Module 4: Neurologic Medications

Tasks
Study tip: For each chapter, read "Special Concerns for Rehabilitation Patients" and "Case Study" prior to chapter content. Answer the
case study questions while you read the chapter, and then compare your answers to Appendix C.
Ch. 6 (Sedative-Hypnotic and Antianxiety Drugs)
Ch. 7 (Drugs to Treat Affective Disorders: Depression and Bipolar Syndrome)
Ch. 9 (Antiepileptic Drugs)
Ch. 10 (Pharmacological Management of Parkinson Disease)
Ch. 11 (General Anesthetics)
Ch. 19 (p. 290 – 293: Clinical applications, problems, and adverse effects of cholinergic stimulants)

Medication Cabinet
alprazolam (Xanax) levetiracetam (Keppra)
amitriptyline (Elavil) levodopa- carbidopa (Sinemet)
clonazepam (Klonopin) lorazepam (Ativan)
diazepam (Valium) meperidine (Demerol)
donepezil (Aricept) phenobarbital (Solfoton)
duloxetine (Cymbalta) phenytoin (Dilantin)
escitalopram (Lexapro) sertraline (Zoloft)
fluoxetine (Prozac) triazolam (Halcion)
gabapentin (Neurontin) zolpidem (Ambien)
imipramine (Tofranil)

1. Recall which two suffixes are common for benzodiazepines?

–epam, –olam
2. Identify 3 medications in neurologic and pain cabinets.
diazepam (Valium); gabapentin (Neurontin); meperidine (Demerol)

Learning Objectives
1. Compare and contrast mechanisms of action for benzodiazepines vs. non-benzodiazepine sedative-hypnotics.
1. Benzodiazepine- triazolam (Halcion)
1. Increase inhibitory effects at CNS synapses that use neurotransmitter GABA
2. Benzodiazepines bind to a specific receptor located at certain inhibitory synapses in the reticular formation
of the CNS (presence of this GABA-benzodiazepine-chloride ion channel receptor that accounts for MOA)
1. GABA initiates an increase in chloride conductance through the channel resulting in
hyperpolarization, or a deceased ability to raise the neuron to its firing threshold
2. GABAA (most common) and GABAC MOA: by increasing chloride entry into neuron
3. GABAB cause inhibition by affecting potassium channels and decreasing calcium entrance into
CNS neurons
4. GABAA subunits mediate different effects (selective vs nonselective benzodiazepine)
1. Sedation: alpha-1, beta-2, and gamma-2 subunits
2. Decreased anxiety: alpha-2, beta-3, and gamma-2 subunits
3. Antianxiety properties similar/identical to sedative-hypnotic MOA
1. Also seem to increase inhibition in the spinal cord, which produces some degree of skeletal muscle
relaxationà individual feels more relaxed
2. Nonbenzodiazepine
1. Barbiturates phenobarbital (Solfoton)
1. GABA-benzodiazepine-chloride ion channel receptor like benzodiazepines
1. Bind directly to the GABAA receptor at a site that is different from the binding site for
GABA or benzodiazepines
2. At higher doses, barbiturates directly increase the release of inhibitory transmitter such as glycine
and reduce the effects of excitatory transmitters such as glutamate
3. Specificity for neurons in the midbrain portion of the reticular formation as well as limbic structures

2. Nonbenzodiazepine sedative-hypnotics zolpidem (Ambien)

1. Bind to the GABAA receptor, which then causes GABA to bind more effectively, thus increasing
chloride conductance and the level of inhibition in the neuron.
2. Bind preferentially to the alpha-1 subunit of GABAA
2. Classify sedative-hypnotic and antianxiety drugs by half-life (short-intermediate vs. long).

Sedative-Hypnotic Drugs
Short Half-Life Intermediate Half-Life Long Half-Life
triazolam (Halcion)
zolpidem (Ambien)

Antianxiety Drugs
Short Half-Life Intermediate Half-Life Long Half-Life
alprazolam (Xanax) diazepam (Valium)
Lorazepam (Ativan)
clonazepam (Klonopin)

3. Identify adverse effects of sedative-hypnotic and antianxiety drugs that may influence rehabilitation interventions and
timing.
1. Sedative-hypnotics
1. Residual hangover effect- drowsiness and decreased motor performance the next day
1. If patients are prone to residual effects, try taking drug with a shorter half-life (zolpidem, zaleplon,
eszopiclone, ramelteon)
2. Therapy sessions that require the patient to actively participate in activities such as gait training or
therapeutic exercise will be useless and hazardous if the patient is extremely drowsy
1. Scheduling patients for certain types of rehab within several hours after administration of
sedative-hypnotics or sedative-like anxiolytics is counterproductive and should be avoided
2. Anterograde amnesia- patient may have trouble recalling events that occurred for a certain period of time
before the drug was taken (could exacerbate a pre-existing memory problem)
3. GI discomfort (nausea, vomiting), dry mouth, sore throat, and muscular incoordination; cardiovascular and
respiratory depression may also occur
4. Benzodiazepines and other drugs used to treat sleep disorders and anxiety are often associated with falls
and subsequent trauma, including hip fractures, especially in older adults.
1. Therapists can intervene to help prevent this through balance training, environmental modifications
2. Antianxiety drugs
1. Sedation, psychomotor impairments (especially during activities that require alertness)
2. Patient will be much calmer and more relaxed, thus offering the potential benefit of gaining the patient’s full
cooperation during PT
1. Anxiolytic benzodiazepines typically reach peak blood levels 2-4 hours after oral administration, so
scheduling the rehab session during that time may improve the patient’s participation in treatment
4. Classify specific antidepressant drugs by mechanism of action and identify those also indicated for chronic pain.
1. Selective-serotonin reuptake inhibitors (SSRIs)
1. Includes: fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro)
2. Work by blocking the reuptake of serotonin into the presynaptic terminal at locations in the brainàby
inhibiting the enzyme responsible for the active transport (reuptake) of serotonin, SSRIs allow the released
serotonin to remain in the synaptic cleft and continue to exert its effects for a longer period of time
3. fluoxetine (Prozac): used to treat chronic pain associated with diabetic neuropathic pain, fibromyalgia,
Raynaud's phenomenon)
2. Serotonin-norepinephrine reuptake inhibitors (SNRIs): Target serotonin and norepinephrine reuptake without an
appreciable effect on dopamine synapses
1. Includes: duloxetine (Cymbalta): used to treat chronic pain (diabetic peripheral neuropathic pain,
fibromyalgia, OA, back pain)
3. Tricyclics: Work by blocking the reuptake of amine neurotransmitters into the presynaptic terminal; not very selective
in their effects and tend to affect synapses using all three primary amines: serotonin, NE, and dopamine
1. Includes: amitriptyline (Elavil), imipramine (Tofranil)
2. amitriptyline (Elavil): used to treat chronic pain (fibromyalgia, neuropathic pain, headache, low back pain)
3. imipramine (Tofranil): used to treat chronic pain associated with diabetic neuropathic pain, fibromyalgia,
Raynaud's phenomenon
4. Monoamine oxidase Inhibitors (MAOIs)
1. Nonselective inhibition of monoamine oxidase (type A and B) enzymes (located at the amine synapses) from
removing the released transmitters through enzymatic destruction à allowing more of the transmitter to
remain in the synaptic cleft and continue to exert an effect
2. Directly increase activity at amine synapses, which can bring about beneficial changes in receptor sensitivity
and neuronal function at these synapses

5. Compare profiles for multi-system adverse effects among antidepressant drug classes: SSRI, SNRI, tricyclics, MAOI.
1. SNRIs and SSRIs: Low incidence of CV problems (arrhythmias, orthostatic hypotension) and anticholinergic effects
(dry mouth, constipation, urinary retention, confusion)
1. GI symptoms such as N/V, diarrhea or constipation are most common
2. Cause less sedation compared to tricyclics
3. Serotonin syndrome- often happens when SNRIs and SSRIs are used in high doses or when 2 or more
antidepressants are administered concurrently
1. If serotonin reaches excessive levels- symptoms: sweating, agitation, restlessness, shivering,
increased HR (tachycardia), neuromuscular hyperexcitability (tremor, clonus, hyperreflexia,
fasciculations, rigidity)
4. SSRIs- may cause sexual dysfunction (decreased libido, impotence); anxiety, nausea, insomnia
5. SNRIs- may cause GI problems (nausea, constipation) and male sexual dysfunction; slightly higher risk of
agitation or increased mania
2. Tricyclics: Feelings of lethargy and sluggishness
1. Significant anticholinergic properties- act as if they are blocking certain central and peripheral Ach receptors
1. Impairment of central Ach transmission may cause delirium and confusion
2. Peripheral anticholinergic properties symptoms: dry mouth, constipation, urinary retention,
confusion, tachycardia
3. CV problems include arrhythmias and orthostatic hypotension
4. Increase seizure activity
5. Highest potential for lethal overdose (fatal cardiac arrhythmias)
3. MAOIs: Tend to produce CNS excitation resulting in restlessness, irritability, agitation, and sleep loss
1. Central and peripheral anticholinergic effects (tremor, confusion, dry mouth, and urinary retention) (occur to
a lesser extent than with the tricyclics)
2. Because of systemic MAO inhibition, excess activity at peripheral sympathetic adrenergic terminals may
cause profound increase in BP, leading to hypertensive crisis
3. “Cheese” effect- additive effect of increased catecholamine release (because of the ingested tyramine in
fermented cheese) and decreased catecholamine breakdown (because of MAO inhibition) can lead to
excessive catecholamine levels, thereby causing a hypertensive crisis that leads to MI or stroke
6. Classify antiseizure drugs by mechanism of action.
1. Barbiturates: Includes: phenobarbital (Solfoton)
1. Potentiate inhibitory effects of GABA; may also inhibit the release of Ca into excitatory presynaptic nerve
terminals, thereby decreasing the release of excitatory neurotransmitter such as glutamate
2. Benzodiazepines: Includes: diazepam (Valium), clonazepam (Klonopin), lorazepam (Ativan)
1. Potentiate inhibitory effects of GABA
3. Hydantoins: Includes: phenytoin (Dilantin)
1. Primary effect is to stabilize neural membrane and decreased neuronal excitability by decreasing Na entry
into rapidly firing neurons;
1. Basically, inhibits the ability of Na channels to reset from an inactive to active state after the neuron
has fired an AP
2. By inhibiting the reactivation of Na channels, phenytoin prolongs the time between APs (absolute
refractory period) so that the neurons must slow their firing rate to a normal level
2. At higher doses, may also decrease neuronal excitability by increasing the effects of GABA and by
influencing the movement of K and Ca across the nerve membrane
4. Iminostilbenes: similar to hydantoins; may also inhibit the presynaptic uptake and release of NE
5. Succinimides: appears to inhibit spontaneous firing in thalamic neurons by limiting Ca entry
6. Valproates:
1. May inhibit Na channels, limiting Na entry into rapidly firing neurons
2. Increase K conductance and efflux from certain neurons, thereby hyperpolarizing the neurons and
decreasing its excitability
3. Higher doses increase CNS GABA concentrationsàincreased GABAergic inhibition
7. Identify adverse effects common across classes of antiseizure drugs.
Sedation (dizziness, Cerebellar signs and movement disorders Skin
GI distress lethargy, fatigue) (nystagmus, ataxia, dyskinesia) Headache
problems
Barbiturates X X X
Benzodiazepine X X
Hydrantoins X X X X X
Iminostilbenes X X
Succinimides X X X X
Valproates X
1. Barbiturates: sedation (primary problem), nystagmus, ataxia, folate deficiency, vitamin K deficiency, skin problems
1. Paradoxical increase in seizures and an increase in hyperactivity may occur in some children
2. Benzodiazepines: sedation, ataxia, and behavioral changes
3. Hydrantoins: gastric irritation, confusion, sedation, dizziness, headache, cerebellar signs (nystagmus, ataxia,
dysarthria), gingival hyperplasia, increased body and facial hair (hirsutism), and skin disorders
4. Iminostilbenes: dizziness, drowsiness, ataxia, blurred vision, anemia, water retention (because of abnormal ADH
release), cardiac arrhythmias, and CHF
5. Succinimides: GI distress (N/V), headache, dizziness, fatigue, lethargy, movement disorders (dyskinesia,
bradykinesia), and skin rashes and itching
6. Valproates: GI distress, temporary hair loss, weight gain or loss, and impaired platelet function

8. Explain fluctuations in clinical response to levodopa (end-of-dose akinesia, on-off phenomenon) and purpose of a
drug holiday.
1. End-of-dose akinesia- the drug’s effectiveness simply seems to wear off prior to the next dose
1. Usually resolved by adjusting the quantity and timing of levodopa administration (smaller doses may be
given more frequently) or by using a sustained release form of the drug
2. On-off phenomenon- effectiveness of levodopa may suddenly and spontaneously decrease, resulting in the abrupt
worsening of parkinsonian symptoms (the “off” period). Remission of symptoms may then occur spontaneously or
after taking a dose of levodopa (the “on” period). This on-off pattern may repeat itself several times during the day
1. Off periods are directly related to diminishing plasma levels of levodopa. Off periods can be eliminated by
administering levodopa continuously by IV infusion, thus preventing the fall in plasma levels
3. Drug holiday- used in patients who have become refractory to the beneficial effects of levodopa or who has had a
sudden increase in adverse side effects
1. During this period, the patient is gradually removed from all anti-Parkinson medication for 3 days to 3 weeks
while under close medical supervision
2. Purpose: to allow the body to recover from any toxicity or tolerance that may have developed because of
prolonged use of levodopa at relatively high dosages.
3. They are done with hope that levodopa can eventually be resumed at a lower dosage and with better results
4. No longer routinely used because of their potential risk to the patient

9. Describe the four stages of general anesthesia.

1. Stage I: Analgesia: patient begins to lose somatic sensation but still conscious and somewhat aware of what is
happening
2. Stage II: Excitement (Delirium): patient is unconscious and amnesiac but appears agitated and restless. This
paradoxical increase in level of excitation is highly undesirable because patients may injure themselves
while thrashing about. An effort is made to move as quickly as possible through this stage.
3. Stage III: Surgical Anesthesia: this level is desirable for the surgical procedures and begins with the onset of regular,
deep respiration.
4. Stage IV: Medullary Paralysis: marked by the cessation of spontaneous respiration because respiratory control
centers located in the medulla oblongata are inhibited by excessive anesthesia. The ability of the medullary
vasomotor center to regulate BP is also affected, and cardiovascular collapse ensues. If this stage is inadvertently
reached during anesthesia, respiratory and circulatory support must be provided or the patient will die

10. Describe clinical indications for different classes of preoperative medications.

1. Benzodiazepine (Diazepam, Lorazepam): decrease anxiety and tension; provide sedation and amnesia
2. Barbiturates (Phenobarbital): decrease anxiety; facilitate induction of anesthesia
3. Opioids (Meperidine): provide analgesic, antianxiety, and sedative effects
4. Antihistamines: provide sedative-hypnotic effects; reduces vomiting
5. Anticholinergics: prevent excessive salivation and respiratory tract secretions; reduce postoperative N/V
6. H2 Receptor Blockers: reduce gastric acidity; help prevent aspiration pneumonitis
7. 5-HT3 (Serotonin) Receptor Antagonists: reduce postoperative nausea and vomiting

11. Identify clinical indications for cholinergic stimulants.