Neuroanatomy-Narcotics Flashcards
Opiates
Heroine and Codine are both actually pro-drugs of Morphine.
Mechanism:
- Inhibit cAMP, activate K channels -> Hyperpolarize (post synapse). ALSO inhibit Ca channel activation on presynapse. -> Depresses Neurotransmitter (NE, DA,5-HT,ACh,Substance P)
Uses:
-Analgesia, Preanesthetic Medication (sedative), Pulmonary Edema, Anesthesia, Spinal Analgesia, Cough, Diarrhea (causes constipation), Recreation
Opiopeptins:
- Endorphin(POMC), Enkephalins, Dynorphin (Proenkephalin A and B) (different places in the body, so activate different things)
- POMC is pain and Pancrease
- Proenkephalin A and B: Widespread pain, motor, and behavior.
Benefits:
Analgesia: Mu Receptors change perception of pain, change reaction to pain, raise threshold for pain
- Side Effects: Drowsiness, impairment. If lots of pain, side effects aren’t that bad. If not in that much pain, then side effects are worse.
- Mechanism:
1. ) Ascending Pathways-spinothalamic tract (blocked)
2. ) Descending Pathways-bulbospinal pathways inhibit pain. GABA normally inhibits this pathway -> But GABA is now blocked, so it activates inhibition of pain.
Euphoria: Mu and Delta receptors inhibit GABA (see image)
Dysphoria: Kappa receptors on the Mesolimbic dopamine neurons stop Dopamine production (see image)
Alter Hypothalamic Heat Regulatory Mechanism (turn down temp)
Miosis- (mu and kappa)- Stimulation (disinhibition) of PNS innervation of pupil (pin point pupils)
Antitussive (anti-cough) and Anti-Nausea effects. These are unclear how they work. Stimulation of medullary cough centers, and CTZ respectively.
Respiration: Suppresses control rhythm, and CO2 centers. However, Hypoxic Stimulation Intact - O2 —> apnea
Bronchoconstriction: Depression of respiration and suppression of cough reflex. Not good for Asthmatics.
Hypotension when standing.
May Increase CSF Pressure, so not for head injuries.
Dyspnea/Pulmonary Edema-Left Ventricular Failure, Reduction in fear/anxiety, Reduction in peripheral, resistance. unclear if anything else is at work.
Tolerance: Mostly in the CNS. Everywhere else, its not a major issue.
Antagonists- substitutions at 17 position (or at 14).
Morphine
first pass oral ~ 25% bioavailable.
IV Route more lipophilic- more penetrance of BBB
Metabolism: Glucuronidation of the 3 or 6- OH. Morphine 6-Glucuronide is a potent analgesic (more potent)
Codeine
first pass oral ~ 60% bioavailable.
IV Route more lipophilic- more penetrance of BBB
- less potent than morphine
- 10% metabolized to morphine-accounts for analgesia!
- oral- with aspirin or acetaminophen
- antitussive (cough) in its own right
Fentanyl/Sufentanil
redistribution (crosses BBB well BUT turns off quickly via lipophilic)
- analgesia >> morphine
- short duration
- useful in anesthesia
- postoperative analgesia
Methadone
Strong Opiate Agonist
- similar analgesic action as morphine
- better bioavailability than morphine
- analgesic and addiction therapy
Meperidine
- less potent but higher availability than morphine
- antimuscarinic actions
- less constipating
- not antitussive (which is not a Mu receptor)
- no effects on labor
Propoxyphene
- related to methadone
- potency between aspirin and codeine
- no antitussive effect
- oral- with aspirin, acetaminophen
Diphenoxylate/Loperamide
- not analgesic (low Mu receptor effect)
- low abuse potential
- antidiarrheal activity (main function)
Mixed Drugs
Developed for analgesia with less liability
kappa agonists
mu antagonists or weak agonists
- This class of drugs is basically a Kappa agonist only with little to no Mu effects.
Pentazocine
Mixed drug
Compared to Morphine:
-Less potent, addictive liability
-Precipitates withdrawal
-Similar respiratory depression
Butorphanol
Mixed Drug
- Similar to Pentazocine
- kappa agonist
- mu antagonist
-More potent than morphine
-Increases in cardiac workload, Nausea, sweating, etc.
Buprenorphine
- Partial mu agonist
- kappa antagonist?
- More potent than morphine
- Can precipitate withdrawals
-Addictive Liability
_Might be a question on this one. Significant pain, but don’t want to give Opiate. Give a Mixed agonist. Mu agonist is better than a Kappa Agonist for withdrawal. _
Naloxone
Opiate Antagonist
- Rapid Acting
- Short Duration, Multiple Doses
Treatment:
Careful with Addicts on withdrawal. Use small amounts at first and watch respiration, etc.
Naltrexone
Opiate Angatonist
-Orally Effective
-Treatment for Alcoholism (longer acting than Naloxone so not as good for opiate and better for alcoholism)
-Liver Dysfunction
Opiate Toxicity
Triad
- Pinpoint Pupils
- LOW Respiratory Rate
- Stuporous –> Comatose
Death- Respiratory Failure
