T or F. Pain is only experienced in the "conscious" brain
Which type of pain has a fast, reflexive "first pain"?
Does somatic or visceral pain have a progressive and summation quality.
What is the major cause of pain after tissue damage?
local release of inflammatory mediators
What are the local mediators involved in the inflammatory response causing pain?
- -Leukotrienes D4/B4
Activation of high threshold nociceptors results in:
Spinal level of pain occurs where?
What neurotransmitters INCREASE nociception? (3)
- 1. Substance P
- 2. bombesin
- 3. VIP
What NTs REDUCE nociception?
- 1. galanin
- 2. somatostatin
- 3. GABA
Supraspinal perception of pain is associated with activity in:
thalamus & primary/secondary cortex
Mediators involved at the brainstem & dorsal columns to dorsal horns are:
- -Endogenous opioids
Explain the inflammatory response starting at the "disease" or "trauma".
- 1. Inflammatory stimulus
- 2. release arachidonic acid
- 3. cyclooxygenase catalyzes arachidonic acid to prostaglandins & leukotrienes
- 4. prostaglandins create inflammatory response
Which COX has a stable concentration in the tissue?
What is the job of COX 1?
-converts arachidonic acid to prostaglandins--> stimulate body functions
T or F. COX 1 enzymes are tissue specific
Which COX is not normally located in the tissue but can be "induced"?
What is the role of COX 2 in the inflammatory response?
- -increase macrophage activity
- -Produce prostaglandins
What is the main function of NSAIDS?
Inhibit enzyme cyclooxygenase
ASA reversibly/irreversibly binds to platelet COX.
Irreversibly (8-10 days)
What is the anti-inflammatory dose of ASA? Anti-platelet dose?
- -Anti-inflammatory1200 to 1500
- -Anti-platelet--> 81-325mg
Discuss the elimination of aspirin from the body.
- -Lower dose aspirin (<600mg)--> 1st order
- -Higher dose aspirin--> zero-order (capacity-limited)
ASA is selective or non-selective COX inhibitor.
Non-selective COX inhibitor
What are 2 major GI side effects of ASA?
- 1. GI upset--> mucosal irritation, inhibition of protective prostaglandin
- 2. GI bleeding--> erosive gastritis (upper)
What are the CNS side effects of ASA?
-High doses--> "salicylism", tachypnea
What are the symptoms of "salicylism"?
- -decreased hearing
Low toxic salicylate levels can induce:
initial respiratory alkalosis (due to increase ventiliation)--> accumulation of salicylic acid derivatives--> respiratory depression--> acidosis
Discuss Samter's Triad.
- -Hypersenstivity rxn--> leukotriene mediated
- 1. asthma patients
- 2. Nasal polyps
- 3. associated: bronchoconstrictions/shock
Patient with SLE or JRA may experience what adverse effects with ASA.
-mild typically asymptomatic hepatitis
T or F. ASA can increase uric acid levels and should be avoided in people with gout
What are the steps to perform in ASA overdose?
- 1. gastric lavage
- 2. if hyperthermic--> ice packs
- 3. Manage acid/base
- 4. Insure high urine volume
- 5. Urine alkalinization
ASA displaces drugs from protein binding sites. Which drugs should be carefully monitored or avoided?
What are the 3 MOAs added in the newer NSAIDs?
- 1. chemotaxis inhibition
- 2. interleukin 1 down- regulation
- 3. interference w/ ca-mediated intracellular processes
Which NSAID works as a result of prostaglandin synthesis inhibition (inhibition of COX 2)?
What are the 4 properies of NSAIDs?
- 1. analgesic
- 2. antipyretic
- 3. anti-inflammtory
- 4. platelet-aggregation inhibition
- 5. gastric irritation--> less than ASA
- 6. Nephrotoxicity
What do NSAIDS cause nephrotoxicity?
-Non-specific cox inhibitors leads to ⇓ in Prostaglandin synthesis--> so renal arteries have unoppossed vasoconstrition--> kidneys can't compensate during periods of decreased BF
What protein are NSAIDS often highly bound to?
T or F. Celecoxib does not affect platelet function.
True (at usual doses)
T or F. Cardioprotective effect of ASA is improved with concommitant use of NSAID
What patients are contraindicated in the use of motrin?
- Samter's triad
- 1. patients w/ nasal polyps
- 2. angioedema
- 3. aspirin sensitivity--> bronchospasm
What are side effects of ibuprofen? (4)
- 1. GI
- 2. tinnitis
- 3. aseptic meningitis
- 4. H/A
T or F. Ibuprofen is highly metabolized in the liver before excreted.
True, very little is excreted unchanged
How should Caldolor be administered?
- Dose: 400-800mg q 6hr
- -Ensure pt well hydrated
- -Administer dose over 30min, diluted
T or F. Indomethacin is mainly marketed for analgesic purposes, not inflammatory purposes?
False--> Indomethacin is just anti-inflammatory
When is the only situation that Indomethacin should be used in children?
Patent ductus arteriosus
What 4 GI disturbances can occur in Indomethacin?
- 1. abdominal pain
- 2. GI hemorrhage
- 3. pancreatitis
- 4. diarrhea
T or F. Ketorolac is mainly marketed for analgesia not anti-inflammtory purposes.
What percentage does ketorolac decrease opioid requirements?
What is the net effect of a partial agonist?
Reduction in drug effect (through competitive action) so it can act as either an agonist or antagonist.
What receptors are most responsible for many of the opioid side effects, including respiratory depression?
T or F. A opioid might be an agonish at 1 receptor subtype but only a partial agonist/possibly antagonist at another subtype.
What area of the body is the largest reservoir for opioids?
Skeletal muscle (highest concentration in tissue is a function of perfusion)
Opioids with hydroxyl groups are likely conjugated with?
Esters-type opioids are hydrolized by:
What is the primary route of phenylpiperdine opioid metabolism?
Oxidative metabolism (fentanyls)
How are opioids most secreted?
Via renal and bile
What are the receptor types for opioids?
- 1. Mu (m)
- 2. Delta (d)
- 3. Kappa (k)
The physiological effects of Mu-receptors are: (4)
- 1. analgesia
- 2. euphoria
- 3. respiratory depression
- 4. physiological dependence
What are the physiological effects of the Delta and Kappa receptors?
Which of the opioid receptors is most acted on?
Discuss the 2 cellular action of Opioids.
-Decrease NT release by closing voltage-gated Ca+ channel on PRE-synaptic terminals
-Inhibit POST-synaptic neurons by increasing K+ channel conductance (hyperpolarization)
What is the cellular action of opioids causing PERIPHERAL analgesia?
-Reduce NT by closing voltage-gated Ca+ channel at PRE-synaptice terminals
What is the the cellular action of opioids causing SPINAL analgesia?
-Inhibit postynaptic neurons by increasing K+ channel conductance (hyperpolarization)
What are the CNS effects of opioids? (4)
- -Mu mediated
- 1. analgesia
- 2. sedation
- 3. euphoria
- 4. respiratory depression
Opioids have the greatest effect on sensory or affective pain components?
Greatest effect on AFFECTIVE (emotional) pain component
Opioid effect the spinal cord by increasing or decreasing nociceptive impulse afferent transmission
Decrease nociceptive impulse afferent transmission
What is the effect of opioids on the spinal cord on the primary presynaptic afferent nociceptors?
-DECREASE substance p release
T or F. Bolus dosing of opioids is not correlated well with analgesia effects.
True (constant/slow changing concentrations is well correlated with analgesic intensity)
One CNS effect of opioids is mitosis or miosis?
Miosis--> pupillary constriction
T or F. Opioid tolerance can be judged by a lack of miosis effect with opioid administration.
False- no miosis tolerance develops
T or F. Miosis correlates with opioid-induced respiratory depression.
True (except severe opioid induced respiratory depression--> hypoxemia--> precipitate pupillary dilation
What are the 3 respiratory effects of opioids?
- 1. Respiratory depression (poorly tolerated in asthma/COPD
- 2. Cough suppression (esp codeine)
- -Can cause secretion accumulation
- 3. Truncal rigidity (decreased thoracic compliance), esp lipophilic (fentanyl)
What are the cardio effects of opioids?
- 1. Minimal effects (some brady)
- 2. BP--> some histamine release possible leading to hypotension in hypovolemic patients
What are the GI effects of opioids?
- 1. Stomach-->Increase GI tone-
- 2. Small intesting--> decrease propulsion
- 3. Large intestines--> ⇑ tone, ⇓peristalsis (sometimes used in diarrhea management)
8 common reactions to Opioids?
- 1. dysphoria (hyperactivity)
- 2. respiratory depression
- 3. N/V
- 4. Increased ICP
- 5. Hypotension
- 6. constipation
- 7. urinary retention
- 8. urticaria, itching
What are some phenanthrenes drugs?
- -Strong agonist--> morphine, dilaudid
- -Mild/mod agonist--> codeine, hydrocodone, oxycodone (combos w/ ASA/Tylenol)
What is an example of Phenylheptylamine opioid?
What are the main differences in morphine and methadone?
-methadone-->longer acting than morphine, had decreased tolerance and physical dependence
What opioid is useful for detoxification in maintenance of chronic, heroin addict?
What are 2 examples of Phenylpiperidines?
Which phenylpiperidine has significant anticholinergic effects?
When is demerol contraindicated?
-presence of underlying tachycardia
What are 2 side-effects of Demerol
- 1. anticholinergic (antimuscarinic) effects
- 2. risk of seizures (accum of metabolite in CNS)
Which fentanyl group drug is most potent?
Sufenta (5-7x more)
Which fentanyl group drug is most rapid acting?
Which fentanyl group is metabolized rapidly, women in labor?
What receptors does Nubain (nalbuphine) act on and what is it's action on them?
Kappa agonist and Mu antagonist
What are 2 Phenanthrenes (Mixed agonist/antagonist & partial agonists)
- 1. Nalbuphine (nubain)
- 2. Buprenorphine
Between nalbuphine & buprenorphine, which is a partial Mu "agonist" and which is a Mu antagonist?
- Nalbuphine--> Mu antagonist
- Buprenorphine--> Mu agonist
What opioid antagonists are PURE antagonists?
- 1. Naloxone (Narcan)
- 2. Naltrexone (Revia)
- 3. Nalmefene (Revex)
What are the effects of pure opioid antagonist in a patient with acute opioid overdosage?
- -Level of consciousness
- -pupil size
T or F. No tolerance develops with opioid antagonists.
True (no abstinence syndrome)