RESP: PHARM Flashcards
What type of cell does Cromolyn Sodium and Nedocromil target? What is their effect on this type of cell?
Mechanism: Stabilization of mast cells (cellular mechanism unclear), causing ↓ degranulation
What medication used to treat asthma and allergic rhinitis works by preventing mast cell degranulation? Can this medication be used in an emergency to reverse bronchospasm?
Cromolyn sodium is administered either via a metered dose inhaler or as a nasal spray, and works by preventing mast cell degranulation. It can be used as an adjunct treatment of asthma (inhaler) and can also be used to treat allergic rhinitis (nasal spray). It does not reverse bronchospasm, and is thus it can only be used as a prophylactic treatment for asthma.
What is the mechanism of action of Zileuton?
Zileuton inhibits 5-lipoxygenase (LOX), resulting in decreased production of all leukotrienes. It has similar uses to the leukotriene receptor antagonists (montelukast and zafirlukast), but it has a faster onset than those agents. A side effect of zileuton is hepatotoxicity.
By what mechanisms do inhaled glucocorticoids treat asthma?
The mechanism of inhaled glucocorticoids is thought to be mediated by several different molecular mechanisms.
- Inhibition of phospholipase A2 (mechanism under investigation) causes decreased synthesis of arachidonic acid and its inflammatory metabolites (prostaglandins and leukotrienes).
- Inactivation of NF-κB (pro inflammatory transcription factor) causes decreased production of TNF-alpha and other inflammatory agents
Prostaglandins and leukotrienes are known to contribute to thepathogenesis of bronchospasm. Inhibition of their synthesis is one mechanism by which inhaled glucocorticoids help in the treatment of asthma.
Glucocorticoids also stimulate synthesis of β2 receptors in the lung and nasal mucosa. This is why they are commonly co-administered with long acting β2 agonists, to prevent down regulation of β2 receptors (caused by chronic β2 agonist use).
Where does codeine act to help suppress coughing?
Coughing is caused by chemical or mechanical stimulation of irritation cough receptors in the epithelium of the respiratory tract. The afferent axons of these receptors stimulate the “cough center” in the medulla, which sends efferent motor signals to muscles that produce the cough.
Codeine is an opiate that acts as a cough suppressant by direct action in the medulla. It is recommended that it only be used for short term symptomatic relief of a cough.
Dextromethorphan (structurally similar to codeine) decreases sensitivity of cough receptors as well as depresses the medullary cough center.
Metaproterenol, albuterol, and terbutaline belong to what class of medication? What is this class of medication used to treat?
Short acting ß2 agonists are used to treat acute bronchospasm. This class of medications includes:
Metaproterenol
Albuterol
Terbutaline
How do inhaled glucocorticoids help to treat asthma? With what other type of agent are they commonly co-administered? Why are they co-administered with those types of agents?
Prostaglandins and leukotrienes are known to contribute to thepathogenesis of bronchospasm. Inhibition of their synthesis is one mechanism by which inhaled glucocorticoids help in the treatment of asthma.
Glucocorticoids also stimulate synthesis of β2 receptors in the lung and nasal mucosa. This is why they are commonly co-administered with long acting β2 agonists, to prevent down regulation of β2 receptors (caused by chronic β2 agonist use).
Name one side effect of zileuton.
A side effect of zileuton is hepatotoxicity.
Because of the lipophilic nature of first generation antihistamines, what two “adverse effects” can be utilized for clinical benefit?
Since first generation antihistamines are lipophilic and as such readily cross the blood-brain barrier, they cause significant sedation through blockade of central histamine and adrenergic receptors and can be used as a sedative/sleep aid.
Their antimuscarinic effects are also sometimes utilized by using these agents to treat motion sickness.
What are the 3 toxicities of theophylline that are potentially life threatening?
Theophylline has a low therapeutic index. Life-threatening toxicities of theophylline include:
- Seizure
- Hypotension
- Cardiac arrhythmia
Theophylline is metabolized by CYP450 enzymes in the liver. As such, the dose of theophylline must be adjusted in patients with hepatic impairment, as well as when it is co-administered with known CYP450 inhibitors.
What are the 3 mechanisms of action of pseudoephedrine?
Nasal congestion can have a variety of potential causes. The treatment of nasal congestion focuses primarily on promoting local vasoconstriction in the nasal mucosa to reduce blood flow and edema, and loosening thick mucous that may be contributing to congestive symptoms.
Pseudoephedrine acts as a:
- Direct α agonist
- Direct β agonist
- Indirectly sympathomimetic activity (causing release of NE)
Because of its use in the production of amphetamines, pseudoephedrine has been moved behind the counter.
Phenylephrine is a potent α1 agonist that causes vasoconstriction, which results decongestion. Unlike pseudoephedrine, it does not have any β adrenergic activity. A reflex response to increased blood pressure (from α agonism) can also cause reduced heart rate and cardiac output.
Topical nasal decongestants should NOT be used regularly as they cause significant rebound rhinitis.
The following agents act as cough expectorants. Both are mucolytic agents that act to decrease mucous viscosity and help with secretion management, which is especially useful in patients with cystic fibrosis.
Guaifenesin increases respiratory fluid secretion, thereby decreasing mucous viscosity
N-acetylcysteine (when INHALED) loosens mucous by cleaving disulfide bonds in mucous
N-acetylcysteine is also administered via IV as an antidote for acetaminophen toxicity.
How does the naming of first generation antihistamines differ from the naming of second generation antihistamines?
The names of first generation antihistamines contain “-en/-ine” or “-en/-ate.” In contrast, the names of second generation antihistamines usually end in “-adine.”
Loratadine, cetirizine, and fexofenadine belong to what class of medications? What is their only use?
Second generation antihistamines are only used to treat allergies:
Loratadine
Desloratadine
Fexofenadine
Cetirizine
What effect does omalizumab have on mast cells and basophils? How does omalizumab mediate this effect?
Omalizumab is a recombinant humanized IgG against IgE.
Mechanism: Blocks the ability of IgE to bind to the Fc receptor on mast cells and basophils.
↓ IgE activation of basophils and mast cells → ↓ release of inflammatory mediators of type I hypersensitivity.
Over time, omalizumab leads to decreased levels of circulating IgE
Use: Approved for the treatment of allergic asthma in patients who arerefractory to corticosteroids.
Note: Because of the mechanism of this drug, it is only useful in patients who are proven to have IgE mediated sensitivity.
By what 2 general mechanisms do medications that treat nasal congestion work?
Nasal congestion can have a variety of potential causes. The treatment of nasal congestion focuses primarily on promoting local vasoconstriction in the nasal mucosa to reduce blood flow and edema, and loosening thick mucous that may be contributing to congestive symptoms.
What 5 antihistamines can be used for allergies, motion sickness, and as sleep aids?
First generation antihistamines are used to treat allergies, motion sickness, and as a sleep aid:
Diphenhydramine
Dimenhydrinate
Chlorpheniramine
Promethazine
Hydroxyzine
First generation antihistamines also have antimuscarinic and anti alpha adrenergic properties, which is the primary reason for the adverse effects seen with their administration.
