L15 - Principles of Respiratory Pharmacology Flashcards
Definition of Agonist
- Drugs bind to a receptor and initiate a change in cellular function (i.e. mimic physiologic activation)
- An agonist has both high affinity and efficacy
Definition of antagonist
Function of Respiratory Stimulants
- to help increase the urge to breathe in the treatment of respiratory failure
Example of respiratory stimulants
Doxapram
Doxapram properties (function, mechanism, effect, administration, usage)
1) Function: as respiratory stimulant to help increase the urge to breathe in the treatment of respiratory failure
2) Mechanism: a CNS stimulant drug that acts on both carotid chemoreceptors and the respiratory centre in the brainstem to increase respiration
3) Effect: increase in respiratory rate and tidal volume with a fall in pCO2 and a rise in pO2
4) Administration: Intravenous administration (patients ususally connected to machines)
5) Usage: used primarily to help preterm infants who have apnea, but also helpful in older patients with sleep apnea and in COPD patients with acute respiratory failure
Examples of drugs depressing respiration
1) Ethanol
2) Narcoltic analgesics (opioids) - morphine and codeine
3) H1-histamine receptor antagonists – promethazine
4) Psychotic drugs - Antidepressants, barbiturates, benzodiazepines
Mechanism of respiratory depression by ethanol
by diffusing into the cell membranes of nerve cells and inhibiting the passive neuronal flux of Na+
Consequence of excess dosage of respiratory depressants
Excessive dosage - decrease in sensitivity of respiration to CO2 and hypoxic drive (a form of respiratory drive)
Drugs that provokes asthma
1) Aspirin and other nonsteroidal anti-inflammatory drugs (NSAID; e.g. ibuprofen)
2) Beta-adrenergic receptor antagonists (blockers)
How NSAID provokes asthma
Through lipoxygenase that converts membrane arachidonic acid to leukotrienes (LT), which will then cause bronchoconstiction
How beta blockers provoke asthma
By binding to ß2-receptors and preventing bronchodilation
Three categories of drugs to treat coughs
1) Antitussives
2) Expectorants
3) Mucolytics
Two basic types of coughs (characteristics and treatment)
1) Productive cough (aka congestive cough)
- removes excess secretions
- do not use antitussives
2) Non-productive cough (i.e. dry cough)
- use antitussives
What are antitussives
Drugs used to suppress the intensity and frequency of coughinh
Possible sites of action of antitussives
Peripheral (above and below larynx) or central (CNS)
Dosage form and mechanisms of peripheral antitussives
- Above larynx: syrups and lozenges as demulcent
- Below larynx: water aerosol inhalation and warm environment
- Mechanism: decreasing the sensitiveity of peripheral sensory ‘cough receptors’ in the pharynx to irritation
Mechanism of central antitussives
By decreasing the cough reflex in the medulla; decreasing the sensitivity of CNS cough centres to peripheral stimulus
What are two examples of central antitussives
1) Codeine
2) Dextromethorphan
Codeine (classification, usage, mechanism,, side effects, special sidenotes)
1) Classification: opioid (aka opiate agonist) antitussive
2) Usage: used for non-productive cough (dry cough), strongly effective cough supressant
3) Mechanism: central acting (By decreasing the cough reflex in the medulla; decreasing the sensitivity of CNS cough centres to peripheral stimulus)
4) Side effects: Produce constipation, nausea and respiratory depression; has addictive liability
5) Sidenotes: rarely recommended to children; not used for congestive/productive cough accompanied with excessive secretions
Dextromethorphan (classification, usage, mechanism, advantages, side effects, sidenote)
1) Classification: non-opoiod antitussive (central acting)
2) Usage: supressing dry cough
3) Mechanism: Selectively depresses the cough center in the medulla (By decreasing the cough reflex in the medulla; decreasing the sensitivity of CNS cough centres to peripheral stimulus)
4) Advantages: No respiratory depression, no physical dependence (addictive liability), no euphoria
5) Side effects: mild and rare - e.g. dizzines, drowsiness, nausea
6) Side note: it is the most popular cough depressant; not used for productive cough
Expectorants (therapeutic effects, mechanism, site of action, example)
1) Therapeutic effects: Used to assist in the removal of secretions or exudates from the trachea, bronchi or lungs
2) Mechanism:
- stimulate the mucin secreting cells to hyperactively produce mucin, which will thin and liquefy bronchial secretion (increased amount with decreased viscosity) witha higher water content
- the increased volume of thinner mucin helps to stimulate the cough centre, thus stimulating coughing the the clearance of the bronchial tract
3) Site of action: act locally to signal the body
4) Example: Guaifenesin
Guaifenesin (class, therapeutic effect, mechanism, site of action)
1) Class: Expectorants
2) Therapeutic effects: Used to assist in the removal of secretions or exudates from the trachea, bronchi or lungs
3) Mechanism:
- stimulate the mucin secreting cells to hyperactively produce mucin, which will thin and liquefy bronchial secretion (increased amount with decreased viscosity) witha higher water content
- the increased volume of thinner mucin helps to stimulate the cough centre, thus stimulating coughing the the clearance of the bronchial tract
4) Site of action: act locally to signal the body
Mucolytics (function, mechanism, sidenote, example)
1) Function: Make mucus more water (decreasing viscosity of mucin) and easier to cough up
2) Mechanism: Breaks the disuphide bonds cross-linking mucus glycoprotein molecules, thus making the mucin thinner and more easily transported out of the lungs
3) sidenote: usually used in the case of bronchitis - in which thick sputum with polysccharide fibres can be observed
4) example: N-acetylcysteine (oral administration)
N-acetylcysteine (class, function, mechanism, sidenote, route of administration)
1) Class: mucolytics
2) Function: Make mucus more water (decreasing viscosity of mucin) and easier to cough up
3) Mechanism: Breaks the disuphide bonds cross-linking mucus glycoprotein molecules, thus making the mucin thinner and more easily transported out of the lungs
4) sidenote: usually used in the case of bronchitis - in which thick sputum with polysccharide fibres can be observed
4) Route of administration: oral administration
Difference between expectorants and mucolytics
The mechanism is differnt:
An expectorant works by signaling the body to increase the amount or hydration of secretions, resulting in more yet clearer secretions and as a byproduct lubricating the irritated respiratory tract.
A mucolytic agent is an agent which dissolves thick mucus and is usually used to help relieve respiratory difficulties. It does so by dissolving various chemical bonds within secretions, which in turn can lower the viscosity by altering the mucin-containing components.
Recombinant human deoxyribonuclease I (commercial name, function, mechanism, route of administration)
1) Commercial name: dornase
2) Function: Reduce viscosity of mucin to facilitate its removal; Used in the case of cystic fibrosis (or bronchiectasis) in which patients produce thick and tenacious mucin. [in CF, when a neutrophil dies, its DNA leaks out of the cell and when it comes into contact with mucin, it makes the mucin very thick and tenacious (i.e. viscous purulent exudate]
3) Mechanism: rhDNase I is an enzyme that cleaves DNA left behind by neutrophils in the lungs, thus the viscosity of the mucin is decreased, promoting increased clearance
4) Route of administration: Inhalation
Dornase (scientific active ingredient, function, mechanism, route of administration)
1) Scientific name: Recombinant human deoxyribonuclease I
2) Function: Reduce viscosity of mucin to facilitate its removal; Used in the case of cystic fibrosis (or bronchiectasis) in which patients produce thick and tenacious mucin. [in CF, when a neutrophil dies, its DNA leaks out of the cell and when it comes into contact with mucin, it makes the mucin very thick and tenacious (i.e. viscous purulent exudate]
3) Mechanism: rhDNase I is an enzyme that cleaves DNA left behind by neutrophils in the lungs, thus the viscosity of the mucin is decreased, promoting increased clearance
4) Route of administration: Inhalation
Pulmonary surfactants (function, mechanism, active ingredient, case of usage, route of administration, example)
1) Function: Prevent alveoli collapse
2) Mechanism: Decrease surface tension of the alveoli, thus preventing alveoli collapse
3) Active ingredient: synthetic phospholipids
4) Case of usage: used in the management of respiratory distress syndrome, common amongst premature infants
5) Route of administration: via endotrracheal tubes directly into the pulmonary tree
6) example: colfosceril
Colfosceril (class, function, mechanism, active ingredient, case of usage, route of administration)
1) Class: Pulmonary surfactant
2) Function: Prevent alveoli collapse
3) Mechanism: Decrease surface tension of the alveoli, thus preventing alveoli collapse
4) Active ingredient: synthetic phospholipids
5) Case of usage: used in the management of respiratory distress syndrome, common amongst premature infants
6) Route of administration: via endotrracheal tubes directly into the pulmonary tree
Oxygen therapy (usage, targeted cases, usage parmeters)
1) usage: increase tissue oxygenation
2) Targeted cases: used in the management of acute pulmonary disorders, chronic obstruictive diseases, in which there is inadeequate tissue oxygenation
3) Usage parameters: when PaO2 falls below 7.3 kPa (55 mmHg)
Allergic rhinitis (definition, popular name, presentation, treatment)
1) Defintion: Inflammation of nasal mucosa caused by a type I hypersensitivity reaction to allergens
2) Popular name: Hay Fever
2) Presentation: Nasal mucosa inflammation, nasal congestion, itching, redness, sneezing and runny nose
3) treatment: H1 Antihistamines (H1 receptor antagonist); Decongestants; Anti-allergic mast-cell stabalisers
Mechanism of H1 antihistamines against alletgic rhinitis
Ratinoale: histamine binds with H1 receptors to cause vasodilation and increases capillary permeability
1st generation H1 Antihistamine (usage, other action, ADRs, sidenote, example)
1) Usage: allergic rhinits
2) Other action: anti-nausea, anti-emetic (anti-vomit), and local anaethesia (first generation only(
3) ADRs: drowsiness, dizziness, hypotension and xerostomia/dry mouth)
4) sidenote: Sedative as it pases through the BBB
5) examples: Chlorphenamine (chorpheniramine), Diphenhydramine (Benadryl)
2nd generation H1 Antihistamine (usage, mechanism, sidenote, examples)
1) Usage: Allergic rhintis
2) mechanism: work peripherally to block the actions of histamines
3) sidenote: does not pass through the BBB, therefore non-sedative
4) Example: Telfast (fexofenadine), Zyrtec (centirizine), Claritin (loratadine)
Decongestants (function and types)
1) Function: drugs that reduce congestion of nasal passages, which in turn open clogged nasal passages and enhances drainages of the sinuses (usually against allergic rhinitis)
2) Types: - á1-Adrenergic agonists
- Glucocorticoids
á1-Adrenergic Agonist (Classification, function, mechanism, dosage forms, example)
1) Classification: Decongestant
2) Function: Reduce congestion of nasal passages which in turn opens clogged nasal passages and enhances drainages of the sinuses (usually against allergic rhinitis)
3) Mechanism: Cpmstricts dilated arterioles in the nasal mucosa and reduces airway resistance
4) Dosage form: i) aerosol (rapid onset of action with shorter duration; fewer systemic effects) ii) oral (slower onset of action with longer duration; more systemic effects)
5) example: phenylephrine
Phenylephrine (Classification, function, mechanism, dosage form)
1) Classification: Decongestant, á1-Adrenergic agonsit
2) Function: Reduce congestion of nasal passages which in turn opens clogged nasal passages and enhances drainages of the sinuses (usually against allergic rhinitis)
3) Mechanism: Cpmstricts dilated arterioles in the nasal mucosa and reduces airway resistance
4) Dosage form: i) aerosol (rapid onset of action with shorter duration; fewer systemic effects) ii) oral (slower onset of action with longer duration; more systemic effects)
Glucocorticoids
1) Classification: Decongestant
2) Function: Reduce congestion of nasal passages which in turn opens clogged nasal passages and enhances drainages of the sinuses (usually against allergic rhinitis)
3) Dosage form: Nasal Spray
Anti-allergic mast cell stabalisers (function, example)
1) Function: prophylatic; Prevent nasal airway congestion due to hypersensitivity (usually against allergic rhinitis)
2) Sidenote: Prophylatic - must be used before mast cells release histamine, otherwise useless
Routes of Administration for respiratory drugs
1) Oral
2) Inhalation
3) Nasal spray (topical)
4) Tracheal intubation (endotracheal, esp. for surfactant replacement therapy)
Inhalation devices
1) [pressurized] Metered-dose inhaler (MDI/pMDI)
2) Dry-powder inhaler (DPI)
3) Nebulizer
Pressurised MDI (definition, characteristics, color codes)
1) Definition: Metered-dose inhaler
2) Characteristics: i) CFC propellant (replaced by HFA)
ii) require co-ordinated activation/inhalation
3) Color Codes: i) Blue - short acting ß2 agonist
ii) Green - salmeterol
iii) Brown - BDP or budesonide
iv) Orange - fluticasone
