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60 Cards in this Set
- Front
- Back
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Where are neuropeptides synthesized?
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in the cell bodies
they are packaged into large dense core vesicles in the Golgi apparatus and transported down the axon to the nerve terminal |
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What is the difference in elimination of neuropeptides versus that of classical neurotransmitters?
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Elimination of neuropeptides from the synapse is slower and their effects are longer
Neuropeptides are NOT taken up by either the presynaptic nerve terminal or glia. They are eliminated from the synapse by diffusion and metabolism by proteolytic enzymes in the extracellular fluid |
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What opiate peptide is known as "endogenous morphine"
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Beta-Endorphin
This protein includes Met-ENK |
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What ENK do the dynorphins contain?
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Leu-ENK
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Where are most enkephalin neurons found?
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in interneurons in local circuits
widely distributed in CNS Major projection pathway is from the caudate nucleus to the globus pallidus. ENKs are also found in adrenal medulla and enteric nervous system. |
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ENKs are found in areas that modulate what? (5)
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1. Nociception (SC, spinal trigeminal N., pariaqueductal gray)
2. Affective behaviors (limbic) 3. Motor control (cuneate N., globus pallidus) 4. Autonomic fxn (medulla) 5. Neuroendocrine fxn (hypothalamus) |
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Cell containing Beta-endorphin are localized where?
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hypothalamus and medulla (NTS)
Beta-endorphin is also found in the anterior pituitary |
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Where are dynorphin cells found?
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throughout CNS
esp. in hypothalamus, brain stem, and posterior pituitary *Similar to ENKs, dynorphin neurons terminate in regions involved in affective, motor, endocrine, and nociceptive fxn* |
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How many Met-ENKs does proenkaphalin have?
How many Leu-ENKs? |
Met-ENKs-5
Leu-ENKs-1 |
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What makes up "Preprodynorphin"
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signal sequence
Dyn A (with Leu-ENK at N-terminus) Dyn B (w/ Leu-ENK at N-terminus) |
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mu-opiate receptor (MOR)
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beta-endorphin receptor
(>enkaphin>dynorphins) |
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delta-opiate receptor (DOR)
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enkephalin receptor
(>Beta-endorphin and dynorphin) |
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Kappa-opiate receptor (KOR)
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dynorphin receptor
(>>Beta-endorphin and enkephalins) |
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How do opiate receptors inhibit their target cell?
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activation of all the opiate receptors inhibits Ca++ conduction into presynaptic nerve terminals to produce presynaptic inhibition
also stimulate K+ conduction on postsynaptic neurons causing hyperpolarization |
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What functions are modulated by opiate peptides and opiate pathways?
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1. nociception
2. cardiovascular function 3. temperature 4. feeding 5. sexual activity 6. memory |
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What is the difference between an opiate and an opioid?
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opiates- drugs derived from the opium poppy plant, Papaver somniferum - this included morphine and codeine
opioid--any drug, natural/synthetic that have similar pharmacological actions and mechanisms of action as opiates |
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What is the primary therapeutic use of Opiates/opiods?
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analgesia (both at the spinal and central levels) by activating MOR or KOR.
*Opioids also reduce the affective or emotional responses to nociceptive information |
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Do opioids work on all somotosensory modalities such as moderate temperature, touch, vibration, and propioception?
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no - only analgesic
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Do opioids work better on a fixed-interval/sustained release or dosing on demand?
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fixed-interval/sustained release
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What is the primary site of action for opioids in the supraspinal region?
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periaquaductal gray region of the midbain
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What do opioids inhibit?
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opioids inhibit GABAergic neurons
These neurons inhibit the descending pathway The descending pathway inhibits transmission of nociceptive info. |
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Where are opiate receptors located in the spinal mechanism?
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on presynaptic nerve terminal of the primary afferent neurons AND on the cell body of the second order neurons
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What is the mechanism of action of opioids in the spinal mechanism?
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Opioids inhibit the release of Glutamate from the primary afferent neuron through inhibition of Ca++ channels and Hyperpolarize the second order neuron by activating K+ channels
This prevents activation of the Spinothalmic tract. |
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Besides analgesia, what are other therapeutic indications for opioids?
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Decrease GI motility & Secretions (diarrhea)
Antitussive (inhibits cough reflex in medulla) |
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What is the major side effect of opioids?
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RESPIRATORY DEPRESSION
due to the inhibition of the respiratory control center in the medulla |
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Repeated administration of opiods (days to weeks) causes pharmacodynamic tolerance and decreases the response to the drug.
What causes this physiologically? |
tolerance produces a decreased number of receptors or a decreased coupling of the receptor to the signal transduction system
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List the order that tolerance develops (effects)
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1. euphoria - tolerance quickly developes
2. respiratory depression & sedation 3. GI motility: slow to develop 4. NO tolerance of miosis Cross tolerance occurs*** |
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What happens if you give a partial agonist w/ a full agonist?
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the partial agonist will reduce the response of the full agonist
therefore, you could precipitate withdrawal in a pt who is dependent on a full agonist |
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Where are most opioids metabolized?
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liver
many have extensive first pass metabolism |
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Morphine and morphine analogs target what opioid receptors ?
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MOR (lower affinity for KOR and DOR)
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What is the drug of choice in severe pain?
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Morphine
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What are specific side effects of morphine and what causes them?
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vasodilation and bronchoconstriction
morphine causes the release of Histamine from mast cells |
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What synthetic opioid has similar effects of morphine but may produce less nausea and vomiting?
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Levorphanol
*extended half-life useful in cancer patients* |
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What MOR agonist may not cause as much constipation and urinary retention as morphine, however it may have CNS exciatatory effects and precipitate tremors and seizures due to its METABOLITE
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Meperidine
Only used parenterally |
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What Meperidine analogs are used only to treat diarrhea
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Diphenoxylate
Loperamide |
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What high affinity MOR agonist is 100 times more potent than morphine and has RAPID onset due to high lipid solubility and SHORT half-life due to redistribution into fat
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Fetanyl
*transdermal patches available for chronic pain* |
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What MOR agonist is extensively used for anastesia in cardiac surgery due to its little affect on the myocardium and it does NOT release histamine?
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Fetanyl
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What drug is 5-7 times more potent than fentanyl and binds to MOR, DOR, & KOR?
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Sufentanil
PARENTERAL ONLY |
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What MOR agonist is used as IV continuous infusion for short surgical procedures where rapid recovery from respiratory depression is desired?
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Remifentanil
(onset 1-2 min/ HL=15 min) NOT used for post-operative analgesia |
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Besides MOR what else does Methadone block?
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NMDA type glutamate receptors and monoamine reuptake transporters
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What oral analgesic is often used to manage pain in cancer or neuropathic pain but is also used to treat opioid abuse as a substitute?
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Methadone
Methadone is sufficient to prevent withdrawal from heroin, but not high enough to produce the euphoria and reinforcing effects of opioids |
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What are the partial MOR agonists?
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Codeine
Oxycodone Hydrocodone |
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Which partial MOR agonist is the most potent and used for moderate to severe pain?
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Oxycodone
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What drug is a high affinity, partial MOR agonist and KOR antagonist and is used as a second-line agent for moderate to severe pain?
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Buprenorphine
long acting opioid |
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Besides methadone, what analgesic is used as a heroin substitute and detoxification for opioid addiction?
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Buprenorphine
dependence occurs w/ prolonged administration (7-14) days, but the withdrawal is not as severe as morphine |
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Which drug is a KOR agonist and a weak MOR antagonist or partial agonist?
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Pentazocine
Oral ONLY |
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Which analgesic causes dysphoria and psychomimetic effects at high doses?
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Pentazocine
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Does Pentazocine increase or decrease blood pressure?
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increases blood pressure and heart rate
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What drug is a strong KOR agonist and MOR antagonist?
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Nalbuphine
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What drug at high doses produces dysphoric effects, racing thoughts and distortions of body image?
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Nalbuphine
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What drug is primarily a KOR agonist?
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Butorphanol
It also has weak MOR antagonist/partial agonist activity *has psychomimetic effect but less so than pentazocine* |
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Which drug has a formulation for intranasal administration?
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Butorphanol
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Which drug is a weak MOR agonist and NSRI?
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Tramadol
effective in mild to moderate pain |
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What drug may produce seizures or exacerbate seizures in pts w/ epilepsy?
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Tramadol
should not be given w/ SSRI or MAOIs or other drugs that lower the seizure threshold |
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What drug is used only for cough suppresion but block NMDA receptors and cause CNS depression at high doses
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Dextromethrophan
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What drug is a non-selective opiate receptor antagonist?
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Naloxone
Binds MOR w/ high affinitiy and binds DOR and KOR with lower affinity Has no pharm. effects when administered alone, but rapidly reverses opioid effect within minutes of injection |
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What drug is primarily used to reverse the effects of opiod overdose?
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naloxone
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What drug is like naloxone but has a longer duraiton of action (24hours) and is used in treatment of alcohol addiction?
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naltrexone
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What is special about Methylnaltrexone?
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it is an analog of naltrexone but does NOT cross the blood brain barrier
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what drug is used to prevent constipation in pts who receive sustained opioid therapy for chronic pain or methadone therapy?
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methylnaltrexone
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