PHARMACOLOGY

PART 4 Drugs Acting on the Central and Peripheral

Nervous Systems

1. Introduction to Nerves and the Nervous System

 Although nerves do not reproduce, they can regenerate injured parts if the soma and axon hillock
remain intact.
 Efferent nerves take information out of the CNS to effector sites; afferent nerves are sensory
nerves that take information into the CNS.
 When the transmission of action potentials reaches the axon terminal, it causes the release of
chemicals called neurotransmitters, which cross the synaptic cleft to stimulate an effector cell,
which can be another nerve, a muscle, or a gland.
 A neurotransmitter must be produced by a nerve (each nerve can produce only one kind), it must
be released into the synapse when the nerve is stimulated, it must react with a very specific
receptor site to cause a reaction, and it must be immediately broken down or removed from the
synapse so that the cell can be ready to be stimulated again.
 Much of the drug therapy in the nervous system involves receptor sites and the release or reuptake
and breakdown of neurotransmitters.
 The CNS consists of the brain and spinal cord, which are protected by bone and meninges. To
ensure blood flow to the brain if a vessel should become damaged, the brain also has a protective
blood supply moderated by the circle of Willis.
 The hindbrain, the most primitive area of the brain, contains the centers that control basic, vital
functions. The pons, the medulla, and the RAS, which regulates arousal and awareness, are all
located in the hindbrain. The cerebellum, which helps to coordinate motor activity, is found at the
back of the hindbrain.
 The midbrain consists of the hypothalamus, the thalamus, and the limbic system. The limbic system
is responsible for the expression of emotion, and the thalamus and hypothalamus coordinate
internal and external responses and direct information into the cerebral cortex.
 The cerebral cortex consists of two hemispheres, which regulate the communication between
sensory and motor neurons and are the sites of thinking and learning.
 The mechanisms of learning and processing learned information are not understood. Emotion-
related factors influence the human brain, which handles stimuli and responses in complex ways.
Much remains to be learned about the human brain and how drugs influence it. The actions of
many drugs that have know
 2. Anxiolytic and Hypnotic Agents

 Anxiolytics, or minor tranquilizers, are drugs used to treat anxiety by depressing the CNS. When
given at higher doses, these drugs may be sedatives or hypnotics.
o anxiety: unpleasant feeling of tension, fear, or nervousness in response to an environmental
stimulus, whether real or imaginary
 Sedatives block the awareness of and reaction to environmental stimuli, resulting in associated CNS
depression that may cause drowsiness, lethargy, and other effects. This action can be beneficial
when a patient is very excited or afraid.
o sedation: loss of awareness of and reaction to environmental stimuli
 Hypnotics further depress the CNS, particularly the RAS, to inhibit neuronal arousal and induce sleep.
o hypnosis: extreme sedation resulting in CNS depression and sleep
 Benzodiazepines are a group of drugs used as anxiolytics. They react with GABA-inhibitory sites to
depress the CNS. They can cause drowsiness, lethargy, and other CNS effects.
 Barbiturates are an older class of drugs used as anxiolytics, sedatives, and hypnotics. Because they
are associated with potentially serious adverse effects and interact with many other drugs, they are
less desirable than the benzodiazepines or other anxiolytics.
 Buspirone, a newer anxiolytic drug, does not cause sedation or muscle relaxation. Because of the
absence of CNS effects, it is much preferred in certain circumstances (e.g., when a person must drive,
go to work, or maintain alertness).
 Newer hypnotic agents act in the RAS to affect serotonin levels (zaleplon and zolpidem) or to affect
melatonin levels in the brain (ramelteon).
 3. Antidepressant Agents

 Depression is a very common affective disorder; it is associated with many physical manifestations
and is often misdiagnosed. It could be that depression is caused by a series of events that are not
yet understood.
o affect: feeling that a person experiences when he or she responds emotionally to the
environment
 Antidepressant drugs—TCAs, MAOIs, and SSRIs— increase the concentrations of the biogenic
amines in the brain.
o tricyclic antidepressant (TCA): drug that blocks the reuptake of norepinephrine and
serotonin; relieves depression and has anticholinergic and sedative effects
o monoamine oxidase inhibitor (MAOI): drug that prevents the enzyme monoamine oxidase
from breaking down norepinephrine (NE), leading to increased NE levels in the synaptic cleft;
relieves depression and also causes sympathomimetic effects
o selective serotonin reuptake inhibitor (SSRI): drug that specifically block the reuptake of
serotonin and increases its concentration in the synaptic cleft; relieves depression and is not
associated with anticholinergic or sympathomimetic adverse effects
 Selection of an antidepressant depends on individual drug response and tolerance of associated
adverse effects. The adverse effects of TCAs are sedating and anticholinergic; those of MAOIs are
CNS related and sympathomimetic. The adverse effects of SSRIs are fewer, but they do cause CNS
changes.
 Other antidepressants with unknown mechanisms of action are also effective in treating depression.
4. Psychotherapeutic Agents

 Mental disorders were once attributed to environmental influences and life experiences such as
poor parenting or trauma. Mental disorders are now thought to be caused by some inherent
dysfunction within the brain that leads to abnormal thought processes and responses.
o schizophrenia: the most common type of psychosis; characteristics include
hallucinations, paranoia, delusions, speech abnormalities, and affective problems
o mania: state of hyperexcitability; one phase of bipolar disorders, which alternate
between periods of severe depression and mania
o bipolar disorder: behavioral disorder that involves extremes of depression alternating
with hyperactivity and excitement
o narcolepsy: mental disorder characterized by daytime sleepiness and periods of sudden
loss of wakefulness
o attention-deficit disorder: behavioral syndrome characterized by an inability to
concentrate for longer than a few minutes and excessive activity
 Lithium, a membrane stabilizer, is the standard antimanic drug. Because it is a very toxic salt,
serum levels must be carefully monitored to prevent severe toxicity. Many other CNS drugs are
now approved for use in bipolar disorder.
 CNS stimulants, which stimulate cortical levels and the RAS to increase RAS activity, are used to
treat attention-deficit disorders and narcolepsy. These drugs improve concentration and the
ability to filter and focus incoming stimuli.
 5. Antiseizure Agents

 Epilepsy is a collection of different syndromes, all of which have the same characteristic: a sudden
discharge of excessive electrical energy from nerve cells located within the brain. This event is called
a seizure.
 Seizures can be divided into two groups: generalized and partial (focal).
o Generalized seizures can be further classified as
 tonic-clonic (grand mal)
 absence (petit mal)
 myoclonic
 febrile
 rapidly recurrent (status epilepticus)
o Partial (focal) seizures can be further classified as
 simple
 complex
 Drug treatment depends on the type of seizure that the patient has experienced and the toxicity
associated with the available agents.
 Drug treatment is directed at stabilizing the overexcited nerve membranes and/or increasing the
effectiveness of GABA, an inhibitory neurotransmitter.
 Adverse effects associated with antiepileptics (e.g., insomnia, fatigue, confusion, GI depression,
bradycardia) reflect the CNS depression caused by the drugs.
 Patients being treated with an antiepileptic should be advised to wear or carry a Medic Alert
notification to alert emergency medical professionals to their epilepsy and their use of antiepileptic
drugs.
 Patients being treated with antiepileptic are often on long-term therapy, which requires compliance
with their drug regimen and restrictions associated with their disorder and the drug effects.
 6. Antiparkinsonism Agents

 Parkinson’s disease is a progressive, chronic neurological disorder for which there is no cure.
o Parkinson’s disease: debilitating disease, characterized by progressive loss of coordination
and function, which results from the degeneration of dopamine-producing cells in the
substantia nigra
o parkinsonism: Parkinson’s disease–like extrapyramidal symptoms that are adverse effects
associated with particular drugs or brain injuries
 Loss of dopamine-secreting neurons in the substantia nigra is characteristic of Parkinson’s disease.
Destruction of dopamine-secreting cells leads to an imbalance between excitatory cholinergic cells
and inhibitory dopaminergic cells.
o substantia nigra: a part of the brain rich in dopamine and dopamine receptors; site of
degenerating neurons in Parkinson’s disease
 Signs and symptoms of Parkinson’s disease include tremor, changes in posture and gait, slow and
deliberate movements (bradykinesia), and eventually drooling and changes in speech.
 Drug therapy for Parkinson’s disease is aimed at restoring the dopamine–acetylcholine balance. The
signs and symptoms of the disease can be managed until the degeneration of neurons is so
extensive that a therapeutic response no longer occurs.
 Anticholinergic drugs are used to block the excitatory cholinergic receptors, and dopaminergic
drugs are used to increase dopamine levels or to directly stimulate dopamine receptors.
 Many adverse effects are associated with the drugs used for treating Parkinson’s disease, including
CNS changes, anticholinergic effects when using the anticholinergics (atropine-like or
parasympathetic blocking effects), and dopamine stimulation (sympathetic-type effects) in the
peripheral nervous system when using the dopaminergics.
 7. Muscle Relaxants

 Upper-level controls of muscle activity include the pyramidal tract in the cerebellum, which
regulates coordination of intentional muscle movement, and the extrapyramidal tract in the
cerebellum and basal ganglia, which coordinates crude movements related to unconscious muscle
activity.
 Damage to a muscle or anchoring skeletal structure may result in the arrival of a flood of impulses to
the spinal cord. Such overstimulation may lead to a muscle spasm or a state of increased contraction.
 Damage to motor neurons can cause muscle spasticity, with a lack of coordination between muscle
groups and loss of coordinated activity, including the ability to perform intentional tasks and
maintain posture, position, and locomotion.
 Centrally acting skeletal muscle relaxants are used to relieve the effects of muscle spasm.
Dantrolene, a direct-acting skeletal muscle relaxant, is used to control spasticity and prevent
malignant hyperthermia.
 The botulinum toxin type B is used to reduce the severity of abnormal head position and neck pain
associated with cervical dystonia. Botulinum toxin type A is used to improve the appearance of
moderate to severe glabellar lines and to treat cervical dystonia, severe primary axillary
hyperhidrosis, and strabismus and blepharospasm associated with dystonia. Incobotulinumtoxin A is
also used to decrease the severity of head position with cervical dystonia and to treat
blepharospasm in adults previously treated with botulinum A
 8. Narcotics, Narcotic Antagonists, and Antimigraine Agents

 Pain occurs any time that tissue is injured and various chemicals are released. The pain impulses are
carried to the spinal cord by small-diameter A-delta and C fibers, which form synapses with
interneurons in the dorsal horn of the spinal cord.
 Opioid receptors found throughout various tissues in the body react with endogenous endorphins
and enkephalins to modulate the transmission of pain impulses.
 Narcotics, derived from the opium plant, react with opioid receptors to relieve pain. In addition,
they lead to constipation, respiratory depression, sedation, and suppression of the cough reflex;
they also stimulate feelings of well-being or euphoria.
 Because narcotics of all kinds are associated with the development of physical dependency, they are
controlled substances.
 The effectiveness and adverse effects associated with specific narcotics are associated with their
particular affinity for various types of opioid receptors.
 Narcotic agonists react with opioid receptor sites to stimulate their activity.
 Narcotic agonists–antagonists react with some opioid receptor sites to stimulate activity and block
other opioid receptor sites. These drugs are not as addictive as pure narcotic agonists.
 Narcotic antagonists, which work to reverse the effects of narcotics, are used to treat narcotic
overdose or to reverse unacceptable adverse effects.
 Migraine headaches are severe, throbbing headaches on one side of the head that may be
associated with an aura or warning syndrome. These headaches are thought to be caused by arterial
dilation and hyper-perfusion of the brain vessels.
 Treatment of migraines may involve either ergot derivatives or triptans. Ergot derivatives cause
vasoconstriction and are associated with sometimes severe systemic vasoconstrictive effects,
whereas triptans, a newer class of selective serotonin receptor blockers, cause CNS vasoconstriction
but are not associated with as many adverse systemic effects.
 9. General and Local Anesthetic Agents

 General anesthetics result in analgesia, amnesia, and unconsciousness; they also block muscle
reflexes that could interfere with a surgical procedure or put the patient at risk for harm.

 The use of general anesthetics involves a widespread CNS depression that could be harmful,
especially in patients with underlying CNS, cardiovascular, or respiratory diseases.
 Anesthesia proceeds through four predictable stages from loss of sensation to total CNS depression
and death.
 Induction of anesthesia is the period of time from the beginning of anesthesia administration until
the patient reaches surgical anesthesia.
 Balanced anesthesia involves giving a variety of drugs, including anticholinergics, rapid intravenous
anesthetics, inhaled anesthetics, NMJ blockers, and narcotics.
 Patients receiving general anesthetics should be monitored for any adverse effects; they need
reassurance and safety measures until the recovery of sensation, mobility, and ability to
communicate.
 Local anesthetics block the depolarization of nerve membranes, preventing the transmission of pain
sensations and motor stimuli.
 Local anesthetics are administered to deliver the drug directly to the desired area and to prevent
systemic absorption, which could lead to serious interruption of nerve impulses and response.
 Ester-type local anesthetics are immediately destroyed by plasma esterases. Amide local anesthetics
are destroyed in the liver and have a greater risk of accumulation and systemic toxicity.
 Nursing care of patients receiving general or local anesthetics should include safety precautions to
prevent injury and skin breakdown; support and reassurance to deal with the loss of sensation and
mobility; and patient teaching regarding what to expect, to decrease stress and anxiety.
 10. Neuromuscular Junction Blocking Agents

 The nerves communicate with muscles at a point called the NMJ, using ACh as the neurotransmitter.
 NMJ blockers interfere with muscle function. The two groups of NMJ blockers are nondepolarizing
and depolarizing agents.
 The nondepolarizing NMJs include those agents that act as antagonists to ACh at the NMJ and
prevent depolarization of muscle cells. The depolarizing NMJs act as an ACh agonist at the junction,
causing stimulation of the muscle cell and then preventing it from repolarizing.
 NMJ blockers are primarily used as adjuncts to general anesthesia, to facilitate endotracheal
intubation, to facilitate mechanical ventilation, and to prevent injury during electroconvulsive
therapy.
 Adverse effects of NMJ blockers, such as prolonged paralysis, inability to breathe, weakness, muscle
pain and soreness, and effects of immobility, are related to muscle function blocking.
 Care of patients receiving NMJ blockers must include support and reassurance because
communication is decreased with paralysis; vigilant maintenance of airways and respiration;
prevention of skin breakdown; and monitoring for return of function.

Reference:
Karch, A. M. (2013). Focus on nursing pharmacology. Sixth edition. Philadelphia: Wolters Kluwer.