Pain & Opiates Flashcards
What 2 elements make up pain?
- Local irritation (stimulation of peripheral nerves)
- Recognition (CNS)
What are the 4 stages of nociception?
- Transduction/ Nociception
- Transmission
- Perception
- Modulation
What drugs act on the transduction/ nociceptors?
- Local anesthetics
- NSAIDs
What does transmission connect?
The PNS and CNS
What tract does pain ascend through the spinal cord?
- Spinothalamic tract
What types of drugs act on the trasmission stage of nociception?
- Local anesthetics
- Opioids
- Alpha-2 agonists
Where is pain perceived?
CNS/ cerebrum
What drugs act on the perception stage of nociception?
- Opioids
- Alpha-2 agonists
What do the descending tracts of modulation of nociception act on in the spinal cord?
The dorsal horn cells
What are nociceptors? (anatomically)
Peripheral nerve endings
Where are nociceptors found?
- Skin
- Muscle
- Joints
- Bones
- Viscera
What is the novel stimulus of nociception?
Tissue injury
What do the peripheral nerves of nociceptors synapse on in the transmission phase of nociception?
- 2nd order neurons in the dorsal horn
What neurotransmitters relay pain signals from peripheral nerves to the CNS?
- Glutamate
- Substance P
Are Glutamate and Substance P excitatory or inhibatory?
Excitatory
What is the inhibitory neurotransmitters of pain in the CNS?
- GABA
- Serotonin
What structure PERCEIVES pain?
The brain
What is involved in perception of pain?
- Integration of all nociceptive impulses and giving meaning to the sensory input
From where in the CNS does descending inhibition originate?
Midbrain
What 2 neurotransmitters are involved in the modulation of pain through descending inhibition?
- Serotonin
- Norepinephrine
What non-neurotransmitter also modulates pain through descending inhibition?
- Endogenous opioids
What type of mechanism do endogenous opioids use to reinforce desirable behavior?
Positive reinforcement
What activity is most correlated with endogenous opioid release?
Sex
What ANS are endogenous opioids related to?
Symapthetic
How is pain modulation by opioids achieved?
- Opioid receptor/ activity
- Dynorphins
Is nociceptive pain acute or chronic?
Can be either
Is neuropathic pain acute or chronic?
Chronic because it can’t be changed or alleviated
What is required for nociceptive pain to occur?
All “neural equipment” needs to functioning normally
What 3 factors will affect the choice of analgesia for nociceptive pain?
- Type
- Duration
- Intensity
What causes neuropathic pain?
Injury to the nervous system
What trauma, illnesses, and disease cause neropathic pain?
- Surgery
- Diabetes
- Stroke
- Chemotherapy
What is allodynia?
Interpretation of non-pain stimuli as painful
What is hyperpathia?
Exaggerated or prolonged response to painful stimuli
What receptors do opioids act on?
- Mu
- Delta
- Kappa
Do opioids act on acute or chronic pain?
Both
By what 2 methods do stimulation of opiate work?
- Inhibit transmission of pain signals
- Stimulate pain control circuits in spinal cord
What are endorphins?
Peptides released opioid receptor
Where are endorphins produced?
In the pituitary and hypothalamus
Where are enkephlins produced?
Throughout CNS and peripheral nerve endings
Where are dynorphins produced?
Nerve endings
Which peptide is selective for mu receptors?
Endorphins
Which peptide is selective for delta receptors?
Enkephlins
Which peptide is selective for kappa receptors?
Dynorphins
How do synthetic opioids work?
Bind to opioid receptors, and activate them
Describe how opioids work on both pre and post-synaptic receptors.
- Opioid restricts amount of Ca++ entering pre-synaptic nerve slowing the release of neurotransmitter
- Opioid increases permeability of K+ in post-synaptic neuron causing hyperpolarization
What are the 4 clinical effects of mu opiate receptors?
- Euphoria
- Physical dependence
- Respiratory depression
- Supraspinal analgesia
What are the 4 clinical effects of kappa opiate receptors?
- Miosis (constriction of pupil)
- Sedation
- Spinal analgesia
- Respiratory depression
What are the 4 clinical effects of sigma opiate receptors?
- Dysphoria
- Hallucinations
- Respiratory stimulation
- Vasomotor stimulation
What are the 9 additional pharamacological effects of opioids in addition to pain control?
- Anti-tussive
- Alterations in smooth muscle tone
- Inhibition of parasympathetic stimulation (constipation)
- Decreased urine formation (stimulates release of ADH)
- Miosis
- Mood alteration
- Respiratory depression
- Nausea/ emetic effect (stimulation of CTZ)
- Direct release of histamines (hives, itching, flushing)
What is typically used to treat the nausea associated with opioids? How does this drug work?
- Zophran
- Blocks CTZ and sensation
What are the 3 categories opioids are classified by?
- Source
- Potency
- Special features
What are the 2 natural occurring opiates?
- Morphine
- Codeine
Which of the 2 naturally occurring opiates are stronger for pain control?
Morphine
What does codeine have a high potency as?
An anti-tussive
Do morphine and codeine have strong PO effects?
Morphine: Poor
Codeine: Strong
Which natural occurring opiate releases histamine? Why?
- Morphine
- It is a base
What are the 3 semisynthetic narcotics?
- Heroin
- Dihydromorphone (Dilaudid)
- Oxycodone (OxyConin, Percocet)
What C:P ratio?
Central to Peripheral effects
What is the most prevalent street narcotic?
Heroin
What is the significance of acetyl groups in heroin?
Facilitates passage through blood-brain barrier
What semisynthetic narcotic has an excellent C:P ratio?
Dihydromorphone/ Dilaudid
Which semisynthetic narcotic is used in over 40 products in which it is combined with non-narcotics?
Oxycodone
Is oxycodone long or short-acting?
Short
What is the synthetic narcotic?
Methadone (Dolophine)
Is methadone stronger or weaker than morphine?
Equal
How long is the half-life of methadone?
Extremely long
Why is methadone so effect in preventing withdrawl symptoms?
- Accumulates if taken daily
- Maintains steady plasma concentration that is easy to maintain in plateau
Besides maintenance and weaning programs, what is the other use of methadone?
Chronic pain treatment
What is meant by equianalgesic dose?
Equivalence of drug for analgesic effect compared to morphine
Is an equianalgesic dose of 0.1 or 100 stronger?
0.1
What is tolerance?
A drug loses effectiveness over time and increased dosage is required to produce therapeutic effect
What is physical dependence?
Dependence on a drug to maintain a normal homeostasis of the body
What is drug withdrawl?
Set of symptoms consistant with stoppage of a drug that produces physical dependence
What are some symptoms of opiate withdrawl?
- Excessive yawning
- Tearing
- Runny nose
- Restlessness
- Increased pain sensitivity
- Nausea
- Vomiting
- Diarrhea
- Cramps
- Muscle aches
- Sweating
- Dysphoric mood
- Goose bumps
- Sweating
When are opioid antagonists used?
To treat overdose
What are 3 common opioid antagonists?
- Naloxone
- Naltrexone (trexan, vivitrol)
- Nalmefene
What is antagonist precipitated withdrawal?
Withdrawl effects onset rapidly when drug is administered
What is the mechanism of action of naloxone?
- Competitive blocking of mu and kappa receptors
What drug administration route are naltrexone and nalmefene effective through?
PO
How is naloxone administered?
- Parenterally
Does naloxone have quick or slow action?
Very quick
Do naltrexone and nalmefene long or short-acting?
Long-acting
What are naltrexone and nalmefene used to treat?
- Prevent addicts from getting high on street narcotics
- Reduce craving, relapse, and drinking in alcohol troubled persons
Why do patients overdosing on heroin need to be monitored after administration of naloxone?
The half-life of heroin is longer than naloxone
What populations should be carefully monitored when given opioids?
Patients with a history of addiction
