M3s4 Opioids Flashcards
Opioids
-class of drug naturally found within the opium poppy plant, papaver somniferum
-drugs obtained from papaver somniferum have been used for millennia
-initially, used as crude extract, but for the last 200 years, used as purified substances, producing clinically used drugs which as morphine and codeine
-morphine is one of the most useful drugs known to pharmacologists but renowned for causing opioid use disorder (OUD)
Classes of opioids
-opioid any natural or synthetic substance which exerts action on the body through binding to opioid receptors
-many different types of opioids exist, most being analgesics and having high potential for misuse and OUD
Endogenous opioids:
-not administered drugs but made in body that bind to opioid receptors and exert analgesic effects
-three families of endogenous opioids are: enkephalins, dynorphins, and beta-endorphins (aka endorphins)
-affect perception of pain and the emotional response to pain
-may influence mood and are associated with the reward pathways in brain
Natural opioids:
-not made in Brody but deceived from opium poppy plant
Morphine => binds directly to opioids receptors and used clinically to treat severe acute and chronic pain, and can cause euphoria
Codeine => converted to morphine in body by liver enzymes. Approximately 10 times more potent than codeine. Commonly prescribed drugs containing codeine is Tylenol, a combination of codeine and acetaminophen
Semi-synthetic opioids:
-slightly altered versions of morphine that are chemically changed to obtain different pharmacological properties (ex. Potency, duration of action, distribution) but typically maintain a very similar effect profile
Hydromorphone => clinically used for analgesia, is 5 times more potent than morphine
Diacetylmorphine (brand name heroin)=> used as part of injectable opioid agonist therapy (iOAT) to manage OUD. Limited other clinical uses of diacetylmorphine, therefore, most often synthesized foe illicit use. Is 2-5 times more potent (greater effects) than morphine
Synthetic opioids:
-not derived from morphine
-chemically synthesized to bind to opioid receptor
-designed to elicit similar pharmacological responses to morphine (I.e. analgesia, euphoria) or to be used for other clinical purposes that are related to other functions of opioid receptors
Fentanyl and related compounds => approx. 100 times more potent than morphine and designed to treat severe acute and chronic pain. Illicit synthesis and use of fentanyl, and other new, related and more potent compounds (ie. carfentanyl, furafentanyl) contribute to OUD crisis
Loperamide => over counter drug that leverages a common side effect of opioids, constipation, and used to treat diarrhea. Chemical structure of drug is such that very little enters and remains in the circulation, but instead stays in intestine or quickly metabolized. This prevents illicit use as it does not cause substantial analgesia or euphoria
Methadone=> used for analgesia and can be used in treatment of OUD as it prevents withdrawal symptoms however does not cause euphoria in stabilized patient
Opioid receptors
-located in both the central and peripheral nervous system
-these receptors are also located in the gastrointestinal tract and are responsible for the constipation and caused by opioids
MU (m funky)
-present in all structures of brain and spinal cord
-mediate analgesia and responsible for morphine-mediated depression of respiration in brain stem
-because the same receptor responsible for both effects, it is difficult to obtain drugs with a separation between the two responses
-these receptors also involved in the compulsive misuse of opioids
KAPPA (k)
-involved in analgesia, dysphoria (state of dissatisfaction or unease) and miosis (pinpoint pupils)
DELTA (funky s)
-involved in analgesia at the level of the spinal cord and brain
-may also modulate the emotional response to opioids
Mechanism of action of opioids
-morphine and other opioids will block pain pathways in the spinal cord and brain
-effect is primarily exerted through activation of mu opioid receptors
Reduce neurotransmitter release
-prevent pain signals from travelling by reducing neurotransmitter release from presynaptic neurons and reducing the effect on postsynaptic neurons
Reduce emotional reaction
-reduce emotional reaction to pain through modulation of the limbic system
*refer to goodnotes for image
Long term use of opioids
Marked physiological deterioration or psychological impairment does not seem to occur with long-term use of opioids
Short-term effects of opioids
-morphine may be taken orally in tablet form, administered intravenously, smoked, or sniffed to produce its effects
Analgesia
-indifference in pain, reducing intensity of pain and the perception or reaction to pain
-no ceiling to the intensity of which pain can be relieved
-respiratory depression is the limiting factor
Sedation and hypnosis
-produce sedation and hypnosis but not as intense as that produced by CNS depressants. Usually the patient can be aroused but may experince a drowsy, dreamy, mild dozing state. All opioid analgesics produce sedation
Suppression of cough centre
-relief or prevention of cough occurs through suppression of the cough centre in the medulla
Respiratory depression
-suppress the respiratory centre in the brain stem
-particularly, response to respiratory drive by carbon dioxide is blunted
-receptors that mediate this effect are mu and delta
-depression of respiration is the single most important side effect of the opioids and usually the cause of death in overdose
Endocrine effects
-reduces release of hormone that responsible for regulating the release of sex hormones from hypothalamus
-results in reduction in the production of testosterone, estrogens and progesterone
-overall result is a drop in libido in men
Miosis
-cause constriction of pupils of the eyes or miosis
-all opioids that gain access to the CNS will cause pinpoint pupils (indicator someone has opioid in their system)
Heart rate and thermoregulation
-with high doses of opioids, the heart rate is irregular, body temperature is low, and skin is cold and clammy
Decreased intestinal motility
-all individuals taking opioids will experince constipation as an adverse effect
Therapeutic use of opioids
(These three therapeutic uses apply to morphine and most of the other opioids)
Relief of severe pain
-analgesia major use for opioids
Ex. May be used to mitigate post-surgical pain and pain experienced by some terminally ill patients
Treatment of diarrhea
-loperamide is an over-the-counter opioid that not an analgesic and does not produce withdrawal but controls diarrhea
Cough suppression
-all opioids are effective in cough suppressants, however better alternatives with lower misuse potential
Opioids potential for misuse
Note: opioids like morphine are usually taken alone but may be found in combination with other drugs like cocaine and methamphetamine
Misuse potential
-most opioids have powerful euphoric effects, so large misuse possible
Inherent harmfulness:
Low-moderate doses -> not very high for morphine
High dose -> life threatening. Those taking illicit opioids are higher risk as not always sure of actual dose, and a lethal dose can be administered inadvertently
Risks of injections
-individuals who administer drugs by injection at greater risk of developing abscesses at site of administration as well as other infections (ex. Infected heart valves)
-if contaminated needles are used, also risk for spreading diseases (ex. Hepatitis, AIDS)
Overdose
-medical emergency
-all opioid overdoses can produce profound respiration depression, which can cause death
-treatment consists of opioid antagonists and support of respiration and other vital functions
-opioid antagonist naloxone is primary used to treat opioid overdose
- interestingly enough, naltrexone another opioid antagonist, used to treat alcohol use disorder
Risk of OUD
Tolerance
-occurs to most pharmacological effects of opioids, except constriction of pupils and constipating effect
-develops more slowly to respiratory depression than to the analgesic effects of opiates
-tolerance reverses in a few days after the opioid is discontinued
-cross-tolerance between all opioids analgesics occurs, providing they act on same receptor, therefore, those with a tolerance to morphine will also have a tolerance to methadone, as both drugs bind to opioid receptors
Withdrawal
-pronounced withdrawal syndrome can occur after opioid discontinuation
Opioid withdrawal is not life threatening and manifests as
-restless, anxiety, insomnia
-sweating, fever, chills
-increased respiratory rate
-cramping, retching and vomiting
-diarrhea
Specific symptoms and severity and duration determined by particular drug, chronicity and pattern of use, typical daily dose, route of administration, and whether there is concurrent use of other drugs
Addiction
-craving and compulsion can develop
-basis for addiction is the euphoric action of opioids, resulting in very powerful reinforcement
-use of opioids with other psychoactive drugs (ex. Cocaine) can occur in attempt to achieve an even greater euphoria
*refer to goodnotes for image
Opioid use during pregnancy
-increase risk of premature delivery and low birth weight infant
-at birth, infant undergoes an abrupt termination of opioid exposure, resulting in specific withdrawal reaction including irritability, sleep disturbances, poor feeding, and occasional seziures. Could last weeks to months
Treatment of OUD
-in Canada, only few options
-psychosocial support, counselling and treatment of concurrent physical and mental health issue should be considered to optimize recovery
Buprenorphine/naloxone
-long-acting synthetic opioid that binds to mu opioid receptors
-provides enough opioid agonist activity to prevent withdrawal symptoms, while having decreased euphoria and sedation compared to other opioid agonists
In Canada, Buprenorphine combined with antagonist naloxone. If injected, the naloxone blocks the opioid receptors, which causes withdrawal symptoms. When taken sublingually/orally, naloxone mainly broken down before getting into the circulation and therefore no significant effects on individual
Methadone
-synthetic opioid that effective following oral administration and long duration of action
-misuse potential much lower than other opioids like morphine, due to number of factors
-as taken orally, removes the potential risk of injections, leads to slower onset of pharmacological effects and therefore less euphoria
-since methadone long-acting, also taken less often, which again leads to lower misuse potential
Summary opioids
-powerful analgesics with high potential for misuse due to their euphoric effects
*refer to summary in goodnotes!!!
