exam 3 - inflammatory response, opioids, nsaids, anti migraines

inflammation

response to tissue injury and caused by release of chemical mediators that trigger both vascular and the migration of fluid and cells 

process of inflammation

protective mechanism where the body attempts to neutralize and destroy harmful agents at site of injury and establish conditions for tissue repair

cardinal signs of inflammation

rubor (redness/erythema) tumor (swelling/edema) dolor (pain) calor (heat) and loss of function

response to tissue injury

Vasoconstriction (momentary literally like half a second) and release of chemical mediators (histamines, kinins, and prostaglandins) —> dilated arterioles, increased capillary permeability, pain, fever —> rubor, tumor, dolor, calor —>tumor and dolor create loss of function

vascular phase of inflammation

10-15 minutes after injury; vasodilation and increased permeability during which blood substances and fluid leave plasma to go to injured site 

delayed phase of inflammation

when leukocytes infiltrate the inflamed tissue

hageman factor

released when tissue is injured; starts clotting factor and activates the kinin system

leukocytes

WBCs - eosinophils, basophils, and neutrophils

lymphocytes

WBCs - T cells, B cells, and NK cells

B cells

plasma cells which become antibodies

T cells

cytotoxic T cells, helper T cells, and suppressor T cells 

effector and cytotoxic cells

immediately destroy foreign cells

helper T cells

stimulate immune and inflammatory

suppressor T cells

dampen immune and inflammatory response to save energy and prevent cells damage

macrophages

mature leukocytes that are capable of phagocytizing antigens 

Major Histocompatibility complex (MHC)

distinguish genetic id code on chromosome that identify self cells from foreign invaders 

Mast cells

release histamine

Cyclooxygenase (COX)

enzyme responsible for converting arachidonic acid into prostaglandins and their products; synthesis of prostaglandins causes inflammation and pain at injury site

COX 1

stomach lining, blood clotting, and sodium and water retention (edema and hypertension) 

COX 2

triggers pain and inflammation

5 groups of NSAIDs 

salicylates, para-chlorobenzoic acid derivatives (indoles), propionic acid derivatives, oxicams, and selective cox 2 inhibitors 

Salicylates (aspirin/acetylsalicylic acid) (ASA)

• cox1+2 inhibitor —>inhibit synthesis of prostaglandins 

• oldest anti inflammatory and first used as an analgesic

• 3 A’s: anti inflammatory, antipyretic (fever), antiplatelets

• drug interactions: increased bleeding with other anticoags. and other NSAIDs; risk for hypoglycemia with oral antibiotics; don’t take with warfarin or tylenol

• avoid during last trimester of preg and dont give to kids bc it may lead to reye syndrome. don’t take if u have asthma or COPD

• side effects: GI distress (hard on your stomach) ulceration and bleeding, tinnitus, vertigo, hearing loss, and bronchospasm

Acetic acid (KID: ketorolac, indomethacin, and diclofenac)

• decrease prostaglandin synthesis by inhibiting cox1+2

• use for rheumatoid, osteo, and gouty arthritis

• Side effects: neuro, NVC, sodium and water retention and increased bp, hyper-kalemia and natremia

  • TAKE WITH FOOD

Propionic acid derivatives (ibuprofen and naproxen —> aleve)

• blocks arachidonic acid binding by inhibiting cox1+2

• most widely used NSAID

• use for pain, osteo and rheumatoid arthritis

• side effects are neuro, insomnia, blurred vision, tinnitus, GI distress/bleeding, edema

  • increased bleeding with warfarin AND SSRIs

Oxicams (pir-, mel-)

• decreases prostaglandin by inhibiting cox1+2

• for rheumatoid and osteo arthritis

• side effects neuro, gi distress and bleeding, edema

• well tolerated and good for chronic use because of a long half life

  • increased risk of bleeding if taken with SSRIs

Selective Cox 2 inhibitors (celecoxib → celebrex)

• selectively inhibits Cox 2 w no Cox 1 interference 

• used for o and r arthritis, ankylosing spondylitis (bone fusion), pain, and dysmenorrhea (painful menstruation) 

• side effects: neuro, sinitus, anorexia, peripheral edema, diarrhea and flatulence

• increased bleeding with SSRIs

corticosteroids (prednisone, prednisolone, dexamethasone)

• control inflammation by suppressing/preventing components of inflammatory response AT SITE

• use for arthritic flare ups (but not to control bc of neuro side effects), asthma, and skin conditions

• inhalers can cause oral thrush and dermals can cause rashes and skin thinning

• taper off over 5-10 days to allow adrenal glands to produce hormones on their own again

• Ss of steroids: Sugar (hyperglycemia), Soft bones (osteoporosis), Sick (decreases immunity/sepsis), Sad (depression), Salt (water and salt retention → hypertension), Sex (decreased libido), Swollen (water gain=weight gain), and Sight (risk for cataracts)

• taken with NSAIDs increases risk of ulcers

  • adrenal gland suppression → withdrawal syndrome

• Makes you incredibly hungry and angry→uncontrolled hormones 

DMARDs (Disease Modifying Antirheumatic Drugs)

• Immunosuppressive agents, immunomodulators, and antimalarials

• Tumor necrosis factors (TNF) blockers (tnf kills cancer and starts inflammatory process)

• use to alleviate symptoms of RA, for psoriasis, autoimmune diseases, ankylosing spondylitis

• Long half life so take in a monthly dose

• dont take if: pregnant (it crosses the placenta), acute infection, latex allergy, kidney/liver disease, other immunosuppressants, live vaccines, or heart failure

gout

defect in purine metabolism leads to uric acid buildup. inflammatory disease of joints, tendons, and other tissues. usually in great toe. don’t eat purine containing foods (organ meats, sardines, salmon, gravy, herring, liver, meat soup, and alcohol (especially beer)

Antigout drugs

colchicine, allopurinol, and probenecid

colchicine (anti inflammatory gout drug)

• acute gout

• inhibits the migration of leukocytes (cause inflammation) to inflamed site→alleviates symptoms 

• Side effects: NVD, abdominal pain, GI distress, kidney stones

• take with food 

• avoid purine foods

• contraindications: severe renal, cardiac, or GI problems

• no grapefruit garlic or ginko 

Allopurinol (xanthine oxidase inhibitor)

• chronic gout

• inhibit xanthine oxidase enzyme blocking metabolism to uric acid→ reduces uric acid production and increases UA excretion

• use to prevent gout attacks 

• side effects: neuro, GI, arthralgia (joint pain), weakness, edema, bradycardia, hyperglycemia

• dont take if asian descent

• take with lots of fluid (kidney stones)

• interacts with diuretics, bp meds, immunosupp., and penicillin (rash) 

• more potent if taken with probenecid  

probenecid (uricosuric)

• chronic gout

• blocks reabsorption of of uric acid which increases UA excretion 

• dont take with kidney disease

• Side effects: flushed skin, fever, neuro, gi distress, kidney stones

• more potent when taken with allopurinol 

acetaminophen (tylenol)

• not an NSAID 

• Action: inhibits cox 2 → prostaglandin synthesis inhibited 

• Use: muscular aches/pain, fever

• Max dose for adults: 4g/day, if taken freq=2g/day; kids max dose: 10-15mg/kg/day dont exceed 60

• side effects: anxiety, headaches, insomnia, fatigue, constipation, peripheral edema

• toxic effects: hepatic/renal failure, nausea, abdom. pain, diarrhea, blood dyscrasias, hearing loss 

• if od, antidote is NAC 

  • low incidence of gi distress

pain

5th vital sign

pain threshold

amt of stimulus needed to cause pain

pain tolerance

how much pain you can handle

analgesics

opioid for mod-sev pain, nonopioids for mild-mod pain

nociceptors 

pain receptors 

neuropathic pain 

nerve pain 

gate theory

spinal cord contains a “gate” that can block pain signals from reaching the brain

opioid analgesics

• mod/sev pain, antitussive (anticough), and antidiarrheal 

• action: CNS (opioid receptors, suppress pain impulses, and respiration/coughing

• side effects: NVC, urinary retention, ortho hypotension, reps. depression

  • low and slow give naloxone 

opioid agonists

• controlled substances → rising problem of addiction

• act on opioid receptors and cause analgesia, sedation, or euphoria 

• sev/chronic pain and analgesia during anesthesia 

• contras: GI obstruction and diarrhea caused by toxins

• cautions: resp. dysfunction, alcoholism, recent GI or GU surgery, head injury, preg/labor

• adverse: resp. depression, o hypotension, constipation, neuro effects

• drug interactions: other cns depressant 

Morphine (opioid agonist)

• for acute pain (preg/labor), relieve preop anxiety

• side effects: neuro, blurred vision, miosis, o hypotension, sedation, constipation, dyspnea, dependence, GI distress, flatulence, urinary retention, resp depression, 

• antidote is naloxone (narcan)

meperidine (demerol)

• acute  

• Use: primarily effective in GI procedures, preferred to morphine for pregnancy

• caution: large doses in older adults and cancer patients 

• neurotoxicity - nervous, agitation, irritable, tremors, seizures

• side effects: hypotension, dizzy, drowsy, euphoria, confusion, constipation, dependence

• less constipation and urinary retention than morphine 

hydromorphone (dilaudid)

• use: analgesic effect 6x more potent than morphine 

• side effects: dizzy, drowsy, confused, miosis, ortho hypotension, weakness, constipation, urinary retention, tolerance, dependence, respiratory depression

• less hypnotic effects and GI distress than morphine 

Fentanyl 

• mod/sev pain

• anesthesia induction and maintenance 

• side effects: dizzy, drowsy, confused, miosis, ortho hypotension, weakness, constipation, urinary retention, tolerance, dependence, respiratory depression

• iv push slow to avoid chest wall rigidity 

oxycodone (oxycontin)

• mod/sev pain

• acute pain, postop pain, chronic pain

• side effects: dizzy, drowsy, confused, miosis, ortho hypotension, weakness, constipation, urinary retention, tolerance, dependence, respiratory depression

• PO; often taken at home but not for a long time

Patient controlled analgesia (PCA)

• morphine, fentanyl, and hydromorphone

• loading dose, predetermined safety limits, lockout mechanism, near constant analgesic level

Opioid antagonists

• block receptor and displace the opioid 

• have a higher affinity to opioid receptor than opioid that was taken

Naloxone (narcan)

• antidote for opioid od

• reverse effects of resp depression, sedation, and hypotension

• also causes reversal of analgesia, monitor for need of another analgesia

Naltrexone

used long term to assist in relapse from opioid withdrawal

Migraine headaches

• unilateral throbbing pain, N+V, photophobia, visual aura, more common in females 20-30 y/o (also tension)

• triggers: cheese, chocolate, red wine, aspartame, fatigue, stress, missed meals, odors, light, hormonal, changes, drugs, weather, cleep changes

• pathophysiology theory is that it is due to neurovascular 

Cluster headaches

• severe unilateral non throbbing pain, around/behind eye, cluster attacks (one or more every day for sev. weeks), no aura, no nausea and vom, more common in males 

analgesics (headache meds)

• aspirin with caffeine, acetaminophen 

• NSAIDs: ibuprofen and aleve (naproxen) 

opioid analgesics (headache meds)

• meperidine (demerol) butorphanol nasal spray

Ergot alkaloids (headache meds)

• dihydroergotamine (migranal) - intranasal

• ergotamine (ergomar) - sublingual 

Selective serotonin 1 receptor agonists, -triptans (headache meds)

sumatriptan (imitrex), zolmitriptan, rizatriptan (maxalt)