Pharmacology in Pregnancy and Pediatrics

Over-the-Counter (OTC) Drugs

• Objectives for common OTC drugs: identify pathophysiology of diseases/disorders, mechanism of action (MOA) of drugs, adverse effects, and drug interactions.
• Objectives for common vitamins, minerals, enzymes & herbs: identify diseases/disorders and acceptable products, and MOA (if noted).
• Handbook of Nonprescription Drugs (20th edition) by Daniel L. Krinsky, Stefanie P. Ferreri, Brian A. Hemstreet, Anne L. Hume, Carol J. Rollins, Karen J. Tietze.

Headaches

• Primary Headaches:
  • Tension (episodic or chronic)
  • Migraine (without or with aura)
  • Cluster
• Secondary Headaches:
  • Stroke
  • Substance abuse
  • Infection
  • Others...
• Tension Headaches: Myofascial tissues & pericranial nociceptors, episodic peripheral nervous system, chronic central nervous system. 15+ days per month for three months.
• Migraines (without aura): Pain pathways are stimulated; messenger molecules (nitric oxide, serotonin, calcitonin gene-related peptide.) Stimulation of trigeminal sensory fibers in large cerebral and dural vessels. Neuropeptide release occurs with consequent inflammatory and vasodilation, along with platelet/mast cell activation.
• Migraines (with aura): Neuronal depolarization. Magnesium deficiency. 
• Sinus headaches & Estrogen withdrawal headaches.

Headaches - Characteristics

• Tension-Type Headache:
  • Bilateral location
  • Diffuse ache, tightening, pressing, constricting nature
  • Mild to moderate intensity
  • Gradual onset
  • 30 minutes to 7 days duration
  • Aggravating factors: stress and anxiety.
  • Non-headache symptoms: scalp tenderness, neck pain, and muscle tension.
• Migraine Headache:
  • Usually unilateral location
  • Throbbing or pulsating nature
  • Moderate to severe intensity
  • Sudden onset
  • 4-72 hours duration
  • Aggravating factors: physical activity, light, sound, nausea, vomiting, aura
  • Non-headache symptoms: None listed
• Sinus Headache:
  • Face, forehead, or periorbital area
  • Pressure behind eyes or face, dull and bilateral pain.
  • Mild to severe intensity
  • Sudden onset
  • Days – resolves with sinus symptoms
  • Aggravating factors: Nasal congestion
  • Non-headache symptoms: nasal congestion, nasal discharge

Acetaminophen (Tylenol / APAP)

• Central inhibition of prostaglandin synthesis.
• FDA warning about hepatotoxicity.
• Metabolized in the liver by the cytochrome P450 enzyme system. Results in a hepatotoxic intermediate metabolite that is detoxified within Phase II conjugation with glutathione.
• Treatment may include activated charcoal or acetylcysteine to supplement glutathione.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Relieve pain through central and peripheral inhibition of cyclooxygenase (COX). With subsequent inhibition of prostaglandin synthesis.
• Examples include Ibuprofen (Advil) and Naproxen (Aleve).
• Adverse effects: GI ulceration, perforation, and bleeding, increased risk of myocardial infarction (MI), heart failure, hypertension and stroke, sodium/water retention causing edema, nephrotoxicity with chronic use.
• Drug interactions: decreased clearance of methotrexate, increased risk of bleeding with P2Y12 inhibitors & SSRIs, increased risk of GI bleeding/ulceration with bisphosphonates, displacement from protein-binding sites with phenytoin.

Salicylates (aspirin)

• Inhibits prostaglandin synthesis from arachidonic acid (by inhibiting both isoforms of the COX enzyme)
• Uncommon intolerance: Cutaneous (urticaria, angioedema), respiratory (bronchospasm, laryngospasm, rhinorrhea)
• Avoid in patients with gout, hyperuricemia, hypoprothrombinemia, vitamin K deficiency, hemophilia, or a history of bleeding disorders.
• Contraindicated in children/teens with influenza or chicken pox (risk of Reye's syndrome)

Dosing (examples)

• 7-month-old, 18 lbs patient: Acceptable ibuprofen dose is based on weight (5 mg/kg). 100 mg/5 mL concentration of ibuprofen. The calculation determines the mL needed for the dose.
• Eight-year-old patient with periorbital cellulitis: The provided ICD-10 code and patient weight are used to calculate the appropriate Clindamycin dosage.

Fever

• Core body temperature regulated by hypothalamus and feedback system.
• Pyrogens (exogenous or endogenous) activate body's host defenses, increasing set point.
• Treat with APAP or ibuprofen (consider alternating).

Musculoskeletal Injuries and Disorders

• Somatic pain transmission from peripheral nociceptors to the central nervous system.
• Inflammatory response through multiple mediators, including histamine, bradykinin, serotonin, leukotrienes, and prostaglandin E.

Genitourinary System

• Vulvovaginal Candidiasis (VVC):
  • Thick, white ("cottage cheese") discharge without odor.
  • Often associated with vaginal itching and irritation, and sometimes dysuria.
  • The absence of a foul odor increases the likelyhood of VVC..
• Bacterial Vaginosis (BV):
  • Thin (watery), white, gray or sometimes foamy discharge.
  • Characteristically has an unpleasant "fishy" odor, more pronounced after intercourse or menses.
  • pH >4.5
• Trichomoniasis:
  • Frothy, malodorous, yellow-green or discolored discharge
  • Symptoms may include vaginal irritation, pruritus, and dysuria. ~50% of infected women are initially asymptomatic.
• Atrophic Vaginitis:
  • Vaginal dryness, burning, itching, and dyspareunia (painful sexual intercourse).
• Overactive Bladder:
  • Oxybutynin patches (Oxytrol)
  • Mechanism of action (MOA): antimuscarinic.

Respiratory System

• Colds:
  • Rhinoviruses, coronaviruses, parainfluenza, respiratory syncytial virus (RSV), adenoviruses, and human metapneumovirus.
  • Viral infection that causes inflammation, congestion, sore throat, runny nose, cough, and possible fever.
• Allergic rhinitis:
  • Sensitization phase: allergen stimulates beta-lymphocyte-mediated IgE production.
  • Early phase: rapid release of mast cell mediators (histamine, proteases, prostaglandins, kinins, leukotrienes). Cellular recruitment.
  • Late phase: Leukocytes (eosinophils) attract to mucosa, release more inflammatory mediators, mucus hypersecretion.
• Cough:
  • Initiated by chemical and mechanical stimulation of sensory nerve terminals in the pharynx, larynx, esophagus, and tracheobronchial airway epithelium.
  • "Clear" cough: usually associated with acute bronchitis (a bacterial infection.)
  • "Purulent" cough: usually associated with a bacterial infection, could also be chronic bronchitis if persistent and associated with smoking.
• Decongestants:
  • Adrenergic agonists, stimulation of alpha-adrenergic receptors constrict blood vessels (reducing inflammation and swelling). Examples include phenylephrine and oxymetazoline.
  • FDA warnings possible, limit use of certain sprays/medications.
• Antihistamines:
  • Compete with histamine at histamine type-1 (H₁) receptor sites.
  • Second generations (ex. loratadine, cetirizine) are less sedating than first generations (ex. diphenhydramine).
• Nasal Sprays: New to OTC market as of 2022. Azelastine 0.15%; indicated for the treatment of allergic and non-allergic rhinitis.
• Intranasal Corticosteroids (INCS):
  • Inhibit multiple mediators (e.g., histamine)
  • Effective for allergic cascade
  • Include: Budesonide, Fluticasone, Triamcinolone.
• Cromolyn Sodium:
  • Mast cell stabilizer, blocks calcium influx into mast cells (prevents degranulation, leukotriene release).
• Antitussives (cough suppressants):
  • Examples include Codeine; some have extensive metabolism and can be very dangerous in some patient populations.
  • Some are opioids and should be avoided (excitement can lead to drug dependence.)
  • Dextromethorphan (DM or DXM): noncompetitive antagonist for NMDA and glutamate (excitation.)
• Expectorants:
  • Guaifenesin (Mucinex): Loosens and thins respiratory tract secretions, making minimally-productive coughs more productive.

Gastrointestinal System

• Heartburn: Acidic stomach content regurgitation via lower esophageal sphincter. Mucosal chemoreceptors trigger response. 
• Dyspepsia: discomfort/pain originates from stomach/duodenal area. May include symptoms such as persistent postprandial fullness (feeling full after eating) and early satiation (feeling full quickly). Could have epigastric pain (upper middle abdomen) and/or burning sensations.
• Antacids:
  • Onset: 5 minutes. Mechanism of action (MOA): buffering agents.
  • Examples: Sodium bicarbonate, calcium carbonate, aluminum hydroxide, magnesium hydroxide, bismuth subsalicylate.
  • Adverse effects: magnesium: diarrhea, avoid with CrCl <60 mL/min; aluminum: constipation; calcium: renal calculi (possible when already experiencing renal failure.); and, sodium bicarbonate: alkalosis (possible if preexisting impairment.)
  • Drug interactions: chelation, doxycycline, ciprofloxacin, levofloxacin (amongst others).
• H2 Receptor Antagonists (H2RAs):
  • Onset: 30-45 minutes.
  • MOA: inhibiting histamine (on H₂ receptors, which are on parietal cells, responsible for HCl production)
  • Examples: cimetidine (Tagamet), famotidine (Pepcid) ranitidine (Zantac).
  • Adverse effects: cimetidine: antiandrogenic effect (decreased libido, impotence, gynecomastia.)
• Proton Pump Inhibitors (PPIs):
  • Onset: 60 minutes (can take several days to reach full efficacy),
  • MOA: inhibit hydrogen-potassium ATPase (the proton pump), which blocks the final step in gastric acid secretion.
  • Examples: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix).
  • Adverse effects: C. difficile infection, increased risk for spontaneous bacterial peritonitis in those with cirrhosis, and osteoporosis-related fractures.
• Constipation:
  • Polyethylene glycol 3350 (Miralax): hyperosmotic, increases osmolality in the GI canal, water/solutes move into canal and thus, relief of constipation.
  • Wheat dextrin (Benefiber): Fiber supplement
  • Docusate (Colace): stool softener.
  • Magnesium citrate: saline laxative.
  • Bisacodyl (Dulcolax): stimulant laxative.

Ophthalmic and Otic Products

• Dry eye and allergic conjunctivitis:
  • Includes: phenylephrine, naphazoline, oxymetazoline, tetrahydrozoline, brimonidine, olopatadine, Ketotifen.
• Excess cerumen:
  • Carbamide peroxide (6.5% in anhydrous glycerin) – Debrox (ear drops)

Dermatologic Disorders

• Atopic Dermatitis:
  • Characterized as dry, chronically inflamed, scaly skin in plaques, papules, and/or vesicles.
  • May be affected areas by red, raised, plaques with exudate (fluid leaks from blisters and/or pustules).
  • Inflammation due to increased cytokines (IL-4 and IL-13)
  • Treatment includes topical hydrocortisone. Treatment includes topical corticosteroids.
• Xerosis:
  • Dry skin; treatments include moisturizers: creams, ointments, lotions.
• Acne:
  • Multifactorial disorder of the pilosebaceous glands.
  • Adapalene (Differin), retinoid, benzoyl peroxide (2.5% - 10%); keratolytic and antibacterial properties, bleach fabrics.  
  • Salicylic acid (0.5 - 2%) – comedolytic.
  • Sulfur (3% - 10%) – keratolytic and antibacterial.
  • Photoaging - Glycolic Acid (derivative of Vitamin A-Alpha hydroxy acid), Tretinoin 0.5%, Retinol)
• Minimizing scarring (skin):
  • Silicon sheeting or gels, Vitamin E liquid.
• Warts:
  • HPV infection of basal keratinocytes.
  • Treatments include: salicylic acid, cryotherapy.
• Alopecia (hair loss):
  • Minoxidil 2 - 5% (Rogaine), vasodilator, increases cutaneous blood flow around follicles, increase in follicle hypertrophy.
• Pediculosis capitis (lice):
  • Pediculus humanus capitis
  • Treatments: Permethrin 1% (Nix) (Acts on sodium channels in nerve cells), Ivermectin 0.5% (Sklice) (acts on glutamate-sensitive chloride channel currents in helminths).

Vitamins, Minerals, Enzymes & Herbs

• Vitamin B12 (cyanocobalamin):
  • Macrocytic anemia, decreased intrinsic factor (particularly in older adults and patients with metformin).
• Vitamin B9 (folic acid):
  • Neural tube defects.
• Calcium and vitamin D:
  • Osteoporosis, Vitamin D dosing in IU's (international units) is still common practice, but conversion to mcg is encouraged to avoid errors/confusion in dosing.
• Iron:
  • Microcytic anemia.
• Vitamin E:
  • Topically for minimizing scars.
• Coenzyme Q10:
  • Rate-limiting cofactor in mitochondrial ATP formation.
  • Reduces statin-associated adverse effects.
• Fish oil:
  • Omega-3 fatty acids: DHA/EPA.
• Red Yeast Rice:
  • Molecular structure similar to statins, useful for hypercholesterolemia.
• Niacin (Vitamin B3):
  • NAD & NADP for mitochondrial redox (reductive-oxidative reactions)
  • Useful for hypercholesterolemia.
• Ginkgo biloba:
  • Neuroprotective properties.
  • For treatment of Alzheimer's, dementia, ADHD, tardive dyskinesia, intermittent claudication, tinnitus, acute mountain sickness, age-related macular degradation.
• Melatonin:
  • Hormone and potent antioxidant (pineal gland).
  • Useful for insomnia and jet lag.
• St. John's wort:
  • Hypericum perforatum flower, useful for depression, anxiety, and OCD.
• Valerian root:
  • Valeriana officinalis, useful for insomnia and anxiety.
• Kava:
  • Piper methysticum, ceremonial tranquilizers for Pacific Islanders.
  • May cause severe liver damage.
• Kratom:
  • Mitragyna speciosa, psychoactive effects (both stimulant and opioid-like).
• CBD:
  • Cannabis sativa.
• Probiotics:
  • GI flora restorations; Florajen, VSL
• Glucosamine and Chondroitin:
  • Stimulates chondrocytes (cartilage production), synoviocytes (synovial fluid production), and inhibits matrix metalloproteinase and inflammatory cytokines.
• Saw palmetto:
  • Inhibits 5-alpha-reductase and cytosolic androgen receptor. Treatment for BPH (benign prostatic hyperplasia) 
• Black cohosh:
  • Cimicifuga racemose, useful for premenstrual syndrome, dysmenorrhea, and menopause.
• Evening primrose oil:
  • Oenothera biennis, useful for PMS and menopause.

This quiz focuses on the pharmacological considerations when prescribing medications to pregnant women and pediatric patients. It covers the use of NSAIDs, dosage calculations, and the interactions of specific drugs, providing a holistic view of safe practices in medicine. Test your knowledge on proper analgesic options and important drug interactions.