Pharmacology - CNS Drugs Notes PDF

NCM106: PHARMACOLOGY CNS Drugs  ANTIPSYCHOTIC Antipsychotic drugs are used mainly for the treatment of psychosis, a severe mental disorder characterized by disordered thought processes (disorganized and often bizarre thinking); blunted or inappropriate emotional responses;...

NCM106: PHARMACOLOGY CNS Drugs  ANTIPSYCHOTIC Antipsychotic drugs are used mainly for the treatment of psychosis, a severe mental disorder characterized by disordered thought processes (disorganized and often bizarre thinking); blunted or inappropriate emotional responses; bizarre behavior ranging from hypoactivity to hyperactivity with agitation, aggressiveness, hostility, and combativeness; social withdrawal in which a person pays less-than-normal attention to the environment and other people; deterioration from previous levels of occupational and social functioning (poor self care and interpersonal skills); hallucinations; and paranoid delusions.  Schizophrenia Positive symptoms are characterized by central nervous system (CNS) stimulation and include agitation, behavioral disturbances, delusions, disorganized speech, hallucinations, insomnia, and paranoia. Negative symptoms are characterized by lack of pleasure (anhedonia), lack of motivation, blunted affect, poor grooming and hygiene, poor social skills, poverty of speech, and social withdrawal.  Schizophrenia The disorder is caused by imbalances in neurotransmitters in specific brain areas. This theory suggests the possibility of overactive dopaminergic pathways in the basal nuclei, an area of the brain that controls the motor activity. The basal ganglia with associated nuclei are responsible for starting and stopping synchronized motor activity such as leg and arm motions during walking.. Symptoms of schizophrenia seem to be associated with the dopamine 2 receptor. The basal nuclei are particularly rich in D2 receptors whereas the cerebrum contains very few. All antipsychotic drugs act by entering dopaminergic synapses and competing with dopamine. By blocking a majority of the D2 receptors, antipsychotic drugs reduce the symptoms of schrizophrenia.  Antipsychotic Medications Antipsychotic drugs are derived from several chemical groups. These drugs may be broadly categorized as “typical,” conventional, or first- generation agents (phenothiazines and older nonphenothiazines, such as Haloperidol (Haldol) with similar pharmacologic actions, clinical uses, and adverse effects), or as “atypical” or second-generation agents, which can also be called newer nonphenothiazines. Mechanism of Action  Phenothiazines PROTOTYPE DRUG: Chlorpromazine Hydrochloride (Thorazine) THERAPEUTIC CLASS: Conventional Antipsychotic, schizophrenia drug PHARAMCOLOGIC CLASS: D2 dopamine receptor anatagonist; phenothiazine ACTIONS: It provides symptomatic relief of positive symptoms of schizophrenia and control manic symptoms in patients with schizoaffective disorder. Many patients must take chlorpromazine for 7 0r 8 weeks before they experience improvement. Extreme agitation may be treated with IM/IV injections which begin to act within minutes. It can also control severe nausea and vomiting.  Phenothiazines Fluphenazine decanoate and enanthate (Prolixin Decanoate; Prolixin Enanthate) Fluphenazine hydrochloride (Prolixin, Permitil) Perphenazine (Trilafon) Prochlorperazine (Compazine) Trifluoperazine (Stelazine)  Nonphenothiazines PROTOTYPE: Haloperidol (Haldol) First-Generation “Typical” Antipsychotics Frequently used, potent, long-acting drug. It is well absorbed after oral or intramuscular (IM) administration, is metabolized in the liver, and is excreted in urine and bile. It may cause adverse effects similar to those of the phenothiazines. Usually, it produces a relatively low incidence of hypotension and sedation and a high incidence of extrapyramidal effects. Loxapine (Loxitane), Molindone (Moban), Pimozide (Orap), Thiothixene (Navane) Side Effects  NMS Neuroleptic malignant syndrome—fever (may be confused with heat stroke), muscle rigidity, agitation, confusion, delirium, dyspnea, tachycardia, respiratory failure, acute renal failure A rare but potentially fatal reaction that may occur hours to months after initial drug use. Symptoms usually develop rapidly over 24–72 hours. Treatment includes stopping the antipsychotic drug, giving supportive care related to fever and other symptoms, and drug therapy (dantrolene, a skeletal muscle relaxant, and amantadine or bromocriptine, dopamine-stimulating drugs). Second-Generation “Atypical” Antipsychotics PROTOTYPE: Clozapine (Clozaril) Clozapine is chemically different from the older antipsychotic drugs. It blocks both dopamine and serotonin receptors in the brain. It is indicated for clients with schizophrenia, including those who have exhibited recurrent suicidal behavior. Advantages of clozapine include improvement of negative symptoms, without causing the extrapyramidal effects associated with older antipsychotic drugs.  Clozapine The reason for the second-line status of clozapine is its association with Agranulocytosis, a life-threatening decrease in white blood cells (WBCs), which usually occurs during the first 3 months of therapy. Weekly WBC counts are required during the first 6 months of therapy; if acceptable WBC counts are maintained, then WBC counts can be monitored every other week. In addition, clozapine is reportedly more likely to cause constipation, dizziness, drowsiness, hypotension, seizures, and weight gain than other atypical drugs. Olanzapine (Zyprexa), Quetiapine (Seroquel), Risperidone (Risperdal), Ziprasidone (Geodon), Aripiprazole (Abilify)  Nursing Management 1. Supervise ambulation to prevent falls or other injuries if the client is drowsy or elderly or has postural hypotension. 2. Several measures can help prevent or minimize hypotension, such as having the client lie down for approximately an hour after a large oral dose or an injection of antipsychotic medication; applying elastic stockings; and instructing the client to change positions gradually, elevate legs when sitting, avoid standing for prolonged periods, and avoid hot baths (hot baths cause vasodilation and increase the incidence of hypotension). In addition, the daily dose can be decreased or divided into smaller amounts. 3. Dry mouth and oral infections can be decreased by frequently brushing the teeth; rinsing the mouth with water; chewing sugarless gum or candy; and ensuring an adequate fluid intake. Excessive water intake should be discouraged because it may lead to serum electrolyte deficiencies. 4. The usual measures of increasing fluid intake, dietary fiber, and exercise can help prevent constipation.  DRUGS FOR BIPOLAR DISORDERS Mania at the opposite pole from depression occurs in individual with bipolar disorder who experiences a period of depression followed by a period of mania. BIPOLAR DISORDER – involves extremes of depression alternating with hyperactivity and excitement. This condition may reflect a biochemical imbalance followed by overcompensation on the part of neurons and their inability to reestablish stability. Signs and Symptoms  THERAPEUTIC ACTIONS Lithium alters sodium transport in nerve and muscle cells; inhibits the release of norepinephrine and dopamine but not serotonin from stimulated neurons; increases the intraneuronal stores of norepinephrine and dopamine slightly and decreases intraneuronal content of second messengers. This last mode of action may allow it to selectively modulate the responsiveness of hyperactive neurons that might contribute to the manic state.  PHARMACOKINETICS Lithium is readily absorbed from the GI tract, reaching peak levels in 30 minutes-3 hours. It follows the same distribution pattern in the body as water. It slowly crosses the blood-brain barrier. Lithium is excreted from the kidney, although about 80% is reabsorbed. During period of sodium depletion or dehydration, the kidney reabsorbs more lithium into the serum, often leading to toxic levels. Patients must be encouraged to maintain hydration while taking this drug. Lithium crosses placenta and enters breast milk and has been associated with congenital abnormalities.  CONTRAINDICATIONS 1. Presence of hypersensitivity to lithium (to prevent hypersensitivity reactions). 2. Significant renal or cardiac disease (could be exacerbated by the toxic effects of the drug 3. History of leukemia, metabolic disorders including sodium depletion, dehydration and diuretic use (it depletes sodium reabsorption and severe hyponatremia may occur). Hyponatremia leads to lithium retention and toxicity. 4. Pregnancy and lactation (potential for adverse effects on the fetus or neonate). While using lithium, women of childbearing age should be advised to use birth control 5. Protacted diarrhea or excessive sweating 6. Suicidal or impulsive patients and in patients who have infection with fever (could be exacerbated by the toxic effects of the drug).  Nursing Management 1. obtain baseline: renal, cardiac, thyroid 2. Monitor WBC for Leukocytopenia and Agranulocytosis 3. Increase fluid intake 4. Avoid excessive exercises and warm environment 5. Assess for signs of lithium toxicity 6. Therapeutic level of lithium: 0.5 to 1.5meq/L Maintenance dose - 0.6 to 1.2 meq/L Elderly - 0.5 to 1.0 meq/L  Antidepressant Drugs Depression is a mental health issue that starts most often in early adulthood. It’s also more common in women. However, anyone at any age may deal with depression. Signs and Symptoms  Selective Serotonin Reuptake Inhibitors (SSRIs) SSRIs are the most commonly prescribed class of antidepressants. An imbalance of serotonin may play a role in depression. These drugs fight depression symptoms by decreasing serotonin reuptake in the brain. This effect leaves more serotonin available to work in the brain. Sertraline (Zoloft) Fluoxetine (Prozac, Sarafem) Citalopram (Celexa) Escitalopram (Lexapro) Paroxetine (Paxil, Pexeva, Brisdelle) Fluvoxamine (Luvox)  Common side effects of SSRIs include: nausea trouble sleeping nervousness tremors sexual problems SSRI’s can also be indicated to: obsessive-compulsive disorder (OCD) panic disorder bulimia post-traumatic stress disorder (PTSD) premenstrual dysphoric disorder (PMDD) hot flashes caused by menopause anxiety  How SSRI’s Work Serotonin is one of many brain chemicals that transmit messages between brain cells. It has been called the “feel-good chemical” because it causes a relaxed state of well-being. Normally, serotonin circulates in the brain and then absorbs into the bloodstream. Depression is linked with low levels of serotonin (as well as low levels of dopamine, norepinephrine, and other brain chemicals). SSRIs work by preventing blood from absorbing some of the serotonin from brain. This leaves a higher level of serotonin in the brain, and increased serotonin can help relieve depression. SSRIs don’t cause the body to make more serotonin, however. They simply help the body use what it has more effectively.  PHARMACOKINETICS SSRIs are well absorbed from the GI tract, metabolized in the liver and excreted in the urine and feces. The half-life varies widely with the drug being used. CAUTION Patients with impaired renal or hepatic functions (could alter metabolism and excretion of drug leading to toxic effects). Severely depressed/suicidal patients especially children, adolescents and young adults (risk of increased suicidality). Pregnancy (associated with congenital anomalies)  NURSING CONSIDERATIONS 1. Assess for any known allergies to SSRIs (avoid hypersensitivity reactions) 2. Severe depression, angle-closure glaucoma, bipolar disorder (could be exacerbated by these drugs). 3. Assess impaired liver and renal functions (could alter metabolism and excretion of the drug) 4. Assess female patients if pregnant or breastfeeding 5. Assess vital signs, weight, skin color and lesions, affect, orientation and reflexes, vision, bowel sounds (baseline status for beginning therapy and fort potential adverse effects.  Tricyclic antidepressants (TCAs) TCAs are often prescribed when SSRIs or other antidepressants don’t work. It isn’t fully understood how these drugs work to treat depression. TCAs include: amitriptyline amoxapine clomipramine (Anafranil) desipramine (Norpramin) doxepin imipramine (Tofranil)  Side Effects Common side effects of TCAs can include: Constipation Dry mouth Fatigue The more serious side effects of these drugs include: Low blood pressure Irregular heart rate Seizures  How TCA’s Work Tricyclic antidepressants help keep more serotonin and norepinephrine available to the brain. These chemicals are made naturally by the body and are thought to affect the mood. By keeping more of them available to your brain, tricyclic antidepressants help elevate your mood. Some tricyclic antidepressants are also used to treat other conditions, mostly in off-label uses. These conditions include obsessive compulsive disorder (OCD) and chronic bedwetting. In lower doses, cyclic antidepressants are used to prevent migraines and to treat chronic pain. They are also sometimes used to help people with panic disorder. Tricyclic antidepressants treat depression, but they have other effects on your body as well. They can affect automatic muscle movement for certain functions of the body, including secretions and digestion. They also block the effects of histamine, a chemical found throughout your body. Blocking histamine can cause effects such as drowsiness, blurred vision, dry mouth, constipation, and glaucoma. These may help explain some of the more troublesome side effects associated with these drugs.  PHARMACOKINETICS TCAs are well absorbed from the gastrointestinal tract, reaching peak levels in 2-4 hours. They are highly bound to plasma proteins and are lipid soluble; this allows then to be distributed widely in the tissues including the brain. The TCAs cross the placenta and enter breast milk. CAUTIONS Patients with preexisting cardiovascular disorders (because of the cardiac stimulatory effect of the drug and with any condition that would be exacerbated by the anticholinergic effects).  CAUTION Angle-closure glaucoma, urinary retention, prostate hypertrophy, GI or gentourinarysurgery Psychiatric patients (may exhibit worsening of psychoses or paranoia). Manic-depressive patients (may shift to a manic state) Children, adolescent and young adults (risk of suicidality). History of seizures and elderly(seizure threshold may decreased secondary to stimulation of the receptor sites) Hepatic or renal disease (could interfere with metabolism and excretion of these drugs and lead toxic levels  Interactions 1. Alcohol – decreases effectiveness, increases sedation effects 2. Tricyclic antidepressants can increase the effects of Epinephrine in the heart. This can lead to high blood pressure and problems with heart rhythm.  NURSING CONSIDERATIONS 1. Assess for any known allergies of these drugs (to avoid hypersensitivity reactions) 2. Assess liver or kidney function (could alter metabolism and excretion of the drug). 3. Assess Glaucoma, benign prostatic hypertrophy, cardiac dysfunction, GI obstruction, surgery or recent myocardial infarction (all of which could be exacerbated by the effects of the drug). 4. Assess for history of seizures/psychiatriuc problems/suicidal thoughts, myelography within the past 24 hours or in the next 48 hours or is taking MAOIs (to avoid potentially severe adverse reactions). 5. Assess vital signs, weight, skin color and lesions, affect, orientation, reflexes, vision and bowel sounds on abdominal examination (This determines baseline status before beginning therapy and for any potential adverse effects).  Monoamine Oxidase Inhibitors (MAOIs) MAOI’s are older drugs that treat depression. They work by stopping the breakdown of norepinephrine, dopamine, and serotonin. They’re more difficult for people to take than most other antidepressants because they interact with prescription drugs, nonprescription drugs, and some foods. They also can’t be combined with stimulants or other antidepressants. MAOIs include: Isocarboxazid (Marplan) Phenelzine (Nardil) Selegiline (Emsam), which comes as a transdermal patch Tranylcypromine (Parnate)  SIDE EFFECTS nausea dizziness drowsiness trouble sleeping Restlessness INTERACTIONS Foods – avoid Tyramine rich foods and beverages(aged cheese, soy sauce, tofu, draft beer) Other Antidepressant drugs It can dangerously cause high levels of serotonin (serotonin syndrome)  PHARMACOKINETICS The MAOIs are well absorbed from the GI tract, reaching peak levels in 2-3 hours. They are metabolized in the liver primarily by acetylation and are excreted in the urine. Patients with liver or renal impairment and those known as “slow acetylators” may require lowered doses to avoid exaggerated effects of the drugs.  NURSING CONSIDERATIONS 1. Assess for any known allergies to these drugs (avoid hypersensitivity reactions) 2. Assess impaired liver and renal functions (could alter metabolism and excretion of drug). 3. Cardiac dysfunction, GI or GU obstruction(could be exacerbated by the drug) 4. Seizure disorders, psychiatric conditions or suicidality and occurence of myelopathy within the past 24 hours or in the next 48 hours to avoid the possibility of severe reactions. 5. Determine whether female patients are pregnant/breastfeeding (should not be used during pregnancy and lactation). 6. Assess vital signs, weight, skin color and lesions, affect, orientation and reflexes, vision and bowel sounds (determine baseline status and for any potential adverse effects before beginning therapy  ANXIETY Anxiety - is a state of “apprehension, tension or uneasiness that stems from the anticipation of danger, the source with is largely unknown or unrecognized. Generalized Anxiety Disorder (GAD) - is a difficult to control, excessive anxiety that lasts 6 months or more. - it focuses on a variety of life events/activities and interferes with normal day-to-day functions. Panic Disorder - characterized by intense feelings of immediate apprehension, fearfulness, terror or impending doom, accompanied by ↑ ANS activity.  Anxiety Related Disorders Phobias - are fearful feelings attached to situation or objects. Common phobias: fear of snakes, spiders, crowd ( social anxiety)and heights Obsessive Compulsive Disorder - involves recurrent, intrusive thoughts/repetitive behaviors that interfere with normal activities/relationship Post Traumatic Stress Disorder (PTSD) - a type of situational anxiety that develops in response to re-experiencing a previous life event Signs and Symptoms restlessness, fatigue, muscle tension, nervousness, inability to focus/concentrate, and overwhelming sense of dread and sleep disturbance.  BENZODIAZEPINES USED AS ANXIOLYTICS 1. Alprazolam (Xanax) 2. Chlordiazepoxide (Librium) 3. Clorazepam (Klonopin) 4. Clorazepate (Tranxene) 5. Diazepam (Valium) 6. Lorazepoam (Ativan) PHARMACOKINETICS The benzodiazepines are well absorbed from the GI tract, with peak levels achieved in 30 minutes to 2 hours. They are lipid soluble and well distributed throughout the body, crossing the placenta and entering breast milk. Patients with liver disease must receive a smaller dose and bemonitored closely. Excretion primarily through the urine.  CONTRAINDICATIONS 1. Allergy to any benzodiazepine to prevent hypersensitivity reactions 2. Psychosis which could be exacerbated by sedation 3. Acute narrow-angle glaucoma 4. Shock,coma or alcoholic intoxication 5. Pregnancy because a predictable syndrome of cleft lip/palate, inguinal hernia, cardiac defects, microcephaly or pyloric stenosis occurs when they are taken in the first trimester 6. Breastfeeding is contraindicated becasue of potential adverse effects on the neonate 7. Elderly/debilitated patients because of possible unpredictable reaction. Note: The risk of CNS depression increases if benzodiazepines are taken with alcohol or other CNS depressants, so much combinations should be avoided.  BARBITURATES AS ANXIOLYTICS-HYPNOTICS Drugs derived from barbituric acid Former mainstay drug used for the treatment of anxiety and for sedation and sleep induction Associated with potentially severe adverse effects and many drug-drug interactions, which make it less desirable than some of the newer agents Overdose results in profound respiratory depression, hypotension and shock THERAPEUTIC ACTION Barbiturates are general CNS depressants that inhibit neuronal impulse conduction in the ascending RAS, depress the cerebral cortex, alter the cerebellar function, depress motor output. They can cause sedation, hypnosis, anesthesia and in extreme cases coma  PHARMACOKINETICS Barbiturates are absorbed well, reaching peak levels in 20-60 minutes. They are metabolized in the liver to varying degrees, depending on the drug, and excreted in the urine. The long-acting barbiturates tend to be metabolized slower and excreted to a greater degree unchanged in the urine. They are known to induce liver enzyme systems, increasing the metabolism of barbiturate broken down by that system as well as that of any other drug that may be metabolized by that enzyme system.  ADVERSE EFFECTS Drowsiness, somnolence, lethargy, ataxia, vertigo, a feeling of a “hangover”, thinking abnormalities, paradoxical excitement, anxiety and hallucinations, nausea, vomiting, constipation, diarrhea and epigastric pain, hypoventilation, laryngospasm Cardiovascular effects: bradycardia, hypotension (IV administration) and syncope Hypersensitivity reactions: rash, serum sickness and Steven-Johnson sydrome NURSING CONSIDERATIONS Assess for contraindications or cautions: Known allergies to prevent hypersensitivity reactions Assess for baseline status before beginning the therapy and for the occurrence of any potential adverse effects.(Vital signs, weight, tissue perfusion: skin color and lesions, affect, orientation, reflexes, bowel sounds)