Drugs That Act On Opioid Receptors Flashcards
Differentiate between opioids and opiates
Opioids are drugs with morphine like activity that produce analgesia without the loss of consciousness (at therapeutic doses) and can induce tolerance and physical dependence
Opiates are drugs derived from opium, for example, morphing in heroine
List the opioid receptors and the actions they mediate
- Mu (4) receptors (MOPr): Supraspinal and spinal analgesia, respiratory depression, euphoria, sedation, pupil constriction, GIT effects (reduced GI secretions, constipation), dependence
- Kappa (K) receptors (KOPr): Supraspinal and spinal analgesia, sedation, dysphoria, pupil constriction, psychotomimetic effects, GIT effects (as u receptors)
- Delta (8) receptors (DOPr): modulation of hormone and neurotransmitter release, supraspinal and spinal analgesia and GIT effects (as y receptors)
- Opioid receptor-like subtype 1 (ORL,) receptors (NORr): anti-opioid (reverse the supraspinal analgesic effects of endogenous and exogenous mu-opioid receptor agonists, spinal analgesia and catatonia
What are endogenous opioid receptor agonist?
The endogenous opioid receptor agonists are peptides. They are called opiopeptins. They are released in conditions of stress and in acupuncture. They include:
Beta endorphins: mu, kappa and delta
Enkephalins: mu and delta
Dynorphins: mu, kappa and delta
Orphanin FQ/nociceptin: ORL1
List the locations of opioid receptors and the actions they mediate
Brainstem: Respiratory depression, cough suppression, nausea and vomiting, lowering of blood pressure, pupillary constriction
Medial thalamus: Suppression of deep pain that is poorly localized and emotionally influenced
Spinal cord: Receipt and integration of incoming sensory information leading to attenuation of painful afferent stimuli
Hypothalamus: Affect neuro-endocrine secretions
Limbic system: Influence emotional behavior
Periphery: Inhibition of release of excitatory mediators such as substance P from nerve endings
What happens when opioid receptors are activated?
Opioid receptors are G-protein coupled receptors. Their activation results in:
Inhibition adenylyl cyclase (reduce cyclic AMP)
Opening of potassium channels (hyper-polarisation)
Inhibition of calcium channel opening on presynaptic neurons (results in inhibition of release of neurotransmitters such as glutamate, substance P, acetylcholine, norepinephrine and serotonin)
What is the MoA of opiod agonists?
Opioid agonists have the following actions which result in their analgesic effects:
Activate the descending pathways from the midbrain and brain stem and exert a strong inhibitory effect on dorsal horn transmission
Inhibit excitation of sensory nerve terminals in the periphery (increase pain threshold)
Classify opioids
Which opioids are full agonists?
Include morphine, heroin, methadone, hydromorphone, oxymorphone, fentanyl, sufentanil, alfentanil, remifentanil, pethidine, levorphanol and oxycodone
Which opioids are partial/weak agonists?
Codeine & hydrocodone: Weak agonists on mu receptors
Butorphanol: Partial agonist on mu receptors and full agonist on kappa receptors
Which opioids are mixed agonists/antagonists?
Pentazocine and nalbuphine: Agonist on kappa receptors and antagonist on mu receptors
Buprenorphine: Partial agonist on mu receptors, and antagonist on delta and kappa receptors
List the high efficacy opioids
Include morphine, diamorphine (heroin), oxymorphone, hydromorphone, etorphine, fentanyl, alfentanil, sufentanil, remifentanil, methadone, pethidine, levorphanol and buprenorphine
List the mild to moderate efficacy opioids
Include codeine, oxycodone, hydrocodone, propoxyphene, dextropropoxyphene, pentazocine and nalbuphine
Describe the effects of morphine on the CNS
- Analgesia
Pain consists of both sensory and affective (emotional) components.
Opioid analgesics reduce both aspects of the pain experience, especially the affective aspect.
In contrast, nonsteroidal anti-inflammatory analgesic drugs have no significant effect on the emotional aspects of pain. - Euphoria
intravenous drug users experience a pleasant floating sensation with lessened anxiety and distress (DA release in nucleus accumbance).
However, dysphoria, an unpleasant state characterized by restlessness and malaise, may sometimes occur. - Sedation
Drowsiness
clouding of mentation
little or no amnesia
No motor incoordination
Sleep is induced in the elderly (can be easily aroused from this sleep) - Respiratory Depression
by inhibiting brainstem respiratory mechanisms.
Alveolar PCO2 may increase, but the most reliable indicator of this depression is a depressed response to a carbon dioxide challenge.
In individuals with increased intracranial pressure, asthma, chronic obstructive pulmonary disease, or cor pulmonale, this decrease in respiratory function may not be tolerated - Cough Suppression
Codeine in particular
However, cough suppression by opioids may allow the accumulation of secretions and thus lead to airway obstruction and atelectasis. - Temperature regulating center depression
chances of hypothermia - Vasomotor center depression
Fall in BP - Miosis
Constriction of the pupils
By stimulating Edinger Westphal nucleus of III nerve
Miosis is a pharmacologic action to which little or no tolerance develops
valuable in the diagnosis of opioid overdose - Truncal Rigidity-
Truncal rigidity reduces thoracic compliance and thus interferes with ventilation.
Truncal rigidity may be overcome by the administration of an opioid antagonist, which of course will also antagonize the analgesic action of the opioid.
Preventing truncal rigidity while preserving analgesia requires the concomitant use of neuromuscular blocking agents
Describe the effects of morphine on the peripheral system
- Cardiovascular System
Bradycardia
Meperidine is an exception (can result in tachycardia)
Hypotension - due to
-peripheral arterial and venous dilation
-depression of vasomotor centre
-release of histamine.
Increased PCO2 leads to cerebral vasodilation associated with a decrease in cerebral vascular resistance, an increase in cerebral blood flow, and an increase in intracranial pressure. - Gastrointestinal Tract
Constipation
no tolerance
Opioid receptors exist in high density in the gastrointestinal tract
constipating effects of the opioids are mediated through an action on the enteric nervous system as well as the CNS
gastric secretion of hydrochloric acid is decreased
propulsive peristaltic waves are diminished
tone is increased, this delays the passage of the fecal mass and allows increased absorption of water, which leads to constipation
so this drug can be used in the management of diarrhea - Biliary Tract
sphincter of Oddi may constrict
contract biliary smooth muscle
result in biliary colic - Renal
Renal function is depressed by opioids
decreased renal plasma flow
enhanced renal tubular sodium reabsorption
Ureteral and bladder tone are increased
Increased sphincter tone may precipitate urinary retention
ureteral colic caused by a renal calculus is made worse by the opioid-induced increase in ureteral tone. - Uterus-
may prolong labor
both peripheral and central actions of the opioids can reduce uterine tone - Neuroendocrine-
stimulate the release of ADH, prolactin, and somatotropin
inhibit the release of luteinizing hormone - Pruritus-
CNS effects and peripheral histamine release may be responsible for these reactions
pruritus and occasionally urticaria (when administered parenterally)
List the clinical uses of opioids
Analgesia
Cough
Diarrhea
Acute Pulmonary Edema
Balanced anaesthesia
Preanaesthetic medication
Relief of anxiety and apprehension
