Opioids: Pharmacology, therapeutic uses, side effects

Question 1

Where did opioid therapy originate from, and where is this origin extracted from?

Answer 1

Originates from opium

Which is extracted from seed capsules of opium poppies (papaver somniferum)

Question 2

When opioid therapy was initially used, what were the 2 routes of administration?

Answer 2

Orally inhaled

Ingested

Question 3

When opioid therapy was initially discovered, what 2 conditions was it used to treat?

Answer 3

Diarrhoea

Cough

Question 4

When opioid therapy was initially discovered, what were the 3 main effects?

Answer 4

Recreational
Sedative
Analgesic

Question 5

What instrument led to significant changes in the use of opioid therapy?

Answer 5

Hypodermic syringe and needle

Question 6

What makes an synthetic opioid drug effective?

Answer 6

It has morphine-like effects

Question 7

What are the 2 most commonly used opioid drugs?

Answer 7

Morphine
Codeine

Question 8

Why are most pill forms of opioids given several times a day, but patches are not?

Answer 8

Pills have short half-life

Patch has much longer half-life, so lasts several days

Question 9

Give 3 examples of alkaloids that are directly extracted from opium poppy, and describe this substance?

Answer 9

Directly extracted as white, milky latex substance

Morphine, thebaine, codeine

Question 10

After alkaloids have been directly extracted from opium poppies, what are the 2 methods of further processing to obtain more morphine?

Answer 10

Alkaloids (white, milky latex substance) is purified to obtain more morphine

Other alkaloids processed to obtain morphine derivatives

Question 11

Which 2 opioid drugs are produced from chemical modification of morphine?

Answer 11

Heroin
Codeine

Question 12

Which 2 opioid drugs are produced from chemical modification of thebaine?

Answer 12

Oxycodone
Hydrocodone

Question 13

What are the lab designs of synthetic opioid drugs based on, and give 3 examples?

Answer 13

Fentanyl, methadone, buprenorphine

Designs target opioid receptors

Question 14

In the 1950s, what was discovered about the targeting/binding mechanism of opioid peptides?

Answer 14

Opioid peptide binds to different types of opioid receptor (G-coupled receptor), which are widely distributed in CNS and PNS eg. GI tract

Question 15

What are the 3 opioid receptors that are widely distributed in the CNS and PNS?

Answer 15

Mu
Kappa
Delta

Question 16

Which opioid receptor mostly causes respiratory side effects of opioid therapy, and give examples of other unwanted effects caused by this receptor?

Answer 16

Mu receptor

euphoria, respiratory depression, constipation, mental clouding, urinary retention, cough suppression

Question 17

What is the desirable effect of opioid therapy that is induced by mu receptors?

Answer 17

Analgesia

Question 18

Give 3 examples of opioid drugs that preferentially target mu receptors, and are these commonly or rarely prescribed?

Answer 18

Preferentially targeted by morphine, fentanyl, codeine (most commonly prescribed)

Question 19

What is the desirable of effect of the kappa receptor targeted by opioid therapy, and give 3 unwanted side effects?

Answer 19

Binding to kappa receptor induces analgesia in periphery

Hallucinations, paranoia, dysphoria (unease and dissatisfaction)

Question 20

What opioid receptor is preferentially targeted by ketocyclazocine?

Answer 20

Kappa receptor

Question 21

What is the desirable effect of delta receptors targeted by opioids, and how was this discovered?

Answer 21

Delta receptor induces analgesia in spine

Discovered when delta receptors were found in vans deferens of mice

Question 22

As well as exogenous opioids (eg. morphine, codeine), what other molecule can bind to opioid receptors to induce effects?

Answer 22

Opioid peptides which are produced by brain in response to physiologic stressors

Question 23

Are opioid peptides structurally similar to other endogenous body peptides, and what is the characteristic feature of opioid peptides?

Answer 23

Yes

Characteristically have tyrosine at n-terminus

Question 24

What are the 3 classes of naturally-occurring opioid peptides that are produced by the brain?

Answer 24

Beta-endorphins

Dynorphin (binds to Kappa receptor)

Leu-enkephalin, Met-enkephalin

Question 25

Give 2 presentations of pain, for which morphine is the gold-standard opioid to prescribe?

Answer 25

Acute severe pain Chronic pain in palliative care

Question 26

Give 6 examples of administration routes for morphine?

Answer 26

Oral (PO) IV IM Subcutaneous injection Epidural Intrathecal

Question 27

Why do injections of morphine need to be given in lower dose then oral routes?

Answer 27

Injection releases quicker and more consistently

Question 28

Are morphine liquids, tablets and capsules given PO (oral) only available in immediate-release formulations?

Answer 28

No, tablets and capsules are also available in extended-release formulations

Question 29

After administration, how is morphine metabolised and how long is its half-life?

Answer 29

Morphine is broken down in liver to become active metabolite form morphine-6-glucuronide (strong analgesia), which has short half-life of 3-4 hours Morphine-6-glucuronide eliminated in kidney

Question 30

Why shouldn't morphine be prescribed to patients with impaired renal function/dialysis?

Answer 30

Active metabolite morphine-6-glucuronide (strong analgesia) is eliminated in kidney Impaired renal function/dialysis can cause metabolite to accumulate

Question 31

Why is the short-half life of morphine and other opioid drugs problematic?

Answer 31

Shorter the half-life, the more of the drug a person may be tempted to take to treat their symptoms continuously, so more likely to develop tolerance

Question 32

What are the 4 CNS effects of morphine?

Answer 32

Pupil constriction (pin-point pupil) Strong analgesia Acute sedation Euphoria

Question 33

What brain region causes the pupil constriction side effect of morphine and why?

Answer 33

Oculomotor nucleus in brainstem which gives rise to oculomotor/3rd cranial nerve which supplies intrinsic muscles for pupils

Question 34

What brain region do mu opioid receptor agonists such as morphine selectively bind to, in order to cause 2 common GI effects?

Answer 34

Selectively bind to mu receptors in the Chemical Trigger Zone (CTZ) in medulla Induces nausea, acute vomiting

Question 35

How do side effects of limited mobility and muscle tightening commonly present, due to use of opioids?

Answer 35

Constipation

Question 36

Which 2 classes of drugs can be used to treat constipation and vomiting caused by opioid use?

Answer 36

Vomiting: Anti-emetic (vomiting) such as metoclopramide, ondansetron Constipation: laxative such as senna

Question 37

Even though all opioid drugs have respiratory effects, why do mu opioid receptor agonists cause the largest degree of acute respiratory depression?

Answer 37

They selectively bind to mu receptors brainstem respiratory centres

Question 38

What are the 2 respiratory effects of morphine?

Answer 38

Acute respiratory depression Cough suppression

Question 39

How does recurrent use of mu opioid receptor agonists cause tolerance?

Answer 39

Recurrent use of opioid drugs such as morphine can cause desensitisation of mu receptors, so increased doses are needed to achieve same degree of analgesia: tolerance

Question 40

What is the usual initial dose of morphine, and how can opioid tolerance be regulated?

Answer 40

starting dose 5-10 mg morphine increase by 30-50% if no response, increase again by 30-50% if still pain recurs review every few days

Question 41

When physical dependence on opioid drug has developed, when do withdrawal symptoms present and give 5 examples?

Answer 41

Withdrawal symptoms present when person stops taking drug abruptly Restlessness, shivering, aggressiveness, diarrhoea, runny nose

Question 42

Describe the main feeling that develops when a person has psychological dependence on a opioid drug?

Answer 42

Craving for the drug which can last for months to years

Question 43

What is the IUPAC name of heroin/diamorphine?

Answer 43

3-6-diacetylmorphine

Question 44

Which opioid drug is heroin a prodrug of, and what are the 2 active metabolite forms that are produced from heroin?

Answer 44

Prodrug of morphine Active forms: morphine, 6-monoacetylmorphine

Question 45

Does heroin have a high or low affinity for mu receptors, and why is heroin an effective prodrug?

Answer 45

Heroin has low affinity for mu receptors, but it is converted to active forms morphine and 6-monoacetylmorphine which have high affinity for mu receptors Therefore heroin is an effective prodrug

Question 46

When heroin/diamorphine is administered by IM injection, why is the dose 50% of the morphine dose that would have been used for IM injection?

Answer 46

Heroin is more lipid-soluble than morphine, so is more potent and has a more rapid onset

Question 47

What is the main effect of heroin when administered by IV injection, and why does this occur?

Answer 47

Heroin crosses blood-brain barrier easily when administered by IV injection which provides rapid high

Question 48

Give 2 presentations of pain for which diamorphine/heroin is commonly used?

Answer 48

Chronic pain in palliative care, where high doses need to be given in small volume syringes Postoperative pain after major surgery

Question 49

Is methadone a natural or synthetic opioid drug?

Answer 49

Synthetic opioid

Question 50

What is the half-life and bioavailability of methadone compared to morphine?

Answer 50

Methadone has much longer half-life (24-30hrs) but morphine is short (3-4 hrs) Methadone has much higher bioavailability especially when administered orally (80% dose absorbed)

Question 51

Who uses methadone as substitution therapy and why, and why is it effective in a supervised regime?

Answer 51

IV users/addicts with Opioid Use Disorder (OUD) to reduce reduce IV morphine/heroin abuse Can relieve withdrawal symptoms and reduce cravings for morphine/heroin

Question 52

Why must the time of administered doses of methadone be monitored very closely?

Answer 52

If methadone is administered too often, overdose can occur which is very toxic due to long half-life

Question 53

What is the most common route of administration of fentanyl and buprenorphine, and why?

Answer 53

Patch Long-lasting so is more convenient than giving doses more often

Question 54

What is the IUPAC name of codeine?

Answer 54

3-methoxymorphine

Question 55

How is codeine converted to morphine?

Answer 55

Codeine (3-methoxymorphine) is demethylated in liver by CYP2D6 enzyme to morphine

Question 56

Why does codeine only induce moderate analgesia even though it is well-absorbed orally?

Answer 56

Only some is converted to morphine, so it has a much lower efficacy which results in moderate analgesia

Question 57

How does genetic variation influence an individual's response to codeine?

Answer 57

Genetic variation of liver CYP enzymes causes unpredictable response to codeine

Question 58

If NSAIDs and paracetamol are both ineffective/unsuitable to prescribe to a patient, what opioid drug is prescribed?

Answer 58

Codeine

Question 59

How can the analgesic effect of a single dose of codeine be increased?

Answer 59

It is combined with ibuprofen, aspirin or paracetamol

Question 60

What 2 drugs is co-codamol a combination of?

Answer 60

Compound analgesic compromising codeine and paracetamol

Question 61

What 2 drugs is co-dydramol a combination of?

Answer 61

Compound analgesic compromising dihydrocodeine and paracetamol

Question 62

Is dihydrocodeine a natural or synthetic opioid, and what is the active form that it is metabolised to?

Answer 62

Semi-synthetic prodrug that is metabolised to dihydromorphine

Question 63

What pain intensity is dihydrocodeine prescribed for?

Answer 63

Mild-moderate pain

Question 64

What is dyspnea, and what opioid drug is prescribed for severe dyspnea?

Answer 64

Dyspnea: sensation of running out of the air, not being able to breathe fast/deeply enough Treated by dihydrocodeine

Question 65

What is meant by dihydrocodeine having an antitussive effect?

Answer 65

Antitussive: cough suppressant

Question 66

Give 3 common side effects of codeine?

Answer 66

Constipation Cough suppression Severe toxicity in suspected children

Question 67

Should opioid receptor agonist drugs be prescribed for neuropathic pain?

Answer 67

No, as neuropathic pain is partially sensitive to opioids Deafferentation pain: subdivision of neuropathic pain that occurs when somatosensory system is damaged and is insensitive to opioids

Question 68

Give 2 reasons why opioid therapy shouldn't be prescribed for migraines and tension headaches?

Answer 68

Risk of dependency Adverse effects such as medication overuse headaches

Question 69

Why shouldn't opioid therapy be prescribed for low back chronic pain?

Answer 69

No proven significant clinical benefits, so can cause unnecessary side effects

Question 70

What is the most commonly used opioid antagonist drug?

Answer 70

Naloxone

Question 71

What is the mechanism of action of naloxone and other opioid antagonists drugs, in reversing the effects of morphine and other opioid agonist drugs?

Answer 71

Naloxone/opioid antagonist drug blocks mu receptors so that morphine/mu-receptor opioid agonist drug can’t bind, which reverses effect

Question 72

What is the route of administration of naloxone/opioid antagonist to reverse acute opioid toxicity?

Answer 72

Injection

Question 73

Give 5 side effects of naloxone/opioid antagonist drugs?

Answer 73

Breathing problems Low oxygen stats Drowsiness Altered mental state Small pupils

Question 74

What are the 2 formulations of naloxone that are available in the community?

Answer 74

Prenoxad (pre-filled syringe) Nyxoid (nasal spray)

Question 75

Which 2 opioid antagonist drugs have peripheral action to prevent GI effects of morphine/opioid agonist drugs?

Answer 75

Methylnaltrexone, naloxegol

Question 76

What is naltrexone prescribed for in programmes?

Answer 76

Aids detox in opioid and alcohol withdrawal programmes