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DRUGS AFFECTING MOBILITY:
MUSCLE SPASMS, SPASTICITY AND
LOSS OF MUSCLE CONTROL
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Cholinergic Function
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Function of the Autonomic
Nervous System
• The autonomic nervous system (ANS) is an
involuntary system responsible for the control of
smooth muscle, cardiac muscle, and exocrine
glands.
• The sympathetic (SNS) and parasympathetic
nervous systems (PNS) work either as
complementary or oppositional systems to
maintain the involuntary functions of the body.
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Cholinergic Neurotransmitters
• Cholinergic drugs act on the parasympathetic
nervous system.
• Acetylcholine (ACh) is the presynaptic and
postsynaptic neurotransmitter in the
parasympathetic nervous system.
• ACh is released in response to an action
potential. It diffuses across the synaptic cleft,
and binds to cholinergic receptors on the target
organs or tissues – both in the brain and in the body.
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Types of Cholinergic Receptors
• Nicotinic receptors
• Activation of nicotinicN receptors in the adrenal
glands results in the release of epinephrine.
• Stimulation of nicotinicM receptors results in
skeletal muscle contraction.
• Useful in industrial insecticides
• Muscarinic receptors
• Stimulation of these receptors results in the
pharmacologic response of vasodilation resulting
in decreased blood pressure.
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Direct-Acting Muscarinic Agonists
• Direct-acting muscarinic agonists are drugs that
bind to the muscarinic receptors located in
various tissues and organs throughout the body.
• Their activation elicits a response that resembles
the action of the parasympathetic nervous
system.
• Many drugs can have muscarinic side effects.
This means that they may inadvertently lower
blood pressure!
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Cholinergic Antagonists
• The cholinergic antagonists are drugs that
antagonize, or block, muscarinic or nicotinic
receptors directly.
• May be used to reverse toxicity of highly
cholinergic drugs (e.g. insecticides)
• The clinical importance is in decreasing blood
pressure.
Prototype drug: atropine
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Atropine: Core Drug Knowledge
• Pharmacotherapeutics
• Cardiac arrhythmias
• Preoperatively, it is used to decrease respiratory
secretions (“dry up” the patient)
• Severe diarrhea
• Pharmacokinetics
• Based on route of administration
• Pharmacodynamics
• Competitive inhibitor of cholinergic receptors
• Reduces secretions, mydriasis (eye dryness), changes in
heart rate, smooth muscle (bladder and GI) contractions
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Atropine: Core Drug Knowledge
• Contraindications and precautions
• Myasthenia gravis
• Side effects
• Blurred vision, dry mouth, constipation, and
urinary retention
• Sexual dysfunctioning (erectile and ejaculation)
• Adverse effects
• Confusion, agitation in higher doses
• Drug interactions
• Antipsychotics
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Atropine: Planning and
Interventions
• Maximizing therapeutic effects
• Assess for peptic ulcer disease.
• Minimizing adverse effects
• Good oral hygiene
• Use sunglasses
• Do not perform strenuous exercise
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Myasthenia Gravis
• Myasthenia gravis (MG) is an autoimmune disorder
that impairs the receptors for acetylcholine at the
myo-neural junction.
• It occurs more frequently in men over 50 years of
age.
• The first symptoms of MG are usually weakness of
the eye muscles and ptosis.
• Cholinesterase inhibitors are the drugs of choice,
e.g. neostigmine.
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Indirect-Acting Cholinergic
Agonists
• After the neurotransmitter crosses the synaptic gap and
binds to a receptor, the neurotransmitter is cleared from the
synaptic gap.
• Acetylcholine is cleared from the synaptic gap by the
enzyme acetylcholinesterase.
• Any drug that inhibits cholinesterase will be the functional
equivalent of a cholinergic receptor.
Prototype drug: neostigmine (Prostigmin)
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Neostigmine: Core Drug
Knowledge
• Pharmacotherapeutics
• Myasthenia gravis: enhanced muscle
contraction
• Pharmacokinetics
• Administered: oral and parenterally.
Metabolism: liver. Excreted: kidneys. Onset:
varies with the route of administration.
• Pharmacodynamics
• Acts as a cholinergic agent by increasing the
synaptic presence of acetylcholine
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Neostigmine: Core Drug Knowledge
• Contraindications and precautions
• Gastrointestinal and urinary tract obstruction
• Side effects
• nausea, vomiting, diarrhea, miosis (slowed pupillary
reaction), salivation, diaphoresis (sweating)
• Adverse effects
• Cholinergic crisis, bradycardia, and bronchospasm
• Drug interactions
• Steroids, aminoglycoside, depolarizing muscle
relaxants, and magnesium
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Neostigmine: Planning and
Interventions
• Maximizing therapeutic effects
• Administered at regular intervals throughout
the day
• Minimizing adverse effects
• Availability of the antidote
• If the patient has a history of chronic
respiratory conditions, careful monitoring of
the first few doses of neostigmine is required.
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Fun Quiz:
1. Identify this plant.
2. What are it’s
effects if ingested
or smoked?
3. What is it’s
antidote?
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Answers:
• Datura stramonium (Jimson weed or loco weed) is a plant in
the deadly nightshade family.
• Tomatoes are also in this family, but are not toxic
• Datura has been used as a herbal medicine to relieve asthma
symptoms and as an analgesic during surgery or bone-setting.
• It is also a powerful hallucinogen used spiritually for the
intense visions once ingested or smoked.
• However, plant is fatally toxic in only slightly higher amounts
than the medicinal dosage, and careless use results in
hospitalizations and deaths.
• It has been responsible for sickness and death in cattle when
accidentally mixed into hay cut in pastures.
• It’s antidote is either atropine or pilocarpine.
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Drugs Affecting Muscle
Spasm
and Spasticity
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Physiology – Muscle Spasm
• The human body contains approximately 600
skeletal muscles.
• Skeletal muscle movement is voluntary and is
composed of two contractile proteins.
• Muscle contraction is triggered by a sudden inflow
of calcium ions (Ca2+).
• Muscle contraction stops when Ca2+ is removed
from the immediate environment.
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Muscle
Fibers
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Pathophysiology
Muscle spasm
• A muscle spasm is a sudden,
violent involuntary contraction
of a muscle or group of muscles.
• Spasms are related to a localized skeletal muscle
injury or an imbalance in electrolytes.
• Tonic spasm is characterized by an unusually
prolonged and strong muscular contraction
(think about a leg cramp).
• Clonic spasms have intermittent contraction with
release.
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Pathophysiology (cont.)
Spasticity
• Spasticity is a condition in which certain muscles
are continuously contracted.
• This contraction causes stiffness or tightness of
the muscles.
• Spasticity may be associated
with spinal cord injury or with
cerebral palsy.
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Centrally Acting Muscle Relaxants
• Centrally Acting Muscle Relaxants act in the central
nervous system (CNS).
Prototype drug: cyclobenzaprine (Flexeril)
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Cyclobenzaprine: Core Drug
Knowledge
• Pharmacotherapeutics
• Manages muscle spasms associated with acute
musculoskeletal disorders
• Pharmacokinetics
• Administered: oral. Metabolism: liver. Excreted:
urine and bile. Onset: 1 hour. Duration: 12 to 24
hours.
• Pharmacodynamics
• Relieves muscle spasms through a central (brain)
action
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Cyclobenzaprine: Core Drug Knowledge
• Contraindications and precautions
• Hyperthyroidism
• 14 days within use of MAOIs
• Side effects
• Drowsiness
• Changes in blood pressure
• Adverse effects
• Cardiac arrhythmias, seizures, and MIs
• Drug interactions
• Tramadol (Ultram), histamine-1 blocking agents,
and various herbal remedies
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Cyclobenzaprine: Planning and
Interventions
• Maximizing therapeutic effects
• Take with full glass of water at evenly spaced
intervals.
• Coordinate physical therapies with administration.
• Minimizing adverse effects
• Assess for excessive sedation.
• Caution the patient about the potential for
orthostatic hypotension.
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Centrally Acting Spasmolytics
• The centrally acting spasmolytics work in
the CNS to reduce excessive reflex activity.
• Allow muscle relaxation
Prototype drug: baclofen (Lioresal)
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Baclofen: Core Drug Knowledge
• Pharmacotherapeutics
• Relieves some components of spinal spasticity
• Pharmacokinetics
• Administered: oral. Distribution: crosses blood–
brain barrier. Metabolism: liver. Excreted: urine
and bile. Peaks: 2 to 3 hours
• Pharmacodynamics
• Acts specifically at the motor neurons at GABAB
receptors to cause hyperpolarization – GABA is an
inhibitory chemical neurotransmitter.
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Baclofen: Core Drug Knowledge
• Contraindications and precautions
• Hypersensitivity and spasticity of cerebral origin
• Side effects
• Drowsiness, weakness, dizziness, headache, nausea
and vomiting, hypotension, constipation, lethargy
and fatigue, insomnia, and urinary frequency
• Adverse effects
• Confusion, hallucinations or delusions
• Drug interactions
• CNS depressants and some antidepressants
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Baclofen: Planning and
Interventions
• Maximizing therapeutic effects
• Take with full glass of water at evenly spaced
intervals.
• If GI distress occurs, coordinate with meals.
• Minimizing adverse effects
• Have patient to sit or stand slowly
• Do not abruptly stop the medication.
Video: Spasticity & the Baclofen Pump
https://www.youtube.com/watch?v=ShxnYYA_sVg
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Drugs Treating Parkinson’s
Disease
and Other Intentional
Movement Disorders
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Physiology
• The extrapyramidal system (EPS) in
the brain is responsible for control
of voluntary muscles.
• Motor activity requires integration of the actions of
the cerebral cortex, basal ganglia, and cerebellum.
• The regulatory neurotransmitter dopamine is
produced in the brain and adrenal glands and is then
transmitted to the basal ganglia.
Peripherally, dopamine has circulatory and
cardiac adrenergic effects
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Dopamine: Core Drug Knowledge
• Pharmacotherapeutics
• Used to correct the hemodynamic imbalances present
in shock. Only given in acute care settings and only
given IV.
• Pharmacokinetics
• Distribution: throughout the tissues. Metabolism:
kidney, liver, and plasma. Excreted: kidneys. Onset: 5
minutes. Duration: 10 minutes.
• Pharmacodynamics
• Stimulates alpha-1 and beta-1 receptors: increased
cardiac output
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Dopamine: Core Drug Knowledge
• Contraindications and precautions
• Pheochromocytoma (excessive blood iron),
uncorrected cardiac arrhythmias, and ventricular
fibrillation
• Side effects
• nausea and vomiting, headache
• Rapid heart rate (tachycardia)
• Shortness of breath (dyspnea)
• Hypotension
• Adverse effects
• Ectopic beats (extra heart beats), arrthymias
• Angina
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Pathophysiology
Major pathological disorders that are centrally-driven
but affect the peripheral nervous system include:
Parkinson’s disease
Amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s
disease)
Myasthenia Gravis
Multiple sclerosis
Huntington’s disease
Gilles la Tourette’s syndrome (Tourette’s disorder)
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Parkinson’s Disease
• Parkinson disease generally
afflicts patients aged 50 years
and older and progresses
slowly.
• This disease is naturally
occurring in that an external
stimulus, such as a virus or
trauma, does not trigger it.
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Parkinson’s Disease (cont.)
• In PD, degeneration of the neurons that supply
dopamine to the striatum occurs, resulting in
reduced dopamine in the nerve terminals of the
nigrostriatal tract.
• Dopamine is the neurotransmitter that sends
information to the parts of the brain that control
movement and coordination.
• As the disease progresses, messages from the brain
telling the body how and when to move are
delivered more slowly.
Video:
http://www.youtube.com/watch?v=IHDFQfmkKlg
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Parkinson’s Disease:
An imbalance of DA and ACh
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Antiparkinson Drugs
• The reduction in dopamine combined with the
relative excess of ACh causes the symptoms of
Parkinson disease.
• The goal of therapy is to restore the balance
between dopamine and acetylcholine.
• Drugs used to treat Parkinson disease increase
dopamine levels, stimulate dopamine receptors,
extend the action of dopamine in the brain, or
prevent the activation of cholinergic receptors.
Prototype:
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carbidopa-levodopa (Sinemet)
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Carbidopa-Levodopa: Core Drug
Knowledge
• Pharmacotherapeutics
• Combination drug used in treating Parkinson
disease
• Pharmacokinetics
• Administered: oral. Metabolism: peripherally.
Onset: 1 to 2 months. T1/2: 1 to 2 hours
• Pharmacodynamics
• Diffuses levodopa into the central nervous system
(CNS), where it is converted to dopamine
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Carbidopa-Levodopa: Core Drug Knowledge
• Contraindications and precautions
• Caution in psychotic disorders, e.g. schizophrenia
• Side effects
• Teeth grinding (bruxism), nausea, vomiting loss of appetite
• Adverse effects
• Orthostatic hypotension
• Abnormal movements
• Drug interactions
• Dilantin, some antidepressants and all antipsychotics
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Carbidopa-Levodopa: Planning
and Interventions
• Maximizing therapeutic effects
• Take on an empty stomach.
• Monitor diet for high protein and pyridoxine
(B6) as this drug competes with protein and B6
for absorption.
• Minimizing adverse effects
• Administer carbidopa-levodopa at evenly
spaced intervals.
• Titrate the dose.
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Amyotrophic Lateral Sclerosis (ALS)
“Lou Gehrig’s Disease”
• ALS is a progressive neurologic
disorder that affects motor
function.
• The cause of ALS is unknown.
• ALS affects both the upper motor
neurons in the cerebral cortex and
the lower motor neurons in the
brain stem and spinal cord.
• One of its classic features is that it
spares the sensory system.
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Amyotrophic Lateral Sclerosis
(cont.)
• The disease begins in the distal neurons.
• The loss of upper motor neurons results in spastic
paralysis and hyper-reflexia.
• The loss of lower motor neurons results in decreased
muscle tone and reflexes and flaccid paralysis.
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Centrally Acting Anticholinergic
Drugs
• The centrally acting anticholinergic drugs work by
blocking the access of acetylcholine to cholinergic
receptors in the striatum.
• Centrally acting anticholinergic drugs are less
effective than carbidopa-levodopa.
• Historically, there has not been specific
pharmacotherapy for treating ALS.
In December 1995, the FDA approved riluzole
(Rilutek), as the first drug for treatment of ALS.
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Multiple Sclerosis
• 4 types of MS: relapsing-remitting, primary
progressive, secondary progressive, and
progressive-relapsing.
• More than one area of inflammation and scarring
of the myelin in the brain & spinal cord occurs.
• Messages between the brain and other parts of the
body are affected.
• Most common symptoms of MS include fatigue,
weakness, spasticity, balance problems, bladder and
bowel problems, numbness, vision loss, tremor, and
vertigo.
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Anti–Multiple Sclerosis Drugs
• There is no cure for MS but various drugs are
available to modify the disease course, treat
exacerbations, and manage symptoms.
• Pharmacotherapy for MS uses a multilayered
approach.
• Drugs are:
• interferon beta-1a (Avonex),
• interferon beta-1b (Betaseron), and
• glatiramer (Copaxone).
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Huntington’s Disease
• Huntington’s disease is a genetically inherited
disorder.
• The two main symptoms of the disease are
progressive mental status changes and choreiform
muscle movements.
• The inhibitory neurotransmitter GABA is depleted in
the basal nuclei and substantia nigra of the brain.
• There is currently no effective treatment to
prevent or delay the progression of Huntington
disease.
• Newer drug treatments block multiple
neurotransmitters to delay deterioration.
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Gilles de la Tourette Disease
“Tourette’s disorder”
• Tourette’s is an autosomal dominant inherited tic
disorder appearing in childhood.
• Motor and vocal tics from this disease may respond
to haloperidol (Haldol) or other dopamine-blocking
antipsychotic drugs e.g., aripiprazole (Abilify)
• Pimozide (Orap) is another drug used for TS.
• Another drug useful in treating TS is clonidine
(Catapres).
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Case Study
Bill is a 72-year old farmer who started to have a very flat
facial expression and seemed to be staring intently (masked
face) and he walked very slowly with a shuffling gait and very
little arm swinging. At times he seemed to have difficulty in
initiating movement (bradykinesia). His hand and head
movements were very pronounced and they had an irregular,
jerking quality (cogwheel rigidity). When sitting, Bill was
rocking back and forth slowly and clutching the arms of the
chair, and it was noted that his fingers curled in and out in a
rhythmic manner (pill-rolling tremor). On further
examination, Bill had reduced DTR’s (deep tendon reflexes),
difficulty with handwriting (dysgraphia, micrographia) and a
low, monotonous voice (hypophonia).
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Case Study
Write out your answers and turn in for 10 in-class
activity points:
1. What type of neuro-muscular disorder does Bill
probably have?
2. What is the drug-of-choice for this disorder?
3. What are some typical side effects of this
medication?
4. What dietary education is important for this
medication?
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