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Year 2 Collin > Pharm 19 - Opiates/Opioids > Flashcards

Pharm 19 - Opiates/Opioids Flashcards

1
Q

What is an opiate?

A

Alkaloid derived from Opiate poppy (Papaver somniferum)

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2
Q

What are the 4 most common opiates

A

Morphine
Codeine
Thebaine
Papaverine

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3
Q

Describe the structure of opiates

A
  1. Tertiary N present - this is what gives opiates an analgesic effect
  2. Hydroxyl groups on 3’ and 6’ positions - they help secure the molecule at the receptor

(OH group on 3’ is required for binding - hence

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4
Q

What happens if the side chain on the tertiary N has more than a 3 C side chain?

A

It becomes an antagonist

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5
Q

Heroin and codeine are what of morphine

A

Derivates/prodrugs

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6
Q

Heroin is much more soluble than morphine. Why?

A

Because the 3’ and 6’ OH group is replaced by acetyl groups

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7
Q

Fentanyl is a very potent opioid compared to morphine. One reason for this?

A

Morphine = quaternary carbon

Fentanyl = tertiary carbon

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8
Q

Methadone conforms to the morphine rule in what sense?

A

It has a tertiary N, quaternary C, Phenyl group

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9
Q

Opioids are weak bases. Where will they be most readily absorbed?

A

In the SI - as they are mainly unionised here.

In stomach, they are ionised so less absorption

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10
Q

What process decreases the bioavailability of opioids?

A

First pass metabolism

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11
Q

Blood has a pH of 7.4. Opioids have a pKa of >8. Therefore what state are they in the blood

A

Ionised

<20% of opioids are unionised in blood - it is these opioids that can access tissues

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12
Q

pKa and pH must be roughly the same in order for the drug to be…?

A

Heavily unionised

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13
Q

Rank the lipid solubility of the opioids

A
  1. Fentanyl
  2. Methadone
  3. Heroin
  4. Morphine

(more lipid soluble = more potent)

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14
Q

Morphine is metabolised in the liver and excreted in the …?

A

Bile - undergoes enterohepatic cycling - returns to blood to have more of an effect

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15
Q

What are the 2 main active metabolites of morphine?

A
  1. Morphine-3-Glucuronide (M3G)

2. Morphine-6-Glucuronide (M6G)

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16
Q

Most opioids aside from morphine are excreted by the…?

A

Kidneys

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17
Q

Fentanyl is very addictive because?

A

It has a very fast clearance (because it is broken down in the blood by plasma cholinesterase’s)

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18
Q

Why is methadone used to wean people off heroin?

A

It has a slow clearance - low addictive potential as it remains in blood for longer

19
Q

Why is methadone metabolised very slowly?

A

It is a poor substrate for CYP450

20
Q

Which 2 enzymes metabolise the majority of opioids in the liver.

In the case of codeine, what do these 2 enzymes do

A
  1. CYP2D6 -activates codeine into morphine (slow process)
  2. CYP3A4 - deactivates codeine into inactive metabolites (fast process)

Consequently, only 10% of codeine is converted into morphine - this is what gives codeine its analgesic effect

21
Q

A polymorphism in the CYP2D6 means what for people who take codeine?

A

Codeine cant be activated - doesn’t have much effect

22
Q

Name 3 types of endogenous opioid peptides (they act on opioid receptors)

A
  1. Endorphins
  2. Enkephalins
  3. Dynorphins / neoendorphins
23
Q

Which type of opioid receptor do endorphins act on?

A

Mu receptors (or delta)

Pain/sensorimotor parts of the brain

24
Q

Which type of receptor do enkephalins act on?

A

Delta

Motor/cognitive function parts of the brain

25
Q

Which type of receptor do dynorphins act on?

A

Kappa

Neuroendocrine part of the brain

26
Q

What are the 3 means through which opioids have a depressive effect?

A
  1. Hyperpolarisation - increased K efflux
  2. Reduce Ca influx - important for Neurotransmitter exocytosis
  3. Reduce adenylate cyclase activity - general reduction in cellular activity
27
Q

What are the 7 main effects of opioids?

A
  1. Analgesic
  2. Euphoria
  3. Anti-tussive (depression of cough centre)
  4. Respiratory depression - most dangerous side effect
  5. Pupillary constriction
  6. Nausea/vomiting
  7. GI effects
28
Q

Generally speaking, how do opioids have their analgesic effects?

A

Increase pain tolerance

Decrease pain perception

29
Q

Where are the targets of opioids in terms of analgesia

A
  1. Dorsal horn - increases inhibition of sensory neurones
  2. PAG - enhances PAG firing
  3. NRPG - activates this

Opioids work by switching off GABA

30
Q

How do opioids cause euphoria

A
  1. Binds to Mu receptors on GABA interneurones - inhibits GABA
  2. Less inhibitory GABA input on dopaminergic neurones of the VTA
  3. Increased dopamine release at the nucleus accumbens
31
Q

What are the 2 means by which opioids exert an antitussive effect?

A
  1. Inhibits motor neurones linking the cough centre to the larynx. This Inhibition of 5HT1A receptor increases serotonin levels in the cough centre, decreasing cough reflex.
  2. Preventing transmission of information from sensory nerves to vagus
32
Q

Where are 5HT1A receptors found?

A

Dorsal raphe nucleus

33
Q

How do opioids cause nausea and vomiting

A
  1. Activate mu receptors in chemoreceptor trigger zone (CTZ)
  2. Activates medullary vomiting centre
  3. Stimulants from the stomach and intestines send signals to chemoreceptor trigger zone and medullary vomiting centre
  4. Opioids switch off GABA receptors which inhibit CTZ
34
Q

Opioids cause pupil constriction. Why?

A
  1. Oculomotor nerve is preganglionic PNS nerve to the eye - causes pupil constriction (nerve originates from Edinger-Westphal nucleus)
  2. Opioid receptors present on GABA receptors on Edinger-Westphal nucleus
  3. Less GABA inhibition of oculomotor nerve
35
Q

What is the pre-Botzinger complex and what does it do

A

Small area in the ventrolateral medulla - generates respiratory rhythm

36
Q

How can opioids cause respiratory depression

A
  1. Inhibits pre-botzinger complex (which is active in inspiration)
  2. Inhibits central chemoreceptors (chemoreceptors which provide tonic drive to respiratory motor output - sense changes in pH)

Ultimately opioids depress firing rate of central chemoreceptors - interfering with ability of brain to control respiration

37
Q

What are the main effects that opioids have on the GI tract

A
  1. Decreases gastric emptying
  2. Decreases gastric motility
  3. Less water absorption

ALL CAUSE CONSTIPTAION

38
Q

Which opioid receptor types are found on myenteric neurones?

A

Kappa and Mu

39
Q

Why are opioids good for preventing diarrhoea?

A

Depress intrinsic nervous system of GIT

40
Q

Symptoms of opioid use include itching, hives, hypotension, though opioids do not cause an allergic response. Whats going on?

A
  1. Opioids bind to mast cells in skin - promote histamine release
  2. Hydroxyl group at position 6 vital in this - only if this present can histamine release occur
41
Q

How does tolerance to opioids occur?

A

Receptor internalisation due to arrestin upregulation (if long term use)

42
Q

Opioids have a powerful physical withdrawal. How?

A

Body compensates for decreased adenylate cyclase function (when opioids were used) by upregulating adenylate cyclase function ; leading to shakes, sickness, etc

  • withdrawal symptoms resemble flu
43
Q

What are features of opioid OD

A
  1. Coma
  2. Respiratory depression
  3. Pinpoint pupils
  4. Hypotension
44
Q

What is the treatment for opioid OD and why

A

Naloxone - opioid receptor antagonist (it has a tertiary N with extended side chain)

Year 2 Collin (114 decks)

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