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Pharm Exam 2 > Bannon: Opiod Drugs > Flashcards

Bannon: Opiod Drugs Flashcards

1
Q

Hydromorphone (Dilaudid)

A

Older semi-synthetic morphine derivative used as painkiller

More potent than morphine; equivalent efficacy

Oft-requested in ER
Was used primarily as immediate release, but now other formulations (extended-release in ‘11)

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2
Q

Opiate Receptors:

A

Mu
Kappa
Delta

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3
Q

Mu:

Encoded by:

A

Mu: for morphine (endogenous ligands are beta-endorphin and more recently recognized endomorphins)

  • Encoded by MOP gene
  • Many opioid agonists and antagonists show preference here
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4
Q

Kappa:
Encoded by:
What is relatively strong here?
In some cases, have actions opposite to:

A

Kappa: for ketoclazocine (endogenous ligand is dynorphin)

  • Encoded by KOP gene
  • Partial agonists relatively strong here
  • May have more importance in spinal anesthesia
  • In some cases, have actions opposite to mu receptors
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5
Q

Delta:
Encoded by:
Morphine and other opioid drugs:

A

Delta: for vas deferens (endogenous ligand is enkephalin)

  • Encoded by DOP gene
  • Morphine and other opioid drugs weaker here
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6
Q

Opioid-Like Receptor NOP:

Insensitive to:
Elicits : (2)

A

Opioid-Like Receptor NOP: nociceptin/orphanin FQ peptide receptor
o Insensitive to classical opioid antagonists
o Elicits hyperalgesia (increased sensitivity to pain) and anti-opiod effects suprasinally
o Elicits antinociceptive spinal effects

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7
Q

Single Gene Results in Several Receptor Subtypes Seen Pharmacologically
Example:

A

Single Gene Results in Several Receptor Subtypes Seen Pharmacologically:

Example: MOP gene elicits μ1, μ2, and μ3

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8
Q

Single Gene Results in Several Receptor Subtypes Seen Pharmacologically

Possible Explanations: (3)

A

Alternative splicing of common gene products (really not important)

Receptor dimerization to give different subtypes (may be important)*

Interaction of common gene product with signaling proteins (may be important)*
- For example, drug dependent activation of signaling pathways (which pathway gets activated depends on which drug bind)

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9
Q

Morphine (Gold Standard)

Absorption:
Metabolism:

A

Absorption: well absorbed by multiple routes of administration (oral, IM, IV, subQ, rectal, epidural or intrathecal)

Metabolism: extensive first-pass metabolism limits oral use (~35% bioavailability)

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10
Q

Morphine (Gold Standard)

Excretion:

A

Polar metabolites excreted in the urine

  • After chronic use, polar metabolite morphine-6-glucuronide is responsible for analgesic effects
  • Therefore, toxicity may result in renal insufficiency due to decreased clearance of this active metabolite (confusion, agitation)
  • Morphine-3-glucuronide is another minor metabolite that may be proconvulsant (CNS excitatory properties; again, take care with renal insufficiency)

Glucoronide conjugates also secreted in bile

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11
Q

Morphine (Gold Standard)

Formulations: (4)

A

Long-Acting SR Beads
Morphine SR + Naltrexone (Embeda)
Post-Surgical Formulations (DepoDur)
Infumorph/Astromorph/Duramorph

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12
Q

Morphine

Long-Acting SR Beads:

A

Long-Acting SR Beads: to be swallowed; if chewed or combined with alcohol, can cause release of too much morphine

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13
Q

Morphine

Morphine SR + Naltrexone (Embeda):

A

Morphine SR + Naltrexone (Embeda): for continual use with decreased risk of abuse (if crushed, opioid antagonist naltrexone will be freed)

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14
Q

Morphine

Post-Surgical Formulations (DepoDur):

A

Post-Surgical Formulations (DepoDur): single liposomal injection (last 48 hours)

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15
Q

Morphine

Infumorph/Astromorph/Duramorph:

A

Infumorph/Astromorph/Duramorph: continual epidural or intrathecal infusion formulations

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16
Q

Uses/Effects of Morphine:
Analgesia
Basics:

A

Basics:

  • Pain relief without general sensory loss or loss of consciousness
  • Pain reported as present but no longer bothers the patient
  • Better against continuous dull pain than sharp, intermittent pain
  • Multiple supraspinal (ie. brain) and spinal sites of action
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17
Q

Uses/Effects of Morphine:
Analgesia
Issues: (2)

A

SIGNIFICANT tolerance to this effect (as well as most others)

Paradoxical hyperalgesia may occur (MOA unclear- possibly increased glutamate transmission in the dorsal horn)

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18
Q

Uses/Effects of Morphine:
Analgesia
Use:

A

Use: surgical anesthesia (in combination with other drugs- multimodal anesthesia)

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19
Q

Uses/Effects of Morphine
Mood and Cognitive Effects
Basics:

In normal (Pain-Free) Individuals:

A

Basics: cause euphoria and tranquility

Normal (Pain-Free) Individuals: often unpleasant
o Dysphoria (intense feelings of depression or discontent)
o Difficulty thinking
o Drowsiness
o Nausea

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20
Q

Uses/Effects of Morphine
Mood and Cognitive Effects

Site of Action:
Side Effects:
Use in Combat Injured Subjects:

A

Site of Action: unclear (locus ceruleus, mesolimbic DA, nucleus accumbens all possible)

Side Effects: confusion and sedation (especially in the elderly)

Use in Combat Injured Subjects: prompt administration of morphine reduced risk for PTSD

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21
Q

Uses/Effects of Morphine
Miosis

Cause:
Sign of Toxicity/Abuse:

A

Cause: excitation of the PS innervation to the pupil

Sign of Toxicity/Abuse: little/no tolerance to this effect with chronic use

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22
Q

Uses/Effects of Morphine
Cough Inhibition

Mechanism:

A

Mechanism: depression of cough reflex mediated by medullary cough center (can administer a dose that easily provides cough suppression without respiratory depression)

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23
Q

Uses/Effects of Morphine
Respiratory Depression

Mechanism:
Importance:

A

Mechanism: dose-related depression mediated via brainstem centers

  • Decreased response to CO2
  • Synergistic depression seen with many other CNS drugs

Importance: especially of concern in patients with COPD and pain

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24
Q

Uses/Effects of Morphine
Increased Intracranial Pressure

Mechanism:
Importance:

A

Mechanism: due to increased pCO2 (causes cerebrovascular dilation)

Importance: needs to be taken into consideration with head trauma

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25
Q

Uses/Effects of Morphine
Nausea/Emesis
Mechanism:

A

Mechanism: mediated by area postrema chemoreceptor trigger zone

  • Relatively uncommon in supine patients but common in ambulatory patients (hints at possible vestibular component to mechanism)
  • Tolerance to this effect develops rapidly
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26
Q

Uses/Effects of Morphine
Cardiovascular

Effects:
Mechanism:

A

Effects: peripheral vasodilation (reduced peripheral resistance) and inhibition of baroreceptor reflex
- Not evident in supine patient, however, orthostatic hypotension and fainting can be seen upon standing

Mechanism: may be due in part to histamine release

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27
Q

Uses/Effects of Morphine
Cardiovascular

Use:

A

Use: IV morphine used for immediate relief of dyspnea from acute pulmonary edema associated with left ventricular failure
- Decreases anxiety, venous tone and peripheral resistance

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28
Q

Uses/Effects of Morphine
GI

Effects:

A

Effects: decreased propulsive contractions (leads to increased water absorption and constipation)
- Little tolerance to this effect and therefore can be a problem with chronic use

29
Q

Uses/Effects of Morphine

Ureter:
Uterus:
Itching:

A

Ureter: increase sphincter tone to decrease urinary output (especially in the elderly)

Uterus: leads to prolongation of labor (also need to worry about fetal effects)

Itching: due to effects on CNS and peripheral nerves
- Mechanism: probably substance P and/or histamine related

30
Q

Morphine
Toxicity

Causes:

A

Causes: clinical overuse, renal insufficiency, accidental OD or suicide attempt

31
Q

Morphine
Toxicity

Key Signs:

A

Key Signs: coma, respiratory depression and pinpoint pupils

32
Q

Heroin

A

Potent and fast-acting (“heroic”)

Converted to morphine by deacetylation in vivo

33
Q

Oxycodone

Use:

Cancer patients:
with aspirin:
acetaminophen:
ibuprofen:

A

Use: painkiller (has a morphine backbone) for the short-term relief of moderate pain

  • Cancer patients (ER release form)
  • In combination with aspirin (Percodan)
  • In combination with acetaminophen (Percocet)
  • In combination with ibuprofen (Combunox)
34
Q

Oxycodone

Absorption:
Efficacy:

A

Absorption: more orally active than morphine

Efficacy: roughly equivalent maximal efficacy to oral morphine

35
Q

Oxycodone:

Acurox:

A

Popular Drug of Abuse: possibly lethal

Acurox: recently FDA approved drug used as a deterrent for abuse

  • Combination of niacin (unpleasant effects) and inactive ingredients that convert to a gel upon attempted extraction
  • Unfortunately, has driven up abuse of other opiates
36
Q

Meperidine

Use:

A

Use: painkiller whose use is now limited to acute pain management (ie. post-surgical)

  • Rapid onset and short duration of action
  • Irritating to tissue if given IM
37
Q

Meperidine

Unique Toxicity:

A

Unique Toxicity:

  • Seizures, twitching, delirium and psychiatric changes
  • Due to accumulation of a long-lived metabolite
38
Q

Codeine

MOA:

A

MOA: weak full agonist with modest analgesic activity after deacetylation to morphine
- However, 10% of the population lack the enzyme for conversion

39
Q

Codeine

Pharmacokinetics; (3)

A

Absorption: good oral absorption

Highly protected from first pass glucuronidation

High oral:parenteral potency ratio

40
Q

Codeine

Use:

A
  • Most often given in combination formulations (ie. Tylenol 3)
  • Also a sustained release formulation
  • Antitussive effects (possibly through distinct receptors; efficacy questioned for this use)
41
Q

Fentanyl
Pharmacokinetics

Potency:
Duration of Action:

A

Potency: 80-100x more potent than morphine (effective but potentially dangerous)

Duration of Action: short (with no active metabolites)

42
Q

Fentanyl

Use: (2)

A
  • IV use for surgical anesthesia (often with droperidol)

- Acute post-op pain (patient controlled analgesia by transdermal iontophoresis)

43
Q

Fentanyl

Other unique delivery routes for pain in opioid-tolerant patients:

A

Transdermal patch (change every 48-72 hours)
o Be careful of exposure of patch to heat
o Be careful with concurrent use of CYP3A4 inhibitors (ie. clarithromycin, ketoconazole)

Effervescent buccal tablet, buccal film or lonzenge on a stick (for breakthrough pain)

44
Q

Propoxyphene (Darvon)

MOA:
Efficacy:
Safety:

A

MOA: partial agonist painkiller

Efficacy: very low

Safety: low therapeutic index (not very safe)

45
Q

Propoxyphene (Darvon)

Formulations:
Toxicity:

A

Formulations:

  • Combinations with aspirin/caffeine (Darvon compound)
  • Combinations with acetaminophen (Darvocet)

Toxicity: accumulation of a toxic metabolite can lead to a variety of effects
- Cardiotoxicity, convulsions, OD (being pulled from the market!)*

46
Q

Nalbuphine/Butophanol/Pentazocine

MOA:
Side Effects:

A

MOA: kappa agonists and weak mu mixed agonists or antagonists

Side Effects:
- More adverse behavioral symptoms (psychomimetic effects/Salvinorin-A like effects)

47
Q

Nalbuphine/Butophanol/Pentazocine

Effects: (4)

A

Effects:

  • Less analgesia
  • Less respiratory depression
  • Less tolerance
  • Less naloxone reversibility*
48
Q

Tramadol

Structure:
MOA:
Use:

A

Structure: synthetic codeine derivative

MOA: active metabolite is a weak mu agonist

  • Also blocks 5HT and NE uptake
  • Some GABA mechanisms also suspected

Use: should be limited to chronic neuropathic pain (due to need for slow titration); however, being seen more and more for use in acute pain

49
Q

Tramadol

Formulations:

A
  • Extended release

- In combination with acetaminophen (Ultracet)

50
Q

Tramadol

Side Effects: (3)

A
  • Reports of increased frequency of seizures
  • Esp. in patients with seizure history or on antidepressant medications
  • DDIs may lead to serotonin syndrome (buildup of serotonin)
51
Q

Tapentadol

Structure:
MOA:
Risks:

A

Structure: tramadol-like compound

MOA: weak mu agonist (also a NE reuptake inhibitor; NOT 5HT)

Risks: risk of abuse and serotonine syndrome unclear at this point

52
Q

Methadone

MOA:
Pharmacokinetics:
Half-life:

A

MOA: full agonist

Pharmacokinetics:

  • Long Half-Life: slow metabolism in most people and high fat solubility
  • Need careful initial titration
  • Hepatic metabolism: no active metabolites, and therefore safe in patients with renal problems
53
Q

Methadone

Use:

A

Chronic pain (esp. in patients with renal issues)

Addict detoxification or maintenance

54
Q

Buprenorphine

MOA:
Pharmacokinetics:
Duration:

A

MOA: partial agonist at mu receptor (but more potent than full agonist methadone)

Pharmacokinetics:
- Long Duration of Action: very slow dissociation from receptor (resistance to naloxone receptor)

55
Q

Buprenorphine

Use:
Formulations: (3)

A

Use:
- Opiate dependence (can be prescribed in office setting)

Formulations:

  • Sublingual formulation
  • Combination with naloxone (Suboxone) to prevent abuse
  • Sustained release formulation (once a month dosing) currently being tested
56
Q

Naloxone and Naltrexone

MOA:

A

MOA: opiate receptor antagonists (mu > kappa and delta)

57
Q

Naloxone:

A

ER form for opiate OD

Blocks antidiarrheal, antitussive and analgesic effects of opioids

58
Q

Naltrexone:

A

Oral form used for prevention of relapse to heavy drinking

  • Poor compliance
  • Hepatotoxicity if taken at 3-4x the recommended dose

Recently approved injectable ER formulation (once a month) to maintain alcohol abstinence

59
Q

Naltrexone SR + Buprenorphine SR (Contrave):

A

Naltrexone SR + Buprenorphine SR (Contrave): recently approved for obesity treatment

  • Modestly effective
  • Concerns about cognitive and CV side effects
60
Q

Methylnaltrexone

MOA:
Administration:
Use:

A

MOA: opiate antagonist that does NOT cross BBB (therefore, will not affect analgesia)

Administration: injectable

Use: approved recently for opioid-induced constipation in terminal patients under palliative care

61
Q

Diphenoxylate/Loperamide

MOA:
Action:

A

MOA: mu receptor agonists

Action: meperidine congeners that have very poor absorption from the gut (exclusive use in diarrhea)

62
Q

Diphenoxylate/Loperamide

Formulations: (2)

A

Diphenoxylate + Atropine (Lomotil)

Loperamide (Immodium)

63
Q

Dextromethorphan

Structure:
MOA:

A

Structure: D isomer of methylated levorphanol (does not have typical opioid effects)

MOA: NMDA receptor antagonist and sigma receptor agonist

64
Q

Dextromethorphan

Use: (2)

A

Antitussive (MOA unclear, efficacy questioned but seems to work)

Abuse potential now evidence

65
Q

Dextromethorphan

Contraindications:

A

Contraindications: young children; also discouraging use of combination products (ie. with antihistamines etc.)

66
Q

Nalfurafine

MOA:
Use:

A

MOA: new kappa opioid receptor agonist (no action at mu receptors)

Use: relief of itching
- However, taking a kappa agonist should be VERY unpleasant (recall psychomimetic effects)

67
Q

Current Investigative Uses of Opioid Drugs: (3)

A
  • Antidepressants
  • Anti-addiction
  • Cardioprotection

.

68
Q

General Principles of Therapeutic Use of Opioids: (2)

A

Only symptomatic relief: do not treat underlying disease

Tolerance: repeated administration can lead to tolerance and physical dependence; however, important to note that most people that are using prescribed opioids do NOT become addicts

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