2. 2© Paradigm Publishing, Inc. Chapter 7 The Nervous System and Drug Therapy

3. Chapter 7 Topics Anatomy and Physiology of the Nervous System Seizure Disorders Parkinson’s Disease Dementia and Alzheimer’s Disease Attention-Deficit Hyperactivity Disorder (ADHD) Drugs that Affect the Autonomic Nervous System Herbal and Alternative Therapies 3© Paradigm Publishing, Inc.

4. Anatomy and Physiology of the Nervous System The Nervous System Senses and interprets surroundings and controls vital bodily functions Contains two divisions of the nervous system which are the CNS and the peripheral nervous system  CNS  Is made up of the brain and spinal cord  Processes information received outside the body  Peripheral nervous system  Is all the nerves outside the brain and spinal cord  Brings signal to the CNS for interpretation 4© Paradigm Publishing, Inc.

5. Anatomy and Physiology of the Nervous System Peripheral Nervous System Contains two divisions called the somatic nervous system and the autonomic nervous system  Somatic nervous system  Controls intentional, voluntary movement  Autonomic nervous system  Controls involuntary and automatic body functions, like heart rate, respiration, and digestion 5© Paradigm Publishing, Inc.

6. Anatomy and Physiology of the Nervous System Autonomic Nervous System: Two Divisions Sympathetic nervous system  Uses adrenergic receptors and some cholinergic receptors Parasympathetic nervous system  Uses cholinergic receptors The Brain: Two Sections Cerebrum, including the cerebral cortex  Performs high cognitive functions, such as thinking and memory Cerebellum  Coordinates movement and balance 6© Paradigm Publishing, Inc.

7. Anatomy and Physiology of the Nervous System © Paradigm Publishing, Inc.7 Anatomy of the Nervous System Anatomy of the Brain

8. Anatomy and Physiology of the Nervous System Pons and Medulla Located in the brain stem Regulate automatic and reflex functions of the body Thalamus and Hypothalamus Are in the middle of the brain Control various functions, including hormone regulation and body temperature Pituitary Gland Helps regulate hormones and controls the growth cycle throughout life 8© Paradigm Publishing, Inc.

9. Anatomy and Physiology of the Nervous System Blood-Brain Barrier (BBB) Protects delicate CNS tissue from potentially harmful chemicals  Oxygen, carbon dioxide, small molecules like glucose, and small lipid-soluble drugs pass easily from blood to CNS  Water-soluble molecules, like drugs and most pathogens, do not easily enter the brain or spinal cord Must be overcome so that drug therapy can enter the CNS 9© Paradigm Publishing, Inc.

10. Anatomy and Physiology of the Nervous System © Paradigm Publishing, Inc.10 Neurotransmission Nerve signals are carried from cell to cell by neurotransmitters

11. Anatomy and Physiology of the Nervous System Six Neurotransmitters and Their Actions Acetylcholine (ACh)  Used in the parasympathetic nervous system to control blood pressure, digestion, heart rate, and in exocrine glands Dopamine (DA)  Used in CNS to control mood and coordinated movement Epinephrine (adrenaline)  Used in the sympathetic nervous system to regulate cardiac function and bronchodilation GABA (gamma-aminobutyric acid)  Used in the brain to regulate signal delivery 11© Paradigm Publishing, Inc.

12. Anatomy and Physiology of the Nervous System Six Neurotransmitters and Their Actions (continued) Norepinephrine  Used in the CNS and sympathetic nervous system  Involved in mood and emotion in the brain  Acts on receptors to control blood pressure, cardiac function, and digestion in the periphery Serotonin (5-HT)  Used in the peripheral nervous system and CNS  Acts on receptors in smooth muscle in the periphery  Involved in mood and emotions in the brain Altered production, release, or metabolic breakdown of neurotransmitters causes many nervous system conditions 12© Paradigm Publishing, Inc.

13. Anatomy and Physiology of the Nervous System © Paradigm Publishing, Inc.13 Autonomic Nervous System Autonomic nerves  Are located close to the spinal column  Regulate involuntary body functions

14. Anatomy and Physiology of the Nervous System Autonomic Nervous System: Fight or Flight Response Sympathetic nerves release norepinephrine in scary or surprising situations; adrenal medulla releases epinephrine  Increases heart and respiration rates and blood pressure  Sympathetic nerves are called adrenergic Parasympathetic nerves release ACh to regulate body functions when relaxed or resting  Heart rate and breathing slow, and digestion and urination can occur  Parasympathetic nerves are called cholinergic 14© Paradigm Publishing, Inc.

15. Anatomy and Physiology of the Nervous System Alpha and Beta Adrenergic Receptors Activated by norepinephrine and epinephrine Alpha receptors  Found in blood vessels; when stimulated blood vessels constrict, raising blood pressure and when blocked by drugs blood pressure decreases Beta-one and beta-two receptors  Beta-one mostly in the heart; stimulation increases heart rate and contraction force  Beta-two in smooth muscle; stimulation causes blood vessels and bronchioles to dilate  When blocked by drugs heart rate, blood pressure, and respiration decrease 15© Paradigm Publishing, Inc.

16. Seizure Disorders About Seizures (Convulsions) Are uncoordinated bursts of neuronal activity that result in brain dysfunction Common causes include alcohol or drug withdrawal, high fever, stroke, shock, low or high blood sugar, and infection One in ten individuals will have unprovoked seizure in lifetime Epilepsy  Is a chronic seizure disorder  All patients with epilepsy have seizures, but not all patients with seizures have epilepsy 16© Paradigm Publishing, Inc.

17. Seizure Disorders Types of Seizures Partial seizure  Most common type  Affects localized brain area and specific body area  Causes twitching or muscle tightness in specific body areas  Loss of consciousness usually does not occur and patient can communicate Generalized seizures  Loss of consciousness usually occurs  Afterward, patient has a period of memory loss, confusion, and tiredness 17© Paradigm Publishing, Inc.

18. Seizure Disorders Antiepileptic Drugs (AEDs) Anticonvulsants  Are drugs used to treat seizure disorders  Mechanism of Action: varies; can work by multiple mechanisms at once  Affect the influx of sodium, calcium, or chloride ions across the nerve cell membrane which slows erratic nerve impulses Glutamate  Excitatory neurotransmitter that affects sodium and calcium influx GABA  Neurotransmitter inhibitor that affects chloride influx 18© Paradigm Publishing, Inc.

19. Seizure Disorders Antiepileptic Drugs (AEDs) (continued) Mechanism of Action: some work directly on ion channels; others inhibit glutamate or enhance GABA  Some work in multiple ways, such as topiramate Drug therapy regimens are highly individualized for each patient; take up to a month for full benefit from AEDs Status epilepticus (an emergency) treatment includes 1 of 2 benzodiazepines (diazepam or lorazepam), plus phenytoin or fosphenytoin  Phenobarbital also may be used  Storage: this drug combination found in crash cart kits; pharmacy technicians often maintain 19© Paradigm Publishing, Inc.

20. Seizure Disorders Antiepileptic Drugs: Side Effects Many are dose-dependent; blood levels monitored for highest (peak) and lowest (trough) concentrations Phenytoin, valproate, and carbamazepine undergo zero- order pharmacokinetics which results in severe toxicity Can cause drowsiness, dizziness, and mental confusion, but these effects can improve in time May have dulling effect on ability to think which is common in children Rare and serious effects include Stevens-Johnson syndrome (severe and sometimes fatal rash) and blood abnormalities Phenytoin can cause gingival hyperplasia 20© Paradigm Publishing, Inc.

21. Seizure Disorders Antiepileptic Drugs: Cautions Do not take with alcohol Avoid abrupt withdrawal Several anticonvulsants are in pregnancy category D Do not take zonisamide if allergic to sulfa drugs Zonisamide and topiramate can cause kidney stones Phenytoin interacts with many other medications Routes: all oral (fosphenytoin is IM, IV); others also IV  Valproate and valproic acid swallow whole Controlled substances are barbiturates (phenobarbital, amobarbital, and mephobarbital) and primidone 21© Paradigm Publishing, Inc.

22. Your Turn Question 1: What is the function of the parasympathetic nerves? Answer: They regulate restful body functions. When relaxed or resting, the heart and breathing are slow, digestion occurs, and urination is possible. Question 2: A child took an antiepileptic drug for 3 months during the school year. During that time, his grades began to drop. What could have caused this to happen? Answer: Antiepileptic drugs can have a dulling effect which affects the ability to think. The child may have experienced this side effect, which impacted his school performance. 22© Paradigm Publishing, Inc.

23. Parkinson’s Disease About Parkinson’s Disease (PD) Is characterized by tremors, muscle rigidity, difficulty moving, and balance problems; quite debilitating Is most common among elderly; 1% over age 60 have PD in the U.S. Is a disorder of the CNS in which cells are lost in the substantia nigra (region in midbrain)  These cells produce dopamine, a neurotransmitter used in initiating and coordinating muscle movement Is progressive and has no cure Drug therapy can relieve symptoms, allowing movement 23© Paradigm Publishing, Inc.

24. Parkinson’s Disease About Parkinson’s Disease (continued) Symptoms: shuffling gait, lean forward, somewhat off-balance, tremors, and inability to move Symptoms (other): anxiety, depression, fatigue, slow thinking dementia, fragmented sleep, and hallucinations PD-Type Symptoms Some drugs cause PD-type symptoms, but the effects are usually reversible when drug is stopped  Antipsychotics, metoclopramide, phenothiazine antiemetics, pimozide, amoxapine, lithium, and serotonin reuptake inhibitors 24© Paradigm Publishing, Inc.

25. Parkinson’s Disease Drugs for PD Initial therapy starts with one drug: an anticholinergic agent or a dopaminergic agent such as levodopa Eventually, adjunct therapy added for symptom control  COMT inhibitors, selegiline, apomorphine, amantadine Drugs for PD: Dopamine Agents Are mainstay of treatment for PD Levodopa  Is most effective treatment because it greatly improves movement and significantly restores normal function  Effects wear off over time 25© Paradigm Publishing, Inc.

26. Parkinson’s Disease Drugs for PD: Dopamine Agents (continued) Other dopaminergic agents used as an alternative to levodopa but not always as effective Will work without significant side effects about five years Mechanism of Action: replaces dopamine or mimics its action in the brain Dopamine itself cannot cross the BBB, so its prodrug, levodopa is given; the brain breaks it into dopamine  Carbidopa is also often given with levodopa to slow its breakdown before it reaches CNS; more enters brain Routes: all are oral, except apomorphine is SC injection 26© Paradigm Publishing, Inc.

27. Parkinson’s Disease Drugs for PD: Dopamine Agents (continued) Side Effects of Levodopa/Carbidopa (common): nausea and dyskinesias (involuntary movements of limbs, neck, and mouth) Side Effects of Dopamine Agonists (common): dizziness, constipation, nausea, insomnia, daytime sleepiness, “sleep attacks,” yawning, hallucinations, and mood elevations Caution: do not take apomorphine with antiemetic agents  Self-injected pen used for acute“off” times; not used regularly; pharmacist needs to teach use how to use  Storage: refrigerate prefilled syringes for one day 27© Paradigm Publishing, Inc.

28. Parkinson’s Disease Drugs for PD: Anticholinergics and Amantadine Indication (early in PD): mostly for tremors Indication (later in PD): adjunct for side effects of levodopa Anticholinergics  Mechanism of Action: block muscarinic receptors in the brain, reducing tremors  Side Effects: anxiety, confusion/memory impairment, drowsiness, dry nose and mouth, blurred vision, constipation, difficulty urinating, and possible heatstroke Amantadine  Mechanism of Action: inhibits reuptake of dopamine Cautions: drowsiness and confusion; do not take with alcohol 28© Paradigm Publishing, Inc.

29. Parkinson’s Disease Drugs for PD: COMT Inhibitors Indication: adjunct therapy (not monotherapy)  Help when levodopa starts to wear off at the end of each dosing interval  Are given with levodopa to increase “on” time Mechanism of Action: block an enzyme that metabolizes dopamine and boost effects of levodopa and dopamine Routes: all are oral Side Effects (Entacapone): dyskinesia worsening, nausea, diarrhea, abdominal pain, and postural hypotension Caution (Entacapone): can cause urine discoloration 29© Paradigm Publishing, Inc.

30. Parkinson’s Disease Drugs for PD: MAOIs Indication (early in PD): mild dopamine-boosting Indication (later in PD): adjunct therapy Mechanism of Action: block MAO, an enzyme that breaks down dopamine in neurons Routes: all are oral Side Effects: insomnia, confusion, hallucinations, euphoria, dizziness, and postural hypotension Cautions: limit intake of tyramine-rich foods (beef, sausage, aged and pickled foods and beverages)  Technicians remind patients to limit consumption 30© Paradigm Publishing, Inc.

31. Dementia and Alzheimer’s Disease About Alzheimer’s Disease Is a form of dementia Is a degenerative brain disorder leading to loss of memory, intellect, judgment, orientation, and speech 250,000 people diagnosed each year Can cause depression and anxiety “Failure to thrive” level reached and death results; no cure Drugs for Alzheimer’s Disease Goal is to maintain cognitive function and alertness for as long as possible Indications: mild symptoms early in disease progression 31© Paradigm Publishing, Inc.

32. Dementia and Alzheimer’s Disease Drugs for Alzheimer’s Disease (continued) Mechanism of Action: inhibit enzymes that break down acetylcholine Routes: all are oral; rivastigmine is also transdermal Later in the disease antidepressants given for depression; benzodiazepines for anxiety and sleep problems; antipsychotics for hallucinations Side Effects (Cholinesterase Inhibitors): nausea, vomiting, agitation, rash, loss of appetite, weight loss, and confusion Cautions: tacrine has many drug interactions; if taking donepezil avoid NSAIDs, theophylline, and nicotine 32 © Paradigm Publishing, Inc.

33. Your Turn Question 1: What is the function of carbidopa when administered with levodopa? Answer: Carbidopa slows the breakdown of levodopa before it reaches CNS, so more of it enters the brain. Question 2: What is a restriction of donepezil? Answer: Patients with cardiac disease, liver problems, or Parkinson’s disease should not take donepezil. In addition, patients taking donepezil should avoid nonsteroidal anti- inflammatory drugs, theophylline, and nicotine. 33© Paradigm Publishing, Inc.

34. Attention-Deficit Hyperactivity Disorder (ADHD) About ADHD Is characterized by inattention, impulsivity, and hyperactivity Affects 3 to 10% school-aged children, whereas 5% of adults are affected Onset occurs by age 3 and is more prevalent in boys Drugs for ADHD Public controversy around the overdiagnosis and overmedication of ADHD For best results use drugs with behavioral therapy 34© Paradigm Publishing, Inc.

35. Attention-Deficit Hyperactivity Disorder (ADHD) Drugs for ADHD: CNS Stimulants Is the first-line drug therapy for children and adults Immediate-release products usually used first and then extended products are used for longer effects Mechanism of Action: enhance the release and block the reuptake of dopamine and norepinephrine in nerve cells Routes: all are oral; extended release also transdermal Side Effects (common): headache, stomachache, loss of appetite, weight loss, insomnia, and irritability Side Effects (severe): growth suppression in children, liver dysfunction (very rare), and jaundice 35© Paradigm Publishing, Inc.

36. Attention-Deficit Hyperactivity Disorder (ADHD) Drugs for ADHD: CNS Stimulants (continued) Cautions: Rare but serious (even fatal) cardiac abnormalities Caution for Adderall XR: do not use if cardiac abnormalities Are controlled substances (Schedule II)  No refills and limited supplies given at a time  Patients and their parents required to submit new written prescription for each refill Pharmacy technicians should remind patients or caregivers about refill requirements with first prescription 36© Paradigm Publishing, Inc.

37. Attention-Deficit Hyperactivity Disorder (ADHD) © Paradigm Publishing, Inc.37 Controlled Substances The CII on the label indicates that the agent is a controlled substance that must be stored separately from other inventory and locked

38. Attention-Deficit Hyperactivity Disorder (ADHD) Drugs for ADHD: Nonstimulant Drugs Atomoxetine  Is an alternative to CNS stimulants  Not a controlled substance  Mechanism of Action: increases norepinephrine and/or dopamine in brain and increases focus and curbs impulsivity  Side Effects (common): nausea, heartburn, fatigue, and decreased appetite  Side Effects (severe): liver injury Other nonstimulant drugs include antidepressants as well as clonidine and guanfacine for patients with tics or insomnia 38© Paradigm Publishing, Inc.

39. Drugs that Affect the Autonomic Nervous System Adrenergic Inhibitors Block alpha and beta receptors Causes increased heart rate and blood pressure, vasoconstriction, and delayed bladder emptying Adrenergic Inhibitors: Alpha Blockers Indications (primary): HTN and useful in men with BPH Side Effects (common): headache, dizziness, nausea, and fatigue/tiredness Side Effects (rare): priapism (erection longer than 4 hours) Cautions: may cause hypotension and heart palpitations; avoid alcohol or taking verapamil 39© Paradigm Publishing, Inc.

40. Drugs that Affect the Autonomic Nervous System Adrenergic Inhibitors: Beta Blockers Indications: HTN, angina, arrhythmias, and also recommended for heart attack patients  Less commonly used for migraine headaches, mild anxiety, and glaucoma Beta blockers make up the entire Class II of anti-arrhythmic agents Cardioselective beta blockers  Inhibit only beta-one receptors in the heart  Indications: angina and certain arrhythmias without causing bronchoconstriction 40© Paradigm Publishing, Inc.

41. Drugs that Affect the Autonomic Nervous System Adrenergic Inhibitors: Beta Blockers (continued) Side Effects (common): headache, dizziness, lightheadedness, nausea, and fatigue/weakness  Associated with increased incidence of depression  If difficulty breathing, seek medical help right away Routes: All are oral, except esmolol is IV only Caution: do not use beta-two blockers if impaired respiratory function like asthma or COPD Cautions: do not stop taking abruptly because this can cause severe cardiac problems; avoid oral decongestants if taking beta blockers for high blood pressure; some take with food or and others no food 41© Paradigm Publishing, Inc.

42. Drugs that Affect the Autonomic Nervous System Adrenergic Agonists Stimulate autonomic nervous system to produce sympathetic activity, such as increased heart rate and blood pressure, and bronchodilation Are vasopressors and sympathomimetics Vasopressors and Sympathomimetics Sympathomimetics  Mimic effect of stimulating sympathetic nervous system  Indications: respiratory distress, allergic reactions, sinus congestion, and glaucoma  Epinephrine  Indication: anaphylactic reactions  Routes: SC injection, IV, inhalation, and nasal 42© Paradigm Publishing, Inc.

43. Drugs that Affect the Autonomic Nervous System Vasopressors and Sympathomimetic (continued) Vasopressors  Increases the heart rate and blood pressure  Indications: cardiac arrest and shock situations Adrenergic Agonists Routes: IV, oral, and IM Side Effects (common): headache, excitability, fast heart rate, restlessness, and insomnia. Side Effects (rare): arrhythmia  Use these medications only when needed due to these side effects 43© Paradigm Publishing, Inc.

44. Drugs that Affect the Autonomic Nervous System Adrenergic Agonists: Cautions Pharmacy technicians may handle IV forms of these agents only if they supply the emergency room or critical care unit Mixed as needed in the unit for cardiac code situations  Mixed in dextrose solution Stocked in emergency drug kits that technicians maintain Epinephrine in autoinjector form (for life-threatening allergies) prescribed and dispensed in outpatient setting  Pharmacists should counsel patients how to inject into the thigh, not the buttocks  Do not use medication if expired 44© Paradigm Publishing, Inc.

45. Drugs that Affect the Autonomic Nervous System Anticholinergic Drug Effects Includes dry mouth, dry eyes, constipation, urinary retention, and blood pressure rises  Caused by blocking cholinergic activity in the parasympathetic system Caution: do not use anticholinergics if patient has urinary difficulty or bowel problems Opioid pain medications and bladder spasticity agents  Causes significant constipation and dry mouth Pharmacy technicians should be aware of interaction warnings 45© Paradigm Publishing, Inc.

46. Herbal and Alternative Therapies Ginkgo biloba  Has modest benefits for early Alzheimer’s disease  Causes serious side effects such as bleeding, seizures, and coma  Do not use if taking warfarin or aspirin for coagulation  Interacts with other prescription drugs, particularly anticonvulsants Ephedra (ma huang)  Is a dietary supplement banned in the U.S. in 2004  Can cause heart palpitations, tremors, and insomnia  Has caused deaths from cardiac arrest 46© Paradigm Publishing, Inc.

47. Summary A variety of antiepileptic drugs are used to control seizures Dopamine, agonists, anticholinergics, and COMT inhibitors are used to treat Parkinson’s disease CNS stimulants are used to treat ADHD Alpha and beta blockers used for parasympathetic actions Adrenergic agonists used to stimulate sympathetic actions Epinephrine is used in anaphylactic reactions Many drugs cause anticholinergic side effects 47© Paradigm Publishing, Inc.