Opioid Analgesics Flashcards
What are the medical circumstances in which opioids are indicated and contraindicated?
Most dangerous side effect is respiratory depression. This is the primary cause of opioid-induced death. Therefore is contraindicated in case of suspected head injury and use caution when respiratory function is compromised (asthma, emphysema, severe obesity)
What are the potential adverse interactions of opioids with other drugs?
- CNS Depressants: Barbituates can can have additive or synergistic CNS depression. Can increase metabolism of some opioids
- Phenothiazines (antipsychotics): Increases respiratory depression and hypotensive effects of opioids. Some can reduce analgesic actions of opioids
- MAO inhibitors and Tricyclic Antidepressants: Increases respiratory depression. Can induce CNS excitation, delirium and seizures
What are the life-threatening side effects of opioid drugs, and the appropriate means to avoid/treat these actions?
Most dangerous side effect is respiratory depression. This is the primary cause of opioid-induced death.
What is the mechanism by which opioids act upon the central and peripheral nervous systems?
There are three major classes of opioid receptors- u, d, k- which are all coupled to GTP-binding proteins. There is a unique distribution of the receptors throughout the CNS and PNS.
Opioid receptor G-protein signaling mechanisms DECREASE neuronal excitability by inhibiting VGCCs or by activating potassium channels or inhibiting cAMP synthesis
What are the definitions of tolerance and dependence, and the degree to which these phenomena develop in various opioid-sensitive systems
Tolerance: A decreased response to a drug as a result of previous exposure. The ned for an increased dose of a drug to produce the same pharmacological effect (commonly seen over 2-3 weeks of normal use at therapeutic doses)
Dependence: Easily produced by opioids; most common in pain-free individuals abusing opioid drugs of long-term chronic pain treatment. Physically need the continued use of drug to maintain a normal physiological state. The continued use of a drug is to prevent withdrawal. Also have the psychological, continued desire or craving for a drug
What are the sites of opioid action in the CNS and periphery?
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Know that in the case of chronic pain associated with terminal malignancy the responsibility of the physician is to ensure that the patient is pain-free and comfortable.
Will do!
What are the different classes of endogenous opioids, and representatives of each class?
- Morphine and other opioid phenanthrenes (agonsits at the u receptor) Examples: Morphine, Heroin, Codeine, Oxycodone, Hydrocodone, Tramadol
- Meperidine and other phenylpiperidnes (agnosits at u receptors). Examples: Meperidine, Loperimide, Fentanyl
- Methadone and other phenylheptamines (agonsits of u receptors). Examples: Methadone,
- Mixed Agonist/Antatgonist and Partial Agonists (Benxomorphans). Example: Buprenorphine, Pentazocine,
- Opioid Antagonists. Example: Naloxone (Narcan), Naltrexone, Alvimopam,
Learn the names and uses of opioid agonists from each classification.
Morphine: severe pain (post-op, severe trauma)
Heroin: no medicinal use
Codeine: most common opioid analgesic
Oxycodone: equipotent with morphine
Hydrocodone: antitussive, weak analgesic
Tramadol: blocks monoamine uptake to potentiate descending pain pathway
Meperidine: treat severe pain (faster onset than morphine)
Loperimide: anti-diarrheal
Fentanyl: 100 times for potent than morphine
Methadone: opioid maintenance theraphy for addiction
Buprenorphine: long-acting, maintenance therapy
Pentazocine: spinal analgesia with less respiratory depression
How do opioids inhibit transmission in pain pathways?
- INHIBITION of spinal cord/ascending pain pathway. Inhibition of presynaptic excitatory neurotransmitter release from primary afferent terminals in dorsal horn of the spinal cord (substance P, glutamate). Inhibition of excitatory postsynaptic spinothalamic “ascending” output neurons
- ACTIVATION of descending pain pathway. Activation of “descending” inhibitory output systems in the medulla, periaquedcutal gray and locus coeruleus. Mediated by 5-HT and NE
Side Effects of Opioids
Behavioral: Euphoria, Dysphoria, Sedation, Lethargy, Behavioral Excitation
Nausea and Vomiting (more common in ambulatory pts). In high doses, suppresses vomiting
Cough Suppression; inhibitory effects of cough center in the medulla
Miosis
Constipation
Urine retention
Effects on biliary tract- for bile stone pain, must prescribe opiod + smooth muscle relaxant or the pain will become worse
Many opiates can cause histamine release from mast cells- possible anaphylaxis
