CN the great lock in of this century

what is the pathophys of migraines

trigeminal nerve (CN V) releases neuropeptides → intracranial vasodilation → neurogenic inflammation within the meningeal vasculature

what is aura

1. visual changes (glashing lights, spots, lines zig zags, loss of vision)

2. sensory changes (pins + needles, numbness)

3. speech disturbances and difficulty

Develops over 5-20 minutes and lasts from 5 minutes to an hour

75% of migraines are without aura

what are the causes of migraines

1. genetics (tend to run in families)

2. hormones (estrogen)

3. foods/smells (aged cheese, chocolate, msg)

what are the symptoms of migraine without aura

• unilateral pain, throbbing, pulsatile

• N/V

• sensitivity to light and sound

what are the symptoms of migraine with aura

same as migraine without aura

• unilateral pain, throbbing, pulsatile

• N/V

• sensitivity to light and sound

however, preceded with visual, sensory, and speech disturbances

• aura onset < 1 hr before the migraine

what are the non-pharmacological treatments of migraine

• adequate sleep

• regular meals

• hydration, exercise, relaxation

• go to a cold, dark room

what are the two types of pharmacologic medications for migraines

1. abortive: stop migraine once it starts

2. preventative: reduce frequency/severity

what abortive medication do you use for a mild to moderate migraine and why

NSAIDs (naproxen, ibuprofen, ketorolac) + Excedrin (aspirin-actaminophen-caffiene)

• Migraines involve inflammation + prostaglandins

• NSAIDs block prostaglandin production, which reduces pain and inflammation

• Excedrin: caffeine causes vasoconstriction to counter migraine mechanisms + combo gives stronger pain relief

what abortive medications do you use for moderate to severe migraines and why

Triptans + Ergot Alkaloids

They stimulate serotonin, cause vasoconstriction, block CGRP release

what other meds can you give for migraine and why

Antiemetics: Prochlorperazine (Compazine), Metoclopramide (Reglan)

• they treat N/V, act on the dopamine receptors in the brain, can enhance pain relief + improve med absorption

what three types of preventative meds can you give for migraine

1. beta blockers

2. anti-seizure

3. TCAs

why give beta blockers for migraine and which ones

Propranolol, Metoprolol, Timolol

calm vessel tone + sns

decrease neuronal excitability

why give anti-seizure meds and which ones

Valproic acid, topiramate

• Migraines involve overactive neurons so they calm down the excitability

• reduce abnormal electrical activity

why give tricyclic antidepressants and which ones

Amitriptyline, Imipramine

increase serotonin and norepinephrine, affect pain pathways, regulate sleep + mood

what is a seizure

abnormal, excessive, uncontrolled electrical discharge of neurons in the brain that interrupt normal function

what is epilepsy

chronic disorder of recurrent seizures unprovoked by illness or other circumstances

what is convulsion

spasmodic motor seizure of the entire body

what are the two types of seizures

generalized: involving the whole brain

focal (partial): part of brain

what are the main types of generalized seizures

1. Tonic-clonic

2. Absence seizures

3. Febrile seizures

what is tonic-clonic seizure

1. tonic: stiffening of muscles + cheek/tongue biting, salivation, cyanosis, impaired breathing

2. clonic: rhythmic jerking (rapid, rhythmic, symmetric)

loss of consciousness

3. postictal phase: after-period where pt experiences soreness, fatigue, confusion, weakness, nausea, and no memory of seizure

what are absence seizures

brief staring spells (zoning out appearance)

common in children

what are febrile seizures

tonic-clonic seizure occuring in young children (6m -5yo) with fever

what are the main types of focal (partial) seizures

1. Focal aware (simple partial)

• consciousness is preserved

• person is aware but they make experience jerking in one limb or sensory changes (tingling, visual changes)

2. Focal impaired awareness (complex partial)

• dreamlike alterations or total loss of consciousness

focal seizures can turn into tonic-clonic seizures (focal to bilateral tonic-clonic)

myoclonic, atonic, tonic, clonic

• Myoclonic: brief muscle contraction, single/irregular pattern

• Atonic: sudden loss of muscle tone, “drop attacks”

• Tonic: stiffening or extension of arm(s)/leg(s)

• Clonic: rhythmically repetitive, muscle contraction

what is status epilepticus

medical emergency

seizures occur in succession without recovery → LOC, hypotention, hypoxia, dysththmias, permanent brain damage if not treated

Treated with IV benzodiazepines + other antiepileptic drugs if not resolved within 15 minutes

what are the 5 mechanisms of actions for seizure meds and why are they important

1. Suppression of sodium influx: action potentials decrease

2. Suppression of calcium influx: slows transmitter activity (calcium triggers neurotransmitter release)

3. Promotion of potassium efflux: slows repetitive firing (maintain hyperpolarization, which makes it harder to excte)

4. Antagonism of glutamate: decreases neuronal excitability

5. Potentiation of GABA: decreases neuronal excitability (strong calming effect on the brain)

what traditional AEDs do you use for tonic-clonic seizures

1. Phenytoin (Dilantin)

2. Valproic acid

3. Carbamazepine (Tegretol)

4. Phenobarbitol (Luminal)

what newer AEDs do you use for generalized tonic-clonic

1. Levetiracetam (Keppra)

2. Lamotrigine (Lamictal)

3. Topiramate (Tomamax)

what traditional AEDs do yuse for absence generalized seizure

1. ethosuximide (Zarontin)

2. Valproic acid

what newer AEDs do you use for absence generalized seizures

lamotrigine (lamictal)

what traditional AEDs do you use for focal seizures

Phenytoin (Dilantin)

Valproic acid

Carbamazepine (Tegretol)

Phenobarbitol (Luminal)

These meds are same as you would give generalized tonic-clonic

what newer AEDs would you give for focal seizures

1. levetiracetam (Keppra)

2. oxycarbazepine

3. Gabapentin (Neurontin)

4. Lamotrigene (Lamictal)

5. Pregabalin (Lyrica) - adjunct

6. Lacosamide

what do you give for status epilepticus

IV benzodiazepines

what are two IV benzodiazepines

1. diazepam (Valium)

2. Lorazepam (Ativan)

what is the side effect of phenytoin (Dilantin)

gingival hyperplasia. this is overgrowth of gum tissue, occurs in 20% of Dilantin patients → leads to periodontal disease, tooth decay, oral infections

what is the size effect of carbamazepine (Tegretol)

Stevens-johnson syndrome = toxic epidermal necrolysis

this is a life-threatening skin reaction that causes peeling skin, rash, blisters, mucosal sores, skin necrosis

what does phenytoin do and what is its size effects

stabilizes neuronal membrane by delaying influx of Na+ ions

side effects: gingival hyperplasia → educate on oral care + nystagmus (rapid eye movement) with toxicity

what does carbamazepine do and what are its size effects

it inhibits Na+ to inhibit polysynaptic responses (prevent the cascade of seizure activity with multiple synapses)

side effects: aplastic anemia (bone marrow suppression so you should watch CBC) + steven johnson syndrome (necrosis skin condition)

what does valproate (valproic acid) do

increases GABA effects + inhibits Na+ and Ca2+ to decrease electrical activity

valproate is usually tolerated well, but it can cause liver failure

what does phenoarbital do

decrease CNS by potentiating GABA (GABA = chill pill)

you should monitor for sedation

what do benzodiazepines do and what are some side effects

potentiates effects of GABA

side effects: CNS depression, risk of dependence

what does levetiracetam do and its side effects

inhibits abnormal neuronal firing

Newer AED, so less AE

emotional lability, fatigue, decreased RBC, WBC

what are the important patient teaching considerations

Pregnancy and AEDs:

• many interfere with oral contraceptives, should use alternative form

• increase risk for congenital anomalies (cleft palate, NTDs)

• drug monitoring, aim for minimal effective dose

General population:

• should taper AEDs when discontinuing

• delayed or missed doses may exacerbate seizures

• abrupt discontinuation may cause status epilepticus

what is the pathophys of parkinson’s disease

1. there is a loss of dopamine producing cells in the substantia nigra of the basal ganglia

2. there is not enough doapmine

3. low dopamine causes bradykinesia

4. now there is too much ACh since dopamine inhibits ACh

5. high Ach = over activity of skeletal muscles

also dopamine helps with coordination

what are clinical manifestations of PD

TRAP

T = tremors (pill rolling)

R = rigidity (jerking, cog wheel)

A = akinesia/bradykinesia (reduced or no movement)

P = postural disturbance (stooped posture)

nonmotor symptoms = autonomic dysfunction, sleep disturbances, depression, psychosis, dementia

drooling, sweating, constipation, urinary retention

what PD drugs increase net increase of dopamine in the synapse

1. Levodopa/carbidopa (dopamine replacement)

2. Entacapone (COMT inhibitor)

3. Selegiline (MAO-B inhibitor)

what pd drugs increase the stimulation of dopamine receptors

Dopamine agonsists

1. Bromocriptine

2. Ropinirole

3. Pramiprexole

4. Rotigotine

what pd drugs increase the synthesis and release of dopamine

Amantadine (dopamine releaser)

what pd drugs decrease stimulation of muscarinic receptors

Anticholinergics (antimuscarinics, which decrease muscle activity)

1. Benztropine

2. Diphenhydramine

3. Trihexyphenidyl

what does MAO-B and COMT do and why use MAO-B or COMT inhibitor for pd

they break down dopamine, so you prevent dopamine breakdown to increase avaliability

COMT also breaks down levodopa

what medications do you use for early or mild symptoms of pd

1. MAO-B inhibitors (selegiline)

2. Anticholinergics (Benztropine, Diphenhydramine, Trihexyphenidyl)

what medications do you use for mild to moderate symptoms of pd

1. dopamine agonists (Bromocriptine, ropinirole, pramiprexole, rotigotine_

2. dopamine releasers (Amantadine)

what medications do you use for severe pd

1. levo, adjunct with COMT inhibitors (Entacapone)

2. dopamine agonists (Bromocriptine, ropinirole, pramiprexole, rotigotine_

3. dopamine releasers (Amantadine)

what is levodopa carbidopa

levodopa = precursor to dopamine, which cross the BBB

99% is converted to dopamine in the periphery, so you combine with carbidopa, which decreases peripheral conversion.

this leads to more levodopa in the brain

what are the side effects of levo

1. N/V: activate DA receptors in chemoreceptic trigger zone (CTZ, which is nausea center of the medulla)

2. Dyskinesia: erractic uncontrolled muscle movement (use amantadine to decrease symtpoms)

3. change in behavior, personality, psychosis

4. postural hypotension + dysrhythmias

5. hypertensive crisis with non-selective MAO inhibitor

what is dyskinesia vs. dystonias

dyskinesia = involuntary movements

dystonias = painful muscle contractures, abnormal postures, involuntary twisting

what do you do when levo effects are weaing off

increase dose

decrease dosing interval (less time inbetween)

pair with COMT inhibitor to prolong levodopa ½ life

what are surgical treatments for pd

1. thalamotomy : thalamus since it helps relay motor signals

2. pallidotomy: GPi overactivity which inhibits movement, done to improve rigidity, bradykinesia, tremors (globus pallidus)

3. deep brain stimulator: electrodes to send electrical signals to regulate abnormal brain activity

what is MS

it is an autoimmune disease that results in demylineation + inflammation of myelin sheath of the CNS, esepcially in the brain, spinal cord, and optic nerve. This affects the conduction pathway leading to decreased velocity of the electricity signals

what is the function of the myelin sheath

electrical insulator, when attacked there is a loss of insulation, which disrupts nerve signal transmission

why does the myelin sheath get attacked

T and B cells cross the BBB and mistake the oligodendrocytes as foreign

Plaques form, which leads to axonal damage and scarring, which leads to impaired conduction and progressive neurological dysfunction

what are the s/s or clinical manifestations of ms

1. fatigue, pain, brain fog

2. eyes: diplopia, blurry visian, scotoma (partial loss of visual field), nystagmus, orbital pain

3. ears: tinnitus, vertigo, hearing loss

4. mouth: dysphagia changes in speech

Motor: fatigue/stiffness of extremities, unsteady gait, weakness, flexor spasms, hyperactive, deep tendon reflexes

Cerebellar: loss of balance, poor coordination, intention tremor, clumsy motor movements

Sensory changes: paresthesia, lhermitte sign, decreased temperature perception, bowel/bladder dysfunctions, alteration in sex needs

what is intention tremor (usually found in ms)?

occurs when you reach for something but then your hand starts shaking

similar to parkinsons, ms is symptom management only with no cure (t/f)

true

what pharmacological treatments are used for MS

1. corticosteroids: flares

2. immunomodulators: first-line treatments

3. immunosuppressants: when interferon-beta fails to suppress symptoms/disease

4. antispasmodic drugs: reduce spasms, contractures

what is guillain-barre syndrome (GBS)

autoimmune attack of peripheral nerve myelin, which casuses rapid demyelination, slowing conduction

it is an acute, life threatening disorder

• mostly affects lower motor neurons, which leads to ascending motor paralysis (starts in feet, progresses upwards)

what are the clinical manifestations of gbs

1. respiratory weakness + resp muscle paralysis (this can cause death), ANS dysfunction

2. sensory and motors affected

3. ascending motor paralysis, numbness/tingling in distal extremities

describe MS disease courses

1. relapsing-remitting (most common), alternative episodes of worsening and recovery

2. primary progressive

3. secondary progressive

4. progressive relapsing

(t/f) ms manifestations vary based on lesion (plaque) location

true

optic nerve is most commonly affected

what is lhermitte sign

often seen in MS

• electrical sensation that is felt down the arms, back or lower trunk when the patient flexes their neck

what often causes gbs

viral GI or respiratory infection

• EBV : epstein-barr virus

• CMV: cytomegalovirus

• mycoplasma pneumoniae

• zika virus

what is gbs treatment

1. high-dose IV immunoglobulins: this neutralizes antibodies causing GBS

2. plasmapheresis = selectively filter and remove antibodies

3. airway management

what are other GBS clinical manifestations

1. distal to proximal weakness / paresthesisa

2. autonomic dysfunction (dysautonomia): postural hypotension, facial flushing, arrhythmias, decreased sweating/salivation, urinary retention

3. hyporeflexia (reduced reflexes) → paresis (weakness of voluntary muscles) → quadriplegia -(weakness and paralysis of all 4 limbs)

4. dysaytonomia

upward weakness starting from feat to the head

what are the stages of GBS

1. acute/inital period (1-4 weeks)

2. plateau (days to weeks)

3. recover phase (4-6 months up to 2 years), usually in one year

• remyelination and axonal regeneration

what is myasthenia gravis

it is the autoimmune attack of ACh receptors at the neuromusclar junction. It is antibody mediatied (autoimmune). antibody (compliment) mediated destructing of ACh, nicotonic, receptors in NMJ

So when acetylcholine is blocked from binding to the recptor, muscles dont get the signal to contract → muscle weakness that worsens with activity (fatigable weakness generally in those innervated by the cranial nerves + skeletal + resperitary muscles)

most patients have thymus dysfunction

clinical manifestations of myasthenia gravis

1. rapid onset fatigue

2. muscle weakness: ocular signs = ptosis (eyelid droop), diplopia (double vision)

3. facial weakness

4. dysphagia

5. dysarthria (difficulty articulating words)

6. respiratory compromise, SOB

7. unstable wadding gait

what are the pharm interventions for MG

1. acetycholinesterase inhibitor (inhibits the enzyme that break down ACh)

• Neostigmine, pyridostigmine (-stigmine)

2. corticosteroids, immunosuppresants: suppress immune response, used if inhibitor is ineffective

what are the two emergency crisis of myasthenic gravis?

1. myasthenic crisis

2. cholinergic crisis

a tensilon test is used to distinguish between the two

what is mysathenic crisis

exacerbation of the myasthenic symptoms caused by stressors (infection, surgery, pregnancy), undermedication, or spontaneous occurence

undermedication is important cause

what are the myasthenic symptoms

1. increased pulse, RR, BP

2. bowel and bladder incontinence

3. extreme muscle weakness → death

you should maintain adequate respiratory function + ventilator supprot

administer neostigmine, immunosuppressants

what is cholinergic crisis

acute exacerbation of muscle weakness caused by overmedication with cholinergic (anticholinesterase) drugs

*overmedication = too much ACh = muscle overstimulation + excessive muscarinisc activity

what are the s/s of cholinergic crisis

1. muscle related: recepters get overloaded leading to weakness or paralysis

2. SLUDGE = too much PSNS stimulation

S = salivation

L = lacrimation (tearing)

U = urination

D = defecation

G = Gi distress

E = emesis (vomiting)

how do you treat cholinergic crisis

1. hold anticholinesterase drugs while client is maintained on a ventilator

2. atropine may be given and repeated (displaces acetylcholine, decrease SLUDGE symptoms)

3. improvement is usually rapid after appropriate drugs have been given

what is tensilon test

• differentiate cholinergic from myasthenic crisis

• within 30-60 after tensilon injection, most myasthenic clients show imrpovement in muscle tones that last 4-5 minutes

what does tensilon do

endrophonium chloride: prevent the breakdown of acetylcholine (which is why myasethnic clients show improvement since they are undermedicated

what is the antidote for Tensilon

atropine sulfate

how do you treat myasthenic crisis

give neostigmine since ur undermedicated, immunosuppressants