Pharm-opiod analgesics
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- What are the major biologically active opoid compounds?
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metenkephalin
leu-enkephaln
dynorphin A and B - What are the 3 types of opoid receptors
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mu,kappa, delta
mu responsible for therapeutic and SE of morphine - What are the major effector systems of the mu receptor?
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1. potassium channels, agonists open K channels
2. ca channels, agonists reduce opening of voltage activated ca channels
3. adenylate cyclase inhibition - Psychotomimetic effects of opiods?
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opioid drugs bind to sigma and phencyclidine receptors resposible for these SE
-PCP receptor open configuration of a ca channel operated by a glutamate receptor (NMDA type)-functions in synaptic plasticity and momory encoding
***endogenous opiods no affinity for sigma or PCP sites - How do opoids do antitussive effects?
- Codeine-- involves the regular opiod receptors, but Dextromethorphan uses other site not reversible by nalaxone
- What are the properties of morphine?
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*heavily hydroxylated, not extremely lipid-soluble
* modest affinity for mu receptor - How are other opoids related to morphine?
- Codeine and Heroin are prodrugs converted to morphine
- What are the major effects of morphine in the CNS?
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1. Analgesia: SC and supraspinal structures
2. Respiratory depression: medulla oblingata and pons
3.nausea and emesis, cough: depresses cough reflex; N/V from chemotrigger zone and vestibular zone
4. neuroendocrine system (minor)
5. Pupils: constriction
6. Excitatory effects: convulsions at high does - How does morphine produce analgesia?
- 1. SC: descending supraspinal inhibiton: mimicks endogenous opiods; Descending paths (serotonin and NE) from pons potentiate spinal analgesia by opiates.
- What are the pharmacolgical implications of the descending supraspinal tracts.
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1. local opiods in SC cause analgesia
2. TCAs and SSRIs potentiate opiod analgesia
3. By stopping productions of PGs, NSAIDs potentitate effects of opiods - Describe the analgetic effect of morphine?
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1. no LOC
2.pain decreased by morphine, but other modalities not
3. continous dull pain better than sharp intermittent pain
4. Morphine alleviates both sensory and the affective component of pain, need anxiolgytics to dec. pain induced anxiety - How does morphine decrease respiratory drive?
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detectable at low dose and increasies with does.
-Reduces the response to increased PCo2; in OD major respiratory drive is carotid chemoreceptors - What are the neuroendocrine effects of morphine?
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1. hypothermia, lowers set point
2. dec. urinary output, inc. adh release
3. hyperglycemia-slight
4. dec release of pituitary gonadatrophic hormones - how does morphine effect the pupils
- central effect on Edinger-Westphal nucleus; "pin-point" pupils are a sigh of toxiticy not change with tolerance
- What are morphine's effects on the heart
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1. peripheral vasodilation, dec sympathetic tone and baroreflex, release histamine
2. postural hypotention
3. dramatic hypotension in hypovolemic pt that is dependent on high sympathetic output - What are the GI and urinary effects of morphine?
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1. acts on intrinsic nerve plexus of GI tract: decrease peristaliss, causes increased tone of circular muscles
2. Atropine partially antagonized the spasm of morphine and helps with perpulsion
3. inc. tone of external urethral sphincter - What are the pharm properties of morphine?
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1. abs from GI, nasal mucosa, lungs,SQ, IM,IV
2.poor penetration of CNS
3. half: 4hrs
4.Conjugated in liver
5. 90%urinary/10%biliary; GFR effects - What are the signs of acute morphine poisening?
- sx: pinpoint pupils, coma, depressed respiration, bp falls from hypoxia, temp low, and muscles flaccid, convulsion
- How do you treate morphine toxicity?
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1. ventilation
2. repeat injections of naloxone - What is codeine?
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semisynthetic morphine; oral and IV/IM.
Well absorbed
slowly demethylated and longer half - What is hydromorhpone?
- more potent than morphine; Dilaudid, IM or PO
- What is oxymorphone?
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more potent than morphine
IM or PO - What is oxycodone and hydrocodone?
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Used in combo with other drugs: antitussive, antipyretics/NSAID/
Equipotent with morphine, better oral absorption
*Slow release oxycodone=oxycontin=wide distribution - What is heroin?
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Pro-drug of morphine and drug of abuse
*Rapid action by penetrtion of BBB. - What is levorphanol?
- Oral/paretental potency > than morphine; like morphine otherwise
- What are the phenylpiperidine derivatives?
- Meperidine and diphenoxylate
- What is Meperidine
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DEMEROL
*phenylpiperidine derivative
**All routes; equianalgesic with morphine x less spasmogenic, less constipation and retention; not inhibit cough
*Preferred opiate for Obstetrics; less respiratory depreesion in neonates; not change oxytocin in labor - What is Diphenoxylate
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phenylpiperidine derivatve
**insoluble
Treat: diarrhea in combo with atropine; no CNS effects - What is Fentanyl?
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80x more potent than morphine
Anesthetic in combo with droperidol (neuroleptic) - What are the properties of methadone?
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*oral/parenteral better availb then mor
*met liver; ex bile and urine
*long half 15hrs
*identical to morphine pharmaco/does have tolerance and dependence - What is methadone used for?
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1. Relief of moderate to severe pain; superior to morphine b/c less withdrawal
2. replacement therapy for opiod addtiction - What is propoxyphene?
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DARVON
*close to methadone
*less effective than codein
*relief of mild-mod pain
*less abuse than codein; toxicity keeps from high doses
***Rx in lieu of codeine - What is 1-acetylmethadol?
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Depot opiate; long lasting; produces methadone
1. used to tx opiate addcition; q2-3 days - What are the properties of Pentazocin?
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-weak antagonist of mu receptor and powerful kappa agonist
-analgesia like morphine; but less respiratory; but get high incidence of dysphoria
-less potent than morphine - What are the SE of Pentazocin?
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anxiety, disturbing thoughts, nightmares, hallucinations
-reduces morphine analgesia; can make withdrawal
-high dose: inc BP and HR; in plasma NE and Epi - What are the opiate antagonists
- naloxone (iv)and naltrexone (oral)
- What are the effects of opiate antagonists in the presence of opiods?
- naloxone antag all effects x those not at opiate receptors; can produce withdrawal
- What is dextromethorphan?
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methoxylated form of dexrorphan; antitussive
-no analgesi potency; no affinity at opiod recptor; minimal txoicty
CNS only at very high doese - What are the therapeutic uses of opiods?
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1. Analgesia
2.Diarrhea
3. Cough
3. Anesthesia - What are the 3 main criteria for analgesia use of opiods; what do you use?
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1. type of pain
2. Require duration of action
3. Intensity of pain - What are the long-acting opiods
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methadone
morphine
oxymorphone - What are the short acting opiods
- meperidine; short surgery or obstetrics
- How are opiods usedin anesthesia?
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1. balanced anesthesia:
Ultrashort Barbituate + NO2+ opiod analgesic (fentanyl, sufentanyl)
2. Neuroletanaglgesia:
Droperidol + fentanyl=no LOC
3. neuroleptanesthesia:
droperidol, neuroleptic,+ fentanyl+ NO2 - What is the treatment for opioid abuse?
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1. Replacement therapy (methadone, acetyl-methadol)
2. antagonists (naltrexone-long acting-good in early phase)
3. Clonidine= reduces aversive quality of physical withdrawal period and attenuated intensity of autonomic componen; dec. cravings
4. psychotherapy - What drug used for acute pain?
- opiates of increasing potency depending on intensity
- What drugs used for chronic non-malignant pain (inflamm)
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Not severe: NSAIDS only
Sever: add oral opiate + NSAID - What use for chronic pain of neoplastic origin?
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NSAID + Opiate of adequate poetncy
Very sever: Fentanyl patch or opiate IV
Can add D-amphetamine to enhance opiate - What drug for neuropathic pain?
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NSAIDS, amitryptiline, carbamezepine, some phenothiazines, gabapentin
IV Lido
Opiates, but need soemthing else too - MI
- Morphine or Meperidine
- Complex regional pain syndromes what drug?
- nerve block with local anesthetics and/or a1-antagonist (prazosin, phenoxybenzamine may help)
- What drug for acute pulmonary edema due to LVF?
- morphine if ventilation controlled
- What durg obstetric analgesia?
- Meperidine if ipiate needed
- What drug for GI and UTI
- Meperidine
- What drug for Anesthesia
- Keterolac IM (NSAID) and or opiate agonist