Brainscape's Knowledge GenomeTM

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


See full index

RW Respiratory > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What are the 3 main categories of drugs for asthma?

A

Relievers, Controllers/Preventers and those that are both (methylxanthines)

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

Reminder, what is the inflammatory cascade for airflow asthma?

A
  1. Genetic predisposition + triggers 2. Eosinophilic Inflammation 3. Mediators (TH2 cytokines) 4. Twitchy smooth muscle (hyper-reactivity) (Need to treat the top, down - as this dampens the downstream events)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is SMART therapy?

A

Single maintenance and reliever therapy (combining bronchodilator relievers and corticosteroids for long-term therapy)

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

**What are the steps in the pharmacological management of asthma?

A

Step 1 Intermittent: SABA

Step 2 Mild Persistent: SABA + ICS

Step 3 Moderate Persistent: SABA + ICS + LABA

Step 4 Severe Persistant: SABA + ICS + LABA + add on drug eg. cyst-leukotriene receptor antagonists, theophylline or B2 agonist tablet

Step 5: all of these + oral steroids

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

What classes as ‘brittle asthma’?

A

Wide PEF variability or sudden attacks when otherwise well controlled

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the main types of anti-inflammatories?

A
  • Corticosteroids - Chromones - Leukotriene Receptor Antagonists - Anti IgEs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the mechanism of action of corticosteroids

A

Counteract key underlying process of airway inflammation by suppressing genes for inflammatory proteins and activate genes which code for anti-inflammatory mediators

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

What is a main possible side effect of corticosteroids in COPD patients?

A

Pneumonia due to local immune suppression

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

What are the main advantages of inhaled steroids (e.g. beclamethasone) over oral steroids (e.g. prednisolone)?

A
  • Higher therapeutic ratio - Better local therapy (goes where needed) - Used for maintenance therapy, while oral is only acute - Smaller dose - Gives a more stable peak flow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are Beclometasone, budesonide or fluticasone propionate?

A

inhaled corticosteroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Prednisolone

A

Oral steroid

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

What is Cushings Syndrome?

A

Pathological hypercortisolism (caused by excessive oral steroids)

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

What are the advantages of spacers?

A

-Avoids coordination problems with pMDI -Reduces oropharyngeal and laryngeal side effects • E.g. oral thrush - Reduces systemic absorption from swallowed fraction - Acts a holding chamber for aerosol - Reduces particle size and velocity - Improves lung deposition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are Dry powder inhalers (e.g. acuhaler/turbohaler)?

A

Breath actuated - release a dose automatically when breath taken

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

When are cromones used?

A

Only used in asthma but has relatively poor efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the mechanism of action of CysLT1 (leukotriene) receptor agonists?

A

They act competitively at the CysLT1 receptor and stop CysLT1s (metabolites of arachidonic acid from inflammatory cells) from causing muscle contraction, mucus secretion and oedema.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How and when are Leukotriene Receptor Antagonists taken?

A

Orally and as an add on therapy in asthma in Step 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Montelukast or zafirlukast

A

Leukotriene receptor antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is an example of Anti-IgE treatment?

A

Omalizunab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What do Anti IgEs do?

A

Only used in patients with raised IgE-mediated allergic asthma who aren’t controlled by inhaled corticosteroid or LABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What drugs are in development for asthma?

A

Monoclonal antibodies for severe refractory asthma: anti TH2 cytokines e.g. Mepolizumab for anti-Il5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the main bronchodilators?

A
  • B2 agonists - Anti-cholinergics - Methylxanthines - Magnesium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What do B2 agonists do?

A

Stimulate bronchial smooth muscle beta 2 receptors to increase cAMP and promote sympathetic system to cause bronchodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

When are SABAs used?

A

Acute relief in both asthma and COPD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Salbutamol and terbutaline

A

SABAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

When are LABAs used?

A

Step 3, as an add on to SABAs and inhaled corticosteroids (often as a combined inhaler)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Salmetarol and formetarol

A

LABAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is an example of a SMART combination inhaler?

A

beclometasone (cotricosteroid) and formoterol (LABA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the advantage of formetarol over salmetarol?

A

Is has both a longer duration and faster onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What do anticholinergics /anti-muscarinics do?

A

Block post junctional end plate M3 receptors by ACh- essentially block bronchoconstrictor and hyper secretion effect of vagal nerve stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

When are anti-muscarinic bronchodilators used?

A

Mostly in COPD to reduce exacerbations, or as an add on in asthma at step 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Ipratropium and tiotropium

A

Antimuscarinic bronchodilators (SAMA and LAMAs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the main short acting muscarinic antagonist (SAMA)?

A

Ipratropium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the main long acting muscarinic antagonist (LAMA)?

A

Tiotropium and glycopyrronium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How do methylxanthines work?

A

They inhibit the metabolism of cAMP by enzyme phosphodiesterase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What type of drug has both bronchodilator and anti-inflammatory activity?

A

Methylxanthines (eg. theophylline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the aims of treatment of chronic asthma?

A
  • Abolish symptoms
  • Minimise B2 use
  • Normalise FEV1
  • Reduce PEF variability
  • Reduce exacerbations
  • Prevent long term airway remodelling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How would you treat acute asthma exacerbation?

A
  • Oxygen (60%)
  • Nebulised high dose salbutamol (2.5-5mg)
  • Hydrocortisone (oral) 100mg
  • Ipitropium 500mcg nebuliser
  • Theophylline: aminophylline infusion
  • Magnesium sulphate 2g IV
  • Escalate to mechanical intubation if going into respiratory failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are non-pharmacological treatments of COPD?

A
  • Smoking cessation - Immunisation against influenza and pneumococcal - Physical activity - Oxygen - Lung volume reduction surgery - Stenting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the main pharmacological treatments of COPD?

A

Step 1: SABA/SAMA

Step 2: if FV1 is >60% then LABA or LAMA ; if it is <60% then LAMA or LAMA/ICS combination inhaler

Step 3: LABA/combined inhaler or LAMA + LABA + ICS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What aren’t steroids used much in COPD treatment?

A

Because it is neutrophils, rather than a eosinophilic inflammatory response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

How would you treat acute COPD

A
  • Nebulised high dose ipratropium
  • Nebulae high dose salbutamol
  • Oxygen
  • Amoxicillin if infective
  • Oral prednisolone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What kind of transmission causes contraction of airway muscle?

A

Cholinergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Where are parasympathetic cell bodies of the preganglionic fibres are located?

A

Brainstem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Where are parasympathetic cell bodies of the postganglionic fibres are located?

A

Walls of the bronchi and bronchioles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What occurs with stimulation of postganglionic cholinergic fibres on M3 muscarnic ACh receptors?

A
  • Bronchial smooth muscle contraction - Increased mucus secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What neurotransmitter is always used in preganglionic cells?

A

Acetylcholine (cholinergic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What different types of post ganglionic fibres are there?

A
  • Cholinergic - Nitric (VIP or NO)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is caused by stimulation of postganglionic parasympathetic noncholinergic fibres?

A

Bronchial smooth muscle relaxation mediated by NO and VIP

50
Q

What does VIP stand for?

A

Vasoactive Intestinal Peptide

51
Q

Why is ASM relaxation a non-direct process?

A

ASM doesn’t receive a postganglionic sympathetic innervation

52
Q

What ares do receive post ganglionic sympathetic innervation?

A

Submucosal glands and smooth muscle of blood vessels

53
Q

What are the effects of stimulation of sympathetic system on ASM?

A
  • Bronchial smooth muscle relaxation via B2 adrenoreceptors activated by adrenaline from adrenal gland
  • Decreased mucous secretion
  • Increased mucociliary clearance
  • Vascular smooth muscle contraction
54
Q

What are the 2 processes of contraction in smooth muscle?

A

1) Via GPCRs and IP3 receptors 2) Via Calcium Induced Calcium Release

55
Q

What are the steps in excitation-contraction coupling via GPCRs and IP3 receptors?

A

1) Transmitter or hormone activates GPCR 2) GPCR couples with Gq/11 3) Activated Gq/11 activated Phospholipase C in membrane 4) PLC degrades PIP2 into IP3 5) IP3 activates IP3 receptors, which opens and allows calcium to move down gradient from SR into cell

56
Q

What are the steps in excitation-contraction coupling via calcium-indued calcium-release?

A

1) Depolarisation activated calcium channel 2) Influx of calcium activates ryanodine receptors on the SR, releasing calcium into the cell down gradient

57
Q

How does calcium cause contraction once in the cell?

A

1) Calcium enters the cell and binds to calmodulin (a calcium binding, regulatory molecule) to become Ca2+-calmodulin complex
2) This activates inactive myosin light chain kinase (MLCK) enzyme
3) Active MLCK produces phosphorylation reactions, converting ATP to ADP
4) Stripped inorganic Pi added to inactive myosin cross bridge
5) Forms an active phosphorylated myosin cross bridge which binds actin
6) Myosin and actin then slide over each other to contract as normal

58
Q

How does relaxation of smooth muscle occur (overview)?

A

Dephosporylation of MLC by myosin phosphatase (opposite of contraction which occurs via phosphorylation of MLC)

59
Q

What governs whether relaxation or contraction occurs?

A

Balance between rate of phosphorylation and dephosphorylation, dependent on the levels of intracellular Ca2+

60
Q

Where does salbutamol act and how?

A

Inhibits myosin light chain kinase to prevent MLC phosphorylation and cause relaxation

61
Q

What is the process of relaxation in smooth muscle?

A

1) Adrenaline activates B2 receptors which are linked to Gs GPCRs
2) These activate adenylate cyclase enzyme
3) This concerts ATP to cAMP
4) cAMP binds to protein kinase A
5) PKA phosphorylates and inhibits MLCK to inhibit contraction
6) It also phosphorylates and stimulates myosin phosphatase which dephosphorylates myosin light chain

62
Q

In what direction of respiration does asthma affect?

A

Outward direction (on expiration). In normal expiration the airways become narrower, however in asthma the airways are too narrowed already and can collapse

63
Q

What are the long-term pathological changes to bronchioles that occur due to chronic inflammation from asthma?

A

1) Increased mass of smooth muscle
2) Accumulation of interstitial fluid
3) Increased secretion and accumulation of mucus
4) Epithelial damage
5) Sub-epithelial fibrosis (les compliance)

64
Q

What is a consequence of epithelial damage and exposure of sensory nerve endings?

A

Increased sensitivity of the airways to bronchoconstrictor influences and neurogenic inflammation

65
Q

What can be used to reveal hyper-responsiveness?

A

Provocation tests with inhaled bromchocontrictors e.g. histamine

66
Q

What are the two components to hyper-responsiveness?

A

1) Hypersensitivity (less bronchoconstrictor is needed to cause a response) 2) Hyper-reactivity (theres is a greater fall in FEV1)

67
Q

What are the two phases of an asthma attack?

A

1) Immediate phase (mainly bronchospasm) 2) Delayed phase (mainly inflammatory)

68
Q

What type of hypersensitivity reaction is the immediate bronchospasm phase?

A

Type I

69
Q

What type of hypersensitivity reaction is the delayed inflammation phase?

A

Type IV

70
Q

What is the difference in response to phagocytosis of allergens in non-atopic individuals vs. atopic individuals?

A

In non-atopic, there is a low level TH1 reponse, which is a cell-mediates immune response involving IgG and macrophages. While in atopic, there sis a strong Th2 response which is antibody mediated involving IgE

71
Q

What are the steps in the induction phase of the development of allergic asthma?

A

1) Initial presentation of antigen causes adaptive immune response
2) Antigen recognised by APC
3) Antigen is process and then presented with MHCII to T CD4+ cells
4) These then activate TH0 cells - from here can be atopic or non-atopic route
5) In atopic route, Th0 cells mature and proliferate into Th2 cells
6) They bind to B cells and also produce IL-4
7) B cells interact with IL-4 and undergo clonal expansion
8) Eventually mature into plasma cells which secrete IgE eventually

72
Q

What are the steps in the Effector phase of the development of allergic asthma?

A

1) Plasma cells start to produce IgE
2) IgE receptors then expressed on the surface of these cells under direct of IL-4 and IL-3 for mast cells, and IL-5 for eosinophils
3) IgE can then be bound to these cells

73
Q

What happens in subsequent exposure to allergens in the development of an allergic response (late phase)?

A

1) Antigens bind to the IgE receptors in mast cells and forms cross links between IgE receptors
2) This stimulates calcium entry into mast cells and also the release of calcium
3) Calcium causes released of secretory granules containing preformed mediators including histamine, leukotrienes, and other pro-inflammatory factors to the ares e.g. Prostaglandins (basically invasion of inflammatory cells)

74
Q

What effect do these inflammatory cells have on the airways?

A

They act as spasmogens and cause the ASM to contract. They also cause hyper-responsiveness due to epithelial damage from eosinophils and further inflammation.

75
Q

What are the advantages of aerosol treatment over oral?

A

-Slow absorption with rapid clearance of anything not absorbed - Low dose - rapidly to target - Low systemic concentration - low risk of adverse effects

76
Q

What are the advantages of oral treatment over aerosol?

A
  • Distribution unaffected by airway disease - Ease of administration - Effective even in severe disease
77
Q

When is the maximal effects and duration of SABAs?

A

Maximal effect at 30 mins, and lasts for 3-5 hours.

78
Q

What are the adverse effects of SABAs?

A

Fine tremor, tachycardia, dysrhythmia and hypokalaemia

79
Q

When should LABAs not be used?

A
  • As acute relief (can actually worsen asthma) - As a mono therapy (but always be given with glucocorticoid)
80
Q

How long to LABAs normally last for?

A

Around 8 hours (so useful for nocturnal therapy)

81
Q

When shouldn’t leukotriene receptors be used?

A

-As a mono therapy (should be used as add ons) - For acute relie

82
Q

What are the disadvantaged of methylxanthines?

A
  • Very narrow therapeutic window - Adverse effects including dysrhtymia, seizures, hypotension, GI issues - Several drug interactions
83
Q

When should methylxanthines be used?

A

As second line drugs along side B2 agents and glucocorticoids

84
Q

What is the main use of glucocorticoids?

A

Prophylaxis of asthma to reduce underlying inflammation

85
Q

Why are synthetic derivates of cortisol used, rather than cortisol itself used?

A

Avoids the retention of salt and water caused by mineralocorticoids, as endogenous steroids may have both glucocorticoid and mineralocorticoid actions

86
Q

What are some of the cellular effects of glucocorticoids relevant to asthma?

A
  • decrease numbers of eosinophils, macrophages, meat cells, cytokines and dendritic cells - decreases cytokine mediators in epithelial cells - decrease leak from endothelial cells, reducing oedema - Increases B2 adrenoceptors in ASM, which improves responsiveness to SABAs/LABAs - Decrease mucous secretion
87
Q

What are the main adverse effects of glucocorticoids?

A
  • dysphonia (hoarse and weak voice) - oropharyngeal thrush
88
Q

What are the main actions of cromones?

A

‘mast cell stabilisers’ - suppress histamine release from mast cells

89
Q

What are main examples of glucocorticoids?

A

Beclometasone, budesonide or fluticasone

90
Q

What is the function of omalizumab?

A

Monoclonal antibody against IgE, by preventing attachment to Fce receptors to prevent degranulation

91
Q

What is the function of mepolizumab?

A

Monoclonal antibody against IL-5 which play a role in the development of asthma

92
Q

What are the disadvantages of monoclonal antibodies as treatment?

A
  • Very expensive - Inconvenient as need IV administration 2x weekly
93
Q

What is the specific agent of cromones?

A

Sodium cromoglicate

94
Q

What is the cornerstone of treatment of COPD?

A

Reducing parasympathetic activity with muscarinic receptor antagonists

95
Q

How are SAMAs and LAMAs given?

A

Inhalation

96
Q

Why is tiotropium superior to ipratropium?

A

Ipratropium is a non-selector muscarinic blocker so blocks M1-3, while tiatropium is selective to M3. Dont want to block M2 as that increases the release of ACh from parasympathetic postganglionic neutrons

97
Q

What are ultra-LABAs and what is an example?

A

Bronchodilator with rapid onset of action and long duration - example is Indacaterol

98
Q

Why are LABA/LAMA combinations so effective e.g. salmetarol/tiotropium?

A

They have a synergistic effect - they work by different but complimentary mechanisms

99
Q

What is rhinitis?

A

Common and often debilitating disease involving acute, or chronic, inflammation of the nasal mucosa which is characterised by • rhinorrohea (‘runny nose’ ) • sneezing • itching • nasal congestion and obstruction

100
Q

What are 3 main types of rhinitis?

A

1) Allergic (seasonal/perennial/episodic) 2) Non- allergic 3) Mixed

101
Q

What are the steps in allergic rhinitis?

A

1) Inhalation of allergic increase specific IgE levels
2) IgE binds to receptors on mast cells and basophils
3) Re-exposure cause mast cell and basophil degranulation
4) Release of mediators including histamine and cysLT1a and prostaglandins cause symptoms
5) Delayed response caused by recruitment of lymphocytes and eosinophils to nasal mucosa which contributes to congestion

102
Q

What is non-allergic rhinitis?

A

Any rhinitis, acute or chronic, that does not involve IgE

103
Q

What are some of the causes of non-allergic rhinitis?

A

•Infection - infectious rhinitis (largely viral) •hormonal imbalance - hormonal rhinitis (e.g. pregnancy) •vasomotor disturbances - vasomotor rhinitis • Nonallergic rhinitis with eosinophilia syndrome (NARES) • Medications - drug induced rhinitis

104
Q

What happened to blood flow in rhinitis and rhinorrhea?

A
  • increased mucosal blood flow - increased blood vessel permeability
105
Q

What are the main targets of treatment of rhinitis and main treatment for these?

A

1) Anti-inflamamtory
2) Mediator receptor blockade
3) Nasal blood flow
4) Anti-allergic

106
Q

What is main treatment for the anti-inflammatory target of rhinitis?

A

glucocorticoids

107
Q

What is main treatment for the mediator receptor blockage target of rhinitis?

A

histamine and cysLT1 receptor antagonists

108
Q

What is main treatment for the nasal blood flow target of rhinitis?

A

vasoconstrictors

109
Q

What is the mechanism of glucocorticoids in rhinitis?

A

Reduce vascular permeability, activity of inflammatory cells and the release of cytokines and mediators

110
Q

What is main treatment for the anti-allergic target of rhinitis?

A

sodium cromoglicate

111
Q

How are glucocorticoids most often administered in rhinitis?

A

Nasal spray often as a monotherapy

112
Q

What is the mechanism of anti-histamines (H1 antagonists) in rhinitis?

A

Competitive antagonists of H1 receptors reduce effects of mast cell derived histamine that include:

  • vasodilatation and increased capillary permeability
  • activation of sensory nerves
  • mucus secretion from submucosal glands
113
Q

What are the effects of anti-histamines?

A

-reduced vasodilatation and increased capillary permeability -reduced activation of sensory nerves -reduced mucus secretion from submucosal glands

114
Q

What are examples of anti-histamines?

A

Loratadine, Fexofenadine and cetirizine

115
Q

What is the main function of anti-muscarinics in rhinitis?

A

inhibit the production of secretion from nasal glands due to ACh released from parasymp. fibres

116
Q

What is the main anti-muscarinic used in rhinitis?

A

Ipratropium

117
Q

What is the main leukortrine receptor antagonist used in rhinitis?

A

Montelukast

118
Q

What is mechanism of vasoconstrictors in rhinitis?

A

Mimic the effects of noradrenaline to have vasoconstrictive actions via alpha 1 adrenceptors. This reduces the swelling in vascular mucosa.

119
Q

What is the main vasoconstrictor used in rhinitis?

A

Oxymetazoline - a selective alpha 1 adrenorecepetor agonist

120
Q

Where are the M3, M2 and M1 receptors located?

A

M1 - ganglia

M2 - postganglionic

M3 - smooth muscle (present in the airways)

RW Respiratory (17 decks)

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