Term
| Where are action potentials conducted to? |
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Definition
The dorsal horn of the spinal cord
They are generated through a noxious stimulus to the peripheral terminal |
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Term
| T/F: the circuit of transmission of pain impulse contribute to descendong modulatory control? |
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Definition
|
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Term
| What are chemical stimuli? |
|
Definition
- Acid sensitive ion channels (ASIC)
- ATP-sensitive P2X or P2Y channels
- Kinin-sensitive B1 or B2 receptors |
|
|
Term
| What are thermal stimuli: heat sensitive cation channels? |
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Definition
Transient receptor potential (TRP) vanilloid receptor 1 (TRPV1)
TrP vanilloin-receptor like protein 1 (TRPV2) |
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Term
| Which neurotransmitters are relased presynapticly they interact with postsynaptic receptors and cause postsynaptic depolarization? |
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Definition
| Glutamate, CGRP and Substance P |
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Term
| T/F: Opoids, NE, 5-HT, GABA, released by ascending and/or local-circuit inhibitory neurons, act both presynaptically and postsynaptically to inhibit neurotransmission? |
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Definition
|
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Term
| T/F: The presynaptic inhibition is mediated primarly by enhanced chloride influx and potassium efflux? |
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Definition
False, this is the definition for postsynaptic inhibition
Presynaptic inhibition is mediated through reduced activity of voltage sensitive calcium channels |
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Term
| What happens in postsynaptic inhibition, secondary relay neuron? |
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Definition
| We will have increase conductance of Cl- (in) and K+ (out) which leads to postsynaptic hyperpolarization, decrease voltage gated Na+ channels reaching threshold. This will decrease action potential generation |
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Term
| The descending projections of NE from brainstem to spinal cord activate alfa2-adrenergic receptor, G-protein coupled and cause? |
|
Definition
- Inhibits presynaptic Ca-channels
- Reduce presynaptic cesicle release
- Opens postsynaptic potassium channels
- Membrane hyperpolarization |
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|
Term
| T/F: Activation of 5HT ligand-gated channel in the spinal cord is excitatory? |
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Definition
|
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Term
| T/F: 5-HT G-protein-coupled receptors mediate inhibitory action of serotonin? |
|
Definition
|
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Term
|
Definition
| Acts through inhibiting NE/5-HT reuptake |
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Term
| T/F: Duloxetine (NE/5-HT reuptake inhibitor) has analgesic activity? |
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Definition
|
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Term
| Difference in pharmacologic effect of opoid receptor (mu, delta, kappa) |
|
Definition
- mu has supraspinal analgesia effect while delta and kappa don't
- mu also has euphoria effect while delta and kappa don't
- kappa is only receptor that has dysphoria effect
- Physical dependence is seen more w/ mu receptor, seen with kappa not delta
- Delta does not have peripheral analgesia, sedation, and pupil constriction
- All have reduced GI motility (mu>delta>kappa)
- Kappa does not have respiratory depression
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Term
| T/F: Endogenous opoids are released by interneurons in the dorsal horn in response to severe/ persistent pain? |
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Definition
| True, opids bind to G proteins associated w/ mu-type opoid receptors |
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Term
| What opiate-like peptides are contained in Pro-orphanin (larger precursor)? |
|
Definition
| Nociceptin or orphanin, FQ |
|
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Term
| What opiate-like peptides are contined in Pro-dynorphin? |
|
Definition
| Endorphins, enkephlins and dynorphins |
|
|
Term
| what opiate-like peptides are contained in Pro-opiomelanocortin? |
|
Definition
|
|
Term
| T/F: opiates are drugs derived from opium, and they include morphine, codeine, and thebaine, and many semisynthetic derivatives? |
|
Definition
|
|
Term
| What are endogenous opoid peptides? |
|
Definition
| They are naturally occuring ligands for opoid receptors |
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|
Term
| What are semi-synthetic opoids? |
|
Definition
- Hydromorphone (dilaudid)
- Oxymorphone (opana)
Hydrocodone (vicoden)
- Oxycodone (percodan, oxycontin) |
|
|
Term
| What are synthetic opoids? |
|
Definition
- Meperidine (demerol)
- Methadone (dolphine)
- Propoxyphene (darvon)
- Levorphanol |
|
|
Term
| What are pure opoid antagonists? |
|
Definition
- Naloxone
- Naltrexone
- Nalmefine |
|
|
Term
| What are patiel opoid agonists? |
|
Definition
- Pentazocine
- Buprenorphine
- Butorphanol
- Nalbuphine |
|
|
Term
| Which opoid agonist act on both mu and kappa (lower activity) receptors? |
|
Definition
|
|
Term
| Which which patial agonist opoid has only activity on mu receptor? |
|
Definition
|
|
Term
| Which patial agonist has only activity on kappa receptor? |
|
Definition
|
|
Term
| T/F: analgesis occurs with loss of consciousness? |
|
Definition
|
|
Term
| T/F: nociceptive pain is responsive to opoid unlike neuropathic pain which respond poorly? |
|
Definition
|
|
Term
| What is the analgesic MOA of opoids? |
|
Definition
| Opoids directly inhibit ascending transmission of nociceptive information from the spinal cord and activate pain control circuits that descend from the midbrain to the spinal cord dorsal horn |
|
|
Term
| T/F: in the presynaptic terminal, mu-opoid receptor activation decreases ca2+ influx in response to an incoming action potential? |
|
Definition
|
|
Term
| Post-synaptoc mu-opoid receptor activation increases K+ conductance and therby decreases the postsynaptic response to excitatory neurotransmission? |
|
Definition
|
|
Term
| Which medications have no analgesia effect? |
|
Definition
- Dextromethorphan
- Diphenoxylate
- Loperamide
- Naloxone
- Naltrexone |
|
|
Term
| T/F: Codeine has an exceptionally high affinity for opoid receptors, and the analgesic activity is due to its conversion to morphine by CYP2D6? |
|
Definition
False, low affinity
Analgesia is affected by possible metabolic enzyme polymorphism |
|
|
Term
| T/F: Tramadol, a synthetic codeine derivative is a weak mu-opoid receptor agonist? |
|
Definition
|
|
Term
| What is the mechanism of analgesia of tramadol? |
|
Definition
| inhibition of uptake of NE and serotonin |
|
|
Term
| T/F: Propoxyphene binds to mu-opoid receptors, but more selective than morphine? |
|
Definition
|
|
Term
| T/F: The mixed agonists/antagonists exert analgesic action by acting as agonist at kappa receptors? |
|
Definition
|
|
Term
| T/F: Mechanisms of drug-induced reward involve interactions between opoids and dopamine in the nucleus accumbens? |
|
Definition
|
|
Term
| T/F: Selective mu and delta agonists produce positive motivational effects by decreasing dopamine release? |
|
Definition
| False, by increasing dopamine release |
|
|
Term
| T/F: selective kappa receptor agonists produce aversive effects by inhibiting dopamine release? |
|
Definition
|
|
Term
| T/F: When equianalgesic doses are used, there is no difference between morphine and morphine-like opoids in regards to respiratory depression? |
|
Definition
|
|
Term
| What are CNS effect of opoids? |
|
Definition
Sedation, drowsiness, and mental clouding
Emetic effects: N/V are due to direct stimulation of CTZ and high doses depress comting center
Antitussive: direct action on medulla cough center to suppress cough reflex
Miosis: (pin point pupils)
Muscle rigidity-due to increased tone to spinal motor neurons at high dose
Convulsion at high doses |
|
|
Term
| What are alternative route of administration of morphine, used to maximize benefit and minimize SE? |
|
Definition
| PCA (pts controlled analgesia), epidural, transdermal, transmucosal and intra-articular |
|
|
Term
| T/F: morphine-6-glucuronide is 4-6 times more potent than morphine and may contribute significantly to analgesia? |
|
Definition
|
|
Term
| T/F: Morphine-3-glucuronide lack analgesic effect but can cause dysphoric SE or seizures? |
|
Definition
|
|
Term
| What are acute toxicity symptoms of morphine? |
|
Definition
Triad coma, pinpoint pupils, respiratory depression
Tx: IV naloxone (opoid antagonist) (may precipitate withdrawal symp) |
|
|
Term
| What are DI with morphine? |
|
Definition
- MAOIs, phenothiazines, tricyclic antidepressants, alcohol (exaggerated CNS depressant effect)
- Tranquilizers, sedative-hypnotics, alcohol (general anethetics)-Increase respiratory depression
- Amphetamine (small dose) enhance analgesic and euphorant effects of morphine
- antideppressant and aspirin enhance analgesia |
|
|
Term
| What are morphine contraindications? |
|
Definition
| Bronchial astham, emphysema, liver damage, head injuries, acute alcohol use, previous dependence, convulsive disorders, abd pain unknown origin |
|
|
Term
| What are the differences between morphine and meperidine? |
|
Definition
Meperidine has faster onset, shorter duration of action
- No antitussive activity w/ meperidine
- Less constipation
- Increased CNS excitability and seizures (due to toxic metabolite normeperidine-long t1/2, & pts w/ chronic kidney dz)
- Mydriasis rather than miosis |
|
|
Term
| What are DI with meperidine? |
|
Definition
Serotonin syndrome with MAOIa
Chlorpromazine-enhanced respiratory depression and sedation
Promethazine-enhanced sedation
Amphetamine-enhanced analagesic while counteracting sedation |
|
|
Term
| T/F: sufentanil is 10-15 * more potent than fentanyl? |
|
Definition
|
|
Term
| Which fentanyl subgroup has ultra short duration and rapid metabolism by esterases? |
|
Definition
|
|
Term
|
Definition
Diphenoxylate: derivative of meperidine, combined w/ atropine (lomotil)
Loperamide (imodium): derivative of diphenoxylate, effective antidiarrheal with little abuse potential |
|
|
Term
| What are differenced between methadone and morphine? |
|
Definition
Methadone: has extended duration of action, slow onset and long t1/2, tolerance develops more slowly, withdrawal syndrome develop slowly and is mild, used for tx of opoid abuse
Hepatic dysfunction associated wth overdose-respiratory depression, and rarely QT prolongation |
|
|
Term
| Which synthetic opoid overdose causes toxic psychosis (involved increasing incidence of deaths, mostly suicides)? |
|
Definition
| Propoxyphene (only PO available) |
|
|
Term
| Which synthetis opoid is contraindicated in pts w/ hx of epilepsy? |
|
Definition
Tramadol (risk of seizures)
no report of respiratory depression or cardiovascular toxicity
inhibits NE and 5HT reuptake
not strictly an opoid analgesic |
|
|
Term
| T/F: degree of physical dependance of opoids is related to the amount, frequency and duration of drug use? |
|
Definition
|
|
Term
| Withdrawal syndrome intensity with opoids is inversely related to t1/2? |
|
Definition
| True, shorter t1/2 more intense the symptoms (Fentanyl) |
|
|
Term
| What are symptoms of withdrawal? |
|
Definition
| Anxiety and dysphoria, vraving and drug seeking behavior, sleep disturbance, N/V, lacrimation, rhinorrhea, yawning, sweating, diarrhea, mydriasis, abd cramping, hyperpyrexia, tachycardia and HTN |
|
|
Term
| Which opoid has no antitussive effect? |
|
Definition
| Meperidine, diphenoxylate, loperamide propoxyphene (o to low) |
|
|
Term
| Which opoids have the least constipation effect? |
|
Definition
Meperidine, propoxyphene and tramadol
Dextromethorphan has none |
|
|
Term
| which opoid has the most analgesic effect? |
|
Definition
|
|
Term
| Which mixed apoid agonist-antagonist has antitussive effect? |
|
Definition
| Buprenorphine, all other have zero effect |
|
|
Term
| Which opoids has no alangesic effect? |
|
Definition
| Dextromethorphan, diphenoxylate and loperamide |
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