N241 Chap 13, 14, 15 W22 (4) PDF - Pharmacology Notes

Chapter 13 CENTRAL NERVOUS SYSTEM STIMULANTS AND RELATED DRUGS 2 Very complex system in the human body Central Nervous System CNS activity is regulated by a “checks-andbalances system.” Excessive stimulation of excitatory neurons or blockade of inhibitory neurons. Receptors in the CNS Copyright © 20...

Chapter 13 CENTRAL NERVOUS SYSTEM STIMULANTS AND RELATED DRUGS 2 Very complex system in the human body Central Nervous System CNS activity is regulated by a “checks-andbalances system.” Excessive stimulation of excitatory neurons or blockade of inhibitory neurons. Receptors in the CNS Copyright © 2020 Elsevier Inc. All Rights Reserved. CNS Stimulants  CNS stimulant drugs act by stimulating the excitatory neurons in the brain.  Neurons contain receptors for excitatory neurotransmitters, including dopamine (dopaminergic drugs), norepinephrine (adrenergic drugs), and serotonin (serotonergic drugs).  Sympathomimetic drugs 3 Classification  4 Classified according to  Chemical structural similarities: amphetamines, serotonin agonists, sympathomimetics, and xanthines  Site of therapeutic action in the central nervous system (CNS)  Major therapeutic uses: anti–attention deficit disorder, antinarcoleptic, anorexiant, antimigraine, and analeptic drugs Attention Deficit Hyperactivity Disorder (ADHD)  Most common psychiatric disorder in children, affecting 4% to 10% of schoolage children of which approximately 6% are treated with medication  Boys are affected from three times more often than girls.  Primary symptoms of ADHD are inappropriate ability to maintain attention span or the presence of hyperactivity and impulsivity.  Drug therapy for both childhood and adult ADHD is the same. Copyright © 2020 Elsevier Inc. All Rights Reserved. 5 Narcolepsy  Incurable neurologic condition in which patients unexpectedly fall asleep in the middle of normal daily activities. These “sleep attacks” are reported to cause car accidents or nearmisses in 70% or more of patients.. Copyright © 2020 Elsevier Inc. All Rights Reserved. 6 Drugs for Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy 7 CNS stimulants are first line drugs.  Amphetamines: methylphenidate  Nonamphetamine stimulants  Atomoxetine: nonstimulant drug that is also used to treat ADHD  Modafinil  indicated for improvement of wakefulness in patients with excessive daytime sleepiness associated with narcolepsy  Copyright © 2020 Elsevier Inc. All Rights Reserved. 8 Mechanism of Action and Drug Effects   Amphetamines  increase the effects of norepinephrine and dopamine in CNS synapses by increasing their release and blocking their reuptake. Then, noriepi & dop are in contact with their receptors longer, which lengthens their duration of action.  Stimulate areas of the brain associated with mental alertness CNS effects  Mood elevation or euphoria  Increased mental alertness and capacity for work  Decreased fatigue and drowsiness  Prolonged wakefulness Copyright © 2020 Elsevier Inc. All Rights Reserved. Mechanism of Action and Drug Effects (Cont.)  Respiratory effects  Relaxation  Increased  Dilation of bronchial smooth muscle respiration of pulmonary arteries 9 Indications/Contraindications Indications: ADHD Narcolepsy Obesity Contraindications: Known drug allergy Cardiac structural abnormalities Recent MAOI usage Copyright © 2020 Elsevier Inc. All Rights Reserved. 10 Adverse Effects  Wide range; dose related  Tend to “speed up” body systems  Common adverse effects include:  Palpitations, tachycardia, hypertension, angina, dysrhythmias, nervousness, restlessness, anxiety, insomnia, nausea, vomiting, diarrhea, dry mouth, increased urinary frequency, others Copyright © 2020 Elsevier Inc. All Rights Reserved. 11 Principal Drugs Used to Treat ADHD and Narcolepsy    Copyright © 2020 Elsevier Inc. All Rights Reserved. 12 Amphetamines  Amphetamine sulfate Amphetamine aspartate (Adderall): one of the most commonly prescribed drugs for ADHD Nonamphetamine stimulants  Atomoxetine: nonstimulant drug also used for ADHD Atomoxetine (Strattera)  Approved for treating ADHD in children older than 6 years of age and in adults  Not a controlled substance   lacks addictive properties In September 2005, the FDA issued a warning describing cases of suicidal thinking and behavior in small numbers of adolescent patients receiving this medication. Copyright © 2020 Elsevier Inc. All Rights Reserved. 13 Methylphenidate (Ritalin) First prescription drug indicated for ADHD Also used for narcolepsy Extended-release dosage forms Ritalin SR Concerta Metadate CD Copyright © 2020 Elsevier Inc. All Rights Reserved. 14 Nursing Implications  15 Drugs for ADHD  Last daily dose should be given 4 to 6 hours before bedtime to reduce insomnia.  Take on an empty stomach 30 to 45 minutes before meals.  Drug “holidays” may be ordered.  Instruct parents to keep a journal to monitor the child’s response to therapy.  Monitor the child for continued physical growth, including height and weight. 16 Obesity  According to the National Institutes of Health and the Centers for Disease Control and Prevention, approximately 35% of Americans are obese, and nearly two thirds (64.5%) are overweight.  More than 78 million obese adults  Many associated health risks 17 Anorexiants  Any substance that suppresses appetite  Used to treat obesity  Anorexiants  Benzphetamine (Regimex)*  Methamphetamine (Desoxyn)* *Only ones approved for treatment of obesity. 18 Mechanism of Action  Suppress appetite control centers in the brain  Increase the body’s basal metabolic rate  Mobilization of adipose tissue stores  Enhanced cellular glucose uptake  Reduce dietary fat absorption 19  Other Drugs to Treat Obesity Orlistat (Xenical): related nonstimulant drug used to treat obesity  Mechanism of action: works locally in the small and large intestines, where it inhibits absorption of caloric intake from fatty foods.  Inhibits enzyme lipase  Reduces fat absorption by roughly 30%  Restricting dietary intake of fat to less than 30% of total calories can help reduce GI adverse effects.  Oily spotting, flatulence, fecal incontinence 20 Indications Used to treat obesity along with behavior modifications (diet, exercise) Most often used in higher-risk patients Contraindications Indications/Contraindications of Anorexiants Drug allergy Severe cardiovascular disease Uncontrolled HTN Hyperthyroidism Eating disorders MAOI usage Copyright © 2020 Elsevier Inc. All Rights Reserved. 21 Adverse Effects of Anorexiants  Possible elevated blood pressure and heart palpitations  Anxiety  Agitation  Dizziness  Headache  Orlistat: fecal incontinence with oily stools 22  Nursing Implications Anorexiants  Follow instructions for diet and exercise.  Take in the morning.  Avoid caffeine  Fat-soluble vitamin supplementation may be needed. Migraine Copyright © 2020 Elsevier Inc. All Rights Reserved. 23  Common type of recurring headache, usually lasting from 4 to 72 hours  Typical features: pulsatile quality with pain that worsens with each pulse  Most commonly unilateral but may occur on both sides of the head  Associated symptoms: nausea, vomiting, photophobia (avoidance of light), and phonophobia (avoidance of sounds)  Aura Antimigraine Drugs  Antimigraine (serotonin agonists; also called triptans)  Sumatriptan (Imitrex)  Almotriptan (Axert) 25 Mechanism of Action and Drug Effects  Triptans  Stimulate 5-HT receptors in cerebral arteries, causing vasoconstriction and reducing headache symptoms  Reduce the production of inflammatory neuropeptides  Abortive therapy for migraines 26 Adverse Effects of Antimigraine Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved.  Triptans  Vasoconstriction  Irritation at injection  Tingling, flushing site 27 Serotonin Receptor Agonists Sumatriptan (Imitrex)  Original prototype drug for this class  Seven triptans   Relief from moderate to severe migraines within 2 hours  Action:  Copyright © 2020 Elsevier Inc. All Rights Reserved. Effects are comparable overall.  Stimulate 5-HT1 receptors in the brain; causing vasoconstriction  reduce the production of inflammatory neuropeptides. Oral, sublingual tablets, SC injection, and nasal sprays 28  Selective serotonin receptor agonists (SSRAs) or Triptans  Dissolvable Nursing Implications (Cont.) wafers, nasal spray, and self-injectable forms  Provide specific teaching about correct administration.  Instruct patients to keep a journal to monitor response to therapy. Copyright © 2020 Elsevier Inc. All Rights Reserved. 29 Monitor ADHD: decreased hyperactivity, increased attention span and concentration Anorexiant: appetite control and weight loss Narcolepsy: decrease in sleepiness Serotonin agonist: decrease in frequency, duration, and severity of migraines Monitor for adverse effects Nursing Implications Therapeutic Responses Copyright © 2020 Elsevier Inc. All Rights Reserved. 30 Copyright © 2020 Elsevier Inc. All Rights Reserved. Chapter 14 ANTIEPILEPTIC DRUGS Epilepsy 32  Syndrome of CNS dysfunction  Most common chronic neurologic illness  Results from excessive electrical activity of neurons located in superficial area of brain (gray matter)  Up to 50% of patients with epilepsy have normal EEGs  History  skull radiography, computed tomography, and magnetic resonance imaging  rule out structural causes of epilepsy, such as brain tumors. Epilepsy (Cont.) 33  Following terms are often used interchangeably but they do not have the same meaning.  Seizure   Convulsion   Brief episode of abnormal electrical activity in nerve cells of the brain Involuntary spasmodic contractions of any or all voluntary muscles throughout the body, including skeletal, facial, and ocular muscles Epilepsy  Chronic, recurrent pattern of seizures Epilepsy (Cont.)  Primary (idiopathic)  Cause cannot be determined  Roughly  50% of epilepsy cases Secondary (symptomatic)  Distinct cause is identified.  Trauma,  Febrile infection, cerebrovascular disorder in young children 34 Status Epilepticus Multiple seizures occur with no recovery between them. Result: hypotension, hypoxia, brain damage, and death True medical emergency 35 Antiepileptic Drugs (AEDs) (anticonvulsants) Goals of therapy To control or prevent seizures while maintaining a reasonable quality of life To minimize adverse effects and drug-induced toxicity AED therapy is usually lifelong. Seizure free for 1 to 2 years antiepileptic drugs can eventually stop taking them with medical supervision. Abrupt discontinuation of these drugs can result in withdrawal seizures. Combination of drugs may be used. 36 37 Single-drug therapy is started before multiple-drug therapy is tried. Antiepileptic Drugs (Cont.) Serum drug concentrations must be measured. Therapeutic drug monitoring Serum concentrations of phenytoin, phenobarbital, carbamazepine, levetiracetam, and primidone correlate better with seizure control and toxicity than do those of valproic acid, ethosuximide, and clonazepam. Copyright © 2020 Elsevier Inc. All Rights Reserved. Antiepileptic Drugs (Cont.)  Antiepileptic drugs traditionally used to manage seizure disorders include:  Barbiturates  Hydantoins  Iminostilbenes  Second- plus valproic acid and third-generation antiepileptics 38 Mechanism of Action and Drug Effects  Exact mechanism of action is not known.  Less excitable cell membranes.  Reduce 39 nerve’s ability to be stimulated  Suppress transmission of impulses from one nerve to the next  Decrease speed of nerve impulse conduction within a neuron 40 Prevention or control of seizure activity Antiepileptic Drugs: Indications Long-term maintenance therapy for chronic, recurring seizures Acute treatment of convulsions and status epilepticus Other uses Copyright © 2020 Elsevier Inc. All Rights Reserved. Antiepileptic Drugs: Adverse Effects Numerous adverse effects; vary per drug Black box warning as of 2008 Suicidal thoughts and behavior Adverse effects often necessitate a change in medication. Long-term therapy with phenytoin (Dilantin) may cause gingival hyperplasia, acne, hirsutism, and Dilantin facies. 41 Antiepileptic Drugs: Interactions 43  Drug interactions are numerous.  Many antiepileptic drugs interact with each other.  Induce hepatic metabolism resulting in reduction of effects of other drugs.  Interfere with birth control.  Avoid grapefruit with carbamazepine. Antiepileptic Drug Listing 44 Valproic acid Gabapentin (Neurontin) Lamotrigine (Lamictal) Levetiracetam (Keppra) Topiramate (Topamax) Pregabalin (Lyrica) Hydantoins: Phenytoin (Dilantin) 45  Phenytoin (Dilantin) has been used as a firstline drug for many years and is the prototypical drug.  Adverse effects: gingival hyperplasia, acne, hirsutism, Dilantin facies, and osteoporosis  Therapeutic drug levels are usually 10 to 20 μg/mL.  Highly protein bound Hydantoins: Phenytoin (Dilantin) (Cont.)  46 Intravenous (IV) administration  Very irritating to veins  Slow IV directly into a large vein through a largegauge (20-gauge or larger) venous catheter  Diluted  Filter in normal saline (NS) for IV infusion must be used.  Saline flush Hydantoins: Fosphenytoin (Cerebyx) 47  Injectable prodrug of phenytoin  Water-soluble phenytoin derivative that can be given intramuscularly or intravenously— by IV push or continuous infusion—without causing burning on injection associated with phenytoin  Adverse effects Levetiracetam (Keppra)  Adjunct therapy for partial seizures with and without secondary generalization  Contraindication: known drug allergy  Mechanism of action: unknown  Adverse effects: generally well tolerated, CNS  No drug interactions 48 Safety: Look-Alike/SoundAlike Drugs  Be careful with drug names!  When using trade names, Cerebyx and Celebrex sound and look very much alike … but they are quite different!  Use both trade and generic names when ordering medications. 49 Nursing Implications of Antiepileptic Drugs  Assessment  Health history, including current medications  Drug allergies  Liver function studies, complete blood count  Baseline vital signs Copyright © 2020 Elsevier Inc. All Rights Reserved. 51  Oral drugs  Take regularly, same time each day. Nursing Implications of Antiepileptic Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved.  Take with meals to reduce GI upset.  Do not crush, chew, or open extended-release forms.  If patient is NPO for a procedure, contact prescriber regarding AED dosage. 52  Intravenous forms  Follow Nursing Implications of Antiepileptic Drugs manufacturer’s recommendations for IV delivery—usually given slowly.  Monitor vital signs during administration.  Avoid fluids. extravasation of  Use only normal saline with IV phenytoin (Dilantin). Copyright © 2020 Elsevier Inc. All Rights Reserved. 53  Nursing Implications of Antiepileptic Drugs (Cont.)    Copyright © 2020 Elsevier Inc. All Rights Reserved. Teach patients to keep a journal to monitor:  Response to AED  Seizure occurrence and descriptions  Adverse effects Instruct patients to wear a medical alert tag or ID. AEDs should not be discontinued abruptly. Follow driving recommendations. 54 Nursing Implications of Antiepileptic Drugs (Cont.) Copyright © 2020 Elsevier Inc. All Rights Reserved.  Teach patients that therapy is long term and possibly lifelong (not a cure).  Monitor for therapeutic effects:   Decreased or absent seizure activity Monitor for adverse effects:  Mental status changes, mood changes, changes in level of consciousness or sensorium  Eye problems, visual disorders  Sore throat, fever (blood dyscrasias may occur with hydantoins)  Many others 55 Chapter 15 ANTIPARKINSON DRUGS Parkinson’s Disease (PD)  Chronic, progressive, degenerative disorder  Affects dopamineproducing neurons in the brain  Caused by an imbalance of two neurotransmitters  Dopamine  Acetylcholine (ACh) 57 Parkinson’s Disease (Cont.) 58  Symptoms occur when about 80% of the dopamine stored in the substantia nigra of the basal ganglia is depleted.  Symptoms can be partially controlled as long as there are functioning nerve terminals that can take up dopamine.  A progressive condition  Rapid swings in response to levodopa occur (“on-off phenomenon”)  PD worsens when too little dopamine is present.  Dyskinesia occurs when too much dopamine is present.  “Wearing-off phenomenon”  PD-associated dementia Dyskinesia Copyright © 2020 Elsevier Inc. All Rights Reserved.  Difficulty in performing voluntary movements  Two common types:  Chorea: irregular, spasmodic, involuntary movements of the limbs or facial muscles  Dystonia: abnormal muscle tone leading to impaired or abnormal movements 61 Treatment of Parkinson’s Disease Full explanation of disease to the patient PT, OT, speech therapy important Treatment centers on drug therapy Severe cases: Deep brain stimulation 62 Pharmacology Overview 63 PD is thought to be caused by an imbalance of dopamine and Ach, with a deficiency of dopamine in certain areas of the brain. Drug therapies are aimed at increasing the levels of dopamine or antagonizing the effects of Ach. Unfortunately, current drug therapy does not slow the progression of the disease but rather is used to slow the progression of symptoms. Indirect-Acting Dopaminergic Drugs: Monoamine Oxidase Inhibitors 65  MAOIs break down catecholamines in the CNS, primarily in the brain.  Selegiline (Eldepryl) and rasagiline (Azilect) are selective MAOB inhibitors.  Cause an increase in levels of dopaminergic stimulation in the CNS  Do not elicit the “cheese effect” of the nonselective MAOIs used to treat depression (if 10 mg or less is used) Dopamine Modulator Amantadine (Symmetrel) Indirect acting    Causes release of dopamine from storage sites in the presynaptic fibers of nerve cells within the basal ganglia Blocks the reuptake of dopamine Result: higher levels of dopamine in the synapses between nerves and improved dopamine neurotransmission between neurons  Used early; effective for only 6 to 12 months  Used to treat dyskinesia associated with carbidopalevodopa  Common adverse effects mild; dizziness, insomnia, and nausea.  Drug interactions: increased anticholinergic adverse effects when given with anticholinergic drugs Dopamine Replacement Drugs   67 Replacement drugs (presynaptic)  Levodopa: biologic precursor of dopamine required by the brain for dopamine synthesis  Levodopa is able to cross the blood-brain barrier, and then it is converted to dopamine. Replacement drugs  Carbidopa is given with levodopa.  Carbidopa does not cross the blood-brain barrier and prevents levodopa breakdown in the periphery.  As a result, more levodopa crosses the blood-brain barrier, where it can be converted to dopamine. Levodopa Therapy 68  Levodopa is taken up by the dopaminergic terminal, converted into dopamine, and then released as needed.  As a result, neurotransmitter imbalance is controlled in patients with early PD who still have functioning nerve terminals.  Ultimately, levodopa no longer controls the PD, and the patient is seriously debilitated.  This generally occurs between 5 and 10 years after the start of levodopa therapy.  Contraindicated in cases of angle-closure glaucoma  Use cautiously in patients with open-angle glaucoma  Adverse effects: cardiac dysrhythmias, hypotension, chorea, muscle cramps, and GI distress Carbidopa-Levodopa (Sinemet) Sinemet CR: increases “on” time and decreases “off” time Carbidopa-levodopa: best taken on an empty stomach; to minimize GI side effects, it can be taken with food 69 Anticholinergic Therapy 70 Anticholinergics block the effects of Ach. Used to treat muscle tremors and muscle rigidity associated with PD These two symptoms are caused by excessive cholinergic activity. Does not relieve bradykinesia (extremely slow movements) 71 SLUDGE: Ach is responsible for causing increased salivation, lacrimation (tearing of the eyes), urination, diarrhea, increased GI motility, and possibly emesis (vomiting). Anticholinergic Therapy (Cont.) Anticholinergics have the opposite effects: dry mouth or decreased salivation, urinary retention, decreased GI motility (constipation), dilated pupils (mydriasis), and smooth muscle relaxation. Copyright © 2020 Elsevier Inc. All Rights Reserved. Anticholinergics and Other Drugs Used for Treatment of PD 72  Benztropine (Cogentin)  Anticholinergic drug used for PD and extrapyramidal symptoms from antipsychotic drugs  Caution during hot weather or exercise because it may cause hyperthermia  Adverse effects: tachycardia, confusion, disorientation, toxic psychosis, urinary retention, dry throat, constipation, nausea, and vomiting  Anticholinergic syndrome  Avoid alcohol 73 Perform a thorough assessment, nursing history, and medication history. Nursing Implications Include questions about the patient’s: CNS GI and GU tracts Copyright © 2020 Elsevier Inc. All Rights Reserved. Psychologic and emotional status Nursing Implications (Cont.) 74 01 02 03 04 Assess for signs and symptoms of PD Assess for conditions that may be contraindications. Administer drugs as directed by manufacturer. Provide patient education regarding PD and the medication therapy. Masklike expression Speech problems Dysphagia Rigidity of arms, legs, and neck Copyright © 2020 Elsevier Inc. All Rights Reserved. Nursing Implications (Cont.) Inform Assist Inform patient not to take other medications with PD drugs unless he or she checks with physician When starting dopaminergic drugs, assist patient with walking because dizziness may occur. Copyright © 2020 Elsevier Inc. All Rights Reserved. Administer Administer oral doses with food to minimize GI upset. 75 Encourage Encourage patient to force fluids to at least 3000 mL/day (unless contraindicated). Nursing Implications (Cont.) 76 Taking levodopa with MAOIs may result in hypertensive crisis. Patient should be taught not to discontinue antiparkinson drugs suddenly. Teach patient about expected therapeutic and adverse effects with antiparkinson drug therapy. Copyright © 2020 Elsevier Inc. All Rights Reserved. 77  Nursing Implications (Cont.) Monitor for response to drug therapy:  Improved sense of well-being and mental status  Increased appetite  Increased ability to perform ADLs, to concentrate, and to think clearly  Less intense parkinsonian manifestations, such as less tremor, shuffling gait, muscle rigidity, and involuntary movements