NPLEX Combination Review

Neurology - C

Paul S. Anderson, ND

Medical Board Review Services

Copyright MBRS
Headache
 Headache Comparison
Feature Cluster Migraine Tension
Gender male female equal
Age/onset 20-50 yrs 10-40 yrs Any age
Frequency 1-8/d 1-8/mo daily
Duration ½-4 hrs 4-72 hrs. steady
Intensity severe moderate Dull ache
Location unilateral Unilat/bilat bilateral
 Headache Comparison
Feature Cluster Migraine Tension

Nasal con 70% none none

Teary eye common none rare

N and V rare common rare

nocturnal common rare rare

Behavior restless hibernates hibernates

Family Hx 7% 90% + with stress

 Headache – As a Sign:
• Infectious • Tumor
– Encephalitis • Eye
– Meningitis • Vascular • Sinus
• AVM
• Aneurism • Cluster
• HTN • Tension
• Giant • Migraine
• [Trigeminal
Cell Neuralgia]
Arteritis
 Tension headache
• Most common type of headache
– Muscle tension of scalp and neck
– Steady vice-like pain
– Usually bilateral, starting in occiput and
spreads to frontal/temporal areas
• Can recur daily more in p.m.
– May last for days to months
– Not associated with nausea/vomiting
– May overlap with / trigger migraines
 Migraine headaches - 1
• Common:
– without aura
• Classic:
– With aura prodrome
• Complicated:
– associated with sensory or motor neurological defects

• Diagnosis made clinically

– Look for + F.H.
– Exclude other causes,
• e.g. tumor, sinusitis, glaucoma, temporal arteritis, etc.
 Migraine headaches - 2
• Paroxysmal disorder characterized by
recurrent attacks of headache, with or
without associated visual, neuro or G.I.
symptoms
• Associated with vasodilatation and
vasoconstriction of intracranial arteries
• Intracranial a/v malformations, tumor,
heredity, estrogens, foods are triggers
 Migraine Myths
• Migraine is neither an "extreme headache" nor a
psychosomatic condition, as many patients and
some healthcare providers continue to believe.
• One of the most pervasive misconceptions is that
migraine is a vascular disease.
– Current and emerging evidence disproves this notion and
has established that migraine has a distinctive
physiology based on a neurological process.
• Due to poor understanding about the condition,
migraine is often misdiagnosed – or not diagnosed at
all.
• It is frequently mistaken for tension-type or sinus
headache, even though headache specialists
consider the latter to be relatively rare
Cady R, Dodick D, Levine H, et al. Sinus headache: a neurology, otolaryngology,
allergy, and primary care consensus on diagnosis and treatment. Mayo Clinic
Proc. 2005:80(7):908-916.
 Pathophysiology - Wenzel
• Migraine is now known to be a neurological
process of the trigeminovascular system, rather
than a vascular event. The vascular theory has been
debunked for several reasons:
– vascular changes do not explain the premonitory and
other symptoms linked with migraine.
– some useful migraine treatments have little effect on
vasculature.
– according to blood flow studies, vascular changes only
occur randomly in migraine attacks and do not correlate
with the clinical features of the condition.
• Migraine is a neurochemical chain reaction that
involves 5 distinct phases of a neurological process:
prodrome, aura (may or may not be present), mild,
moderate, or severe pain, and postdrome.
 Pathophysiology - Wenzel
• Once the reaction is "triggered", fluctuation in neuronal
activity may activate the trigeminovascular system in the
meninges.
– Once activated, the trigeminal afferent can release various
vasoactive peptides, producing an inflammatory response that
probably causes head pain.
• In turn, the inflammatory response lowers the sensory threshold of
the trigeminal afferents, increasing the flow of sensory traffic to the
second-order neurons in the brainstem, especially the trigeminal
nucleus caudalis.
– The sensory material is allowed to reach high centers of the thalamus
and cerebral cortex – the central areas of pain perception.
• Migraine symptoms follow the escalating neuronal process.
Migraine attacks tend to build in pain intensity and frequency over
hours or days. The activation of the trigeminal system also
explains facial pain and neck pain that can occur during migraine
and that are often mistaken for symptoms of either a sinus or
tension-type headache.
Hargreaves RJ, Shepheard SL. Pathophysiology of migraine–new insights. Can J Neurol Sci.
1999;26(suppl 3):S12-S19.
Triggers:
 Migraine
• Goal generally is vasoconstriction

• Triptans are specific 5HT effectors

• Ergot drugs are alpha effectors

 “Triptans” ; Sumitriptan
Mechanism of Action
• Sumatriptan is an agonist for a vascular 5-
hydroxytryptamine1 receptor subtype having only a
weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors.
• The vascular 5-HT1 receptor subtype that sumatriptan
activates is present on cranial arteries in both dog and
primate, on the human basilar artery, and in the
vasculature of human dura mater and mediates
vasoconstriction.
– This action in humans correlates with the relief of migraine
headache.
– In addition to causing vasoconstriction, experimental data from
animal studies show that sumatriptan also activates 5-HT1
receptors on peripheral terminals of the trigeminal nerve
innervating cranial blood vessels.
– Such an action may also contribute to the antimigrainous effect
of sumatriptan in humans.
 “Triptans” ; Sumitriptan
Indications and Usage for Imitrex
• Imitrex Tablets are indicated for the acute treatment of migraine attacks with or without
aura in adults.
– Imitrex Tablets are not intended for the prophylactic therapy of migraine or for use in the
management of hemiplegic or basilar migraine.
– Safety and effectiveness of Imitrex Tablets have not been established for cluster headache,
which is present in an older, predominantly male population.
Contraindications
• Imitrex Tablets should not be given to patients with history, symptoms, or signs of
ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition,
patients with other significant underlying cardiovascular diseases should not receive
Imitrex Tablets. Ischemic cardiac syndromes include, but are not limited to, angina
pectoris of any type (e.g., stable angina of effort and vasospastic forms of angina such
as the Prinzmetal variant), all forms of myocardial infarction, and silent myocardial
ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any
type as well as transient ischemic attacks. Peripheral vascular disease includes, but is
not limited to, ischemic bowel disease.
– Because Imitrex Tablets may increase blood pressure, they should not be given to patients
with uncontrolled hypertension.
– Concurrent administration of MAO-A inhibitors or use within 2 weeks of discontinuation of
MAO-A inhibitor therapy is contraindicated.
– Imitrex Tablets should not be administered to patients with hemiplegic or basilar migraine.
– Imitrex Tablets and any ergotamine-containing or ergot-type medication (like
dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor
should Imitrex and another 5-HT1 agonist.
– Imitrex Tablets are contraindicated in patients with hypersensitivity to sumatriptan or any of
their components.
– Imitrex Tablets are contraindicated in patients with severe hepatic impairment.
 Ergot Alkaloids
Ergot MOA Uses Adverse Effects Other
Migraine
Medications /
Uterine
Stimulants
Ergonovine Vasoconstriction, Migraine; Hypertension, Acute dosing
Induce contractions of seizures, is Sub-Q
DHE or the uterine smooth Prevention and injection;
muscle treatment of may cause infant
Methyl- postpartum or mortality if given Not for labor
ergonovine post abortion before delivery induction
[Methergine] hemorrhage
 Cluster headache
• Lasts 15 to 180 min, severe, unilateral, located
periorbitally, can occur 6-8x’s/day, associated
with tearing, red eye, stuffy nose or miosis
• More in men 30-60 yrs
• Etoh, stress, lack of sleep can trigger
• Usually occurs in spring and fall
• Rapid onset, often at night; pain is severe
• Unlike migraines, no n/v
 Infection (meningitis, encephalitis)
• Usually gradual onset of headache,
severe,
nuchal rigidity present with meningitis
• Diagnosis made by L.P.
– MRI, CT
• Fever usually present, plus other findings
of infection
 Encephalitis
• Severe:
– Headache with systemic sn/sx (fever, n/v…)
– Often focal neurological deficit
• Sub-acute:
– Like a severe viral illness.
– Headache PERSISTS even as the systemic
sn/sx wane.
Headache

Severity

Other Sn/Sx
Time
 Trigeminal neuralgia
• Shooting pain in face from 5th C. nerve
– Lower 2 divisions of 5th usually involved

• Attacks occur in spring and fall

• Pain is lancinating; can be triggered by

touch, drafts, brushing teeth

• No sensory loss or motor weakness

 Giant cell arteritis
• Symptoms include malaise, proximal muscle
pain, jaw claudication, tender scalp arteries

• Untreated, blindness results in 50% of

pts who present with headache

• Lab shows ESR over 100/+ biopsy of artery

Carbon monoxide exposure
 Pain
Pharmacology
Pain and CNS / Pain Medications
• Central Pain Control
– Central Muscle Relaxants – non-DEA
– Central Pain Control
• DEA Scheduled
• Non-DEA Scheduled

• Peripheral Pain Control

– Non-DEA Scheduled
In the US – the DEA regulates certain drugs as “scheduled” or
“Controlled” – They are on this list due to the potential for
Diversion.

• All prescription drugs are considered

“Legend” substances.

• Only some Legend substances are

Controlled or Scheduled.
– The DEA Schedule of controlled substances
stratifies these drugs by an arbitrary system of
“most chance for diversion to least chance for
diversion”.
 ANALGESICS AND ANTIINFLAMMATORIES
• D.E.A. Classifications (Class I – V)
– A classification of drug agents (analgesic, and other categories) based on potential for
abuse and addiction.

• Specific Drugs, as classified:

– C-1: Heroin, L.S.D., Peyote, Marijuana
– C-2: Dronabinol (Marinol), Morphine, Oxycodone(Percodan /
Percocet), [**Hydrocodone and Codeine – plain form] Fentanyl (and all
its family), Methadone, Meperidine (Demerol), Hydro & Oxymorphone.
– C-3: Codeine + ASA or APAP (Tylenol 1,2,3,4), Hydrocodone +
APAP or Ibuprophen (Vicodin, Vicoprophen), Codeine or
Hydrocodone antitussive syrups (Hycodan, Robitussin AC, DAC).
[Testosterone]
– C-4: Pentazocine (Talwin), Propoxyphene (Darvon, Darvocet),
Butorphanol (Stadol [NS or Inj.]). [Diazepam…Barbital…Chloryl
Hydrate]
– C-5: Buprenorphine inj., Dilute forms of Codeine / Hydrocodone
– No DEA designation: Tramadol (Ultram), Nalbuphine inj.
Muscle MOA Uses Adverse Effects Other
Relaxants

Methocarbamol Unknown; may Muscle pain and Drowsiness, syncope, Do not inject in
carbamate derivative of modify central tetanus headache, hypotension, patients with
guaifenesin
pain perception management diplopia, nystagmus, GI impaired renal
upset and anaphylactic function or seizure
without changing reactions disorder
reflexes

Carisoprodol Modify Acute painful Drowsiness, dizziness, Avoid CNS

perception of musculo- orthostatic hypotension, depressants
(Soma) N/V, irritability, including alcohol
pain by blocking skeletal
headache, rash and
activity in conditions anaphylaxis
descending RAS

Cyclobenzaprine Unknown Muscle spasm Drowsiness, dizziness, Do not use with

Tricyclic seizures, dry mouth, MAO inhibitors
hydrochloride syncope and
(Flexeril) derivative
tachycardia and GI LONG t ½
upset
Quinine Affects calcium Prevention of Seizure, cardiac Contraindicated
distribution nocturnal leg arrest, cardiotoxic, in tinnitus, optic
within muscle muscle cramps and chinchonism neuritis, G6PD
fibers to deficiency,
decrease thrombocyto-
excitability of penia or
motor-end plate hypersensitivity
to quinine

Cinchonism!
• Quinine AND Quinidine:
• Tinnitus / Hearing Loss
• Headache / Nausea
• Dizziness / Vertigo
• Visual changes
 Opiate Drugs
• All have Central (Kappa / mu) receptor
activity causing pain dissociation
– Overdoes = Death from respiratory distress.

• ALL have Parasympatholytic activity

– Constipation
– Nausea
– Vomiting
– Rebound insomnia
Opiates: MOA Uses Adverse
Effects
Codeine Opiate receptor Mild to moderate SAME
[Tylenol-3, 222 …] agonist, pain and non-
suppresses productive coughs respiratory
cough reflex depression,
Often mixed with
Tylenol or
Ibuprophen for pain
Sedation,
dizziness,
Hydrocodone Opiate receptor Moderate to severe nausea,
[Vicodin / agonist pain vomiting,
Vicoprophen] constipation,
diaphoresis,
Oxycodone hypotension
[Percocet /
Percodan /
Oxycontin]
 Morphine
Morphine Opiate Severe Constipation, Tolerance
receptor pain respiratory often
agonist depression, develops
orthostatic
hypotension,
nausea,
vomiting,
euphoria,
shock, cardiac
arrest
 Other Opioids and Relatives
• Heroin
– Strong injectable Opiate
– Same potential S/E’s as Morphine
• Methadone
– Mu and NMDA binding (no Kappa)
– Used for addiction (“Opiate replacement”) and pain
– Same potential side effects
• Naloxone
– Central Opiate Receptor Blocker
– Used in EMS (IV) – For Opiate Overdose
• Naltrexone
– Same as Naloxone – Also used orally LOW DOSE in
Cancer and Autoimmunity
 Propoxyphene
• Synthetic Opiate Agonist
• Trade Name: [Darvon, Darvocet] (US – CIV)
– Essentially the same effect / side effect profile as
Hydrocodone.
• November 19, 2010 — The US Food and Drug
Administration (FDA) has asked that propoxyphene …
be removed from the market.
• New clinical data showing that the drug puts patients
at risk for potentially serious or even fatal heart rhythm
abnormalities has prompted regulators to act. An
estimated 10 million patients have used these
products.
 Non-Controlled Pain Drug
• Ultram (tramadol HCl)
– Centrally acting synthetic opioid analgesic
• Seizure risk in normal and above normal doses.
Elevated in patients taking SSRI’s, Tricyclics and
other Opioids.
– Immediate Release
• 50 mg tablets
• Sig. 50 to 100 mg q. 4-6 hrs up to 400 mg/d dose
– Extended Release
• 100, 200 and 300 mg ER tablets
• Sig. 100 to 300 mg ONCE daily, up to 1- 300mg ER
tablet daily.
Acetaminophen MOA Uses Adverse Effects Other

[Tylenol] Exact MOA Fever Adult dose Acetylcysteine

[Paracetamol] unknown. and pain. threshold is 4 (NAC –
Weak Grams / 24 hours. Mucomyst)
“APAP”
analgesic, assists in
anti-pyretic. Newer “public” acetamino-
recommendations phen
Thought to have a 3 Gram cap. excretion.
elevate pain
threshold and Single dose liver Normally
act in the toxicity 7-10 grams used if dose
hypothalamic (140mg/kg). > 140mg/kg
temperature
center. Toxic dosages can
cause hepatic
necrosis – ETOH
increases
hepatotoxicity at 3
drinks / day.
Peripheral Pain Control

• NSAIDS

• Steroids

• Gout Medications
 EICOSANOIDS

MEMBRANE PHOSPHOLIPID
Stimulated by: Angiotensin - 2 /
Bradykinin / Epinephrine /
Phospholipase A2
Thrombin

Inhibited by: CORTICOSTEROIDS

ARACHADONATE
Inhibited by:
Lipoxygenase Cyclooxygenase NSAID’S

PROSTAGLANDINS /
LEUKOTRIENES
THROMBOXANES
NSAIDS MOA Uses Adverse Effects Other

Aspirin Blocks prostaglandin Anti- Salycism: tinnitus, Stops

synthesis inflammatory, hearing loss, production of
anti-thrombotic vertigo histamine 2 to
Also: GI upset, decrease the
nausea, amount of
thrombocytopenia, occult mucus
bleeding, dyspepsia, rash,
anaphylaxis and Reye’s produced in
syndrome stomach

Ibuprofen Unknown, possibly Inflammatory Headache, Monitor blood

blocks prostaglandin conditions dizziness, GI levels for
synthesis distress, peripheral toxicity when
edema, tinnitus, used with
acute renal failure, digoxin, lithium
peptic ulcer, occult or
blood, bronchospasm, anticoagulants
Stevens-Johnson
syndrome

Naproxen Unknown, possibly Inflammatory GI distress, Better tolerated

[Naprosyn] blocks prostaglandin conditions, mild Headache, than aspirin
synthesis to moderate drowsiness, dizziness,
pain edema, tinnitus,
nephrotoxicity, rash
Cox 2
Inhibitors

Rofecoxib
[Vioxx]
Blocks Inflammatory Less GI distress Expensive
Cyclooxygenase-2 conditions than aspirin,
Celocoxib Activity indigestion, gas,
[Celebrex] diarrhea,
abdominal pain
 Toradol (ketorolac tromethamine)
• Moderately severe to severe pain only.
– NSAID
– Not for use over 5 days in duration
– No pediatric use.
– Dose adjusted in patients over age 65 or with
impaired GFR

• IV/IM form as well as 10 mg tablets

– Dosage:
• IM: 60 mg; IV 30 mg single dose
• Oral: 10 – 20 mg loading dose, then 10 mg q. 4-6 hrs
– not to exceed 40 mg daily
Steroids MOA Uses Adverse Effects Other

Hydrocortisone Act by binding Inflammation, Adrenal Prednisone

(Physiologic to cortisol adrenal suppression, longer acting than
oral dose (35) receptor sites insufficiency osteoporosis, skin hydrocortisone
25-80 mg.) (replacement), atrophy, glucose
immunosu- intolerance,
pression growth
Prednisone suppression, Abrupt withdrawal
(Physiologic osteopenia may be fatal
oral dose (7.5)
5-20 mg.)

Other steroids: Triamcinolone, Dexamethasone…

Cortisone: Hydrocortisone USP
Same as above (also a glucocorticoid)
Bio-identical to human cortisol
REMEMBER: dose from Prednisone to Cortisone conversion is a 4 to 1 ratio.

5 mg. Prednisone = 20 mg Cortisone

Physiologic dose of Cortisone is 25 to 40 mg. orally.
 Oral Steroids
• Methylprednisolone 4mg pack [Medrol
DosePak]
– Pre set does of 24 mg day 1 – tapering over 1
week
– Easy to use, and LOW dose
• Other:
– In some urgent cases you may need a
starting dose of 60, 80 or higher mg, then a
taper over 3-6 weeks.
 Gout Pain
Antigout MOA Uses Adverse Effects Other

Colchicine Unknown, reduces Gout: acute GI upset, nausea, Contraindicated in

inflammation or vomiting, gastric patients with CV,
maintenance pain, with long hepatic, renal or
therapy term use: aplastic GI disease
anemia

Allopurinol Inhibits xanthine Gout, GI upset, hepatitis, Monitor blood

oxidase which reduces hyperuricemia hepatic necrosis, levels for toxicity
uric acid production renal failure, rash, when used with
Stevens-Johnson digoxin, lithium or
syndrome anticoagulants

Use of oral prednisolone or naproxen for the treatment of gout arthritis: a

double-blind, randomised equivalence trial.
Lancet. 2008; 371(9627):1854-60 (ISSN: 1474-547X)
Rx either prednisolone (35 mg once a day; n=60) or naproxen (500 mg twice a
day; n=60), for 5 days

“Oral prednisolone and naproxen are equally effective in the initial treatment of
gout arthritis over 4 days.”
Local MOA Uses Adverse Effects Other
Anesthetics
Lidocaine Reduces Topical Drowsiness, Rapid onset
permeability of anesthesia, dizziness, may and medium
sodium influx into sedation, cause heart block duration.
neuronal arrhythmia’s and arrhythmias. Amide
membranes. prototype.

Bupivacaine Same as Nerve block, Same as Slow onset

lidocaine. spinal and lidocaine. and long
epidural. duration.
Amide.

NO I.V.

Procaine Same as Ester

lidocaine. prototype.
Metabolizes to
PABA