Respi: Cough and Cold Flashcards
What is a common cold?
A URTI by viruses like rhinoviruses, coronaviruses, and RSVs.
What classes of drugs are used for a common cold?
H1-Antihistamines Antipyretics Analgesics Antitussive Mucoactives Nasal decongestants Multi-symptom relief formulations
NO aspirin in <16y/o -> Reyes
Examples of antitussives?
Opiates e.g. morphine, codeine, hydrocodone
What is the MOA of antitussives (opiates)?
Opiates are centrally acting antitussive agents.
Opioid receptors are found in the cough centre in the brain. Opioids are opioid receptor agonists.
Codeine is metabolised to morphine by liver enzyme CYP2D6. If poor metaboliser, then may be toxic. If good metaboliser, may not work. Hydrocodone is more potent, but also have more side effects.
Side effects of opiates?
Sedation Constipation Nausea, vomiting Itching Addiction Respiratory depression
Not for <18y/o
Example of a non-opioid antitussive?
Dextromethorphan
MOA of dextromethoprhan?
Non-narcotic, no analgesia, no addiction.
Will not bind to opioid receptor. Instead, will act centrally:
- blocking NMDA receptors
- stimulating Sigma-1 receptors. When activated, Sigma-1 receptors in the ER channel Ca2+ into the mitochondria and modulates channel function. This reduces cough severity.
Cannot be used <4 y/o.
Side effect of dextromethorphan?
Confusion, excitement, irritability, nervousness
At high dose: N/V, headache
At very high dose: euphoria, dissociative effect
Name 4 groups of mucoactive agents.
- Mucolytics
- Expectorants: cough-inducing
- Mucokinetics: mucus transport facilitating
- Mucoregulators
Effect of mucolytics?
Mucolytics = mucus thinning
- Breakdown polymers of mucin glycoproteins
- Cleave filaments of DNA and F-actin from cell debris in phlegm
- Decrease elasticity and viscosity of mucus
- Facilitate coughing up of sputum that is too thick, sticky or viscous
Effect of expectorants?
Expectorants = cough-inducing
- Increase volume or hydration of airway secretion
- Liquefy mucus, decrease thickness and viscosity into watery state
- Increases the mucus flow to help removal from bronchi
- When person coughs, mucus is removed more easily
- Will also suppress mucin production and has a slight effect on promoting mucociliary transport (overlaps with mucokinetics)
Effect of mucokinetics?
Mucokinetics = mucus transport facilitating
- Increases mucociliary transportability of mucus
Effect of mucoregulators?
Suppresses the volume of airway mucus secretion.
Name 2 mucolytic agents.
Aerosolised N-Acetylcysteine (NAC)
Carbocisteine
MOA of aerosolised N-Acetylcysteine?
NAC is a pro-drug that must be converted to L-cysteine.
- The free thiol group is a nucleophile capable of severing disulfide bonds in mucus
- Therefore, it can depolymerise mucin polymers, decreasing the viscosity of sputum
- This facilitates mucus clearance
- As an antioxidant: protects against free radical damage
- As an anti-inflammatory agent: it inhibits neutrophil infiltration
Administration of aerosolised NAC?
Oral
Inhalation
Alternative to aerosolised NAC?
NAC lysine salt (Nacetelyn, NAL)
The salt has a neutral pH and the solution is acidic.
Use of aerosolised NAC?
Mucus hypersecretion in conditions like:
URTI
COPD
Asthma
Cystic fibrosis
What is the MOA of carbocisteine?
Has 2 forms: carbocisteine (SCMC) or the lysintae form (SCMC-Lys).
- Breaks disulfide bridges between macromolecules in mucus, reducing viscosity
- Anti-oxidant, anti-inflammatory
- Increases sialomucin synthesis by increasing sialyl transferase activity (so less adhesion to epithelium)
- Restores viscoelastic properties of mucus
- Increase Cl- and GSH secretion into airway lumen with increased H2O transport
- Reduce IL-8
- Reduce adherence of viruses to ciliated epithelial cells
Administration of carbocisteine?
Oral (syrup or capsule only)
Name an expectorant.
Guaifenesin
Do not used expectorants in…
<2 y/o
Side effects of expectorants?
N/V Kidney stone (drink more water)
MOA of guaifenesin?
- Increase parasympathetic stimulation
- Increase mucosal gland secretion, decrease mucin production (so more watery)
- Increase mucociliary transport
2 types of mucoregulators?
Anticholinergic agents
Macrolide antibiotics
Name 2 anticholinergic agents.
Ipratropium bromide
Tiotropium bromide
Name 3 macrolides.
Erythromycin
Clarithromycin
Azithromycin
MOA of anticholinergic agents?
- Blocks inflammation-induced cholinergic receptor (M3) activation of submucosal glands
- Decreased stimulated glandular output and sputum volume
- Will not dry basal secretion and will not increase normal viscosity
MOA of macrolide antibiotics?
- Reduce sputum production by goblet cells by inhibiting MUC5AC gene expression and production
- Inhibit IL-13-induced mucus production
- Interferes with intracellular Ca2+ handling
- Inhibits neutrophil chemotaxis
