Medications related to the MS System

Acute pain

Acute pain

7-10 days

Chronic pain

10 months or longer

afferent pathways

begin in the PNS, travel to the spinal gate in the dorsal horn and then asc

Interpretive Centers

located in the brainstem, midbrain, thalamus and cerebral cortex

Efferent Pathways

descend from the CNS back to the dorsal horn of the spinal cord

Adjuvant Analgesic Drugs

drugs that are added for combined therapy with a primary drug and may have additive or independent analgesic properties

agonists

substances that bind to a receptor and cause a response

agonist- antagonists

substances that bind to a receptor and cause a partial response that is not as strong as that cause by agonists

partial agonists

another name for agonist-antagonists

analgesic ceiling effect

the effect that occurs when a particular pain drug no longer effectively controls a patients pain despite the administration of the highest safe dosages

analgesics

medications that relieve pain

antagonists

substances that bind to a receptor and prevent/block a response, resulting in inhibitory or antagonistic drug effects, also known as inhibitors

nociceptors

nerve fibers that when stimulated produce the sensation of pain

nociception

the sensation of pain

4 stages of nociception

Transduction, transmission, perception of pain, modulation

transduction

injured tissue releases chemicals that propagate pain message, action potential moves along an afferent fiber to the spinal cord

transmission

the pain impulse moves from the spinal cord to the brain

third step or nociception

perception of pain

modulation

neurons from brainstem release neurotransmitters that block the pain impulse

glutamate

neurotransmitter released from the end of presynaptic neuron

spinothalamic pathway

spinal cord-> spinothalamic tract-> medulla -> thalamus -> thalamus generates pain

pain can be modulated

the amount of injury is not necessarily correlated to the amount of pain perception

endogenous analgesic system

the body's own system of turning off pain or reducing pain

endogenous opioids

family of morphine like neuropeptides that inhibit transmission of pain impulses in the periphery, spinal cord and brain by binding with mu, kappa and delta receptors

opioid receptors

widely distributed throughout the body, responsible for general well-being and modulation of respiratory and cardiac functions, stress and immune responses, GI function, reproduction, and neuroendocrine control

frontal lobe's role in turning off pain

processes survival is necessary and turns pain off. These impulses go to the hypothalamus

pain inhibition process

chemical transmitters from the descending analgesic pathways fit into pre and postsynaptic sites between the peripheral nerve and spinal nerve in the dorsal horn of the spinal cord, Inhibits ongoing propagation of the nerve impulse in the spinal cord

gate control theory & Ascending Inhibition

Belief is noxious afferents can be blocked at the spinal cord level ex: touch sensation at the same time reduces pain impulse transmission through the dorsal horn, pain impulses also can't get through at the same time

opioids

most effective pain relievers

three main classes of opioid receptors

mu, kappa, and delta

Mu receptors

analgesia, respiratory depression, euphoria, sedation, and physical dependence

kappa receptors

analgesia and sedation, kappa activation may underlie psychotomimetic effects seen with certain opioids

source of morphine

seedpod of the poppy plant

morphine can cause

respiratory depression (always check respirations before administration), constipation, urinary retention, orthostatic hypotension, emesis, miosis (excessive constriction of the pupil of the eye), cough suppression, biliary colic, tolerance and physical depenence

tolerance of morphine

increased doses needed to obtain the same response, can also be cross tolerance to other opioid agonists

morphine solubility

not very soluble, does not cross blood- brain barrier easily, only small fraction of each dose reaches site of analgesic action

clinical use of opioids

postoperative pain, obstetric analgesia, myocardial infarction, head injury, cancer related pain, chronic non-cancer pain

opioid drug interactions

CNS depressants, anticholinergic drugs, hypotensive drugs

signs of opioid toxicity

coma, resp depression, pinpoint pupils

treatment of opioid toxicity

ventilatory support, naloxone (narcan)

guidelines for opioid administration

monitor vital signs before giving, give on a fixed schedule

narcotics control regulations

securely stored and handled throughout the medication management system

inflammation

normal, necessary and nonspecific general response in an attempt to minimize injury an maintain homeostasis

cyclooxygenase inhibitors

suppress inflammation, relieve pain, and reduce fever

prostaglandins

phospholipids from injured cell membranes released to tissue spaces

phospholipase Enzyme A

stimulated by prostaglandins and produces arachidonic acid

arachidonic acid

stimulates a tissue enzyme called cyclooxygenase (COX 1 & COX 2) which stimulates the release of prostaglandins

NSAIDs mechanism of action

inhibition of the leukotriene pathway, the prostaglandin pathway or both. Blocking the chemical activity of the enzyme COX

COX 1

Has a role in maintaining the GI mucosa

COX 2

promotes synthesis of prostaglandins involved in the inflammatory process

activation of the arachidonic acid pathway causes

pain, headache, fever, inflammation

Inhibition of COX 1

causes harmful effects such as gastric erosion and ulceration, bleeding tendencies, renal impairment

Inhibition of COX 2

results in largely beneficial effects such as suppression of inflammation, alleviation of pain, reduction of fever, protection against colorectal cancer

1st Generation NSAIDs

Nonselective: block both COX 1 & COX 2 ex: aspirin, ibuprofen, naproxen, diclofenac and ketorolac

2nd Generation NSAIDs

Selective COX 2 inhibitor ex: celecoxib

analgesic NSAIDs

for treatment of headaches, mild to moderate pain, and inflammation. Block the chemical activity of either or both cyclooxygenase (COX) enzymes (prostaglandin [PG] pathway) and lipoxygenases (leukotriene [CT] pathway)

antipyretic NSAIDs

to reduce fever by inhibiting prostaglandin E2, within the area of the brain that controls temperature

Salicylates NSAIDs

have antiplatelet activity, inhibit platelet aggregation

Contraindications for NSAIDs

drug allergy, conditions that place the patient at risk for bleeding, severe kidney or liver disease, lactation

salicylates are contraindicated

in children with flulike symptoms, as its use is strongly associated with Reye's Syndrome

Adverse effects of NSAIDs

GI (dyspepsia, heartburn, epigastric distress, nausea, Gi bleeding, ulcers), Renal (reductions in creatine clearance, acute tubular necrosis with renal failure), Cardiovascular (noncardiogenic pulmonary edema)

Salicylates (ASA, Aspirin)

Analgesic, antipyretic, anti-inflammatory, antithrombotic, antiarthritic, prevent thrombotic events, treat pain associated with headache, neuralgia, myalgia and arthralgia

salicylates

better tolerated with food, milk or antacid

adverse effects of NSAIDs

can be treated with misoprostol (Apo-Misoprostol)

Salicylate is typically excreted

by the liver but during overdose renal excretion is vital

salicylate toxicity

can be acute (ingesting 150mg/kg) or chronic where the patient is ingesting more over time than they can excrete

signs and symptoms of salicylate toxicity

hyperventilation, damages glucose metabolism, cerebral and pulmonary edema, tinnitus and hearing loss, hyperthermia

Aspirin (ASA)

shown to reduce cardiac death after myocardial infarction (MI)

daily Aspirin tablet

(81 mg or 325 mg), prophylactic therapy for adults who have strong risk factors for developing coronary artery disease or cardiovascular accident

Salicylate toxicity treatment

may need mechanical intervention, dextrose IV for possible CNS hypoglycemia,

signs of salicylate toxicity

most common manifestations in children are hyperventilation and CNS effects

salicylate toxicity arises

when serum levels exceed 2.89 - 4.3 mmol/L

NSAIDs and Kidney Function

disruption of prostaglandin function by NSAIDs is sometimes strong enough to precipitate acute or chronic kidney injury or failure

patients at risk for impaired kidney function with use of NSAIDs

patients with dehydration, heart failure, or liver dysfunction, or with the use of diuretics or angiotensin-converting enzyme inhibitors

Warning from Health Canada concerning NSAIDs

increased risk of adverse cardiovascular thrombotic effects, including fatal MI and stroke, they also cause in increased risk of serious GI adverse events, older adults are at greater risk

Acetaminophen

has analgesic and antipyretic properties equivalent to aspirin but is devoid of clinically useful anti-inflammatory and antirheumatic actions, also does not decrease renal blood flow or cause renal impairment

acetaminophen overdose

can cause severe liver injury

acetaminophen inhibits

cyclooxygenase, and is limited to the CNS (reducing fever and pain)

acetaminophen overdose

hepatic necrosis progressing to hepatic failure, coma and death ( 72h after drug ingested, over 4000mg/day but lower doses needed in alcoholics, malnourshed individuals or those with liver disease)

early symptoms of acetaminophen overdose

nausea, vomiting, diarrhea, sweating, abdominal pain,

treatment of acetaminophen overdose

acetylcysteine (mucomyst) - needs to be given within 8-10h of overdose to prevent severe liver injury

acetaminophen has been associated with

the development of Steven Johnson's syndrome (red rash)