Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Respiratory > Drugs > Flashcards

Drugs Flashcards

1
Q

Parasympathetic innervation
What chemical is used to transmit impulses?
What two things doe stimulation of postganglionic cholinergic fibres cause?
What type of M receptor does this involve?
What does stimulation by non-cholinergic fibres cause?
What are the mediators of this?

A

Acetyl choline
1. Bronchial SM contraction mediated by M3 muscarinic Ach receptors
2. Increased mucus secretion mediated by M3 receptors on goblet (gland cells)
Noncholinergic –> bronchial SM relaxation mediated by NO and VIP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What doe stimulation of the sympathetic system do to airway SM?
How does it do this?

A

Bronchial SM relaxation via B2-ADR on ASM cells, activated by adrenaline released from the adrenal gland
Decreased mucus secretion mediated by B2-ADR on goblet cells
Increased mucociliary clearance mediated by B2-ADR on epithelial cells
Vascular SM contraction, through A1-ADR on vascular SM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What ion causes SM contraction?
What are the steps in this pathway?
What two ways can this ion be activated in a cell?

A

Ca2+
Increased intracellular Ca2+ converts inactive myosin light chain kinase (MLCK) into active MLCK, which phosphorylates the myosin light chain.
Intracellular Ca2+ can be increased by either Ca2+ channels or G-protein coupled receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What enzyme causes SM relaxation?

What are the steps in this pathway?

A

Myosin phosphatase
MP dephosphorylates MLC causing SM relaxation.
In the presence of elevated intracellular Ca2+ the rate of phosphorylation exceeds the rate of dephosphorylation. Relaxation thus requires return of intracellular Ca2+ concentration to basal level – achieved by primary and secondary active transport.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What two types of reaction can occur in asthma?

Clue - they relate to time

A
  1. Initial type 1 hypersensitivity reaction - early phase bronchospasm and acute inflammation
  2. Type IV hypersensitivity reaction - late phase bronchospasm and delayed inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the immunology associated with the initial presentation of antigen to IgE being secreted?
What is IgE?

A 
Antigen is recognised by antigen presenting cells. This is processed, then presented to T cells called TCD4+, leading to the development of T-helper 0 lymphocytes, which mature into either T-helper 1 or T-helper 2 cells. T-helper 2 cells then physically bind to B cells in the blood, activating them and causing them to mature into IgE secreting plasma cells. 
Immunoglobulin E (IgE) is a type of antibody that is present in minute amounts in the body but plays a major role in allergic diseases. IgE binds to allergens and triggers the release of substances from mast cells that can cause inflammation. When IgE binds to mast cells, a cascade of allergic reaction can begin.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the immunology of step two in an asthma attack?

This involves IgE and mast cells.

A

Eosinophils differentiate and activate in response to IL-5 released fromTH2 cells.
Mast cells in airway tissue (express IgE receptors in response to IL-4 and IL-13 released from TH2 cells).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the immunology of step two in an asthma attack?

This involves IgE, Ca and granules.

A

IgE which is bound to antigen binds to an IgE receptor of a cell, causing:

(i) calcium entry into mast cells
(ii) release of Ca2+ from intracellular stores evoking:
- Release of secretory granules containing preformed histamine and the production and release of other agents (e.g. leukotrienes LTC4 and LTD4) that cause airway smooth muscle contraction
- Release of substances (e.g. LTB4 and platelet-activating factor (PAF) and prostaglandins (PGD2)) that attract cells causing inflammation (e.g. mononuclear cells and eosinophils) into the area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name the three types of drug used as “relievers” in asthma.

What general affect do these drugs have on the lungs?

A
  1. Short acting B2-agonists (SABAs)
  2. Long acting B2-agonists (LABAs)
  3. CysLT1 receptor antagonists
    These all act as bronchodilators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name three types of drug used as “preventors” in asthma.

What general effect do these drugs have on the lungs?

A
  1. Glucocorticoids
  2. Cromoglicate
  3. Humanised monoclonal IgE antibodies
    These act as anti-inflammatory agents that reduce airway inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the BTS guidelines for management of asthma?

A

Step 1- very mild intermittent asthma – short-acting 2-adrenoceptor agonist
Step 2- if short-acting B2-adrenoceptor agonist needed more than once a day, add a regular, inhaled, glucocorticoid (inhaled corticosteroid, ICS)
Step 3 - if control is inadequate, add a long-acting B2-adrenoceptor agonist (LABA). Monitor benefit – if good continue LABA, if of benefit but not adequate, increase dose of ICS. If no response to LABA stop administration of LABA, increase dose of ICS. If control still inadequate, institute trial of other therapies (e.g. cysLT1 receptor antagonist, or theophylline)
Step 4 - if asthma is persistent and poorly controlled, increase dose of ICS. Add a fourth drug (e.g. cysLT1 receptor antagonist, theophylline, oral B2 agonist)
Step 5- control still inadequate, introduce oral glucocorticoid – refer patient to specialist care

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What principally do B2 agonists do to cause bronchodilation?

What are the side effects of them?

A

B2-Adrenoceptor agonists - act as physiological antagonists of all spasmogens. They do not block the effect of parasympathetic stimulation – they just block the consequences of parasympathetic stimulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do SABAs in particular do to the airways?
What are their side effects?
Examples

A

Increase mucus clearance and decrease mediator release from mast cells and monocytes
Have few adverse effects (due to unwanted systemic absorption) when administered by the inhalational route, fine tremor being the most common. However, tachycardia, cardiac dysrhythmia and hypokalaemia can occur
E.g. salbutamol, albuterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q 
LABAs
What are they not recommended for?
What are they good for?
How should they be used?
Examples
A

-Are NOT recommended for acute relief of bronchospasm (salmeterol, but not formoterol, is slow to act)
-Are useful for nocturnal asthma (act for approximately 8 hours)
Should not be used as monotherapy, but can be used as add-on therapy in asthma inadequately controlled by other drugs (e.g. glucocorticoids), LABAs must always be co-administered with a glucocorticoid [for this purpose combination inhalers such as Symbicort® (budesonide and formoterol) and Seratide® (fluticasone and salmeterol) are available, but are relatively costly].
E.g.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are some things to note before prescribing bronchodilators?

A
  1. The use of selective B2-adrenoceptor agonists reduces potentially harmful stimulation of cardiac B1-adrenoceptors. Non-selective agonists (e.g. isoprenaline) are redundant.
  2. The use of non-selective B-adrenoceptor antagonists (e.g. propranolol) in asthmatic patients is contraindicated – risk of bronchospasm
  3. LABAs alone may worsen asthma by several mechanisms and cause an increased incidence of asthmatic deaths
    E.g. salmeterol, formoterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do CysLT1 receptor antagonists work?

Examples

A 
Cysteinyl leukotriene (CysLT1) receptor antagonists - act as competitively at the CysLT1 receptor. CysLTs (LTC4, LTD4 and LTE4) derived from mast cells and infiltrating inflammatory cells cause smooth muscle contraction, mucus secretion and oedema. 
E.g. montelukast. zafirlukast
17
Q 
CysLT1 receptor antagonists
When are they effective?
What effect do they have on the lungs?
How are they administered?
What are they not recommended for?
SE?
A
  • Are effective as add on therapy against early and late bronchospasm in mild persistent asthma and in combination with other medications, including inhaled corticosteriods in more severe conditions
  • Are effective against antigen-induced and exercise-induced bronchospasm
  • Relax bronchial smooth muscle in response to cysLTs
  • Are administered by the oral route
  • Are not recommended for relief of acute severe asthma (bronchodilator activity
18
Q 
Xanthines (methylxanthines)
Examples
What is special about them?
What do they do to the diaphragm?
When are they used?
How are they administered?
SE and therapeutic window?
A

E.g. theophylline & aminophylline

  • Combine bronchodilator (at high doses) and anti-inflammatory actions, inhibit mediator release from mast cells, increase mucus clearance)
  • Increase diaphragmatic contractility and reduce fatigue – may improve lung ventilation
  • Theophylline activates histone deacetylase (HDAC – see below) which may potentiate the anti-inflammatory action of glucocorticoids
  • Are second line drugs used in combination with B2-adrenoceptor agonists and glucocorticoids
  • Are administered by the oral route as sustained release preparations
  • Have a very narrow therapeutic window and exert adverse effects at supra-therapeutic concentrations that result from actions involving the CNS, CVS, G.I. tract and kidney including: (i) dysrhythmia, (ii) seizures, (iii) hypotension
  • At therapeutic concentrations frequently cause nausea, vomiting, abdominal discomfort and headache
19
Q

What genetic effects do glucocorticoids have?

Examples

A

Glucocorticoids inhibit genes which encode inflammatory proteins.
Glucocorticoids promote genes which encode anti-inflammatory proteins.
- They decrease formation of TH2 cytokines and cause apoptosis
- They prevent production of IgE
E.g. beclomethasone

20
Q

Oral corticosteroids
Example
When are they used?

A
  • Oral prednisolone may be used in combination with an inhaled steroid to reduce the oral dose required and minimise unwanted systemic effects. Bronchodilator drugs are co-administered
  • Patients should be strongly encouraged to take sufficient inhaled glucocorticoids to control symptoms and avoid disease progression, which may be irreversible
21
Q 
Cromones. 
When are they used?
Example
How is it administered?
What does it act on?
Who is it more effective in?
A

Are second line drugs now infrequently used prophylactically in the treatment of allergic asthma
Specific agent – sodium cromoglicate:
- Delivered by inhalation – little systemic adsorption
- Can reduce both phases of an asthma attack, but efficacy may take several weeks to develop to block late-phase reaction – requires frequent dosing
- Is more effective in children and young adults than older patients
ma.

22
Q

Monoclonal Antibodies directed against IgE
Example
How does it work?
How is it administered?

A

E.g. omalizumab

  • Binds IgE via Fc to prevent attachment to Fc receptors – suppresses mast cell response to allergens
  • Reduces the expression of Fc receptors on various inflammatory cells
  • Expensive treatment
  • Requires intravenous administration
23
Q

Monoclonal antibodies directed against IL-5
Example
Associated with what inflammatory molecule?

A

E.g. mepolizumab

  • Recently introduced treatment for asthma associated with severe eosinophilia
  • Very expensive
24
Q

How do muscarinic acetyl choline receptor agonists treat COPD?

A

Muscarinic acetylcholine receptor antagonists - act as pharmacological antagonists of bronchoconstriction caused by smooth muscle M3 receptor activation in response to ACh released from parasympathetic fibres (and non-neural cells also).

25
Q 
Short acting muscarinic antagonists
Examples
How are they delivered?
Time frame of action?
What effect do they have on the lungs?
A

Ipratropium, oxitropium
Inhalational route
Have a delayed (>30 min) onset of action
They relax brochospasm caused by irritable stimuli
Decrease mucus secretion
Effect is mainly paliative –> don’t stop the progression of the disease
Have few adverse side effects
-Ipratropium is a non-selective blocker of M1, M2 and M3 receptors

26
Q 
Long acting muscarinic antagonists
Example
How are they delivered?
Time frame of action?
What effect do they have on the lungs?
A

E.g. tiotropium, aclidinium
Have a delayed (>30 min) onset of action
They relax brochospasm caused by irritable stimuli
Decrease mucus secretion
Effect is mainly paliative –> don’t stop the progression of the disease
Have few adverse side effects
Tiotropium is M3 selective

27
Q

Combination in the treatment of COPD.

Review the answers

A
  • B-adrenoceptor agonists administered by inhalation in the treatment of COPD include salbutamol (short acting) and salmeterol and formoterol (long acting). Provide some bronchodilatation but have no effect on underlying inflammation
  • A combination of a LABA and a LAMA (e.g. salmeterol/tiotropium) is superior to either drug alone in increasing FEV1. Recommended for moderate COPD
28
Q

Phosphodiesterase-4 (PDE4)
What is this and how can it be utilised to treat COPD?
Example

A

Phosphodiesterase-4 (PDE4) is the prominent PDE expressed in neutrophils, T cells and macrophages – inhibition of PDE4 may have inhibitory effects upon inflammatory and immune cells.
E.g. Rofumilast, a selective PDE4 inhibitor, suppresses inflammation and emphysema in animal models of COPD. Approved as oral treatment for severe COPD accompanied by chronic bronchitis, but has limiting adverse gastrointestinal effects

Respiratory (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions