Pharmacology Chapter Review

Over-the-Counter (OTC) Drugs

• Objectives for common OTC drugs include identifying the pathophysiology of diseases/disorders, mechanism of action (MOA) of drugs, adverse effects, and drug interactions.
• Objectives for common vitamins, minerals, enzymes, and herbs involve identifying diseases/disorders and acceptable products, along with MOA (if noted).
• Handbook of Nonprescription Drugs (20th Edition) is an interactive approach to self-care, authored by Daniel L. Krinsky, Stefanie P. Ferreri, Brian A. Hemstreet, Anne L. Hume, Carol J. Rollins, and Karen J. Tietze.

Headaches

• Primary headaches include tension (episodic or chronic), migraine (without or with aura), and cluster headaches.
• Secondary headaches stem from stroke, substance abuse, infection, and other causes.
• Tension headaches involve myofascial tissues and pericranial nociceptors, episodic peripheral nervous system, and chronic central nervous system involvement (15 or more days per month for at least 3 months).
• Migraine headaches involve stimulated pain pathways with messenger molecules like nitric oxide, serotonin, and calcitonin gene-related peptide. Stimulus involves the trigeminal sensory fibers in cerebral and dural vessels, causing neuropeptide release, inflammation, vasodilation, and platelet/mast cell activation. In Aura-type migraines, neuronal depolarization spreads slowly across the cerebral cortex, potentially influenced by magnesium deficiency.
• Sinus headaches and estrogen withdrawal headaches are other types.

Table 5-1: Characteristics of Tension-Type, Migraine, and Sinus Headaches

• Tension-type headaches are bilateral, diffuse, mild-moderate, and gradual onset. The duration is 30 minutes to 7 days, aggravated by stress and anxiety. Non-headache-related symptoms are scalp tenderness, neck pain, and muscle tension.
• Migraine headaches are usually unilateral, throbbing/pulsating, moderate-severe in intensity, and sudden in onset. Duration is 4-72 hours, aggravated by physical activity, light, sound, nausea, vomiting, and aura. Symptoms can include pressure behind eyes or face, or dull bilateral pain; non-headache symptoms include nausea, vomiting and aura.
• Sinus headaches are positioned on the facial/forehead/periorbital area, pressure behind the eyes, and dull bilateral pain. The intensity is mild-severe, the onset is sudden, and duration is days which resolves with sinus symptoms. Aggravating factors include nasal congestion. Non-headache related symptoms include nasal congestion, nasal discharge.

Table 5-3: Recommended Dosages of Nonprescription Analgesics for Adults and Children (12 years and older)

• Acetaminophen (Tylenol/APAP) dosages vary from 325-1000 mg every 4-6 hours (3000 or 4000 mg with supervision of HCP) for immediate-release products or 650-1300 mg every 8 hours (3000, or 4000 mg with supervision of HCP) for extended-release products, as needed.
• Ibuprofen dosages range from 200-400 mg every 4-6 hours (max 1200 mg) as needed.
• Naproxen sodium dosages vary from 220 mg every 8-12 hours (660 mg), with initial dose of 2 tablets within first hour.
• Aspirin dosages vary from 325-1000 mg every 4-6 hours (max 4000mg) as needed.
• Maximum daily dosages may vary depending on product type (regular-strength, extra-strength, extended-release).

Acetaminophen (Tylenol/APAP)

• Acetaminophen (Tylenol/APAP) inhibits prostaglandin synthesis centrally.
• A boxed warning on acetaminophen products addresses its potential for hepatotoxicity.
• It's metabolized by the cytochrome P450 enzyme system resulting in a hepatotoxic intermediate metabolite detoxified by glutathione conjugation.
• Activated charcoal or acetylcysteine may be used to supplement glutathione.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs relieve pain through central and peripheral inhibition of cyclooxygenase (COX), leading to prostaglandin synthesis inhibition. Common examples include ibuprofen (Advil) and naproxen (Aleve).
• Adverse effects include GI ulceration, perforation and bleeding, increased risk for myocardial infarction (MI), heart failure, hypertension, and stroke, sodium/water retention causing edema, and nephropathy with chronic use.
• Drugs interacting with NSAIDs include methotrexate (decreasing clearance), P2Y12 inhibitors & SSRIs (increased risk of bleeding), bisphosphonates (increased GI risk), digoxin (decreased renal clearance), and phenytoin (displacement from protein-binding sites).

Salicylates (Aspirin)

• Aspirin inhibits prostaglandin synthesis from arachidonic acid by inhibiting COX-1 and COX-2 enzymes.
• A positive result on fecal occult blood testing is possible after use, requiring discontinuation for at least 3 days before testing.
• Aspirin use or salicylate use is contraindicated in patients with gout, hyperuricemia, hypoprothrombinemia, vitamin K deficiency, hemophilia, and bleeding disorders.
• Warnings from the American Academy of Pediatrics, FDA, the Centers for Disease Control and Prevention, and the Surgeon General caution against aspirin/salicylate use in children and teens with influenza or chickenpox due to Reye's syndrome risk.

Combination OTC Products

• Combination products for headaches containing caffeine, nasal decongestants or diphenhydramine are available.
• Caffeine use may be problematic.
• Caution is advised for OTC analgesic use in patients taking blood thinners or consuming alcohol.
• Concomitant use of ethanol (EtOH) with APAP or NSAIDs requires caution.

Pregnancy/Lactation/Pediatrics

• Pregnancy: NSAIDs are contraindicated in the third trimester due to potential delayed parturition, prolonged labor, and increased postpartum bleeding. Premature ductus arteriosus closure is also a risk. APAP is safe.
• Lactating: Ibuprofen's infant dose ranges from 0.6%-0.9%, and acetaminophen's dose is 3.98%. Avoid aspirin.
• Pediatrics: APAP is safe for all ages. Ibuprofen doses are age and weight-dependent. Doses for acetaminophen are also age & weight dependent.

Dosing Considerations

• Various dosing scenarios are presented, involving calculation of appropriate medication amounts and volumes for different age groups and weights.

Fever

• Body temperature is regulated by the hypothalamus through a feedback system involving the anterior hypothalamus and thermosensitive CNS neurons.
• Pyrogens (exogenous or endogenous) activate the body's immune defenses and increase the set point, resulting in fever.
• Treating fever involves APAP or ibuprofen, potentially alternating use of both.

Musculoskeletal Injuries and Disorders

• Somatic pain is transmitted from peripheral nociceptors to the central nervous system causing pain.
• Inflammatory responses occur through multiple mediators such as histamine, bradykinin, serotonin, leukotrienes, and prostaglandin E.

Genitourinary System

• Common vaginal infections (bacterial vaginosis, trichomoniasis, and vulvovaginal candidiasis) are discussed using a table differentiating their classic signs, differentiating findings, and etiology/epidemiology.
• OTC treatments for vulvovaginal candidiasis (VVC) like azoles (topical, 7-day therapy preferred if pregnant—Clotrimazole, Miconazole, Tioconazole) are discussed.
• Vaginal itching and irritation are addressed with topicals such as hydrocortisone (1%), and benzocaine (5-10%)/resorcinol (2-3%).

Respiratory System

• Common respiratory conditions (colds, allergic rhinitis, cough), decongestants (adrenergic agonists like phenylephrine and oxymetazoline), antihistamines (first-generation—diphenhydramine, and second-generation—loratadine, cetirizine, levocetirizine, and fexofenadine), nasal spray (azelastine), cough suppressants (codeine, dextromethorphan), expectorants (guaifenesin), and intranasal corticosteroids (budesonide, fluticasone, and triamcinolone).
• Mechanism of action, adverse effects, precautions (including pregnancy and lactation) and drug interactions are described for these categories.

Gastrointestinal System

• Common gastrointestinal issues (heartburn, dyspepsia, diarrhea, constipation) and treatments (antacids, H2 blockers, proton pump inhibitors, and laxatives).
• Lifestyle modifications for gastrointestinal health, including weight loss, diet changes, and medication usage considerations, particularly in pregnancies and children.
• Specific details on the mechanism of action, adverse effects, warnings, and drug interactions for various medication categories are provided for the conditions.

Ophthalmic and Otic Products

• Dry eye and allergic conjunctivitis treatment options (decongestants such as phenylephrine, naphazoline, oxymetazoline, and tetrahydrozoline) and antihistamine/mast cell stabilizers (olopatadine and ketotifen).
• OTC treatments for excess cerumen (carbamide peroxide 6.5% with glycerin) and ear drops (isopropyl alcohol with glycerin) are discussed .

Dermatologic Disorders

• Common skin conditions such as atopic dermatitis (eczema), xerosis (dry skin), acne, photoaging, warts, alopecia (minoxidil), and pediculosis capitis (lice) are discussed.
• Treatments include topical corticosteroid (e.g., Hydrocortisone 1%), moisturizers (creams, ointments, and lotions), retinoids (adapalene), benzoyl peroxide, salicylic acid for acne, glycolic acid and retinol for photoaging, cryotherapy, and antiparasitic agents (permethrin and ivermectin).

Vitamins, Minerals, Enzymes & Herbs

• Various vitamins, minerals, enzymes, and herbs are discussed, along with their intended uses, mechanisms, cautions, and potential interactions. Topics include: B12 and B9, calcium and vitamin D, iron, coenzyme Q10, fish oil, red yeast rice, niacin, gingko biloba, melatonin, St. John's wort, valerian root, kava, kratom, CBD, cannabis sativa, echinacea, sambucus nigra (elderberry), vitamin C, zinc, probiotics (e.g., Florajen, VSL), glucosamine & chondroitin, saw palmetto, and other herbal remedies.

Natural Medicines in the Library

• Resources for researching natural medicines within a library.

Updates/Important Note

• Recent approvals of Narcan and Opill for OTC use in 2023.

Test your knowledge on pharmacology, including the risks associated with codeine use and the implications of various medications. This quiz covers metabolism, dosing guidelines for children, and contraindications during pregnancy. Enhance your understanding of drug interactions and their effects on different populations.