Step 1 - Neuro 4

denniskwinn's version from 2015-04-25 16:12


Question Answer
Primary brain tumors clinicalseizures, dementia, focal lesions (due to mass effects). Rarely metastasize. Majority in adults supratentorial, majority in childhood infratentorial. Half of adult tumors are mets (well circumscribed, usually present at gray-white junction)
Glioblastoma multiforme (grade IV astrocytoma)1. Most common primary adult 2. bad prognosis (<1yr) 3. Found in cerebral hemispheres - can cross corpus callosum 4. Stain astrocytes for GFAP 5. Pseudopalisading pleomorphic tumor cells - border central areas of necrosis and hemorrhage
Meningioma1. 2nd most common primary adult 2. Most often in convexities of hemispheres & parasaggital region. 3. from arachnoid cells external to brain 4. Resectable
Schwannoma1. 3rd most common primary adult 2. Schwann cell origin 3. Often localized to CNVIII→acoustic schwannoma 4. Resectable 5. Usually found at cerebellopontine angle 6. S-100 positive
OligodendrogliomaRelatively rare, slow growing. Most often in frontal lobes. Chicken-wire capillary pattern
Pituitary adenomamost common prolactinoma. Bitemporal hemianopia due to pressure on optic chiasm & hyper or hypopituitarism as sequale
Pilocyte (low-grade) astrocytoma1. Primary childhood 2. Most in posterior fossa 3. May be supratentorial 4. GFAP positive 5. Benign, good prognosis 6. Often Rosenthal fibers are present
Rosenthal fiberseosinophilic corkscrew fibers on H&E.
MedulloblastomaPrimary childhood Highly malignant cerebellar tumor. Primitive neuroectodermal tumor (PNET). Can compress 4th ventricle, causing hydrocephalus. Rosettes or perivascular pseudorosette patter of cells (solid small blue cells. . Radiosensitive
Ependyoma1. Primary childhood 2. Ependymal cell tumors most commonly in 4th ventricle 3. Can cause hydrocephalus 4. Poor prognosis 5. Perivascular pseudorosettes, rod shaped blepharoplasts found near nucleus
Hemangioblastoma1. Primary childhood 2. Most often cerebellar 3. Assoc w/Hippel-Lindau syndrome when found with retinal angiomas. 4. Can produce EPO - secondary polycythemia 5. Foamy cells and high vascularity are characteristic
Craniopharyngioma1. Benign childhood 2. Confused with pituitary adenoma (also causes bitemporal hemianopia) 3. Most common childhood supratentorial 4. Derived from remnants of Rathke’s pouch 5. Calcification is common (tooth-enamel like)



Question Answer
Ipsilateral dilated pupils/ptosis from uncal herniationstretching of CNIII (innvervates levator palpebrae)
Contralateral homonymous hemianopia from uncal herniationcompression of IL posterior cerebral artery
IL paresis from uncal herniationcompression of CL crus cerebri (Kernohan’s notch)
Duret hemorrhages - paramedian artery rupture from uncal herniationcaudal displacement of brain stem
Ring enhancing brain lesion ddxMetastases, abscesses, toxoplasmosis, AIDS lymphoma
Uniformly enhancing brain lesion ddxlymphoma, meningioma, metastases (usually ring enhancing)
Heterogeneously enhancing brain lesion ddxGlioblastoma multiforme
Alpha agonists for glaucoma1. Epinepherine, Brimonidine 2. ↓ aqueous humor synthesis due to vasoconstriction 3. Epi SE = mydriasis, stinging, do not use in closed angle glaucoma
Beta blockers for glaucoma1. Timolol, betaxolol, carteolol 2. ↓ aqueous humor secretion 3. No pupil or vision changes
Diuretic for glaucoma1. Acetazolamide 2. ↓ aqueous humor secretion due to ↓ bicarb (via inhibition of carbonic anhydrase) 3. SE = no pupil or vision changes
Direct Cholinomimetics for glaucoma1. Pilocarpine (emergencies), carbachol 2. ↑ outflow of aqueous humor; contract ciliary muscle and open trabecular meshwork 3. SE = miosis, cyclospasm
Indirect cholinomimetics1. Physotigmine, echothiophate 2. Open meshwork into canal of schlemm 3. SE = miosis, cyclospasm
Prostaglandins for glaucoma (1. Latanoprost (PGF2alpha) 2. ↑ outflow of aqueous humor. 3. SE - darkens color of iris (browning)
Opioid analgesics (Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan
Opioid mechanismagonist at opioid receptor - modulate synaptic transmission. Open K+ channels, close Ca2+ channels →↓ synaptic transmission. Inhibit release of ACh, NE, 5-HT, glutamate, substance P.
Opioid Clinical usePain, cough suppression (dextro), diarrhea (loper and diphen), acute pulmonary edema, maintenance for addicts (methadone)
Opioid toxicity (Addiction, resp depression, constipation, miosis (pinpoint pupils), additive CNS depression, Tolerance does not develop to miosis and constipation. Toxicity treated with naloxone or naltrexone (opioid receptor antagonist)
Butorphanol mechanismpartial agonist at opioid mu receptors, agonist at kappa receptors
Butorphanol clinical usePain, causes less resp depression than full agonists
Butorphanol toxicitycauses withdrawal if on full opioid agonist
Tramadol mechanismvery weak opioid agonist; also inhibits serotonin and NE reuptake (works on multiple neurotransmitters)
Tramadol clinical usechronic pain
Tramadol toxicitysimilar to opioids - decreases seizure threshold
Epilepsy drugs table make the table - page 428
Benzodiazepines toxicitiessedation, tolerance, dependance
Carbamazepine toxicitiesDiplopia, agranulocytosis, aplastic anemia, liver toxicity teratogenesis, induction of cytochrome, P-450, SIADH, stevens-johnson syndrome
Ethosuxamide toxicitiesGI distress, fatigue, headache, urticaria, S-J syndrome (EFGH)
Phenobarbitol toxicitiesSedation, tolerance, dependence, induction of cytochrome p450
Stevens-Johnson syndromeprodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital) - skin lesions progress to epidermal necrosis and sloughing
Phenytoin toxicitiesNystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, megaloblastic anemia, teratogenesis, SLE-like syndrome, induction of cytochrome p-450
Valproic acid toxicitiesGI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain, contraindicated in pregnancy
Lamotrigine toxicitiesStevens-Johnson syndrome
Gabapentin toxicitiessedation, ataxia
Topiramate toxicitessedation, mental dulling, kidney stones, weight loss
Phenytoin mechanismuse-dependent blockade of Na+ channels, ↑ refractory period; inhibition of glutamate release from excitatory presynaptic neuron
Phenytoin clinical usetonic-clonic seizure. Also a class IB antiarrhythmic
Phenytoin toxicityNystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome P-450, chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia (↓ folate absorption). Teratogenic (fetal hydantoin syndrome)
BarbituratesPhenobarbitol, pentobarbital, thiopental, secobarbital
Barbiturates mechanismFacilitate GABAa action by ↑duration of CL- channel opening thus ↓ neuron firing
Barbiturates clinical useSedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
Barbiturates toxicityDependence, additive CNS depression effects w/alcohol, respiratory or cadriovascular depression (can lead to death), drug interaction owing to induction of liver microsomal enzymes. Treat overdose with symptom management (assist respiration (↑BP))
BenzodiazepinesDiazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alpraxolam
Benzodiazepam mechanismFacilitate GABAa action by ↑ frequency of Cl- channel opening ↓ REM sleep, most have long half lives and active metabolites
Benzodiazepines clinical useAnxiety, spasticity, status epilepticus, detoxification (especially alcohol withdrawal), night terrors, sleepwalking, general anesthetic (amnesia, muscle relazation), hypnotic(insomnia)
Short acting benzodiazepinesTriazolam, Oxazepam, Midazolam, Highest addictive potential - TOM Thumb
Benzodiazepines Toxicity Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates.
Benzodiazepine toxicity treatmentTreat overdose w/flumazenil (competitive antagonist at GABA benzodiazepenic receptor)
Anesthetics general principles1. CNS drugs must be lipid soluble (cross the BBB) or be actively transported 2. Drugs w/↓ solubility in blood =rapid induction and recovery times 3. Drugs w/↑ solubility in lipids = ↑ potency = 1/MAC (minimum alveolar concentration at which 50% of population is anesthetized) 4. Varies with age
N2O has low blood and lipid solubility = fast induction and low potency
Halothtanehigh lipid and blood solubility = high potency and slow induction
Anesthetics mechanism in lungs↑ rate + depth of ventilation = ↑ gas tension
Anesthetics mechanism in blood↑ blood solubility = ↑blood/gas partition coefficient = ↑solubility - ↑gas required to saturate blood = slower onset of action
Anesthetics mechanism in tissue (e.g. Brain)AV concentration gradient ↑ = ↑solubility =↑gas required to saturate tissue = slower onset of action
Inhaled anesthetics (Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
Inhaled anesthetics mechanismunknown
Inhaled anesthetics toxicityHepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), malignant hyperthermia (rare), expansion of trapped gas (NO)
Barbiturates IV anestheticsThiopental - high potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and short surgical procedures. Effect terminated by rapid redistribution into tissue and fat. ↓ cerebral blood flow
Benzodiazepines IV anesthesiaMidazolam most common drug for endoscopy 2. Used adjunctively with gaseous anesthetic and narcotics. May cause severe postoperative respiratory depression. ↓BP (treat overdose with flumazenil) and amnesia
ArylcyclohexylaminesKetamine - PCP analogs that act as dissociative anesthetics. Block NMDA receptors. CV stimulants, causes disorientation, hallucination and bad dreams. ↑ cerebral blood flow
Opiates IV anestheticsmorphine, fentanyl used with other CNS depressants during general anesthesia
Propofol IV anestheticsUsed for rapid anesthesia induction and short procedures. Less postoperative nausea than thiopental. Potentiates GABAa
Local anestheticsEsters - procaine, cocaine, tetracaine, amides - Lidocaine, mepivacaine, bupivcaine
Local anesthetics mechanismBlock Na+ channels by binding to specific receptors on inner portion of channel. Preferentially bind to activated Na+ channels so most effective in rapidly firing neurons. Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
Local anesthetics principles1. In infected (acidic) tissue, alkaline anesthetics are charged and can’t bind (need higher dose) 2. Order of nerve blockade = small diameter fibers > large diamter. Myelinated fibers > unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated fibers> small unmyelinated > large myelinated fibers > large unmyelinated. 3. Order of loss - pain>temp>touch>pressure 4. Usually given with vasoconstriction (except for cocaine) - enhances local action - ↓bleeding, ↑anesthesia by ↓systemic concentration
Clinical use of local anestheticsMinor surgical procedures, spinal anesthesia, if allergic to esters, give amides
Local anesthetic toxicityCNS excitation, severe CV toxicity (bupivicaine), HTN, hypotension, arrhythmias
NM blocking drugsused for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. Autonomic) nicotinic receptor
NM blocking drugs (depolarizing)1. Succinylcholine 2. Complications include hyperCa and hyperK 3. Phase I (prolonged depolarization) - no antidote -block potentiated by cholinesterase inhibitors 4. Phase II (repolarized but blocked) - antidote consists of cholinesterase inhibitors
NM blocking drugs (nondepolarizing)1. Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium 2. Compete with ACh for receptors 3. Reversal of blockade - neostigmine, edrophonium, and other cholinesterase inhibitors
Dantrolene usetreatment of malignant hyperthermia, caused by concomitant use of inhalation anesthetics (except N2O) and succinylcholine. Also to treat neuroleptic malignant syndrome (toxicity from antipsychotic drugs)
Dantrolene mechanismprevents release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
Parkinson’s treatment pnemonicBALSA (Bromocriptine, Amantadine, Levodopa (w/carbidopa), Selegiline (and COMT inhibitors), Antimuscarinics
Parkinsons disease drugs that agonize dopamine receptorsBromocriptine, pergolide (ergot alkaloid and partial dopamine agonist), pramipexole, ropinirole, non-ergots are preferred
Parkinsons disease drugs that ↑ dopamineAmantadine, L-dopa/carbidopa 2. Amantadine toxicity = ataxia
Parkinsons disease drugs that prevent dopamine breakdown1. Selegine, entacapone, tolcapone (COMT inhibitors - prevent L-dopa degradation increasing availability)
Parkinsons disease drugs that curb excess cholinergic activity1. Benztropine (antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia)
L-dopa/carbidopa mechanism↑ level of dopamine in brain- crosses BBB and converted to dopamine in CNS
L-dopa/carbidopa clinical useParkinson's
L-dopa/carbidopa toxicity1. Arrhythmias (peripheral conversion to dopamine) 2. Long-term use→dyskinesia following administration, akinesia b/w doses 3. Carbidopa, a peripheral decarboxylase inhibitor is given with L-dopa in order to increase bioavailability of L-dopa in brain
Selegiline mechanismselectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5-HT, thereby increasing the availability of dopamine
Selegiline clinical useAdjunctive agent to L-dopa in treatment of parkinson’s disease
Selegiline Toxicitymay enhance adverse effects of L-dopa
Memantine mechanism1. Alz drug 2. NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)
Memantine toxicityDizziness, confusion, hallucinations
Donepezil, galantamine, rivastigmine mechanismAcetylcholinesterase inhibitors
Donepezil, galantamine, rivastigmine toxicityNausea, dizziness, insomnia
Huntington’s drugs1. Disease causes ↑ dopamine, ↓ GABA+Ach. 2. Reserpine+tetrabenazine - amine depleting 3. Haloperidol - dopamine R antagonist
Sumatriptan mechanism5-HT agonist -> vasoconstriction, inhibition of trigeminal activation and vasoactive peptide release. 1/2 life<2hours
Sumatriptan clinical useAcute migraine, cluster headache attacks
Sumatriptan ToxicityCoronary vasospasm (contraindicated in patients with CAD or Prinzmetal’s angina), mild tingling