Neuro Flashcards
1
Q
Arnold-Chiari Type I
A
Adults: low-lying cerebellar tonsils below formen magnum–> vertebral canal
- Symptoms: headaches, cerebellar symptoms (ataxia), syringomyelia
2
Q
Arnold-Chiari Type II
A
Babies: Cerebellar tonsil and vermian heniation through foramen magnum
- Aqueductal stenosis and hydrocephalus
- Thoraco-lumbar myelomeningocele
- paralysis below defect
Symptoms: difficulty swallowing, dysphonia, stridor, apnea
3
Q
Dandy-Walker syndrome
A
Agenesis of cerebellar vermis with cystic enlargement of 4th ventricle (fills posterior fossa)
- hydrocephalus
- Spina bifida
Symptoms: postural instability, gait problems
4
Q
Meissner’s corpuscles
A
Large, myelinated fibers (adapt quickly)
Seen in glabrous (hairless) skin
Dynamic, fine/light touch; position sense
5
Q
Pacinian corpuscles
A
Large, myelinated A-beta fibers
- Deep skin layers, ligaments, joints
Rapid vibration, pressure sense
6
Q
Merkel’s discs
A
Large, myelinated fibers; adapt slowly
- Hair follicles
Pressure, deep static touch (shapes, edges), position sense
7
Q
Endoneurium
A
Invests single nerve fibers
- Guillain-Barre= inflammation of endoneurium
8
Q
Perineurium
A
Surrounds fasicle of nerve fibers
- Permeability layer
- Rejoined in microsurgery for limb reattachment
9
Q
Epineurium
A
Surrounds entire nerve (dense connective tissue)
10
Q
Golgi Tendon Organ
A
Sensory receptor at muscle-tendon junction
- in SERIES with extrafusal muscle fibers
- Ib innervation–> inhibitory
GTO activated with excess contraction—> relaxation
11
Q
Intrafusal muscle spindles
A
Ia and II innervation
- Sensitive to stretch (stops excess stretch force)
12
Q
Locus Ceruleus
A
Site of NE formation
- SAM required to transform NE to epi
NE= tyrosine derived (like DA, epi)
13
Q
Dopamine
A
Tyrosine-derived neurotransmitters
- Found in Ventral tegmentum, SNc (substantia nigra pars compacta)
14
Q
5-HT (serotonin)
A
Tryptophan–> BH4 (pyridoxine= B6)–> 5-hydroxytryptamine–> serotonin
- found in Raphe nucleus (pons)
15
Q
Basal nucleus of Meynert
A
ACh synthesis
- Decreased in Alzheimer’s, Huntington’s
- Increased in REM sleep
16
Q
Metencephalon
A
Pons and cerebellum
+ Upper part of 4th ventricle
Part of Hindbrain (Rhombencephalon)
17
Q
Myelencephalon
A
Medulla
+ Lower part of 4th ventricle
Part of Hindbrain (Rhombencephalon)
18
Q
Diencephalon
A
Thalamus + Third ventricle
19
Q
Mesencephalon
A
Midbrain + aqueduct
20
Q
Nucleus accumbens
A
Site of GABA synthesis
- Glutamate converted to GABA by glutamate decarboxylase
*Decreased synthesis in anxiety, Huntington’s
GABA receptor types:
- GABA(A)= Cl- influx in brain (ion channel)
- GABA(B)= K+ efflux, decreased Ca+2 influx inhibit adenylyl cyclase (G-protein)
- GABA(C)= Cl- influx in retina
*Decreased GABA(A) in long term EtOH/benzo use–> withdrawal seizures
21
Q
Cross BBB
A
Glucose and AA by carrier-mediated transport (slow)
Non-polar/lipid-soluble cross rapidly
Specialized areas with fenetrated capillaries:
- Area postrema (vomiting post-chemo)
- OVLT (osmotic sensing
- Neurosecretory products (neurohypophysis–> ADH)
- Hypothalamic inputs/outputs
22
Q
Hypothalamus areas
A
Lateral: regulates hunger
- Inhibited by leptin
- Destruction–> anorexia
Ventromedial: regulates satiety
- Stimulated by leptin
- Destruction (craniopharyngioma)–> hyerphagia
Anterior: cooling, parasympathetic
Posterior: Heating, sympathetic
Suprachiasmatic nucleus: circadian rhythm
**Posterior pituitary (neurohypophysis) recieves axonal projections from supraoptic nuclei (ADH) and paraventricular nuclei (oxytocin)
- Anterior pituitary (adenohypophysis) recieves stimulation from hypothalamus:
- DA–> inhibits Prolactin
- GHRH–> GH release
- LHRH–> LH release, FSH release
- CRH—> ACTH release
- TRH–> TSH release
23
Q
Thalamus
A
VPL: Pain, temp, pressure, touch, vibration, proprioception
VPM: Face sensation and taste (Makeup on the face)
LGN: Vision
MGN: Hearing
VL: motor
Thalamus strok= post-stroke pain (burning/stabbing sensation)
24
Q
Cerebellar peduncles
A
Input= climbing, mossy fibers
- Inferior: ipsilateral proprioceptive info
- Middle: Contralateral cortex
Output= Purkinje fibers
- Superior: Deep nuclei to contralateral cortex
- Deep nuclei (lat–> med): Dentate, Emboliform, Globose, Fastigial (Don’t Eat Greasy Foods)
25
Mesolimbic pathway
Dopaminergic pathway
Midbrain VTA--> Limbic nucleus accumbens
* Stimulation--> delusions, hallucinations, pleasure (Pathway to addiction)
* D3, D4 receptors, inhibited by atypical antipsychotics
26
Mesocortical pathway
Dopaminergic pathway
Midbrain VTA--> limbic cortex (dorsolateral prefrontal)
* Cortex= cognition; defects--> negative symptoms of psychosis
* D3, D4 receptors, inhibited by atypical antipsychotics
27
Nigrostriatal pathway
Dopaminergic pathway
Substantia nigra--> basal ganglia (striatum)
*Movement pathway ("nigrostride"); damage--> Parkinson's
28
Tubuloinfunibular pathway
Dopaminergic pathway
Arcuate nucleus (hypothalamus)--> anterior pituitary
* Inhibit DA--> increased prolactin productions
29
Basal ganglia nuclei
Striatum:
- Putamen (motor) and caudate (cognitive)
Lentiform:
- Putamen and globus pallidus
30
Hemiballismus
Contralateral subthalamic nucleus
- Lacunar stroke
Sudden, wild flailing of 1 arm +/- ipsilateral leg
31
Kluver-Bucy syndrome
Lesion of amygdala, associated with HSV-1
Symptoms:
- Hyperorality (taste, eat anything)
- Hypersexuality
- Disinhibited behavior
32
Cerebellar hemisphere lesion
Intention Tremor, limb ataxia, loss of balance
Damage--> ipsilateral deficits--> fall toward lesion
33
Cerebellar vermis lesion
Truncal ataxia, dysarthria
34
Paramedian pontine reticular formation lesion
Eyes look away from side of lesion
35
Frontal eye field lesion
Eyes look towards lesion
36
Conduction aphasia
Poor repetition with fluent speech, in tact comprehension
- Damage to arcuate fasciculus (connecting Wernicke's to Broca's)
Can't repeat phrase: "No ifs, ands, or buts"
37
Therapeutic hyperventilation and cerebral perfusion
Cerebral perfusion regulated by PCO2 (except in severe hypoxia= PO2 < 60)
Hyperventilation--> decreased CO2--> decreased ICP in cases of acute cerebral edema (stroke, trauma)--> decreases cerebral perfusion
38
Lateral striate artery
Supplies striatum, internal capsule
Lesion--> contralateral hemiparesis, hemiplegia
* *Posterior internal capsule stroke has pure motor/pure sensory deficits
* * Genu of internal capsule= dysarthria-clumsy hand syndrome
39
Anterior spinal artery (ASA)
Supplies:
- Lateral corticospinal tract
- Medial lemniscus
- Caudal medulla (hypoglossal nerve)
** Lesion= Medial medullary syndrome
Stroke: commonly bilateral
- Contralateral hemiparesis, proprioception
- Ipsilateral hypoglossal dysfunction (tongue deviates to side of lesion)
40
PICA (posterior inferior cerebellar artery)
Supplies:
- Lateral medulla: vestibular nuclei, lateral spinothalamic tract, spinal trigeminal nucleus, nucleus ambiguus, sympathetic fibers, inferior cerebellar peduncle
Lesion= Lateral medullary (Wallenberg's) syndrome
- Dysphagia, Hoarsenss, decreased gag reflex
- Vomiting, vertigo, nystagmus
- Decreased pain and temperature sensation to limbs/face
- ipsilateral Horner's
- Ataxia, dysmetria
41
AICA (anterior inferior cerebellar artery)
Supplies:
- Lateral pons (cranial nerve nuclei)
- Vestibular nuclei, facial nucleus
- Spinal trigeminal
- Cochlear nuclei
- Sympathetic fibers
- Middle and inferior cerebellar peduncles
Symptoms:
- Paralysis of face
- Decreased lacrimation, salivation, taste of anterior 2/3 of tongue, corneal reflex
- Decreased pain, temp sensation on face
- Ipsilateral decreased hearing, Horner's syndrome
- Vomiting, vertigo, nystagmus
- Ataxia, dysmetria
42
PCA (posterior cerebral artery)
Supplies:
- occipital cortex, visual cortex
Symptoms:
- Contralateral hemianopia with macular sparing
43
Anterior communicating artery (AComm)
Saccular/berry aneurysm site--> impinge cranial nerves
| - Visual field defects
44
Posterior communicating artery (Pcomm)
Berry aneurysm
| - CNIII palsy (eye down and out, ptosis, pupil dilation
45
Charcot-Bouchard microaneurysm
Associated with chronic HTN (small vessels in basal ganglia, thalamus)
- Visible on CT
46
Epidural hematoma
Accumulation of blood between cavarium and dura
- Creates high-pressure system within the skull
- Usually results from trauma to side of head
Ex: Fracture of temporal bone--> transection of middle meningeal artery
Symptoms:
- Lucid interval after trauma
- Expansion--> transtentorial herniation, CNIII palsy
CT:
- biconvex (lentiform), hyperdense blood collection
- Does not cross suture lines, but can cross falx, tentorium
47
Subdural hematoma
Rupture of bridging veins
- Slow onset (venous blood- less pressure)
- Seen in elderly, alcoholics, blunt trauma, shaken baby (brain atrophy, shaking/whiplash)
CT:
- Crescent-shaped hemorrhage crosses suture lines
- midline shift
- Cannot cross falx, tentorium
48
Subarachnoid hemorrhage
Rupture of aneurysm (berry) d/t Marfan's, Ehlers-Danlos, ADPKD, or AVM
- Rapid onset
- Worst Headache of my Life (WHOML)
Bloody/yellow spinal tap
Risk of vasospasm due to blood breakdown products: avoid with nimodipine (Ca+2 channel blocker)
* * Spontaneous intracranial hemorrhage due to AVM, ruptured crerebral aneurysms, cocaine use
- Berry aneurysms associated with coarctation of aorta (HTN in branches proximal to arch--> increased pressure on cerebral arteries)
49
Intraparenchymal (HTN) hemorrhage
Systemic hypertension, amyloid angiopathy, vasculitis, neoplasm
Occurs in bassal ganglia, internal capsule (Charcot-Bouchard aneurysm)
* *Amyloid angiopathy= recurrent hemorrhagic stroke w/o HTN (milder onset)
- Seen in cerebral hemispheres (vs basal ganglia)
50
Noncommunicating hydrocephalus
Structural blockage of CSF circulation in ventricular system (stenosis of aqueduct of sylvius)
Due to:
- Type II Arnold-Chiari malformations (babies)
- Hereditary aqueductal stenosis
- Prenatal infections (toxoplasmosis)
Presentation:
- Irritable, poor feeding
- Periventricular pyramid tracts stretched---> UMN damage
- Hypertonic muscles, hyperreflexia
51
Dorsal column
Tract: medial lemniscus
Function: ascending pressure, vibration, fine touch, proprioception
Synapse 1: ipsilateral nucleus cuneatus (Upper body) or gracilis (lower body)
Synapse 2: decusses in medulla --> contralateral medial lemniscus--> VPL (thalamus)
52
Spinothalamic tract
Function:
- Lateral= pain, temperature
- Anterior= crude touch, pressure
Synapse 1: ipsilateral gray matter (spinal cord)
Synapse 2: decussates at AWC--> ascends contralaterally--> VPL (thalamus)
53
Poliomyelitis, Werdnig-Hoffmann disease
LMN lesion: destruction of anterior horns
--> flaccid paralysis, weakness, atrophy, fasciculations, hyporeflexia, muscle atrophy
Poliomyelitis: fecal-oral transmitted Picorna virus (ssRNA+, non-enveloped)
- Replicates in oropharnx, small intestine--> bloodstream, CNS
- Diagnosis: CSF with increased WBCs with slight protein elevation (no glucose changes); recover virus from stool, throat
Werdnig-Hoffman: congenital degeneration of anterior horns of spinal cord
- -> "Floppy baby" with hypotonia, tongue fasciculations
- Autosomal recessive
- Death by 7 months
54
ALS (amyotrophic lateral sclerosis)
UMN and LMN deficits
- No sensory, cognitive, oculomotor deficits
Defect in superoxide dismutase 1
Tx: Riluzole: decreases presynaptic Glutamate release--> increased survival
55
Tabes dorsalis
Tertiary syphillis--> demyelination of dorsal columns, roots
--> lose sensation, proprioception, sensory ataxia
Conditions:
- Charcot's joints
- Shooting pain
- Argyll Robertson Pupils: small bilateral pupils constrict to accomodation, not light
- Absent DTRs, positive Romberg (UMN and LMN signs)
56
Syringomyelia
Syrinx (cyst in spinal cord) expands--> damage AWC (anterior white commisure) of spinothalamic tract
- -> bilateral loss of pain and temp (C8-T1)= Cape-like loss of sensation
- Seen in Arnold-Chiari I malformation
57
Vitamin B12, Vitamin E deficiency
Subacute combined degeneration- demyelination of:
- Dorsal columns
- Lateral corticospinal tracts
- Spinocerebellar tracts
Symptoms:
- Ataxic gait
- Paresthesias
- Impaired position, vibration sense
58
Friedreich's Ataxia
Autosomal recessive trinucleotide repeat disorder (GAA on Chromosome 9)
--> mitochondrial function impaired
1. Cerebellar dysfunction--> ataxia
- staggering gait, frequent falling, nystagmus (saccades), dysarthria
2. Degeneration of dorsal columns--> loss of position, vibration sensation
- pes cavus, hammer toes
- May see DM in 10%
Presents in childhood with kyphoscoliosis
Death due to hypertrophic cardiomyopathy:
- Arrhthmias
- CHF
- Bulbar dysfunction (can't protect airway)
59
Brown-Sequard Syndrome
Lateral hemisection of spinal cord:
- Ipsilateral UMN signs below lesion, LMN signs at lesion, loss of tactile sensation, discrimination below lesion, loss of all sensation at lesion
- Contralateral pain and temp loss (2-3 segments below where AWC knocked out)
Lesion above T1: may see Horner's syndrome (damage sympathetic ganglion)
60
Cauda equina syndrome
Damage to S2-S4 nerve roots
- Low back pain radiating to leg(s)
- Loss of ankle jerk reflex with plantar weakness
- Saddle anesthesia, loss of anocutaneous reflex (sphincter pinprick--> contraction)
61
Conus medullaris Syndrome
Lesion at S2-->
- Flaccid paralysis of bladder, rectum, impotence
- S3-S5: saddle anesthesia
- Mild weakness of leg muscles if it spares cord/ roots
62
Moro reflex
"Hang on for life" reflex:
| - Abduct/extend limbs when startled, then draw together
63
Parinaud syndrome
Lesion of brainstem superior colliculi (damage to oculomotor, trochlear nerves, Edinger-Westphal nucleus):
- Paralysis of conjugate vertical gaze
- Absent pupillary light reflex, failure to converge
- Wide-based gait
- Caused by pinealoma
* Inferior colliculi= auditory center
64
Cranial nerve nuclei: location of emergence from brainstem
Midbrain: CN III, IV
Pons: CN V, VI, VII, VIII
Medulla: CN IX, X, XII
Spinal cord: CN XI
* * Medial nuclei= Motor (basal plate)
* * Lateral nuclei= Sensory (aLar plate)
65
Vagus branches
Superior laryngeal nerve:
- External branch= cricothyroid m (runs with superior thyroid artery and vein)
- Internal branch: Sensory above vocal cords
Recurrent laryngeal:
- All laryngeal muscles (-ary-) except cricothyroid
- Sensory below vocal cords
66
Nucleus solitarius
Visceral Sensory information (taste, baroreceptors, gut distention)
CN VII, IX, X
67
Nucleus aMbiguus
Motor innervation of pharynx, larynx, upper esophagus
CN IX, X
68
Dorsal motor nucleus
Parasympathetic (autonomic) innervation to heart, lungs, upper GI
CN X
69
Cavernous sinus syndrome
Cavernous sinus= venous sinus around pituitary
- Blood from eye/superficial cortex--> cavernous sinus--> internal jugular vein
- Contains CN III, IV, V1, V2, VI and postganglionic sympathetic fibers
Mass effect, fistula, thrombosis:
- Decreased corneal, maxillary sensation with normal vision
70
Hearing loss types
Conductive:
- AbnL Rinne test (Bone > air)
- Weber test localizes to affected ear (vibration>air conduction)
- Ex: middle ossicle otosclerosis; rupture of tympanic membrane d/t loud sound
Sensorineural
- normal Rinne test
- Weber localizes to unaffected ear (normal ear picks up sound/vibration, other doesn't)
Noise-induced:
- Damage to stereocilliated cells in organ of corti (shearing forces against tectorial membrane
- Loss of high-frequency hearing 1st
Acoustic reflex: dampen effects of prolonged noise by contracting tensor tympani muscle (via chorda tympani)--> decreased ossicle responsiveness
71
Muscles of mastication
CN V
Open mouth: Masseter, Temporalis, Medial pterygoid
Close mouth: Lateral pterygoid (Lateral Lowers jaw)
72
Accomodation
Focus on near objects--> ciliary muscle tightens--> zonular fibers relax--> lens becomes more convex
- Occurs with convergence, miosis
* * Presbyopia= sclerosis, decreased elastility of lens--> decreased ability to focus during accomodation
- Myopes see improvement in distance vision as lens scleroses--> decreased elasticity, changes in lens curvature, decreased ciliary muscle strength
73
Uveitis
Inflammation of uveal coat (iris, ciliary body, choroid)
- Associated with inflammatory disorders (RA, sarcoid, TB)
- HLA-B27 associated conditions
74
Pupillary miosis
Parasympathetic constriction
1st neuron: Edinger-Westphal nucleus to ciliary ganglion (via CNIII)
2nd neuron: short ciliary nerves--> pupillary sphincter muscles
75
Pupillary mydriasis
Sympathetic dilation
1st neuron: hypothalamus--> ciliospinal center of Budge (C8-T2)
2nd neuron: Exit T1--> superior cervical ganglion (along cervical sympathetic chain near lung apex)--> subclavian vessels
3rd neuron: plexus along internal carotid--> cavernous sinus--> orbit (long ciliary nerve)--> pupillary dilator muscles
76
Pupillary light reflex
Light--> CNII--> pretectal nuclei--> midbrain bilateral Edinger Westphal nuclei--> bilateral contraction
Marcus Gunn pupil= afferent pupillary defect (optic nerve damage, retinal detachment)
- Decreased constriction when light shined in affected eye during "swinging flashlight test"
77
CN III components
Motor= interior of nerve
- Vascular disease--> decreased O2, nutrients--> ptosis, down and out gaze (seen in Diabetes: glucose--> sorbitol)
Parasympathetic: outer part of nerve
- Affected first by compression (PCA aneurysm, uncal herniation)
- Diminished/absent pupillary light reflex ("blown out" pupil)
78
Meyer's loop
inferior retina: Carries superior visual field
- Temporal lobe
- Loops around inferior horn of lateral ventricle
- more susceptible to damage
79
Dorsal optic radiation
Superior retina: inferior visual field
- Parietal lobe
- Shortest path via internal capsule (retrolenticular limb)
- Projects onto occipital cortex
80
Internuclear ophthalmoplegia (INO)
MLF (medial longitudinal fasciculus)= tract communicating between CN VI (lateral rectus) and CN III (medial rectus) to coordinate horizontal gaze
Normal:
- R CN VI activates (abduct R eye)--> R nucleus of CN VI--> Left MLF--> L CN III activation (adduct L eye)
Lesion:
- R abducts--> L MLF lesioned--> no L eye adduction
- Right then develops nystagmus to compensate for Left= Left INO
** Seen in Multiple Sclerosis
81
Alzheimer's disease
Inheritance:
1. Down's syndrome: increased risk due to Amyloid precursor protein (APP) expression on Chrom 21
2. Familial form: 10%:
- Early onset: APP (chrom 21), presenilin-1 (chrom 14), presinilin-2 (chrom 1)
- Late onset: ApoE4 (chrom 19)= protective
Pathophys:
1. Widespread cortical atrophy--> decreased Ach (deficiency of choline acetyltransferase on nucleus basalis of Meynert + hippocampal changes)
2. Plaques form first--> Neurofibrillary tangles
Amyloid plaques:
- Extracellular accumulation of A-beta (fragment of the amyloid precursor protein)
- Abnormal processing of APP critical to pathophysiology of Alzheimer’s disease
Neurofibrillary tangles:
- Intracellular, paired helical structures composed of hyperphosphorylated tau.
- Correlate well with disease severity and neuronal death.
82
Neural tube defect markers
Low serum folate
Elevated fetal, maternal serum alpha-fetoprotein (AFP)
Elevated amniotic AchEsterase
83
Epinephrine
Alpha-agonist used for Glaucoma
MOA: Decrease aqueous humor synthesis via vasoconstriction
Tox: Mydriasis (do NOT use in closed-angle glaucoma)
84
Brimonidine
Alpha-2 agonist for Glaucoma
MOA: decrease aqueous humor synthesis
Tox: blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritis
85
Timolol, betaxolol, carteolol
Beta-blockers for glaucoma
MOA: decrease aqueous humor synthesis
86
Acetazolamide
Diuretic used for Glaucoma
MOA: Carbonic anhydrase inhibitor--> decreased aqueous humor synthesis
87
Pilocarpine, carbachol
Direct cholinomimetics for glaucoma
MOA: Increase outflow of aqueous humor via contraction of ciliary muscle, opening meshwork
** Use pilocarpine in emergencies (opens canal of Schlemm)
Tox: miosis, cyclospasm (contraction of ciliary muscle)
88
Physostigmine, echothiophate
Indirect cholinomimetics for glaucoma
MOA: Increase outflow of aqueous humor via contraction of ciliary muscle, opening meshwork
Tox: miosis, cyclospasm (contraction of ciliary muscle)
89
Latanoprost
Prostaglandin for glaucoma
MOA: increases outflow of aqueous humor
Tox: darkens iris (brown)
90
Opioid analgesics
Morphine, fentanyl, codeine, heroine, methadone, meperidine, dextromethorphan, diphenoxylate
MOA:
- Agonist at opioid receptors: Mu= morphine, delta= enkephalin, kappa= dynorphin
- Modulates synaptic transmission:
- Opens K+ channels--> hyperpolarization--> stop pain transmission
- Closes Ca+2 channels
- Inhibits cAMP formation
- Decreased synpatic transmission
- -> inhibit release of ACh, NE, 5-HT, glutamate, substance P
Use:
- Pain
- Cough suppression (dextromethorphan)
- Diarrhea (loperamide, diphenoxylate), acute pulmonary edema
- Maintenance: potent, long-acting opiate with good bioavailability (Methadone)
Tox:
- Addiction
- Respiratory depression, additive CNS depression with other drugs
- Constipation, miosis (tolerance does NOT develop)
** Overdose: Naloxone, Naltrexone)
91
Butorphanol, Nalbuphine, Pentazocine
Mixed agonist/antagonist
- K and Mu agonist (without other opioid)
- Antagonist of Mu in presence of other opioids
Uses:
- Counteract AEs of opioids (respiratory depression, constipation)pain)
- Central Kappa effect: dysphoria
- Labor pain
92
Tramadol
Dual action: Mu opioid receptor (weak), NE and serotonin reuptake inhibitor
Use: chronic pain
Tox: similar to opioids, decreased seizure threshold
93
Phenytoin
Treats:
- GTC (1st line**), Focal seizures
- Status Epilepticus prophylaxis (1st line**)
- Class Ib Antiarrhythmic
MOA:
- Na+ channel block in cortical neurons (can't recover from depolarization)
AEs:
- Purple glove
- Gingival hyperplasia
- Nystagmus, diplopia, ataxia, sedation
- Hirsutism
- Megaloblastic anemia
- Teratogenic (fetal hyantoin syndrome)
- SLE-like syndrome (slow alkylators)/ serum sickness
- Generalized lymphadenopathy
- Stevens-Johson
- Osteopenia
- Teratogenic: fetal hydantoin syndrome= microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, mental retardation
94
Carbamazepine
Treats:
- GTC (1st line**), focal seizures (1st line**)
- Bipolar disorder
- Trigeminal neuralgia
MOA:
- Na+ channel block in cortical neurons (can't recover from depolarization)
AEs:
- Reacts with everything
- Autoinducer
- Must perform HLA-typing
- DON'T use in myoclonic, absense, aclonic seizures
- SIADH
- Stevens-Johnson
- Diplopia, ataxia
- Blood dyscrasias (agranulocytosis, aplastic anemia)
- Teratogen= neural tube defects, craniofacial defects, fingernail hypoplasia, developmental delay, IUGR
95
Lamotrigine
Treats:
- ALL seizure types
- GOOD Bipolar med
MOA:
- Na+ channel block
AEs:
- Toxic epidermal necrolysis!!
96
Gabapentin
Treats:
- GTC, focal seizures
- pain
MOA:
- alpha-2 delta subunit of Ca+2
Tox:
- Sedation, ataxia
97
Topiramate
Treats:
- ALL seizure but absence type
- Migraine
- Weight loss
MOA:
- Increase GABA
- Decrease NMDA (Na+ channel block)
- CA inhibitor
- Ca+2 block in hippocampus
AEs:
- Kidney stones
- Weight loss
- Sedation, mental dulling
98
Phenobarbital
Treats:
- GTC, focal seizures in INFANTS
MOA:
- Opens Cl- channel LONGER in GABA
- In high enough dose--> binds GABA receptor directly--> opens channel w/o GABA
AEs:
- Overdose- don't use except in children
- Sedation, tolerance, dependence
- CyP-450 induction
99
Benzodiazepines
Treats:
- ALL seizure types
- Status epilepticus (1st line for acute**)
- EtOH withdrawal
- Anxiety
- Sleep (decreases REM sleep)
- Night terrors, sleepwalking
- General anesthetic (amnesia, muscle relaxation)
MOA:
- Increases Cl- channel opening FREQUENCY in GABA
- Long term: decreased GABA receptors
AEs:
- Withdrawal seizures
- Do not take with EtOH
- Respiratory depression
** Treat overdose with Flumazenil
100
Valproic acid
Treats:
- ALL seizure types
- 1st line for Tonic-Clonic**
- Bipolar disorder
- Migraines
MOA:
- GABA increase
- Block NMDA receptors (K+) in hippocampus
- Na+ channel block in cortical neurons (can't recover)
AEs:
- Thrombocytopenia
- Children: Pancreatitis, Hepatitis
- Neural tube defects (due to inhibition of folate absorption)
- Tremor, weight gain
101
Ethosuximide
Treats:
- Absence seizures (1st line**)
MOA:
- T-type Ca+2 channels in Thalamus--> hyperpolarization
Tox:
- GI distress, Fatigue, H/A, urticaria
- Stevens-Johnson
102
Tigabine
Treats:
- partial seizures
MOA:
- GABA increase (inhibits GABA reuptake)
103
Vigabatrin
Treats:
- Partial seizures
MOA;
- Irreversibly inhibits GABA transaminase--> increased GABA
104
Levitiracetam
Treats:
- GTC
- Focal epilepsy
- Myoclonic epilepsy
MOA:
- SV2A
105
Zolpidem, Zaleplon, Eszopiclone
MOA: Act via BZ1 subunit of GABA receptor
Use: Insomnia
Tox:
- Ataxia, H/A, confusion
- Modest day-after psychomotor depression, fewer amnestic effects
- Lower dependence risk than benzos
**Reverse effects with flumazenil
106
Principles of anesthetics
CNS drugs must be lipid soluble (cross BBB) or actively transported
- Drugs with decreased solubility in blood= rapid induction, recovery
- Increased solubility in blood= high AV concentration gradient, slow onset, slow recovery
- Drugs with increased solubility in lipid= increased potency
Potency= 1/MAC
MAC= minimal alveolar concentration at which 50% of population anesthetized
- Varies with ambient temperature and AGE (NOT surgery type, duration of administration, sex, height, weight)
Arterial tension curve:
- Depends on solubility of anaesthetic in blood
- Less soluble in blood: steeper curve (partial pressure of substance in blood increases steeply)
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Inhaled anesthetics
Halothane, -fluranes, NO
MOA: unknown
Effects:
- Decreased myocardial contractility--> decreased renal, hepatic blood flow
- Decreased respiratory drive
- Decreased pulmonary vascular resistance
- Decreased mucocillary reflex
- N/V
- **Increased Cerebral blood flow (increased ICP)**
Tox:
- Hepatotoxic (halothane)
- Nephrotoxic (methoxyflurane)
- Proconvulsant (enflurane)
- Malignant hyperthermia (all but NO)--> reverse with dantrolene sodium
- Expansion of trapped gas in body (NO--> the bends)
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Thiopental
IV anesthetic= Barbituate
- High potency, high lipid solubility (rapid entry into brain)
- **DECREASES CBF: used in stroke to decrease cerebral edema
Use: induction of anesthesia, short procedures
- Terminated by rapid redistribution into tissue (skeletal muscle)
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Midazolam
IV anesthetic= benzo
Use: endoscopy
- Used with gaseous anesthetics, narcotics
Tox: respiratory depression (post-op)
- Decreased BP (tx overdose with flumazenil)
- Amnesia
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Ketamines
IV anesthetic
Arylcyclohexylamines= PCP analogs
- Dissociative anesthetics
- Block NMDA receptors (via glutamate + glycine)
Tox:
- CV stimulants
- Disorientation, hallucinations, nightmares
- Increase CBF
111
Propafol
IV anesthetic
Use: sedation in ICU
- Rapid anesthesia induction
- Short procedures
* * decreased postoperative nausea than thiopental
- Potentiates GABA(A)
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Local anesthetics
```
Esters= procaine, cocaine, tetracaine
Amides= 2 I's in name
```
MOA: block Na+ channels by binding receptor on inner channel
- Bind to activated Na+ channels (most effective in rapidly firing neurons
- Tertiary amines penetrate membrane uncharged and bind ion channels in charged form
Principles:
- Given with vasoconstrictors
- Acidic tissue (infected)--> charges alkaline anesthetics--> can't penetrate membrane--> need to administer more
- Order of blockade: small myelinated > small unmyelinated (C-fibers) > large myelinated > large unmyelinated
- Lose: 1. pain, 2. temp, 3. touch. 4. pressure
Use: minor surgical procedures, spinal anesthesia
Tox: CNS excitation
- CV toxicity (bupivacaine)
- HTN, hypotension
- Arrhythmias (cocaine)
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Succinylcholine
Depolarizing NM blocking drug
MOA: Ach receptor agonist--> sustained depolarization, prevents muscle contraction
- Reverse blockade in 2 phases:
1. Prolonged depolarization (no antidote): block potentiated by AchE-I
2. Repolarized but blocked: Ach receptors available but desensitized
- Antidote= AchE-I (neostigmine)
"Train of 4 response"
- Slow metabolizers take longer to enter phase 2 (antidote won't work until then)
Tox: hypercalcemia, hyperkalemia, malignant hyperthermia
114
Tubocurarine, Atacurium, mivacurium, pancuronium, vecuronium, rocuronium
Nondepolarizing NM blocking drugs
MOA: Competitive antagonist of Ach receptors
Reversal: neostigmine, edrophonium, AchE-I
115
Bromocriptine
Ergot dopamine agonist
116
Pramipexole, Ropinerole, pergolide
Non-ergot dopamine agonist
| - Used in treatment of Restless leg syndrome
117
Amantadine
Increases dopamine release
- Also used as antiviral against rubella, Influenza A
Tox: ataxia
118
Benzotropine
Antimuscarinic/anticholinergic drug used to improve tremor and rigidity associated with Parkinson's
- Can also be used to treat EPS due to antipsychotic antagonism of DA receptors
119
L-dopa
Increases dopamine in brain (can cross BBB)
- Converted by dopa decarboxylase to DA in CNS
Tox:
- Long term use: dyskinesia after administeration, akinesia between doses
- w/o Carbidopa: postural hypotension, N/V, Arrhythmias (increased peripheral catecholamine formation)
- Anxiety, agitation, insomnia, confusion, hallucinations (too much DA)
** Vitamin B6 (pyridoxine)= cofactor for DOPA metabolism (therefore supplements can enhance degradation)
120
Carbidopa
Peripheral dopa decarboxylase inhibitor
- Prevents peripheral formation of dopamine
- Increases CNS levels, limits peripheral side effects
121
Selegiline
Selective MAO-B inhibitor: decreases central DA degradation
| - MAO-B= metabolizes DA over NE/serotonin
122
Entacapone, Tolcapone
COMT inihibtors: prevent L-dopa degradation
- Entacapone= prevents peripheral breakdown
- Tolcapone= prevents peripheral and central breakdown
123
Memantine
NMDA receptor antagonist
- Used in Alzheimer's
- Prevents excitatoxicity (mediated by Ca+2 influx)
Tox: dizziness, confusion, hallucinations
124
Donepezil, galantamine, rivastigmine
AchE-Inhibitors used in Alzheimer's
Tox: Nausea, dizziness, insomnia
125
Huntington's treatments
Tetrabenzine, Reserpine: block VMAT: limit DA packaging and release
Haloperidol: DA receptor antagonist
126
Sumatriptan
Serotonin 1B/1D agonist
- Inhibits trigeminal nerve activation
- Prevents Vasoactive peptide release
- Induces vasoconstriction
Use: acute migraine, cluster headache
Tox: coronary vasospasm (avoid in CAD, Prinzmetal angina), mild tingling
127
Tetrodotoxan
Puffer fish venom
- Blocks voltage-gate Na+ channels in nerve cell membranes
- -> inhibits passive sodium transport
128
Primidone
Antiepileptic drug
- Metabolized to phenobarbital and phenylethylmalonamide
- Used in treatment of essential tremor
129
Alcohol and CNS
Thiamine deficiency:
- Cerebellar atrophy--> Ataxia (weeks to months)= wide-based gait, truncal instability, intention tremor, "Parkinsonian tremor"
- Loss of Purkinje cells in anterior lobes, cerebellar vermis
- Wernicke-Korsakoff syndrome= confusion, ophthalmoplegia, ataxia; memory loss (antero- and retrograde), confabulation, personality changes
130
Pontine hemorrhage
Pinpoint pupils
Loss of horizontal gaze
Quadriparesis
Decerebrate posturing (prostrate position, lesion below red nucleus)--> coma--> death
**Decorticate posturing (bent arms) due to lesion ABOVE red nucleus
131
Thalamic hemorrhage
Contralateral sensory loss, aphasia, temporary homonymous hemianopia (unilateral abducens palsy, pupil asymmetry, nonreactive downward gaze)
132
Peripheral vertigo
More common type
- Inner ear etiology (semicircular canal debris, vestibular nerve infection, Meniere's disease)
- Positional testing-> delayed horizontal nystagmus
133
Central vertigo
Brainstem/cerebellar lesion (vestibular nuclei stroke or posterior fossa tumor)
- Directional change of nystagmus
- Skew deviation, diplopia, dysmetira
- Positional testing--> immediate nystagmus in any direction, may change directions
