1. Drugs affecting the Central-Nervous- System (CNS) & PAIN medications Chapters 12 and 13 MR160

2. Central Nervous System (the CNS) Stimulants – increase brain & spinal cord activity Depressants – decrease CNS activity, either specifically or generally (ANESTHESIA) Anti-convulsants (epilepsy) – goal is to depress the Motor Cortex Anti-parkinsonian – physical therapy used in early stages, then medication

3. CNS Stimulants ADD & ADHD therapy Adderall (amphetamine salts) - oral Concerta (E/R methylphenidate) – oral Daytrana (methylphenidate) – skin patch! Ritalin (methylphenidate) – oral Strattera (atomoxetine) – not controlled! Narcolepsy – Provigil promotes wakefulness

4. CNS Depressants (page 1) the STAGES of General ANESTHESIA are characterized by the level, or ‘depth’ Stage I – Analgesia: euphoria, amnesia Stage II – Delirium: increase involuntary muscle activity, irregular breathing, HTN, tachycardia Stage III – Surgical Anesthesia: until spontaneous respiration ceases, watch eyes & reflexes Stage IV – Medullary Depression: pupils fixed & dilated … no lid or corneal reflexes

5. CNS Depressants (page 2) HYPNOTICS and SEDATIVES Daytime sedation – small doses Sleep induction – larger doses CAUTION: mixing w/ alcohol, antihistamines morning ‘Hangover’ effect - greatly reduced by use of short-acting agent or lower doses Barbiturates – phenobarbital, secobarbital Non-barbiturates – Ambien, flurazepam

6. --- Restless Leg Syndrome --- DOPAMINE RECEPTOR AGONISTS to treat Restless Leg Syndrome (RLS) technically –NOT- CNS-depressants ! Mirapex (pramipexole) – also sometimes effective in Parkinsonism Requip (ropinirole) – Parkinsonism also, but may cause patient to fall asleep during daily activities!

7. Narcotic Analgesics OPIATES – derived from Opium (morphine, codeine) OPIOIDS – synthetic drugs with actions similar to opium/opiates The term ‘Narcotic’ includes both opiates & opioids (all are Controlled-substances) Most effective, but most ADDICTIVE analgesics CAUTION: tolerance, physical dependence

8. ------ OPIATES ------ MORPHINE SULFATE MS Contin – controlled release MSIR – immediate release Roxanol – oral solution & concentrate CODEINE * opiate or opioid OVERDOSE treatment = Narcan (naloxone) … ‘antidote’

9. ----- OPIOIDS ----- hydrocodone (Vicodin, Lortab, Norco) oxycodone (OxyContin, OxyIR) meperidine (Demerol) methadone – some history --- alternate dosage-forms --- fentanyl (Duragesic) – skin patches butorphanol (Stadol) – nasal spray

10. non-Narcotic analgesics acetaminophen (APAP) – Tylenol aspirin (ASA) --- chewable (Bayer, St. Joseph’s) --- buffered (Bufferin) --- enteric-coated (Ecotrin) tramadol (Ultram) – abuse potential ! propoxyphene (Darvon) – no longer on the market --abuse potential !

11. Drugs for MIGRAINE The TRIPTAN’s – not related to other analgesics ‘selective Serotonin Agonists’ Primarily effective on headaches that are vascular in nature …(not tension, cluster) MOA = constricts vessels, blocks nerves Imitrex (sumatriptan)-oral, injectable, nasal Axert (almotriptan)

12. EPILEPSY SEIZURE TYPES Tonic-Clonic (Grand Mal) – last 2 – 5 minutes, often followed by deep sleep Absence (Petit Mal) – 1 to 30 seconds Complex Partial – brief period of confusion Epileptic ‘equivalents’ – these episodes ‘resemble’ seizures … causes? ---tetanus ---hypoglycemia ---drug-withdrawal

13. Drugs for Epilepsy (Seizures) pg 113-115 ANTICONVULSANTS --Dilantin(phenytoin) --Tegretol(carbamazepine) BENZODIAZEPINES --Klonopin(clonazepam) – Ativan (lorazepam) -- Valium(diazepam) …others … Neurontin(gabapentin) – also for ‘neuralgia’ Lamictal(lamotrigine) – stabilizes neuronal membranes

14. PARKINSON agents PARKINSON’S DISEASE has no known cause, but seems to be related to depletion of dopamine in the brain “Secondary parkinsonism” may be caused by drugs (antipsychotic meds), toxins, or degenerative diseases (Alzheimer’s Disease) DOPAMINERGIC drugs --- levodopa/carbidopa (Sinemet) *see Table 12-4 for non-dopaminergic agents

15. Analgesics/Antipyretics Chapter 13 15

16. Analgesics & Pain What does “pain” look like? Pain evaluation is based on: – Location of pain – Duration – Intensity (1-10 scale) – Precipitating factors Pain may be Acute or Chronic: – Acute-short duration, responds to analgesics – Chronic-over time, less responsive to analgesics, tolerance 16

17. Types of Analgesics 3 Classes Opioid Non-opioid Adjuvant 17

18. Opioids & Opiates (Narcotics) OPIOID – a derivative of opium OPIATE – a synthetic chemical that produces an analgesic effect similar to opium. Examples: codeine, morphine (opioids) & oxycodone, fentanyl, meperidine (opiates) Reduces pain from any origin CAUTION: Tolerance and physical dependence Many are Schedule II controlled substances 18

19. Narcotic Analgesics Side Effects Euphoria, Sedation, Confusion Slowed reaction time Respiratory depression (in major overdose situations) Nausea, stomach upset Constipation “Idiosyncratic” (restlessness & agitation) 19

20. Drug Interactions with Narcotics Alcohol & other CNS depressants can lead to Respiratory depression *Sedatives *Antihistamines * benzodiazepines What drug is used to treat narcotic overdose? --- naloxone (Narcan) 20

21. Non-opioid Analgesics For mild to moderate pain 1. Not related to morphine 2. Work on peripheral nervous system, not the CNS (outside brain, spinal cord) 3. Do not produce physical dependency and tolerance 4. Do not alter consciousness or mental function 21

22. Non-opioid Analgesics low-intensity pain of inflammation and dull aches and vague pain Fever reduction Used as -analgesic -antipyretic, and/or - anti-inflammatory Not every drug in this class has all 3 effects 22

23. more info on Non-opioid Analgesics Typically the first step in pain control OTC or Rx Less expensive that Narcotics combined with narcotics to become Rx items: * Hydrocodone+APAP *Hydrocodone+ibuprofen *Oxycodone+APAP May be combined with non-narcotics to become Rx or OTC items: – ASA+caffeine -APAP+caffeine+butalbital (Fiorocet) 23

24. Salicylate Analgesics (aspirin”ASA”) Oldest non-opioid analgesics; not for children Four distinct therapeutic actions of ASA: – 1. Analgesic – inhibits prostaglandin release from damaged tissues – 2. Anti-inflammatory—reducing prostaglandin synthesis – 3. Anti-pyretic—reduces fever by causing vasodilation – 4. Anti-coagulant—prevents platelets from aggregating (clump) to decrease clot formation Beware GI effects, bleeding out 24

25. Acetaminophen (APAP) Analgesic & Antipyretic actions ONLY why use APAP over ASA? – Can be used in all ages (including children) – Rarely causes GI upset and bleeding – ok with anticoagulation medications Main disadvantage –liver damage w/ long term use, high dosages, or heavy alcohol use NMT (no more than) 3 grams (3000-mg) in 24 hours for adults with normal liver function! 25

26. Non-steroidal Anti-inflammatory (NSAID’s) ibuprofen (Advil®, Motrin®), naproxen (Aleve®) for mild to moderate pain for inflammatory conditions, dysmenorrhea, dental pain S/E- GI … stomach upset, bleeding Do not take with ASA, APAP or other NSAID’s. Time limits: 10 days for pain, 3 days for fever or as directed by MD 26

27. World Health Organization (WHO) Pain Ladder Mild Pain- take APAP, ASA, or NSAIDS around the clock Moderate Pain- add mild opioid (codeine or hydrocodone) Severe Pain-D/C mild Opioid, give strong opioid (hydromorphone or morphine), while continuing the non-opioid. [a word about meperidine (Demerol)] 27

29. Adjuvant Analgesic Used to enhance analgesic efficiency and prolong effects of opioid medications Typically not prescribed alone for pain Goal = Decreasing amount of pain medication while increasing pain control to reduce side effects of analgesics (ex: nausea) Examples: – Tricyclic Antidepressants (amitriptyline) *treat dull aches – Corticosteroids (prednisone) *treat inflammation – Anti-Convulsants (lorazepam, phenytoin, gabapentin) *treat sharp, shooting, or burning pain – Antihistamines (hydroxyzine) *treat anxiety/nausea 29

30. ------ THANKS ------ Have a great week! 30