Respiratory- Chapter 54

Chapter 54: Drugs Acting on the Upper Respiratory Tract
Drugs Used to Treat Upper Respiratory Infections

Antitussives

  • Block the cough reflex.

Decongestants

  • Reduce blood flow in the upper respiratory tract, which decreases swelling and secretion production.

Antihistamines

  • Block histamine (a chemical causing secretions and airway narrowing) to reduce allergic reactions.

Expectorants

  • Thins mucus to make coughs more productive (effective) in clearing airways.

Mucolytics

  • Thins and loosens thick respiratory secretions to help clear airways.

Use of Upper Respiratory Tract Agents Across the Lifespan

Children

  • Often used for children.

  • Many have pediatric guidelines.

  • Use with caution: Can cause sedation, confusion, and dizziness.

  • Precautions:

    • Cough/cold meds: NOT for children under 4 years.

    • Extreme caution for ages 4-6 years.

  • Parental Guidance:

    • Read labels and follow dosages to prevent overdose.

    • Non-drug methods are best:

      • Drink fluids.

      • Use a humidifier.

      • Avoid smoke and allergens.

      • Wash hands often (cold/flu season).

Adults

  • Risk of accidental overdose when mixing multiple OTC drugs.

  • Always ask about OTC or herbal remedies before prescribing.

  • Non-drug methods are also encouraged.

  • Pregnancy/Lactation: Many drug safety is unknown. Can harm fetus or transfer through breast milk.

Older Adults

  • Often prescribed to older adults.

  • High risk for side effects: Sedation, confusion, dizziness (can affect walking/balance).

  • Kidney or liver problems: Can change how drugs are processed and removed.

  • Recommendations:

    • Start with lower doses if kidney/liver problems exist.

    • Monitor closely and adjust doses.

    • Warn about interactions with OTC products.

Sites of Action of Drugs Working on the Upper Respiratory Tract
Antitussives

Traditional Antitussives

  • Examples:

    • Codeine

    • Hydrocodone

    • Dextromethorphan

Locally Acting Antitussive

  • Example: Benzonatate (Tessalon)

Therapeutic Actions

  • Traditional: Works on the brain's cough center to reduce the cough reflex.

  • Benzonatate: Acts as a local anesthetic in the respiratory system, blocking signals that cause coughing.

Indications

  • For uncomfortable, dry coughs (coughs that produce no mucus).

Pharmacokinetics

  • Traditional:

    • Absorbed fast, processed by liver, removed by urine.

    • Can cross placenta and enter breast milk.

  • Benzonatate:

    • Processed by liver, removed by urine.

Contraindications

  • Don't use if cough is needed to keep airways open.

  • Head injury or impaired CNS.

  • Pregnancy and lactation.

Cautions

  • Conditions like asthma or emphysema.

  • Allergies (hypersensitivity).

  • History of narcotic addiction (for codeine/hydrocodone).

Adverse Effects

  • Traditional:

    • Dry mouth/membranes.

    • CNS side effects (e.g., drowsiness).

  • Benzonatate:

    • Stomach upset.

Drug–Drug Interactions

  • Interacts with MAOIs (Monoamine oxidase inhibitors).

Antitussive Prototype

Prototype Summary: Dextromethorphan

  • Purpose: Lowers cough symptoms.

  • How it works: Slows down the cough center in the brain to stop cough spasms.

  • When it works:

    • Oral: Starts in 25-30 min, peak at 2 hrs, lasts 3-6 hrs.

    • Half-life: 2-4 hrs; processed by liver, removed by urine.

  • Side effects: Dizziness, slow breathing, nausea, dry mouth.

Topical Nasal Decongestants

Drugs

  • Examples:

    • Naphazoline

    • Oxymetazoline (Afrin)

    • Phenylephrine

    • Tetrahydrozoline

    • Xylometazoline

  • Many are OTC.

  • Responses can vary by patient.

Therapeutic Actions

  • Acts like the sympathetic nervous system (sympathomimetic).

  • Causes blood vessels to constrict (vasoconstriction), which reduces swelling and inflammation in the nose.

Indications

  • Relieves stuffy nose from colds, sinus infections (sinusitis), and allergies (allergic rhinitis).

Pharmacokinetics

  • Starts almost immediately.

  • Usually not absorbed into the whole body. Any absorbed part is processed by the liver and removed by urine.

Cautions

  • If there are sores or damage in the nasal lining.

  • Conditions made worse by sympathetic nervous system activation (e.g., high blood pressure).

  • Pregnancy or lactation.

Adverse Effects

  • Local stinging/burning.

  • Risk of rebound congestion (worsening congestion after stopping use).

  • Sympathetic nervous system effects (e.g., increased heart rate).

Drug–Drug Interactions

  • Interacts with other drugs that affect the sympathetic nervous system.

Topical Nasal Decongestant Prototype

Prototype Summary: Tetrahydrozoline

  • Purpose: Relieves stuffy nose from colds, hay fever, or other allergies.

  • How it works: Acts like the sympathetic nervous system, releases norepinephrine, causing blood vessels to constrict to reduce swelling and inflammation.

  • When it works:

    • Nasal spray: Peak in 5-10 min, lasts 6-10 hrs.

    • Half-life: Unknown; processed by liver, very little absorbed into the body.

  • Side effects: Disorientation, confusion, light-headedness, nausea, vomiting, fever, trouble breathing (dyspnea), rebound congestion.

Oral Decongestants

Drugs

  • Examples: Pseudoephedrine, Phenylephrine (found in Sudafed and many combos).

Therapeutic Actions

  • Shrinks nasal membranes by affecting alpha-adrenergic receptors.

  • This improves sinus drainage and airflow.

Indications

  • Reduces stuffy nose from colds, sinus infections, allergies.

  • Relieves pain and stuffiness from middle ear infections (otitis media).

Pharmacokinetics

  • Well absorbed and spreads throughout the body.

  • Processed by liver, mostly removed by urine.

Cautions

  • Conditions made worse by sympathetic nervous system activation.

  • Pregnancy and lactation.

Adverse Effects

  • Risk of rebound congestion and sympathetic nervous system effects.

  • Avoid overdose by being careful with OTC combinations.

Drug–Drug Interactions

  • Mixing with other OTC products containing these drugs can cause overdose.

Oral Decongestant Prototype

Prototype Summary: Pseudoephedrine

  • Purpose: Relieves stuffy nose from colds, hay fever, sinus infections; helps drain nose and sinuses; eases ear tube (eustachian tube) stuffiness.

  • How it works: Causes blood vessels in the nose to constrict, helping drainage and airflow.

  • When it works:

    • Oral: Starts in 30 min, lasts 4-6 hrs.

    • Half-life: 7 hrs; processed by liver, removed by urine.

  • Side effects: Anxiety, restlessness, headache, dizziness, drowsiness, vision changes, seizures, high blood pressure (hypertension), irregular heartbeats (arrhythmias), nausea, vomiting, trouble urinating, breathing difficulty.

Steroid Nasal Decongestants

Drugs

  • Examples:

    • Beclomethasone

    • Budesonide

    • Flunisolide

    • Fluticasone (Flonase)

    • Triamcinolone

Therapeutic Actions

  • Exact way it works isn't fully known.

  • Has anti-inflammatory effects by blocking the body's inflammatory response.

Indications

  • Treats allergic rhinitis (hay fever).

  • Reduces inflammation after nasal polyp surgery.

  • Often the first choice for nasal congestion.

Pharmacokinetics

  • May take up to 1 week to see effects.

  • Usually not absorbed into the body, avoiding wide-reaching steroid side effects.

Contraindications

  • Acute (sudden, severe) infections.

Cautions

  • If active infections are present.

  • Avoid exposure to airborne infections.

  • Pregnancy and lactation.

Adverse Effects

  • Local burning, irritation, stinging, dry nose, headache.

  • Can slow healing after nasal surgery or injury.

Drug–Drug Interactions

  • Discuss with a doctor if using other nasal medications.

Steroid Nasal Decongestant Prototype

Prototype Summary: Flunisolide

  • Purpose: Relieves symptoms of seasonal/year-round allergic rhinitis and non-allergic rhinitis; reduces inflammation after nasal polyp removal.

  • How it works: Acts as an anti-inflammatory by blocking reactions that cause inflammation.

  • When it works:

    • Nasal spray: Starts fast (<30 min), peak in 10-30 min, lasts 4-6 hrs.

    • Half-life: Not generally absorbed throughout the body.

  • Side effects: Local burning, irritation, stinging, dry nose, headache; increased risk of infections.

Antihistamines

Overview

  • Many are found in OTC products.

  • Choice often depends on how the patient reacts.

  • Often misused for colds and flu (they are for allergies).

First Generation Antihistamines

  • Examples:

    • Brompheniramine

    • Clemastine

    • Cyproheptadine

Second Generation Antihistamines

  • Examples:

    • Azelastine

    • Cetirizine (Zyrtec)

    • Desloratadine (Clarinex)

Therapeutic Actions

  • Blocks histamine-1 receptors, which reduces allergic reactions.

  • Also has anticholinergic (drying) and anti-itch (antipruritic) effects.

Indications

  • Relieves symptoms of:

    • Allergic rhinitis (seasonal/year-round hay fever).

    • Allergic conjunctivitis (itchy eyes).

    • Hives (urticaria) and angioedema (deep tissue swelling).

  • Manages allergic reactions to blood transfusions.

  • Used as an add-on treatment for severe allergic reactions (anaphylaxis).

Pharmacokinetics

  • Well absorbed when taken by mouth.

  • Processed by liver, removed by urine and feces.

  • Can cross placenta and enter breast milk.

Contraindications

  • Pregnancy and lactation.

Cautions

  • Patients with kidney or liver problems.

  • History of irregular heartbeats (arrhythmias) or prolonged QT intervals (especially with first-generation types).

Adverse Effects

  • Often cause drowsiness and sedation.

  • Also likely to have anticholinergic effects (e.g., dry mouth, blurred vision, urinary retention).

Drug–Drug Interactions

  • Vary by specific drug.

Antihistamine Prototype

Prototype Summary: Diphenhydramine

  • Purpose: Relieves symptoms of year-round/seasonal allergies (allergic rhinitis, itchy eyes, hives, swelling); helps with motion sickness and Parkinson's symptoms; also used as a sleep aid and cough suppressant.

  • How it works: Blocks histamine-1 receptors, reducing histamine effects; has drying (anticholinergic) and sedating effects.

  • When it works:

    • Oral: Starts in 15-30 min, peak in 1-4 hrs, lasts 4-7 hrs.

    • IM (injection): Starts in 20-30 min, peak in 1-4 hrs, lasts 4-8 hrs.

    • IV (into vein): Starts fast, peak in 30-60 min, lasts 4-8 hrs.

    • Half-life: 2.5-7 hrs; processed by liver, removed by urine.

  • Side effects: Drowsiness, sedation, dizziness, stomach upset, thicker lung secretions, trouble urinating, rash, slow heart rate (bradycardia).

Expectorants

Overview

  • Found in many OTC combo products.

  • Guaifenesin (Mucinex) is the only one sold alone.

Therapeutic Actions

  • Increases respiratory fluid, making mucus less sticky and easier to move.

  • Leads to a more productive cough and clearer airways.

Indications

  • Helps clear secretions in various respiratory conditions.

Pharmacokinetics

  • Absorbed fast; how it's processed and removed isn't fully known.

Contraindications

  • Known allergies to the drug.

Cautions

  • Pregnancy and lactation.

  • If cough lasts, see a doctor (it might hide a serious issue).

Adverse Effects

  • Stomach upset, headache, dizziness.

  • Long-term use can hide signs of a serious illness.

Drug–Drug Interactions

  • No major interactions known; but be careful with OTC combinations as they might interact with other drugs.

Expectorant Prototype

Prototype Summary: Guaifenesin

  • Purpose: Thins mucus in respiratory conditions, helps expel it, and reduces congestion.

  • How it works: Increases respiratory fluid, making mucus less sticky and easier to remove.

  • When it works:

    • Oral: Starts in 30 min, lasts 4-6 hrs. (Peak and half-life unknown).

  • Side effects: Nausea, vomiting, headache, dizziness, rash.

Mucolytics

Drugs

  • Examples:

    • Acetylcysteine

    • Dornase alfa (Pulmozyme)

Therapeutic Actions

  • Acetylcysteine: Breaks apart bonds in mucus, making it less thick.

  • Dornase alfa: Breaks down mucus by separating DNA from proteins (often used in cystic fibrosis).

Indications

  • Helps thin and clear thick secretions.

  • Treats collapsed lung areas (atelectasis) from thick mucus, especially in cystic fibrosis (CF) patients.

Pharmacokinetics

  • Acetylcysteine: Processed by liver, partly removed by urine.

  • Dornase alfa: Processed by proteases (enzymes that break down proteins).

Contraindications

  • History of allergies to the drug.

Cautions

  • Asthma.

  • Pregnancy and lactation.

Adverse Effects

  • Stomach upset, mouth sores (stomatitis), runny nose (rhinorrhea), bronchospasm (airway tightening), rash.

Drug–Drug Interactions

  • No known interactions.

Mucolytic Prototype

Prototype Summary: Acetylcysteine

  • Purpose: Thins thick mucus in lung disorders (short-term and long-term); also protects the liver from Tylenol (acetaminophen) overdose.

  • How it works: Breaks down mucus proteins to make secretions less thick; protects liver cells from Tylenol damage.

  • When it works:

    • Instillation/Inhalation: Starts in 1 min, peak in 5-10 min, lasts 2-3 hrs.

    • Oral: Starts in 30-60 min, peak in 1-2 hrs, duration unknown.

    • Half-life (T1/2T1/2): 6.25 hrs; processed by liver, removed by urine.

  • Side effects: Nausea, mouth sores (stomatitis), hives (urticaria), airway tightening (bronchospasm), runny nose (rhinorrhea).

Questions & Answers

Question #1: Antitussive Agents and Addiction

  • Statement: Certain antitussive agents should be used with caution in patients who have a history of addiction.

  • Answer: True

  • Rationale: Caution should be used due to potential for dependence (codeine, hydrocodone).

Question #2: Adverse Reactions to Steroid Nasal Decongestants

  • Options: A. Increased nasal drainage B. Rebound effect C. Drying of the mucosa D. Sedation

  • Correct Answer: C. Drying of the mucosa

  • Rationale: Common side effects include local burning, irritation, stinging, dry mucosa, and headache.

Question #3: Drug for Productive Cough

  • Question: Which drug thins secretions for more productive cough and enhances patency of airways?

  • Options: A. Guaifenesin B. Flunisolide C. Acetylcysteine D. Dextromethorphan

  • Correct Answer: A. Guaifenesin

  • Rationale: Guaifenesin enhances fluid output in the respiratory tract by reducing surface tension of fluids, allowing for easier removal of less thick secretions.