Pain: Pathways and Prostaglandins

a symptom, detrimental to healing → causes adrenergic response, epinephrine released which increases heart rate, vasoconstriction so less blood flow to other tissues (stimulates sympathetic nervous system )

Ruffini's endings
Pacinian corpuscles
Krause end bulbs

Meissner's corpuscles
Merkel Disc
Root hair plexus

respond to pain and temperature

Thought to increase the sensitivity of pain receptors by enhancing the pain provoking effect of bradykinins

nociceptors => A or C nerve fibers of the PNS (1st order neuron)=> spinal nerve => dorsal root & ganglion => posterior horn synapse ('substance P' neurotransmitter) => 2nd order neuron - decussates (cross over) => ascends spinal cord's white matter column via the 'spinothalamic tract' (lateral) => thalamus ('relay station')=> synapse with 3r order neuron => somatosensory cortex in the brain - localization: specific body part of the sensory homunculus => awareness !

Signals from Aa or AƁ fibers reach SC and close gate before slower C fibers reach the region.

Can also be closed when flooded with non-nociceptor impulses. Explains process of massage, acupuncture, electrical nerve stimulation to alleviate pain.

endorphins, enkephalins, dynorphins

natural pain suppression system of the body

Acetaminophen (Tylenol) - non-opioid centrally acting agents

Opioids- 'narcotics'

NSAIDS are ___________ analgesic drugs

Ibuprofen + muscle relaxant

muscle relaxant calms the nerve to decrease sensory nervous stimulation which ends up relaxing muscle

non-opioid medications
PO
NSAIDs, Tylenol

opioids

PO
Codeine, combination (non opioid + opioid) , Morphine

higher potency opioids
IV route, pure form
Consider PCA

a drug delivery system that uses a computerized pump with a button the patient can press to deliver a dose of an analgesic through an intravenous catheter

centrally acting analgesic

not anti-inflammatory

Antipyretic (vasodilation)

administration: PO; q4h

Centrally acting analgesics → CNS
agonists for receptors mu, kappa, delta → inhibit release of Substance P

Fentanyl

hydromorphone (Dilaudid)

meperidine (Demerol)

Morphine

methadone (Metadol)

hydrocodone

oxycodone
(OxyNeo)

oxycontin

tramadol (Ultram)

oxycodone + acetaminophen

oxycodone + aspirin

hydrocodone + acetaminophen

tramadol + acetaminophen

drugs with acetaminophen

opioid analgesic
mixture of codeine, caffeine and acetaminophen

makes patient more alert - inverse agonist of opioid, also makes more lipophilic so more easily absorbed

Sedation
Nightmares (psychomimetic)

Euphoria
Substance dependence

Respiratory depression
Hypotension

Pruritus (itchy) (histamine release) - morphine
Decreased GI motility
Urinary retention

Opioid receptor Antagonist (mu & kappa receptors)

onset - 2-4 minutes

Duration of action = 45 min

Intramuscular

Synthetic opioid that helps suppress withdrawal symptoms in morphine/ heroin addict. This was sometimes a drug of choice for some drug users.

a localized response to an injury or to the destruction of tissues

1. Release of inflammatory and chemotactic factors

2. Vascular changes including vasodilation, increased capillary permeability, and clotting

3. Recruitment of immune cells by Margination, Diapedeis, and Chemotaxis

4. Neutrophils and macrophages phagocytose pathogens and cell debris at the site and the tissue heals

Inhibit prostaglandin formation via COX enzyme inhibition
- modulate pain & fever (analgesic, antipyretic)

Arachidonic acid (fatty acid) precursor + COX → inflammatory sequelae

protects gastric mucosa, supports renal function, promotes platelet aggregation,

peptic ulcers, GI bleeding, kidney failure

triggers inflammation and pain

Celecoxib (Celebrex)

found to have severe cardiac effects → only used for patients who can't take ibuprofen anymore

aspirin, ibuprofen, Ibuprofen-like drugs

Diclofenac (Voltaren)

Naproxen (Aleve, Naprosyn)

Ketorolac (Toradol)

Indomethacin (20xASA potency) = Rx only

20X Aspirin potency

hormone produced by the adrenal cortex with a role in carbohydrate metabolism

Adrenal cortex secretion

Lipophilic - Nuclear receptor binding

high efficiency!

ideal for acute or severe cases

during fasting - stimulates gluconeogenesis, stimulates protein degradation,
facilitates lipolysis

Prostaglandin synthesis inhibition (COX-2 only)

Suppression of phagocytes/lymphocytes

Histamine release suppression

formation of glucose from noncarbohydrate sources

- monitor liver profile
- Avoid in active untreated infections
- may cause CNS alterations
- may cause peptic ulcers
- may cause Cushingoid appearance (buffalo hump, moon face)
- Weight gain
- Osteoporosis
- Decrease wound healing
- May elevate blood sugars
- May increase cholesterol and lipid values

(suffix: -one)
Hydrocortisone, Cortisone
Prednisone, Prednisolone
Methylprednisolone
Dexamethasone

ADME
Lipophilic
Overall highly PPB
Prednisone (Prodrug)

Lipophilic
Overall highly PPB
Prednisone (Prodrug)

Autoimmune: e.g. IBD, Lupus
used as adjunct
Drug: Dexamethasone (PO, low dose, daily)

*class*: antiasthmatics, corticosteroids

*Indication*:Manage cerebral edema,

assess for Cushing's Disease

*Action*: Suppress inflammation and normal immune response. Used in inflammatory states to decrease inflammation.

Cortisone injection in local area
Allergic Rhinitis

budesonide (Rhinocort)

fluticasone (Flonase)

mometasone (Nasonex)

inhalation - into bronchioles

Pulmicort (Budesonide),
Qvar (Beclomethasone),
Flovent (Fluticasone)

Anti-inflammatory medications = 'controllers'

Glucocorticoids
Leukotriene modifiers
Mast cell stabilizers

(asthma rescue drugs)

B2 adrenergic agonists

Anticholinergics - atrovent

Epinephrine

Anticholinergic

Relaxes muscles in the airways and increase airflow to the lungs.

Short acting beta-2 adrenergic receptor agonist.

Used for the relief of bronchospasm in asthma or COPD.

short acting beta agonist

Class of drugs used to treat asthma and other pulmonary diseases by causing smooth muscle relaxation, resulting in dilation of bronchial passages

short onset, short t1/2 (IM/IV in advanced rescue)

nonselective - fight or flight activated

Primary mediator of sensory stimulated inflammation

stored within the mast cells - released upon mast cell contact with allergen

- binds to H1-receptors ('G-protein' type)

H1 receptor antagonists

First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier.


Second-generation antihistamines mainly block histaminic receptors and do not pass the blood-brain barrier.

block both histamine and muscarinic receptors as well as passing the blood-brain barrier.

Diphenhydramine (Bendaryl®)

Chlorpheniramine (Benylin)

Block H1 histamine receptors

Decreased CNS distribution
'non-drowsy'


fexofenadine (Allegra)

loratadine (Claritin)

cetirizine (Reactin)

desloratadine (Aerius)

(Reactin) fast melt tabs
Onset 10-20 min
Duration 24 hrs

eye drops for allergic reaction eye symptoms

A respiratory drug that prevent asthma attacks by blocking leukotriene (a bronchoconstrictor) from binding to receptors in respiratory tissues.

leukotriene receptor antagonist medication used when higher exposure levels anticipated, longer term

CNS depression of cough reflex
Caution - not always desirable, cough is protective reflex which can increase infection
Codeine (opioid) - CNS depression
Dextromethorphan (direct CNS acting)

Codeine (opioid) - CNS depression

Dextromethorphan (direct CNS acting)

activate alpha1-adrenergic receptors on nasal blood vessels, which causes vasoconstriction, which in turn causes shrinkage of swollen membranes followed by nasal drainage.

Ephedrine, Pseudoephedrine