Antipsychotic and Antidepressant Drugs Flashcards
The nervous system - Anatomy
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The nervous system has two divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
The brain and spinal cord make up the CNS.
The nerves make up the peripheral nervous system.
The brain is divided into specific regions; each region is responsible for the performance of specific functions within the body.
The brain consists of four parts: the cerebrum, diencephalon (thalamus and hypothalamus), cerebellum, and brain stem.
The main functions of the cerebrum include the controlling of consciousness, memory, emotions, sensations, and voluntary movements.
The thalamus receives sensory stimuli (except the sense of smell), relaying them to the cerebral cortex.
The hypothalamus (located just below the thalamus) activates, controls, and integrates the peripheral autonomic nervous system. It also controls endocrine system processes, body temperature, appetite,
sleep, and other sensory functions.
The cerebellum, attached to the brain stem, maintains muscle tone, and coordinates balance and movement.
The brain stem controls blood pressure, respiration, pulse, and other body functions; it connects the hypothalamus with the spinal cord.
The basic functional unit of the nervous system is the neuron.
There are three types of nerves: sensory nerves transmit information that produces sensation and feelings, motor nerves transmit information that produces movement and function, mixed nerves
transmit information that produces both sensation and movement.
The spinal cord provides a two-way communication system between the brain and body parts outside of the nervous system.
Neurotransmitters
The term neurotransmitter is defined as a biochemical that is formed in and released from a neuron in order to stimulate or inhibit the actions of another cell.
Examples of neurotransmitters include acetylcholine, dopamine, noradrenaline, serotonin, glutamate, and GABA.
Disorders in the production and function of neurotransmitters may contribute to psychiatric illnesses.
Neurotransmitters - Acetylcholine
Acetylcholine plays a major role in cognitive function and memory formation as well as motor control.
It was the first neurotransmitter to be
identified.
Acetylcholine allows neurons to communicate with each other.
This neurotransmitter is released by the axon terminals in response to a nerve impulse.
In relation to motor function, the release of acetylcholine will cause a change in the muscle cell and elicit a contraction of the muscle, producing movement.
Neurotransmitters - Dopamine
Dopamine is a naturally produced agent that, in the brain, functions as a neurotransmitter.
Dopamine release and dopamine levels within the brain affect motor control, memory, attention span, the ability to problem solve, motivation, pleasure, and creative thought.
Alterations in dopamine production and secretion play a role in disorders such as Parkinson’s disease, attention deficit disorder, and schizophrenia.
It is also believed to play a role in addiction to drugs.
Neurotransmitters - Norepinephrine and Serotonin
Both norepinephrine and serotonin seem to be involved in similar functions within the brain: regulation of appetite, sleep, arousal, mood, temperature, and hormone release.
Norepinephrine is also known as noradrenaline. As a stress hormone, it affects parts of the human brain where attention and responding actions are controlled. It is released from the medulla of the adrenal glands as a hormone into the blood, but is also a central and sympathetic nervous system neurotransmitter.
Serotonin is a neurotransmitter synthesized in the CNS as well as the gastrointestinal tract. It is believed to play an important role in regulating anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite.
It was initially identified as a vasoconstrictor present in blood serum, and it was from here that its name was derived.
Serotonin (also known as 5-hydroxytryptamine or 5-HT) may also have a role in pain perception and behavior. It acts as an inhibitory neurotransmitter.
A rare condition known as serotonin syndrome, also known as serotonin toxicity, can result from intentional self-poisoning with serotonin, use of the drug therapeutically, or from inadvertent drug interactions.
This condition includes progressively worsening symptoms such as: mental confusion, shivering or muscle twitching, sweating or fever, hallucinations, hypertension, tachycardia, headache, tremor, nausea, diarrhea, coma, and death.
Neurotransmitters - Glutamate
Glutamate is an amino acid, however, not one of the essential amino acids.
It is a key molecule in cellular metabolism. Glutamate plays an important role in the body’s disposal of excess or waste nitrogen. It is important for the ability to perceive taste sensations.
Glutamate is distributed throughout the CNS. It is considered the major excitatory CNS neurotransmitter. It can stimulate a number of receptor types in the brain and spinal cord.
Glutamate is involved in the facilitation of learning and memory. The brain is very vulnerable to glutamate-mediated over-excitation. This results in excitotoxicity, which causes cell integrity to be disrupted and nerve cells to die.
Excitotoxicity has been demonstrated
in strokes and some neuro-degenerative diseases. Glutamate has also been
implicated in the development of epilepsy.
Neurotransmitters - Gamma-Aminobutyric Acid
Gamma-aminobutyric acid (GABA) is distributed throughout the brain and spinal cord.
It is now considered to be the major inhibitory neurotransmitter in the CNS and it acts to modulate the activity of excitatory pathways.
It is formed from the excitatory neurotransmitter glutamate.
Motor control, consciousness, levels of arousal, and memory formation are all inhibited by GABA.
GABA has mostly excitatory effects during early development. It has been purported to increase the amounts of human growth hormone.
It is unknown if GABA can cross the blood-brain barrier.
Mental Disorders - Schizophrenia
Schizophrenia is a mental illness characterized by distortion of reality, disorganized thought patterns, social withdrawal, hallucinations, and poor judgment.
Schizophrenia is one of the most devastating forms of mental illnesses. It occurs in approximately 1 percent of the population.
Schizophrenia includes a variety of syndromes, presented differently
in each individual.
Although the cause of this disorder has not been fully determined, some common changes do occur in the brains of patients
suffering from schizophrenia, including reduction of the cortex (outer portion) of the temporal lobes, enlargement of the third and lateral ventricles, excessive dopamine secretion, and decrease blood flow to the front of the brain.
The cause of schizophrenia may be genetic, along with brain damage in the fetus caused by perinatal complications or viral infections in the mother during pregnancy.
The onset of schizophrenia usually occurs
between ages 15 and 25 in men, and between 25 and 35 in women.
Stressful events appear to initiate the onset and recurrence of the disorder.
Mental Disorders - Bipolar Disorder
Bipolar disorder is a mental illness characterized by periods of extreme
excitation or mania, and deep depression.
It is not commonly understood why it takes months to move from one of these extremes to the other. Some patients have predominantly manic episodes or predominantly depressive episodes. Few patients experience the classic swing from mania to depression and back.
Bipolar disorder is also called manic-depressive illness.
Mental Disorders - Depression
Depression is classified as a mood disorder, of which there are several subgroups.
Major depression, or unipolar disorder, is a chemical deficit within the brain, and a precise diagnosis is based on biologic factors or personal characteristics.
The causes of depression include genetic and psychosocial stressors. Depression may also occur as a reactive episode, a response to a life event, or secondarily to many systemic disorders (including cancer, diabetes, heart failure, and AIDS).
This condition is a common problem, and many patients with milder forms may be misdiagnosed and not receive treatment.
Mental Disorders - Eating Disorders
Anorexia nervosa is a complex psychological state characterized by the fear of being overweight. Often, patients’ perceptions are distorted to the extent that they believe they are overweight despite appearing emaciated to others. Without proper treatment, anorexia nervosa may be fatal.
Bulimia nervosa is another eating disorder that is characterized by recurrent (at least twice a week) episodes of binge eating, during which the patient consumes large amounts of food and feels unable to stop eating. This is followed by inappropriate compensatory effects to avoid weight gain, such as self-induced vomiting, laxative or diuretic abuse, vigorous exercise, or
fasting.
Mental Disorders - Dementia
Dementia is a chronic deterioration of intellectual function and other cognitive skills severe enough to interfere with the ability to perform activities of daily living.
Dementia may occur at any age and can affect young people as the result of injury or hypoxia. However, it is mostly a disease of
the elderly.
Antipsychotic Drugs, also called neuroleptic drugs
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Antipsychotic Drugs - Mechanism of Action
Antipsychotic drugs act by blocking receptors for dopamine, acetylcholine, histamine, and norepinephrine.
The current suggestions are that conventional antipsychotic drugs suppress symptoms of psychosis by blocking dopamine receptors in the brain.
Antipsychotic Drugs - Indications
Schizophrenia is the primary indication for antipsychotic drugs.
These agents effectively suppress symptoms during acute psychotic episodes and, when taken chronically, can greatly decrease the risk of relapse.
Selection among these drugs is based primarily on their adverse effect profiles, rather than on therapeutic effects.
In addition to their antipsychotic properties, some of these drugs, such as prochlorperazine, are also used as antiemetics.
Chlorpromazine is used for treating hiccups and lithium for managing bipolar disorders.
Small doses of neuroleptics can be effective to control acute agitation in the elderly.
Antipsychotic Drugs - Adverse Effects
Antipsychotic drugs frequently cause a wide variety of adverse effects, which include dry mouth, blurred vision, urinary retention, orthostatic hypotension, tachycardia, sedation, headache, and behavior changes.
These drugs may also produce agitation, confusion, lethargy, and paranoid reactions.
Antipsychotic agents commonly cause adverse effects related to excessive
extrapyramidal (nerves in the brain controlling movement) activity (or
parkinsonian signs).
Involuntary muscle spasms in the face, neck, arms, or legs (dystonia) may be present.
Tardive dyskinesia may be present, such as chewing or grimacing, repetitive jerky or writhing movements of the limbs, tremors,
or a shuffling gait.
Extrapyramidal effects usually diminish with a decreased dosage of the antipsychotic medication.
Antipsychotic Drugs - Contraindications and Precautions
Antipsychotic drugs are contraindicated in patients with a known hypersensitivity, severe depression, blood dyscrasias, liver dysfunction, severe hypotension or hypertension, and Parkinson’s disease.
Safe use of antipsychotic drugs during pregnancy and lactation has not been established.
These agents in pregnancy are category C (except for clozapine, which is category B).
Antipsychotic agents should be used with caution in patients with glaucoma, asthma, epilepsy, prostatic hypertrophy, peptic ulcer, renal dysfunction, and in those who have been exposed to extreme heat.
Antipsychotic Drugs - Drug Interactions
Antipsychotic medications may have drug interactions with antihistamines, alcohol, tranquilizers, narcotics, and barbiturates.
They may result in additive CNS depression.
Mood Altering Drugs
Bipolar disorder is treated with three major groups of drugs:
- mood stabilizers
- antipsychotics
- antidepressants
The mainstays of therapy are lithium and valproic acid, drugs with the ability to stabilize mood.
In addition, benzodiazepines are commonly used for sedation.
Antipsychotic drugs were discussed before, and antidepressants will be discussed later in this chapter.
The following is a discussion of mood stabilizers.
The principal mood stabilizers are lithium and two drugs originally developed for epilepsy: valproic acid and carbamazepine.
Lithium has a low therapeutic index. As a result, toxicity can occur at blood levels only slightly greater than therapeutic levels. Accordingly, monitoring of lithium levels is mandatory.
Mood Altering Drugs - Mechanism of Action
The precise mechanism of action of lithium is unknown. The lithium ion behaves in the body much like the sodium ion, but its exact mechanism of action is unclear.
Lithium competes with various physiologically important cations: Na+, K+, Ca++, and Mg++.
At the synapse, it accelerates catecholamine
destruction, inhibits the release of neurotransmitters, and decreases sensitivity of postsynaptic receptors.
Mood Altering Drugs - Indications
Lithium is a drug of choice for controlling acute manic episodes in patients with bipolar disorder, and for long-term prophylaxis against recurrence of mania or depression.
In manic patients, lithium reduces euphoria,
hyperactivity, and other symptoms, but does not cause sedation.
Anti-manic effects begin five to seven days after the onset of treatment, but full benefits may not develop for two to three weeks.
Mood Altering Drugs - Adverse Effects
Adverse effects of lithium, such as nausea, diarrhea, abdominal bloating, and anorexia are common but transient.
The other adverse effects include
fatigue, muscle weakness, headache, confusion, memory impairment,
polyuria, and thirst.
Lithium-induced tremors can be augmented by stress and fatigue.
Mood Altering Drugs - Contraindications and Precautions
Lithium is contraindicated in patients with known hypersensitivity, in those with significant cardiovascular or kidney disease, brain damage, dehydration, or sodium debilitation.
Lithium is also contraindicated in pregnancy, especially during the first trimester (category D), lactation, and
in children younger than 12 years of age.
Lithium should be used with caution in older adults and in patients suffering from thyroid disease, epilepsy, cardiac disease, dehydration, diarrhea, renal impairment, and seizure disorders.
Mood Altering Drugs - Drug Interactions
Diuretics promote sodium loss and can thereby increase the risk of lithium toxicity.
Nonsteroidal anti-inflammatory drugs can increase lithium levels and increase renal reabsorption of lithium.
Anticholinergics can cause urinary hesitancy coupled with lithium-induced polyuria.
Antidepressants
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Tricyclic Antidepressants - Mechanism of Action
The term tricyclic derives from the common three-ringed structure of the drug molecule itself.
Tricyclic antidepressants inhibit the reuptake of serotonin and noradrenaline
into nerve terminals.
Tricyclic Antidepressants - Indications
Tricyclic antidepressants are mainly used for major depression, and imipramine may be used for the treatment of nocturnal enuresis (nighttime bedwetting) in children.
Tricyclic Antidepressants - Adverse Effects
Common adverse effects of tricyclic antidepressants include dry mouth,
blurred vision, postural hypotension, constipation, and urinary retention.
Other adverse effects may be sedation, drowsiness, cardiovascular symptoms
(such as dysrhythmias), and extreme hypertension.
Tricyclic Antidepressants - Contraindications and Precautions
The TCAs are contraindicated in patients with known hypersensitivity to these drugs.
They are also contraindicated in patients with glaucoma, hypertrophy of prostate gland, and during pregnancy or lactation.
Like other antidepressants, the tricyclics should be used with caution in patients who have heart disease (angina or paroxysmal tachycardia), hepatic or renal dysfunction, or a history of seizures.
Tricyclic Antidepressants - Drug Interactions
The TCAs, with concurrent use of other CNS depressants, including alcohol, may cause sedation.
If taking clonidine, patients may experience a decrease in the antihypertensive effects of the drug and are at an increased risk for CNS depression.
Cimetidine (a histamine blocking agent) may
prevent the metabolism of imipramine, leading to increased serum levels and toxicity.
Selective Serotonin-Reuptake Inhibitors - Mechanism of Action
They are now considered the first-line drugs in the treatment of major depression.
SSRIs block the presynaptic amine reuptake pump, as do the TCAs.
However, the SSRIs primarily affect serotonin reuptake.
Selective Serotonin-Reuptake Inhibitors - Indications
SSRIs are used in major depression and may be prescribed for obsessive-compulsive and eating disorders.
Selective Serotonin-Reuptake Inhibitors - Adverse Effects
Common adverse effects of SSRIs include headache, vomiting, diarrhea,
nausea, insomnia, and nervousness.
Generally, the adverse effects of SSRIs
are relatively mild, of shorter duration, and cease as treatment continues.
Cardiac toxicity and the risk of death after overdose are less likely than with the TCAs.
Selective Serotonin-Reuptake Inhibitors - Contraindications and Precautions
SSRIs are contraindicated in patients with known hypersensitivity to these agents and during pregnancy.
SSRIs should be used with caution in patients with hepatic or renal dysfunction, diabetes mellitus, and during lactation.
Selective Serotonin-Reuptake Inhibitors - Drug Interactions
Concurrent use of SSRIs with benzodiazepines may cause increased adverse CNS effects.
Beta blockers may cause decreased elimination of SSRIs, resulting in hypotension or bradycardia.
Clozapine, phenytoin, and theophylline may interact with SSRIs and decrease their elimination and their toxicity.
Monoamine Oxidase Inhibitors - Mechanism of Action
Monoamine oxidase inhibitors (MAOIs) were the first drugs approved for the treatment of depression.
MAOIs inhibit monoamine oxidase (an enzyme) that stops the actions of dopamine, norepinephrine, epinephrine, and serotonin. Therefore, these drugs intensify the effects of norepinephrine in adrenergic synapses.
Monoamine Oxidase Inhibitors - Indications
MAOIs are used to manage symptoms of depression not responsive to other types of pharmacotherapy.
The effect of these drugs may continue for
two to three weeks after therapy is discontinued.
Monoamine Oxidase Inhibitors - Adverse Effects
Common adverse effects of the MAOIs include dizziness, vertigo, dry mouth,
nausea, diarrhea or constipation, loss of appetite, orthostatic hypotension, and
insomnia.
Hypertensive crisis (severe hypertension) may occur if ingesting foods containing tyramine while taking MAOIs.
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Monoamine Oxidase Inhibitors - Contraindications and Precautions
MAOI agents are contraindicated in patients with known hypersensitivity to these drugs;
in patients with hepatic or renal disease, hypertension,
congestive heart failure,
cerebrovascular disease
in the elderly.
MAOI drugs should be used with caution in patients with liver dysfunction, diabetes, hyperthyroidism, and history of seizures.
Monoamine Oxidase Inhibitors - Drug Interactions
MAOIs may interact with other antidepressant drugs such as SSRIs and
TCAs, resulting in elevation of body temperature and seizures.
Meperidine should be avoided with MAOIs due to increased risk of respiratory failure or hypertensive crisis.
Atypical Antidepressants
Atypical antidepressants are also called miscellaneous agents.
They are frequently prescribed to alleviate symptoms of depression for patients with bipolar disorder.
Atypical antidepressants are chemically unrelated to other antidepressants.
They include trazodone, mirtazapine, and
bupropion.
Atypical Antidepressants - Mechanism of Action
Atypical antidepressants inhibit the reabsorption of serotonin and norepinephrine.
They elevate mood by increasing the levels of dopamine, serotonin, and norepinephrine in the central nervous system.
Atypical Antidepressants - Indications
Atypical antidepressants are indicated for mental depression.
Since bupropion has been associated with increased risk of seizures, it is not the
agent of first choice.
It is also used as an adjunct for smoking cessation.
Venlafaxine is also used for generalized anxiety disorder and social anxiety
disorder.
Atypical Antidepressants - Adverse Effects
Common adverse effects of atypical antidepressants include dry
mouth, blurred vision, dizziness, headache, nausea, vomiting, orthostatic
hypotension, increased appetite, and insomnia.
Atypical Antidepressants - Contraindications and Precautions
Atypical antidepressants are contraindicated in patients with known
hypersensitivity to these agents.
These drugs should be avoided in patients
with hepatic diseases, pregnancy (category C), lactation, suicidal thoughts,
and in children less than 8 years of age.
Atypical antidepressants must be used cautiously in patients with renal failure, hepatic impairment, history of mania, acute closed-angle glaucoma, cardiac disorders, hypertension, hyperthyroidism, and history of seizures or seizure disorders.
Atypical Antidepressants - Drug Interactions
Atypical antidepressants may increase metabolism of carbamazepine,
cimetidine, phenytoin, and phenobarbital.
They may increase incidence of adverse effects of levodopa and MAOIs.
They may cause additive cognitive and motor impairment with alcohol or benzodiazepines, and increase risk of hypertensive crisis with MAOIs.
Antihypertensive agents may potentiate hypotensive effects of atypical antidepressants.
Levels of digoxin or phenytoin may be increased if used concurrently.
Levels and toxicity of ketoconazole, indinavir, and ritonavir may be increased with concurrent use.
