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opiates Flashcards

1
Q

what is the difference between opium and opiate and opiod?

A

opium: dried powdered mixture containing 20 alkaloids obtained from the unripe seed capsules of the poppy

opiate: alkaloids extracted from the opium poppy

opioid: substances that mimic the effects of morphine
Can be endogenous OR exogenous

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1
Q

what is a narcotic?

A
  • to make numb
  • Federal government uses the term narcotic synonymously with illicit drugs
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2
Q

what are the different types of opiates?

A
  • natural: Harvested from the opium plant (ex. thebaine, morphine, codeine)
  • semisynthetic: created from natural opioids (ex. heroin)
  • synthetic: completely created in lab (ex. fentanyl, methadone)
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3
Q

why is fentanyl a dangerous fully synthetic opiod?

A

it is 50 times more potent than heroin and 100 times more potent than morphine.

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4
Q

what schedule drugs are most opiate drugs?

A

schedule 2 but varies substantially in abuse liability and medical uses

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5
Q

what type of schedule drug is heroin?

A

schedule 1

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6
Q

what was the opioid epidemics?

A

when some pharmaceutical companies made a push to reduce opioid stigma & increase prescriptions - opioid overdoses quadruples

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7
Q

what is the route of admin of opiates?

A
  • orally (as pills or liquids - vicodine, oxycodone low bioavialbility)
  • “skin-popping”: Subcutaneous injection (heroin)
  • “mainlining”: IV injection (heroin)
  • intra-muscular injection for medical use of morphine
  • Nasal, inhalation (smoking- “chasing the dragon”), & rectal use also occur
  • Transdermal patches for sustained pain relief used in medical settings (Lower risk for abuse)
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8
Q

what is the absorption of opioids?

A

Opioids have lower bioavailability if taken orally due to first-pass metabolism
Rapid absorption when injected/ snorted!

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9
Q

how are opiates removed from the body? which form of kinetics?

A

by urine and feces

first order kinetics

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10
Q

what are the dangers of fentanyl?

A

the more fentanyl a person ingests, the more they risk death

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11
Q

what are the 3 major families of endogenous opioid neuropeptides?

A
  • endorphins
  • enkephalins
  • dynorphins
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12
Q

where are endorphins synthesized and what responses do we see with these?

A

synthesized: hypothalamus and pituitary gland

responses: analgesia, euphoria/ reinforcing aspects of opioid use, constipation, respiratory depression

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13
Q

where are enkephalins synthesized and what responses do we see with these?

A

synthesized: CNS and adrenal medulla in PNS

responses: analgesia, euphoria

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14
Q

where are dynorphins synthesized and what responses do we see with these?

A

synthesized: hypothalamus, striatum, hippocampus, spinal cord

responses: DEPRESSED, pain/stress, learning, and memory

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15
Q

what are the 3 major classes of opioid receptors?

A
  • mu receptors
  • delta receptors
  • kappa receptors
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16
Q

what are the endogenous opioid peptide that comes to mu receptors? what effects do they produce and what part of the brain?

A

Endogenous peptides: Endorphin

Analgesia— thalamus, periaqueductal gray, raphe, spinal cord
Reinforcement—nucleus accumbens
Mood —amygdala
Cardiovascular and respiratory depression, cough control, nausea and vomiting—brainstem
Sensorimotor integration—thalamus, striatum

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17
Q

what are the endogenous opioid peptide that comes to delta receptors? what effects do they produce and what part of the brain? where are these receptors found?

A

Endogenous peptides: endorphin & enkephalin

δ-receptors found in cerebral cortex, thalamus, striatum, spinal cord
Role for δ-receptors in olfaction, motor integration, reinforcement, and cognitive function.
Areas of overlap with μ-receptors implicated in analgesia.

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18
Q

what are the endogenous opioid peptide that comes to kappa receptors? what effects do they produce and what part of the brain? where are these receptors found?

A

Dynorphin = major peptide

Found in the striatum, hippocampus, amygdala, hypothalamus and pituitary

hippocampus, amygdala, pituitary: dysphoria, stress, memory
hypothalamus: gut motility/ feeding

Also pain perception

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19
Q

what are the 3 ways opioids inhibit neuron activity?

A

(A) Postsynaptic inhibition—binding of opioids to postsynaptic receptors hyperpolarize the postsynaptic cells, reducing firing rate.

(B) Axoaxonic inhibition— binding to receptors close presynaptic Ca2+ channels in axon terminals, reducing the release of neurotransmitter.

(C) Presynaptic autoreceptors reduce release of a co-localized neurotransmitter from presynaptic neuron.

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20
Q

how do opioids alter mesolimbic dopamine?

A
  • Activity of DA neurons in the VTA are controlled by local GABA interneurons
  • β-endorphin & opioid drugs increase VTA cell firing by inhibiting the inhibitory GABA cells - INCREASING DOPAMINE (disinhibition)
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21
Q

how does dynorphin affect the mesolimbic dopamine if it has depressive qualities?

A

Dynorphin acts on κ-receptors on DA neuron terminals and can reduce release of DA, causing dysphoria.

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22
Q

how does most opiates act at receptors?

A

full agonist

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23
Q

how does buprenorphine (surgical anethetic) act at receptors?

A

partial agonists

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24
how do interventions like narcan act at receptors?
antagonist
25
what are subjective effects of opiates that a person may feel?
Rush: rapid onset of euphoria seconds after injection; Sensation of heroin entering system High: feelings of joy/ ease pleasure Nod: feelings of calm/ disinterest ;Semi- or unconscious state Straight: period of normalcy; Not sick
26
what is true about the effects of opioids on CNS?
depends on dose and rate of absorption
27
what are the opiate user's desired effects?
Analgesia (pain management) Cough suppression Sedation Anti-diarrhea Euphoria
28
what does low moderate doses of opiates do?
analgesic, constricted pupils, sense of relaxation and drowsiness/sleep, inability to concentrate
29
what does high doses of opiates do?
euphoria/ elation, but… coma and death
30
what medication do some individuals take , not for its instrumental purpose, to get the opiate feel?
- immodium (loperamine) : anti- diahrreal Opioid addicts sometimes take very high doses of loperamide to produce euphoria and reduce withdrawal symptoms
31
how do opiates work to relieve pain?
both dull and sharp pain pathways contain mu receptors. the ascending pain pathways (spinothalamic pathways) is Nociceptors -> Spinal cord ->thalamus -> S1 Opiates will shut down pain signals from ever reaching the thalamus
32
how does the descending pain pathways work?
the descending pain pathway (turning pain off pathways) - originates in PAG - After pain signal reaches S1, descending pain pathway can reduce pain signals by shutting down pain signals at level of the spinal cord
33
why does acupuncture work?
it releases endogenous opioids that trains your body to suppress pain
34
where does opioids inhibit pain transmission?
spinal and supraspinal levels 1. Hypothalamus, limbic structures like ACC, amygdala, and nucleus accumbens. 2. emotional component of pain showed significant negative correlation between μ-opioid activity in the NAcc, amygdala, and thalamus and physical pain scores.
35
what are acute effects of opiate intoxication?
Euphoria Drowsiness/ Nodding Heavy feeling in limbs Decreased sexual desire Impaired social interactions Body warmth/ flushing but lowered core body temp Miosis Hypotension, bradycardia (slow heart rhythm)
36
what are adverse effects that are seen with opiate use?
dysphoria restlessness and anxiety, nausea and vomiting morphine affects the area postrema in the brainstem that elicits vomiting.
37
what effects occur with taking high doses?
sedative effects may lead to unconsciousness Respiratory failure body temperature and blood pressure fall
38
what are long term effects of opiates?
Impotence Constipation Hypoxia Collapsed veins Decreased immune function
39
what is responsible for tolerance, sensitization, and dependence by opiates?
neuroadaptive changes from chronic use
40
what types of tolerance do we see?
Behavioral Pharmacodynamic :Opioid receptor desensitization & receptor internalization with chronic use Opioid overdose: *Respiratory failure. Why? Cross-tolerance among the opioids
41
what do opiods generally do? what do we see with withdrawal?
Opioids in general depress CNS function; opioid withdrawal is rebound hyperactivity.
42
what is the classic triad of opiate overdose symptoms? what should we also look for?
Miosis (pinpoint pupil) Coma (level of consciousness) Respiratory depression also look for Pulmonary edema excess fluid in the lungs
43
what are opioid risk factors?
- using an opioid after not using it for a period of time after detox, jail, etc - using street drugs with unknown strength and purity - using an abusive method such as snorting or injecting - mixing with other drugs or with alcohol - using drugs without anyone around
44
what is used for opiod overdose intervention?
narcan (naloxone): Competitive antagonist for Mu receptor can be used to intervene during an active opioid overdose Displaces opioid agonists from the opioid receptor Higher binding affinity than the opioid drugs Only effective for opioid related overdoses Works for ~30 min
45
what is the relapse rate of opiate addiction?
high; 70-90%
46
what are methods for combating opioid dependence?
Reformulating opioids to make them harder to use; Ex: oxycontin reformulation makes it harder to crush/ dissolve Psychotherapy to learn social triggers that may increase risk of relapse; Group therapy, family counseling, cognitive-behavioral therapy Drug replacement Administer safer opioid with weaker effects to reduce withdrawal symptoms Methadone, suboxone, etc.
47
what is the most effect treatment with opiate addiction?
Rapid detoxification is most effective: in-patient treatment; briefly anesthetized and treated with Naltrexone (antagonist)
48
how can we combat withdrawal with other drugs?
Methadone: Agonist for µ-opioid receptor. Generates effects. Lesser high. - Long half-life, cross-tolerance to euphoria between heroin/ morphine & methadone - Allows addicts to avoid uncomfortable withdrawal symptoms & prevents craving Suboxone: Buprenorphine + Naloxone - Buprenorphine: high affinity + low efficacy at mu receptors, antagonist at kappa receptors Less euphoria, less respiratory depression risk Naltrexone: Antagonist. Blocks effects.
49
what is methadone?
synthetic opioid analgesic with full agonist activity at the µ-opioid receptor
50
describe methadone in comparison to heroine/morphine
Does NOT produce the rush, drowsiness (nod) or impairment in thinking/ emotion/ sensation with prescribed use Potential for misuse because higher doses can produce euphoria
51
what is the route of admin of methadone?
oral - most common
52
what is the absorption and distribution of methadone?
Lipid soluble & well absorbed from the GI tract Bioavailability ~80% after oral ingestion Initial effects appear within ~30 min, peak effects & peak plasma levels ~2-4 hours post administration Steady state blood plasma levels generally achieved within 5-7 days Moderate-significant depot binding
53
what is the metabolism of methadone?
Metabolized in the liver by CYP450 enzymes INACTIVE metabolites!
54
what is the excretion, kinetics, and half life of methadone?
Excreted in the urine Methadone is eliminated via first-order kinetics. LONG half-life ~55 hours in non-addicted individuals ~24 hours in individuals who show opioid tolerance
55
what are acute effects of methadone?
Decreased reaction time & impaired motor coordination Decreased attention span/ cognitive ability Drowsiness Dry mouth Muscle weakness Decreased body temperature Constipation Euphoria (only at higher doses)
56
what is chronic effects of methadone?
Liver damage Loss of white matter in the brain Cardiovascular issues Depression Cognitive decline Physical dependence
57
what type of dependence do we see with methadone users?
Physical dependence may occur because of neuroadaptations of the opioid receptors
58
what withdrawal symptoms do we see with methadone?
Withdrawal symptoms include: body aches/ severe pain, loss of appetite, nausea/ stomach cramps, nervousness or restlessness, fever, palpitations, etc. Withdrawal symptoms emerge ~24-48 hrs after last use, peak 3-21 days, & persist for ~6-7 weeks
59
what is still possible with methadone?
overdose; Circulatory collapse, cardiac arrest, and death may occur following administration of high doses

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