© Paradigm Publishing, Inc.1 Chapter 8 Drugs for Central Nervous System Disorders.

© Paradigm Publishing, Inc. 1

Chapter 8

Drugs for Central Nervous System

Disorders


Learning Objectives

• Develop an understanding of the physiologic processes that occur in epilepsy.

• Classify seizures and the goals of their therapy.

• Understand that specific drugs are used in different classes of seizures.


Learning Objectives

• Be familiar with Parkinson disease and the drugs used in its treatment.

• Identify the drugs and goals of therapy for attention-deficit disorders.

• Realize that some drugs may be used for several disease states.

• Recognize drugs used to treat Alzheimer disease.

4© Paradigm Publishing, Inc.

Epilepsy

• Common neurologic disorder with sudden and recurring (paroxysmal) seizures

• Caused by abnormal electrical impulses in the brain

• All epilepsy patients have seizures; not all with seizures have epilepsy

• 1% to 2% have chronic epilepsy


Seizures

• Disturbances of neuronal electrical activity that interferes with normal brain function

• Behavior change patient not aware of

• Conscious periods may or may not lose control over movement

• Loss of body control may affect one area or entire body


Convulsions

• Excessive firing of neurons can result in a convulsion– Involuntary contraction or series of

contractions of the voluntary muscles


Causes of Seizures

• Imbalance of excitatory and inhibitory neurotransmitters– GABA: excitatory– Glutamate: inhibitory– Other neurotransmitters can be involved

• Enzymes control neurotransmitter levels• Disruption in enzymes = disruption of

neurotransmitters


Causes of Seizures

• Alcohol or drug withdrawal• Epilepsy• High fever• Hypoglycemia, hyperglycemia• Infection (meningitis)• Neoplasm (brain tumor)• Trauma or injury (head, hematoma)


Two Classes of Seizures

• Partial– Simple partial– Complex partial

• Generalized– Tonic-clonic (was called grand mal seizure)– Absence (was called petit mal seizure)– Myoclonic– Atonic


Partial Seizures

• Localized in a specific area of the brain• Almost always results from injury to

cerebral cortex• Occurs in about 65% of people with

epilepsy• Can progress to generalized seizures


Two Classes of Partial Seizures

• Simple Partial– No loss of consciousness– May have muscle twitching or sensory

hallucinations

• Complex Partial– Impaired consciousness– Confusion, blank stare, and postseizure

amnesia


Generalized Seizures

• Involves both hemispheres of the brain, no specific location

• Four types

• Tonic-Clonic– Absence– Myoclonic– Atonic


Tonic-Clonic Seizures

• Tonic: body becomes rigid, patient may fall, lasts a minute or less

• Clonic: starts with muscle jerks, may be accompanied by shallow breathing, loss of bladder control, and excess salivation– Lasts a few minutes


Absence Seizures

• Interruption of activities by blank stare, rotating eyes, uncontrolled facial movements, rapid eye blinking, twitching or jerking of an arm or leg

• No generalized convulsions• Usually lasts 30 seconds or less• Most prevalent first 10 years of life. 50% of

children have tonic-clonic as grow older


Myoclonic Seizures

• Occurs with sudden, massive, brief muscle jerks which may throw patient down or nonmassive, quick jerks

• Consciousness is not lost

• Can occur during sleep


Atonic Seizures

• Begins with sudden loss of muscle tone and consciousness

• Patient may collapse, head drop, arm or leg may go limp

• Lasts few seconds to a minute, then patient can stand and walk again


Status Epilepticus

• Continuous tonic-clonic seizures, with or without return to consciousness

• Last at least 30 minutes

• High fever and lack of oxygen that can cause brain damage or death


Two Goals of Antiepileptic Therapy

• Seizure control or lessen the frequency

• Prevent emotional and behavioral changes that may result from seizures


Antiepileptic Drug Therapy

• Different seizure types require different drugs

• Start with monotherapy at low dose and increase slowly over 3 to 4 weeks

• Medication must be maintained at steady therapeutic levels

• If insufficient response, polytherapy can be considered


Antiepileptic Drug Therapy

• Newer drugs are seizure-specific• High potential for drug interactions• Anticonvulsants have narrow therapeutic

ranges• Minor dosage changes can result in loss of

seizure control or toxicity• Prescribers often write for the brand name


Drug ListAnticonvulsants

– carbamazepine (Epitol, Tegretol)

– clonazepam (Klonopin)

– diazepam (Valium)

– divalproex (Depakote)

– ethosuximide (Zarontin)



– fosphyenytoin (Cerebyx)

– gabapentin (Neurontin)

– lamotrigine (Lamictal)

– levetiracetam (Keppra)

– lorazepam (Ativan)



– oxcarbazepine (Trileptal)

– phenobarbital (Luminal Sodium)

– phenytoin (Dilantin)

– pregabalin (Lyrica)

– primidone (Mysoline)



– tiagabine (Gabitrol)

– topiramate (Topamax)

– valproic acid (Depakene)

– zonisamide (Zonegran)


Dispensing Issues of Anticonvulsants

• Prescribers often do not allow generic drugs

• Pharmacy technicians watch for DAW

• If computer changes drug to generic, technicians often change drug to brand

Warning!


carbamazepine (Epitol, Tegretol)

• Effect on sodium channels which may alter synaptic transmission

• Blood monitoring important

• Many interactions with other drugs

• Side effects can be serious


clonazepam (Klonopin)

• Prophylaxis of seizures

• Depresses nerve transmission in the motor cortex

• C-IV controlled substance (benzodiazepine)


gabapentin (Neurontin)

• Used as adjunct

• No significant drug interactions, well-tolerated, easy to use

• Used for many other disorders, particularly neuropathic pain


Dispensing Issues of Neurontin

• Sound-alike drugs, but different strengths– Neurontin, usually 100 mg– Noroxin (antibiotic), usually 400 mg

Warning!


lamotrigine (Lamictal)

• Add-on therapy for adults with partial seizures

• Blocks sodium channels which reduces neuron excitation

• Call physician immediately if rash appears, do not discontinue abruptly


Dispensing Issues of Lamictal

• Look-alike and sound-alike– Lamictal– Lamisil (terbinafine), antifungal– Lomotil (diphenoxylate-atropine),

diarrhea

Warning!


Dispensing Issues of Lamictal

• Black Box warning about fatal rashes, most serious warning

• Boxed warnings are special warnings about a drug highlighted in the FDA-approved product information

Warning!


phenytoin (Dilantin)

• May be used to prevent seizures• Promotes sodium outflow from cells,

stabilizing the neuronal membrane• Be cautious of drug interactions• IV phenytoin must be mixed carefully


Side Effects of Phenytoin: Dose Related

• Ataxia

• Diplopia

• Dizziness

• Drowsiness

• Encephalopathy

• Involuntary movements


Side Effects of Phenytoin: Non-Dose-Related

• Gingival hyperplasia

• Peripheral neuropathy (pain in extremities

• Vitamin deficiencies


pregabalin (Lyrica)

• Reduces release of neurotransmitters glutamate, norepinephrine, substance P

• Similar to gabapentin, more potent. Fewer side effects than other anticonvulsants

• Controlled substance, Schedule V

• Also approved to treat diabetic neuropathy


taigabine (Gabitrol)

• Blocks reabsorption of GABA, allowing it to bind to nerve cells which enhances normal brain activity

• Should be taken with food• Can cause seizures if patients who do not

have epilepsy use it off-label

• FDA has issued off-label use warning


topiramate (Topamax)

• Thought to block sodium channels which increases GABA activity and decreases glutamine activity

• Causes significant cognitive effects

• Drink fluids to decrease risk of kidney stones


Discussion

Which neurotransmitters play the greatest role in seizures?

The neurotransmitters are glutamate (excitatory) and GABA (inhibitory).


Terms to Remember

epilepsy

seizure

convulsion

partial seizure

generalized seizure

tonic-clonic seizure


Terms to Remember

grand mal seizure

absence seizure

petit mal seizure

myoclonic seizure

atonic seizure

status epilepticus


Terms to Remember

anticonvulsant

adjunct

ataxia

substance P


Parkinson Disease

• Characterized by tremor when resting, rigidity, and akinesia (absence of movement)

• Poor posture control, shuffling gait, loss of overall muscle control

• Usually affects people over 60


Physiology of Parkinson Disease

• Parkinson disease is result of alterations in the extrapyramidal system– Part of the CNS that controls motor activities

– Made up of the basal nuclei (basal ganglia)

• Most common extrapyramidal disease

• Parkinson has no definitive test, diagnosed by symptoms


Cutaway View of the Brain


Physiology of Parkinson Disease

• For normal muscle movement to be performed, 2 main neurotransmitters must be in balance– Dopamine (inhibitor)

– Acetylcholine (stimulator)

• In Parkinson disease, these neurotransmitters are not in balance


Dopamine and Parkinson Disease

• In the substania nigra, insufficient dopamine is released to counteract effects of Ach

• This causes excessive motor nerve stimulation


Substantia Nigra


Parkinson Disease Drug Therapy

• Improves functional ability and clinical status of patients

• Aims at symptomatic relief, does not alter disease process. No cure.

• Temporary or prolonged remission

• Side effects can be a problem


Drug ListAnti-Parkinson Agents

– amantadine (Symmetrel)– benztropine (Cogentin)– bromocriptine (Parlodel)– entacapone (Comtan)– levodopa (Dopar)– levodopa-carbidopa (Sinemet)


Drug ListAnti-Parkinson Agents

– levodopa-carbidopa-entacapone (Stalevo)

– pramipexole (Mirapex)– rasagiline (Azilect)– ropinirole (ReQuip)– selegiline (Eldepryl)– tolcapone (Tasmar)


levodopa (Dopar)

• Metabolized to dopamine in brain, but brain does not receive a full dose

• Very undesirable effects, including nausea, vomiting, cardiac arrhythmia

• After about 5 years of therapy, 2/3 of patients experience on-off phenomenon


levodopa-carbidopa (Sinemet)

• Probably most common drug used in Parkinson disease

• Carbidopa allows for lower doses of levodopa to be used which decreases side effects


rasagiline (Azilect)

• Monoamine oxidase inhibitor (MAOI), blocks breakdown of dopamine

• Initial therapy to improve symptoms

• Possible hypertensive crisis if patient consumes foods with tyramine (aged cheeses, cured meats, soy sauce)


entacapone (Comtan)

• Second in class of anti-Parkinson agents known as catechol-O-methyl transferase (COMT) inhibitors

• Indicated for patients who have a deteriorating response to levodopa

• Less toxic than tolcapone (Tasmar)

• Taken without regard to food


Terms to Remember

Parkinson disease

basal nuclei

substantia nigra

on-off phenomenon

catechol-O-methyl transferase (COMT)


Other Central Nervous System Disorders

• Myasthenia gravis

• Attention-deficit hyperactivity disorder and attention-deficit disorder

• Amyotrophic lateral sclerosis (ALS)

• Multiple sclerosis (MS)

• Alzheimer disease


Myasthenia Gravis

• Autoimmune disorder of the neuromuscular junction

• ACh receptors are destroyed at the motor end plate

• Characterized by weakness and fatigability, especially of skeletal muscles


Motor End Plate


Presenting Signsof Myasthenia Gravis

• Ptosis (drooping eyelid)

• Diplopia (double vision)

• Dyarthria (speech)

• Dysphagia (swallowing)

• Extremity weakness

• Respiratory difficulty


Treatment of Myasthenia Gravis

• Acetylcholinesterase drugs can produce improvements in all forms of myasthenia gravis

• Drug therapy does not inhibit or reverse the immunologic flaw


Drug ListAgents for Myasthenia Gravis

– azathioprine (Imuran)– cyclophosphamide (Cytoxan)– edrophonium (Enlon, Reversol)– neostigmine (Prostigmin)– pyridostigmine (Mestinon)


pyridostigmine (Mestinon)

• Blocks destruction of ACh

• Allows for ACh accumulation at the synaptic junction

• Take with food or milk and at same time each day


cyclophosphamide (Cytoxan)

• Prevents cell division by targeting the auto-immune portion of the disease

• Use chemotherapeutic precautions


Attention-Deficit Disorders

• Attention-Deficit Hyperactivity Disorder (ADHD)

• Attention-Deficit Disorder (ADD)


Attention-Deficit Hyperactivity Disorder (ADHD)

• Neurologic disorder characterized by hyperactivity, impulsivity, and distractability

• Symptoms can persist into adult life

• Most drugs used are amphetamines and amphetamine derivatives, C-II


Drug ListAttention-Deficit Disorders Agents

– atomoxetine (Strattera)

– dexmethylphenidate (Focalin), C-II

– dextroamphetamine-amphetamine (Adderall), C-II

– lisdexamfetamine (Vyvanse)


Drug ListAttention-Deficit Disorders Agents

– methylphenidate (Concerta, Daytrana Metadate, Metadate ER, Methylin, Ritalin, Ritalin-SR), C-II

– modafinil (Provigil, Sparlon)


Dispensing Issues of Attention-Deficit Disorders Agents

• ADHD drugs used for treatment as a group must provide a medication guide to patient or caretaker

• Technicians—check for mediation guide when drug is handed to patient or caretaker, even if drug is not C-II

Warning!


atomoxetine (Strattera)

• Nonstimulant indicated for treatment of ADHD in patients 6 years and older

• Controls impulsivity and activity

• Not a controlled substance, refills can be called in


methylphenidate (Concerta, Daytrana Metadate, Metadate

ER, Methylin, Ritalin, Ritalin-SR)

• Drug of choice to treat attention-deficit disorders

• CNS stimulant, C-II controlled substance• Improved dosage allows the drug to be

taken only in the morning• One form comes in a patch, improving

compliance


methylphenidate (Concerta)

• Dosed once a day, in morning

• Outer layer dissolves to release part of drug immediately

• Rest of drug is OROS tablet– Slowly releases through pores in tablet,

leaving a ghost


methylphenidate (Daytrana Metadate)

• Patch form of methylphenidate

• Worn for 9 hours, then removed

• Drug is in the adhesive


dextroamphetamine-amphetamine (Adderall)

• C-II controlled substance

• Effects last about 6 hours

• Primary side effect is depression as drug wears off


Dispensing Issues of Adderall

• Look-alike and sound-alike– Adderall (ADHD)– Inderal (propranolol), beta blocker used

to treat anxiety

Warning!


Modafinil (Provigil, Sparlon)

• Sparlon is nonstimulant medication

• Indicated for treatment of ADHD in patients 6 years and older

• Increases mental alterness


Amyotrophic Lateral Sclerosis (ALS)

• Also known as Lou Gehrig disease

• Progressive degenerative disease of the nerves

• Muscle weakness, paralysis, and eventually death

• Cause: excessive levels of glutamate


Drug ListAgent for Amyotrophic Lateral Sclerosis

– riluzole (Rilutek)


riluzole (Rilutek)

• First drug approved for amyotrophic lateral sclerosis

• Inhibits release of glutamate

• Seems to improve survival rate by 3 months in some patients


Multiple Sclerosis (MS)

• Autoimmune disease in which myelin sheaths around nerves degenerate

• Patient loses use of muscles, and often eyesight is affected

• Some drugs can slow progression

• No cure


Drug ListMultiple Sclerosis Agents

– baclofen (Lioresal)– glatiramer acetate (Copaxone)– interferon beta-1a (Avonex, Rebif)– interferon beta-1b (Betaseron)– mitoxantrone (Novantrone)– tizanidine (Zanaflex)


glatiramer acetate (Copaxone)

• Seems to block the autoimmune reaction against myelin that leads to nerve damage

• Decreases frequency of relapses

• Not been shown to slow disease progress

• Given everyday by subcutaneous injection

• Must be frozen


tizanidine (Zanaflex)

• Indicated to reduce muscle spasticity in MS and spinal cord injuries

• Oral drug

• Side effects: dry mouth, sedation, dizziness, and hypotension


Alzheimer Disease

• Progressive form of dementia

• Changes personality and behavior

• No treatments can cure or reverse

• Drugs can slow the disease

• Depression often treated with antidepressants according to symptoms


Progression of Alzheimer Disease

1. Memory deficit, forgetfulness, misplacements of ordinary items

2. Inability to complete complex tasks

3. Complete incapacitation, disorientation, and failure to thrive


Drug ListAgents for Alzheimer Disease

– donepezil (Aricept)– galantamine (Razadyne)– ginkgo (many)– memantine (Namenda)– rivastigmine (Exelon)– tacrine (Cognex)


tacrine (Cognex)

• Cholinesterase inhibitor

• Most common side effect: increase in liver lab values

• Taken 4x a day on an empty stomach

• Side effects: nausea, vomiting


donepezil (Aricept)

• Convenient to use

• Few side effects

• Improves memory and alertness

• Give once a day at bedtime


Dispensing Issue of Aricept

• Look-alike and sound-alike– Aricept– Aciphex (rabeprazole), GERD

Warning!


memantine (Namenda)

• May have fewer side effects and better tolerated than other drugs

• Evidence that this drug slows advancement of Alzheimer disease


Terms to Remember

myasthenia gravis

motor end plate

ptosis

diplopia

dysarthia

attention-deficit hyperactivity disorder (ADHD)


Terms to Remember

amyotrophic lateral sclerosis (ALS)

Lou Gehrig disease

multiple sclerosis (MS)

Alzheimer disease

gingko


Assignments

• Complete Chapter Review activities• Answer questions in Study Notes

document• Study Partner

– Quiz in review mode– Matching activities– Drug tables

© Paradigm Publishing, Inc.1 Chapter 8 Drugs for Central Nervous System Disorders.

Documents

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generalized seizures

hematoma slide

minutes slide

chronic epilepsy slide

tonicclonic seizures

different classes of

causes of seizures alcohol