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1

Arnold-Chiari Type I

Adults: low-lying cerebellar tonsils below formen magnum--> vertebral canal
- Symptoms: headaches, cerebellar symptoms (ataxia), syringomyelia

2

Arnold-Chiari Type II

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

Dandy-Walker syndrome

Agenesis of cerebellar vermis with cystic enlargement of 4th ventricle (fills posterior fossa)
- hydrocephalus
- Spina bifida

Symptoms: postural instability, gait problems

4

Meissner's corpuscles

Large, myelinated fibers (adapt quickly)
Seen in glabrous (hairless) skin

Dynamic, fine/light touch; position sense

5

Pacinian corpuscles

Large, myelinated A-beta fibers
- Deep skin layers, ligaments, joints

Rapid vibration, pressure sense

6

Merkel's discs

Large, myelinated fibers; adapt slowly
- Hair follicles

Pressure, deep static touch (shapes, edges), position sense

7

Endoneurium

Invests single nerve fibers
- Guillain-Barre= inflammation of endoneurium

8

Perineurium

Surrounds fasicle of nerve fibers
- Permeability layer
- Rejoined in microsurgery for limb reattachment

9

Epineurium

Surrounds entire nerve (dense connective tissue)

10

Golgi Tendon Organ

Sensory receptor at muscle-tendon junction
- in SERIES with extrafusal muscle fibers
- Ib innervation--> inhibitory
GTO activated with excess contraction---> relaxation

11

Intrafusal muscle spindles

Ia and II innervation
- Sensitive to stretch (stops excess stretch force)

12

Locus Ceruleus

Site of NE formation
- SAM required to transform NE to epi

NE= tyrosine derived (like DA, epi)

13

Dopamine

Tyrosine-derived neurotransmitters
- Found in Ventral tegmentum, SNc (substantia nigra pars compacta)

14

5-HT (serotonin)

Tryptophan--> BH4 (pyridoxine= B6)--> 5-hydroxytryptamine--> serotonin
- found in Raphe nucleus (pons)

15

Basal nucleus of Meynert

ACh synthesis
- Decreased in Alzheimer's, Huntington's
- Increased in REM sleep

16

Metencephalon

Pons and cerebellum
+ Upper part of 4th ventricle

Part of Hindbrain (Rhombencephalon)

17

Myelencephalon

Medulla
+ Lower part of 4th ventricle

Part of Hindbrain (Rhombencephalon)

18

Diencephalon

Thalamus + Third ventricle

19

Mesencephalon

Midbrain + aqueduct

20

Nucleus accumbens

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

Cross BBB

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

Hypothalamus areas

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

Thalamus

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

Cerebellar peduncles

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)

107

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)

108

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)

109

Midazolam

IV anesthetic= benzo

Use: endoscopy
- Used with gaseous anesthetics, narcotics

Tox: respiratory depression (post-op)
- Decreased BP (tx overdose with flumazenil)
- Amnesia

110

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)

112

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)

113

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