followed by irritability, restlessness, ataxia, hallucinations, convulsions, and coma. There may be added evidence of a neuromyopathy presenting as flaccid areflexic paralysis, high serum CK, diminished EMG potentials, and fiber Necrosis.
Other important mushroom toxins are methylhydrazine (contained in the Gyromitra species) and muscarine (Inocybe and Clitocybe species). The former gives rise to a clinical picture much like that caused by the cyclopeptides.
The symptoms of muscarine poisoning, which
appear within 30 to 60 min of ingestion, are essentially those of parasympathetic stimulation-miosis, lacrimation, salivation, nausea, vomiting, diarrhea, perspiration, bradycardia, and hypotension. Tremor, seizures, and delirium occur in cases of severe poisoning.
The mushroom toxins have no effective antidotes. If vomiting has not occurred, it should be induced with ipecac, following which activated charcoal should be administered orally in order to bind what toxin remains in the gastrointestinal tract.
מה לא נכון לגבי הרעל מתנול?
1. חמצת בבדיקת דם
2. עיוורון עם אישונים מגיבים
3. בצקת של הרשתית
4. תתכן תסמונת פרקינסונית
עיוורון עם אישונים מגיבים= לא נכון
האישונים לא מגיבים בהרעלת מתנול
Methyl alcohol (methanol, wood alcohol) is a
component of antifreeze and many combustibles and is used in the manufacture of formaldehyde, as an industrial solvent, and as an adulterant of alcoholic beverages, the latter being the most common source of methyl alcohol intoxication. The oxidation of methyl alcohol to formaldehyde and formic acid proceeds relatively slowly; thus, signs of intoxication do not appear for several hours or may be delayed for a day or longer. Many of the toxic effects are like those of ethyl alcohol, but in addition severe methyl alcohol poisoning may produce serious degrees of acidosis (with an anion gap). The characteristic features of this intoxication, however, are damage to retinal ganglion cells-giving rise to scotomata and varying degrees of blindness, dilated unreactive pupils, and retinal edema and bilateral degeneration of the putamens, readily visible on CT scans. Survivors may be left blind or, less often, with putamenal necrosis and dystonia or Parkinson disease (McLean et al). The most important aspect of treatment is the intravenous administration of large amounts of sodium bicarbonate to reverse acidosis. Hemodialysis and 4-methylpyrazole (fomepizole) may be useful adjuncts because of the slow rate of oxidation of methanol.
אלכוהוליסט מובא למיון מבולבל, בבדיקתו עיוור, בבדיקות דם חמצת מטבולית, בהדמיה פגיעה בפלידום דו”צ.
מה הטיפול?
1. סליין
2. גלוקוז
3. ביקרבונט
4. אשלגן
ביקרבונט
Methyl alcohol (methanol, wood alcohol) is a
component of antifreeze and many combustibles and is used in the manufacture of formaldehyde, as an industrial solvent, and as an adulterant of alcoholic beverages, the latter being the most common source of methyl alcohol intoxication. The oxidation of methyl alcohol to formaldehyde and formic acid proceeds relatively slowly; thus, signs of intoxication do not appear for several hours or may be delayed for a day or longer. Many of the toxic effects are like those of ethyl alcohol, but in addition severe methyl alcohol poisoning may produce serious degrees of acidosis (with an anion gap). The characteristic features of this intoxication, however, are damage to retinal ganglion cells-giving rise to scotomata and varying degrees of blindness, dilated unreactive pupils, and retinal edema and bilateral degeneration of the putamens, readily visible on CT scans. Survivors may be left blind or, less often, with putamenal necrosis and dystonia or Parkinson disease (McLean et al). The most important aspect of treatment is the intravenous administration of large amounts of sodium bicarbonate to reverse acidosis. Hemodialysis and 4-methylpyrazole (fomepizole) may be useful adjuncts because of the slow rate of oxidation of methanol.
מה אינו חלק מתופעות הלוואי של אמפטמין?
1. פסיכוזה
2. סימנים פרקינסונים
3. ווסקולופתיה
4. דימום סובארכנואידלי
סימנים פרקינסונים אינם חלק מתופעות הלוואי של אמפטמין.
The amphetamines (damphetamine, d,lamphetamine, pemoline, methamphetamine, methylphenidate) are analeptics (CNS stimulants) and in addition have significant hypertensive, respiratory stimulant,
and appetite depressant effects. They are effective in the management of narcolepsy but
have been more widely and sometimes indiscriminately used for the control of obesity, the abolition of fatigue, and the treatment of hyperactivity in children (see Chap. 37 for full discussion). Undoubtedly, they are able to reverse fatigue, postpone the need for sleep, and elevate mood but these effects are not entirely predictable and the user must compensate for the period of wakefulness with even greater fatigue and often with depression that follows. The intravenous use of a high dose of amphetamine produces an immediate feeling of ecstasy.
Because of the popularity of the amphetamines and the ease with which they can be procured, instances of acute and chronic intoxication are not uncommon.
Methamphetamine is the most frequently abused in this category, as intravenous “crystal” or smoked as “ice.” The toxic signs are essentially an exaggeration of the activating effects—restlessness, excessive speech and motor activity, tremor, and insomnia. Severe intoxication gives rise to hallucinations, delusions, and changes in affect and thought processes—a state that may be indistinguishable from paranoid schizophrenia. An amphetamine associated vasculopathy and intracerebral and subarachnoid hemorrhage are well recognized but rare complications of chronic or acute intoxication (Harrington et al and Chap. 33). Similar cerebrovascular complications may appear with sympathomimetic agents contained in overthecounter cold medications and in dieting aids. Phenylpropanolamine has been implicated most often but ephedrine, cocaine (see below), and
similar agents rarely have the same effects and induce a vasculopathy. The pathogenesis of the vascular lesion is unknown (both vasospasm and arteritis have been reported).
Chronic use of amphetamines can lead to a high degree of tolerance and psychologic dependence. Withdrawal of the drug after sustained oral or intravenous use is regularly followed by a period of prolonged sleep (a disproportionate amount of which is rapid eye movement [REM] sleep), from which the patient awakens with a ravenous appetite, muscle pains, and feelings of profound fatigue and depression. Treatment consists of
discontinuing the use of amphetamine and administering antipsychosis drugs. Hypertension may need to be treated until the effect of the drug has
waned.
מה אין בתופעת כמילה מאמפטמין?
1. ישנוניות
2. עייפות יתר
3. תאבון
4. הזיות
5. כאבי שרירים
הזיות- חלק מהרעלת אמפטמין ולא מגמילה ממנו
The amphetamines (damphetamine, d,lamphetamine, pemoline, methamphetamine, methylphenidate) are analeptics (CNS stimulants) and in addition have significant hypertensive, respiratory stimulant,
and appetite depressant effects. They are effective in the management of narcolepsy but
have been more widely and sometimes indiscriminately used for the control of obesity, the abolition of fatigue, and the treatment of hyperactivity in children (see Chap. 37 for full discussion). Undoubtedly, they are able to reverse fatigue, postpone the need for sleep, and elevate mood but these effects are not entirely predictable and the user must compensate for the period of wakefulness with even greater fatigue and often with depression that follows. The intravenous use of a high dose of amphetamine produces an immediate feeling of ecstasy.
Because of the popularity of the amphetamines and the ease with which they can be procured, instances of acute and chronic intoxication are not uncommon.
Methamphetamine is the most frequently abused in this category, as intravenous “crystal” or smoked as “ice.” The toxic signs are essentially an exaggeration of the activating effects—restlessness, excessive speech and motor activity, tremor, and insomnia. Severe intoxication gives rise to hallucinations, delusions, and changes in affect and thought processes—a state that may be indistinguishable from paranoid schizophrenia. An amphetamine associated vasculopathy and intracerebral and subarachnoid hemorrhage are well recognized but rare complications of chronic or acute intoxication (Harrington et al and Chap. 33). Similar cerebrovascular complications may appear with sympathomimetic agents contained in overthecounter cold medications and in dieting aids. Phenylpropanolamine has been implicated most often but ephedrine, cocaine (see below), and
similar agents rarely have the same effects and induce a vasculopathy. The pathogenesis of the vascular lesion is unknown (both vasospasm and arteritis have been reported).
Chronic use of amphetamines can lead to a high degree of tolerance and psychologic dependence. Withdrawal of the drug after sustained oral or intravenous use is regularly followed by a period of prolonged sleep (a disproportionate amount of which is rapid eye movement [REM] sleep), from which the patient awakens with a ravenous appetite, muscle pains, and feelings of profound fatigue and depression. Treatment consists of
discontinuing the use of amphetamine and administering antipsychosis drugs. Hypertension may need to be treated until the effect of the drug has
waned.
מה הטיפול בהרעלת כספית?
1. ipecac
2. penicillamine
3. plasme exchange
4. activated charcoal
penicillamine
Treatment consists of removal from the source of mercury exposure, and for acute inorganic mercury poisoning, chelation therapy with penicillamine
or dimercaprol (BAL). No chelator for methylmercury or ethylmercury is approved by the FDA. In the treatment of chronic mercury poisoning,
penicillamine has been the drug of choice, because it can be administered orally and appears to chelate mercury selectively, with less effect on copper,
which is an essential element in many metabolic processes.
סיפור על מטופל עם פולינורופתיה סוב אקוטית, אופתלמופלגיה ואלפוציה. מה ההרעלה?
1. תליום
2. ארסן
3. ויטמין D
תליום
Patients who survive the effects of acute poisoning develop a rapidly progressive and painful sensory polyneuropathy, optic atrophy, and occasionally ophthalmoplegia—followed, 15 to 30 days after ingestion, by diffuse alopecia (see Chap. 43). The latter feature should always suggest the diagnosis of thallium poisoning, which can be confirmed by finding this metallic element in the urine. It is not uncommon for the neuropathy to have a painful component involving acral regions. The condition can end fatally. The use of potassium chloride by mouth may hasten thallium excretion.
Thallium salts, when taken in sufficient amount, produce a clinical picture resembling that of GBS or an acute sensory polyneuropathy. If the salts are taken orally, there is first abdominal pain, vomiting, and diarrhea, followed within a few days by pain and tingling in the toes and fingertips and then rapid weakening of muscles of the limbs, initially the distal ones. As the weakness progresses, the tendon reflexes diminish. Pain sensation is reduced more than tactile, vibratory, and position sense. Persistent acral pain with allodynia has been a major feature in 3 of the 5 patients we have examined; in 2 of our patients there was no weakness, only sensory loss and ataxia. All cranial nerves except the first and eighth may be affected; facial palsies, ophthalmoplegia, nystagmus, optic neuritis with visual impairment, and vocal cord palsies are additional abnormalities but only in the most severely affected patients. The CSF protein rises to more than 100 mg. Death may occur in the first 10 days as a result of cardiac arrest.
The early onset of painful paresthesias, sensory loss, and pain localized to joints, back, and chest, as well as rapid loss of hair (after 1 or 2 weeks), all serve to differentiate this neuropathy from GBS, porphyria, and other acute polyneuropathies. Relative preservation of reflexes is noteworthy and rapidly evolving complete alopecia is a striking feature. Patients with lesser degrees of intoxication may recover completely within weeks or months. Thallium salts act like potassium and a high intake of potassium chloride hastens the excretion of thallium. Chelating agents are of unproven value but are usually included in treatment
בן 40 עםנוירופתיה, כאבי בטן , אובדן שיער , תסמינים נוספים . באיזה הרעלה מדובר?
1. תליום
2. ארסן
3. עופרת
4. מרקורי
תליום
Patients who survive the effects of acute poisoning develop a rapidly progressive and painful sensory polyneuropathy, optic atrophy, and occasionally ophthalmoplegia—followed, 15 to 30 days after ingestion, by diffuse alopecia (see Chap. 43). The latter feature should always suggest the diagnosis of thallium poisoning, which can be confirmed by finding this metallic element in the urine. It is not uncommon for the neuropathy to have a painful component involving acral regions. The condition can end fatally. The use of potassium chloride by mouth may hasten thallium excretion.
Thallium salts, when taken in sufficient amount, produce a clinical picture resembling that of GBS or an acute sensory polyneuropathy. If the salts are taken orally, there is first abdominal pain, vomiting, and diarrhea, followed within a few days by pain and tingling in the toes and fingertips and then rapid weakening of muscles of the limbs, initially the distal ones. As the weakness progresses, the tendon reflexes diminish. Pain sensation is reduced more than tactile, vibratory, and position sense. Persistent acral pain with allodynia has been a major feature in 3 of the 5 patients we have examined; in 2 of our patients there was no weakness, only sensory loss and ataxia. All cranial nerves except the first and eighth may be affected; facial palsies, ophthalmoplegia, nystagmus, optic neuritis with visual impairment, and vocal cord palsies are additional abnormalities but only in the most severely affected patients. The CSF protein rises to more than 100 mg. Death may occur in the first 10 days as a result of cardiac arrest.
The early onset of painful paresthesias, sensory loss, and pain localized to joints, back, and chest, as well as rapid loss of hair (after 1 or 2 weeks), all serve to differentiate this neuropathy from GBS, porphyria, and other acute polyneuropathies. Relative preservation of reflexes is noteworthy and rapidly evolving complete alopecia is a striking feature. Patients with lesser degrees of intoxication may recover completely within weeks or months. Thallium salts act like potassium and a high intake of potassium chloride hastens the excretion of thallium. Chelating agents are of unproven value but are usually included in treatment
תיאור של חולה בקומה, עם אישונים צרים, נשימה שטחית.
1. מלינגרינג
2. הרעלת קוקאין
3. הרעלת בנזודיאזפינים
4. הרעלת אופיאטים
הרעלת אופיאטים
איפה אין רצפטורים אופיאטיים?
1. לוקוס צרולואוס
2. DRG
3. אמיגדלה
4. אדינגר ווסטפל
בלוקוס צרולואוס אין רצפטורים לאופיאטיים
נרקומן מכור לאופיאטים מתאשפז ואין לו גישה לסם.
מהם תסמיני גמילה ראשונים?
א. בחילות, הקאות, שלשולים.
ב. אישונים רחבים ולא מגיבים לאור.
ג. אי שקט קיצוני, אלימות פיזית.
ד. פיהוקים, נזלת, דמעת, סימור שיער
(piloerection) .
פיהוקים, נזלת, דמעת
piloerection
מה נכון לגבי נוירופתיה של ארסן?
1. אקסונלי
2. סגמנטלי דה- מיאלינטיבי
3. wallerian degeneration
אקסונלי מסוג
dying back- axonal degeneration
The effects on the nervous system are those of an encephalopathy or peripheral neuropathy.
The latter may be the product of chronic poisoning or may become manifest between 1 and 2 weeks after recovery from the effects of acute poisoning. It takes the form of a distal axonopathy.
In cases of arsenical polyneuropathy we have cared for, a distal sensorimotor areflexic syndrome developed subacutely. At autopsy there was a dying back pattern of myelin and axons with macrophage and Schwann cell reactions and chromatolysis of motor neurons and sensory ganglion cells. The CNS appeared normal.
The symptoms of encephalopathy (headache, drowsiness, mental confusion, delirium, and convulsive seizures) may also occur as part of acute or chronic intoxication. In the latter case, they are accompanied by weakness and muscular aching, hemolysis, chills and fever, mucosal irritation (in patients exposed to arsine gas), diffuse scaly desquamation, and transverse white lines, 1 to 2 mm in width, above the lunula of each fingernail (Mees lines).
Acute poisoning by the oral route is associated with severe gastrointestinal symptoms, shock and death in a large proportion of patients. The CSF is normal. Examination of the brain in such cases discloses myriads of punctate hemorrhages in the white matter. Microscopically, the lesions consist of capillary necrosis and of pericapillary zones of degeneration, which, in turn, are ringed by red cells (brain purpura).
The diagnosis of arsenical poisoning depends on the demonstration of increased levels of arsenic in the hair and urine. Arsenic is deposited in the hair within 2 weeks of exposure and may remain fixed there for long periods.
Concentrations of more than 0.1 mg arsenic per 100 mg hair are indicative of poisoning. Arsenic also remains within bones for long periods and is slowly excreted in the urine and feces. Excretion of more than 0.1 mg arsenic per liter of urine is considered abnormal; levels greater than 1 mg/L may occur soon after acute exposure
Figure 41-1.
Relation of acute neurologic disturbances to cessation of drinking. The shaded drinking period is greatly foreshortened and not intended to be
quantitative. The periodic notching in the baseline represents the tremulousness, nausea, and so on that occur following a night’s sleep. The time relations of the various groups of symptoms to withdrawal are explained in the text. (Adapted from Victor M, Adams RD: The effect of alcohol on the
nervous system. Res Publ Assoc Res Nerv Ment Dis 32:526, 1953, by permission.)
Figure 41-2.
Toxic reversible posterior leukoencephalopathy (PRES). Axial T2- fluid-attenuated inversion recovery (FLAIR) MRI in a patient with cortical blindness and severe headache days after receiving vincristine. This syndrome and radiographic findings are more typical following the use of cyclosporine, FK506, and other chemotherapies. Compare this image to the similar conditions of hypertensive encephalopathy and toxemia shown in Fig. 33-35.
