Opioid Lecture part 1 Flashcards
General indications for Opiates
- Moderate to severe dental pain that cannot be managed effectively with NSAIDS
- Patients for whom NSAIDS are contraindicated
The word Opiates is used to describe what?
to describe substances from the white liquid extract derived from the seeds of poppy plant
- Alkaloids found in opium
Opioids can be classified in what 3 ways
- Mechanism of action (agonists, partial agonists, mixed opioids, antagonists
- Chemical structure
- Degree of efficacy that they produce
What is the mechanism of action for opioids?
They bind to receptors in both CNS and spinal cord. Produce ALTERED perception of pain reaction
How do opioids produce an analgesic effect?
Produced by midbrain stimulation due to activation of a pain-modulating circuit
- Projects via the medulla to the spinal cord dorsal horn
Descending pain-modulating circuit
***Opiates produce analgesia by direct action on the CNS
Analgesia system of opioids are mediated by what 3 major components
- Periaquaductal grey matter (midbrain)
- nucleus raphe magnus (medulla)
- pain inhibitory neurons (dorsal horns of the spinal cord)
- These areas are the areas in which the chemical mechanisms of opioid analgesics will take place.
The pain suppression system involves what neurotransmitter and is mediated by what?
serotonin as neurotransmitter
- Partially enkephalin-mediated
What activates the pain suppression system pathway?
- Noxious stimuli
- Pain
- Psychological factors, including placebo responders
- Opioids
Endogenous Opioids act as what?
neurotransmitters
3 groups of endogenous substances with opioid-like action
endorphins
enkephalins
dynorphins
Endogenous opioids act through three different receptors
- mu
- delta
- kappa
- G protein-coupled receptors
Descending pain-modulating circuit contains high concentrations of what peptides?
endogenous opioid peptides
Endogenous opioid peptides are produced where?
By the pituitary gland and hypothalamus
- They are located in the CNS (mainly in limbic system and brainstem areas associated with pain reception)
Beta-Endorphin are expressed where via what receptor?
Expressed in cells in the arcuate nucleus of the hypothalamus and in the brainstem
- acts via mu: influences appetite, sexual behavior
Enkephalins are expressed where via what receptor?
widely distributed throughout the brain
- acts via mu and delta
Dynorphins are found where and act via what receptor?
Found in spinal cord and in many parts of the brain, including the hypothalamus
- acts via kappa
Endorphins are derived from what precursor molecules
- Proenkephalin A - many endorphins
- Pro-opiomelanocortin (POMC) - B-endorphin
- Proenkephalin B (prodynorphin) - dynorphins
Enodorphins are found where?
Found in gut (pancreatic islet cells), sympathetic nervous system, adrenal medullary chromatin cells, CNS
Beta-endorphins are distributed where?
In the brain
Endorphins are involved in what physiologic actions
Involved in blood pressure regulation, temperature regulation and food intake
First isolated Enkephalins compounds
- Leucine-enkephalin
2. Methionine-enkephalin
Do Enkephalins mimic opiate activity? Are they strong or weak analgesics?
Mimic opiate activity = weak analgesics
What endogenous opioid may be responsible for producing analgesia in placebo responders and acupuncture?
Enkephalins
Dynorphins are found where?
Found in the spinal cord and in many parts of the brain, including the hypothalamus
Where are the dense concentrations of opiate binding sites?
PAG (periaqueductal gray) and dorsal horn of spinal cord
T or F, Opiate receptors that are found in tissues also are involved in analgesia
False, NOT involved in analgesia
T or F, recognition site of opioid receptors are highly specific. The analgesia produced by endogenous or opioid drugs depends upon their action at specific sites (opioid receptor sites)
True
5 opioid receptor subtypes
- Mu
- Delta
- Kappa
- Epsilon
- Sigma (no longer classified as opioid receptor)
T or F, Binding to receptor subtype on an opioid receptor will cause different responses
True
Mu 1 and Mu 2 receptor functions
Mu1:
- Supraspinal analgesia
- Euphoria
- Physical dependence
Mu2:
- Respiratory depression
Drugs that do what exhibit the best analgesic properties
Drugs that bind to Mu
What must happen for opioid to be physically addicting
Must bind to Mu to be physically addicting
What is the downside to opioid receptors
Always the risk of addiction and risk for respiratory depression
Kappa opioid receptor functions
- Spinal analgesia
- Miosis (pinpoint pupils)
- Sedation
Delta opioid receptor functions
- Analgesia
- Emotion
- Seizures
Epsilon opioid receptor functions
- Analgesia
Strength of attachment of an opioid drug to its binding site (binding affinity) is proportional to what?
Its potency
- The stronger the affinity, the higher the potency
Opioids act by what 3 steps
- Presynaptic inhibition of production of neurotransmitters C-fiber endings
- Postsynaptic suppression of evoked activity in nociceptive path or remove the remaining parts of the regulation of inhibition of nociceptive impulses
- Increased transmission of the descending inhibition of spinal nociceptive conduction
T or F, Opioids cause depolarization of nerve cells, activation of nerve firing and presynaptic activation of transmitter release?
False, Opioids cause HYPERPOLARIZATION of nerve cells, INHIBITION of nerve firing and presynaptic INHIBITION of transmitter release
