Chapter 14 Drugs for Anxiety & Insomnia, p.

161-179 (all)

Chapter 15 Drugs for Seizures (GABA drugs), p. 180-199

Chapter 16 ADHD Drugs, p. 200

14 Pain Medications, p. 239

Chapter 22 Substance Abuse , p. 313

Chapter 33 Drugs for Inflammation & Fever, p. 500

I. Inflammation
a. Function - natural, nonspecific (innate), body defense R/T toxin, extreme heat,
cell death; rids body of Ag, self-limiting usually
limits spread of invading microbes or injury contain or destroy and remove
repair process faster
II. Signs of inflammation erythema, edema, pain, warmth; affects any tissue/ organ system
III. Classification of inflammation
a. Acute inflammation immediate, several days 8-10 d
i. Reaction: Cellular injury mast cell chemical mediators effects:
1. vasodilation (redness, heat)
2. edema
3. pus (cellular infiltration
4. clots (thrombosis)
5. pain (stimulation of nerve endings)
b. Chronic inflammation if acute inflam not controlled, becomes chronic; months,
years, slower onset, prolonged period
i. Arthritis most common d/o, leading cause of disability
ii. Autoimmune d/o e.g. systemic lupus erythrematosus (SLE) and RA lasts
years, progressively worse symptoms
iii. Seasonal allergy
 iv. may just be minor, annoying sypmtoms

IV. Some diseases make inflam worse severe pain, fever, distress needs
pharmacotherapy
V. What triggers the inflammatory response?
a. Release of chemical mediators r/t pathogens, chemicals, and physical trauma
i. Histamine key mediator in inflam, released by mast cells in tsu space
under epithelial mb (skin bronchi, GIT, bv)
1. Vasodilation leaky caps affected area swell with blood
edema and pain
2. Drugs that act as antagonists at histamine receptors tx allergic
rhinitis
ii. Leukotrienes
iii. Bradykinin vasodilator cause pain; similar effects to his, (broken
down by ACE (angiotensin-converting enz)
iv. Complement cascade of 20+ protein, stim his relase
v. Prostaglandins (PG) lipid present in most tissues and stored and
released by mast cells,
1. fxn:
a. increase capillary permeability
b. Attract WBC to inflam site
c. Causes pain, induces fever
2. Drugs can target certain mediators, e.g. aspirin and ibuprofen are
PG inhibitors tx: fever, pain, inflam
b. Anaphylaxis - Rapid and large-scale of mediators SHOCK, DEATH

VI. How to treat Inflammation?

a. Nonpharmacologic therapy for mild syptoms, ice pack, rest
b. Pharmacologic therapy nonspecific
1. Goal of pharmacology drugs
a. prevent or decrease intensity of inflammatory response
b. reduce fever if present
2. tx Common dz allergic rhinitis, anaphylaxis, ankylosing
spondylitis, contact dermatitis, Crohn's dz, peptic ulcer dz, RA,
SLE, ulcerative colitis
3. The more specific the anti-inflammatory drug for certain d/o, the
more serious the adverse effect than NSAIDs
ii. Topical drugs fewer adverse effects vs oral/parenteral drugs
1. Good for skin and mucus inflam of nose, mouth, rectu, vagina
2. OTC anti-inflam cream, ointment, patch, supp, nasal spray
iii. Oral drugs
1. Two primary drug classes: NSAIDs and corticosteroids
a. Nonsteroidal anti-inflam drugs (NSAIDs) - primary for
tx mild to moderate pain, inflamm; fever; Preferred class of
drugs for moderate pain; cheap, available, OTC (aspirin,
ibuprofen, naproxen (aleve)); differ in duration of action
 i. Ibuprofen and similar drugs
1. Aspirin and ibuprofen
a. Analgesic, antipyretic, antinflam
b. Prototype: ibupofen (Advil, Motrin,
others)
ii. Selective COX-2 inhibitors
1. less GI distress, but signif CV s/e
2. prototype: celebrex
iii. causes more than 16k deaths/yr R/T GI
complications

b. systemic corticosteroids tx: acute or severe inflamm,

severe disabling inflam but only S/T use then NSAIDs
i. overtreatment Cushing's syndrome (serious)
ii. prototype: prednisone
iii. corticosteroid natural horm rel by adrenal cortex
powerful effect on EVERY CELL in body

A.) Treating inflammation with NSAIDs

- MOA: inhibit PG synthesis by blocking cyclooxygenase
- (COX) key enzyme in PG synth
o COX 1 in all tsus, protective
Reduce gastric secretion
Promote renal bf
Regulate smooth musc tone in bv and bronchia tree
o COX 2 formed after tissue injury, promotes inflammation
o First gen NSAIDS block COX 1 and COX 2, e.g. aspirin and iuprofen
Blocking COX 1 undesirable effects e.g. bleeding, gastric upset,
reduced kidney fxn
Adverse effects of aspirin and ibuprofen are due to
- high safety margin, accessible OTC drug of choice for mild-moderate inflammation
- all NSAIDs have same efficacy but diff adverse effects
o nonspecific, nonselective
- fxn: mild to mod ifnlamm, analgesic, antipyretic
- acetaminophen is also analgesic and antipyretic but it does not tx inflam not a NSAID

I. Salicylates
o Aspirin mild pain and inflammation; protect cardiovascular sys, prev DVT MI
stroke
highly used, bind to COX-1 and COX-2 prev infl PG & prolonged anti-
PLT
lg dose cause
lots adverse effect on GIT ( gastric acid secretion, irritate stomach
epigastric pain, hearburn, ulcer, bleeding.
 o Buffered formulation or enteric coating to protect GIT
Salicylism syndrome tinnitus, dizziness, headache, sweating
II. Ibuprofen and Ibuprofen-like NSAIDS COX 1 and COX2 inhibition but
REVERSIBLE, treats pain, fever, inflammation
o Ibuprofen Motrin, Advil
o Ibuprofen-like NSAIDs
Low incidence of adv/e when used intermittently
s/e:
n&v (gastric ulcer, bleeding) lower incidence than aspirin
kidney toxicity (renal pt should take acetaminophen for
pain/fever)
Anti-PLT, lower risk than aspirin
can be combined with a drug that protects GIT (ibuprofen + famotidine)
o ibuprofen + other NSAIDs risk: thrombus, stroke, MI; worsen/ cause HTN

III. COX-2 inhibitors newer NSAID

o Moderate-severe inflammation
o Reduce # colorectal polyps in FAP pts
FAP familial adenomatous polyposis inherit mutation hundreds of
polyps, definitely colon cancer
o Pain, infammation, fever w/o s/e on GIT and does not affect PLT

B.) Corticosteroids (Glucosteroids)

Treating acute or severe inflammation with corticosteroids

- MOA: Inhibit synth of PG but with many MOAs
o Suprress his release
o Inhibit fxn of of immune cells (phagocytes, lymphocytes)
20x higher than endogenous amt
Most effective medication for severe inflam d/o but serious s/e
o s/e: suppress normal fxn of adrenal gland adrenal insufficiency,
hyperglycemia, mood change, cataracts, peptic ulcers, electrolyte imbal,
osteoporosis
o adverse effect:
can mask infections because it depresses inflam even though there is
infection in pt infn grows rapidly, undetected
contradication: active infection, should not use steroids
suprress his release
inhibit immune fxn
Tx: neoplasia, asthma, arthritis, corticosteroid defiiency
 Short term control acute dz. If longer tx, low doses then alternate day therapy so adrenal
gland can function.
Body gets used to high doses, so pt must d/c gradually
Abrupt w/d acute lack of adrenal fxn

VII. How to treat Fever?

a. Acetaminophen
b. NSAIDs
VIII. Fever can be drug-induced may be mild to life threatening.