Cough Suppressants, Decongestants, Mucolytics Flashcards
Describe the 3 phase expulsive motor act of cough
- Inspiratory effort (Inspiratory Phase)
- Forced expiratory effort against a closed glottis (Compressive Phase)
- Opening of the glottis and rapid expiratory airflow (Expulsive Phase)
Pathophysiology of Enhanced Cough Reflex
Laryngeal and pulmonary receptors, such as rapidly adapting receptors, C-fibers, and slowly adapting fibers, and cough receptors provide input to the brainstem medullary central cough generator through the intermediary relay neurons in the **nucleus tractus solitarius. **
Central cough generator then establishes and coordinates the output to muscles that cuase cough.
Cerebral cortex can control the motor output of cough volitionally, or influence the urge-to-cough sensation.
Define:
- Acute Cough
- Subacute Cough
- Chronic Cough
- Acute Cough: < 3 weeks
- Subacute Cough: 3-8 weeks
- Chronic Cough: > 8 weeks
Describe Productive Cough
Wet cough with secretions
- Clear - bronchitis
- Purulent - Bronchial infection
- Yellow - Inflammatory disorders
- Malodorous - Anaerobic Infection
Describe Non-Productive Cough
Dry hacking cough that does not remove sputum from the respiratory tract
- Viral illness
- Bronchospasm
- Allergies and Asthma
- Airway Obstruction
- GERD
Describe the pharmacologic treatment options for cough
Antitussives: OTC for nonproductive coughs
- Systemic Agents: Dextromethorphan, Diphenhydramine, Codeine
- Topical Agents: Camphor, Menthol (act on TRP channels)
Expectorants: OTC for productive coughs with thick secretions
- Guaifenesin
Dextromethorphan (DXM, DM, dextro isomer of levomethorphan) MOA
Supresses the cough reflec by a direct action on the cough center in teh medulla of the brain
- Active ingrediant in many cold and cough medicines (e.g. Robitussin, NyQuil, etc)
- Metabolized by CYP2D9 into active metabolite dextrorphan
- Wide margin of safety
Dextromethorphan Side Effects and Contraindications
Side Effects: dizziness, drowsiness, nausea, upset stomach, vomiting, diarrhea, irritability, excitability, light headedness, trouble sleeping.
Contraindications: monoamine oxidase inhibitor ntidepressants, advanced respiratory insufficency or hepatic disease
Diphenhydramine (Benadryl) MOA
Antihistamine-H1 receptor antagonist that suppresses the cough reflex by a direct effect on the cough center.
- Antitussive effects due to its anticholinergic effects
- Second line agent - indicated for nonproductive cough caused by irritation
- Other uses: common cold, allergic rhinitis, chronic urticaria, motion sickness, parkinsonism, insomnia
Diphenhydramine (Benadryl) Side Effects and Contraindications
Side Effects: drowsiness, respiratory depression, blurred vision, dry mouth, urinary retention, constipation
Contraindications: prostate hypertrophy, urinary obstruction, asthma, COPD, peptic ulcer, MAOI’s
Codeine (3-methylmorphine) MOA, Side Effects, Contraindications
MOA: opioid analgesic and antitussive related to morphine that acts on mu receptors but has lower affinity than morphine. It depresses the cough reflex by a direct action on the cough center in CNS.
Side Effects: constipation, sedation, histamine release, vasodilation, orthostatic hypotension, dizziness
Contraindications: hypersensitivity, labor of premature birth, pregnancy category C, prostatic hypertrophy, individuals on sedatives, in patients with acute respiratory depression, asthma or COPD
Guaifenesin (Mucinex, Albatussin EX, Alfren Jr, Alorant, Amibid) MOA, Side Effects, Contraindications
MOA: loosens and thins respiratory tract secretions by increasing the volume and reducing the viscosity of secretions
- symptomatic relief of productive coughs
- not used for chronic coughs
- only FDA approved expectorant
Side Effects: dizziness, dry mouth, rash, diarrhea, drowsiness, n/v, stomach pain, diarrhea, uric acid nephrolithiasis
Contrindication: hypersensitivity
What are nasal decongestants?
- vasoconstrictive drugs that reduce nasal congestion
- do not affect release of histamine or any other mediators involved in the allergic reaction
- commonly formulated with antihistamines
MOA of nasal decongestants
- alpha-adrenergic agonists (sympathomimetic)
- stimulation of alpha-adrenergic receptors constricts blood vessels through the body
- reduces the supply of blood to the nose
- decreases the amount of blood in the sinusoid vessels
- decreaes mucosal edema
What are the oral (system) decongestants
Pseudoephedrine: releases NE from adrenergic nerves
- metabolized to only a minor extent, by N-demethylation to norpseudoephedrine. Up to 88% of dose is excreted unchanged in 36h urine
- better bioavailability than PE, but both have short half lives
Phenylephrine (PE): stimulates alpha-adrenergic receptors on postsynaptic sites
- rapidly metabolized by MOA and COMT in the GI mucosa, liver and other tissues
What are the side effects of systemic decongestants?
- CV stimulation: increase BP, tachycardia, palpitation, arrhythmias (note that ACh will cause reflex BRADYCARDIA via baroreceptor reflex)
- CNS stimulation: restlessness, insomnia, anxiety, tremors, fear, hallucinations
- Children and elderly are more likely to experience
- Cause of rebound congestion: ischemic as a result of local vasoconstriction or irritation of the drug
What are the precautions and contraindications of systemic decongestants?
- In children and elderly
- Hyperthyroidism
- Bradycardia (PE)
- Partial heart block
- Hypersensitivity
- Uncontrolled HTN
- Ventricular tachycardia
What are the topical nasal decongestants?
Sprays, drops, inhalers
What are the two sprays approved for nasal decongestion?
Oxymethazoline: do not use more than 3-5 days becuase it can cause rhinitis medicamentosa; preferred topical agent in pregnancy
PE
What are the advantages and disadvantages of sprays?
Advantages:
- fast onset of action
- inexpensive
- simple to use
- cover a large surface area
Disadvantages:
- imprecise dosage administration
- tip tends to get blocked
What are the advantages and disadvantages of drops?
Advantages:
- for small children
Disadvantages:
- awkward to use
- cover a limited surface area
- pass easily into larynx
- easily contamined if dropper touches nose
What are the two types of inhalers?
Vicks Vapor (Levamfetamine)
- Does not cause nasal rebound for 7 days
- Labeling advises to see MD if Sx persist for more than 3 days
Benzadrex (Propylhexadrine)
- Abused
What are mucolytics and when are they used?
Promote the breakdown of mucus and are used in diseases in which there is increased mucus production (e.g. CF, COPD, Bronchiectasis, TB)
Describe the structure and fucntion of mucus
Glycoprotein with chemical bonds that “hold” mucus together
- Intramolecular (dipeptide links) connect AA
- Intermolecular (disulfide and H-bonds) connect adjacent macromolecules
How can you facilitate mucus clearence?
- Provide adequate hydration by increasing fluid intake orally or IV
- Remove causative factors (smoking, pollutants, allergens)
- Optimize tracheobronchial clearence
- Reduce inflammation
N-Acetyl cysteine, Acetadote, Erdosteine, Carbocysteine MOA and Side Effects
MOA: breaks the bonds by substituting a sulfhydryl radical
Adminstration
- given by aerosal or direct instillation into ET tube
- given orally (N-acetylcysteine) to reduce liver injury with acetominophen overdose.
Side Effects
- Bronchospasm: ma be a problem during acute asthma attack
- Increase mucus production
- Do not mix with ABX in same nebulizer
- N/V
- Diagreeable odor d/t hydrogen sulfide
Sodium Bicarbonate
- Increase pH of mucus by weakening carbohydrate side chains
- Can be injected directly into the trachea or aerosolized
- Can be irritating
Dornase Alfa (Pulmozyme)
MOA: Clone of the natural human pancreate DNase enzyme which digests extracellular DNA.
- Recombinant human deoxyribonuclease (rhDNase)
- Reduce viscosity of secretions during an infection by breaking down extracellular DNA
Indications: CF, chronic bronchitis or bronchiectasis. Has no effect on non-infected sputum
Side Effects: voice alteration, pharyngitis/laryngitis, rash, chest pain, conjunctivitis
Contraindications: in patients hypersensitive to Chinese Hamster Ovary Cell products
Amiloride (Midamor)
Na-channel blocker diuretic that can be given by aerosol for patients with CF.
- In CF, Na+ is absorbed into the epithelium along with H20, leaving the mucus thick and dehydrated. By blocking Na absorption, dehydration of mucus is prevented.
Denufosol Tetrasodium
Enhances mucosal hydration and mucus clearence by activating Cl- secretion and inhibiting epithelial Na+ transport via activation of P2Y2 receptors
