Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Phys/Pharm Drugs Of Abuse > Opioids > Flashcards

Opioids Flashcards

1
Q

Opium and Opioids mentioned in history (4)

A
  • Opos: Greek for “juice”
  • Opium poppies sprung from the tears of Aphrodite when she mourned for her
    beloved Adonis
  • The first written reference appears in a Sumerian text data 4000 BC
  • Homer’s Odyssey (8th BC Greece) describe opiate use as a drug called “Nepenthe”: But then Helen ”…had a happy thought. Into the bowl in which their wine was mixed, she slipped a drug that had the power of robbing grief and anger of their sting and banishing all painful memories
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where do opium poppies grow?

A

Golden triangle : b/w Myanmar, Thailand + Laos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

A Brief History of uses (7)

A
  • Beneficial (analgesic, hypnotic) and harmful effect known for centuries
  • 1527: Paracelsus formulated Laudanum
  • 17th C: China outlawed tobacco so opium became popular
  • Opium was the cause of China-England wars when China outlawed opium
  • 1803: Serturner isolated morphine
  • Mid 1800’s medicinal use of morphine widely spread
  • 1939: First synthetic opioid, meperidine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are opioids? (5)

A

– Endogenous or synthetic substance with morphine-like effects, antagonized by naloxone

– ‘Opiate’ synthetic morphine-like drug with non-peptide structure

– Opioid actions include analgesia, respiratory depression, euphoria and sedation

  • Led to discovery of receptor subtypes
    – Morphine analogues
  • Agonists - morphine, diamorphine (heroin), codeine
  • Antagonists – naloxone
    – Synthetic derivatives: pethidine, fentanyl, methadone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Heroin

A

Heroin was first made by Alder Wright in 1874 from morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Methadone (5)

A
  • During WWII the supply of opium was cut off from Germany so painkilling morphine became short in supply
  • Methadone was developed as a synthetic derivative in Germany around 1937 to 1939 by Gustav Ehrhart
  • Successful analgesic acting on opioid receptors
  • Used as a treatment for opiate dependence in 1960s after WWII heroin epidemic
  • The pain-relieving effects last about six hours after a single dose. After long-term use, in people with normal liver function, effects last 8 to 36 hour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Fentanyl (4)

A
  • Fentanyl was first made by Paul Janssen in 1960
  • 100x more potent than morphine
  • Given for acute pain, postoperative pain anaesthesia, obstetrics, chronic pain (patches), palliative pain
  • As of 2017, fentanyl was the most widely used synthetic opioid in medicine.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Oxycodone (3)

A

Synthetic opioid developed by Purdue Pharma to treat moderate to severe pain

  • The extended-release form of this medicine is for around-the-clock treatment of pain. This form of oxycodone is not for use on an as-needed basis for pain.
  • In the U.S., extended-release oxycodone is approved for use in children as young as 11 years old. The approved uses is for relief of cancer pain, trauma pain, or pain due to major surgery, in children already treated with opioids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Opioid use for pain treatment (5)

A

morphine -9%
Tramadol-11%
Fentanyl-17%
Oxycodone-26%
Others=37%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Agonists

A

bind to the mu-opioid receptor and stimulate physiological
activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Partial agonists

A

bind to the mu receptor but do not produce maximum
stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Antagonists

A

have no intrinsic
pharmacological effect, but bind to the receptor and can block the action of an agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Morphine - heroine

A

morphine w/ addition of an acetyl group = heroine (=synthetic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

History of opioids in the brain (6)

A

1973 Discovery of opioid receptors

1975 Discovery of enkephalin

1976 Evidence for multiple opioid receptors

1979 Cloning of opioid peptide precursors

1992 Cloning of opioid receptors

1994/1995 Cloning of ORL1(NOP) receptor and nociceptin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

4- Opioid peptide families and opioid receptors (4)

A

beta-endorphin (beta has high affinity for mu + de) = MOP (mu) + DOP (delta)

Enkephalins= Dop (delta)

Dynorphins= KOP (kappa)

Nociceptin/OFQ = NOP (ORL-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mu opiate receptor vs peptides (2)

A

receptor = GPCR

peptides = made up w/ A.A.’s - same seq homology b/w all important endo peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Pharmacological effects of Opioids (3)

A

(highly localised in reward system + thalamus-pain) mu: superspinal, spinal = analgesia major -ve RD(death) , in GI =constipation

delta: spinal analgesia, little bit of RD,

kappa: possibly peripheral pian (itching), responsible for dysphoria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Respiratory depression (4)

A

– decreased sensitivity (desensitised) of respiratory centre to CO2 (medulla)
= asphyx

– Mediated by mu receptors

– Most troublesome side effect, occurs at therapeutic doses

  • Commonest cause of death in opiate poisoning
19
Q

Opioid Analgesics (3)

A
  • Enalodine, U50488 (KOP)/low dependence liability BUT psychotomimetic effect (withdrawn)
  • Peripheral acting KOP for peripheral pain and itching
  • DOP agonists poor analgesics but have antidepressant properties. However, proconvulsant effects
20
Q

Opioid effects on body systems (5)

A
  • Cough reflex
    – Codeine used in cough medicine to suppress cough
  • Mechanism unclear, can occur at subanalgesic doses
  • Nausea and vomiting (Q. how?)
    – Occurs in 40% of patients
    – Opioid action in CTZ (delta) and vomiting centre (mu)
  • Pupil constriction
    – Pinpoint pupils used as diagnostic feature in opiate poisoning
  • Other causes of respiratory depression & coma cause pupil
    dilatation
  • GI tract
    – inc. tone and dec. motility, constipation
  • Other actions
    – Morphine releases histamine from mast cells - itching
21
Q

Effector mechanisms: Opioid receptors: mu, delta, kappa/ inhibition: (5)

A

– G-protein coupled receptors (Gi/Go) - inhib cAMP (dec cAMP)

  • inc. K+ channel opening= hyperpolarization
  • dec. opening of voltage-gated Ca2+ channels (less +ve = further hyperpolarisation)
  • Reduce neuronal excitability (K+) and reduce neurotransmitter release (Ca2+)
  • Inhibition of adenylyl cyclase, decrease cAMP, PKA
22
Q

Pain pathway - normal (5)

A

1) Injury caused by mechanical, chemical, inflammation = pain

2) detected by the peripheral nociceptors, in the afferent neurones= depolarisation of the neurone

3) initiating an AP to travel up the periphery nerve, to the dorsal root ganglia project on the dorsal horn

4) propagation of AP’s= release of Glutamate and Substance P, which projects onto neighbouring neurones

5) = launches pain signal upwards to the brain, causing the sensation of pain

23
Q

Opioids in peripheral neurones

A

1) opioids inhibit adenylyl cyclase

2)= causing a decrease in the cyclic adenosine monophosphate (cAMP)

3)This results in an increased number of potassium channels opening, causing hyperpolarisation, and the closing of voltage-gated calcium channels.

4) = This causes further hyperpolarisation, reducing the neuronal excitability and neurotransmitter release, reducing the likelihood of neuronal stimulation

24
Q

Opioids on Dorsal spinal cord - pre + post synaptic (4)

A

1) act on the neurone, pre and post synaptically

2) Presynaptic action causes inhibition of Glutamate and Substance P

3) post synaptic action causes hyperpolarisation of the neurones, causing difficulty to stimulate it.

This joint mechanism completely inhibits the transmission of pain.

25
Q

Descending Control System (4)

A

1) Opioids excite the PAG neurons and neurons in the nucleus reticularis paragigantocellularis (NRPG) stimulating
neurons in the nucleus raphe magnus
(NRM) (release of ser = blocks pain info from peripheral to spinal cord)

2) The 5-HT and enkephalin neurons of the NRM run to the dorsal horn and inhibit
transmission

3) Opioids can act directly on the dorsal
horn (and on peripheral terminals)

4) NAergic neurons of locus coeruleus also
inhibits dorsal horn

26
Q

Opioid Analgesics - now (7)

A
  • Diamorphine (MOP)
    – Used as analgesic in UK
    – Tissue injury, tumour growth - acts more quickly = hyperphilic
  • Oxycontin - chronic pain use (epidural)
  • Pethidine (MOP)
    – Favoured for analgesia during labour as no dec. in uterine contraction - can go to placenta = need to give antagonist before = avoid RD
    – Pethidine slowly eliminated in the neonate, naloxone may be needed to reverse
    respiratory depression
  • Fentanyl (MOP)
    – More rapid onset and shorter duration than morphine
    – Main uses: anaesthesia, patient-controlled infusion, severe pain
  • Codeine
    – Readily absorbed, only 20% potency of morphine
    – Used as oral analgesic for mild pain
    – No euphoria, constipation
  • Dihydrocodeine
    – Useful in 10% of population who are resistant to codeine – lack demethylating
    enzyme converting codeine to morphine
  • Tramadol
  • opioid agonist and weak NA reuptake inhibitor
  • Naloxone, antagonist which do not cross BBB for opioid constipation
27
Q

Uses of Opioid receptor
antagonists (2)

A

 Naloxone use to reverse opioid-induced
overdose: hence epipen of this helps overdose - however huge withdrawal symptoms

 Naltrexone use for treatment of opioid
addiction and alcoholism- also blocks r’s for alcoholism induced euphoria

28
Q

Drug overdoes in US causes (4)

A
  • increase heroin use?

-Increased use of painkillers?

-black market prescription of medication w/o MD supervision

-Change in attitude of health care providers

  • increased encouragement of prescription opioid usage
29
Q

What do we know about prescription opioids and the opioid crisis? (4)

A

 21-29% of patients prescribed opioids for
chronic pain misuse them

 8-12% develop an opioid use disorder

 4-6% who misuse prescription opioids
transition to heroin

 80% of people who use heroin first misused prescription opioids

30
Q

Opioids and gateway drug (3)

A

can be discussed as gateway drug for addiction as seen by US data

opioids - heroin gradual deaths

heroin - fentanyl = inc in deaths

31
Q

Truths about chronic pain treatment and addiction (3)

A

-addiction varies 3-40%, depending on diff’s in treatment, duration, assessment

  • properly managed ST medical use rarely causes addiction but physical dependence is more common
  • risk of addiction inc. when used in other ways (high doses, injections, alc, history of comorbid, psych disorders, genetic Polymorphisms, age)
32
Q

Stages in addiction cycle

A

image

33
Q

Opioid disninhibiton effect (3)

A

mesolimbic pathway: neurons project - VTA - nucleus accumbens

drug will act on opioid r (inhibitory) = inhib release of GABA + DA

= disinhib effect - locomotion, sensitisation, drug seeking, self-admin

34
Q

Morphine in MOP K/O mice (2)

A

mu r responsible for DA release

saline + Morphine - decreased DA in morphine

35
Q

Addiction facts (4)

A

Biggest hurdle: Maintenance
of drug-free state as 70% relapse

Current pharmacotherapy
ineffective at maintaining this

Physical withdrawal symptoms
decrease over time whereas emotional withdrawal symptoms persist for months

40% co morbidity b/w
opioid addiction and anxiety, depression
Impairment of social behaviour in heroin abstinent individuals

36
Q

Tolerance definition

A

homeostatic mechanisms that opposes pharm effect of drug

37
Q

How do opioids act on a molecular level? (5)

A

homeostatic mechanisms that opposes pharm effect of drug

1) GCPR + drug
2) recruit GRK
3) Phosphorylation
4) Recruits beta-restin = inactive/desensitised (doesn’t induce 2nd messenger)

38
Q

Withdrawal syndrome - phys + psych (2)

A

Physical - abstinence syndrome (LC):
sweating, gooseflesh (cold turkey), irritability, aggression, restlessness, insomnia, bone pain, diarrhoea, vomiting, involuntary leg movement

psychological; craving to avoid withdrawal effects

39
Q

Mechanism of Dependence (Homeostatic compensatory
neuroadaptation) +proof (4)

A

When dependent + withdrawn from drug:

1) Hyperactivity of noradrenaline system

2) hyperactivity of neurons = major release of NA

= underlies physical withdrawal symptoms - know this is true because if drug (lofexatine) used to block NA release = reduces these symptoms

40
Q

Mechanism of dependence - HPA (4)

A

-heroin addicts: HYPOresponsivity HPA axis

-Cocaine addicts: HYPERresponsivity HPA axis

-CRF in extended amygdala inc. in withdrawal

animal models:
CRF dysregulation long lasting (tolerance kicks in)

41
Q

Function of opioid peptides (7)

A

reg:
-pain
-emotion
-reward
-motivation, drug addiction
- stress responses
-ANS control (resp, GIT, CVD)

alterations in endo opioid involved in addiction, ASD, chronic/neuropathic pain, Parkinson’s, seizure, neuroprotective mechanisms + depression

42
Q

What induces opioid release?

A

analgesia + mood enhancement

43
Q

Role of endogenous opioids in addiction (4)

A

 Drugs of abuse including nicotine, alcohol, cocaine induce the release of enkephalins and endorphins

 Release of endogenous opioid mediate the pleasurable effect of some drugs of abuse (as well as palatable food)

 Cocaine induced the release of dynorphins in the striatum thus
mediating the aversive effects of cocaine

 Cocaine induces MOP and KOP upregulation

Phys/Pharm Drugs Of Abuse (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions