L15 - Principles of Respiratory Pharmacology

Question 1

Definition of Agonist

Answer 1

• 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

Question 2

Definition of antagonist

Question 3

Function of Respiratory Stimulants

Answer 3

• to help increase the urge to breathe in the treatment of respiratory failure

Question 4

Example of respiratory stimulants

Answer 4

Doxapram

Question 5

Doxapram properties (function, mechanism, effect, administration, usage)

Answer 5

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

Question 6

Examples of drugs depressing respiration

Answer 6

1) Ethanol
2) Narcoltic analgesics (opioids) - morphine and codeine
3) H₁-histamine receptor antagonists – promethazine
4) Psychotic drugs - Antidepressants, barbiturates, benzodiazepines

Question 7

Mechanism of respiratory depression by ethanol

Answer 7

by diffusing into the cell membranes of nerve cells and inhibiting the passive neuronal flux of Na+

Question 8

Consequence of excess dosage of respiratory depressants

Answer 8

Excessive dosage - decrease in sensitivity of respiration to CO2 and hypoxic drive (a form of respiratory drive)

Question 9

Drugs that provokes asthma

Answer 9

1) Aspirin and other nonsteroidal anti-inflammatory drugs (NSAID; e.g. ibuprofen)
2) Beta-adrenergic receptor antagonists (blockers)

Question 10

How NSAID provokes asthma

Answer 10

Through lipoxygenase that converts membrane arachidonic acid to leukotrienes (LT), which will then cause bronchoconstiction

Question 11

How beta blockers provoke asthma

Answer 11

By binding to ß₂-receptors and preventing bronchodilation

Question 12

Three categories of drugs to treat coughs

Answer 12

1) Antitussives
2) Expectorants
3) Mucolytics

Question 13

Two basic types of coughs (characteristics and treatment)

Answer 13

1) Productive cough (aka congestive cough)
- removes excess secretions
- do not use antitussives
2) Non-productive cough (i.e. dry cough)
- use antitussives

Question 14

What are antitussives

Answer 14

Drugs used to suppress the intensity and frequency of coughinh

Question 15

Possible sites of action of antitussives

Answer 15

Peripheral (above and below larynx) or central (CNS)

Question 16

Dosage form and mechanisms of peripheral antitussives

Answer 16

• 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

Question 17

Mechanism of central antitussives

Answer 17

By decreasing the cough reflex in the medulla; decreasing the sensitivity of CNS cough centres to peripheral stimulus

Question 18

What are two examples of central antitussives

Answer 18

1) Codeine
2) Dextromethorphan

Question 19

Codeine (classification, usage, mechanism,, side effects, special sidenotes)

Answer 19

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

Question 20

Dextromethorphan (classification, usage, mechanism, advantages, side effects, sidenote)

Answer 20

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

Question 21

Expectorants (therapeutic effects, mechanism, site of action, example)

Answer 21

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

Question 22

Guaifenesin (class, therapeutic effect, mechanism, site of action)

Answer 22

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

Question 23

Mucolytics (function, mechanism, sidenote, example)

Answer 23

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)

Question 24

N-acetylcysteine (class, function, mechanism, sidenote, route of administration)

Answer 24

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

Question 25

Difference between expectorants and mucolytics

Answer 25

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.

Question 26

Recombinant human deoxyribonuclease I (commercial name, function, mechanism, route of administration)

Answer 26

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

Question 27

Dornase (scientific active ingredient, function, mechanism, route of administration)

Answer 27

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

Question 28

Pulmonary surfactants (function, mechanism, active ingredient, case of usage, route of administration, example)

Answer 28

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

Question 29

Colfosceril (class, function, mechanism, active ingredient, case of usage, route of administration)

Answer 29

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

Question 30

Oxygen therapy (usage, targeted cases, usage parmeters)

Answer 30

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 P_aO₂ falls below 7.3 kPa (55 mmHg)

Question 31

Allergic rhinitis (definition, popular name, presentation, treatment)

Answer 31

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

Question 32

Mechanism of H₁ antihistamines against alletgic rhinitis

Answer 32

Ratinoale: histamine binds with H₁ receptors to cause vasodilation and increases capillary permeability

Question 33

1^st generation H₁ Antihistamine (usage, other action, ADRs, sidenote, example)

Answer 33

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)

Question 34

2^nd generation H₁ Antihistamine (usage, mechanism, sidenote, examples)

Answer 34

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)

Question 35

Decongestants (function and types)

Answer 35

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

Question 36

á1-Adrenergic Agonist (Classification, function, mechanism, dosage forms, example)

Answer 36

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

Question 37

Phenylephrine (Classification, function, mechanism, dosage form)

Answer 37

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)

Question 38

Glucocorticoids

Answer 38

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

Question 39

Anti-allergic mast cell stabalisers (function, example)

Answer 39

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

Question 40

Routes of Administration for respiratory drugs

Answer 40

1) Oral 2) Inhalation 3) Nasal spray (topical) 4) Tracheal intubation (endotracheal, esp. for surfactant replacement therapy)

Question 41

Inhalation devices

Answer 41

1) [pressurized] Metered-dose inhaler (MDI/pMDI) 2) Dry-powder inhaler (DPI) 3) Nebulizer

Question 42

Pressurised MDI (definition, characteristics, color codes)

Answer 42

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