Action

There are two commonly used classes of drugs used in migraine treatment: (1) ergot alkaloids; and (2) triptans. Both of these drug classes stimulate serotonin (5-hydroxytryptamine [5-HT]) and affect the many serotonin receptor subtypes found throughout the CNS. There are a variety of other anticonvulsant, antidepressant, beta-adrenergic blockers, or calcium channel blockers that may be used to treat severe migraines. Riboflavin (Vitamin B₂) and feverfew are alternative therapies some have found to be effective.

The process that produces migraine headaches is thought to be local dilation of the blood vessels in the cranium or the release of sensory neuropeptides through nerve endings in the trigeminal system. The vascular 5-HT receptor is present on the human basilar artery and in the vessels of human dura mater. Use of the 5-HT, or serotonin, receptor antagonists results in cranial vessel constriction (narrowing) and blocking of neuropeptides that cause inflammation, which happens at the same time the patient feels the relief from migraine headache. Some of these products also cross the blood-brain barrier, produce central activity on the trigeminovascular system, and stop nerve depolarization at peripheral sites in the cranium.

Additionally, adrenergic-blocking agents dilate the veins in smooth muscle tissue in the peripheral vascular system, reducing cerebral blood flow and arterial pulsing, which reduces headache pain. Other actions include dilation of veins in the uterus, an increase in uterine contractions (oxytocic effect), and a decrease in blood pressure.

Uses

Antimigraine agents are used in both the prevention and treatment of vascular headaches. They relieve the pain of vascular headaches by narrowing dilated cerebral arteries. OTC drugs such as ibuprofen or aspirin are usually started first. If these drugs are not helpful, triptans such as sumatriptan (Imitrex) are used. The triptans come in a variety of forms, including injection and inhalation, so that if the patient has nausea or vomiting, he or she may still take the drug. The action of 5-HT agonists is not affected by whether or not the person with the migraine has an aura or by the length of the attack, sex or age of the patient, relationship to menstrual periods, or the use of other common migraine prevention drugs. Ergot alkaloids like ergotamine (Ergonal) are used if triptans are not effective, although less commonly. Ergot alkaloids are also used for pregnant women for oxytocic (labor-inducing) and other smooth-muscle spasmogenic effects. They are not used in early pregnancy as they are pregnancy category X drugs.

Adverse Reactions

Adverse reactions to antimigraine agents in general include heart murmurs, brief tachycardia (rapid heartbeat), confusion, depression, dizziness, drowsiness, fixed miosis (constriction) of the pupil of the eye, paresthesias (numbness and tingling) in the toes, weakness (especially in legs), nausea and vomiting, leg cramps, localized pruritus (itching) and edema (fluid buildup in the body tissues), and neutropenia of the blood. Symptoms of overdosage include numb, cold, pale extremities; constant muscle pain, even at rest; decreased or absent arterial pulses; drowsiness; confusion; depression; convulsions; hemiplegia; and fixed miosis. Because of the potential for 5-HT agonists to cause coronary vasospasm, patients with ischemic heart disease or other major cardiovascular disease, or uncontrolled hypertension (high blood pressure) should not use these products.

Drug Interactions

When antimigraine agents are used with other vasoconstrictors, vasoconstriction may be increased. The 5-HT agonists may not be used within 24 hours of taking an ergotamine-containing preparation and may not be used at the same time with monoamine oxidase (MAO) inhibitor therapy, selective serotonin reuptake inhibitors (SSRIs) serotonin/norepinephrine reuptake inhibitors (SNRIs), lithium (given for depression), and many other drugs. Some of the different triptans cannot be used within 24 hours of each other because of drug interactions.

Nursing Implications and Patient Teaching

Action

A number of drugs control seizures through depression or slowing of abnormal electrical discharges in the CNS. These products work in a variety of ways. There is usually one drug that is more effective than another for a patient, depending on the type of seizure activity. Patients with newly diagnosed and acute seizure disorders are often started on parenteral injection therapy; when seizure activity has come under control, oral therapy is started.

Uses

Barbiturates, which have a long duration of action, are an important category of prescription anticonvulsants and are used for their sedative effect on the brain. They may be used in combination with medications from the other three groups. Benzodiazepines are useful with some problems but also have a lot of serious adverse effects. Hydantoins have a wide range of uses, and phenytoin (Dilantin) is by far the most commonly used anticonvulsant. Succinimides are used to control petit mal seizures. GABA analogs have wide use for many types of seizures. Each of these five groups, along with a variety of other newer miscellaneous anticonvulsants, are discussed in this section.

Because of the variety of drugs and the many possible side effects, the choice of an anticonvulsant tends to be a trial or experiment for each patient. When seizures are not stopped with one drug, another may be added, or the first drug may be stopped and another product used instead.

Action

Barbiturates are CNS depressants. They act primarily on the brainstem reticular formation, reducing nerve impulses that go to the cerebral cortex. Barbiturates depress the respiratory system and slow the activity of nerves and muscles (smooth, skeletal, and cardiac). Barbiturates also raise the seizure threshold, or the level of electrical activity that must be produced before a seizure will occur. Barbiturates may be short-acting, intermediate-acting, or long-acting.

Uses

Long-acting barbiturates are used as anticonvulsants to control and prevent grand mal seizures. They are sometimes used if other drugs do not help to treat status epilepticus, a condition in which a series of severe grand mal seizures occur one after another without stopping. They may also be used to treat seizures caused by tetanus, fever, or drugs.

Adverse Reactions

Adverse reactions to barbiturates include worsening of symptoms of certain organic brain disorders in older adult patients, dizziness, drowsiness, hangover, headache, lethargy (sleepiness), paradoxical restlessness or excitement, unsteadiness, photosensitivity (abnormal response to exposure to sunlight), rash, diarrhea, nausea, hepatitis with jaundice, vomiting, anemia, decreased platelet counts, unusual bleeding or bruising, urticaria (hives), joint and muscle pains, tolerance (increased resistance to the drug caused by repeated use), and withdrawal symptoms due to physical dependence when discontinued.

In cases of acute overdose, the patient may show exaggerated CNS depression, slow, shallow respirations, miosis, tachycardia, areflexia (absence of reflexes), shock, or coma. Death may occur as a result of cardiorespiratory failure.

Drug Interactions

Because barbiturates act through the P450 enzyme system to speed up the metabolism of some drugs in the liver, they reduce the activity of anticoagulants, corticosteroids, and digitalis preparations. MAO inhibitors may increase the depressant effects of the barbiturates. There may be significant additive effects if barbiturates are used along with alcohol, antihistamines, benzodiazepines, methotrimeprazine, narcotics, and tranquilizers.

Action

Benzodiazepines are CNS depressants. Their exact mechanism of action is not known, but they are thought to act on the hypothalamus and limbic system of the brain, decreasing the vasopressor response and increasing the arousal threshold. Benzodiazepines suppress the electrical spike-and-wave brain discharge in seizures and decrease the frequency, amplitude, duration, and spread of the discharge in minor motor seizures.

Uses

Benzodiazepines are used to treat partial seizures and also to treat Lennox-Gastaut syndrome (petit mal variance) and for patients who have failed to respond to succinimide drugs such as ethosuccinimide (Zarontin). Three benzodiazepines are approved for use as anticonvulsants. Diazepam (Valium) is used intravenously to control seizures and is the drug of choice for treatment of status epilepticus. Clonazepam (Klonopin) is used for oral treatment of petit mal seizures in children, and clorazepate (Tranxene) is used with other antiepileptic agents to control partial seizures.

Drug Interactions

Alcohol, other sedatives and hypnotics, antidepressants, anticonvulsants, and narcotics may produce additive sedative effects if used with benzodiazepines. Some combinations of anticonvulsants may result in an antidepressant effect or provoke additional seizures.

Action

Hydantoins act primarily on the motor cortex, where they stop the spread of seizure activity by blocking neuronal sodium and calcium channels. This stabilizes the nerve cell against hyperexcitability and reduces the maximal activity of brainstem centers responsible for the tonic phase of grand mal seizures. It also has an antiarrhythmic property.

Uses

Hydantoins are used to treat tonic-clonic and psychomotor seizures. Sometimes they are used to treat status epilepticus, migraine, and trigeminal neuralgia. They are also used in some nonepileptic psychotic patients.

Adverse Reactions

Adverse reactions to hydantoins include ataxia (poor coordination), dizziness, drowsiness, hallucinations, inattentiveness, nystagmus (rhythmic movement of the eyes), ocular disturbances, poor memory, slurred speech, constipation, nausea, vomiting, blood cell disturbances, purpura (bruising), acnelike eruptions, gingival hyperplasia (overgrowth of gums), lupus erythematosus, hepatitis with jaundice, and lymph node hyperplasia. Hydantoins are also teratogenic-category D (producing changes in the fetus). Overdosage may produce ataxia, coma, dysarthria, hypotension, nystagmus, and unresponsive pupils.

Drug Interactions

Hydantoin drug interactions are frequent and often substantial. Even when given alone, the drug requires careful monitoring of the patient. It is very important to see the patient regularly when it is used with any other medication or vitamins because the dose that prevents seizure is very close to the toxic dose. It may also alter the results of various laboratory tests.

Action

Succinimide-type anticonvulsants raise the seizure threshold in the cortex and basal ganglia, making seizures less likely and reduce response at the nerve synapse to some specific types of nerve stimulation.

Uses

Succinimides are used to control absence seizures.

Adverse Reactions

Adverse reactions to succinimides include dizziness, headaches, hiccups, hyperactivity, lethargy, mood or mental changes, rashes, blurred vision, photophobia (intolerance to light), anorexia, abdominal pain, diarrhea, nausea, vomiting, urinary frequency, vaginal bleeding, blood cell changes, alopecia (hair loss), muscular weakness, systemic lupus erythematosus, dis­turbances of sleep, inability to concentrate, mental slowness, and night terrors.

Drug Interactions

If these drugs are used with other anticonvulsants, they can result in increased sex drive (libido) or increased frequency of tonic-clonic seizures. Bone marrow–depressing drugs used with succinimides can result in significant and fatal blood dyscrasias or conditions.

Action

The mechanism of action for GABA analogs is not clearly understood. All of these drugs are chemically unrelated but they all increase the actions of GABA, which is an inhibitory neurotransmitter. It is thought that they might slow the sodium channel, helping to stabilize the neuronal membranes. Some of the newer GABA analogs also increase the action of GABA, block voltage of sodium channels, antagonize glutamate, and modulate calcium channels.

Uses

Although relatively new drugs, GABA analogs are used in the treatment, along with other anti­epileptic drugs, for simple partial, complex partial, secondarily generalized, generalized tonic-clonic, and absence seizures. These medications are also used in treating peripheral neuropathy, post-herpatic neuralgia, and fibromyalgia.

Drug Interactions

Increased CNS depression may occur when valproic acid is administered with other CNS depressants, including other anticonvulsants and alcohol. These drugs interact with many other CNS drugs and may increase or decrease their blood levels. This is particularly true of phenytoin. It is advisable to monitor serum concentrations of any other anticonvulsants being used with these drugs to prevent overdosage.

Nursing Implications and Patient Teaching

Action

The vomiting center of the brain may be stimulated by many factors: drugs, metabolic disorders, radiation, motion, gastric irritation, and vestibular neuritis. Vomiting is produced by direct action on the vomiting center of the brain, by indirect action through stimulation of the chemoreceptor trigger zone, and through increased activity of chemical neurotransmitters. Nausea and vomiting resulting from motion are probably caused by impulses to the vestibular network of the labyrinth system of the ear, which is located near the vomiting center. The impulses are conducted to the vomiting center by cholinergic nerves. Thus drugs that inhibit cholinergic nerve impulses should be effective in treating motion sickness.

Uses

Antidopaminergic agents such as chlorpromazine (Thorazine) and prochlorpromazine (Compazine) are used almost exclusively to control nausea and vomiting. Selected first generation H1 blocker antihistamine/anticholinergic medications are used to control motion sickness. Meclizine (Antivert) and dimenhydrinate (Dramamine) are the only products used to control acute vertigo. 5-HT₃ antagonists such as ondansetron (Zofran) are routinely used prophylactically in patients expected to have nausea (e.g., patients undergoing chemotherapy).

Adverse Reactions

Drowsiness or sedation is the most common side effect of the anticholinergics, but tolerance to this reaction usually develops with long-term therapy. Patients may also feel dry mouth, stuffy nose, blurred vision, constipation, urinary retention, and other anticholinergic reactions.

Drug Interactions

The sedative effect of some antiemetic medications is increased (or potentiated) by other CNS depressants. Anticholinergic antiemetics can increase the anti­cholinergic side effects of many other drugs. The drug interactions may vary, depending on the type of antiemetic-antivertigo drug, but would be similar to other anticholinergic or antidopaminergic products. (See the earlier discussions about anticholinergic and antidopaminergic actions at the beginning of this chapter.)

Nursing Implications and Patient Teaching

Uses

Antiparkinsonian agents are anticholinergic and dopaminergic drugs used to control the symptoms of Parkinson disease. Amantadine (Symmetrel) was originally introduced as an antiviral agent for the prophylaxis of Influenza A but was unexpectedly found to cause improvement in symptoms. The patient may achieve good control of symptoms for a while with these drugs but patients develop tolerance to the drugs, requiring frequent readjustment of doses and medications.

Adverse Reactions

Dopaminergic agents may produce dysrhythmias (irregular heartbeats), muscle twitching, psychotic reactions, rigidity, diarrhea, epigastric distress, GI bleeding, nausea, vomiting, blurred vision, alopecia, bitter taste, hot flashes, rash, and urinary retention.

Anticholinergic agents may cause postural hypotension (low blood pressure when a person suddenly stands up), tachycardia, agitation, confusion, depression, headache, memory loss, muscle cramping, constipation, vomiting, diplopia (double vision), increased intraocular pressure, decreased sweating, flushing, dry mouth, and skin rash.

Early signs of toxicity in the patient taking dopaminergic agents include muscle twitching and blepharospasm (eyelid spasms). Overdosage is a common phenomenon, particularly with long-term drug therapy. It is recognizable because the patient experiences a sudden onset of progressively worsening parkinsonian symptoms. These drugs should be tapered gradually.

Drug Interactions

Common drug interactions differ, according to whether the preparation is an anticholinergic or a dopaminergic agent. These drugs commonly interact with many types of medications; product information must be closely studied. These patients often take antipsychotics, which have the potential to interact with these antiparkinson drugs. Two herbal products, ginkgo and grape seed, are commonly used to treat symptoms of Parkinson disease. The Complementary and Alternative Therapies box summarizes these products and their drug interactions.

Nursing Implications and Patient Teaching

Action

Benzodiazepines are thought to act at the limbic, thalamic, and hypothalamic levels of the CNS, producing a calming effect.

Uses

Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium), as well and nonbenzodiazepines, are used to relieve anxiety, tension, and fears that occur by themselves or as the result of illness. Other indications include management of delirium tremens after alcohol withdrawal; premedication for surgical and endoscopic procedures or electric cardioversion; treatment of convulsive disorders (diazepam only); and relief of muscle spasm.

Adverse Reactions

Adverse reactions to antianxiety agents include hypotension, tachycardia, clumsiness, confusion, de­pression, drowsiness, fatigue, headache, insomnia, paradoxical reactions (excitement, hallucinations, agitation, hostility, or rage), syncope (light-headedness and fainting), unsteadiness, visual disturbances, weakness, anorexia, constipation, difficulty swallowing, dry mouth, hiccups, jaundice, nausea, vomiting, urinary retention, blood cell changes, pruritus, skin rash, joint pain, and unexplained sore throat and fever.

Overdosage may produce sleepiness, confusion, coma, diminished reflexes, and hypotension. Tolerance is easily developed.

Drug Interactions

Giving benzodiazepines along with any of the following substances may increase the effect of either agent: alcohol; anesthetics; MAO inhibitors; or CNS depressants such as antihistamines, barbiturates, phenothiazines, narcotics, sedatives, tranquilizers, hypnotics, anticonvulsants, or tricyclic antidepressants (TCAs). Caffeinated products and excessive cigarette smoking can antagonize (decrease) the anxiolytic (antianxiety) effect of these drugs. Herbal products are also often used by patients to treat stress and anxiety. The Complementary and Alternative Therapies box summarizes herbal preparations the patient may be using and their drug interactions.

Nursing Implications and Patient Teaching

Action

The antidepressant effect of tricyclics is not completely understood. It is thought that tricyclic antidepressants (TCAs) potentiate the effects of or inhibit the uptake of norepinephrine andserotonin (biogenic amines) by the presynaptic neuronal membrane in the CNS, thereby increasing the concentration of these biogenic amines at the synapse.

Uses

TCAs are used primarily to relieve the symptoms of severe depression that has internal biologic causes (endogenous depression). They may also be used to treat mild depression caused by factors in the patient’s life (exogenous or reactive depression), which is not self-limiting and does not interfere with usual activities of daily living. They are less commonly used for bipolar disorders as adjunctive or additional therapy.

Adverse Reactions

Adverse reactions to TCAs include dysrhythmias, postural hypotension, confusion, headache, drowsiness that lasts a long time, constipation, nausea, vomiting, blood dyscrasias, fever, photosensitivity, pruritus, skin rash, muscle twitching, tremors, urinary hesitancy or retention, altered liver function tests, blurred vision, and nervousness.

Overdosage may initially produce stimulation of the CNS, resulting in irritability, agitation, hallucinations, delirium, twitching, hypertonia, hyperreflexia, nystagmus, hyperpyrexia (very high body temperature), hypertension, and seizures (more commonly seen in children). This initial CNS stimulation is followed by CNS depression, causing drowsiness, areflexia, hypothermia (abnormally low body temperature), hypotension, dysrhythmias, respiratory depression, coma, or cardiorespiratory arrest.

Drug Interactions

TCA increase the CNS depressant effect of alcohol and other CNS depressants, particularly ethchlorvynol (Placidyl). The effects of anticonvulsants may be decreased when used with TCAs. The antihypertensive effects of guanethidine (Ismelin) and clonidine (Catapres) may be blocked when used with most TCAs, with the exception of doxepin (Sinequan). There may be a reduction in the antidepressant effect of tricyclics and an increase in their side effects when used concurrently with estrogen, including oral contraceptives containing estrogen. An increased incidence of cardiac dysrhythmias has been found with concurrent use of thyroid medication and TCAs. Severe hypertension or hyperpyrexia may result when TCAs are used with MAO inhibitors or sympathomimetics.

Nursing Implications and Patient Teaching

Action

MAO is an enzyme found in the mitochondria of cells located in nerve endings and other body tissues such as the kidney, liver, and intestines. This enzyme normally acts as a catalyst by inactivating dopamine, norepinephrine, epinephrine, and serotonin (biogenic amines) and therefore regulating the intracellular levels of these neurotransmitters. MAO inhibitors block the inactivation of the biogenic amines, resulting in an increased concentration of dopamine, epinephrine, norepinephrine, and serotonin at neuronal synapses. The antidepressant effects of MAO inhibitors such as phenelzine (Nardil) or tranylcypromine (Parnate) are thought to be directly related to this increased concentration of biogenic amines.

Uses

MAO inhibitors are used to relieve the symptoms of severe reactive or endogenous depression that have not responded to TCA therapy, electroconvulsive therapy, or other modes of psycho­therapy. Effects may be seen within days but the full antidepressant effect is often delayed for weeks. MAO inhibitors are considered second-line treatment for depression because of their serious adverse effects. MAO inhibitors are not approved for use in children.

Adverse Reactions

Adverse reactions to MAO inhibitors include postural hypotension, dysrhythmias, ataxia, drowsiness, hallucinations, headache, hyperactivity, insomnia, seizures, tremors, vertigo, anorexia, constipation, diarrhea, nausea, vomiting, fever, photosensitivity, skin rash, dysuria (painful urination), incontinence, blurred vision, dry mouth, edema, and impotence.

Overdosage produces mental confusion, restlessness, hypotension, respiratory depression, tachycardia, seizures, and shock, which may persist for 1 to 2 weeks.

Drug and Food Interactions

MAO inhibitors have many drug interactions. The potential for drug interactions differs between agents based upon the type of MAO inhibition that occurs. Drugs that inhibit MAO A may interact with other serotonergic agents, causing a potentially fatal serotonin syndrome characterized by mental status changes, myoclonus, fever, and tremor. Therefore, concurrent use of MAO A inhibitors with medications such as SSRIs, meperidine, dextromethorphan, sumatriptan, and buspirone should be avoided. Conversely, MAO B inhibitors, such as selegiline, may interact with other dominergic drugs such as amantadine and bromocriptine.

MAOIs may potentiate the CNS depressant effect of alcohol, anesthetics, sedatives, hypnotics, and narcotics and may cause severe hypertension and hyperpyrexia. If they are used with anticonvulsants, they may cause a change in the seizure pattern of the patient, and the dosage of the anticonvulsant medication may have to be adjusted accordingly. The hypotensive effects of diuretics and antihypertensives may be enhanced when those agents are used with MAO inhibitors. The hypoglycemic effects of insulin or oral hypoglycemics may be enhanced by MAO inhibitors, and dosages may require adjustment accordingly. MAO inhibitors and tricyclic antidepressants are generally not used together because hyperpyrexia, severe convulsions, hypertensive crisis, and death may result. MAOIs should not be given with other MAOIs drugs.

Foods with more than 6 mg of tyramine per serving must be avoided: These include aged and mature cheeses, air-dried sausages (e.g., pepperoni), fermented soy products (soy and teriyaki sauce), sauerkraut, and all tap beers, to name a few.

Nursing Implications and Patient Teaching

Action

Since the beginning of the 1980s, a series of new antidepressant medications have been available. Some are chemically unrelated to one another, but all act in some way to prolong serotonin in the brain. Their differences are often in terms of side effects.

Among the selective SSRIs, several products have become very well known: Their antidepressant action is thought to be linked to their inhibition of CNS neuronal uptake of serotonin. These products are powerful and selective inhibitors of neuronal serotonin reuptake. Other medications have been developed that work by SNRIs or norepinephrine/dopamine reuptake inhibiton (NDRIs). Because these more focused products cause far fewer side effects than other antidepressant medications, they have become extensively used and are considered the drugs of choice in the treatment of depression.

There are also other antidepressant products that have an effect on serotonin uptake but that are chemically unrelated to the SSRIs, but are all tetracyclic compounds. Trazodone (Desyrel) and nefazodone (Serzone) are serotonin 2-agonists/blockers/serotonin reuptake inhibitors (SARIs/SSRIs)—A totally new classes of drugs. Nefazodone (Serzone) inhibits neuronal uptake of serotonin and norepinephrine, but the mechanism for this action is unknown.

Mirtazapine (Remeron) is an α₂ noradrenergic antagonist, another new drug class. Tetracyclic compounds enhance central noradrenergic and serotonergic activity through an unknown mechanism. They have different amounts of antagonistic activity toward alpha2 and5-HT2 receptors. These products inhibit the uptake of serotonin at the neuronal synaptosomes in the brain and enhance the behavioral changes caused by serotonin. The action of these drugs is more selective than that of other types of antidepressants. They have less effect on the cardiac conduction system than do tricyclic antidepressants, and they cause almost no CNS stimulation, which occurs frequently with MAO inhibitors.

Uses

SSRI drugs are the drugs of choice for most depressive disorders due to their low adverse effect profile and for short-term treatment (less than 5 weeks) of out­patients with a diagnosis that is listed in the category of major depressive disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. They have also been used extensively for long-term therapy in patients with dysthymic depressive disorders and minor depressive episodes. Fluoxetine (Prozac) is the only SSRI approved for treating depression in the pediatric population and it is only given to those children older than 8 years of age.

Some of these antidepressant agents are approved to treat specific anxiety and eating disorders, assist in smoking cessation (bupropion [Wellbutrin]), or obcessive compulsive disorders.

Adverse Reactions

Adverse reactions to these drugs in general include dizziness, drowsiness, tachycardia, dysrhythmias, hypertension, hypotension, rash, pruritus, constipation, weight loss, nausea and vomiting, anorexia, weight gain, diarrhea, appetite increase, dyspepsia (stomach discomfort after eating), menstrual complaints, impotence, urinary frequency, dry mouth, headache, excessive sweating, tremor, sedation, insomnia, blurred vision, agitation, confusion, hostility, and disturbed concentration.

In nearly 4% of patients taking fluoxetine (Prozac), a rash develops with accompanying fever, leuko­cytosis, arthralgia (joint pain), edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation.

Trazodone (Desyrel) has also produced early menses, hematuria (blood in the urine), urinary frequency, and weight changes.

Patients who abruptly stop taking the medication may experience a sudden increase in dangerous symptoms. Patients must be taught to follow their health care provider’s directions and gradually decrease the amount of medicine taken if the drug is to be stopped.

Drug Interactions

If bupropion (Wellbutrin) is taken with levodopa, the chance of adverse effects increases. If bupropion is used with carbamazepine (Tegretol), cimetidine, phenobarbital, or phenytoin (Dilantin), the hepatic metabolism of the drugs may be increased. Acute toxicity may develop if bupropion is given with phenelzine (Nardil).

Fluoxetine (Prozac) increases the half-life of some drugs and may displace drugs bound to protein, such as warfarin and digitoxin, or be displaced by them. Concurrent use of trazodone (Desyrel) and antihypertensives can cause hypotension. There are many other isolated drug interactions. Trazodone (Desyrel) may increase the effects of alcohol, barbiturates, and other CNS depressants. The drug should be stopped as long as possible before general anesthesia because inter­actions are unknown.

Some antidepressants may cause cardiac repolarization problems shown by prolongation of the QT Interval on the electrocardiogram (ECG). These patients are at risk for sudden death. The more drugs the patients take, the more care should be shown to try to prevent drug interactions that might lead to this problem.

Nursing Implications and Patient Teaching

Action

The conventional phenothiazine antipsychotics first came into the market and, while somewhat effect in treating psychophrenia, had many side effects. It was disappointing for clinicians to find that the nonphenothiazines that were introduced later also had many side effects. They did offer some treatment options for patients.

Uses

Conventional antipsychotics such as chlorpromazine (Thorazine), thioridazine (Mellaril), and promazine (Prozine) are used primarily for reducing or relieving the symptoms of acute and chronic psychoses, including schizophrenia, schizoaffective disorders, and involutional psychosis. The nonphenothiazine class thioxanthene is preferred for use in psychotic patients who are withdrawn or are exhibiting retarded behavior. Clinical evidence has shown that patients with certain types of apathetic psychosis respond well to this drug. Haloperidol (Haldol) may be injected and is often used in calming patients with dementia.

Adverse Reactions

Adverse reactions to phenothiazines and nonphenothiazines include severe extrapyramidal symptoms which may not be reversible: psueoparkinsonism, dystonic reactions (severe spasms, particularly of back muscles, tongue and facial muscles), akathiasia (constant pacing and compulsive movements), tardive dyskinesia (bizarre tongue and face mvoements such as lip smacking an chewing movements). Additionally, the drugs may cause, postural hypotension, tachycardia, confusion, drowsiness, hyperactivity, insomnia, amenorrhea, gynecomastia (enlargement of the breasts in men), hyperglycemia (high blood sugar level), hyperreflexia, tardive dyskinesia, blood cell abnormalities, contact dermatitis, photosensitivity, constipation, dry mouth, dyspnea (uncomfortable breathing), incontinence, nasal congestion, opaque deposits on the cornea and lens, and urinary retention. Production of a severe agranulocytosis has prevented Clozapine (Clorazil) from becoming a first line treatment drug.

In general, the nonphenothiazine agents cause less sedation and fewer anticholinergic side effects than phenothiazine products, but cause an equal or even greater incidence of extrapyramidal symptoms. Therapy with these products and other CNS depressants must be carefully watched because of potential additive effects.

Haloperidol (Haldol) produces orthostatic hypotension, drowsiness, tardive dyskinesia, blurred vision, breast engorgement, constipation, decreased libido, dry mouth, impotence, nausea, and vomiting.

Overdosage produces exaggerated CNS depression, coma, or severe hypotension, and extrapyramidal symptoms, seizures, or cardiac dysrhythmias may appear.

Drug Interactions

Phenothiazines taken concurrently with CNS depressants (alcohol, barbiturates, narcotics, and anesthetics) may increase and prolong the effects of either the CNS depressant or the phenothiazine. The effects of MAO inhibitors and TCAs are increased when they are taken at the same time as phenothiazines, and antacids and antidiarrheal drugs reduce the absorption rate. The effects of many other drugs and the results of laboratory tests are altered by phenothiazines and thioxanthenes.

Haloperidol (Haldol) increases the CNS depressant effects of alcohol, barbiturates, opioids, and anesthetics, and may produce severe hypotension when taken with antihypertensive drugs or epinephrine.

Some of these products have been implicated in causing changes in cardiac repolarization as shown by prolongation of the QT interval on the ECG. This problem places the patient at sudden risk. Any patient taking several antidepressant-antipsychotic medications should be closely monitored for any alteration in ECG.

Nursing Implications and Patient Teaching

Action

The mechanism of action for these products is often not precisely understood but they are thought to act by blocking several different receptor types in the brain. Aripiprazole (Abilify) is the new dopamine system stabilizer. It is thought to be a partial dopamine agonist (whereas other antipsychotic agents are full dopamine agonists) and thus has a targeted mechanism of action.

Uses

These atypical antipsychotic drugs have a broad spectrum of action, controlling both positive and negative symptoms of schizophrenia and have now become the drugs of choice for treating psychoses. These drugs are now used primarily in the treatment of schizophrenia.

The new dopamine system stabilizer apripiprazole (Abilify) shows both negative and positive symptoms of schizophrenia are reduced by this drug. Motor side effects appear to be less of a problem than with other antipsychotics with low incidence of extrapyramidal effects. Overall efficacy appears to be similar to haloperidol (Haldol) and risperidone (Risperdal) in schizophrenia. It has been approved for use in schizophrenia and as adjunctive treatment in major depressive disorder in adults, and in treatment of acute manic or mixed episodes of bipolar I disorder. It has been approved by the Food and Drug Administration as an adjunctive therapy to lithium or valproate (Depakote) in bipolar I disorder and for the treatment of irritability associated with autistic disorder. Some indications are approved for children and adolescents; some indications are reserved for adults.

Adverse Reactions

These drugs do not cause extrapyramidal side effects when taken at therapeutic doses. Although there are fewer side effects with these drugs, most cause weight gain and may cause obesity. Some of these agents may alter glucose metabolism and increase the risk for development of type 2 diabetes. Risperidone (Risperdal) may cause decreased sex drive in men and women and menstrual disorders and osteoporosis in women.

Drug Interactions

Many of these drugs have the same interactions as the phenothiazine drugs. One of the most widely used drugs, haloperidol (Haldol) interacts with many drugs. It may block the action of centrally acting anti­hypertensives. It’s action may be decreased by aluminum- and magnesium-containing antacids, levodopa, lithium, phenobarbital, phenytoin, rifampin, and beta blockers.

Aripiprazole is metabolized by liver enzymes and so has the potential to interact with many different types of drugs. The patient should be monitored very closely when aripiprazole is taken with other drugs because the action of aripiprazole may be increased or decreased or the other drug absorption may be increased or decreased.

Nursing Implications and Patient Teaching

Action

Lithium is the primary drug used to treat patients in manic states. Some other antiseizure drugs are also used for mood stabilization. The exact mechanism of lithium action is not known. The mood-stabilizing effect of the drug may be attributed to its ability to alter sodium transport at the nerve endings, inhibit cyclic AMP formation in nerve cells, and enhance the uptake of serotonin and norepinephrine by nerve cells, thus increasing the inactivation of these neurotransmitters. It has no sedative, depressant, or euphoric actions, making it unique from all other psychiatric drugs.

Uses

Lithium is specifically used for patients with bipolar disorder (manic-depressive psychosis) who are in an acute manic phase. It also may be used to prevent recurrent episodes of mania in the bipolar patient.

Adverse Reactions

Adverse reactions to lithium include dysrhythmias, hypotension, ataxia, coma, dizziness, drowsiness, motor retardation, restlessness, slurred speech, tinnitus (ringing in the ears), pruritus, rash, abdominal pain, anorexia, diarrhea, vomiting, urinary incontinence or retention, polyuria (excretion of a large amount of urine), albuminuria, blurred vision, hyperglycemia, hypothyroidism, leukocytosis, and weight gain.

Overdosage may produce toxicity which will present as diarrhea, vomiting, muscle weakness, drowsiness, and ataxia.

Nursing Implications and Patient Teaching

Action

The cause of ADD or ADHD is not clearly identified, so treatment is been difficult. It is now believed that the hyperactivity may be related to a deficit or dysfunction of neurotransmitters in the brain—particularly dopamine, norepinephrine, and serotonin in the reticular activating system of the brain. The drugs used to treat ADHD are mostly CNS stimulants that increase activity in specific areas of the brain to heighten alertness and help them focus better. The drugs do this by increasing norepinephrine release in some pathways of the reticular activating system. They also directly stimulate the release of dopamine in areas of the brain responsible for concentration. These drugs have some potential for addiction and so most are classified as Schedule II drugs.

Another non-CNS stimulant drug, atomoxetine (Strattera) is approved for treating ADHD. Although the exact mechanism of action is not clear, it is classed as a selective norepinephrine reuptake inhibitor—thus it is not an addictive or Schedule II drug.

The two categories of drug therapy appear to be equivalent in efficacy but patients may respond better to one than the other.

Uses

These drugs are limited to treatment of ADD and ADHD.

Adverse Reactions

These CNS stimulants are associated with a wide variety of symptoms that make some children reluctant to take them. These include anorexia, abdominal pain, depression, dizziness, nausea, nervousness, and weight loss. Common adverse effects of atomoxetine includes headache, cough, decreased appetite, upper abdominal pain, and insomnia.

Nursing Implications and Patient Teaching

Action

At times, people may be unable to sleep because of stresses or anxiety. Difficulty falling asleep is termed initial insomnia. The inability to stay asleep is termed intermittent insomnia, and terminal insomnia refers to early awakening with an inability to return to sleep. Terminal insomnia is often associated with depression.

If warm baths, warm drinks, appropriate temperature, and bedding changes do not help the patient relax, a medication may be prescribed on a short-term basis. A sedative agent is a medication that relaxes the patient and so may lead to sleep. A hypnotic agent actually induces drowsiness and promotes sleep in the patient. Whether a medication acts as a sedative or a hypnotic is often determined not by the drug, but by the dosage used, with smaller dosages producing sedative effects and larger dosages producing hypnotic effects.

The ideal medication would reproduce the normal sleep pattern for the patient; the patient would sleep an appropriate length of time, have no side or adverse effects, and wake up feeling rested and relaxed with no risk of developing drug dependency. Unfortunately, no ideal medication exists.

Postmedication “hangover” from reduced REM time often leads the patient to feel they haven’t slept “well” and may increase their desire for more medicine so that the patient may have a refreshing sleep. This pattern may result in dependency or abuse.

Once a patient has taken sedative-hypnotics, the normal sleep patterns may not return for several weeks. During that time, an increased period of REM will be seen, as if the body is trying to “catch up” for missed time. This may produce long, vivid, or frightening dreams.

Uses

Barbiturates are CNS depressants used for a variety of medical problems. All barbiturates act primarily on the brainstem reticular formation, reducing nerve impulses to the cerebral cortex. Barbiturates also depress the respiratory system and the activity of nerves and muscle (smooth, skeletal, and cardiac), thus producing relaxation and sleep.

Barbiturates are used for short-term treatment of anxiety, agitation, and insomnia caused by transient psychosocial stresses. They are also prescribed at times when rest is mandatory, such as before surgery. Large doses of short-acting barbiturates can produce surgical anesthesia (see the third section of this chapter).

The main action of benzodiazepines is CNS depression. Although the exact mechanism is not known, they are thought to act on the hypothalamus and limbic system of the brain, decreasing the vasopressor response and increasing the arousal threshold. They are used as hypnotic agents to treat insomnia. The therapeutic objective is to prevent insomnia and restore normal sleep patterns. Benzodiazepines are used in patients with acute or chronic medical problems who require restful sleep or sedation (see the third section of this chapter for more detail).

The nonbarbiturate-nonbenzodiazepine sedative-hypnotics include a variety of chemically unrelated medications, as well as the GABA receptor agonists such as eszopiclone (Lunesta), zolpidem (Ambien), and zalepion (Sonata). All produce some effects on REM sleep, and most have a potential for tolerance and habituation and so are schedule IV drugs. Many may produce rebound REM. Ramelteon (Rozerem) is a little different in that it stimulates melatonin, the body’s normal chemical to produce sleep, so it has no addictive properties.

Adverse Reactions

Nonbarbiturate-nonbenzodiazepine sedative-hypnotics may produce drowsiness, decreased emotional reaction, dullness, distortion of mood, impaired coordination, hypersensitivity, lethargy, headache, muscle or joint pain, and mental depression. A feeling of “hangover” commonly occurs with their use.

Drug Interactions

Nonbarbiturate-nonbenzodiazepine sedative-hypnotics increase the sedative effects of CNS depressants, including sleeping aids, analgesics, anesthetics, tranquilizers, alcohol, and narcotics. Chloral hydrate may increase the anticoagulant effects of warfarin.

Nursing Implications and Patient Teaching