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N402 1 Nervous system Central Brain Peripheral Spinal cord Somatic Motor neurons Sensory neurons Autonomic 2 Autonomic Nervous System Sympathetic (fight or flight) Parasympathetic (rest and digest) Adrenergic receptors Cholinergic receptors 3 Stimulate SNS = adrenergic agonists Inhibit SNS = adrenergic antagonists Stimulate PSNS = cholinergics Inhibit PSNS = anticholinergics 4 Adrenergics = sympathomimetics Andrenergic antagonists = sympatholytics Cholinergics = parasympathomimetics Anticholinergics =parasympatholytics (aka cholinergic blocking agents) 5 Identification of the correct medication requires Identifying the maladaptive or undesired response Determine the source Do we want to interrupt the source? Or, Do we want to stimulate a counteracting source? 6 Intense anxiety Other anxiety disorders Generalized anxiety disorder Phobias Panic disorder Social anxiety disorder Obsessive compulsive disorder PTSD 7 Limbic system Emotion Behavior Motivation Long term memory Reticular system Sleep-wake transition Attention 8 Tricyclic antidepressants (TCAs) Monamine oxidase inhibitors (MAOIs) Avoid use with heart disease, asthma Example: Amitriptyline (Elavil) Avoid use with diabetes (potentiates insulin) Selective serotonin reuptake inhibitors (SSRIs) Safer than other classes Can cause sexual dysfunction Examples: Escritalopram (Lexapro), Citalopram (Celexa) 9 Preferred drugs for many anxiety disorders and for insomnia Less physical dependence Do not produce respiratory depression Short term treatment of insomnia Examples: Diazepam (Valium), Lorazepam (Ativan) 10 The treatment is directed to the cause of seizure: Infection Neoplasm Trauma Pediatric disorder Metabolic disorder Vascular disease 11 Disturbance of brain electrical activity Affects consciousness, motor activity, sensation May be either generalized or partial 12 Produced by entire brain Symptoms Generalized tonic-clonic (Grand-mal) Unconsciousness, convulsions, general rigidity Absence Brief loss of consciousness Myoclonic Sporadic jerking movements Clonic Repetitive jerking movements Tonic Muscle stiffness and rigidity Atonic Loss of muscle tone 13 Produced by small part of brain Symptoms Simple: Motor Sensory Psychological Jerking, muscle rigidity, spasms Unusual sensations of 5 senses Memory or emotional disturbances Complex Automatisms such as lip-smacking, fidgeting, chewing, walking Partial with secondary generalization Initially appropriate, self-preserving actions that evolve into loss of consciousness and convulsions 14 Stimulate influx of chloride ions (associated with GABA) Delay influx of calcium Delay influx of sodium 15 Gamma-amniobutyric acid Primary inhibitory transmitter in the brain Signals other cells to subdue them Examples: Phenobarbital (Luminal), Diazepam (Valium) 16 Phenytoin (Dilantin) is oldest and most commonly prescribed antiseizure drug Narrow safety range Frequent monitoring of drug level required Can trigger seizures if used with TCAs Valproic acid (Depakene, Depakote) Preferred for absence seizures Useful in bipolar disorder Used alone or in combination 17 Seizures may be precipitated or enhanced by… Reduction or inadequate treatment with antiepileptic drugs (AEDs) Withdrawal of alcohol or other sedative agents Administration of central nervous system stimulants and anticholinergics including over the counter antihistamines Most dopamine blocking agents Newer antipsychotics, particularly clozapine (Clozaril) Antidepressants, especially buproprion (Wellbutrin) Immune suppressants such as cyclosporine Antibiotics such as quinolones or imipenem/cilastatin Toxins (various) 18 Vital signs, mental status Drug levels, hepatic function Level of consciousness Emotional status—increased risk of depression Assess gums and oral hygiene—gingival hyperplasia) 19 “Depressed affect” At least 5 of 10 common symptoms of depression Symptoms last a minimum of 2 weeks Depression may be… Clinical depression Situational depression Postpartum depression Seasonal affective disorder Psychotic depression 20 Some cultures affix a greater stigma to depression than others Depression may not be discussed or acknowledged May be acknowledged in terms of physical (somatic) manifestations only Consider undiagnosed depression particularly in Asian, Hispanic cultures. 21 Physical assessment ECT if unresponsive Complete history Pharmacotherapy Counseling Behavioral therapies 22 TCAs SSRIs Atypicals MAOIs Inhibit reuptake of norepi and serotonin Primarily used for major depression Orthostatic hypotension can occur Rarely, cardiac dysrhythmias E.g., Amitriptyline (Elavil) Slow the reuptake of serotonin Major advantage is fewer side effects Beneficial effects occur more quickly Sexual dysfunction in ≤ 70% both men and women E.g., Citalopram (Celexa), Escitalopram (Lexapro). Sertraline (Zoloft) Some slow reuptake of serotonin and norepi Also affect level of dopamine Shorter half-life than TCAs E.g., Buproprion (Wellbutrin) Buproprion lowers seizure threshold Limit breakdown of norepi, dopamine, serotonin in the CNS High degrees of drug-drug and food-drug interactions (foods containing tyrine, cheeses, sausage, tap beer, sauerkraut, red wine, soy sauce) → hypertensive crisis 23 May occur when SSRI taken with another medicine affecting the reuptake of serotonin E.g., MAOI, TCA, Lithium Serotonin accumulates in the body Mental status changes HTN Tremors, ataxia Hyperpyrexia, sweating 24 May be due to dysfunction of dopamine, norepinephrine, or serotonin Easy distractibility Difficulty focusing on 1 task at a time Difficulty remembering Inability to stay still 25 Mainstay is CNS stimulants to increase alertness and focus May create increased hyperactivity Adverse effects: insomnia, nervousness, anorexia, weight loss E.g., amphetamine-racemic mixture (Adderall) amd methylphenidate (Ritalin) Nonstimulants are available May be less effective, used adjunctively 26 Acute pain is limited; chronic pain ≥6 months Nocioceptive (Tissue damage) Psychogenic (caused, increased by psychological factors) Neuropathic (Nerve damage) 27 Opioids Non-opioids May be naturally occurring or synthetic Classified as highly effective or moderately effective Constipation with both classes Respiratory depression with highly effective types NSAIDs Combination products Hepatotoxicity from nonnarcotic component E.g., Vicodin (hydrocodone and acetaminophen) and Tylenol with codeine 28 Tylenol #2 Tylenol #3 Acetaminophen 300 mg Codeine phosphate 15 mg Acetaminophen 300 mg Codeine phosphate 30 mg Tylenol #4 Acetaminophen 300 mg Codeine phosphate 60 mg 29 Opioid intoxication is a medical emergency because of severe respiratory depression Opioid antagonists block opioid activity Can reverse symptoms of addiction, toxicity, and overdose Naloxone (Narcan) given IV 0.4 to 2 mg every 2-3 minutes up to 10 mg Also available intranasal 30 Tolerance develops quickly More drug is required to achieve the euphoria Withdrawal symptoms can persist for a week or more Agitation, anxiety, insomnia Muscle aches, abdominal cramping Nausea, vomiting, diarrhea Oral methadone limits withdrawal symptoms without euphoria Allows patient to return to functional activity Continued use required until patient elects to enter withdrawal treatment program 31 Cyclooxygenase enzymes Released in response to inflamed tissue Inhibition of COX can provide relief from symptoms of inflammation and pain COX-1 is found to protect gastric mucosa Therefore, inhibition of COX-1 is not always desirable Inhibition of COX-2 is desirable to provide pain relief 32 Aspirin, ibuprofen available OTC Aspirin has greater anti-platelet activity Both can cause GI bleeding; aspirin has a greater risk Ibuprofen may be given parenterally 33 Tramadol (Ultram) weak opioid activity Inhibits reuptake of serotonin and norepinephrine Tramadol! 34 Alzheimer’s (loss of brain function) Parkinson’s (loss of dopamine) Multiple sclerosis (demyelination of neurons) 35 36 Drugs are intended to restore dopamine and acetylcholine balance in the brain Levodopa is a precursor of dopamine synthesis Creates increased synthesis of dopamine Levodopa can cross the blood-brain barrier and enter CNS Often used in combination with carbidopa to enhance effects Example: levodopa-carbidopa-entacapone (Stalevo) 37 Inhibit the effect of acetylcholine’s stimulation of neurons to decrease symptoms Not as effective as dopaminergic drugs for severe Parkinson’s Used early in disease Sedation, tachycardia, hypotension Example: benztropine (Cogentin) 38 39 Goal is to increase effects of acetylcholine to enhance function of brain synapses Acetylcholine is broken down by acetylcholinesterase Therefore, drugs are designed to inhibit acetylchoninesterase Example: Donepezil (Aricept) Useful in mild-to-moderate disease Results evident after 6 months Does not reverse disease GI, CNS, and musculoskeletal side effects 40