Pharmacology II Exam I: Multimodal

What is the International Association for study of pain definition of pain?

An unpleasant sensory and emotional experience associated with actual ot potential tissue damage described in terms of such patient

___________ = normally nonharmful stimulus that is perceived as painful

allodynia

______=Increased sensitivity to pain

Algesia

____=Pain producing

Alogenic

______________ = absence of pain in the presence of a normally painful stimulus

analgesia

_________________ = unpleasant painful abnormal sensation whether evoked or spontaneous

dysesthesia

_______________ = heightened response to normally painful stimulus

hyperalgesia

_______________ = pain in the distribution of peripheral nerves

neuralgia

________________ = abnormal distrubance in the fx of a nerve

neuropathy

______________ = abnormal sensation whether spontaneous or evoked

paresthesia

T/F: poorly controlled acute pain may lead to chronic pain states

true

acute pain is _____________, and lasts ____________

self-limited; 1-14 days

Chronic pain lasts longer than ___ months and is maintained OR beyond the course of healing

3 months

Malignant chronic pain can be related to

and/or cancer treatment

Non malignant chronic pain can be? (5)

1. Neuropathic
2. Inflammatory
3. Musculoskeletal
4. Idiopathic
5. Combination of any/all

_______________ & ______________ are types of nociceptive pain

somatic and visceral

How is nociceptive pain treated?

Opiods and NSAIDS

somatic pain comes from tissue damage --> activation of _____________ fibers

a delta; C fibers

_________________ pain is described as well localized and sharp

somatic (nociceptive)

_________________ pain is described as dull, cramping, squeezing, vague, and poorly localized

visceral (nociceptive)

what type of pain is often accompanied by ANS reflexes like N/V/D, HR, BP increase

visceral (nociceptive)

____________ pain is caused by damage to CNS or PNS nerves and is due to dysfunction of the CNS (spontaneous excition) --> abnormal processing of painful stimuli that leads to spontaneous excitation of chronic pain states

neuropathic

what pain is described as burning, tingling, shocklike

neuropathic

what are the non-nociceptive pains

neuropathic
idiopathic

T/F: chronic pain often exhibits more than 1 type of pain classification

true

T/F: Idiopathic pain is associated with chronic pain states, pain with no apparent cause and psychological symptoms

True

T/F: opioids normally manage neuropathic pain really well?

What else should they use?

false; normally does not work on neuropathic pain

steroids, anti-convulsants, cannabis- anything to calm down the nerves

what are the four processes of somatic nociceptive pain

1. transduction
2. transmission
3. modulation
4. perception

_______________ = transformation of a noxious stimuli (chemical, mechanical, or thermal) into an action potential

transduction

In transduction, Noxious stimuli is detected by________whoch conduct a noxious stimuli to the dorsal horn of the spinal cord

nociceptors

Large and myelinated fibers are what kind? what pain is sensed?

A delta fibers
fast sharp pain- withdrawal mechanism

Smaller non myelinated fibers are what kind? What pain is sensed?

C fibers
dull, burning, throbbing, aching

T/F: During transduction, there is a release of chemical mediators from inflammatory response and release of neurotransmitters, as well as stimulation of peripheral nociceptors and action potential

True

______________ = process by which an action potential is conducted from the periphery to the CNS

transmission

The ______tract carries signals from the trunk and the lower extremeties

spinothalamic

The primary afferent neurons ( a delta and c fibers) are located where?

dorsal root ganglia of SC

What are the two types of 2nd order neurons?

1. Nociceptive neurons- receive input solely from primary afferents
2. Wide range neurons- input from nociceptive ( a delta and c fibers) efferent fibers and non nocicpetive fibers

2nd order neurons are generated in the ________ , cross the midline of the ________, through the anterior _______, and ascend in the anterolateral pathway to the _____ to synapse with 3rd order neuron

rex laminae I,II, & V
spinal cord
commissure
thalamus

3rd order neurons reside in the lateral _______& intralaminar nuclei and send the action potential to the cerebral cortex for interpretation

thalamus

________________ = the recognition of pain signal from various areas of the brain

perception

Perception happens when recognized by various areas of brain including (4)?

amygdala
somatosensory
hypothalamus
anterior cingulate cortex

________________ = brains response to action potential, alteration of neural afferent activity along the pain pathway (suppresses/enhances pain signals)

modulation

In modulation, the descending axons travel via the ______(DLF) and synapse with the brain and spinal cord

DORSOLATERAL FUNICULUS

Action potentials travel down to the __________via the dorsolateral funiculus and activate the __________releasing hormones

substantia gelatinosa
enkephalin

Enkephalin then binds to opiate receptors ...either presynaptic_____order or postsynaptic ______order

first
second

Enkephalin causes decreased _______(excitatory neurotransmitter) which suppresses the ascending pain transmission

substance P

Inhibitory neurotransmitters released via descending pathway (5)

Glycine
GABA
Enkephalin
Serotonin
Norepinephrine

what is the primary treatment for pain

reducing transduction through inhibiting neurochemical mediators

what areas of the brain are responsible for perception of pain

1. amygdala
2. somatosensory area of cortex
3. hypothalamus
4. anterior cingulate cortex

describe the process of transduction

1. noxious stimuli detected by primary afferent nociceptors (a-delta and C fibers)
2. release of chemical mediators and neurotransmitters
3. stimulate periperpheral nociceptors: depol = Na influx; K efflux = repol
4. AP travels up to dorsal root of spinal cord & pain impulse generated

what is the peptide found and released from the peripheral afferent (sensory) nociceptor C fibers and
involved with slower than other nerve fibers, chronic, pain

Substance P

what receptors does substance P work on? What does this result in?

Acts via the G-protein linked neurokinin-1, neurokin 2

results in vasodilation, extravasation of plasma proteins, degranulation of mast cells, and sensitization of the stimulated sensory nerve

What major excitatory neurotransmitter is released in the CNS and from the Aδ & C primary afferent nerve fibers

and effects are instantaneous = initial, fast, sharp pain

Glutamate

what receptors does glutamate work on

NMDA, AMPA, kainite, mGluR

what are your excitatory neurotransmitters with pain

1. substance P

2. glutamate

What peptide is released during the inflammatory process and is algesic (causing pain) and has direct stimulating effect on peripheral nociceptors via specific bradykinin receptors (B1 & B2)

Bradykinin

What amine is released from mast cell granules, basophils, and platelets via Substance P

and reacts with various receptors to produce edema and vasodilation

Histamine

What amine stored and released from platelets after tissue injury
and reacts with multiple receptor subtypes and exhibits analgesic effects on peripheral nociceptors
•Can potentiate bradykinin induced pain

Serotonin

What receptor does serotonin work on?

5-HT

What is a metabolite of arachidonic acid that is Synthesized from COX-1 and COX-2, Associated with chronic pain and Sensitize peripheral nociceptors causing hyperalgesia

Prostaglandins: (PGE)

What is released
in response to to tissue injury by a variety of immune and nonimmune cells via the inflammatory response- Include interleukin-1β, interleukin-6, and tumor necrosis factor-α

Cytokines

what are your inhibitory neurotransmitters with pain

1. glycine - chloride linked (GlyR)
2. GABA ( GABA a, GABA b, GABA c)
3. enkephalin
4. serotonin
5. norepi (a2 adrenergic)

inhibitory neurotransmitters are released via the ________________ pain pathway

descending

_________________ pain is acute pain on top of chronic pain

breakthrough pain

what are some mechanisms at which acute pain transitions to chronic

1. initiated by either periperhal or central mechanisms (peripheral or central sensitization)
2. hyperexcitable nerve endings (change from direct nerve injury, or sprouting of new nerve endings)
3. neuroma formation
4. damaged nerves have lower pain threshold so respond to non-noxious stimuli

_______________________ hyperalgesia occurs at the original site of injury, enhanced pain from heat and mechanical stimuli

primary

_______________ hyperalgesia occurs in uninjured tissues surrounding the injury, enhanced pain response to mechanical stimuli

secondary

SNS response can depend on what? (4)

1. size of surgical field
2. number of nerve pain receptors in area
3. bleeding, infection
4. coexisting disease

CV physiologic effects of acute pain

1. increased catecholamines
2. increased cortisol --> increased HR, increased vascular resistance, increased myocardial activity, and increased ABP
3. increased myocardial O2 demand & consumption

aggressive pain management is essential to preventing _________________

post-op cardiac complications

respiratory physiologic effects of acute pain

1. decreased TV due to decreased movement
2. muscle spasms = decreased/limited respiratory movement (lose breath)
3. poor cough --> atelectasis and PNA
4. decreased VC, IC & TLC

*Worse in pts with pre-existing pulm dysfunction (Asthma, COPD) or ⬇FRC at baseline (morbidly obese, elderly)*

GI physiologic effects of acute pain

1. decreased gastric emptying
2. decreased intestinal motility
3. increased smooth muscle sphincter tone

what are the coagulation effects of acute pain

1. increasd plt aggregation
2. venostasis

with acute pain immunologic function is ______________

decreased

GU effects of acute pain

increased urinary sphicter tone --> oliguria and urinary retention

psychological effects of acute pain

1. fear
2. anxiety
3. depression
4. helplessness
5. anger

Central sensitization pain

Alteration of central nervous system processing of sensation leading to amplification of pain signals; lower threshold for non painful stimuli

Ex: fibromyalgia

In central sensitization, pain modulation is_________, d/t neuroplastic changes of ______. Repetitive stimuli to injured nerves alters the________levels. This is associated with _______pain states.

enhanced
CNS
neurotransmitter
chronic

T/F: Peripheral sensitization is environmental chemical changes of peripheral nerves
Release of algogenic substances and neurotransmitters
leads to enhanced excitability of nerves- firing and twitchy
which reduces nociceptive thresholds
High-threshold nerve endings become responsive to non-noxious stimuli

True

In the Wind up phenomenon there is sensitization of the ______Neurons, and increased release of neurotransmitters ( esp. glutamate), leading to sustained stimulation of ______fibers--> longer sustained depolarization (basically a repeated stimulus send up an exaggerated response)

WDR
c fibers

what medications act on transduction of pain signals

1. NSAIDs
2. LA
3. steroids
4. antihistamines
5. opioids

what medications act on transmission of pain signals

LA
TCA
Steroids

what mediations act on modulation of pain signals

1. neuraxial opioids
2. NMDA antagonists
3. alpha 2 agonists
4. AChE inhibitors
5. SSRIs
6. SNRIs

what medications act on perception of pain signals

1. GA
2. opioids
3. alpha 2 agonists

What are the groups of NSAIDS (5) and examples

Acetic acid- toradol
Oxicam - mobic
Propionic- Ibuprofen, naproxen
salicylate- aspirin
cox 2 selective- celebrex

MOA of NSAIDs

blocks COX-1 and 2 --> decreased prostaglandin synthesis from arachidonic acid --> decreased nociception and tissue damage/inflammation

The 3 main properties of NSAIDS

antipyretic
analgesic
anti inflammatory

what type of pain responds to NSAIDs the best

nociceptive

NSAIDs are mostly metabolized in the _______________ with excretion into __________________

liver; urine/bile

responsibilities of COX- 1

1. plt aggregation (via thromboxane A2)
2. gasric mucosal integrity
3. renal fx

inhibition of COX-1 -->

1. gastric irritation
2. renal microvascular constriction
3. plt inhibition

COX_____ is widespread throughout the body, necessary for homeostasis and is working all the time

1

______________ is an inducible enzyme that releases prostaglandins in the presence of inflammation, comes into play when theres injury

COX-2

COX _________ mediates pain, fever, and carcinogenesis

2

inhibition of COX2 -->

analgesia

adverse reactions of NSAIDs

1. GI dyspepsia
2. renal dysfx
3. peptic ulcers
4. hepatocellular injury
5. asthma exacerbation
6. allergic reactions
7. tinnitus
8. urticaria

MOA of how NSAIDs --> GI toxicity

decreased prostaglandin synthesis --> decreases in GI blood flow and secretion of mucus

risk factors for GI toxicity with NSAIDs

1. high dose
2. older age
3. H. pylori infection
4. hx of prior ulcer
5. concominant use of low dose ASA, anticoags, or corticosteroids

conventional NSAIDs and COX-1 have what effect of platelets

impairs the ability of the plts to aggregate (i.e. activity)

T/F: COX-2 has no effect on plt aggregation

true