Module 5: Prototype Drugs and Their Mechanisms

beta-adrenergic agonist (albuterol)

To treat asthma and for prophylaxis and treatment of bronchospasm

Mechanism of Action (albuterol)

Stimulates beta2-adrenergic receptors in the lungs, which relaxes the bronchial smooth muscle, thus causing bronchodilation

Side effects (albuterol)

Tremor, dizziness, drowsiness, restlessness, agitation, anxiety, excitability, ataxia, headache, nasopharyngitis, insomnia, weakness, dry mouth, nausea, vomiting, diarrhea, edema, urinary retention, muscle cramps, rhinitis, throat irritation, tooth discoloration, hyperhidrosis

Adverse effects (albuterol)

Palpitations, tachycardia, hypo/hypertension, infection, hyperglycemia, hypokalemia, chest pain, dyspnea

Life-threatening effects (albuterol)

Dysrhythmia, angioedema, bronchospasm, Stevens-Johnson syndrome

anticholinergic (tiotropium)

For maintenance treatment of asthma and COPD

Mechanism of Action (tiotropium)

Blocks muscarinic cholinergic receptors and antagonizes acetylcholine action by inhibiting M3 receptor response to acetylcholine, thereby relaxing smooth muscle of bronchi; dilates bronchi

Side effects (tiotropium)

Insomnia, dizziness, depression, headache, sinusitis, nasopharyngitis, cough, dry mouth, vomiting, abdominal pain, constipation, urinary retention, arthralgia, myalgia, peripheral edema, blurred vision, oral ulceration, candidiasis, infection

Adverse Reactions (tiotropium)

Tachycardia, ileus, dehydration, hyperglycemia, chest pain, GI obstruction, cataracts

Life-threatening effects (tiotropium)

Dysrhythmias, anaphylaxis, angioedema

leukotriene receptor antagonist (montelukast)

For treatment of allergic rhinitis and asthma, for exercise-induced bronchospasm prophylaxis

Mechanism of Action (montelukast)

Binds with leukotriene receptors to inhibit smooth muscle contraction and bronchoconstriction

Side effects (montelukast)

Headache, dizziness, drowsiness, cough, nasal congestion, fatigue, infection, agitation, restlessness, insomnia, confusion, depression, influenza, edema, palpitations, muscle cramps

Adverse Reactions (montelukast)

Bleeding, seizures

Life-threatening effects (montelukast)

Anaphylaxis, suicidal ideation, thrombocytopenia, Stevens-Johnson syndrome, angioedema

glucocorticoid (fluticasone)

To treat respiratory disorders, particularly asthma. Indicated if asthma is unresponsive to bronchodilator therapy or if the patient has an asthmatic attack while on maximum doses of theophylline or an adrenergic drug

Time for effect (fluticasone)

May take 1 to 4 weeks for an inhaled steroid to reach its full effect.

Side Effects (fluticasone)

Throat irritation, hoarseness, dry mouth, coughing

Aminophylline-theophylline

Relaxes the smooth muscles of the bronchi, bronchioles, and pulmonary blood vessels by inhibiting the enzyme phosphodiesterase, resulting in an increase in cAMP, which promotes bronchodilation.

Therapeutic Level (theophylline)

A low therapeutic index and a narrow desired therapeutic range (5 to 15 mcg/mL).

Toxic Serum

Toxicity is likely to occur when the serum level is greater than 20 mcg/mL

Aspirin

Inhibits prostaglandin synthesis; Anti-inflammatory, antiplatelet, antipyretic effects

Aspirin Side Effects

Dizziness, lethargy, Headache, Confusion, agitation, N & GI distress, Diaphoresis, dehydration

Aspirin Adverse Reactions

Tinnitus, hearing loss, Hypo/hyperglycemia, Reye syndrome

Aspirin Caution

Do not take w/ other NSAIDs; Avoid last trimester of pregnancy; Do not give to children with flu or virus symptoms (Reye syndrome)

Ibuprofen

Inhibits COX-1 & COX-2 by blocking arachidonate binding

Ibuprofen Use

Pain, osteoarthritis, rheumatoid arthritis

Ibuprofen Side/Adverse Effects

Drowsiness, Dizziness, Headache, confusion, Blurred vision, hearing loss, Tinnitus, Edema, Gastric distress, Bleeding, Anaphylaxis

Celecoxib

Cox-2 inhibitor

Celecoxib Use

Pain, osteoarthritis, rheumatoid arthritis, Painful dysmenorrhea, Migraine

Celecoxib Side Effects/Adverse

Headache, Dizziness, Sinusitis, N/V/D, GI bleeding, HTN, Hearing loss, Anaphylaxis

Infliximab

Tumor necrosis factor blocker

Infliximab Use

Psoriasis, Rheumatoid Arthritis, Ulcerative colitis, Crohn's disease

Infliximab Side Effects/Adverse

Headache, Dizziness, cough, Fatigue, chills, Rash, Severe infections, Bronchospasm, Leukopenia

Febuxostat

Blocks hypoxanthine & Xanthine metabolism to reduce uric acid; Increases uric acid excretion; Prevents gout attacks

Febuxostat Use

Gout, Hyperuricemia

Febuxostat Side/Adverse Effects

Headache, dizziness, blurred vision, Bradycardia, Hyperglycemia, N/V/D, Thrombocytopenia

Acetaminophen

Inhibits prostaglandin Synthesis

Acetaminophen Uses

Muscular aches & pain, Fever

Acetaminophen Side effects/Adverse

Anxiety, headache, Insomnia, fatigue, Oliguria, Hearing loss, Hepatic/renal failure, Blood dyscrasias - anemia, thrombocytopenia

Morphine Sulfate

Depression of the CNS & pain impulses

Morphine Sulfate Uses

Moderate & severe pain

Morphine Sulfate Side/Adverse Effects

Anorexia, dry mouth, N/D, abd. pain, Constipation, Orthostatic hypotension, Bradycardia/tachycardia, Respiratory depression, Urinary retention

Nalbuphine

Inhibits pain impulses to the CNS; Binds w/opiate receptors & increases pain threshold

Nalbuphine Uses

Moderate & severe pain; Anesthesia induction

Nalbuphine Side/Adverse Effects

Dizziness, drowsiness, headache, Dry mouth, N/V, Bradycardia, dyspnea, hypo/hypertension, Respiratory depression, seizures

Sumatriptan

Inhibits pain impulses to the CNS

Opiate Receptors

Binds w/opiate receptors & increases pain threshold.

Migraine Treatment

Uses: Treat migraine & cluster headaches, vasoconstriction of cranial arteries.

Side Effects of Opiate Receptors

Dizziness, headache, blurred vision, paresthesia, hypo/hypertension, coronary artery vasospasm, dysrhythmias, cardiac arrest.

Insulins

Promote use of glucose by body cells.

Insulin Use

Reduce blood glucose, control diabetes mellitus.

Insulin Interactions

Increase glucose with thiazides, glucocorticoids, estrogen, thyroid drugs; decrease glucose with aspirin, oral anticoagulants.

Oral Insulin

Gastrointestinal secretions destroy insulin structure - therefore, no oral insulin.

Hypoglycemia Symptoms

Nervousness, trembling, lack of coordination, sweating, tachycardia, headache, confusion.

Somogyi Effect

Occurs in predawn hours; rapid decrease in blood glucose during night stimulates hormonal release to increase blood glucose.

Lipodystrophy

Tissue atrophy from frequent injections.

Dawn Phenomenon

Hyperglycemia upon awakening; headache, night sweats, nightmares; increase insulin dose at HS.

Diabetic Ketoacidosis Symptoms

Hyperglycemia - fruity breath, increased thirst, hunger, & urine output (3 P's); leads to fat catabolism - increase in ketones.

Regular Insulin

Short acting (IV) (clear); onset: 30 min, peak: 1.5-3.5 h, duration: 4-12 h.

Lispro Insulin

Rapid acting (clear); subq; onset: 15-30 min, peak: 30-90 min, duration: 3-5 h.

NPH Insulin

Intermediate acting (Cloudy); subq; onset: 1.5 h, peak: 4-12 h, duration: 14-24 h.

Glargine Insulin

Long acting (Cloudy); subcut; onset: 1-1.5 h, peak: None, duration: 24 h.

Glipizide

Directly stimulates beta cells in the pancreas to secrete insulin; indirectly alters sensitivity of peripheral insulin receptors.

Glipizide Side Effects

Drowsiness, dizziness, headache, confusion; adverse reactions: hypoglycemia, hyponatremia, angioedema; life-threatening: agranulocytosis.

Metformin Mechanism of Action

Decreases glucose production in the liver by reducing gluconeogenesis; improves tissue sensitivity to insulin.

Metformin Side Effects

Dizziness, headache, weakness, chills, metallic taste, nausea, diarrhea; adverse reaction: palpitations, chest pain; life-threatening: lactic acidosis and acute renal failure.

Furosemide Action

Act on ascending loop of Henle; excrete sodium, water, K+, Ca+, Mg+.

Furosemide Side Effects

Electrolyte imbalances: notably potassium; orthostatic hypotension, dizziness, headache, weakness, muscle cramps.

Hydrochlorothiazide Action

Act on distal convoluted renal tubule; promote sodium, chloride, water excretion.

Hydrochlorothiazide Side Effects

Orthostatic hypotension; fluid/electrolyte imbalance: especially in the elderly; gout; life-threatening: hypokalemia, renal failure, Stevens-Johnson syndrome.

Spironolactone Action

Block action of aldosterone; promote sodium/water excretion & K+ retention.

Spironolactone Side Effects

Hyperkalemia (potassium-sparing); dizziness, headache, weakness, GI distress.