Dr. Robbins – 26 Questions Predicted cases are below Case 5 • A 31-year-old woman with no family history of neurologic disease and no history of trauma or drug abuse had the spontaneous onset of a horizontal (“no-no”) head tremor. Initially, it was mild and asymptomatic, but as it increased in severity, the patient noted that turning her head to the right seemed to increase the tremor, whereas turning her head to the left decreased the tremor. Her neurologic examination results were otherwise normal, as well as her MRI. Beta-blockers, primidone, and alcohol had little effect on the tremor. Eighteen months later, the patient returned, reporting that driving had become difficult because of a tendency for her head to turn involuntarily to the left, and her attempts to hold her head in the neutral position markedly increased the tremor and caused discomfort in her neck. Stress also caused similar problems. Over time, the involuntary movements were present almost continuously. Mild finger pressure on her left chin dampened the tremor and the involuntary movements of her head. Case 1 A 60 year old male comes to see you for numbness and a slight weakness in his left lower face. He states it was present on awakening yesterday morning. On further questioning he admits that he has noticed numbness and clumsiness in his left hand when buttoning his shirt. Case 2 A 23 year old male presents with numbness and tingling of his right hand. The patient’s hand numbness wakes him up at night and he has to shake it for normal feeling to return. There is a positive Tinel's sign over the median nerve of the wrist. The patient has no other complaints. Case 3 A 23-year-old graduate student was studying late at night for an examination. As he looked at his textbook, he realized he was having difficulty reading through his left eye. When he covered his left eye, his vision in the right eye seemed normal. However, when he covered his right eye, his vision in the left eye was blurred. Other than left ocular pain when he moved his eyes, he had no other symptoms. Case 4 A 65-year-old man with a history of hypertension, coronary artery disease presents with a complaint of sudden onset of double vision. Further questioning reveals the diplopia occurs only on horizontal gaze and not vertical gaze. Other than weakness of the right lateral rectus muscle, there are no other neurological complaints or findings. Case 5 A 2-year-old child was seen by you at 1p.m. due to stumbling and lethargy associated with nausea and vomiting. The mother relates the child was in good health this a.m. but was difficult to arouse from his nap for lunch. You find the patient to be somnolent, arouses to light pressure but falls back to sleep and his pupils are constricted but reactive to light. The temp is normal and no other neurological signs are present. Case 6 A 60-year-old man presents with a 3 month gradual decline of strength in his right face and right upper and lower extremities. He first noticed a weakness in his face then his hand that progressed for 2 months. This was followed by a progressive weakness in his right leg to a point where he is now falling. Case 7 A 58-year-old female with a history of a light stroke 9 years ago that left her with short term memory problems. She smoked ½ pack/day for 25 years and had intermittent low back pain for 20 years. She presents to you with a history of waking up 3 weeks ago with weakness in her right lower extremity associated with a foot drop. It has not progressed or improved. She has dorsiflexion weakness and a numbness from the lateral mid-calf to the dorsum of the affected foot. She has no reflex in her right patella. Case 3 • A 28-year-old accountant and part-time boxer has been brought to the urgent care clinic by his wife because he has become irritable and abusive. She reports that he has had intermittent headaches for 3 months, and the headaches have become more severe and constant in the past month. He has been unable to work for about a week because of excessive drowsiness, and he sleeps for up to 24 hours if not awakened. The patient is poorly cooperative and says only that he has a headache. • On neurologic examination, he is drowsy and irritable but able to follow commands. He has mild to moderate weakness in his left arm and leg, and a left pronator drift. Tendon reflexes are hyperactive on the left. There is a left Babinski’s response. The lower part of his face droops slightly on the left side. Case 4 • A 69-year-old right handed retired executive is seeing her internist for a routine checkup. Her husband mentions that she has undergone a marked personality change over the past several months. He also notes that she has been forgetful for about a year and keeps asking the same things over and over. She no longer seems interested in her personal appearance. The mental status examination confirms these observations. Her speech is fluent, but she frequently pauses because she can’t think of a word. She has difficulty following complicated commands. She can only remember one of three items after a 5 minute delay, and she recalls no current events. She is unable to subtract two-digit numbers in her head. The remainder of her examination is normal. Case 2 A 50 year-old male is seen in your office with the complaint of multiple episodes of visual blindness in his left eye. The episodes are brief lasting seconds. The patient has no eye pain during the events and feels fine otherwise. He has a past history of angina. Based on history alone you suspect; Case 5 A 63 year-old patient presented with a stroke that caused weakness in his left face and upper arm which, for the most part has resolved after 3 days. Currently you find that he is still demonstrating some dysprosody and has some difficulty recognizing familiar objects. You show him a pen, a key, and a paper clip and the patient holds them in his hands and is still unable to name them. You suspect a visual and tactile agnosia. The requirements for making this diagnosis are all of the following except: Case 2 Case 6 Case 2 • Hemiballismus is an unusual condition characterized by an abrupt onset of violent fleeting movements affecting the limbs, neck and trunk on one side of the body. The most common etiologic diagnosis causing this disorder is: A. B. C. D. E. Neoplasm Trauma Vascular Degenerative Inflammatory Case 1 A 38-year-old man who has progressive difficulty concentrating on his job comes to medical attention because of irregular, jerky movements of his extremities. A sister and an uncle died in mental institutions. A younger brother currently has similar symptoms. His mother became demented in her middle age. Case 2 A 64-year-old male presents with frequent falls. He has Parkinson symptoms (resting tremor, bradykinesia, cogwheel rigidity). You notice the patient has reduced voluntary eye (upward) movements and keeps his neck rather rigid and extended. More importantly the patient is falling with out warning and has trouble keeping his balance. When placed on L-dopa (Sinemet) he had only a slight improvement. Case 3 A 72-year-old retired engineer became acutely confused and disoriented. Symptoms resolved as mysteriously as they started. Over the next 3 years, he gradually became depressed and socially withdrawn and had progressive shortterm memory impairment and repetitiveness. During this time, he would occasionally have visual hallucinations associated with periodic confusional states. His gait deteriorated, and he developed postural instability with retropulsion and stooping. There was no response to a trial of carbidopa/levodopa (Sinemet). Examination was notable for symmetric parkinsonian features, masked facial expression, and postural tremor in his hands. Mental status examination revealed profound impairment in delayed recall, with no benefit from cues or practice trials. Brain MRI demonstrated atrophy; EEG showed diffuse slowing. Trials of various SSRI agents, H2 blockers for reflux and neuroleptics caused delirium. The patient continued this downward, fluctuating course until his death in a nursing home 7 years later. Case 4 A 60-year-old woman with a history of hypertension has been brought to the family doctor because her husband “thought she needed to be checked.” The patient reported that nothing was wrong with her and that her husband had always been overly protective. Her husband reminded her that she had had trouble driving recently, getting lost on several familiar streets, and that at a recent reunion; she had been unable to recall friends. She was unable to handle normal household budget, leaving bills unpaid. Recently she is not taking usual care in dressing. The patient responded that he “was making mountains out of anthills.” The patient also thought that the house had been recently burglarized and that people were watching the house. Except for a long history for gout and an ulcer many years ago, the patient has no history of medical problems. The patient takes no medication. Physical examination and Neurological examination were normal except that the patient was making frequent paraphasic errors. She could not recall any of 3 simple objects. She is aware of the clinic name but not the town and says it is “fallish” in 1982. Case 5 A 55-year-old man, premorbidly described by his family as “thoughtful, accomplished, and intelligent,” began neglecting his home and work responsibilities over a 2-year period. He became increasingly inflexible and uncaring. At work he missed several deadlines, and clients complained that he “forgot” about them. Consequently, he stopped working. He became more impulsive, driving late at night without reason. He obsessively checked his furnace numerous times each day and night, unconcerned about this safety risk. His wife became increasingly tearful and anxious, whereas he seemed unaware of her turmoil and his change in personality. The patient’s personal hygiene declined; he stopped shaving and dressed sloppily. At social functions, he interrupted conversations, touched people inappropriately, and spoke in a tasteless and loud fashion, often embarrassing his wife. Despite these changes, he continued to garden and perform other favored activities, albeit with less attention to detail. Examination results revealed a malodorous and unshaven man with disheveled clothes. He spoke out of turn and was repetitive, stating, ‘I have to go.” At times he attempted to leave the examination room but returned with gentle coaxing. His affect was otherwise flat. He gave concrete, terse responses to questions, mostly affirmative, negative, or stating, “I don’t know.” Naming was impaired. He followed some simple commands, but more complex sequences were incomplete or disorganized. His memory was relatively intact, although retrieval of relatives’ names was impaired. He listed only 5 animals in 1 minute, a significant impairment given his postgraduate education level. Other than motor impersistence and mild rooting reflex bilaterally, the results of the neurologic examination were relatively unremarkable. Over the next 2 years, the patient became increasing withdrawn, spoke less, and required prompting for virtually every activity. Case 6 • A 70-year-old man presented with a 3-year history of progressive memory loss, which mainly affected his short term memory. He needed his daughter to remind him of his appointments and some day-to-day activities. He had problems with driving alone as he became confused with the routes, though he had used them for a long time. He could not manage his bills as usual. The physical examination was unremarkable. The Mini Mental State Examination (MMSE) was 20 out of 30. Case 7 • A 65-year-old man with hypertension, diabetes mellitus, and coronary artery disease developed sudden left hemiparesis and dysarthria 6 months ago. Three months later, his wife noticed that he could not name the only two grandchildren he had and could not remember to take his medications. He could neither operate a remote control nor cook meals as usual. On examination, there was only slight pronator drift on his left arm and hyperreflexia of the left extremities. Clinical Differences Between Vascular Dementia and Alzheimer's Disease Clinical features VaD AD History of atherosclerotic disease Transient ischemic attack, strokes, atherosclerotic risk factors eg., DM, HBP Less common Onset Sudden or gradual Gradual Progression Slow or stepwise progression Slow, progressive decline Neurological examination Neurological deficits Normal Gait Often disturbed early Usually normal Memory Mild impairment in early phase Prominent in early phase Executive function Marked impairment and early Impaired later Type of dementia Subcortical Cortical Neuroimaging Infarction or white matter lesions Normal or hippocampal atrophy Muangpaisan W, Seven steps for internists in evaluating cognitive impairment before performing laboratory investigations. Intern Med J Thai 2005;21:151-61. Case 8 A 72-year-old man with a 6-month history of cognitive impairment and visual hallucination presented to an emergency room after repeated falls a few days ago. His wife felt that he had been slow in thinking, speaking, and performing his routine activities for a few months. On examination, he had bilateral rigidity, parkinsonian gait, and masked face. No history of medication could be elicited. Clinical Differences Between Dementia With Lewy Bodies and Alzheimer's Disease Clinical features DLB AD Isolated memory impairment 93.8% 31.3% Parkinsonism More common Less common and usually develops later in the course Psychiatric symptoms More likely to occur with dementia symptoms early in the course Less likely Fluctuation of cognitive function 50-75% When delirious Verbal memory Better Worse Type of memory impairment Semantic memory Episodic memory Executive function Poor early in the course Less severe in the early phase Attention, visuospatial function, construction abilities More impairment Less impairment Visual hallucinations Common since early phase Less prominent in early course Autonomic involvement Common Less common Neuroleptics response Extrapyramidal side effect; may cause death Behavioral response Muangpaisan W, Seven steps for internists in evaluating cognitive impairment before performing laboratory investigations. Intern Med J Thai 2005;21:151-61 . Clinical Differences Between Dementia With Lewy Bodies and Parkinson’s Disease Clinical features DLB PDD Tremor Less common Common Motor symptoms Bilateral Unilateral predominant Axial Predominant ie., postural instability, gait difficulty and masked face Common Less common Parkinsonism at diagnosis 25 to 50% 100% Response to Levodopa Poor Good Cognitive impairment Before or within one year of motor symptoms Usually developed after motor symptoms 4-5 years (at least 1 year) McKeith I, et al. Dementia with Lewy bodies. Lancet Neurol. 2004;3:19-28. Case 9 • A 50-year-old woman presented with behavioral change over the course of two years. She had less concentration to accomplish her assigned tasks and was less responsible to her job. She had begun eating more and had gained 20 pounds in 5 months. She told lies and dirty jokes, stole office stationary, and picked up objects within reach and sight. She had poor personal hygiene and refused to take a bath. Apart from grasp, and palmomental reflexes, the physical examination did not reveal any other abnormality. Her MMSE was 29/30, but her performance on the clock drawing test was poor. Clinical Differences Between Frontotemporal Dementia and Alzheimer's Disease Clinical Features FTD AD Age at onset Rarely > 75 years Increased markedly with age Early behavioral problems Common Unusual Socially inappropriate behaviors Common early in the course Usually in severe case Memory impairment Less prominent in early course Early and profound impairment Language problems May have isolated language problems without memory impairment Usually associated with memory impairment Visuospatial defect Rare in mild to moderately impaired case Common Motor signs More common (in FTD with motor neuron disease Less common Mood Marked irritability, anhedonia, withdrawal, alexithymia (difficulties in understanding, processing, or describing emotions), euphoria, lack of guilt, apathy or suicidal ideations Sadness, tears, anhedonia, apathy, guilt Psychotic features Rare persecutory delusions, usually jealous, somatic, religious, and bizarre behaviors Usually have delusion of misidentification or persecutory type and usually occur in middle or late stage Appetite, dietary change Increased appetite, carbohydrate craving 80%, weight gain Less common: anorexia and weight loss Muangpaisan W, Seven steps for internists in evaluating cognitive impairment before performing laboratory investigations. Intern Med J Thai 2005;21:151-61. Case 3 A 54-year-old man presents with a severalmonth history of progressive dementia, apathy, dysarthria, tremor, and myoclonus. Case 3 This 45-year-old male who is undergoing immunosuppression for Hodgkin disease presents in your office with a 3 week history of personality change and intellectual impairment. He noticed over the past 24 hours he has problems with his vision, stumbling and occasionally is confused. His vital signs are normal and a left homomous hemianopia and ataxia is noted. He has dysmetria bilaterally upper and lower extremities. You suspect a subacute/chronic viral infection complicating his immunosuppression therapy. Case 2 • A 78-year-old man was brought to the sleep specialist by his wife for episodes of disturbed sleep. His wife had recently noted him yelling or kicking in his sleep. On several occasions, he seemed to try to get out of bed. Once she had to wake him because he was punching her, completely contrary to his character and past behavior. When she woke him after this episode, he told her that he had dreamed that someone was trying to attack him. His wife reported that recently her husband had also been having difficulty with memory loss. An all-night sleep test demonstrated abundant tonic muscle activity during REM sleep. Case 3 A 58-year-old man who is a former boxer develops symptoms of dementia associated with psychomotor slowing. The symptoms did not develop until more than 10 years after cessation of the boxing. Case 5 An 80 year-old-male was seen by you in the ER. The patient and family states the patient has been unsteady and falling but is able to get up with help and return to his previous state of function. Your exam revealed a history of incontinence and a progressive decline in mentation associated with a wide based apraxic gait. Your exam reveals hyperactive bilateral DTRs, a dementia like state, an apraxic gait, incontinence and bilateral papilledema. Case 7 A retired NFL football player developed memory difficulties, mood fluctuations varying from depression to rage. At times he has inappropriate behavior associated with hypersexuality. During his career he experienced 20 documented concussions. Case 3 A 52-year-old “street person” who has been living out of a cardboard box in a city park for the past 5 years after loosing everything in the stock market. He presents with a global confusion, ataxic gait, horizontal nystagmus, and conjugate gaze palsies. He looks emaciated and is known to consume alcohol when he has the money. His BP is 100/60, normal respirations, somewhat agitated and unable to follow commands. Case 9 This 80-year-old edentulous female presents with a sensory ataxia, paresthesias, impaired memory, fecal incontinence, and evidence of neuropathy and spinal cord dysfunction. She has noted that at night she has to keep a light on to prevent falling when going to the bathroom. She is being treated for a hiatal hernia and chronic gastritis for the past 10 years. She has been unable to eat food that she has to chew because she cannot afford dentures. Her exam revealed a mild dementia, decreased proprioception and vibration in the lower extremities, absent ankle reflexes and positive bilateral Babinski's and a positive Romberg test. Case 11 A 24 year-old-female is found in here garage with the car running. You see her in the ER initially unresponsive after administering oxygen she becomes lethargic then confused, complaining of headache, nausea, dyspnea. Assuming she survives and your diagnosis was correct. Case 3 A 50-year-old man experienced the sudden onset of vertigo. Examination revealed dysarthria, difficulty in swallowing, a left Horner’s syndrome, left palatal weakness, and loss of pain sensibility over the left face and the right limbs and trunk. He had coarse ataxia and in-coordination of his left arm. Case 10 A 72-year-old woman with history of hypertension noticed tingling in her right arm. Within 30 minutes, her right leg buckled and she fell. Her husband helped her up. She was able to walk without support. She rested, but within an hour, she noted speech difficulties and more definite right-sided weakness. She was brought to the ED and was noted to have mild right arm weakness and some word-finding difficulties. Her blood pressure was 140/80 mm Hg. She got up to go to the bathroom, walked approximately 10 ft, and collapsed on the floor. She was then globally aphasic, with left gaze deviation (i.e., paralysis of gaze to the right) and right hemiplegia. Within 10 minutes, she became unresponsive. Case 11 A 58-year-old woman with substantial history of arterial hypertension presented to the ED with a 1-hour duration of acute-onset headache, gait unsteadiness, and left arm incoordination. On examination, the patient was alert and oriented but had left-sided dysmetria, gait ataxia, and left-sided CNVI and CNVII palsies. Her BP was 200/110 mm Hg. Case 2 A 64-year-old male presents with frequent falls. He has Parkinson symptoms (resting tremor, bradykinesia, cogwheel rigidity). You notice the patient has reduced voluntary eye (upward) movements and keeps his neck rather rigid and extended. More importantly the patient is falling with out warning and has trouble keeping his balance. When placed on L-dopa (Sinemet) he had only a slight improvement. Case 1 • A 60-year-old woman develops paroxysms of sharp stabbing pain in her right malar area and upper lip, gums, and teeth. Each attack lasts a few minutes and is comparable in abruptness and severity to pain produced by a tooth being drilled. It is precipitated by brushing the teeth and by eating, so that over several weeks she has lost nearly 10 pounds. The pain never spreads beyond the region described, and between attacks she is symptom free except for fear of recurrence, which occurs many times throughout the day. Low potency analgesics do not prevent the attacks. • During examination, brief convulsive movements of her face and jaw accompany an attack of pain, and the physician is able to trigger the pain by lightly rubbing her face with a tongue blade. The neurological examination is otherwise normal. Case 2 A 30-year-old woman is seen with new-onset bilateral asynchronous trigeminal neuralgia. It began without warning 5 days ago and over-thecounter medications is not relieving the pain. She has no other complaint and her history and examination confirms trigeminal neuralgia. Question Symptomatic trigeminal neuralgia often occurs with which of the following medical problems? Case 5 A 55-year-old right-handed male is seen in the ER due to sudden weakness in his right hand and face while mowing his yard. He had no pain at the onset and was alert and had fluent speech. His only noticeable problem was weakness of his left hand and face. The symptoms cleared after 45 minutes. Case 9 A 75-year-old man complains of “blurred vision” in his left eye. The symptoms began several days ago and have progressed slowly. There is no eye pain. He also complains that he has been unable to chew meat because of pain in his jaw. With glasses he is barely able to count fingers with the left eye, but right eye visual acuity is normal. He has a left afferent pupillary defect and a swollen left optic disk. The remainder of his examination is normal. Case 4 A 76-year-old man complained of dull, left-sided head pain with some radiation of the discomfort to the right side of the head. He had no nausea or vomiting with the pain, but had lost 10 pounds over the previous 2 months. His erythrocyte sedimentation rate was 102 mm/hr, and he was mildly amenic. An extensive investigation for malignancy revealed no signs of lymphoma, carcinoma, or leukemia. Case 4 A 50-year-old male involved in a fall at home. He struck the side of his head on the wooden arm of a chair during his fall. The patient seemed fine except he complained of a headache. Tylenol did not relieve it and the patient did not want to go to the ER. His wife insisted and by the time he arrived 1 hour later he seemed somnolent and had nausea which he attributed to a ham and cheese sandwich he had eaten earlier. Your examination revealed a mild weakness of his left arm. No other localizing neurological deficits were noted. Case 1 A 72-year-old man presented with distal paresthesias, more pronounced in his hands than in his feet, unsteady gait, and frequent falls. His family noted some memory loss of unclear duration. On examination, he was oriented to self and place but not to month or year. He immediately registered 3 items, but recalled only 1 item at 5 minutes with clues provided. Visual acuity was poor. On motor examination, he had 4/5 lower extremity strength. His gait was broad based, spastic, and ataxic. Romberg sign was positive. He had loss of vibratory sense in the legs, absent position sense in toes, and hyperesthesia to pinprick in distal extremities. Muscle stretch reflexes were normal. Babinski signs were present. The patient’s hematocrit was 29%, with a mean corpuscular volume of µm3. Vitamin B12 level was 34 (reference range, > 190pg/mL). Read case to get pharm answer for headache pharm A 26-year-old graduate student presents to the emergency room with a severe left-sided throbbing headache, associated with nausea, vomiting, and photophobia. She has tried taking ibuprofen without relief. On further questioning, she relates that she has been having similar headaches 3 to 4 times per month for the past year. Her mother had a similar problem. Her examination is normal. Case 2 A 12-year-old girl presented with difficulty running and standing stationary and frequent stumbling. General examination demonstrated scoliosis and pes cavus. On neurologic examination, the patient had truncal and gait ataxia, a positive Romberg sign, areflexia, and extensor plantar responses. Case 6 A 23-year-old man presents with a 7-year history of arm and vocal tremor. The tremor became more noticeable with action and posture, it never occurred at rest. His gait changed as well with mild unsteadiness, and he experiences a slight tremor of his head when walking. Your examination reveals a dysarthric scanning and slightly slow speech accompanied with a vocal tremor. A mild hypotonia without cog-wheeling or bradykinesia on motor exam. Rapid alternating movements were mildly uncoordinated, with dysdiadochokinesis and dysmetria was seen. Sensory and DTR exam was normal. Routine laboratory findings include low platelet count 100,000 (N-165-415). Total bilirubin 2.7mg/dl (N 0.30-1.30) and direct bilirubin 0.8 mg/dl (N 0.04-0.38) were mildly elevated. The remainder of the routine chemistry and hematology studies were normal. An abdominal ultrasound revealed mild hepatomegaly and marked splenomegaly. Case 9 This 80-year-old edentulous female presents with a sensory ataxia, paresthesias, impaired memory, fecal incontinence, and evidence of neuropathy and spinal cord dysfunction. She has noted that at night she has to keep a light on to prevent falling when going to the bathroom. She is being treated for a hiatal hernia and chronic gastritis for the past 10 years. She has been unable to eat food that she has to chew because she cannot afford dentures. Her exam revealed a mild dementia, decreased proprioception and vibration in the lower extremities, absent ankle reflexes and positive bilateral Babinski's and a positive Romberg test. Case 5 A 20-year-old college student is seen by you after experiencing a focal seizure while hiking alone in Yellowstone National Park, involving the left leg, lasting 1 minute. Followed by a headache that resolved over night. When he made it out of the woods he came to the nearest ER. History is significant for migraine headaches, one or two a month which he treats with triptans, an unenhanced CT scan 1 year ago after a severe status migrainosus was normal. no prior seizures, drug use, or trauma. He feels fine now and there is no neurological deficit. Dr. Carlson – 5 questions 1) Voluntary movement: both gamma and alpha motor neurons are activated simultaneously by descending commands during voluntary motor movements. 2) What would happen to stretch reflexes if you lose type Ia primary afferents? I don’t know, but they respond to the rate of change in muscle length as well as the raw change in muscle length. In other words, they carry both static and dynamic info. MY GUESS is that you would be HYPOreflexive. NOT SURE THOUGH. 3) I have no idea what the other 3 questions will be. Dr. Towns – 12 questions 1) Where would the lesion be if you can hold something in your hand but can’t identify it? Stereognosia. Stereognosis tests determine whether or not the parietal lobe of the brain is intact. Or somewhere in the dorsal columns-medial lemniscus pathway. 2) Differences between dominant and non-dominant hemisphere control. 1) Non-dominant hemisphere: agnosia, apraxia, others… 2) Dominant hemisphere: speech – APHASIA (speech problem). 3) Aphasias: Question about disconnection syndrome. Answer is probably along these lines: Poor repetition but fluent speech, intact comprehension. The lesion is in the ARCUATE FASCICULUS that connects Broca’s and Wernicke’s areas. (see page 404 in 2011 First Aid) 4) What arteries are affected if you have hypertension and then have a stroke? Didn’t hear all these but I know middle cerebral artery was one of the options. 5) Know in details what happens in an infarction of the internal capsule. 6) I don’t know anymore of the questions. The pharmacology guys – 3 from Dr. Theobald on Headaches and 6 from Dr. Middlemas (Info from Erin Majchrzak – Thanks) Acute Headache Treatment Triptans: constricts dilated cranial vessels outside the CNS by stimulating 5-HT receptors; stimulates 5-HT receptors on trigeminal vascular neurons Ergot Alkaloids (Ergotamine): agonists of alpha-1 and 2 adrenergic receptors and 5-HT receptors to reduce amplitude of pulsations of cranial arteries Isometheptene: mild symphathomimetic vasoconstrictor NSAIDS: inhibit synthesis of prostaglandins and autacoids; for migraines and tension HA Prophylaxis Headache Treatment 5-HT antagonists (Methysergide, Cyproheptadine) Methysergide: potent serotonin receptor antagonists, vasoconstricts cranial vessels For prophylactic of migraine and vascular headaches Cyproheptadine: 5-HT2 antagonist, H1-antagonist, weak anti-cholinergic and depressant For receptor blocking activity Beta Blockers (Propanalol): unclear MoA Tricyclic Antidepressants (Amitryptyline):unknown MoA For migraines and chronic tension headaches Calcium channel blockers: inhibit vascular smooth muscle by inhibiting Calcium influx For migraines and vascular cluster HA Lithium: unknown MoA; may inhibit enzymes involved in signal transduction of 5-HT3 receptors For chronic cluster HA and episodic type HA Corticosteroids: related to prostaglandin synthesis; suppress inflammation For ACUTE and PROPHYLAXIS of chronic or episodic cluster HA The pharmacology guys – 3 from Dr. Theobald on Headaches and 6 from Dr. Middlemas (Info from Erin Majchrzak – Thanks) Parkinson Drugs Dopamine Agonists: first line drugs; Pramipexole, Ropinivole, Apomorphine Levodopa: converted to dopamine in striated neurons (presynaptic terminals) SE: dyskinesias, nausea, vomiting, postural hypotensions, psychosis Carbidopa: inhibits decarboxylating enzymes in intestines and peripheral tissues SE: dyskinesia and psychiatric problems sooner COMT Inhibitors (tocapone and entacapone): blocks peripheral conversion of L-dopa Anticholinergic Drugs: second line; better tolerated, for young patients Trihexyphenidyl and benztropine: block M receptors in striatum to reduce tremor and rigidity Amantadine: second line; inhibits dopa uptake, stimulates dopa release, blocks cholinergic and glutamate receptors The pharmacology guys – 3 from Dr. Theobald on Headaches and 6 from Dr. Middlemas (Info from Erin Majchrzak – Thanks) Alzheimer’s Disease AChE Inhibitor Agonists (cross BBB, for mild to moderate disease) Tacrine: poor oral availability, Hepatatoxic SE: nausea, vomiting, salivation, sweating, bradycardia, hypotension, fainting Donepezil: selective for AChE, modest effects; good oral availiability Often combined w/Memantine SE: bradycardia, nausea, diarrhea, anorexia, ab. pain, vivid dreams Rivastigmine: AChE and BChE inhibitor; best for those w/hallucinations SE: nausea/vomiting – they’re much worse Galantamine Hydrobromide: high death rate, so not often used NMDA Receptor (glutamate) antagonists: induces receptor activation and thus Calcium in cell death, also causes a release of extra glutamate Memantine: for moderate to severe disease, is uncompetitive w/a moderate affinity for NMDA Has a fast on and off when glutamate activates the receptor; blocking pathological levels w/maintaining physiologically needed glutamate activity Often combined w/Donepezil SE: dizziness, HA, confusion Drugs for Epilepsy and Seizures Types of Seizures Tonic-Clonic (grand-mal): tonic rigidity followed by clonic jerking, loss of consciousness Carbamazepine, Phenobarbital, phenytoin, primidone, valproate Absence (petit-mal): sudden onset, abrupt cessation, altered consciousness Ethosuximide, valproate Simple Partial: focal process, alert during seizure Carbamazepine, valproate, phenytoin Complex Partial: localized onset, widespread, automatism, amnesia from event Carbamazepine, valproate, phenytoin Myoclonic: series of jerky contractions Valproate Status Epileticus Lorazepam, Diazepam Sodium Channel Blockers Phenytoin: for tonic clonic, simple and complex partial and status epileticus; not during pregnancy Locasamide: adjunct to partial onset seizures; dizziness Lamotrigine: single and complex partial, absence, myoclonic, tonic-clonic Fine for pregnancy, dizziness Zonisamide: for complex partial, tonic-clonic and in combo w/others; dizziness, kidney stones Calcium Channel blockers Ethosuximide: absence, combined w/others; causes nausea, GI effects, drowsiness, anorexia GABA + modulators Phenobarbitol (also agonist): for partial seizures and tonic-clonic; sedation Primidone (also agonist): same as phenobarbitol; sedation Lorazepam: status epileticus; drug of choice for this syndrome; drowsiness, tolerance development Diazepam: same as lorazepam Clonazepam: for absence and myoclonic seizures Multiple MoA Cabamazepine, Oxcarbazepine: tonic-clonic, simple and complex partial; SLE, drowsiness, tolerance can quickly develop Valproic acid: absence, tonic clonic, myoclonic, simple and complex partial; hepatic failure Topiramate (NA channel blocker/GABA modulator): obesity, tonic-clonic, partial complex