Pharmacology Flashcards
1
Q
What does stimulation of postganglionic cholinergic fibres cause?
A
- broncial smooth muscle contraction mediated M3 muscarinic ACh receptors on ASM cell
- increased mucus secretion mediated by M3 muscarinic Act receptors on gland cells
2
Q
What does stimulation of postganglionic noncholinergic fibres cause?
A
- bronchial smooth muscle relaxation mediated by Nitric oxide and vasoactive intestinal peptide
3
Q
What does post ganglionic stimulation in the sub mucosal glands and smooth muscle of the blood vessels cause?
A
- bronchial smooth muscle relaxation via B2 adrenoceptors on ASM cells activated by adrenaline released from adrenal gland
- decreased mucous secretion
- increased mucocilary clearance
- vascular smooth muscle contraction
4
Q
describe the initiation of contraction by Ca2+ in smooth muscle?
A
- rise in cytoplasmic Ca2+
- interacts with calmodulin
- activating MLCK
- drives movement of myosin and actin across each other
- causes cell to contract
5
Q
How does relaxation of smooth muscle occur?
A
It results from the dephosphorylation of MLC by myosin phosphatase
6
Q
Describe the pathological changes that occur in asthma?
A
- increased mass of smooth muscle
- accumulation of interstitial fluid
- increased secretion of mucous
- epithelial damage
- sub - epithelial fibrosis
7
Q
Describe the phases of an asthma attack
A
- type 1 hypersensitivity reaction: early phase, bronchospasm and acute inflammation
- type 2 hypersensitivity: late phase: bronchospasm and delayed inflammation
8
Q
Describe the immune reaction to an allergen in an atopic individual?
A
Allergen > phagocytosis > strong Th2 response, antibody mediated immune response involving IgE
9
Q
What do cross liked IgE receptors do?
A
- stimulates calcium entry into mast cells (degranulation)
- simulates release of calcium from intracellular stores (inflammation)
10
Q
What are relievers in the treatment of asthma?
A
- act as bronchodilators
- SABAs
- LABAs
- CysLT1 receptor antagonists
11
Q
what are controllers in the prevention of asthma?
A
- act as anti inflammatory agents that reduce airway inflammation
- glucocorticoids
- cromoglicate
- IgE antibodies
12
Q
SABA B2 adrenoceptor agonists
A
- salbutamol
- relievers taken as needed
- administered via inhalation
- act rapidly
- increase mucous clearance and decrease mediator release from mast cells and monocytes
- few side effects
13
Q
LABA B2 adrenoceptor agonists
A
- salmeterol, formoterol
- not for acute relief of bronchospasm
- useful for nocturnal asthma
- can be used as add on therapy with glucocorticoid
14
Q
CysLT1 receptor antagonists
A
- montelukast, zafirlukast
- add on therapy against early and late bronchospasm in mild asthma
- relax bronchial smooth muscle in response to cysLTs
- oral administration
- side effects: headache, GI upset
15
Q
Xanthines
A
- methylxanthines
- combine bronciodilator and anti inflammatory actions
- administered orally
- very narrow therapeutic window
- many adverse side effects
16
Q
what are synthetic derivatives of cortisol used for?
A
- they are used for their anti inflammatory effects in the treatment of asthma
- delivered via inhalation
17
Q
describe the mechanism of action of glucocorticoids?
A
- signal via nuclear receptors (GRa)
- combine with GRa and produce inhibitory heat shock proteins
- activated receptor monomers assembled to homodimers and bind to GRE
- transcription of genes is either switched on or off
18
Q
What glucocorticoid is given in severe/rapidly deteriorating asthma?
A
- oral predinisolone combination with inhaled steroid
19
Q
What are cromones?
A
- second line drugs infrequently used prophylactically in the treatment of allergic asthma
- delivered by inhalation
- can reduce both phases of an asthma attack
- more effective in children
20
Q
Describe the role of muscarinic receptor antagonists in COPD?
A
They act as pharmacological antagonists of bronchoconstriction caused by smooth muscle M3 activation in response to ACh released from post ganglionic parasympathetic fibres
21
Q
describe the mechanism of COPD?
A
smoking causes the stimulation of resident alveolar macrophages which promotes cytokine production and activation of neutrophils, CD8 T cells and increased macrophage numbers. metalloproteins and free radicals are then released which leads to chronic bronchitis/emphysema
22
Q
what are the characteristics of chronic bronchitis?
A
- inflammation of bronchi and bronchioles
- cough
- clear mucoid suptum
- infections with purulent sputum
increasing breathlessness
23
Q
What are the characteristics of emphysema
A
- distension and damage to alveoli
- destruction of acing pouching in alveolal sacs
- loss of elastic recoil
24
Q
how does the expiration phase differ in a patient with COPD
A
much greater resistance to airflow during expiration
25
Where is the M1 receptor located?
Ganglia
26
where is the M2 receptor located?
post ganglionic neurone terminals
27
where is the M3 receptor located?
airway smooth muscle
28
What are the muscarinic receptor antagonists used in the treatment of COPD?
- ipratropium
- Tiotropium
- Glycopyrronium
- Aclidinium
- Umeclidinium
29
how do LABA/LAMA combinations work in the treatment of COPD
Drugs work by different but complementary mechanisms to cause smooth muscle relaxation
combinations are most effective when both drugs are deposited in the same location
30
What is Rhinitis
- acute or chronic inflammation of the nasal muscosa
31
Describe allergic rhinitis?
allergen triggers mast cell and basophil degranulation which stimulates the release of histamine, cysLT ect which causes the symptoms
32
What is non allergic rhinitis?
Any rhinitis, acute or chronic that doesn't involve IG5 dependent events
many different causes including infection and hormone imbalance
33
What is occupational rhinitis?
May involve both allergic and non allergic components
34
How are glucocorticoids used in the treatment of rhinitis?
- reduce vascular permeability, recruitment and activity of inflammatory cells and the release of cytokines and mediators
35
Give examples of the glucocorticoids used in the treatment of rhinitis?
- beclometasone
- fluticasone
- prednisolone (oral)
36
How are anti histamines used in the treatment of rhinitis?
they are competitive antagonists that reduce the effects of mast cell derived histamine
37
give examples of antihistamines used in the treatment of rhinitis?
- loradtidline
- fexofenadine
- cetirizine
38
How are anti cholinergic drugs used in the treatment of rhinitis?
- ACh released from post ganglionic parasympathetic fibres activates muscarinic receptors on nasal glans causing a watery secretion that contributes to rhinnorhoea - this mechanism is blocked by muscarinic antagonists (ipratropium)
39
How are cysteinyl leukotrine receptor antagonists used in the treatment of rhinitis?
CysLT1 receptor antagonists reduce the effects of CysLTs upon the nasal mucosa
- montelukast
40
how are vasoconstrictors used in the treatment of rhinitis?
- mimic the effect of noradrenaline.
produce vasoconstriction via activation of alpha1 adrenoceptors to decrease swelling in the vascular mucosa
- oxymetazoline
41
What are the BTS asthma guidelines?
- short acting B2 agonists as needed
- inhaled steroids
- + LABA/LAMA + LTRA/theo/cromone
- + oral steroid + anti IgE/anti IL5/anti IL4a
42
what are the actions of a spacer device?
- avoids coordination problems
- reduces oropharyngeal and laryngeal side effects
- reduces systemic absorption
- reduces particle size and velocity
- improves lung disposition
43
describe the anti inflammatory action of cromones?
- only used in asthma
- mast cell stabiliser - weak inflammatory cf steroids
- inhaled route only
44
describe the use of leukotriene receptor antagonists?
- used in asthma
- anti inflammatory
- 2nd line = complementary non steroidal anti inflammatory additive to inhaled steroid
- also used in allergic rhinitis
45
describe the use of montelukast?
- leukotriene receptor antagonist
- oral route
- 1x daily
- high therapeutic ratio
46
describe the mechanism of anti IgE monoclonal antibody (omalizumab)?
- inhibits the binding to the high affinity IgE receptor - inhibits TH2 response and associated mediator release from basophils/mast cells
47
describe the mechanism of anti-IL5 (mepolizumab)?
- blocks the effect of the TH2 cytokine IL5 which is responsible for eosinophilic inflammation in asthma
48
Describe the mechanism of anti IL4a (dupilumab)?
- blocks the effects of the TH2 cytokines IL4/13 which is responsible for eosinophilic inflammation, IgE, airway hyperreactivity and mucin production in asthma
- suppresses IgE and FeNO
49
salbutamol
- bronchodilator
- B2 agonist
- SABA
50
What is the mechanism of muscarinic antagonist bronchodilators?
- block post junctional end plate M3 receptors
- inhaled only
- high therapeutic ratio
51
Roflumilast
- PDE4 inhibitor
- oral tablet
- indicated for COPD only
- minimal effect of FEV1 (anti inflammatory)
- used as additive with LABA/LAMA
52
What are mucolytics?
- reduce sputum viscosity and aide sputum expectoration in COPD
- oral carbocisteine, erdosteine
- only used as an add on
53
Describe the treatment of chronic asthma?
- suppress inflammatory cascade (inh steroid)
- + non steroid anti inflammatory therapy (e.g. theophylline, anti leukotriene cromoglycate)
- +/- stabilise smooth muscle with LABA/LAMA
54
Describe the treatment of acute asthma?
- oral prednisolone
- nebulised high dose salbutamol (+/- Neb ipratropium or IV aminophylline/magnesium)
- at least 60% O2
- ITU assisted mechanical intubated ventilation if failing paO2 and rising PaCO2
55
describe the treatment of COPD?
- smoking cessation
- immunisation
- pharmacotherapy
- pulmonary rehab
- oxygen
56
describe the treatment of acute COPD?
- neb salbutamol + ipratropium
- oral prednisolone
- antibiotic if infection
- 24-28% O2 titrated against PaO2/PaCO2
- physio to aide sputum expectoration
- non invasive ventilation
- ITU intubated assisted ventilation only if reversible component
