Pharm 1 - Control of Pain 1

isabellepjk's version from 2017-05-06 15:56


Question Answer
Definition of pain?Unpleasant sensory & emotional experience in response to actual or potential tissue damage
Definition of suffering?Physical & emotional syndrome that develops as a result of unrelieved, severe pain
How do we know animals feel pain? (3)(1) Similar mechanisms of pain
(2) Similar areas of the brain to process pain
(3) Similar pain behaviors
Assessment of pain is _, & is based on (2 things)SUBJECTIVE
Based on (1) Behavior (2) Physiological changes
How does the type of animal affect the pain behavior?Prey animals will hide pain in order to not be eaten
Ways pain is communicated? (9)Anxiety
Fixed/dilated pupils
Changes in appetite
Changes in personality (biting)
↑ or ↓ physical activity
What are the types of NOCICEPTIVE pain? (4)Heat
Mechanical (tissue damage)
Protons (acid)
By which types of fibers is nociceptive pain transmitted? (2 ways)(1) Unmyelinated C-fibers (0.5-2 m/s, slow, chronic, dull)
(2) Myelinated A-delta fibers (6-30 m/s, fast, sharp, acute)
What substances are released from damaged tissue for the nociceptive pain path? (5)ATP
5HT (serotonin)
What substances are released from mast cells/ neutrophils for the nociceptive pain path?Histamine (which leads to nerve growth factor)
What substance is released from nervous tissue in response to pain or damage?Substance P
Types (/causes) of inflammatory pain? (3)(1) Damaged tissue
(2) Inflammatory cells
(3) Tumor cells
How is inflammatory pain transmitted?Release of chemical mediators to create an inflammatory soup. Can activate or modify stimulus response properties of the nociceptive afferent neurons
List the inflammatory mediators in the inflammatory soup? (10)Histamine
Nerve growth factor
Treatment for inflammatory pain? (2)COX-2 inhibitors, opioids
Types of neuropathic pain? (2)Lesions, dysfunction
Neuropathic pain could be described as a combination of ___ & ___Neuro deficits & pain
Examples of neuropathic pain (3)Carpal tunnel syndrome
Spinal cord injury
Thalamic stroke
*Treatment of neuropathic pain? (5)Anticonvulsants
Na+ channel blockers
NMDA receptor antagonists
Tricyclic antidepressants
*What does the "gate control theory" let the body differentiate?A non-noxious stimulus from pain
*Gate control theory - What are the small nerve fibers? What stim do they deal w/? What do they do?A-delta & C fibers.
They deal w/ thermal & mechanical stimuli.
They stimulate pain by INHIBITING THE INHIBITORY NEURON & opening the pain gate to the brain (so not actually inhibiting...)
*Gate control theory - What are the large nerve fibers? What stim do they deal w/? What do they do?A-beta fibers.
They deal w/ pressure, touch, & position stimuli.
(Beta= bigger)
*Gate control theory - In summary, small fibers = ___ & large fibers = ___small = PAIN. Large = NO pain
How does stimulus transduction travel in ascending paths? (3)STIM → (1) 1⁰ afferent neuron (2) Dorsal horn of spinal cord (3) Thalamus/brainstem
How does stimulus transduction travel in descending path? (2)(1) Descending inhibitory fibers
(2) Dorsal horn of spinal cord
What does the CNS portion of the transduction path accomplish?Recognition of pain & input of its emotional component
What do descending (MODULATORY) fibers help in?Modulate pain so that the pain does not overwhelm the animal's function
What do the descending pathways from the midbrain/brainstem DO?Exert a strong inhibitory effect on dorsal horn transmission
*What is descending inhibition mediated by? (4 substances) (Not drugs. what your body uses)Adenosine
Endogenous opioid peptides
In what way do opioids cause analgesia in terms of the descending pathways?
what are the mediators?
Descending pathways exert a strong inhibitory effect on dorsal horn transmission -->
mediated by endogenous peptides, 5HT, NE and adenosine
*What is wind-up (technical definition)? Is it good or bad? Mechanisms (2)?Repetitive C-fiber activity facilitates transmission through the dorsal horn. We DON'T want this. Mechanisms involve activating
(1) NMDA receptors (Glutamate)
(2) Substance-P receptors
What is wind-ups affects in simple terms?Less & less stim for the same amount of pain
*Two chemicals mainly involved in stimulating mechanisms of wind-up?Glutamate & substance P
What is hyperalgesia?Sensitization of peripheral nociceptive nerve terminals to noxious stimuli
How does hyperalgesia happen (where does it start)?CENTRAL facilitation of transmission at the level of the dorsal horn & thalamus - WIND-UP (Neuroplasticity)
What is allodynia?Pain evoked by a non-noxious stimulus
How does PERIPHERAL sensitization occur?Sensitizing soup DECREASES the threshold to have a pain stim reach the brain
What are the peripheral sensitization chemicals that we counteract?* (2)Bradykinin & prostaglandins
How does the sensitizing soup decrease pain threshold?It changes the signal from a high-threshold-nociceptor to a low-threshold-nociceptor
*(Main path: stim→ C-fiber→ Excitation of xmission neuron) How do NSAIDS affect this path?NSAIDs inhibit the mediator release (BK, 5-HT, PGs, etc)
which increases pain signal before the C-fiber xmmission
*(Main path: stim→ C-fiber→ excitation of xmission neuron) How do Opiates affect this pathway2 ways?
(1) Increase stimulation of descending inhibitory pathways, which inhibit pain transmission at the "excitation of xmission neuron" point
(2) Directly inhibit pain transmission at "excitation of xmission neuron" point
What are the 5 main multimodal analgesia tactics/methods?(1) Transduction
(2) Transmission (outside of SC)
(3) Transmission (inside SC)
(4) Descending modulation
(5) Perception
*Multimodal analgesia (Tx) - explain transduction method of analgesia (4)anticonvulsants,
Local anesthetics
*Multimodal analgesia- explain transmission (before SC) method of analgesia (Tx) (2)Local anesthetics, opioids
*Multimodal analgesia (Tx) - explain transmission (inside SC) method of analgesia (3)Anesthetics, alpha-2-agonists, NSAIDs ("INSIDE me said N-SAAAID")
*Multimodal analgesia (Tx) - explain descending modulation method of analgesia (4)opioids
(descending-DEPRESSED (so take hard drugs along w/ your antidepressants))
*Multimodal analgesia (Tx) - explain perception method of analgesia (8)Opioids
TCA (tricyclic antidepressant)
SSRI (Selective serotonin reuptake inhibitor)
SNRI (Serotonin–norepinephrine reuptake inhibitor)
*What are the 2 therapeutic goals of pain management?(1) Avoid reaching the wind-up phase
(dependent on the activation of NMDA-receptors (preventative pain management))
(2) Interfere w/ physiological mechanisms of pain
(sensitizing soup, gate control mechanism, interfering w/ CNS neurotransmission)


Question Answer
How do opioids affect the ascending path? Descending? (In short)Inhibit ascending & stim descending
Are opioids central or peripheral analgesics?Both
*Species differences on how opioids affect the CENTRAL nervous system?(1) Humans + dogs = depression
(2) Horses + cats = excitation (sometimes).
What is the respiratory depression effect of opioids dependent on? When are these adverse effects most often seen?Dose dependent. Usually seen from PROLONGED use of opioids, but can be possible from 1 really high dose.
*How do opioids affect the GI tract?Increased sphincter tonus = constipation
What are the endogenous ligand analogues of opioids in the body? What is their function?They have REGULATORY functions
endorphines (peptides)
*What TYPE of receptor do opioids use in the cell?G-protein coupled receptors (Gi/o)
*What are the cellular effects of opioids interacting w/ the G-protein coupled receptors?(Gi/o) promote opening of K+ channels, inhibit opening of Ca++ channels
= decrease in neuronal excitability & reduce NT release.
What do opioids do on a biochemical level? What is the result? (How do they cause physical dependence?)Inhibit adenylate cyclase & cause mitogen activated protein (MAP) kinase (ERK) activation. The result of this is long-term adaptive changes (prolonged receptor activation) which leads to PHYSICAL DEPENDENCE (Mu receptor)
Where do opioid receptors live?In brain & spinal cord
*3 main examples of pure agonist opioids?Etorphine
*What is the general preference of pure agonists?High affinity for mu receptors &
generally lower affinity for delta & kappa sites
*Main example of a partial agonist?Butorphanol
*What is the general preference of partial agonists?Partial agonist at mu receptor.
(Strong analgesic, strong resp. depression)
*3 main examples of mixed agonist-antagonists?Nalorphine, buprenorphine, pentazocine (Ag OR antag...tore fanny, 5 times out of indecisiveness)
*What are the 2 opioid antagonists?Naloxone & naltrexone
*What is important to note about opioid antagonists?They have very little effect when given on their own
*What makes tramadol unique?It is centrally acting w/ 4 different mechanisms
*What are the mechanisms of action for tramadol? What do the differences depend on? (4)Depend on R (+) or S/L(-) form!
(1) Complex interaction at mu-opioid receptor (+)
(2) serotonin re-uptake inhibitor (+)
(3) norepi reuptake inhibitor (-)
(4) muscarinic M1 antagonist (That DOL is such a TRAMp, she will do 4 guys at once)
*Which mechanism of action of tramadol is due to - form? Which 1 doesnt depend on the form?Is norepi re-uptake inhibitor, the M1 antagonist doesn’t specify if it is + or -
*What is the pharmacokinetics of tramadol?HIGHLY LIPOPHILIC & a racemic mixture (equal + & -), metabolized into over 30 metabolites
What are the 2 things that opioid effects are dependent on?Species & dose
*What are the central STIMULATING effects of opioids? (4)Stim parts of brain causing
(1) Emesis (due to receptors in the chemoreceptive trigger zone, stim of central dopamine receptors)
(2) Euphoria
(3) Excitation (paradoxical) (rumis & horses)
(4) Gastro-intestinal spasms
*What is apomorphine?NOT AN OPIOID! NO PAIN RELIEF! Just a nonselective dopamine agonist. Pertains to chemoreceptive trigger zone
*What are the central INHIBITING effects of opioids? (6)Inhibit parts of brain regulating these things

ANTI-emetic (in chemo-trigger-zone after initial dose)
Anti-tussive (anti cough)
Bronchoconstriction (histamine release)
Resp depression
Thermoregulation (hypotherm in dog, hypertherm in cat/horse/rumi)
*Is thermoregulation inhibited or stimulated by opioids? Species diffs?Thermoreg part of brain inhibited, which means - (can't regulate).
Dog = HYPOthermia. Cat/horse/rumi = HYPERthermia
What affect do opioids have on broncho (constriction/dilation)? Is this an inhibitory or stim effect? How is this effect achieved?They INHIBIT the CNS, which causes BRONCHOCONSTRICTION via HISTAMINE release
Through which routes of admin are opioids well absorbed?Oral, IM, SQ (Note to self: where da fuck is IV admin on this list?)
*Which opioid has 100% buccal mucosal absorption?Buprenorphine
Why can opioids have erratic plasma concentrations?First pass effect
Why are opioids well distributed throughout the body?They are lipophilic & weak bases
*Which opioid has redistribution? What does this mean?Fentanyl, since it is highly lipophilic is accumulates in the fat & then it is slowly released for a longer effect
How are opioids metabolized & excreted?Hepatic metabolism (I'm assuming glucuronidation) → urinary excretion (enterohepatic circulation)
How do cats metabolize opioids?Sulfate conjugation (they cant glucuronidate)
*Exs) Morphine & methadone are often used in combination therapy with/as? (3)(1) W/ alpha-2 blockers
(2) Premedication/anesthesia
(3) Epidural (pain management)
Exs) Fentanyl is usually used as?Patches for dogs, cats, horses
*Exs) What three drugs are used for pain management in colic?Butorphanol, Nalbuphine, Pentazocine (Nal had colic & tore fanny 5 times)
Notable about buprenorphine in use? (How long is the onset, how long is the action?)Slow onset but long acting
*What are the opioid ADVERSE EFFECTS? (8)Bradycardia
Constipation/urinary retention
Excitatory motor effects
Histamine release
Long term use → hyperalgesia (allodynia)
Resp depression
Tolerance (mu-receptor desensitization)