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Flashcards in opioid analgesics Deck (64)
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1

plant sources of opiods

poppy- source of morphine, codeine

2

Animal sources of opiods

1. Enkephalins- modulatory neurotransmitters at synapses derived from pro-enkephalin. Tyr-Gly-Gly-Phe opiod motif. Rapidly broken down by peptidases so only act at short distances. 2. endorphins- neurotransmitters and heurohormones. Derived from proopiomelanocortin. Beta-endorphin is most active. 3. Dynorphin- derived from prodynorphin. Dynorphin A is most active. K selective. 4. Endomorphins- variation of opiod ligand motif (Tyr-Pro-Trp/Phe-Phe). Mu receptor selective 5. Nociceptin: regulates pain and related to true opiods but binds to distinct receptors.

3

Where are endorphins found

hypothalamic neurons and pituitary

4

antagonist of opiods

naloxone

5

opiod receptors- classes, structures, locations, where opiods bind

classes: Mu, delta and kappa. 65% homology. All are coupled to G proteins Gi and Go. Distributed throughout the CNS and PNS. Exogenous opiods bind to transmembrane domains, endogenous opiods binds both transmembrane and extracellular domains. receptor dimerization and desensitization mechanisms might further determine differences in ligand specificity and response for different receptor subtypes

6

Mu receptor-pharmacological response, endogenous agonists, agonist drugs

analgesia (central) and respiratory depression, Beta-endorphin , morphine

7

delta receptor-pharmacological response, endogenous agonists, agonist drugs

analgesia, Met/Leu-enkephalin plus Beta endorphin, do drugs in clinical use

8

kappa receptor-pharmacological response, endogenous agonists, agonist drugs

spinal analgesia, dynoprhin 1-17, pentazocine

9

Sigma receptor- unique properties

not a true opioid receptor. Actually is a binding site on the NMDA (glutamate) receptor that is a target for some opiate type drugs (dextramethorphan) as well as dissociative agents (ketamine, phencyclidine)

10

where are opiod receptors found

analgesia: periaqueductal gray (descending pain), medulla nuclei (side effect-respiratory depression), spinal cord dorsal horn (ascending pain). limbic and motor CNS regions: amygdala, hippocampus, striatum (affective response to pain). “reinforcement” regions in CNS: ventral tegmentum, nucleus accumbens (addiction-abuse). gut: myenteric plexus (side effect-constipation).

11

Opiod receptor mechanisms

1. decrease neuronal excitability (hyperpolarization). 2. direct inhibition of pre synaptic VG calcium channels, activation of potassium channels (GIRK) and inhibition of neurotransmitter release. 3. inhibition of cAMP synthesis.

12

List major actions of opiods

1. inhibition of transmission in pain pathways 2. reduce subjective response to pain

13

How do opiods inhibit transmission in pain pathway

1. Inhibition of spinal cord/ascending pain pathway:
inhibition of presynaptic excitatory neurotransmitter release from primary afferent terminals in dorsal horn of the spinal cord (substance P, glutamate, others?) and
inhibition of excitatory postsynaptic spinothalamic “ascending” output neurons. 2. Activation of descending pain pathway: activation of “descending” inhibitory output systems in the medulla, periaqueductal gray, and locus coeruleus; mediated by 5-HT and NE
1. Inhibition of spinal cord/ascending pain pathway:
inhibition of presynaptic excitatory neurotransmitter release from primary afferent terminals in dorsal horn of the spinal cord (substance P, glutamate, others?) and
inhibition of excitatory postsynaptic spinothalamic “ascending” output neurons. 2. Activation of descending pain pathway: activation of “descending” inhibitory output systems in the medulla, periaqueductal gray, and locus coeruleus; mediated by 5-HT and NE
1. Inhibition of spinal cord/ascending pain pathway:
inhibition of presynaptic excitatory neurotransmitter release from primary afferent terminals in dorsal horn of the spinal cord (substance P, glutamate, others?) and
inhibition of excitatory postsynaptic spinothalamic “ascending” output neurons. 2. Activation of descending pain pathway: activation of “descending” inhibitory output systems in the medulla, periaqueductal gray, and locus coeruleus; mediated by 5-HT and NE
1. Inhibition of spinal cord/ascending pain pathway:
inhibition of presynaptic excitatory neurotransmitter release from primary afferent terminals in dorsal horn of the spinal cord (substance P, glutamate, others?) and
inhibition of excitatory postsynaptic spinothalamic “ascending” output neurons. 2. Activation of descending pain pathway: activation of “descending” inhibitory output systems in the medulla, periaqueductal gray, and locus coeruleus; mediated by 5-HT and NE

14

How do opiods reduce subjective response to pain

1. inducement of tranquility, euphoria. 2. patients report “feeling pain”, but the response to the pain is lessened. 3. possible involvement of limbic system, locus coeruleus, and ventral tegmentum

15

How do opiods compare to other analgesics (ie. NSAIDs)

more efficacious but more dangerous (respiratory depression)

16

Do opiods affect conciousness

No, they eliminate pain without altering other sensations or conciousness

17

Which type of pain do opiods work better on

Opioid drugs relieve dull, constant pain better than sharp, intermittent pain Opioid drugs reduce nociceptive pain, but do not alter neurogenic pain

18

Are opiods antipyretics

5. Opioid drugs are not antipyretics, but can be combined with antipyretics such as acetomenophen, aspirin, or ibuprofen (i.e. Vicodin®, Percocet®, Percodan®)

19

1.       Know the medical circumstances in which opioids are indicated

pain associated with malignancy: chronic use , painful diagnostic procedures: in combination with other drugs such as local anesthetics and tranquilizers (benzodiazapines), post-operative pain, obstetrical anesthesia, patient-controlled analgesia (PCA), cough (lower doses) : separable from analgesic actions

20

behavioral effects of opiods

euphoria (Mu receptors), dysphoria (kappa receptors, high dose, hallucinations), sedation/lethargy/confusion (common, CNS depression), behavioral excitation (sign of acute toxicity)

21

Opioid actions on brainstem nuclei

respiratory depression, nausea and vomiting (biphasic-activates at low dose, suppresses at high dose at chemoreceptor trigger zone), cough suppression (symptomatic relief, codeine or non-analgesic opiates like dextromethorphan), pupillary constriction (miosis due to excitation of edinger-westphal nucleus)

22

How do opioids induce respiratory depression

Due to a decrease in sensitivity to CO2 in brain stem respiratory centers. increase in blood CO2 levels leads to cerebral vasodilation, vasodilation can exacerbate head injury (ICP increased), opioid drugs contraindicated in case of suspected head injury, use opioid drugs with caution in any case of compromised respiratory function (e.g. asthma, emphysema, severe obesity etc.)
Due to a decrease in sensitivity to CO2 in brain stem respiratory centers. increase in blood CO2 levels leads to cerebral vasodilation, vasodilation can exacerbate head injury (ICP increased), opioid drugs contraindicated in case of suspected head injury, use opioid drugs with caution in any case of compromised respiratory function (e.g. asthma, emphysema, severe obesity etc.)
Due to a decrease in sensitivity to CO2 in brain stem respiratory centers. increase in blood CO2 levels leads to cerebral vasodilation, vasodilation can exacerbate head injury (ICP increased), opioid drugs contraindicated in case of suspected head injury, use opioid drugs with caution in any case of compromised respiratory function (e.g. asthma, emphysema, severe obesity etc.)

23

Opiods effects on smooth muscle

GI: constipation (decreased secretions and gastric motility, increased tonus of sphincters, very little tolerance to GI effects). Biliary tract: constriction of spincter of Oddi causing 10-fold increase in biliary pressure. Ureter and bladder: increased tonus and contraction (urinary retention, rapid tolerance develops)

24

Opiods used for anti-diarrheal or induced constipation

low abuse potential (Schedule IV) due to poor water solubility.Only act locally in GI tract. Not absorbed into bloodstream. a. diphenoxylate b. loperimide (Imodium-AD®, non-prescription). C. Alvimopan-antagonist (new drug that counters constipation from abd surgery and opiod therapy)

25

Treatment of biliary pain

best treated with opioid + smooth muscle relaxant (e.g. atropine) otherwise opioid may make pain worse.

26

Allergic response to opioids

severe allergic responses may include: 1. anaphylaxis is rare, but possible, especially with i.v. administration.
2. usually symptoms resemble mild allergy (respond to antihistamines). a. itching b. urticaria c. local vasodilation d. headache 3. can sometimes exacerbate asthmatic symptoms 4. peripheral vasodilation and decreased blood pressuresevere allergic responses may include: 1. anaphylaxis is rare, but possible, especially with i.v. administration.
2. usually symptoms resemble mild allergy (respond to antihistamines). a. itching b. urticaria c. local vasodilation d. headache 3. can sometimes exacerbate asthmatic symptoms 4. peripheral vasodilation and decreased blood pressuresevere allergic responses may include: 1. anaphylaxis is rare, but possible, especially with i.v. administration.
2. usually symptoms resemble mild allergy (respond to antihistamines). a. itching b. urticaria c. local vasodilation d. headache 3. can sometimes exacerbate asthmatic symptoms 4. peripheral vasodilation and decreased blood pressure

27

Cardiovascular effects of opiods

Usually minimal at therapeutic doses. Indirect effects: 1. decrease in cardiac work load 2. inhibition of baroreceptor reflex possibly leading to orthostatic hypotension 3. Use opioids with caution in cases of hypovolemia due to decreased blood pressure.

28

Cario/pulmonary uses of opiods

MI: fentanyl and morphine good for analgesia, alleviating apprehension, decreasing cardiac load. Pulmonary edema associated with cardiac dysfunction: alleviation of dyspnea.

29

1.       Know the medical circumstances in which opioids are contraindicated.

Head injury (ICP increases due to cerebral vasodilation), compromised respiratory function (emphysema, asthma, sleep apnea, severe obesity), hypovolemia (decreased BP), shock (makes worse), histamine release, hypothyroidism, impaired hepatic function (elderly, infants, alcoholics)

30

2.      List categories of drugs which interact with opioids

CNS depressants, Phenothiazines (antipsychotics), MOAIs and tricyclic depressants