Chapter 11: Psychotropic Drugs

Dopamine

Involved in fine muscle movement

Involved in integration of emotions and thoughts

Involved in decision making

Stimulates hypothalamus to release hormones (sex, thyroid, adrenal)

Decreases:

Parkinson’s disease

Depression

Increases:

Schizophrenia

Mania

Norepinephrine (NE) (noradrenaline)

Causes changes in mood

Causes changes in attention and arousal

Stimulates sympathetic branch of autonomic nervous system for fight or flight in response to stress

Decreases:

Depression

Increases:

Mania

Anxiety states

Schizophrenia

Serotonin (5-hydroxytryptophan [5-HT])

Plays a role in sleep regulation, hunger, mood states, and pain perception

Alters hormonal activity

Plays a role in aggression and sexual behaviour

Decreases:

Depression

I

ncreases:

Anxiety states

Histamine

Involved in alertness

Involved in inflammatory response

Stimulates gastric secretion

Decreases:

Sedation

Weight gain

Gamma-aminobutyric acid (GABA)

Plays a role in inhibition; reduces aggression, excitation, and anxiety

May play a role in pain perception

Has anticonvulsant and muscle-relaxing properties

May impair cognition and psychomotor functioning

Decreases:

Anxiety disorders

Schizophrenia

Mania

Huntington’s disease

Increases:

Reduction of anxiety

Glutamate

Is excitatory

AMPA plays a role in learning and memory

Decreases (NMDA): Psychosis

Increases (NMDA): Prolonged increased state can be neurotoxic

Neurodegeneration in Alzheimer’s disease

Increases (AMPA): Improvement of cognitive performance in behavioural tasks

Acetylcholine (ACh)

Plays a role in learning, memory

Regulates mood, mania, sexual aggression

Affects sexual and aggressive behaviour

Stimulates parasympathetic nervous system

Decreases:

Alzheimer’s disease

Huntington’s disease

Parkinson’s disease

Increases:

Depression

Substance P (SP)

Has antidepressant and anti-anxiety effects in depression

Promotes and reinforces memory

Enhances sensitivity of pain receptors

Involved in regulation of mood and anxiety

Plays a role in pain management

Somatostatin (SST, somatotropin release-inhibiting factor [SRIF])

Alters cognition, memory, and mood

Decreases:

Alzheimer’s disease

Decreased levels of SRIF in spinal fluid of some depressed patients

Increases:

Huntington’s disease

Neurotensin (NT)

Has endogenous antipsychotic-like properties

Decreased levels in spinal fluid of schizophrenic patients

Brainstem

the oldest part and central core of the brain, beginning where the spinal cord swells as it enters the skull; the brainstem is responsible for automatic survival functions

Cerebellum

A large structure of the hindbrain that controls fine motor skills.

Cerebrum

Area of the brain responsible for all voluntary activities of the body

Area of Brain For Memory

hippocampus

Circadian Rhythm

the biological clock; regular bodily rhythms that occur on a 24-hour cycle

CT

Schizophrenia:

Cortical atrophy

Third ventricle enlargement

Cognitive disorders:

Abnormalities

Magnetic resonance imaging (MRI)

Schizophrenia:

Enlarged ventricles

Reduction in temporal lobe and prefrontal lobe

Positron emission tomography (PET)

Schizophrenia:

Increased D2, D3 receptors in caudate nucleus

Abnormalities in limbic system

Mood disorders:

Abnormalities in temporal lobes

Adult ADHD:

Decreased use of glucose

Concordance

how often one twin will be affected by the same illness as the other.

Pharmacogenetics

the study of how genetic variation affects an individual's response to drugs

Benzodiazepines (Pams)

enhance the actions of GABA by binding to a specific location on the GABAA receptor complex. They only have an effect if GABA is also bound to its binding sites on the receptor complex. This interaction decreases the probability that the neuron on which the receptors are found will depolarize and thus leads to an overall decrease in neuronal excitability.

are common in the limbic system, the brain's emotional centre, and enhanced GABA activity is important for decreasing anxiety.

Short Acting Sedative Hypnotc Sleep Drugs

Zopiclone (Imovane) is a member of a newer class of benzodiazepine-like hypnotics. It and the other benzodiazepine-like drugs, zaleplon and zolpidem, have been grouped together into a class colloquially called the Z-drugs. Structurally, zopiclone is not a true benzodiazepine; however, zopiclone displays similar actions as the true benzodiazepines at GABAA receptors. Thus its use also results in a decrease in neuronal excitability. As a result, zopiclone has sedative effects as well as hypnotic, anxiolytic, anti-convulsant, and muscle-relaxant effects. The onset of action is faster than that of most benzodiazepines. It is important to inform patients taking non-benzodiazepine hypnotic drugs about the quick onset and advise them to take the drug only when they are ready to go to sleep.

Busiprone

an anxiolytic drug that is useful for bringing about the short-term relief of excessive anxiety without producing strong sedative-hypnotic effects. Because this drug does not leave the patient sleepy or sluggish, it is often much better tolerated than the benzodiazepines. It is not a CNS depressant, and so the danger of it interacting with other CNS depressants such as alcohol is minimal. Also, there is not the potential for dependence that exists with benzodiazepines.

Treating Anxiety Disorders With Anti-depressant Drugs

he symptoms, neurotransmitters, and circuits associated with anxiety disorders overlap extensively with those of depressive disorders (see Chapter 13), and many drugs used to treat depression have proven to be effective treatments for anxiety disorders (Curtis et al., 2017). SSRIs, medications that preferentially act to increase serotonin levels in the synapse, are often used to treat OCD, social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder (PD), and PTSD. The SNRI venlafaxine (Effexor XR) is used to treat GAD, SAD, and PD. Duloxetine (Cymbalta), another SNRI, is approved for GAD.

Tricyclic Antidepressants

are no longer considered first-line treatment for depression since they have more adverse effects, take longer to reach an optimal dose, and have a greater potential for lethality when taken in overdose situations. They have more recently found a place in the treatment of neuropathic pain. The TCAs are thought to act primarily by blocking the reuptake of serotonin and norepinephrine. TCAs that contain a secondary amine in their structure (e.g., nortriptyline [Aventyl, Norventyl]) primarily block the reuptake of norepinephrine

SSRIs

SSRIs such as fluoxetine (Prozac), paroxetine (Paxil), citalopram (Celexa), escitalopram (Cipralex), and fluvoxamine (Luvox) preferentially block the reuptake of serotonin from the synaptic cleft. Sertraline (Zoloft) inhibits the neuronal reuptake of serotonin but to a lesser degree also inhibits norepinephrine and dopamine neuronal reuptake. SSRIs bind more poorly to acetylcholine muscarinic and H1 receptors than the TCAs and so tend to have fewer adverse effects in comparison. They seem to show comparable efficacy in treating depression without the anti-cholinergic and sedating adverse effects that limit patient adherence to other drug regimens.

SNRIs

medications that increase both serotonin and norepinephrine levels in the brain. Venlafaxine (Effexor XR) and desvenlafaxine (Pristiq) are effective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Thus these neurotransmitters will accumulate in the synapse. Venlafaxine has the dual mechanism of working as an SSRI at lower doses (75 mg/day), affecting the reuptake of serotonin, and as an SNRI at higher doses (150-225 mg/day), affecting the reuptake of both serotonin and norepinephrine.

Duloxetine (Cymbalta) affects norepinephrine and serotonin reuptake equally. Thus it has a greater noradrenergic effect than does venlafaxine at lower doses. This SNRI is indicated for acute and maintenance treatment of major depressive disorder, for acute treatment of GAD, for managing fibromyalgia, and for managing neuropathic pain associated with diabetic peripheral neuropathy

Serotonin Modulator and Stimulator

Vortioxetine (Trintellix) is a serotonin modulator and stimulator. It affects many different serotonin receptors by inhibiting serotonin reuptake like the SSRIs, activating 5-HT1A receptors like buspirone, acting as a partial agonist at 5-HT1B receptor, and blocking 5-HT3, 5-HT1D, and 5-HT7 receptors. Geriatric patients may experience an improvement of cognitive deficits independent of its anti-depressant properties. Common adverse effects include constipation, nausea, and vomiting. More serious side effects are hyponatremia and, rarely, induction of hypomania or mania.

Serotonin and Norepinephrine Disinhibitors

The class of drugs described as serotonin and norepinephrine disinhibitors (SNDIs) is represented by only one drug, mirtazapine (Remeron). This unique drug increases norepinephrine, dopamine, and serotonin transmission by acting as an antagonist at central presynaptic α2-adrenergic receptors. The normal function of these receptors is to inhibit neurotransmitter release when norepinephrine binds to them. Thus any drug that prevents noradrenaline from binding to these receptors will potentiate neurotransmitter release. This is why this drug is called a disinhibitor. Mirtazapine tends to have a more rapid onset of effect than do single neurotransmitter anti-depressant drugs, and this may be because it can simultaneously affect several neurotransmitter systems. Mirtazapine is a potent antagonist of 5-HT2C receptors, which may account for its anti-anxiety and anti-depressant effects, as these receptors, when activated by serotonin, typically inhibit norepinephrine and dopamine release. In addition, this drug acts as an antagonist at 5-HT2A and 5-HT3 receptors, activation of which are thought to mediate sexual dysfunction and nausea. Thus these effects are less likely to occur, and this is an advantage compared to other drugs used in depression. Mirtazapine is also a potent H1-receptor antagonist, which accounts for drowsiness and increased appetite resulting in weight gain

Monoamine Oxidase Inhibitors (Selegine, Phenelzine)

Monoamine oxidase inhibitors (MAOIs) are a group of drugs used to treat depression that prevent the destruction of monoamines by inhibiting the action of MAO. MAOIs illustrate the principle that drugs can have a desired and beneficial effect in the brain, while at the same time having possibly dangerous effects elsewhere in the body. To understand the action of these drugs, keep in mind the following definitions:

Monoamines are a type of organic compound and include the neurotransmitters norepinephrine, epinephrine, dopamine, and serotonin, as well as many different food substances and drugs.

MAO is an enzyme that degrades monoamines and is located in the nerve endings that release dopamine, serotonin, and noradrenaline.

MAOIs inhibit the action of MAO and thereby prevent the degradation of monoamines. Because of the serious dangers that result from inhibition of hepatic MAO, patients taking MAOIs must be given a list of foods high in tyramine and drugs that must be avoided

Other Drugs Used to Treat Depression

Bupropion is effective both as a treatment for depression and as a smoking cessation aid. It seems to act as a dopamine-norepinephrine reuptake inhibitor

Trazodone (Trazodone) is a serotonin antagonist and reuptake inhibitor (SARI) and is not a first choice for treatment of depression. Its anti-depressant effects are seen only at high therapeutic doses.

Ketamine is a potential new drug treatment for depression and has been called one of the most important discoveries in mood research over the last half century (Wei et al., 2020). Unlike traditional anti-depressant drugs, ketamine induces a rapid, long-lasting reversal of symptoms and appears to treat suicidal ideation

Monoamine Theory of Depression

A theory that holds that too much norepinephrine and serotonin leads to mania, while too little leads to depression. It is also sometimes called the catecholamine theory of depression.

Suicide Risk and Anti-depressant Drugs

here is concern that anti-depressant drug use results in an increased risk of suicide. Since first reported, many studies have investigated this relationship. The results of these studies have often been contradictory or inconclusive and have been difficult to reconcile with one another. This is partly because these events are rare and also because of inconsistency in how these events are reported. However, the evidence thus far suggests that suicide risk in adults is likely not increased, and the data are most consistent in showing an increased risk in children and adolescents

Lithium Carbonate

Although the efficacy of lithium carbonate (Carbolith, Lithane, Lithmax) as a "mood stabilizer" in patients with bipolar disorders has been established for many years (Lithium is still a first-line option in the treatment of patients with bipolar disorder,

ts mechanism of action is still far from understood. While it was originally believed to exert its clinical effects via a non-specific disruption of neurotransmission, recent evidence suggests that it may be enhancing neuroprotective pathways and decreasing neuronal injury and death

Lithium commonly induces polyuria (the output of large volumes of urine) as a consequence of decreasing the effectiveness of vasopressin on renal function. Long-term use of lithium can result in thyroid gland enlargement (goiter) and, possibly, hypothyroidism in some patients. In addition, hyponatremia can increase the risk of lithium toxicity because increased kidney reabsorption of sodium leads to increased reabsorption of lithium as well.

Primarily because of its effects on electrical conductivity, lithium has a low therapeutic index. The therapeutic index is a measure of overall drug safety with respect to the risk for overdose or toxicity

Carbamazepine

the primary mechanism of action of carbamazepine is to inhibit neuronal sodium channels during depolarization events, hence reducing neuronal excitability.

Recommended baseline laboratory work includes liver function tests, complete blood count (CBC), electrocardiogram, and electrolyte levels. Blood levels are monitored to avoid toxicity, but there are no established therapeutic blood levels for carbamazepine in the treatment of bipolar disorder.

Valproate

valproate also displays efficacy in treating bipolar disorders. Valproate works through a number of the mechanisms listed earlier. It blocks both sodium and calcium channels and may elevate GABA levels by inhibiting the enzyme that normally degrades this neurotransmitter. Common adverse effects include tremor, weight gain, and sedation. More rarely occurring but serious adverse effects include thrombocytopenia, pancreatitis, and hepatic failure. I

Lamotrigine

erhaps the most effective drug for maintenance therapy of bipolar disorder, but it is not as effective in acute mania (Preston et al., 2013). Lamotrigine is best known for its ability to treat the depressive phase of bipolar disorder, with less risk of causing a switch into mania when compared to anti-depressant drugs

Patients should promptly report any rashes, which could be a sign of life-threatening Stevens-Johnson syndrome. This risk can be minimized by slow titration to therapeutic doses.

First-Generation Antipsychotic Drugs

early neuroleptic medications that reduce psychotic symptoms

A group of drugs, including phenothiazines, that comprised the first wave of antipsychotic drugs and are still in use today.

It is believed that patient adherence is negatively affected due to the numerous and sometimes severe adverse effects of the first-generation drugs used in the treatment of psychosis. A quest for efficacious drugs to treat psychosis with fewer adverse effects led to the development of the second generation of antipsychotic drugs.

Second-Generation Antipsychotic Drugs (1990s)

A relatively new group of antipsychotic drugs whose biological action is different from that of the traditional antipsychotic drugs. Also known as atypical antipsychotic drugs.

Clozapine and olanzapine use has a high risk of causing metabolic syndrome, whereas aripiprazole and ziprasidone use has a lower risk

In addition, it is the antagonism of these receptors that is believed to result in fewer EPS

Clozapine.

Clozapine (Clozaril), the first of the second-generation drugs to be developed, is relatively free of extrapyramidal motor disturbances. It is thought that clozapine preferentially blocks the dopamine receptors in the mesolimbic system, rather than those in the nigrostriatal area. This pattern of selectivity allows clozapine to exert an antipsychotic action while minimizing EPS.

Risperidone

(Risperdal) acts at D2 receptors and is also a potent antagonist at 5-HT2A receptors. This drug has a low potential for inducing agranulocytosis or convulsions. However, high therapeutic doses (greater than 6 mg/day) may lead to motor-related complications. It has the highest risk of EPS among the second-generation antipsychotic drugs and may increase prolactin release, which may lead to sexual dysfunction. Risperidone can cause orthostatic hypotension that can lead to falls, a serious problem among older persons. Weight gain, sedation, and sexual dysfunction are adverse effects that may affect adherence to the medication regimen and should be discussed with patients.

Drug Treatment for Attention-Deficit/Hyperactivity Disorder

e administration of psychostimulant drugs. Both methylphenidate (Biphentin, Concerta, Ritalin) and amphetamines such as amphetamine (Adderall XR) seem to show efficacy in treating these conditions. They block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the concentration of these monoamines in the synaptic cleft. Thus they potentiate the signalling pathways of these neurotransmitters. How this translates into clinical efficacy is far from understood, but it is thought that the monoamines may inhibit an overactive part of the limbic system to prolong periods of concentration and focus on tasks.

Drug Treatment for Alzheimer's Disease

. The first is to attempt to prevent or slow the structural degeneration. Although actively pursued, this approach has been unsuccessful so far. The second is to attempt to maintain normal brain function for as long as possible.

Much of the memory loss in this disease has been attributed to dysfunction of neurons that use acetylcholine as a neurotransmitter. The anti-cholinesterase drugs (also called cholinesterase inhibitors) show some efficacy in slowing the rate of memory loss and, in some patients, may even improve memory. The drugs work by interfering with the action of acetylcholinesterase, an enzyme that normally degrades acetylcholine. Inhibition of this enzyme leads to reduced breakdown of acetylcholine and therefore to a higher concentration in the synapse. Three of the four drugs approved for the treatment of mild to moderate Alzheimer’s disease in Canada are acetylcholinesterase inhibitors: donepezil (Aricept), galantamine (generic only), and rivastigmine (Exelon). The fourth drug is memantine (Ebixa), an NMDA receptor antagonist.

The nurse understands that norepinephrine is involved with the stimulation of which bodily process?

a. The fight-or-flight response to stress

b. The hypothalamus to release hormones

c. Involvement in the inflammatory response

d. The parasympathetic nervous system

a. The fight-or-flight response to stress

4. The nurse is caring for a patient who is taking lithium. Which adverse effect would the nurse anticipate?

a. Oliguria

b. Confusion

c. Constipation

d. Hyperthyroidism

d. Hyperthyroidism

3. Which patient statement would require the nurse to provide further teaching?

a. "I should report any unusual bleeding when I take gingko biloba."

b. "I should not take St. John's wort with sertraline hydrochloride."

c. "Natural health products are safe because they are made with all-natural ingredients."

d. "I will tell my doctor that I am taking a natural health product."

c. "Natural health products are safe because they are made with all-natural ingredients."

2. Which of the following medication orders would the nurse question?

a. Buspirone—take in the morning

b. Temazepam—take at bedtime

c. Zopiclone—take early in the morning

d. Flurazepam—take at bedtime

a. Buspirone—take in the morning

1. Alterations in the activity of which neurotransmitters are important in drug treatment of depression?

a. Acetylcholine and histamine

b. GABA and glycine

c. Dopamine and glutamate

d. Serotonin and norepinephrine

d. Serotonin and norepinephrine