CENTRAL NERVOUS SYS TEM

Epilepsy-common neurologic disorder characterized by paroxysmal (sudden and recurring) seizures.

Disturbances of neuronal electrical activity that interfere with normal brain function.

Seizures- caused by disordered abnormal electrical charges in the cerebral cortex, resulting in change in
behavior wherein a patient is not aware. Sudden, excessive firing of small number of neurons often
without exogenous trigger, and spread of the electrical activity to adjacent neurons. Firings result to
convulsion. 3 states: resting, firing and returning to rest. The balance of excitatory and inhibitory
impulses determines whether a neuron fires. Neurons operate through the movement of ions across the
cell membrane. Chloride (negative ion), sodium or calcium (positive ions). The ion flows are controlled
by molecules in the cell membrane, controlled by neurotransmitters binding to them. Healthy persons
have a balance between excitation and inhibition among the neurotransmitters. When excitation is
excessive leads to seizure. Glutamate, an excitatory AA neurotransmitter, and gamma-aminobutyric acid
GABA (inhibitory) play the greatest role.

Status epilepticus is a serious disorder involving continuous tonic-clonic convulsions with/without return
to consciousness for at least 30 minutes. Characterized by high fever and lack of oxygen enough to cause
brain damage or death. Therapy is aimed at stopping the convulsions and preventing brain damage.
Diazepam as the DOC. Phenytoin follows if does not work.

Partial Seizure: simple- does not lose consciousness, twitching, sensory hallucinations (visual, auditory).
Complex- impaired consciousness, confusion, blank stare and post seizure amnesia.

Generalized Seizures: simultaneous malfunction of both hemispheres of the brain. Classified as tonic-
clonic, absence, myoclonic and atonic.

Tonic-clonic formerly a grand mal seizure. Body becoming rigid and patient may fall. Lasts a minute or
less. Muscle jerks with shallow breathing, loss of bladder control, excess salivation (foaming). After
attack patient is drowsy and confused for hours. Carbamazepine as prophylaxis.

Absence formerly petit mal. Begins with interruption of patient’s activities, blank stare, rotating eyes,
uncontrolled facial movements, chewing, rapid eye blinking, twitching or jerking arm/leg, but no
generalized convulsions. Lasts from 10seconds -2minutes. May have 100 attacks a day. the person has
premonition of the attack through unusual sensations of light, sound and taste known as aura.
Ethosuximide as DOC.

Myoclonic is a sudden, brief jerks which my throw the patient down, consciousness is not lost. Can occur
during sleep.

Atonic sudden loss of muscle tone and consciousness. Patient may collapse, head drop, jaw slacken.
Arm/leg limp. He may stand and walk again.

Most commonly used anticonvulsant Drugs:

Carbamazepine; Tegretol

Clonazepam; Klonopin A schedule IV benzodiazepine, avoid alcohol.

Diazepam; Valium
Divalproex; Depakote

Ethosuximide; Zarontin

Gabapentin; Neurontin

Lamotrigine; Lamictal

Lorazepam; Ativan

Phenobarbital fee-noe-BAR-bi-tal; Luminal Sodium

Phenytoin FEN-i-toyn Dilantin

Primidone PRYE-mih-done Mysoline

Topiramate toe-PYRE-a-mate Topamax

Valproic acid Depakene CI to aspirin could lead to toxicity.

Goals: to control seizures or reduce their frequency so the patient can live normal life

To prevent emotional and behavioral changes that may result from seizures.

SE: sedation, loss of cognitive processes (mental perception, memory, judgement)

Different seizure types require different antiepileptic agents. Dosage should be decreased gradually over
2-6 months. No to abrupt discontinuation.

Phenytoin SE: dose-related: ataxia (muscle action irregularity), diplopia, dizziness, drowsiness,
encephalopathy(degenerative), involuntary movements ( when concentration is greater than
30mcg/mL)

Non-dose related: gingival hyperplasia, peripheral neuropathy, vitamin deficiencies.

Cerebyx looks like Celexa (citalopram, an antidepressant) and Celebrex (celecoxib, used in arthritis pain)
be careful

Neurontin and Noroxin (norfloxacin, an antibiotic can be confused but they can be differentiated by
dosage. Neurontin is usually 100 mg, Noroxin is 400 mg.

Lamictal, Lamisil (terbinafine, an antifungal) and Lomotil (diphenoxylate/atropine)

Boxed warnings are special warnings about a drug highlighted in a box in the FDA approved product
information. A Black Box warning is the most serious.

Depakene and Depakote are easily confused. Remember which is valproic acid and which is divalproex.

PARKINSON DISEASE: muscular difficulties and postural abnormalities affecting 60 years of age and
above. 3 characteristic signs of PD are tremor while resting, rigidity and akinesia (no movement). These
may manifest poor posture control, shuffling gait and loss of overall muscle control.
Physiology of PD: it occurs as a result of pathologic alterations in the extrapyramidal system EPS, a
complex functional unit of the CNS involved in controlling motor activities. EPS is composed of basal
nuclei/ganglia embedded in the lower portions of the cerebral hemisphere. It is the most common EP
diseases. Inclusions of basal ganglia?

Normal movement requires that the 2 primary neurotransmitters- dopamine, an inhibitor and
acetylcholine (Ach), a stimulator be in balance.

In a healthy person, dopaminergic neurons (neurons that release dopamine when they fire) in the
substantia nigra ( a collection of dark gray substance, release an amount of dopamine sufficient to
control the stimulating effect of acetylcholine on large motor and fine muscle movements. In PD, there
is progressive destruction of dopaminergic neurons in the nigrostriatal pathway, so an insufficient
amount of dopamine is produced to counterbalance acetylcholine production. This results in
predominance of cholinergic neuronal activity, which produces excessive motor nerve stimulation.

PD Drug Therapy:

It has greatly improved the functional ability and clinical status of patients. Drug therapy aims only at
symptomatic relief; it does not alter the underlying disease process. Temporary or prolonged remission
allows the patient to live a productive life. Levodopa is considered to be the gold standard. The patient
will need emotional and psychological support as well

Amantadine (Symmetrel) an antiviral as prophylaxis and treatment for influenza is also used to treat PD.
Its anti-Parkinson activity is a result of blocking the reuptake of dopamine into presynaptic neurons and
causing direct stimulation of postsynaptic dopamine receptors. The second dose of the day should be
taken in the early afternoon to decrease the incidence of insomnia. Abrupt discontinuation of therapy
should be avoided.

Amantadine, ranitidine (gastric acid reducer) and rimantadine (another antiviral) look alike.

Dopamine will not cross the BBB.

Sinemet, a levodopa-carbidopa preparation, is probably the most commonly used in PD

Bromocriptine (Parlodel) is also used to dry up breast milk in a nursing mother.

Selegiline (Eldepryl) a MAOI used in PD

Most commonly used anti-Parkinson agents: need to be prescribed.

Amantadine a-MAN-ta-deen; Symmetrel

Benztropine; Cogentin

Bromocriptine; Parlodel, take with food or mild.

Levodopa lee-voe-DOE-pa; Dopar, on-off phenomenon hyper to hypokinetic state (dyskinesia and
akinesia.

Levodopa-carbidopa lee-voe-DOE-pa kar-bi-DOE-pa Sinemet

Pramipexole Mirapex
Rasagiline; Azilect is a MAOI, which blocks the breakdown of dopamine. An initial therapy in early PD to
improve symptoms. Should not be taken for 2 weeks prior to surgery. It can cause hypertensive crisis. If
the patient ingests food that contain tyramine (matured cheeses, cured meats, soy sauce)

Selegiline; Eldepryl, Zelapar)

Selegiline and sertraline (an SSRI-type anti-depressant) both contain a vertical letter. L and t.

Other CNS disorders:

MYASTHENIA GRAVIS a disorder of interface between nerves and muscles resulting from autoimmune
damage to acetylcholine Ach receptors at the motor end plate connection point. Neuromuscular
junction. Characterized by weakness and fatigability, especially in skeletal muscles. Ptosis as the first
symptoms (drooping of upper eyelid), diplopia (double/blurred ) followed by dysarthria ( imperfect
speech articulation), dysphagia.

Acetylcholinesterase inhibitors can produce clinical improvement. And may be used with
corticosteroids.

Most commonly Used MG Agents: generic-pronunciation-brand name

Azathioprine; Imuran

Cyclophosphamide sye-kloe-FOS-fa-mide; Cytoxan

Edrophonium ed-roe-FOE-nee-um; Enlon, Reversol; markedly improves patient’s strength

Neostigmine; Prostigmin

Pyridostigmine peer-id-oh-STIG-meen; Mestinon

SE: salivation, muscle fasciculation (visible contraction under the skin), Imuran leukopenia,
pancytopenia, cyclophosphamide ( cystitis, so fluids should be taken liberally)

ATTENTION-DEFICIT DISORDERS ADHD

Used to treat are amphetamines or amphetamine derivatives. High addictive quality and classified as
Schedule II

Atomoxetine ; Strattera- at-oh-MOX-e-teen ; nonstimulant, selective inhibitor of the reuptake

norepinephrine which controls impulsivity and activity. Treatment of ADHD 6 years old and older. Not a
controlled substance so can be refilled. It can cause weight loss and slow growth.

Dexmethylphenidate; Focalin; C-II consist of dextro isomer. An isomer is one of 2 or more compounds
that contain the same number and type of atoms but have different molecular structures. Many
biologically active substances have isomers whose molecules are mirror images of each other like a pair
of gloves dextro right and levo left.

Dextroamphetamine-amphetamine; Adderall ; its effects can last about 6 hours long enough to get
some children through the school day. SE. depression as the drug wears off. It can look like Inderal
(propranolol, a beta-blocker used as an antianxiety agent) be watchful.
Methylphenidate meth-il-FEN-i-date; Methylin, Ritalin; C-II; DOC . take in the morning and one form
comes as a patch, improving compliance.

AMYOTROPHIC LATERAL SCLEROSIS ALS known as Lou Gehrig disease; after the New York Yankees star
who died of this disease in 1941, a progressive degenerative nerve disease that leads to muscle
weakness, paralysis and eventually death. Caused by excessive levels of glutamate, an excitatory
neurotransmitter that causes nerve damage.

Riluzole (Rilutek) drug to treat this syndrome. It inhibits glutamate release, inactivates sodium channels
and interferes with intracellular events following transmitter binding at excitatory receptors.

MULTIPLE SCLEROSIS (MS) it is an autoimmune disease in which the myelin sheaths around nerves,
which serve as electrical insulation, degenerate. Patient loses use of muscles and eyesight is affected.
Severe trembling in the later stages.

baclofen; Lioseral) muscle relaxant used in MS, spinal cord lesions, intractable hiccups and bladder
spasticity. Should be taken with food or milk and may cause drowsiness.

glatiramer acetate; Copaxone; given daily by SC injection. May cause local injection reactions. Store in
freezer.

interferon beta- 1a; in-ter-FEER-on BAY-ta 1A; injection; Avonex, Refib; prophylaxis with
acetaminophen is indicated to avoid flu-like symptoms. Take at bedtime. Photosensitivity reaction may
occur. Should not be exposed to high temperatures or freezing.

interferon beta 1b; Betaseron

mitoxantrone; Novantrone; is a chemotherapeutic agent. Slow MS progression and reduce relapses.

Can be given intravenously every 3 months.

tizanidine ; Zanaflex, it is the 1st oral drug approved for spasticity since baclofen. It is structurally similar
to clonidine and has similar SE: dry mouth, sedation, dizziness and hypotension.

ALZHEIMER DISEASE it was 1st described by Alois Alzheimer, a German psychiatrist in 1907. A
degenerative disorder of the brain that leads to progressive dementia (loss of memory, intellect,
judgement, orientation and speech) and changes in personality and behavior. In early stage, patient
complains of memory deficit, forgetfulness and misplacement of ordinary items. Depression is a part of
the disease profile. As the disease progresses, complex tasks become impossible (managing finances)
and concentration becomes poor. In the final stage, patient suffers complete incapacitation,
disorientation and failure to thrive.

Drug slow the disease but do not cure or reverse it. Cholinesterase inhibitors which increase the levels
of acetylcholine. Aricept, Razadyne, Exelon, and Cognex)

Namenda which is used early in the disease, blocks hyperactive glutamate receptors.
OTC herbal ginkgo GING-ko has many brand names.

The depression associated with the disease is often treated with antidepressants as determined by
existing symptoms and ADR. Amitriptyline should be avoided in these patients because it blocks
acetylcholine receptors. Agitation and sleep disturbance should be treated with short-acting
benzodiazepines.

tacrine; Cognex; SE: increase in liver function values. Metabolized through cytochrome P-450 so it
interacts with other drugs that are metabolized through that system. Take 4 times a day on empty
stomach because of nausea and vomiting.

donepezil don-EP-a-zil ; Aricept; more convenient that tacrine. Both improve memory and alertness.
But this is more selective for cholinesterase meaning less NVD. Take OD at bedtime. HS

galantamine Razadyne; from daffodil bulbs. Rarely used because of deaths reported in some clinical
trials

ginkgo shown good results in improving cognitive function and social behavior in Alzheimer patient. It
has antioxidant and anti-inflammatory effect. improves blood flow and inhibits platelet aggregation.
Since OTC it is less expensive. Takes 6-12 weeks to see improvement. Patients on warfarin should not
take ginkgo.

memantine; Namenda; it blocks the glutamate receptors known as NMDA receptors because they also
respond to the chemical N-methyl-D-aspartate. Receptors are excitable in AD and can cause neurons to
fire even without the neurotransmitter. Has fewer SE and slows advancement of the disease.

rivastigmine; Exelon;

Study:

DRUGS AFFECTING AUTONOMIC NERVOUS SYSTEM

Identify the key terminologies, functional divisions of peripheral nervous system, effects of sympathetic
and parasympathetic nervous systems.

AUTONOMIC DRUGS:

CLASSIFICATION AND NAMING:

1. Stimulation of the SNS : these drugs are called adrenergic agents or sympathomimetics, they
produce the classic symptoms of fight of flight response. Natural or synthetic agents that
produce a sympathomimetic response include the catecholamines.
2. Inhibition of the sympathetic nervous system:
Also called adrenergic-blocking agents or adrenergic antagonists, and they produce opposite
action. Also called sympatholytics.
3. Stimulation of PNS:
These drugs are the cholinergic agents or parasympathomimetics and they produce the rest-
and-digest response.
4. Inhibition of the parasympathetic nervous system:
These are the so-called cholinergic-blocking agents, anticholinergics, parasympatholytics or
muscarinic blockers and they produce actions opposite those of the cholinergic agents.

Both sympathomimetics and cholinergic-blocking agents increase heart rate and dilate the pupil
The cholinergic agents and the adrenergic-blocking agents slow the heart rate and constricting
the pupil.

Fight or flight inhibits salivation, digestion, relaxes bladder, inhibits sex organs
2 primary neurotransmitters of ANS: norepinephrine (adrenergic) and acetylcholine
(cholinergic)
NE belongs to a class of agents called natural catecholamines involved in neurotransmission.
Natural catecholamines: epinephrine (adrenalin) and dopamine
Synthetic catecholamines: isoproterenol and dobutamine.
Receptors of postganglionic sympathetic neurons are called adrenergic, from the word
adrenalin.
Adrenergic receptors are alpha and beta receptors. Subdivided into subtypes beta1, beta2,
alpha1 and alpha2
Alpha 1- nasal congestion treatment, hypotension, mydriasis
Alpha 2 – treatment of HTN
Beta 1 – cardiac arrest, HF and shock
Beta 2 – asthma and premature labor contractions treatment
NE is synthesized in the nerve terminal that require amino acids phenyl alanine and tyrosine.
The final step is the conversion of dopamine to NE.

Acetylcholine and cholinergic transmission

Nerves releasing Ach are called cholinergic nerves.
2 types of cholinergic receptors that bind Ach
Nicotinic receptors and muscarinic

Adrenergic agents: sympathomimetics

Prototype drug: phenylephrine (Neo-Synephrine)
Pseudoephedrine

Know the nursing responsibilities and client teachings:

Adrenergic blocking agents (Antagonists): prazosin Minipress

And some more

Cholinergic Agents (Parasympathomimetics)

Direct acting: bethanechol (Urecholine)
Cholinesterase inhibitors: Indirect acting

Cholinergic-blocking agents (Anticholinergics)

Atropine- to increase heart rate and dilate pupils
A male client was diagnosed with PD, he is being treated with a regiment of amantadine (Symmetrel) an
indirect-acting dopaminergic agent and benztropine mesylate (Cogentin). The nurse recognizes Cogentin
as an anticholinergic agent. What should the nurse assess this client for? Discuss the potential side
effects of benztropine that the nurse should assess for in this client?

References:

Pharmacology: Ballington , Laughlin

Pharmacology , A Pathophysiological Approach . Adams, Holland