OPIOID ANALGESIC Flashcards by Shahryar Farooq

MOA of Opioid analgesics?

• Opioid agonists produce analgesia by activating
receptors located primarily in brain and spinal
cord involved in transmission and modulation of pain.

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Opioid Receptor Types?

• Three major classes of opioid receptors: mu, delta and kappa.
• The three are G protein linked receptors.
• The three couple to Gi.
• The majority of opioid analgesics act primarily
at the µ receptor.

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Relation of physiological effects to receptor type?

Supraspinal analgesia

Spinal analgesia

Respiratory depression

Reduced GI motility

Psychotomimesis

Sedation

Supraspinal analgesia µ,mu,delta

Spinal analgesia µ,kappa,delta

Respiratory depression µ

Reduced GI motility µ

Psychotomimesis kappa

Sedation µ,kappa

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CELLULAR ACTIONS OF OPIOIDS?

• The opioids have two actions on neurons:
• They close voltage-gated Ca2+ channels on
presynaptic nerve terminals.
• They open K+ channels on postsynaptic
neurons.
• Both actions reduce neurotransmitter release.

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Analgesia effects due to

Inhibit ascending pain transmission.

* Activate descending pain-inhibitory circuits.

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Spinal analgesia is due to opioids inhibiting?

Opioids inhibit ascending pain transmission

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Describe supraspinal analgesia?

• The descending pain-inhibitory neurons are
inhibited by GABA.
• Opioids inhibit GABAergic neurons.
• In this way opioids activate the pain-inhibitory
descending neurons.
• This results in enhanced inhibition of pain
transmission.

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Pure agonists, mixed agonist-antagonist, and antagonist?

Pure agonists
• High affinity for mu receptors.
• Lower affinity for gamma and kappa receptors.
Mixed agonist-antagonists
• Agonist and antagonist activity on different receptors.
Antagonists
• Antagonists at all receptors

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CNS Effects of opioids?

Analgesia
Euphoria
Sedation and drowsiness
Respiratory depression
Cough suppression
Miosis
Truncal rigidity
Nausea and vomiting

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Peripheral effects of opioids?

• Hypotension
• Constipation
• Contraction of biliary smooth muscle. May
result in biliary colic.
• Pruritus

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Metabolism of opioids?

• Opioids are converted mainly to glucuronides,

which are then excreted by the kidneys.

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Metabolism of morphine and Heroine?

Morphine is conjugated to:
• Morphine-3-glucuronide (M3G)
• Morphine-6-glucuronide (M6G)

• Heroin (diacetylmorphine) is hydrolyzed to monoacetylmorphine and to morphine.

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What metabolizes Codeine, oxycodone, and hydrocodone

• Codeine, oxycodone, and hydrocodone are
metabolized by CYP2D6.
• Codeine is converted to morphine.

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Metabolism of Meperidine?

• Meperidine is converted to normeperidine.
• Accumulation of normeperidine, may occur in
patients with decreased renal function.
• In high concentrations, normeperidine may
cause seizures.

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Metabolism of Fentanyl and Methadone?

• Fentanyl is metabolized by CYP3A4 to inactive
metabolites.
• Methadone is metabolized by multiple P450 enzymes.

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Use for opioid analgesics?

• Analgesia: Treatment of moderate to severe
pain.
• Acute Pulmonary Edema
• Cough
• Diarrhea
• Applications in Anesthesia

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AE of opioid analgesics?

Adverse effects of the opioid analgesics include
Nausea
Vomiting
Sedation
Itching
Constipation
Urinary retention
Hypotension
Respiratory depression

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• The most common adverse effects reported with

the use of opioid analgesics are

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Nausea
Vomiting
Sedation
Itching
Constipation

Define dependence and addiction?

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• With frequent administration there is tolerance.
• Physiological dependence develops too.
• Dependence is defined as the occurrence of a
withdrawal syndrome.
• Physical dependence is common when opioids
are used for therapeutic purposes.
• However, addiction is not.

Contraindications and cautions of opiods?

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USE OF PURE AGONISTS WITH WEAK PARTIAL
AGONISTS
• When a weak agonist is given to a patient
receiving a strong agonist, there is a risk of
diminishing analgesia or even inducing a state of
withdrawal.

PATIENTS WITH HEAD INJURIES
• CO2 retention caused by respiratory depression
results in cerebral vasodilation.
• In patients with elevated intracranial pressure, this
may lead to lethal alterations in brain function.

Contraindications and cautions of opioids continued?

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PREGNANCY
• The fetus may become dependent.
PATIENTS WITH IMPAIRED PULMONARY
FUNCTION
• The depressant properties of the opioid
analgesics may lead to acute respiratory failure.
PATIENTS WITH IMPAIRED HEPATIC FUNCTION
• Morphine and its congeners are metabolized
primarily in the liver.
PATIENTS WITH IMPAIRED RENAL FUNCTION
• Half-life of opioids is prolonged

Drug interactions of sedative hypnotics and MAO inhibitors?

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Sedative-hypnotics
• Increase CNS depression, particularly respiratory depression.

MAO Inhibitors
• Some opioids inhibit serotonin reuptake: e.g.,
methadone, meperidine, tramadol, fentanyl.
• The concurrent use of these opioids and an
MAOI may trigger a “serotonin syndrome.”
• Features: Delirium, hyperthermia, headache,
hyper- or hypotension, rigidity, convulsions,
coma, and death.
• Manufacturers of opioids contraindicate the
concurrent use of MAOIs.////

List opioid agonists?

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MORPHINE, HYDROMORPHONE, OXYMORPHONE
HEROIN
MEPERIDINE
FENTANYL
METHADONE
LEVORPHANOL
CODEINE, OXYCODONE, HYDROCODONE

Describe MORPHINE, HYDROMORPHONE &

OXYMORPHONE affinities?

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Useful in treating severe pain.
High affinity for mu receptors.
Lower affinity for delta and kappa receptors.
Morphine is the DOC for severe pain.

Describe heroin metabolism to morphine and consequences of its metabolism?

• Rapidly hydrolyzed to 6-MAM, which is hydrolyzed to morphine. • Both heroin and 6-MAM are more liposoluble than morphine and enter the brain more readily. • Morphine and 6-MAM are responsible for the pharmacological actions of heroin.

Meperidine receptor affinity, recommendation, pk, and ae?

• µ receptor agonist. • Not recommended for chronic pain due to metabolite toxicity. Only used for short-term treatment of acute pain. • Meperidine has a half-life of 3 hours. • The metabolite normeperidine has a half-life of 20 hours. • When doses of meperidine are repeated at short intervals normeperidine accumulates. • This leads to tremors, muscle twitches, and seizures.

Fentanyl affinity, pk, and use?

* mu agonist. * Rapid onset. * Short duration of action (15-30 minutes). * 100 times more potent than morphine. * Used for severe pain.

Methadone spectrum, pk, and moa?

* Less euphoria than morphine. * Longer duration of action than morphine. * Effective in severe pain. * MOA: * μ receptor agonist * NMDA receptor antagonist * 5-HT and NE reuptake inhibitor

Methadone uses?

• Methadone substitution is the preferred method of managing opioid withdrawal for addicted patients. • This is because methadone has a long half-life and less profound sedation and euphoria • Due to the long half-life of methadone, the abstinence syndrome is prolonged but less severe. • Methadone is a useful drug for detoxification and maintenance of the chronic relapsing heroin addict.

Methadone AE?

• QT prolongation, torsades de pointes and death | have been reported.

Action of Levorphanol?

* μ, δ, and κ agonist. * Serotonin and norepinephrine reuptake inhibitor * NMDA receptor antagonist * Used in severe pain.

Difference between oxycodone and hydrocodone?

• Oxycodone is used for moderate to severe pain. Formulated alone or in combination with a nonopioid. • Hydrocodone is used for moderate to severe pain. Only available in combination with acetaminophen or a NSAID.

Codeine use, affinity, and conversion metabolism?

• Codeine is used for mild to moderate pain. • Codeine has low affinity for opioid receptors. • The analgesic effect of codeine is due to its conversion to morphine by CYP2D6.

list the mixed agonist-antagonists?

PENTAZOCINE BUTORPHANOL NALBUPHINE BUPRENORPHINE • The mixed opioid agonist–antagonists are potent analgesics in opioid-naive patients. • They precipitate withdrawal in patients who are physically dependent on opioids.

kappa agonist and a µ antagonists.

* Pentazocine * Butorphanol * Nalbuphine

Buprenorphine affinities?

• Buprenorphine: weak µ agonist and kappa antagonist

PENTAZOCINE, BUTORPHANOL, NALBUPHINE & | BUPRENORPHINE recommendations and ae?

• Not recommended as routine analgesics, because they have ceiling effect. • Pentazocine, butorphanol and nalbuphine may cause psychotomimetic effects. • Buprenorphine is approved for management of opioid addiction.

Tramadol actions, uses, and ae?

``` • Weak mu agonist and norepinephrine and serotonin reuptake inhibitor. • Used to treat moderate pain. • Useful in neuropathic pain. • Increased risk of seizures in patients with a seizure disorder. ```

Naloxone and Naltrexone actions and uses?

• Antagonists at mu, delta, and kappa receptors. • Naloxone is used in the treatment of acute opioid overdose. • Naltrexone is used for opioid and alcohol addiction.

High efficacy Opioids?

``` Morphine Hydromorphone Oxymorphone Methadone Meperidine Fentanyl Levorphanol Nalbuphine Buprenorphine Butorphanol ```

Moderate-high efficacy, moderate, and low efficacy opioids?

Oxycodone: Moderate-High Hydrocodone Pentazocine: Moderate Codeine: Low

ANTITUSSIVES: DEXTROMETORPHAN & CODEINE cough suppressant mechanism?

• Opioid analgesics are very effective for the suppression of cough. • This effect is often achieved at doses below those necessary to produce analgesia. • The receptors involved in the antitussive effect appear to differ from those associated with other actions of opioids.

ANTIMOTILITY AGENTS: | DIPHENOXYLATE AND LOPERAMIDE uses, actions?

• Widely used in the treatment of diarrhea. • Their actions are mediated by µ receptors on enteric nerves, epithelial cells, and muscle. • At usual doses, diphenoxylate and loperamide lack analgesic effects. • They decrease motility of smooth muscle of the intestinal wall.

• Pentazocine • Butorphanol • Nalbuphine action?

Kappa agonist and a µ antagonists.

OPIOID ANALGESIC Flashcards

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