CNS Drugs Student Version PDF

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

Central Nervous System Medications CHAPTERS 12 &14 CNS neurotransmitters Acetylcholine Dopamine (memory & (“Joy” & motor learning) 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) Only 2% reaches the brain Levodopa: Food delays absorption, esp Dopamine meals high in protein replacement Short T1/2 of 1-2 hours Great at first, then… “Loss of Effect” is common by the time it metabolizes its no longer effective  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 This Photo by Unknown Author is licensed under CC BY-NC-ND pill  N/V Dyskinesis (involuntary movt) Cardiovascular (orthostatic hypotension, dysrhythmias) Psychosis (hallucinations, vivid Levodopa: dreams, paranoia, impaired impulse Adverse control) Effects Harmless darkening of sweat & urine 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 Consideratio Darkens sweat & urine ns Report “Loss of Effect” 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 receptors in the Pramipexole: 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, weakness, sleep Pramipexole: changes Pramipexole + Adverse levodopa/carbidopa: orthostatic Effects hypotension, dyskinesias, 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 Phenytoin: 10-20 mcg/mL Traditional Highly protein bound (95%) AED Metabolism prototype Liver easily overwhelmed by this drug = toxic levels 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: Phenytoin Nystagmus, sedation, ataxia, Adverse diplopia, cognitive impairment Effects ◦Gingival hyperplasia ◦Rash ◦Teratogenic ◦Lots of drug interactions Other Traditional AEDs Valproic Acid Phenobarbital MOA: blocks Na and Ca MOA: enhances & mimics channels, may potentiate GABA. Widely used for all major the effects of GABA. seizure types, also for bipolar A barbiturate (sedation) disorder and migraines. Many adverse effects GI effects common, rare hepatoxicity, SERIOUS teratogen  MOA: Blocks overactive sodium channels No drug level monitoring required Adverse Effects Oxcarbaze CNS (dizziness, drowsiness, pine: Newer double vision, nystagmus, AED headache, ataxia) prototype Rare – hyponatremia Serious skin reactions (SJS, toxic epidermal necrolysis) Teratogenic Lots of drug interactions Status Extended period of continuous Epileptic seizure activity us MEDICAL EMERGENCY Goal is to intervene in the first 5 minutes Treatment: Secure airway, give IV This Photo by Unknown Author is or po benzodiazepine, followed by licensed under CC 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 (oral disintegrating tablets) ↑ 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 Defecation (diarrhea, Effects with dehydration) Nursing Gastric upset (dyspepsia) Consideratio 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 Causes: epilepsy, hypocalcemia, chronic muscle or muscle pain syndrome, localized muscle injury group Spasticity: Prolonged muscle Increased muscle tone, spasms, decreased tightness or fine motor control/dexterity, usually also contraction, hyperactive DTRs characteristic finding Causes: Multiple sclerosis, cerebral palsy, in movement stroke, traumatic spinal cord lesions disorders of CNS origin Medications for spasm and spasticity Class Drug Use Centrally acting Cyclobenzaprine Spasm muscle relaxers Centrally acting Baclofen Spasticity muscle relaxers Direct acting muscle Dantrolene Spasticity relaxer Benzodiazepine Diazepam Spasticity Treatment of muscle spasms Physical Medications Local heat Therapy Acetaminoph Stretching, Heating pad, en flexibility whirlpool or Ibuprofen exercises, warm baths Cyclobenzapr TENS ine 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 Dantrolene - acts directly on within the spinal cord to skeletal muscle suppress hyperactive reflexes PO dosing: used for spasticity Diazepam (Valium) – a benzodiazepine IV dosing: malignant hyperthermia Main adverse effect of these two is sedation Not as sedating 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 LO PE D U S I N G : A S S ES S M E N T T EC H N O LO G I ES I N ST I T U T E. ( 2 0 2 3 ). PHA R M AC O LO GY M A D E E ASY 4. 0 A S S ES S M E N T T EC H N O LO G I ES I N ST I T U T E. ( 2 0 2 3 ). R N PH A R M AC O LO GY FO R N U R S I N G E D I TI O N 9. 0