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The Respiratory System > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What does the stimulation of postganglionic cholinergic neurones cause?

A
  1. Bronchial smooth muscle contraction (M3 receptors)
  2. Increased mucus secretion (M3 receptors on goblet cells)
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2
Q

What does the stimulation of postganglionic parasympathetic non-cholinergic neurones cause?

A

Bronchial smooth muscle relaxation

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3
Q

In which four ways does the sympathetic system affect the airways?

A
  1. Bronchial smooth muscle
  2. Mucous secretion
  3. Mucociliary clearance
  4. Vascular smooth muscle contraction
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4
Q

Bronchial smooth muscle is not innervated by sympathetic neurones - how does the sympathetic system influence the bronchi?

A

There is no postganglionic neurone, so innervation of the adrenal gland allows it to act as this neurone, by releasing adrenaline which can cause bronchial smooth muscle by binding to B2 adrenoceptors

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5
Q

What are the receptors associated with the sympathetic system in submucosal glands and what is their activated effect?

A

B2 adrenoceptors (act on goblet cells and epithelium) Reduces mucus secretion and increases clearance (mucociliary elevator)

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6
Q

Which receptor mediated vascular smooth muscle contraction?

A

A1 adrenoceptors

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7
Q

What is the sarcoplasmic reticulum?

A

Type of endoplasmic reticulum that regulates calcium ion concentration in skeletal muscle

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8
Q

During motor neurone conduction in skeletal muscle, what type of receptor is activated after hormone or neurotransmitter release?

A

G protein coupled receptor (Gq and phospholipase)

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9
Q

How is IP3 produced during skeletal muscle contraction?

A

Produced from PIP2 (phosphatidylinositol (4,5) biphosphate after Gq subunit binds to phospholipase

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10
Q

What is the function of IP3 in skeletal muscle contraction?

A

Produced IP3 acts as a substrate for the IP3 receptor (transmembrane) which, when bound, allows efflux of calcium ions out of the sarcoplasmic reticulum and into the cytoplasm. Contraction is now viable

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11
Q

Describe how calcium can aid the pathway of smooth muscle contraction

A

When the impulse arrives, voltage gated calcium channels open calcium an influx of calcium into the cytoplasm. Calcium can then activate ryodine receptors (calcium activated channels). This allows for calcium efflux out of the sarcoplasmic reticulum

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12
Q

Which two main things must be available for muscle contraction to occur?

A
  1. ATP
  2. Calcium
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13
Q

Why is calcium required for muscle contraction?

A

Calcium combines with calmodulin which creates a complex that activates MLCK

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14
Q

What does activated MLCK allow for?

A

Activated MLCK breaks down ATP allowing inactive myosin cross-bridges to enter the cocked position and able to bind with actin filaments

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15
Q

What causes smooth muscle relaxation?

A

Dephosphorylation of MLC by MLC phosphotase

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16
Q

When levels of calcium are high in smooth muscle cells, the rate of phosphorylation will be much higher than dephosphorylation, so for relaxation to occur, what must happen to the levels of calcium

A

They must reduce

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17
Q

What effect does adrenaline have when binding to B2 adrenoceptors in smooth muscle?

A
  • G protein couples receptor activated (Gs)
  • Complex activates adenylyl cyclase which boots cAMP levels
  • cAMP combines to PKA
  • PKA facilitates smooth muscle relaxation
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18
Q

In what 2 ways does PKA stimulate smooth muscle relaxation?

A
  1. Phosphorylating and inhibting MLCK which inhibits contraction
  2. Phosphorylating and stimulating myosin phosphotase which facilitates relaxation
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19
Q

Chronic asthma can have many negative effects, what are some of these?

A
  • Increase in smooth muscle reducing bronchiole diameter
  • Inflammation causes build up of oedema
  • Increased mucus secretion into lungs causes partial obstruction
  • Epithelial lining becomes damaged and cells are shed which exposes sensory nerve endings causing irritability
  • Sub-epithelial fibrosis - epithelial cells deposit excess collagen reducing space further in airways
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20
Q

What causes bronchial hyper-responsiveness in asthma?

A

Epithelial damage leads to C-fibre (irritation receptor) exposure causing increased sensitivity to bronchoconstrictor influences

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21
Q

As a result of epithelial damage in asthma, neurogenic inflammation occurs - what are the cosequences of this?

A

Various peptides are released from these nerve endings

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22
Q

Which two components contribute to the severity of asthma?

A
  1. Hyper-sensitivity - concentration of bronchoconstrictor influences that will evoke asthmatic response
  2. Hyper-reactivity - The severity of the response experienced
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23
Q

What composes the immediate reaction in an asthma attack?

A

Initial bronchospasm and acute inflammation

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24
Q

What composes the delayed reaction of asthma?

A

Continued bronchospasm and delayed inflammation

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25
Q

Due to the two phases to an asthma attack, the FEV1 changes over time, but in what ways?

A

FEV1 - decreases after initial reaction (immediate)

FEV1 - recovers after the immediate reaction

FEV1 - deteriorates again during delayed reaction

FEV1 - recovers fully

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26
Q

How does atopic asthma differ from non-atopic asthma in relation to immune system activation?

A

Non-atopic - low level TH1 response which mediates IgG and macrophages

Atopic - strong TH2 response that is an antibody mediated immune response involving IgE

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27
Q

What are TH0 cells?

A

Precursors

They differentiate to either TH1 or TH2 cells

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28
Q

In the development of allergic asthma describe the induction phase

A
  • The allergen is processed by dendritic cells
  • It is presented to CD4+ cells which become activated
  • TH0 cells are activated
  • Those which differentiate to TH2 activate B cells by physical contact or release of cytokines such as IL-4
  • B cells proliferate and differentiate to plasma cells
  • Antibodies are produced
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29
Q

In the development of allergic asthma describe the effector phase

A
  • Plasma cells secrete IgE antibodies due to interleukin 4 action
  • Interleukin 5 is released from TH2 cells which activates eosinophils
  • Mast cells express IgE receptors and become activated due to release of IL-4 and IL-13
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30
Q

What are the two phases to the development of allergic asthma?

A
  1. Induction phase
  2. Effector phase
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31
Q

How do mast cells become activated in allergic asthma?

A

Antigens combine with IgE antibodies on the surface of mast cells

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32
Q

What happens during mast cell activation in allergic asthma?

A

Calcium enters via calcium channels and it is released from intracellular stores

  • Mast cell secrete histamine, leukotrienes (LTC4, LTD4) - causes contraction of airways
  • Mast cells release substances (chemokines/chemotaxins) that attract inflammation causing cells to the area

This explains the primary and secondary responses to an asthma attack

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33
Q

What happens when mast cells release chemotaxins and chemokines during allergic asthma?

A
  • TH2 cells infiltrate the area with monocytes (TH1 may also be involved)
  • Inflammatory cells such as eosinophils become activated
  • Eosinophils cause damage to epithelium
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34
Q

What are the two main types of drugs are used in asthm anad which drug classes are used for each?

A

Relievers - bronchodilators

  • SABAs
  • LABAs
  • CysLT1 receptor antagonists

Controllers/preventors - anti-inflammatory

  • Glucocorticoids
  • Cromoglicate
  • Humanised monoclonal IgE antibodies
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35
Q

Why are LABAs never given as monotherapy?

A

Monotherapy of LABAs can be harmful

Receptors can lose sensitivity and pharmacological effect over time decreases

This can cause a long-term decrease in the amount of B2 adrenoceptors as they are withdrawn from the surface of cells and potentially broken down by lysomes

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36
Q

During stage 3 of asthma treatment, what happens if there is no response to the added LABA?

A

Dose of ICS is increased

And, if required trial of other therapies such as a CysLT1 receptr antagonist or theophylline is used

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37
Q

What are the three classes of B2-adrenoceptor agonists?

A
  1. SABAs
  2. LABAs
  3. Ultra LABAs
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38
Q

Why are SABAs administered by inhalation?

A

This reduces the dose required and therefore the systemic effects experienced

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39
Q

What are some of the potential side effects to SABAs?

A
  • Tachycardia
  • Cardiac dysrhythmias
  • Hypokalaemia
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40
Q

What 3 things do SABAs achieve?

A
  • Bronchodilatation
  • Increased mucus clearance
  • Decreased mediator release of mast cells and monocytes
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41
Q

LABAs are always co-administered with a ______________

A

Glucocorticoid

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42
Q

What is the benefit that LABAs have over SABAs?

A

They can be used for nocturnal asthma

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43
Q

What is isoprenaline and why is it not frequently used?

A

It is a non-selective beta agonist (works on both B1 and B2 adrenoceptors)

It will stimulate cardiac muscle as well as causing bronchodilatation

Selective B2 agonists are preferred for bronchodilation

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44
Q

Name a non-selective B arencoceptor agonist

A

Isoprenaline

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45
Q

Why is the use of propranolol dangerous in patients requiring bronchodilation therapy?

A

Propranolol is a non-selective B adrenoceptor antagonist

It blocks both B1 and B2 adrenoceptors

Adrenaline is required to bind to B2 adrenoceptors in the airways to ensure a relatively relaxed state is maintained

Upon propranolol administration, this cannot occur and there is a risk of bronchospasm

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46
Q

What happens when phospholipase A2 acts on activated mast cells?

A

Intracellular release of arachidonic acid occurs

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47
Q

After arachidonic acid is released intracellularly in mast cells, what happens when the mast cells are stimulated by 5-lipooxygenase (FLAP)

A

Arachidonic acid is metabolised to leukotriene A4 (LTA4) and then subsequently into LTB4 and LTC4which are both secreted into the extracellular spaceby transport proteins

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48
Q

LTB4 has what effects in the airways?

A

Causes infiltration of other inflammatory cells causing the production and release of other leukotrienes including CysLT1 (cysteinyl leukotriene)

LTB4 will also act as a chemokine attracting this leukotriene into the airway cells

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49
Q

What happens in the airways to LTC4?

A

It is metabolised to LTD4 and LTE4

(LTD4 can also metabolise to LTE4)

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50
Q

Whick leukotrienes will act on the CysLT1 receptor?

A
  • LTD4
  • LTE4
  • CysLT1
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51
Q

Activation of the CysLT1 receptor will lead to what?

A

Contraction of bronchial smooth muscle

(and later, inflammation)

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52
Q

In the USA, which drug is used to block stimulation is mast cells by 5-lipooxygenase?

A

Zileuton

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53
Q

What are two of the main CysLT1 antagonists?

A
  • Montelukast
  • Zafirlukast
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54
Q

Why are CysLT1 receptor antagonistsnot recommended for relief of severe acute asthma?

A

Their bronchodilator activity is less than salbutamol

They are not effective against all contractile stimuli

Salcutamol is effective against any provoking stimulus sue to acting in a physiological manner - cAMP pathway

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55
Q

How are CysLT1 receptor antagonists administered?

A

Orally

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56
Q

What are the two main methylxanthines?

A
  1. Theophylline
  2. Aminophylline
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57
Q

What are the two main actions methylxanthines take to counteract asthma symptoms?

A
  • Bronchodilator action
  • Anti-inflammatory action
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58
Q

Describe the bronchodilator action of methylxanthines

A

Normally cAMP is broken down to 5’AMP by phosphodiesterase enzymes

This prevents smooth muscle relaxation

Methylxanthines (at high doses) inhibit phosphodiesterase (3/4) and allow for smooth muscle relaxation

Levels of cAMP can activate protein kinase A which can phosphorylate and inhibit MLCK, or phosphorylate and stimulate myosin phosphotase - preventing contraction/allowing for relaxation

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59
Q

How is diaphragmatic contractility affected by the use of methylxanthines?

A

It is increased

This can reduce fatigue and improve ventilation

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60
Q

Describe the anti-inflammatory action of methylxanthines

A

At high doses, pro-inflammatory mediator release from mast cells is inhibited and mucociliary clearance is reduced

Methylxanthine can induce intra-cellular effects - they can activate histone deacetylase (HDAC) in the nucleus

HDAC removes acetyl groups (in histone proteins), increasing the +ve charge of histone tails and increasing bond strength between histones and DNA.

This means transcription of inflammatory genes occurs less frequently

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61
Q

Why does HDAC increase the strength of bonds between histones and the DNA backbone?

A

Normally acetylation occurs in histone proteins converting amines to amides which neutralises +ve charges

This reduces the amount of +ve charges from the histone proteins bonded to the -ve DNA backbone

This weakens the attraction and promotes the transcription of genes (inflammatory in the case of pharacology) as chromatin expands

HDAC prevents this acetylation occuring ensuring strong bonds remain between histones and DNA

62
Q

Why are methylxanthines not high on the list for the treatment of asthma?

A

They have serious side effects and very narrow therapeutic window

  • Seizures
  • Hypotension, dysrhthmias
  • GI tract issues - vomiting, discomfort
  • Kidney problems
63
Q

How can methylxanthines negatively impact drug metabolism?

A

They can interfere with enzymes involved in drug metabolism such as the cytochrome P450s

64
Q

What is the adrenal cortex?

A

The outer layer of the adrenal gland

65
Q

Name the layers of the adrenal corex from most superficial to deep

A
  1. Glomerulosa
  2. Fasciculata
  3. Reticularis
66
Q

The different layers of the adrenal cortex can synthesise different _________

A

Steroids

67
Q

The adrenal cortex synthesises which two major classes of steroid hormone?

A
  1. Glucocorticoids - synthesised in zona fasiciculata
  2. Mineralocorticoids - synthesised in zona glomerulosa
68
Q

Are steroid hormones pre-sotred in vasicles or are they synthesised on demand by hormones from the anterior pituitary?

A

Synthesised on demand by the anterior pituitary gland

69
Q

What is the main glucocorticosteriod produced in humans?

A

Cortisol

70
Q

What is the main mineralocorticoid in humans and what are its main effects?

A

Aldosterone

Regulates the retention of water and salt by the kidneys

71
Q

Of the two, which are more useful for asthma treatment, corticosteroids or mineralocorticoids, and why?

A

Corticosteroids

They have anti inflammatory action and they dampen down the immunological response

72
Q

In basic terms, how is cortisol synthetically altered to allow it to be a suitable asthma treatment?

A

Cortisol has both corticoid and mineralocorticoid properties

The mineralocorticoid properties are edited out so only the corticoid properties have influence

73
Q

Give three examples of glucocorticosteroids that are synthetic derivatives of cortisol

A
  1. Beclometasone
  2. Budesonide
  3. Fluticasone
74
Q

Why should glucocorticoids never be administered alone?

A

They have no (direct) effect on bronchospasm and will not relieve it

75
Q

Why should glucocorticoids be administered by inhalation?

A

To avoid systemic effects

76
Q

Where are glucocorticoid receptors in cells?

A

Cytoplasm (or nucleus)

(activation leads to effects in nucleus)

77
Q

How do glucocorticoids enter the nucleus?

A

By diffusion into the cytoplasm

(they are hydrophobic agents - so thier receptor will be intra-cellular)

78
Q

What is the glucocorticoid receptor called?

A

GRα

79
Q

The GRα receptor is normally bound to by _____ ______ __________, specifically _____and when the glucocorticoid binds to the receptor _________ will dissociate

A

Heat shock proteins

HSP90

HSP90

80
Q

Upon glucocorticoid binding to GRα, what occurs initially?

A

The receptor/agonist complex can move to the nucleus aided by specific karyopherins called importins

81
Q

What happens, initially, when the agonist/receptor complex (glucocorticoid/GRα) reaches the nucleus?

A

The receptors (whilst bound to glucocorticoids) pair up forming homodimers

82
Q

What does the creation of (GRα receptor) homodimers in the nucleus allow for?

A
  1. Transactivation - transcription of specific genes is switched on
  2. Transrepression - transcription of specific genes is switched off
83
Q

Where do the GRα homodimers bind?

A

Glucocorticoid response elements (GREs)

(in the promotor region of certain genes)

84
Q

Binding of GRα homodimers to glucocoticoid response elements will result in what?

A
  1. Transactivation
  2. Transrepression

mRNA levels are altered which alters the level of protein synthesis that occurs and therefore the amount of protein expression

85
Q

Glucocorticoids can influence the type and amount of protein transcribed. Which types of genes will be preferentially transcribed and which will not be?

A
  • Anti-inflammatory genes - transactivated
  • Inflammatory genes - transrepressed

Anti-inflammatory genes will be transcribed more and anti-nflammatory proteins will begin to predominate

86
Q

What is chromatin?

A

The state of histone proteins and DNA being tightly bound together

87
Q

Activated TH2 cells affect B cells in what way?

A

They induce maturation and clonal expansion of B cells with become plasma cells

This is due to the release of IL-4 from helper T cells

88
Q

How can glucocorticoids affect the actions of TH2 cells?

A

They suppress the release of IL-4 and IL-5

They also cause apoptosis in TH2 cells

(this suppression indirecetly supresses B cells)

89
Q

Indirect inhibition of B cells by glucocorticoids affects IgE antibody levels in what way?

A

They are reduced

B cells cannot mature to plasma cells since TH2 cell sare both suppressed and forced to undergo apoptosis

90
Q

Glucocortiocoids affect eosinophil influx in which way?

A

It is reduced

Eosinophil influx is mediated by IL-5 which comes from TH2 cells - which glucocorticoids suppress

Glucocorticoids can also induce apoptosis of eosinophils

91
Q

By removing IL-4 (suppressing TH2 cells), what other effect is induced by glucocorticoids?

A

Mast cell recruitment is reduced

92
Q

In which two ways are mast cells affected by glucocorticoids?

A
  1. Their recuitment is reduced (lack of IL-4 due to TH2 supression)
  2. Abundance of Fcε receptor on mast cells are downregulated so they are less likely to be activated by IgE
93
Q

How are endothelial cells affected by glucocorticoids?

A

They become less “leaky” counteracting oedema

94
Q

Give four examples of glucocorticosteroids

A
  1. Beclometasone
  2. Budesonide
  3. Fluticasone
  4. Prednisolone (oral drug)
95
Q

B2 adrenoceptor levels (in airway smooth muscle) are affected by glucocorticoids - in what way?

A

They are upregulated

They airways become more sensitive to adrenaline and pharmacotherapeutics

96
Q

What are the side effects of glucocorticosteroids?

A

When taken by inhalation side effects are due to incorrect administration (deposited at the back of throat or swallowed)

  • Dysphonia - hoarse and weak voice
  • Oropharyngeal candidiasis

The oropharynx becomes immunosuppressed and is vulnerable to infection

97
Q

What is the overarching idea of cromone function?

A

They are mast cell stabilisers

(prevent histamine release)

98
Q

How can cromones affect C-fibres?

A

C-fibres (exposed nerve fibres) have their sensitivity decreased by cromones

99
Q

What is the main cromone administered by inhalation?

A

Sodium cromoglicate

(targets late phase of asthma and takes several weeks to work)

100
Q

How can monoclonal antibodies be used (against IgE) in the treatment of asthma?

A

They can be used against IgE

They bind to IgE via the fixed chain preventing any interaction from IgE with the Fcε receptor on mast cells

This prevents mast cell activation

101
Q

Why is monoclonal antibody treatment inconvenient to the patient?

A

It requires regular IV administration

102
Q

Name a monoclonal antibody treatment against IgE

A

Omalizumab

103
Q

Name a monoclonal antibody treatment against IL-5 for use in asthma

A

Mepolizumab

This is for severe asthma with serious eosinophilia

104
Q

Why are monoclonal antibody treatments seldom used despite their effectiveness?

A

They are very expensive

105
Q

What is the best treatment for COPD?

A

Smoking cessation

106
Q

COPD is composed of which two branches of disease?

A
  1. Chronic bronchitis
  2. Emphysema
107
Q

Describe the pathway to developing COPD

A
  1. A stimulus (smoking) will recruit macrophages resident in alveoli which produce cytokines
  2. Neutrophils, CD8+ and macrophages are recruited (this immunological recruitment varies to asthma)
  3. Proteases are releases such as elastase along with free radicals which will damage lung tissue as well as original stimulus
  4. Resident anti-proteinases cannot inhibit this effect because in smokers they are themselves inhibited
108
Q

Why are glucocorticoids effective in asthma and not COPD?

A

The immunological components recruited in COPD are different to those of asthma

  • COPD - CD8+, neutrophils and macrophages
  • Asthma - macrophages, CD4+ and TH2 cells
109
Q

What is chronic bronchitis?

A

Chronic inflammation of the bronchi and bronchioles

This will include a cough, clear sputum (unless infection is present), increased infection rates and breathlessness

110
Q

What is emphsema?

A

Distension and damage to alveoli

Destruction of alveoli leading to large dead spaces in the lungs contribting to an increased residual volume

111
Q

The cell bodies for smooth muscle preganglionic neurones are present in the ______ ______

A

Brain stem

112
Q

The preganglionic neurones for smooth muscle are part of which nerve?

A

Vagus

113
Q

Where are smooth muscle postganglionic neurones present?

A

In the walls of airway smooth muscle

114
Q

Short postganglionic neurones for smooth muscle will release which neurotransmitter onto smooth muscle cells in the airways?

A

Acetylcholine

115
Q

Stimulation of parasympathetic neurones tht innervate airway smooth muscle has what effect(s)?

A
  1. Bronchoconstriction
  2. Increased mucous production
116
Q

What is the difference between nicotinic and muscarinic receptors?

A

Nitotinic receptors mediate a very fast depolarisation of neurones, whilst muscarinic receptors mediate a much slower depolarisation

117
Q

Where is the M1 receptor located at what is its function?

A

Postganglionic neurone cell body

It functions to mediate a slow excitatory postsynaptic potential which enhnaces cholinergic reflexes

118
Q

Where is the M2 receptor located and what is its function?

A

Present at the postganglionic nerve terminals

They function to stimulate the post synaptic receptors on smooth muscle and also muscarinic receptors on the smooth muscle

This is an inhibitory autoreceptor allowing self regulation of acetylcholine release

119
Q

Where is the M3 receptor located and what is its function?

A

Located on smooth muscle cells (and goblet cells)

They mediate the contraction of smooth muscle in response to acetylcholine stimulation

120
Q

In order to treat COPD which is the main muscarinic receptor that is targeted for inhibition?

A

M3

(not M2, this helps reduce acetylcholine reduction anyway)

121
Q

Muscarinic acetylcholine receptor antagonists have what outcome?

A
  1. Release of mucous is reduced
  2. Smooth muscle contraction is reduced
122
Q

How does the M3 receptor normally confer smooth muscle contraction upon stimulation?

A
  • It is a G-protein coupled receptor which, when activated, will activate Gq11
  • The G protein activates phospholipase C which is a membrane bound enzyme
  • This converts phosphatidlylinosital (4,5) biphosphaste (PIP2) to the soluble messenger molecule inositol (1, 4, 5) triphosphate (IP3)
  • IP3 binds to IP3 receptors on the sarcoplasmic reticulum which induces calcium release allowing for muscle contraction
123
Q

Which two classes of muscarinic receptor antagonists can be utilised to block M3 receptors on smooth muscle and give examples for each

A
  • Short acting muscarinic antagonists (SAMAs) - ipratropium, oxitropium
  • Long acting muscarinic antagonists (LAMAs) - tiotropium, aclidinium
124
Q

SAMAs and LAMAs possess a quaternary ammonium group in their structure - why is this signifiant?

A

Unlike a tertiary group, this is permanent

The postive charge prevents the molecule from travelling systematically and localises it to the airways

This reduces systemic side effects

125
Q

Is ipratropium a selective or non-selective agent?

A

Non-selective

This means M2 receptors are blocked leading to an increase in acetylcholine production meaning the drug has more work to do on M3 receptor inhibition than it would if it were selective

126
Q

Is tiotropium a selective or non-selective agent?

A

Selective

It has a longer half-life than ipratropium (34.7 vs 3.2 hours)

127
Q

Muscarinic receptor antagonists are often used in conjunction with what other drug class?

A

B2 agonists

  • SABAs - salbutamol
  • LABAs - salmeterol, formeterol
  • Ultra LABAs - indacaterol
128
Q

In short, how do B2 agonists function to induce smooth muscle relaxation?

A

They stimulate B2 adrenoceptors which allows for an increase in cAMP which can activate relaxation mechanisms

129
Q

How do B2 agonists contribute to decreased acetylcholine release?

A

They are present alongside M2 receptors at the terminals of postganglionic parasympathetic nerve fibres and their stimulation can aid a decrease in acetylcholine release

130
Q

To obatin the best response in COPD treatment, LABAs and LAMAs should be taken _________

A

Together

(so that they end up in the same location in the airways)

This is done by creating MABAs

(muscarinic antagonist B2 agonists)

131
Q

Desribe the two ways in which phosphodiesterase inhibitors can aid in COPD treatment

A
  1. They limit the breakdown of cAMP in cells allowing for relaxtion to be mainatined in smooth muscle cells
  2. PDE4 is expressed in neutrophils, T cells and macrophages and a build up of cAMP can suppress their function
132
Q

What is the main side effect for using PDE4 inhibitors for COPD?

A

They have GI side effects

There will be increasted secretions and diarrhoea will result

133
Q

For how long should glucocorticoids be used for COPD?

A

Only short term

Long term effects are limited and they should just be used to reduce exacerbationsand stabilised the condition

134
Q

Why are glucocorticoids less effective in COPD than in asthma?

A
  1. There are different immunological processes in COPD
  2. Oxidative/nitrative stress drives COPD inflammation - something glucocorticoids cannot impact
  3. The expression of HDAC2 in COPD sufferers is less so it is harder for glucocorticoids to activate anti-inflammatory genes as the DNA remains more tightly bound
135
Q

What is rhinitis?

A

A cold-like disease involving:

  • Runny nose (rhinorrohea)
  • Sneezing
  • Itching
  • Nasal congestion and obstruction
136
Q

What are the three types of rhinitis?

A
  1. Allergic
  2. Non-allergic
  3. Mixed (combination of the above types)
137
Q

What is allergic rhinitis?

A
  • A specific allergen, when inhaled, will cause the condition
  • A hypersensitivity type 1 reaction will proceed causing IgE levels to rise
  • IgE can activate mast cells and basophils
  • Pro-inflammatory mediators are released (histamine, CysLTs, trytase and prostaglandins)
  • These cause the symptoms
  • A delayed component is present due to the recruitment of lymphocytes and eosinophils which causes nasal congestion and obstruction
138
Q

What is non-allergic rhinitis?

A

It does not have an allergic component do does not involve IgE

Causes can include infection, hormone imbalance, vasomotor disturbances (often idiopathic), non-allergic rhinitis with eosinophila syndrome (NARES) and medications

  • Infectious rhinitis is largely viral
  • Rhinitis by hormone imbalance often occurs in pregnancy
139
Q

What are the major drug classes for the treatment of rhinitis?

A
  • Glucocorticoids - anti-inflammatory
  • CysLT1 receptor antagonists/H1 receptor antagonists - mediator receptor blockers
  • Vasoconstrictors - reduce nasal blood flow
  • Cromones - sodium chromoglicate - antiallergic
140
Q

Give three examples of glucocorticoids that can be used for rhinitis

A
  1. Prednisolone (orally)
  2. Fluticasone
  3. Beclometasone
141
Q

What are anti-histamines?

A

Competitive antagonists of H1 receptors

142
Q

Why are second generation anti-histamines superior to first generations?

A

They cannot cross the blood brain barrier and do not have anti-cholinergic effects

They also have reduced side effects and are less likely to cause lethargy

Despite this, the anti-cholinergic effects of first generation drugs can combat rhinorrhoea

143
Q

Give 3 examples of second generation anti-histamines

A
  1. Loratadine
  2. Fexofenadine
  3. Cetirizine (possesses mild inflammatory action)
144
Q

What is the only muscarinic receptor antagonist used for rhinitis?

A

Ipratropium

145
Q

Which cromone can be used to treat rhinitis and how does it function?

A

Sodium chromoglicate

Acts as a mast cell stabiliser but has a long onset of action usually between 4-7 days

146
Q

How do CysLT1 receptor antagonists function in the nasal mucosa?

A

They block the effects of CysLTs

They are equally as effective as H1 receptor antagonists and when used toegther the effect may be additive

147
Q

What is the only CysLT receptor antagonist to treat rhinitis?

A

Montelukast

148
Q

When will vasoconstriction occur in the nasal mucosa?

A

When alpha1-adrenoceptors are stimulated

149
Q

What is a selective alpha-1 adrenoceptor used in the treatment of rhinitis?

A

Oxymetazoline

Treatment for longer than a few days is not recommended since rhinitis medicamentosa may occur - this is when nasal congestion increased to levels worse than before treatment when treatment is eventually stopped

This occurs due to receptor desensitisation and downregulation due to overstimulation

150
Q

Within the lungs, parasympathetic control is ________ over sympathetic control

A

Dominant

151
Q

How does smoking impact HDAC activity?

A

It reduces the activity

This means the functioning of corticosteroids in COPD may improve if smoking ceases

152
Q

How does the anti-inflammatory component of tiotropium function?

A
  • Acetylcholine release directly results in LTB4 and IL-8 release from mast cells and bronchial epithelium respectively
  • LTB4 increases capillary permeability and adhesiveness
  • IL - causes neutrophil activation and chemotaxis
  • By blocking LTB4 and IL-8, as tiotropium does, their effects do not occur and inflammation is reduced

The Respiratory System (16 decks)

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