CNS Drugs Student Version PDF

Central Nervous System Medications CHAPTERS 12 &14 CNS neurotransmitters Acetylcholine Dopamine (memory & learning) (“Joy” & motor control) GABA Glutamate (memory) (memory & movement) ...

Central Nervous System Medications CHAPTERS 12 &14 CNS neurotransmitters Acetylcholine Dopamine (memory & learning) (“Joy” & motor control) GABA Glutamate (memory) (memory & movement)  Parkinson’s Disease treatments Too little dopamine & Too much acetylcholine Two types of medications: ◦ Dopaminergic agents (more commonly used) ◦ Directly or indirectly activate dopamine receptors ◦ Anticholinergic agents ◦ Blocks receptors for acetylcholine This Photo by Unknown Author is licensed under CC BY-NC-ND  MOA: increases the amount of available dopamine PRODRUG (converted into active form after crossing BBB) Levodopa: Only 2% reaches the brain Dopamine Food delays absorption, esp meals high in replacement protein Short T1/2 of 1-2 hours Great at first, then… “Loss of Effect” is common  carbidopa/levodopa (Sinemet) Works as a crossing guard MOA: Prevents decarboxylase action Allows us to give a lower dose of levodopa Only available in a combo pill This Photo by Unknown Author is licensed under CC BY-NC-ND  N/V Dyskinesis (involuntary movt) Cardiovascular (orthostatic hypotension, dysrhythmias) Psychosis (hallucinations, vivid dreams, Levodopa: paranoia, impaired impulse control) Adverse Harmless darkening of sweat & urine Effects Drug Interactions Bad: meds that block dopamine receptors Good: Anticholinergics block acetylcholine  Education: Take without food GI upset? Take with non-protein meal Requires multiple doses in a day Nursing Darkens sweat & urine Consideratio Report “Loss of Effect” ns Rise slowly from supine or sitting Report any new tremors/twitching Report palpitations, racing heart Report hallucinations, paranoia Questions so far?  MOA: Directly activates dopamine Pramipexole: receptors in the brain Dopamine Often used first line Receptor Used alone in early stages Agonist Used with levodopa/carbidopa in advanced stages  Adverse Effects Produced by receptor activation pramipexole alone: nausea, dizziness, Pramipexole: weakness, sleep changes Pramipexole + levodopa/carbidopa: Adverse orthostatic hypotension, dyskinesias, Effects hallucinations Sleep Attacks Impulse control disorders / Compulsive behaviors  Education: OK to take with meals Nursing Rise slowly from supine or sitting Consideratio ns Report “Sleep Attacks” Report any impulse control concerns Questions about PD drugs?  Drugs for Seizures This Photo by Unknown Author is licensed under CC BY Antiepileptic drugs: AEDs Four ways AEDs work 1. Suppression of sodium influx in cell membranes (decrease ability of neurons to fire at high frequency) 2. Suppression of calcium influx in axon terminals (blocks channels to suppress transmission) 3. Antagonism of glutamate (a neurotransmitter) 4. Potentiation of GABA (a neurotransmitter) Goal is to decrease focal epileptic activity and prevent spread to other areas of the brain Adherence is very important for achieving therapeutic response  Traditional and Newer antiepileptic drugs Traditional Newer Phenytoin (sodium channel suppression) Oxcarbazepine (sodium channel suppression) Phenobarbital (potentiates GABA) Valproic acid (sodium & calcium channel suppression, potentiates GABA) Less expensive $ More expensive $$$ Teratogenic Safer in pregnancy More interactions Less interactions More Adverse Effects Less Adverse Effects  MOA: Inhibits the sodium channels of hyperactive neurons A first-line medication & most widely used NTI drug – therapeutic levels 10-20 mcg/mL Highly protein bound (95%) Phenytoin: Metabolism Traditional Liver easily overwhelmed by this drug = AED toxic levels prototype Half life is dose dependent (8-60 hrs) CYP Enzyme inducer  CNS effects ◦ Levels 10-20: Mild effects – headache, drowsiness, irritability ◦ Levels > 20 mcg/mL: Nystagmus, Phenytoin sedation, ataxia, diplopia, cognitive Adverse impairment Effects ◦ Gingival hyperplasia ◦ Rash ◦ Teratogenic ◦ Lots of drug interactions Other Traditional AEDs Valproic Acid Phenobarbital MOA: blocks Na and Ca channels, may MOA: enhances & mimics the potentiate GABA. Widely used for all major seizure types, effects of GABA. also for bipolar disorder and migraines. A barbiturate (sedation) GI effects common, rare hepatoxicity, Many adverse effects SERIOUS teratogen  MOA: Blocks overactive sodium channels No drug level monitoring required Adverse Effects Oxcarbaze CNS (dizziness, drowsiness, double pine: Newer vision, nystagmus, headache, ataxia) AED Rare – hyponatremia prototype Serious skin reactions (SJS, toxic epidermal necrolysis) Teratogenic Lots of drug interactions Status Extended period of continuous seizure Epileptic activity us MEDICAL EMERGENCY Goal is to intervene in the first 5 minutes Treatment: Secure airway, give IV This Photo by Unknown Author is licensed under CC BY benzodiazepine, followed by antiepileptics Questions about AEDs? Questions? Drugs for Alzheimer’s Disease Patho is unknown very low levels of acetylcholine Ideal Drugs vs. drugs we have Two major drug classes ◦ Cholinesterase inhibitors ◦ NMDA antagonists This Photo by Unknown Author is licensed under CC BY-NC  z MOA: Prevents breakdown of acetylcholine by the acetylcholinesterase enzyme in the CNS Benefits: improved QOL, memory, Donepezil: reasoning Cholinesterase Does not delay disease progression inhibitor (#1) Highly protein bound = long half life Available as ODT ↑ acetylcholine causes cholinergic effects  Salivation Lacrimation Cholinergic Urination side effects: SLUDGE Defecation Gastric upset Emesis  z MOA: Prevents breakdown of acetylcholine by the acetylcholinesterase enzyme in the CNS Rivastigmine: Benefits: improved QOL, memory, Cholinesterase reasoning inhibitor (#2) Does not delay disease progression Available as transdermal patch ↑ acetylcholine causes cholinergic effects  SLUDGE Urination (dehydration) Adverse Effects with Defecation (diarrhea, Nursing dehydration) Consideratio Gastric upset (dyspepsia) ns Emesis (N/V) CV (bradycardia  fainting, falls)  z  MOA: Blocks NMDA receptors and prevents excessive calcium accumulation in the neurons Benefits: slows decline, may improve symptoms Memantine: NMDA Antagonist Does not modify the underlying disease process Minimal adverse effects Potentiated effect: donepezil + memantine Questions about Alzheimer’s meds? Drugs for muscle spasm and spasticity Spasm: involuntary Pain, reduced function contraction of a muscle Causes: epilepsy, hypocalcemia, chronic pain or muscle group syndrome, localized muscle injury Spasticity: Prolonged muscle tightness or Increased muscle tone, spasms, decreased fine motor contraction, control/dexterity, usually also hyperactive DTRs characteristic finding in Causes: Multiple sclerosis, cerebral palsy, stroke, movement disorders of traumatic spinal cord lesions CNS origin Medications for spasm and spasticity Class Drug Use Centrally acting muscle Cyclobenzaprine Spasm relaxers Centrally acting muscle Baclofen Spasticity relaxers Direct acting muscle Dantrolene Spasticity relaxer Benzodiazepine Diazepam Spasticity Treatment of muscle spasms Medications Physical Therapy Local heat Acetaminophen Stretching, Heating pad, Ibuprofen flexibility whirlpool or Cyclobenzaprine exercises, TENS warm baths Drug for Muscle Spasm Cyclobenzaprine: Centrally-acting muscle relaxant Therapeutic uses: ◦ Relief of pain from acute muscle spasm, to increase ROM ◦ Not effective to treat spasticity Adverse effects ◦ CNS effects (drowsiness, dizziness, sedation) ◦ Anticholinergic effects (dry mouth, blurry vision, urinary retention, constipation) ◦ (mnemonic: Can’t pee, can’t see, can’t spit, can’t poop) Interactions ◦ Alcohol and other CNS depressants (additive effect  increased drowsiness) ◦ Antidepressants (risk for serotonin syndrome) Tolerance and dependence can develop Drugs for Spasticity Managed by a combo of drugs and physical therapy Baclofen – CNS drug, acts within Dantrolene - acts directly on skeletal the spinal cord to suppress muscle hyperactive reflexes PO dosing: used for spasticity Diazepam (Valium) – a benzodiazepine IV dosing: malignant hyperthermia Not as sedating Main adverse effect of these two is sedation Main adverse effect is dose-related hepatotoxicity  Questions? M AT E R I A L S I N T H I S C O U R S E W E R E D E V E L O P E D U S I N G : ASSESSMENT TECHNOLOGIES INSTITUTE. (2023). PHARMACOLOGY MADE EASY 4.0 ASSESSMENT TECHNOLOGIES INSTITUTE. (2023). RN PHARMACOLOGY FOR NURSING EDITION 9.0