Pain, Inflammation, and Glucocorticoids

prostaglandins

group of lipid-like compounds that exhibit a wide range of activities

- hormones that act locally to help regulate cell function

- every cell except RBCs produces these

- stored until they are needed

NSAIDs (nonsteroidal anti-inflmmatory drugs)

most widely used medications in the world

mechanism: inhibits the synthesis of prostaglandins by blocking cyclooxygenase

- includes: aspirin, ibuprofen, naproxen, etc.

glucocorticoids

ability to increase the availability of glucose

- supply brain with glucose

- promote protein breakdown providing amino acids for glucose synthesis

- promote fat breakdown leading to free fatty acids

- synthesized when needed & not stored (controlled by ACTH)

- metabolized in liver

Aspirin

low intensity pain killer, lowers fever, and anti-inflammatory in larger doses

- can be used as an antiplatelet

- reduces risk of MI; increase hemmorrhage risk

mechanism of action: irreversible inhibitor of COX

side effects: GI upset

should not use in children

Doan's

related to aspirin, magnesium salicylate

relieve musculoskeletal pain and inflammation

Ben-Gay

related to aspirin, topical application for external use

Ex. Icy Hot

Ibuprofen

Mechanism of action: inhibition of COX

shorter duration of action

used as an anti-inflammatory, a fever reducer, and a pain reliever

safe to use with anti-coagulants

Naproxen

Mechanism of action: inhibition of COX

longer half-life so administered less frequently

used as an anti-inflammatory, a fever reducer, and a pain reliever

Use for bursitis/tendonitis

Indomethacin

mechanism of action: inhibition of COX

antiplatelet effects

increased dose, increased side effects (frontal headaches and seizures)

Fenoprofen

mechanism of action: inhibition of COX

GI side effects are less intense than those occurring with aspirin

used for mild-moderate pain & osteoarthritis and rheumatoid arthritis

Piroxicam

mechanism of action: inhibition of COX

used for rheumatoid and osteoarthritis

high risk for peptic ulcer and bleeding

at high concentrations, decreases free radical production

Celecoxib

mechanism of action: selective COX-2 inhibition

used for rheumatoid and osteoarthritis

causes fewer GI ulcers than other NSAIDs

side effects include renal impairment, sulfa allergy, may increase the risk of serious CV events

acetaminophen

mechanism of action: weak inhibition of COX

only able to inhibit prostaglandins in the CNS

only a pain reliever and fever reduced

COX-1

"housekeeping"

always turned on

functions in platelet, stomach, and kidney

COX-2

rapidly induces inflammation process

has no effects on stomach/GI

DMARDs (disease modifying anti-rheumatic drugs)

takes 6 weeks to 6 months to for effect of drugs to become evident

used for rheumatoid arthritis

Methotrexate

rapid-acting DMARD

may work because of an inhibition of cytokines

side effects: liver fibrosis, bone marrow suppression

Sulfasalazine

treats inflammatory bowel disease

side effects: GI problems & rash

Leflunomide

suppresses immune cell proliferation, reducing inflammation

side effects: GI upset, rash, liver function

biologics

a drug or vaccine made from a living organism

made from proteins, sugars, DNA, cells or living tissue

Entanercept

a biologic; anti-tumor necrosis factor drug

TNF-alpha is produced by macrophages and activated by T cells stimulating the release of cytokines

side effects: increased risk of infection

Adalimumab (Humira)

Anti-TNF-alpha drug; biologic; similar to Entanercept

side effects: increased risk of infection

Tofacitinib (Xeljanz)

Janus kinase inhibitor

possibly inhibit progression of structural damage

side effects: bacterial, fungal, and viral infections

steroids

most potent and effective against chronic inflammatory diseases

mechanism of action: binds to receptor to activate complex to localize the nucleus and causes the induction of repression of certain target genes

inhibit cytokines

Prednisone

used for acute flare-ups of joint disease

gout

metabolic disease due to deposits of urate in the joints and cartilage; recurrent episodes of acute arthritis

Colchicine

prophylaxis of recurrent episodes of gouty arthritis

Probenecid

decreases the net reabsorption of uric acid by affecting transport sites

allopurinol

xanthine oxidase inhibitor that results in no uric acid production

long-term tx to prevent gout attacks

osteoarthritis

intrinsic defect in the joint cartilage,

tx to manage pain and maintain active lifestyle

opioids

any drug that dulls a person's sense of pain and induces sleep

Mu

enkephalins, endorphins

Kappa

dynorphins

Delta

enkephalins

morphine

Mu agonist

relieves patients with painful disorders and sharp stabbing pains, lasts 4-5 hours

side effects: orthostatic hypotension, constipation, respiratory depression, pupil constriction

drug interactions with alcohol and barbiturates

Hydromorphone

Mu agonist

relieves severe pain

side effects: constipation, dizziness

codeine

mild-moderate pain relief

often used in combination with aspirin or acetaminophen

oxycodone

schedule II drugs - very addictive

never achieve morphine-like efficacy

methadone

Mu agonist

longer duration of action; used in tx of opioid abuse

fentanyl

Mu agonist

short acting and 100x more potent than morphine

used for anesthesia, transdermal for chronic pain

tramadol

weak Mu agonist

for mild-moderate pain; useful in chronic neuropathic pain

may cause seizures

nalxone

Mu agonist

used to treat opioid overdoses

opioid agonist-antagonist

agonist at kappa receptors; antagonist as mu receptors

less powerful pain reliever but less addictive

tolerance

rapid: nausea and vomitting

moderate: euphoria and pain relief effects

little/none: constipation and pupil constriction

physical dependence

drug administration stops, the body functions abnormally; can occur as early as 6 hours after withdrawal

symptoms: restlessness, sweating, tremors, irritability, increased HR, dehydration

histamine

from essential amino acid L-histidine

invovled in normal regualtion of physiologic functions

Cromolyn Sodium

stabilizes mast cells and prevents release of contents

aerosol and nasal spray

takes 2-3 weeks to be effective

side effects: burning, itching, coughing, sneezing

H1 blockers

classical type; allergies

for common cold symptom relief, motion sickness, sedative/hypnotic OTC sleep remedies, inhibit GI contractions

H2 blockers

inhibits gastric acid secretion, relieves symptoms of ulcers, GERD

Diphenhydramine (Benadryl)

sedation in 50% of patients

antiemetic

for allergies

Dimenhydrinate (Dramamine)

for motion sickness

causes muscular weakness and drowsiness

Fexofenadine (Allegra)

for allergies

causes less drowsiness

does not cause cardiotoxic effects

Loratadine (Claritin)

for allergies, less sedating

Cimetidine (Tagamet)

inhibits cytochrome P450 metabolism of other drugs

causes headaches, impotence, gynecomastia

Famotidine (Pepcid & Zantac)

heart burn and gastric acid relief

endocrine hormones

transported to a distant organ to work on targeted tissue

paracrine hormones

acts on neighboring tissue within same gland

neurocrine hormones

released by nerves

anabolic steroids

synthetic derivatives of testosterone

corticosteroids

steroid hormones produced in adrenal cortex

mineralocorticoids and glucocorticoids

Hypothalamic-pituitary interface

hypothalamus released releasing or inhibiting factors and factors travel to anterior pituitary or decreases anterior pituitary secretion (ACTH)

Ant. pituitary releases hormones into systemic circulation to reach adrenal gland and releases hormones with biological effect

mineralocorticoids

modulate salt and water balance

aldosterone

promotes sodium reabsorption and potassium/hydrogen excretion

Hydrocortisone

similar to cortisol; has mineralocorticoid properties

treat allergic reaction, inflammation, & cancer at high dosages

fludrocortisone

treats Addison's disease, hypoaldosteronism, and congenital adrenal hyperplasia

too high of dose = salt and water retention

ACTH

controls regualtion/synthesis of glucocorticoids

acute injuries

falls, twists, etc.

NSAIDs are commonly used

corticosteroids will not help in treating acute soft-tissue injuries

chronic injuries

rotator cuff tendonitis, tennis elbow, Achilles tendonitis

injected directly into area around tendon

steroid injection

mechanism of reducing inflammation is unknown

used as last resort after other anti-inflamatories or PT

only temporary relief

asthma

inhaled, liquid, or oral

reduces sensitivity of airways to triggers and prevents swelling in airways

steroid diabetes

taking corticosteroids can result in the development of diabetes due too much insulin in system

adrenal insufficiency

deficiency of enzymes necessary for glucocorticoid synthesis

abrupt discontinuation can be life-threatening

Cushing's Disease

excess of glucocorticoids

characterized by obesity, muscle weakness, stretch marks, moon face

normally requires radiation and surgery

Addison's Disease

deficiency of gluco/mineralcorticoids

characterized by weakness, pigmentation of skin, hypoglycemia, and hyperkalemia

tx with hydrocortisone and add fludrocortisone