Neuro A&P, migraines, PD, MG, MS

Question 1

Explain the diagnostic requirements for migraine

Answer 1

2 features must occur: Unilateral head pain, throbbing pain, worsens with activity, moderate/severe pain.
& one of these: N/V, Photophobia, phonophobia.

Question 2

photophobia

Answer 2

avoidance of light

Question 3

phonophobia

Answer 3

avoidance of sound

Question 4

Define the classifications of migraine

Answer 4

Aura present (visual, sensory, or motor)
Aura not present (most common)
Chronic: 15 days/month for 3 months

Question 5

risk factors for developing a migraine

Answer 5

Family history
Estrogen and progesterone
Genetic and environmental factors

Question 6

Triggers for migraines

Answer 6

Fatigue
Sleep Disturbance: too much or too little
Missed meals
Overexertion
Weather change
Stress
Hormonal changes
Alcohol: red wine
Bright lights or strong smells

Question 7

Pathophysiology for migraines

Answer 7

Change in neurotransmitter levels in CNS.
Blood vessel tone.

Question 8

what are the clinical phases of a migraine?

Answer 8

premonitory phase
migraine aura
headache phase
recovery phase

Question 9

describe the premonitory phase

Answer 9

Hours to days before the onset of the aura or the headache.
1/3 have fatigue, irritability, loss of concentration, stiff neck, food cravings.

Question 10

describe the migraine aura

Answer 10

Up to 1/3 have aura symptoms lasting up to 1 hr.

Question 11

describe the headache phase

Answer 11

Throbbing pain: begins on one side then spreads to the entire head.
Fatigue, N/V, dizziness, hypersensitivity to touch on head.
Last 4 to 72 hrs.

Question 12

describe the recovery phase

Answer 12

Irritability, fatigue, or depression.
Can linger for hours to days

Question 13

Abortive (Symptomatic) Therapy

Answer 13

Aspirin-like drugs: ASA, acetaminophen, NSAIDs.
Serotonin1B/1D Receptor Agonists: sumatriptan (Imitrex).
Calcitonin Gene-related Peptide (CGRP) Antagonist: rimegepant (Nurtec).

Question 14

sumatriptan

Answer 14

Class: Serotonin1B/1D Receptor Agonists
MOA: Constrict intracranial blood vessels, Suppress release of inflammatory neuropeptides, Block brain pathways for pain
indication: migraines
Route: Sub-q, PO, intranasal
SE: injection site reaction (SQ), chest pressure, flushing, weakness, headache, bad taste (nasal)
Considerations: avoid with ischemic stroke or heart disease, and angina

Question 15

rimegepant

Answer 15

Class: Calcitonin Gene-related Peptide (CGRP) Antagonist
MOA: Mediates pain transmission
indication: migraines
Route: PO
SE: GI upset
Considerations: CYP substrate

Question 16

preventative therapy for migraines

Answer 16

Beta-blockers: Propranolol (Inderal)
Tricyclic antidepressants: amitriptyline
Antiepileptic drugs: divalproex (Depakote), topiramate (Topamax)
Estrogens: Menstrual migraine

Question 17

migraines: Preventative Therapy Goals

Answer 17

Reduce attack frequency, severity, and duration.
Improve responsiveness to treatment of acute attacks.
Improve function and reduce disability.
Prevent progression or transformation of episodic migraine to chronic migraine.

Question 18

Discuss the basic organization of the nervous system.

Answer 18

A highly specialized system responsible for control and integration of the body’s activities.
Can be divided into the central nervous system (CNS) and the peripheral nervous system (PNS)

Question 19

the CNS

Answer 19

consists of the brain and spinal cord.
Ascending tracts carry sensory information from the periphery, muscles, and organs to the higher levels of the CNS.
Descending tracts carry impulses from the brain and result in voluntary muscle movement.

Question 20

the PNS

Answer 20

consists of the cranial/spinal nerves and the autonomic nervous system

Question 21

Neurons

Answer 21

the primary functional unit of the nervous system.
Neurons (in general) do not divide or replace themselves.
However, some new neurons may generate from stem cells after a brain injury.

Question 22

Neuroglial cells

Answer 22

more numerous and are supportive to the neuron.
can replicate. provide support, nourishment, and protection to neurons.
They make up almost half the brain and spinal cord and are 5-10x more numerous than neurons.
Different types of glial cells have different functions.

Question 23

Define the 4 main parts of a neuron:

Answer 23

the cell body: the metabolic center of the neuron.
axon: extend varying distances from the cell body and carry nerve impulses. They can be myelinated or unmyelinated.
dendrites: short extensions from the body that receive and conduct nerve impulses.
myelin sheath: a white lipid substance that insulates and helps conduct the impulses.

Question 24

Describe the 3 types of neuroglia

Answer 24

Oligodendrocytes: produce the myelin sheath for nerve fibers in the CNS and help make up the “white matter” of the brain.
Schwann cells: myelinate the nerve fibers in the periphery.
Astrocytes: provide structural support to neurons and form the blood-brain barrier. They are found in the “gray matter” of the brain.

Question 25

Describe how a nerve impulse travels from neuron to neuron.

Answer 25

The initiation of a nerve impulse involves the generation of an action potential. After the action potential is initiated, a series of action potentials travel along the axon. When it reaches the end of the nerve fiber, it is transmitted across the junction (gap) between nerve cells by neurotransmitters.

Question 26

neurotransmitter

Answer 26

a chemical agent involved in the transmission of an impulse across this junction

Question 27

Examples of neurotransmitters

Answer 27

acetylcholine, epinephrine, norepinephrine, serotonin, and dopamine

Question 28

Define Parkinson’s disease

Answer 28

a progressive, degenerative disorder of the basal ganglia function

Question 29

PD is Characterized by...

Answer 29

rest tremors, rigidity, & bradykinesia

Question 30

PD: Primary

Answer 30

Idiopathic = Parkinson’s disease, genetic or sporadic.

Question 31

PD: secondary

Answer 31

Acquired= infection, intoxication, trauma, drug-induced

Question 32

PD: risk factors

Answer 32

age (after 50, peaks at 70, average onset 60), gender: men, genetics: both dominant & recessive, environmental exposures, depression, head trauma, hysterectomy, coffee consumption (protective)

Question 33

PD: Pathogenesis

Answer 33

-Destruction of substania nigra in basal ganglia -Dopamine levels decrease -Imbalance between dopamine & ACH -excess of ACH -Loss of controlled movement & balance

Question 34

why is the substantia nigra significant?

Answer 34

has cells that produce dopamine

Question 35

how does the basal ganglia work in PD?

Answer 35

the basal ganglia works with the cerebellum to make smooth, coordinated movement.

Question 36

dopamine

Answer 36

Inhibitory neurotransmitter Function = message transmission Controls movement and balance Helps muscles work smoothly, controllably, and without unwanted movement

Question 37

Acetylcholine (ACh)

Answer 37

Excitatory neurotransmitter Works in conjunction with dopamine system Balance is CRUCIAL!! Works best when in balance with dopamine

Question 38

PD: Manifestations

Answer 38

Bradykinesia (slowness of movement) Cogwheel rigidity (stiff muscles) Resting tremor (pill rolling tremor) Shuffling gait Mask-like expression Postural instability

Question 39

classic triad of PD

Answer 39

Tremors (@ rest) Rigidity bradykinesia

Question 40

PD: onset?

Answer 40

gradual onset and progression

Question 41

true or false: PD involves both sides of the body at first

Answer 41

FALSE. it may only involve 1 side of the body at first.

Question 42

tremor

Answer 42

Often the first sign Handwriting effected More prominent at rest Aggravated by stress or concentration “Pill roll”

Question 43

Essential tremor

Answer 43

results from faulty neurological impulses Tremors occur with motor function No other manifestations of Parkinson’s Disease

Question 44

Parkinsons tremor

Answer 44

Results from dopamine deficiency Tremors occur with rest and improve with movement Presents with other manifestations of Parkinson’s disease

Question 45

rigidity

Answer 45

Defined = resistance to passive movement “Cogwheel rigidity”: Movements are jerky and slow Associated complaints: Muscle soreness, aches, pain

Question 46

PD: Why does rigidity happen?

Answer 46

Sustained muscle contraction Too much ACh in comparison to dopamine

Question 47

Bradykinesia

Answer 47

Defined = Loss of automatic movements No blinking  No swinging of arms No swallowing of saliva = DROOLING   No self-expression with hands and face = Flat expression Overall lack of spontaneous movement

Question 48

PD: Complications

Answer 48

Dementia (40%) Sleep disturbances Fatigue Depression/anxiety Decreased mobility: malnutrition, aspiration, pneumonia, UTI’s, skin breakdown Drug related complication

Question 49

Treatment goal for PD

Answer 49

to help individuals to maintain motor function

Question 50

How does the pharmacology work for PD?

Answer 50

by correcting the imbalance between dopamine & ACh. Drugs either ENHANCE dopamine or BLOCK the effects of ACH

Question 51

Levodopa/Carbidopa (sinemet)

Answer 51

MOA: Levodopa= converts to dopamine in the brain & activates dopamine receptors; Carbidopa= blocks destruction of levodopa Advantages: most effective drug for PD Disadvantages: takes several months to see improvement, does not work long-term, adverse effects. SE: SE d/t levodopa, N/V- give low dose with food (not protein rich foods), BUT this reduces drug absorption, Dyskinesias- range from annoying to disabling, CV- postural hypotension, dysrhythmias, Psychosis- hallucinations, nightmares, paranoia, Darken sweat & urine, active malignant melanoma. Drug interactions: decreases effects of Levodopa- vitamin B6 (pyridoxine), antipsychotics, protein. Increases effects of levodopa- carbidopa, anticholinergics, MOA inhibitors (can cause toxicity).

Question 52

sinemet: "loss of effects"

Answer 52

Gradual loss of drug effect * Dose wears off * May need shorter dose intervals Abrupt loss of effect * Called the “on-off” phenomenon * Can occur anytime during dosing interval * “Off” periods increase overtime * Can be reduced with drugs and avoiding high-protein meals

Question 53

Duopa

Answer 53

Carbidopa-levodopa infusion instilled via feeding tube into small intestine Gel form (suspension) Continuous infusion for continuous blood level: Up to 16 hours per day. Patients who respond to drug but response fluctuates SE: Falling asleep w/o warning, orthostatic hypotension, hallucinations (visual, auditory, tactile), unusual urges, depression, dyskinesia. Also has SE r/t placement of tube Drug interactions: Do not take within 2 weeks of nonselective MAOI, for depression.

Question 54

Pramipexole (Mirapex)

Answer 54

Class: Dopamine receptor agonist MOA: binds with D2 receptors Indication: Monotherapy in early PD. Combined with Sinemet in advanced PD. Restless leg syndrome. SE: Nausea, sleep attacks, pathologic gambling & other compulsive behaviors. SE In combo w/ Levodopa: orthostatic hypotension, dyskinesias, hallucinations risk doubles.

Question 55

ropinirole (Requip)

Answer 55

Class: Dopamine receptor agonist Indication: idiopathic PD MOA: Unknown but thought to cause an increase in nerve impulses w/in the substantia nigra. SE: similar to other PD drugs; Long term: increased risk of DM & acromegaly.

Question 56

Describe why Levodopa and Carbidopa are given together.

Answer 56

o Carbidopa prolongs the effects of levodopa

Question 57

MS: definition

Answer 57

Chronic, inflammatory autoimmune disorder Potentially disabling disease Brain and Spinal cord: White and gray matter

Question 58

MS: characteristics

Answer 58

Inflammation Demyelination Scar development (Gliosis)

Question 59

MS: risk factors

Answer 59

Age: 20-40 Gender: Women Location: Moderately cool climate (Northern US) Race: Caucasian Genetics: Family history

Question 60

MS: possible RF

Answer 60

Smoking Vitamin D deficiency Obesity Infection: Including Epstein-Barr

Question 61

MS: etiology

Answer 61

unknown, autoimmune may be triggered by infection, genetic predisposition.

Question 62

MS: pathogenesis

Answer 62

Consists of an autoimmune attack against the myelin sheath T lymphocytes migrate to the CNS and cross the blood-brain barrier Antigen-antibody reaction in CNS initiates an inflammatory response Axons are de-myelinated and plaques/sclerosis forms Axons are destroyed

Question 63

how are the Neurons affected by MS in early disease?

Answer 63

Nerve fiber not affected Impulses still transmitted May notice weakness

Question 64

how are the Neurons affected by MS later on in disease?

Answer 64

Axons are destroyed Impulses are totally blocked Permanent loss of function

Question 65

Describe the different types of progression of MS

Answer 65

Benign: after exacerbation they go back to baseline, no loss of function Relapsing-remitting= RRMS: 80-90%, stable between exacerbation, returns a little weaker than baseline. Primary-progressive= PPMS: gradual progression w/o attacks Secondary-progressive= SPMS: initial relapsing/exacerbation followed by remission with some loss of function with each exacerbation Progressive-relapsing= PRMS: gradual progression of symptoms, fewer remission.

Question 66

MS: CM

Answer 66

Cognitive problems: Cog Fog Vision problems Depression Fatigue Pain: Chronic or acute, Burning or stabbing Bowel/bladder Weakness: Including paralysis Sexual issues Muscle stiffness/spasm: Numbness/tingling Walking/balance: Vertigo

Question 67

Is there a cure for MS?

Answer 67

NO

Question 68

MS: goals of therapy

Answer 68

Slow disability Reduce frequency of relapses Reduce new brain lesions

Question 69

what are the drugs for MS used for?

Answer 69

Modify the disease process Treat an acute relapse Manage symptoms

Question 70

Avonex

Answer 70

class: interferon beta-1a/b MOA: Inhibit pro-inflammatory WBCs from crossing BBB SE: Flu-like reactions, Liver toxicity, Bone marrow suppression, Depression, Drug interactions Naturally occurring substance Decrease relapse rate by up to 30% Route: injectable

Question 71

Copaxone

Answer 71

class: glatiramer acetate MOA: Increased production of anti-inflammatory T cells which cross the BBB and suppress inflammation Similar efficacy SE: Injection site reactions; Post-injection reactions-Flushing, palpitations, chest pain, rash, laryngeal constriction, Lasts 15 – 20 minutes, Treatment not necessary.

Question 72

fingolimod(Gilenya)

Answer 72

MOA: Retain lymphocytes in the lymph nodes, preventing them from crossing the BBB – decreasing inflammation Indication: RRMS route: PO

Question 73

dimethyl fumarate (Tecfidera® )

Answer 73

Developed specifically for MS Thought to inhibit immune cells and may have anti-oxidant properties. Route: PO

Question 74

natalizumab (Tysabri)

Answer 74

MOA: Prevents circulating T cells from leaving the vasculature and crossing BBB Therapeutic uses: Multiple sclerosis (reduce relapse by 68%) and Crohn’s disease Monotherapy only: Not used with any other agent, Relapsing form of MS. Route: infusion SE: Most common = Headache, fatigue, Progressive Multifocal Leukoencephalopathy (PML), Hepatotoxicity, Hypersensitivity.

Question 75

alemtuzumab (Lemtrada)

Answer 75

Reserved for patients with poor response to 2 or more MS medications

Question 76

mitoxantrone (Novantrone)

Answer 76

Secondary progressive Progressive-relapsing Worsening RRMS: Without complete remission

Question 77

MS: treating an acute relapse

Answer 77

Preferred treatment: High-dose IV glucocorticoid, Frequent use or long-term use should be avoided. Another option = IV gamma globulin: Used for patients intolerant to glucocorticoids. ACTH (H.P. Acthar Gel): Adrenocorticotropin hormone in gel form, Prolonged release of ACTH after injection, Unable to tolerate steroids or they have not been effective.

Question 78

meds to manage MS symptoms

Answer 78

Urinary frequency/retention- anticholinergics, cholinergic. Constipation- bulk-forming laxatives Fatigue- Amantadine (Symmetrel) Muscle spasms- muscle relaxants Cognitive dysfunction- donepezil (Aricept)

Question 79

what is Myasthenia Gravis?

Answer 79

An autoimmune disease. Characterized by fluctuating weakness of certain muscle groups. Course of the disease is variable: Short-term remission, Stabilization, Severe, progression

Question 80

MG: RF

Answer 80

Age: 10-65 yrs Gender: Women

Question 81

MG: Etiology

Answer 81

Same as every other autoimmune disease! genetic environmental trigger

Question 82

MG: pathogenesis

Answer 82

Antibodies attack ACh receptors: AKA “anti-AChR antibodies” Decrease in ACh receptor sites at the neuromuscular junction This prevents ACh molecules from attaching and stimulating muscle contraction

Question 83

MG: manifestations

Answer 83

Fluctuating weakness of skeletal muscle Strength comes back after resting Muscles involved? Eyes/eyelids, Facial, Speaking, Breathing

Question 84

myasthenic crisis

Answer 84

Acute exacerbation of muscle weakness Triggered by a stressor: Infection, Surgery, Emotional distress, Pregnancy/menses, Inadequate pharmacotherapy or other drugs. Major complication? Breathing muscle weakness Not enough stimulation or acetylcholine Muscles are not stimulated and weak Leading to Respiratory failure

Question 85

cholinergic crisis

Answer 85

Extreme muscle weakness or paralysis S/S of excessive muscarinic stimulation Treatment: Mechanical ventilation Antidote for muscarinic sx = atropine What should the patient wear at all times? Med-alert bracelet Too much acetylcholine or nystigmine overstimulation of muscles and muscles are worn out leading to respiratory failure

Question 86

Name the 2 classes of drugs that are used to treat MG

Answer 86

Immunosuppressants (steroids) Cholinesterase inhibitors

Question 87

Are cholinesterase inhibitors a cure or symptomatic relief?

Answer 87

symptomatic relief

Question 88

How do cholinesterase inhibitors work?

Answer 88

Prevent inactivation of ACh by cholinesterase. Intensify the effects of Ach released from motor neurons– increases muscle strength. Give 30 – 45 min prior to eating to strengthen swallowing muscles

Question 89

Neostigmin (Prostigmin)

Answer 89

Class: Cholinesterase inhibitor (anticholinesterase) Indication: MG MOA: Enhances cholinergic action by facilitating transmission of impulses across neuromuscular actions. In therapeutic doses, this drug affects both muscarinic and nicotinic* receptors route: multiple routes

Question 90

Muscarinic vs. Nicotinic adverse effects of Neostigmin.

Answer 90

Muscarinic: Increased secretions, GI motility, Urinary urgency, Bradycardia, Bronchial constriction, Miosis, near-sightedness Neuromuscular (nicotinic): Therapeutic doses = increased muscle contraction, Toxic doses = reduced contraction, What could toxicity lead to? cholinergic crisis.

Question 91

your patient presents with respiratory insufficiency, extreme muscle weakness, what do you do next to determine if its a MG or cholinergic crisis?

Answer 91

Give EDROPHONIUM: A SHORT ACTING CHOLINESTERASE INHIBITOR, INCREASES ACETYLCHOLINE TEMPORARILY. If they are in a MG crisis, they will improve because there is an increase in acetylcholine. If they are in a cholinergic crisis, they will worsen because they already have too much acetylcholine.