Cough Suppressants and Decongestants Flashcards
Describe the physiological process of coughing
Cough is a 3-phase expulsive motor act characterized byan inspiratory effort (inspiratory phase), followed by a forced expiratory effort against a closed glottis(compressive phase), followed by opening of the glottis and rapid expiratory airflow (expulsive phase).
Neural pathways for cough
Cough receptors at the airway bifurcations in the larynx and at the distal esophagus (innervated by sensory nerve endings), link to cough afferents through the vagus and superior laryngeal nerves to the cough center andcerebral cortex.
How does cough occur?
Laryngeal and pulmonary receptors, RARs, C-fibers, and SARs, provide input to the brainstem medullary central cough generator through the intermediate relay neurons in the nucleus tractus solitaires (NTS). The cough generator then coordinates output to the muscles that cause cough via the phrenic nerves, etc (via release of Ach).
How are afferents relayed?
via TRPV-1 channels (sensitive to temp, capcasin, irritants)
C-fibers are sensitive to what?
TRPM-8 (melastatin-8) channels sensitive to cold or menthol (and pain)
TRPa-1 is sensitive to what?
wasabi, garlic, onion (noxious stimuli)
What is an acute cough?
lasting less than 3 weeks
What is a subacute cough?
lasting 3-8 weeks (chronic 8+)
A productive cough with clear sputum suggests what? Malodorous?
Clear- bronchitisMalodorous- anaerobic infection
A productive cough with purulent sputum suggests what? Yellow?
Purulent- bronchial infectionyellow-inflammation
What things can cause a non-productive cough?
-viral infection-bronchospasm/allergies/asthma-GERD-airway obstruction
What are some systemic antitussives?
- Dextromethorphan2. Diphenhydramine3. Codeine4. Benzonatate (Tessalon Perles)
What are some topical antitussives?
Camphor and Menthol
What does Guaifenesin do?
it is DOC for productive cough with thick secretions to dilute them
Dextromethorphan is the active ingredient in what drugs?
-NyQuil-Muxinex DM-Robitussin-Vicks
How does Dextromethorphan work?
suppresses the cough reflex by a direct action on the cough center in the medulla (non-opioid)not THAT effective
How is Dextromethorphan metabolized?
CYP2D6 (into active dextrorphan)
Large doses of Dextromethorphan can cause what?
dissociative hallucinogenic effect (via antagonizing the NMDA receptor)
What are the AEs of Dextromethorphan?
-dizziness, drowsiness, N/V-constipation-tachycardia ICNREASE SEROTONIN LEVELS
Contraindications of Dextromethorphan
-those taking MAO and serotonin uptake inhibitors-advanced respiratory insufficiency or hepatic disease
What can Dextromethorphan do to children?
can release histamine and cause allergic reaction
What is serotonin syndrome?
causes seizures, aggitation, tachycardia, etc.
What does Diphenhydramine do?
antihistamine H1-receptor antagonist that suppresses the cough reflex by a direct action on the cough center (anticholingeric)
What is Diphenhydramine indicated for?
2nd line for nonproductive cough caused by irritation
What are the other uses of Diphenhydramine (Benadryl)?
cold, allergic rhinitis, urticaria, motion sickness, insomnia, parkinsonism
AEs of Diphenhydramine?
-Drowsiness-respiratory depression-dry mouth-blurred vision-urinary retention/constipation
Contraindications of Diphenhydramine?
-BPH-urinary obstruction-asthma/COPD-peptic ulcer (via H2 receptor blocking- they produce gastric secretions)-MAOIs
T or F. The concurrent use of Diphenhydramine with other serotonin increasing drugs is contraindicated
T.
How does codeine work?
it is an opiod analgesic and antitussive that acts on mu receptors and depresses the cough reflex by direct action
Onset of codeine? DOA?
10-30 minutes and acts 4-6 hrs
AEs of codeine?
constipation, sedation-histamine release-orthostatic hypotensions
Contraindications of codeine?
-hypersensitivity-labor of premature birth-BPH-asthma/COPD/respiratory failure
T or F. Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to death
T.
How does Benzonatate work?
(nonnarcotic) decreases sensitivity of stretch receptors in the airways by its local anesthetic effectstretch= activation of TRP channels
When is Benzonatate indicated?
-cough in emphysema, bronchitis, pneumonia, and influenza
Benzonatate is more effective when used with what?
Mucinex
AEs of Benzonatate?
skin rash, nasal congestion, hallucinations-hypersensitivity reaction (cardiac arrest eventually) if chewed or sucked -headache, NV
Contraindications of Benzonatate?
-antihistamines, sleep or anxiety drugs, muscle relaxants-children under 10-allergies to tetracaine or procaine
How do camphor and menthol work?
initially activating and then desensitizing TRPV1 and TRPA1 and TRPM8 channels
How does Guaifenesin (Mucinex) work?
loosens and thins lower respiratory secretions by increasing the volume and reducing the viscosity of secretions (not for chronic cough)
AEs of Guaifenesin?
-dry mouth, dizziness, N/V-uric acid nephrolithiasis in large doses
Contraindications of Guaifenesin?
Hypersensitivity
What is the main cause of nasal congestion?
mucosal inflammation
What mediators cause congestion?
histamine, PGD2 (chemottractant), others from mast cells which cause increased permeability and inflammation from recruited vessels, as well as venous engorgement
What causes coughing and sneezing in rhinorrhea?
affarents via the trigeminal ganglion stimulates the brain and activation of the parasympathetics (and decrease in SNS action) to produce mucus and substance P and CGRP are produced (cause vasodilation)
How do you treat nasal congestion?
vasoconstrictive drugs (do not affect histamine release but are commonly combined with antihistamines)
How does vasoconstriction occur in the nose?
stimulation of alpha-adrenergic receptors constricting blood vessels throughout the body and reducing blood supply to the nose and mucosal edema
What are some a1 specific agonists?
Phenylephrine and Oxymetazoline (partial a2 agonist)
T or F. PO Phenylephrine is NOT effective as a decongestant
T. Nasally inhalant is though (not metabolized the same way). Oxymetazoline can be given PO
How is Phenylephrine metabolized?
MOA and COMT in the GI mucosa, liver and other tissue
How does Pseudoephreine (Sedated) work as a decongestant?
(PO) releases Nor from a adrenergic nerves (indirect effect)
How is Pseudoephreine metabolized?
only minorly, by N-demethylation
How long can Oxymetazoline be used for?
3-5 days (longer may cause rebound congestion)- rhinitis medicamentosa
What are the advantages of sprays of nasal decongestants?
-faster onset-cheap, easy
What are the disadvantages of sprays of nasal decongestants?
imprecise dose, tip tends to get blocked
What are the advantages of drops of nasal decongestants?
works for small children
What are the disadvantages of drops of nasal decongestants?
-cover a limited surface area, pass easily into the larynx, and can easily be contaminated
What are the side effects of Pseudoephedrine?
-CV stimulation-restlessness, anxiety, tremors, fear(most common in children and elderly)
What are some contraindications for Pseudoephedrine?
-children/elderly-hyperthyroidism-bradycardia/heart block-HTN-ventricular tachycardia -hypersensitivity
What are some inhaled nasal decongestants?
-Levamfetamine (won’t cause rebound)-Prophylhexedrine
What does stimulation of H1 receptors result in?
bronchoconstriciton, vasodilation, urticaria, inflammation,e tc.
What are the 1st gen H1 receptor antagonists?
-Diphenhydramine (Benadryl)-Chlorpheniramine -Promethazine
What are the 2nd gen H1 receptor antagonists?
-Fexofenadine (allegra)-Loratidine (Claritin)-Cetirizine (Zyrtec)
What are the uses of H1 antagonists?
common cold, allergic rhinitis, pruritis, nausea, vertigoto produce sleepatopic dermatitis, sinusitis
AEs of H1 antagonists?
-sedation, dizziness, dry mouth, constipation and urinary retention
What diseases have increased mucus production?
CF, COPD, bronchiectasis, TB
Describe mucus
glycoproteins with polypeptides that make up the backbone held together by disulfide, hydrogen, and dipeptide bonds
What are some basic things that can be done to increase mucus clearance?
provide hydration, remove causative factors, reduce inflammation
What is the main function of bland aerosols?
they function more as an irritant to stimulate cough than a wetter
What are some expectorants?
-Iodides/Iodinated Glycerol -Guiafenesin (at high doses, stimulates bronchial gland secretion)-Bromohexine
How does Bromohexine work?
secretolytic, increases the production of serous mucus in the RT and decreases viscosity of phlegm
How does N-acetyl cysteine work as a mucolytic?
breaks the SH bonds
How can N-acetyl cysteine be given?
-aerosol or by direct instillation into the ET tube-PO to reduce liver injury with acetaminophen overdose
AEs of N-acetyl cysteine?
-bronchospasm (must use with a bronchodilator in asthma)-N/V-increased mucus production -has a bad odor
T or F. N-acetyl cysteine should not be mixed with ABX
T.
How does sodium bicarbonate work as a mucolytic?
increase pH of mucus which weakens polysaccharide chains
How does Dornase Alfa (Pulmozyme) work as a mucolytic?
it is a clone of pancreatic DNase enzyme which digests extracellular DNA and reduced viscosity of secretions during an INFECTION
When is Pulmozyme used?
CF, chronic bronchitis, or bronchiectasis (has no effect on non-infected sputum)
AEs of Pumozyme?
-voice alteration-rash-chest pain-conjunctivitis-pharyngitis/laryngitis
Contraindications of Pulmozyme?
Hypersensitivity to chinese hamster ovary cell products
How does Amiloride work as a mucolytic?
diuretic blocks Na+ absorption and prevents dehydration of mucus
