B2 W2 - Pharmacology of Airway Disease Flashcards
(133 cards)
1
Q
What is the immediate phase of asthma characterised by, and what causes it?
A
The immediate phase of asthma is characterised by episodes of bronchospasm, brought on by allergen triggers.
2
Q
How can drugs target the immediate phase of asthma?
A
Drugs can alleviate the immediate phase by affecting lung smooth muscle function and targeting receptors on mast cells involved in allergen responses.
3
Q
What characterises the late phase of asthma?
A
The late phase of asthma involves a more profound involvement of immune cells recruited to the lung due to chronic inflammation.
4
Q
What types of drugs can alleviate the late phase of asthma?
A
Drugs that target the immediate phase can also help with the late phase, along with corticosteroids, which can modify immune system responses to reduce inflammation and bronchospasm.
5
Q
What are the three main pharmacological strategies for managing chronic airway diseases?
A
The strategies involve
targeting
* nervous system control of airway constriction
* airway hyper-responsiveness,
* chronic inflammation in the lung.
6
Q
What is the primary mechanism for promoting bronchodilation directly?
A
Bronchodilation can be directly promoted by targeting the smooth muscle cells that control airway diameter.
7
Q
What are three ways drugs can target smooth muscle cells to promote bronchodilation?
A
- Activate beta-two adrenergic receptors (β2-Adrenergic Agonists)
- Target acetylcholine responses (Anti-muscarinic drugs)
- Affect adrenergic responses (Methylxanthines.)
8
Q
How can drugs target the immunological aspects of airway diseases?
A
Drugs like corticosteroids and leukotriene receptor antagonists can reduce tissue inflammation and modulate inflammatory responses.
9
Q
What acronym is useful for remembering the steps in emergency asthma care?
A
“OMG SHIT”
10
Q
What does the “O” in “OMG SHIT” represent, and what is its purpose?
A
“O” stands for oxygen, which is the first step in emergency asthma care to address the patient’s immediate need for oxygen.
11
Q
What does the “S” in “OMG SHIT” represent, and how is it administered?
A
“S” stands for salbutamol, a beta-two agonist drug often administered intravenously in emergencies to promote bronchodilation.
12
Q
What does the “H” in “OMG SHIT” represent, and what is its function?
A
“H” stands for hydrocortisone, a corticosteroid drug used to reduce inflammation and help restore airway function.
13
Q
What does the “I” in “OMG SHIT” represent, and what type of drug is it?
A
“I” stands for ipratropium, an anti-muscarinic drug that helps to relax the airways.
14
Q
What does the “T” in “OMG SHIT” represent, and how is it considered in treatment?
A
“T” stands for theophylline, a methylxanthine drug that is a potent but last resort treatment for severe cases.
15
Q
What additional treatment, not included in the acronym, can be used in emergency respiratory care?
A
Magnesium sulphate (Mg) can also be used, and its abbreviation conveniently fits into the acronym.
16
Q
What distinguishes the different phases of asthma?
A
The severity of the pathology
17
Q
What is the immediate phase of asthma characterised by?
A
The immediate phase involves episodes of bronchospasm caused by allergen triggers.
18
Q
What types of drugs can target the immediate phase of asthma?
A
Drugs that affect lung smooth muscle function and target receptors on mast cells involved in allergen responses can target the immediate phase.
19
Q
How is the late phase of asthma different from the immediate phase?
A
The late phase involves a more significant influx of immune cells to the lungs due to chronic inflammation and progressive lung changes.
20
Q
What drugs can alleviate the late phase of asthma?
A
Drugs used for the immediate phase and corticosteroids, which modify immune system responses, can alleviate the late phase.
21
Q
What is the role of glucocorticoids in treating airway diseases?
A
To modify immune system responses to reduce inflammation and bronchospasm in the lungs.
Often used interchangeably with corticosteroids
22
Q
How do leukotriene receptor antagonists function in treating airway diseases?
A
Leukotriene receptor antagonists work by modulating some of the immunological and inflammatory responses in the lungs.
23
Q
What does the acronym ‘SABA’ stand for, and what is an example of this drug class?
A
- SABA stands for short-acting beta-agonist
- E.g Salbutamol.
24
Q
What is the mechanism of action of a SABA?
A
SABAs promote bronchodilation by activating beta-two adrenergic receptors on airway smooth muscle cells.
25
What is a potential side effect of SABAs?
Tremor
26
What does the acronym 'LABA' stand for?
LABA stands for** Long-Acting Beta-Agonist.**
27
Provide an example of a LABA.
Salmeterol
28
What is the mechanism of action of an anti-muscarinic drug for airway disease?
Anti-muscarinic drugs **block acetylcholine receptors** on airway smooth muscle, **preventing bronchoconstriction.**
29
What is a common example of an anti-muscarinic used for airway disease?
Ipratropium bromide
30
What is a potential side effect of ipratropium bromide?
Dry mouth.
31
What is the mechanism of action of methylxanthines in treating airway disease?
Methylxanthines **affect the adrenergic responses** in bronchial smooth muscle cells, **leading to bronchodilation**.
32
What is the main methylxanthine used in treating airway disease?
Theophylline
33
What are two potential side effects of theophylline?
**Nausea** and **tachycardia.**
34
What is the mechanism of action of corticosteroids in treating airway disease?
**Reduce** tissue **inflammation** in the airways.
35
Provide an example of a commonly used corticosteroid in airway disease.
Beclomethasone
36
What is a potential side effect of inhaled corticosteroids?
Oral thrush
37
What is the mechanism of action of leukotriene receptor antagonists?
Leukotriene receptor antagonists **block **the action of **leukotrienes**, which are **inflammatory mediators**.
38
Provide an example of a leukotriene receptor antagonist.
Montelukast
39
Which branch of the nervous system predominantly influences smooth muscle function in the lungs?
Sympathetic nervous system.
40
What is another name for the sympathetic nervous system?
The sympathetic nervous system is also known as the **"fight or flight" **system.
41
What are the nerve fibres associated with the sympathetic nervous system called?
Adrenergic nerve fibres.
42
What is the primary neurotransmitter involved in the sympathetic nervous system's influence on the lungs?
Noradrenaline.
43
What is the primary effect of sympathetic responses in the lungs?
Sympathetic responses primarily cause **bronchodilation, widening the airways to enhance airflow into the lungs.**
44
What is the parasympathetic nervous system often associated with?
It is associated with "rest and digest" responses.
45
What is the primary neurotransmitter of the parasympathetic nervous system?
**Acetylcholine** is the primary neurotransmitter, **acting through cholinergic nerve fibres**.
46
What is the typical effect of parasympathetic responses on the airways?
Parasympathetic responses generally lead to **bronchoconstriction, narrowing the airways.**
47
Which neurotransmitter and type of nerve fibre primarily mediate parasympathetic responses in the lungs?
The parasympathetic nervous system primarily uses **acetylcholine **and **cholinergic nerve fibres.**
48
How do the sympathetic and parasympathetic nervous systems interact in regulating airway diameter?
The parasympathetic nervous system often works **alongside and in opposition** to the sympathetic nervous system, reversing the bronchodilation effect after a predominant sympathetic response.
49
What is the key component of Beta 2 agonist action in the lungs?
The key component is the **Beta 2 adrenergic receptor** found on lung smooth muscle cells.
50
What is the role of Beta 2 agonists in relation to the Beta 2 adrenergic receptor?
Beta 2 agonists, such as salbutamol or salmeterol, act as **stimulants, activating the Beta 2 adrenergic receptor.**
51
What are the natural agonists for the Beta 2 adrenergic receptor?
Noradrenaline and adrenaline
52
What is the purpose of introducing a pharmacological agent like salbutamol?
Introducing salbutamol **enhances** and drives the **adrenergic response** in the lungs.
53
What intracellular change occurs upon salbutamol binding to the Beta 2 adrenergic receptor?
It leads to an **increase** in the concentration **of cyclic AMP (cAMP)** inside the cell.
54
What is the function of cyclic AMP?
Cyclic AMP, a small intracellular mediator, acts to **reduce** cytoplasmic **calcium levels** and, consequently, **smooth muscle contraction**.
55
What is the ultimate outcome of Beta 2 agonist action on smooth muscle?
It **promotes smooth muscle relaxation**, leading to **enhanced airway dilation** and **improved airflow**.
56
What enzyme is activated by the rise in cyclic AMP concentration?
Protein kinase A
57
How does protein kinase A contribute to smooth muscle relaxation?
It affects muscle physiology and calcium balance within the cell, **favouring relaxation.**
58
How is cyclic AMP inactivated?
By **phosphodiesterase enzyme**
59
What are the two main types of Beta 2 agonists and their duration of action?
* Salbutamol is a short-acting Beta 2 agonist
* Salmeterol is a longer-acting one.
60
On which cells do Beta 2 agonists act?
They act on bronchial smooth muscle cells.
61
What is the molecular target of Beta 2 agonists?
Their molecular target is the **Beta 2 adrenergic receptor**, which they stimulate.
62
How do Beta 2 agonists affect calcium ions in smooth muscle cells?
Through protein kinase A activation, they drive calcium ions into storage vesicles, away from the contractile machinery of the muscle.
63
What are two key side effects of Beta 2 agonists? Why might these side effects occur?
* Tremor and tachycardia (increased heart rate)
* These drugs promote a sympathetic ("fight or flight") response, which can affect the cardiovascular system and muscle tone throughout the body.
64
On what cell type do methylxanthines act?
Bronchial smooth muscle cells
## Footnote
Similar to beta-2 agonists.
65
How do methylxanthines differ in their mechanism from beta-2 agonists?
Unlike beta-2 agonists, which stimulate the beta-2 adrenergic receptor, methylxanthines **block** the **phosphodiesterase enzymes** that break down cyclic AMP.
66
What is the effect of methylxanthines on cyclic AMP levels?
**Sustain cyclic AMP** levels in smooth muscle cells, leading to **prolonged muscle relaxation**.
67
What are the administration routes for methylxanthines?
Orally as tablets or intravenously in acute asthma cases.
68
Why do methylxanthines have to be used with particular care intravenously?
Intravenous administration of methylxanthines carries a **risk of serious side effects** but can also be life-saving in emergency situations.
69
What are the key side effects associated with methylxanthines? Why?
Due to their **enhancement of the sympathetic response,** methylxanthines can cause **cardiac arrhythmias** and, in severe cases, **seizures.**
70
At what point in the adrenergic response pathway do methylxanthines act?
Methylxanthines **inhibit** the **breakdown** of **cyclic AMP**, sustaining the adrenergic response and **promoting** smooth muscle **relaxation**.
71
What is the specific muscarinic receptor associated with lung smooth muscle cells?
The M3 muscarinic receptor is particularly associated with lung smooth muscle cells.
72
Do lung smooth muscle cells express other receptors besides the M3 muscarinic receptor?
* **Yes**
* They also express **beta-2 adrenergic receptors**.
73
What is the typical effect of acetylcholine on lung smooth muscle via the M3 muscarinic receptor?
Acetylcholine binding to the M3 receptor triggers events leading to an **increase in inositol triphosphate (IP3),** ultimately causing smooth muscle constriction and bronchial constriction.
74
How do anti-muscarinic drugs affect the M3 muscarinic receptor?
Anti-muscarinic drugs, like tiotropium, act as **antagonists**, **blocking** and **silencing** the **M3** receptor.
75
What is the effect of anti-muscarinic drugs on IP3 production and calcium release?
By blocking the M3 receptor, anti-muscarinic drugs **reduce the production of IP3** and the **release **of **calcium** into the cytoplasm, ultimately **inhibiting** bronchial **constriction**.
76
What is the overall effect of anti-muscarinic drugs on bronchial smooth muscle?
* **promote bronchodilation**
* By inhibiting the pathways that would normally lead to bronchial constriction.
77
Name examples of short-acting and long-acting anti-muscarinic drugs.
* **Ipratropium** is a short-acting example
* **Iotropium** and **glycopyrronium** are long-acting.
78
What is the primary target cell for anti-muscarinic drugs in the context of airway disease?
The target cell is the bronchial smooth muscle cell.
79
What is their specific molecular target?
They target the **M3 muscarinic acetylcholine receptor**.
80
What is the most common side effect of anti-muscarinic drugs used in airway disease?
Dry mouth
81
What is the impact of immune system dysfunction or the build-up of inflammatory responses in the lungs?
Damage and respiratory disease.
82
In asthma, what kind of immune response is triggered by substances like allergens and pollen?
Abnormal hypersensitive immune responses
83
Which cells are activated by allergens in conditions like asthma?
Mast cells and eosinophils
84
What effect do mediators released from activated mast cells have on the airways?
They can cause bronchospasm and worsen immune reactions.
85
What can infiltrates of lymphocytes (like T cells) lead to in chronic respiratory diseases?
A chronic inflammatory state in the lungs, potentially leading to tissue remodelling and destruction, and reduced lung function.
86
Apart from bronchospasm, what other effect do mediators from mast cells have on immune reactions in conditions like late-phase asthma and COPD?
They augment (increase or worsen) further immune reactions.
87
What is a key consequence of a chronic inflammatory state in the lungs, particularly in relation to lung tissue?
Can give rise to pathological **tissue remodelling** and **destruction**.
88
What is the overall impact of chronic inflammation on lung function?
**Reduction** in overall lung function.
89
What opportunity does the immune system's involvement in airway disease provide from a pharmacological perspective?
It presents pharmacological targets that can be used to reduce the inflammatory burden and alleviate disease.
90
What are leukotrienes?
Leukotrienes are lipid-based signalling molecules that have various effects throughout the body, particularly in the lungs.
91
What is the function of leukotriene receptors (LTRs)?
LTRs are receptors found on immune and smooth muscle cells that transduce intracellular signals in response to the presence of leukotrienes.
92
What effect do leukotriene receptors on bronchial smooth muscle cells have?
They **stimulate** an increase in **IP3**, leading to bronchial constriction.
93
What is eosinophil chemotaxis, and how is it related to leukotriene receptors?
* Eosinophil chemotaxis is the movement and recruitment of eosinophils to the site of an allergen.
* Leukotriene receptors on eosinophils guide this process, increasing the inflammatory response.
94
What is the overall effect of leukotrienes in the context of airway inflammation?
Leukotrienes are potent **pro-inflammatory** signalling molecules associated with bronchospasm and bronchial constriction.
95
What is the mechanism of action of leukotriene receptor antagonists?
They block leukotriene receptors, thereby reducing the effects of leukotrienes.
96
Name two common examples of leukotriene receptor antagonist drugs.
Montelukast and zafirlukast.
97
What are the cellular targets of leukotriene receptor antagonists in the lungs?
Eosinophils and bronchial smooth muscle cells.
98
What type of leukotriene receptor is typically targeted by these antagonists?
cysteinyl leukotriene receptors (cysLT)
99
What is the impact of leukotriene receptor antagonists on inflammatory responses during asthma?
They reduce inflammatory responses in both early and late phases of asthma.
100
Can leukotriene receptor antagonists be used with other asthma medications?
* Yes,
* They can be used alongside other medications, such as inhaled corticosteroids.
101
Do leukotriene receptor antagonists have an effect on the chronic remodelling of lung tissue?
* No
* Unlike corticosteroids, they do not affect chronic tissue remodelling.
102
What is the primary therapeutic use of leukotriene receptor antagonists in asthma management?
They are primarily used as **preventer** medications to help prevent asthma attacks and the associated bronchospasm.
103
What are the most common side effects associated with leukotriene receptor antagonists?
Abdominal pain and headache.
104
What is a key difference between the uses of corticosteroids and leukotriene receptor antagonists in medicine?
Corticosteroids have a broader range of uses in medicine compared to leukotriene receptor antagonists, which are mainly used for airway diseases.
105
Apart from airway diseases, what are some other conditions that corticosteroids can be prescribed for?
Rheumatoid arthritis and Crohn's disease.
106
Name three common examples of corticosteroids used in the treatment of airway diseases.
* Beclomethasone (inhaled)
* Prednisolone (oral),
* Hydrocortisone (IV).
107
What are the primary cellular targets of corticosteroids in the context of airway disease?
Immune cells in the lungs such as macrophages, T lymphocytes, and eosinophils.
108
What is the molecular target of corticosteroids within these immune cells?
The **glucocorticoid receptor (GR)**, an intracellular protein.
109
How does the glucocorticoid receptor differ from other receptors like beta-2 adrenergic, muscarinic, and leukotriene receptors?
* The GR is an intracellular protein and acts as a transcription factor, directly influencing gene expression.
* It does not use secondary messenger systems like G-protein coupled receptors.
110
How does the mechanism of action of corticosteroids compare to that of aldosterone and its receptor?
Corticosteroids, like aldosterone, bind to intracellular receptors (GR for corticosteroids and mineralocorticoid receptor for aldosterone) that act as transcription factors, modulating the expression of numerous genes.
111
What is the general effect of corticosteroids on gene expression in macrophages, T cells, and eosinophils?
They generally exert an **anti-inflammatory** effect.
112
Give two examples of anti-inflammatory events triggered by corticosteroids.
* Enhanced expression of anti-inflammatory products (like lipoprotein 1, SPI, and interleukin 10)
* **Suppression of pro-inflammatory mediators** (like TNF-alpha and interleukin 8).
113
Describe the process by which corticosteroids interact with the glucocorticoid receptor.
* Corticosteroids, being hydrophobic, diffuse across the cell membrane and bind to the GR.
* This binding displaces the chaperone protein Hsp90, allowing the activated GR to translocate to the nucleus and alter gene expression.
114
How do corticosteroids affect the expression of beta-2 adrenergic receptors?
They **upregulate** beta-2 adrenergic receptors.
115
What is the potential consequence of this upregulation of beta-2 adrenergic receptors for airway function?
It can potentiate the bronchodilatory effects of beta-2 agonists like salbutamol.
| *Potentiate - Increase the power, effect, or likelihood (especially drug
116
How do corticosteroids affect the number and activity of eosinophils?
They **reduce** eosinophil numbers and **suppress** their activity.
117
What is the impact of corticosteroids on the production of pro-inflammatory cytokines by T lymphocytes?
They **reduce** the production of these cytokines.
118
How are mast cell numbers and activity modulated by corticosteroids?
Corticosteroids generally **reduce** mast cell numbers and dampen their activity.
119
What is the effect of corticosteroids on the production of pro-inflammatory cytokines by macrophages?
They **decrease** the production of pro-inflammatory cytokines by macrophages.
120
How do corticosteroids influence dendritic cell numbers?
Corticosteroids **reduce** the numbers of dendritic cells.
121
How do corticosteroids impact epithelial cells in the lungs?
They **reduce the production of pro-inflammatory cytokine**s by epithelial cells.
122
What effect do corticosteroids have on the permeability of endothelial cells in the lungs?
They make endothelial cells **less permeable**, **reducing** the **leakage** of **inflammatory cells and mediators** into lung tissue.
123
What impact do corticosteroids have on mucus production by mucus gland cells in the lungs?
They decrease mucus production.
124
What underlies the development of Cushingoid features in patients taking corticosteroids?
Corticosteroids mimic the effects of cortisol, and dysregulation of cortisol is implicated in Cushing's disease, which is characterized by similar features.
125
Why do corticosteroids increase the risk of infection?
Corticosteroids have immunosuppressive effects that can compromise the body's ability to fight infections.
126
What is the link between corticosteroid use and impaired wound healing?
Corticosteroids suppress immune responses that are essential for efficient wound healing.
127
What is a hallmark side effect of corticosteroid use, especially in the context of long-term oral treatment?
A distinct facial appearance often referred to as **"moon face"** or Cushingoid features.
128
What other condition shares this distinctive facial characteristic, and what is its relevance to corticosteroid action?
* Cushing's disease, a condition involving cortisol dysregulation, also presents with this facial appearance.
* This is significant because corticosteroids mimic the actions of cortisol in the body.
129
Besides the characteristic facial changes, what are two other common side effects associated with prolonged corticosteroid use?
Poor wound healing and increased susceptibility to infection.
130
Why do patients on long-term corticosteroid therapy often experience poor wound healing?
Corticosteroids suppress the immune system, and a robust immune response is crucial for efficient wound healing.
131
Why do patients on corticosteroids have an increased risk of infection?
* Corticosteroids have an **immunosuppressive** effect
* By suppressing the immune response, corticosteroids compromise the body's ability to effectively fight off infections, making patients more vulnerable.
132
Why is patient consultation, particularly for those prescribed oral corticosteroids, often extensive and significant?
Because corticosteroids influence the expression of multiple genes across various tissues, they can cause a wide range of side effects that require careful management and monitoring.
133
What must be emphasised about the efficacy and potential risks of corticosteroids as a class of drugs?
While corticosteroids are potent and effective drugs that can be life-saving in certain situations, their use carries risks that must be carefully managed.
