L56: Principles Of Respiratory Pharmacology Flashcards
Nervous control of airway
Afferent: sensory nerves from periphery to CNS Efferent: ANS - Vagus nerve supply: —> bronchial smooth muscle (M3 receptor) —> submucosal gland - Cervical thoracic ganglion (Sympathetic nerve) + Adrenal gland supply: —> blood vessels —> submucosal gland
Respiratory stimulant drugs
Doxapram
- CNS stimulant on carotid chemoreceptors (peripheral chemoreceptors), respiratory centre in brainstem
- increase respiratory rate and TV
- IV
- for acute respiratory failure, preterm infant apnea, sleep apnea
Respiratory depression drugs
- Ethanol —> inhibit Na influx
- Opioids: morphine, cocaine
- Barbituates
- Benzodiazepine
Excessive dosage: decrease sensitivity to PCO2 and hypoxic drive
Drugs provoke asthma
- Aspirin and NSAID
- inhibit cyclooxygenase (to inhibit prostaglandin and thromboxane formation)
- promote lipoxygenase pathway
- Leukotriene formation —> bronchoconstriction - Beta-blockers (subsequent beta-agonist is useless due to blocked receptor)
Factors for cough
- Environmental
- URT infection
- Lung infection (acute/chronic)
- Drug-induced (ACE inhibitor)
Drugs for treating cough
- Antitussive
- Expectorants
- Mucolytics
Antitussive
Suppress intensity + frequency of coughing
Peripheral (lessen irritation/reduce sensitivity of peripheral sensory cough receptor):
- syrups and lozenges as demulcents (above larynx)
- water aerosol (below larynx)
Central (reduce sensitivity of medulla oblongata cough centre to peripheral stimulus —> reduce cough reflex)
- Codeine (opioid): dry cough only, constipation, addictive liability, not for children
- Dextromethorphan (nonopioid): dry cough, no respiratory depression, no euphoria, mild adverse effects
Expectorants
- Act locally
- stimulate mucin secreting cells to produce mucin —> increase amount but reduce viscosity (higher water content) —> stimulate cough centre to clear
- Guaifenecin
Mucolytics
- Make mucus more watery / reduce viscosity and easier to cough up
- N-acetylcysteine: break disulphide bond between mucus glycoprotein
- Carbocisteine
- Bromhexine
Recombinant human deoxyribonuclease I (Dornase alpha)
- inhalation only
- cleaves DNA from dead neutrophil which makes mucin thick (purulent exudate)
Pulmonary surfactant
- Natural (curosurf from pig)
- Synthetic (colfosceril)
- reduce surface tension —> prevent alveoli collapse
- via endotracheal tubes into pulmonary tree (invasive)
- for respiratory distress syndrome
Oxygen therapy
- for acute pulmonary disorders / COPD
- only used when PaO2 below 55mmHg (respiratory failure: PaO2<60mmHg)
Drugs used in allergic rhinitis
- inflammation of nasal mucosa (Type 1 hypersensitivity reaction)
- -mine: antihistamine vs -rine: sympathomimetics
- Antihistamine (H1 receptor blocker) —> vasodilation + increased vessel permeability
- 1st generation (sedative, also anti-nausea, anti-emetic and local anaesthesia): chlorphenamine, diphenhydramine
- 2nd generation (non-sedative, do not cross BBB): cetirizine, loratadine, fexofenadine - Decongestant
- Phenylephrine (alpha-1 agonist): constrict arterioles in nasal mucosa, reduce airway resistance
- Pseudoephedrine (sympathomimetic) - Glucocorticoid: Beclomethasone (nasal spray)
- Mast-cell stabilisers: Cromolyn sodium (intranasal) —> prevent mast cell degranulation
Routes of administration
- Oral
- Inhalation (least SE, lowest effective dose)
- MDI (CFC/HFA propellant, required coordination)
- DPI (no propellant, require priming, low PEFR a problem, humidity dependent)
- nebuliser - Nasal spray
Pulmonary vs GI absorption
Pulmonary: At respiratory epithelium
Advantage: avoid hepatic 1st pass
Disadvantage: poor to regulate dose, local irritation, cumbersome
GI:
Advantage: easy to administer
Disadvantage: hepatic 1st pass
