Pain Flashcards
Two types of Pain
Nociceptive and Neuropathic
Nociceptive Pain Defined and Two types
transduction of noxious stimuli, irrespective of cognitive awareness.
1) Somatic: cutaneous or deep tissues
2) Visceral: internal organs
Neuropathic pain defined
Caused by a primary lesion or dysfunction in the nervous system
Itch vs pain
Both mediated by thin unmyelinated nerve fibers from skin
Mediated by different mechanisms
Itch definition and causes
-Unpleasant sensation with desire to scratch
Pruritogens: histamine, environmental chemicals, drugs
Chronic Pain common mediators
Inflammatory
-TNF alpha and IL-1beta
Where do neuroimmune mediators act? Effects?
- peripheral nociceptive nerve terminals
- causes hyperalgesia
- Chronic pain causes synaptic sensitization
Which tract does pain follow? what is it?
Anterolateral Spinothalamic tract
- Synapses in Dorsal horn
- Crosses sides
- next synapse isn’t until the thalamus
Dermatome
Area of skin whoses sensory nerves all come from a single spinal nerve root
Dermatome significance
Why pain associated with a visceral organ (heart) might be perceived as peripheral (arm).
Chemical modulators of pain
Bradykinin (sensory neurons)
- 5HT (platelets)
- Histamine (mast cells)
- Neuropeptides
- ATP, K+ (Injured cells)
- Chemokines
- Ion Channels: Na, Ca, NMDA, AMPA, Kainate, TRPV1, H+ sensing channels
Most important sensitizers of peripheral pain sites
Prostaglandins (PGE2)
Sex differences in Pain
- Women have lower pain thresholds
- Women respond better to Opiod kappa agonists
- Red headed women have even lower threshold: polymorphism to melanocortin-1 receptor
How to trap salicylic acid in urine
increase pH higher percentage ionized, remains in urine
asa metabolism
Mosly 1st pass, some plasma esterase
types of eicosanois
- prostaglandins
- Thromboxanes
- Leukotrienes
Prostanoids
- prostaglandins
- Thromboxanes
Arachidonic Acid Metabolites by Cox:Actions
-Pain & Inflammation: PGE2
- Vasodilation: Prostaglandins
- Vasoconstriction: Thromboxane
- Platelet aggregation: thromboxane
- Platelet dis aggregation: prostacycline
PGE
Pain and inflammation,
inhibit acid secretion
stimulate Mucous secretion
Na and water excretion
Prostaglandins
Pain, Vasodilation, acid secretion, mucous secretion
Prostacyclin
Vasodilation, platelet disaggregation,
inhibit acid secretion
Stimulate Mucous secretion
Na and water excretion
Thromboxane
Vasoconstriction, platelet aggregation
Cox-2 binding site specificity
Val substituted for Ile
Cox2/Cox1 ratio
Relative selectivity
>1 Cox 1 selective
Antipyretic is antifever, what is the difference between fever and hyperthermia?
Fever: elevated temp due to elevated set point
Hyperthermia: Heat production > Heat dissipation
Which hypothalamic nucleus is heat sensitive?
Anterior
Which hypothalamic nucleus is cold sensitive?
Posterior
NSAID Antipyretic MOA
PGE2 increases cAMP production, increases heat generation and decreases heat loss
1) Inhibition of PGE2 prodution
2) Increase heat loss to vasodilation and sweating
COXIs GI Effects
- Gastric intolerance: Chemoreceptor trigger zone stimmmulation and direct irritant
- Ulcer: gastric H+ increases, mucus secretion decreses, bicarbonate decreases, decreased mucosal blood flow (PGI2)
ASA risk
Dose ore Duration?
DDIs?
GI bleeding
Dose
Clopidogrel, warfarin, and other NSAIDs
Does enteric coated ASA cause GI Stomach problems?
Yes, still reaches stomach via blood stream. Duh.
Salicylate and URAT1
URAT1 resporbs uric acid in proximal tubule (is bidirectional)
Low salicylate
decrease urate excretion by competitive transport
High salicylate
increases urate excretion: somehow
ASA and pregers
Category C: no evidence
Avoid near-term as it can increase duration of labor, increase bleeding
Preeclampsia
Sudden spike in BP
Current cure: premature delivery of fetus
Salicylate intoxication
over 40 mg/dl after ingestion
Salicylate poisoning symptoms
Tinnitus N/V Lethargy/excitibility Increase temp Hyperventylation -> respiratory alkalosis
Severe: Metabolic acidosis, seqizures
> 35 mg/dl
Stimulates medullary respiratory center -> hyperventilation -> respiratory alkalosis -> renal excretion of HCO3-, Na+, and K+ to compensate for respiratory alkalosis; reduced buffering capacity
uncoupling of oxidative phosphorylation
Now have compromized respiratory alkalosis
> 50 mg/dl
hypoventilation -> increased CO2 retention, respiratory acidosis,
Cannot compensate due to previous loss of HCO3-
Salicylate intoxication Tx
- Lavage or charcoal for large engestion
- Whole body irrigation with PEG until shitting clear
- Correct for dehydration
- Alkaline diuresis (increase urine pH
Ketorolac
MOA
Time limit
Admin
NSAID (COXI)
5 days
IV,IM, Intranasal
Ibuprofen (Caldolor)
IV formulation
400 - 800 mg over 30 min Q6H
NSAID BBW
Cardiovascular: may increase Thrombolic events
GI: Increased GI bleeds, ulceration, perforation
Nephrotoxicity:
Na/K,Cl retention,
Edema
COX-1 mediated
Risks: kidney function, CHF, diabetes, liver disease, ACEIs, ARBs
Renal Tox and NSAIDS
High NSAID dose increases risk
Indicators of Liver Damage
Serum aminotransferases
- AST aspartate transaminase
- ALT alanine transferase
NSAIDS and pregers
Do not use in 3rd trimester due to closure of ductus arteriosis
What is the only shown benefit of Cox2 selective?
Decreased GI issues
Is Cox2 inhibition cardioprotective in absence of Cox1 inhibition?
No, infact it increased risk of MI
APAP/paracetamol
COX2 selective
Mildly anti inflammatory
Brain selective
Paracetamol and bleeding
Low anti-platelet activity, but
May increase INR respons to warfarin? may inhibit 3A4
APAP toxicity
IMINE Conjugation to proteins
Hepatic enzymes
N-acetylcysteine
Given w/in 8-10h of OD
Oral: mucomyst
IV: Acetadote
How is Naltrexone used to treat ethanol dependence
Decreases ethanol-induced dopamine release in nucleus accumbens
Naloxegol
MOA and use
Opioid antagonist
Not orally absorbed, used to treate opioid induced constipation
Symptoms of Opioid overdose
Euphoria, drive depression CNS/Respiratory depression Miosis, Hyperthermia decreased bowel sounds
Opioid intoxication treatment
- Maintain respiration
2. Reverse OD with antagonist
Opioid tolerance to
Analgesia
CNS depression
Euphoria
No opioid tolerance to
pupillary constriction or increased smooth muscle tone
Opioid tolerance mechanism
increased adenylate cyclase, countering opioid induced decrease in cAMP
Opioid Withdrawal Symptoms
Piloerection Muscle contractions Anxiety restlessness diarrhea lacrimation
Which drugs have most severe withdrawal?
short acting with coadministered antagonist
Neuropathic pain
Hyperalgesia to mechanical and thermal stimuli
Allodynia: pain to normally non-painful stimulus
Why is neuropathic pain not responsive to opioids?
damage to primary afferent neurons decreases expression of opioid receptors
What is most effective in neuropathic pain?
TCAs?
What antiepileptic drugs are approved for neuropathic pain?
Gabapentin and Pregabalin
