19) Opioids Flashcards
Types of opioid receptors
- μ [mu]
- δ [delta]
- κ [kappa]
On the basis of their interaction with several opioid receptors, individual drugs are classified as
- Agonists
- Mixed agonist-antagonists
- Antagonists
Opioids classified based on
- Spectrum of clinical use
- Strength of analgesia
- Ratio of agonist to antagonist effects
Spectrum of clinical uses
- Therapeutic uses (eg, analgesics, antitussives, and antidiarrheal drugs)
Strength of analgesia is based on
- Relative abilities to relieve pain
- May be classified as strong, moderate, and weak agonists
- Classification is independent of potency
Ratio of agonist to antagonist effects
- Agonists (full or partial receptor activators)
- Antagonists (receptor blockers)
- Mixed agonist-antagonists (activate one opioid receptor subtype and block another subtype)
Strong agonists (names)
- Morphine
- Methadone
- Meperidine
- Hydromorphone
- Fentanyl
- Sufentanil
Moderate agonists (names)
- Codeine
- Oxycodone
Weak agonists (names)
- Propoxyphene
Mixed agonist-antagonists (names)
- Buprenorphine
- Nalbuphine
Antagonists (names)
- Naloxone
- Naltrexone
- Nalmefine
Most opioids are well absorbed when taken orally, but theseundergo extensive first-pass metabolism
- Morphine
- Hydromorphone
- Oxymorphone
Opioids are widely distributed to
- Body tissues
With few exceptions, the opioids are metabolized by
- Hepatic enzymes
- Usually to inactive glucuronide conjugates
- Elimination by the kidney
Morphine-6-glucuronide
- Analgesic activity equivalent to that of morphine
- Morphine-3-glucuronide is its primary metabolite (neuroexcitatory)
Codeine, oxycodone, and hydrocodone are metabolized by
- Cytochrome CYP2D6 (isozyme exhibiting genotypic variability)
For codeine, CYP2D6 may be responsible for variability in analgesic response because
- The drug is demethylated by CYP2D6 to form the active metabolite, morphine
Meperidine is metabolized to
- Normeperidine
- May cause seizures at high plasma levels
Receptors for endogenous peptides are located in
- CNS and peripheral tissues
- Distributed in the brain & spinal cord
- Also outside the CNS (vascular tissues, cardia, airway/lung, gut and cells of the immune system)
Three major opioid receptor subtypes have been extensively characterized pharmacologically
- µ (mu)
- δ (delta)
- κ (kappa) receptors
All 3 opioid receptor subtypes appear to be involved in
- Antinociceptive and analgesic mechanisms at both spinal and supraspinal levels
The µ-receptor activation plays a major role in
- Respiratory depressant actions of opioids
- With κ-receptor activation slows GI transit
κ-receptor activation appears to be involved in
- Sedative actions
δ-receptor activation may play a role in
- Development of tolerance
All 3 major opioid receptors are coupled to their effectors by
- G proteins
- Activate phospholipase C or inhibit adenylyl cyclase
Major SE of opioids include
- Analgesia
- Sedation
- Euphoria
- Respiratory depression
- Constipation
- Miosis (pupil constriction)
- Truncal rigidity
- Flushing pruritis (through histamine)
Opioids (with the exception of meperidine) cause contraction of biliary tract smooth muscle, which can result in
- Biliary colic or spasm
- Increased bladder sphincter tone
- Reductionin uterine tone
When used for a prolonged period, these opioids may exacerbate pain (hyperalgesia)
- Morphine
- Fentanyl
- Remifentanil
K agonists, with weak µ-receptor antagonist activity
- Butorphanol
- Nalbuphine
- Pentazocine
_____ may act as a partial agonist or antagonist at the µ receptor
- Butorphanol
Buprenorphine is a µ-receptor partial agonist with weak antagonist effects at κ and δ receptors. These characteristics can lead to
- Decreased analgesia and precipitate withdrawal symptoms when used in patients taking conventional full µ-receptor agonists
The mixed agonist-antagonist drugs often cause
- Sedation at analgesic doses
- Dizziness, sweating, and nausea may also occur
- Anxiety, hallucinations, and nightmares are possible adverse effects
Mixed agonist-antagonist drugs respiratory effects
- Respiratory depression may be less intense than with pure agonists
Chronic use of mixed agonist-antagonist
- Tolerance develops with chronic use, but is less than the tolerance that develops to the full agonists
Pure opioid receptor antagonists that have greater affinity for µ receptors
- Naloxone
- Nalmefene
- Naltrexone
A major clinical use of the opioid antagonists
- Management of acute opioid overdose
Naloxone and nalmefene are given
- Intravenously
Because naloxone has a short duration of action (1–2 h), a _____ preparation of naloxone has recently been made available to treat opioid overdose promptly
- Nasal insufflation
Nalmefene has a duration of action of
- 8–12 h
Naltrexonehas a long elimination half-life, blocking the actions of strong agonists (eg, heroin) for up to
- 48 h after oral use
Unlike the older drugs, two new antagonists,_____and_____ do not cross the blood-brain barrier
- Methylnaltrexone
- Alvimopan
Methylnaltrexone and alvimopan block adverse effects of strong opioids on
- Peripheral µ receptors (including those in the GI tract responsible for constipation)
Naloxegol is a pegylated form of
- Naloxone
- It is also used to reverse opioid constipation
Miscellaneous opioids
- Tramadol
- Tapentadol
Tramadol
- Weak µ-receptor agonist
- Partially antagonized by naloxone
Tramadol analgesic activity
- Mainly based on blockade of the reuptake of serotonin
- Weak norepinephrine reuptake blocker
Tramadol is effective in treatment of
- Moderate pain
- Has been used as an adjunct to opioid analgesics in chronic pain syndromes
Tramadol is contraindicated in
- Patients with a history of seizure disorders
- Risk of the serotonin syndrome if it is co-administered with SSRIs
Tapentadol
- Strong norepinephrine reuptake-inhibiting activity
- Modest µ-opioid receptor affinity
Tapentadol treatment effectiveness
- Less effective than oxycodone in the treatment of moderate to severe pain
- Causes less gastrointestinal distress and nausea
Tapentadol should be used with caution in
- Seizure disorders
Fentanyl brand name
- Duragesic
Hydromorphone brand name
- Dilaudid
Meperidine brand name
- Demerol
Morphine brand name
- MS contin
- Kadian
Methadone brand name
- Methadose
Oxymorphone brand name
- Opana
Sufentanyl brand name
- Sufenta
Tramadol brand name
- Ultram
Codeine brand name
- No brand name listed
Hydrocodone brand name
- Norco
- Vicodin
Oxycodone brand name
- Percocet
- Oxycontin
Buprenorphine brand name
- Subutex
Buprenorphine and naloxone brand name
- Suboxone
Nalbuphine brand name
- Nubain
Naloxone brand name
- Narcan
Naltrexone brand name
- Vivitrol
