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Pharmacology Flashcards

1
Q

Stimulation of post-ganglionic cholinergic fibres in the parasympathetic pathway is mediated by ___ Muscarinic Ach Receptors on ASM

A

M3

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2
Q

What does post-ganglionic stimulation of cholinergic fibres cause?

A

bronchial smooth muscle contraction

increased mucous secretion

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3
Q

Stimulation of post-ganglionic non-cholinergic fibres causes bronchial smooth muscle contraction - true or false?

A

false - causes relaxation by Nitric Oxide and Vasoactive intestinal peptide

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4
Q

Peptides involved in parasympathetic non-cholinergic fibres?

A 
Nitric Oxide (NO)
Vasoactive Intestinal Peptide (VIP)
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5
Q

Which nerve provides parasympathetic stimulation to the airway smooth muscle?

A

Vagus - CN X

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6
Q

There is no sympathetic innervation of bronchial smooth muscle in humans - true or false?

A

true

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7
Q

Stimulation of sub-mucosal glands and smooth muscle of blood vessels by post-ganglionic sympathetic fibres causes…(4)

A
  • bronchial smooth relaxation via b2-adrenoceptors
  • decreased mucous secretion mediated by b2-adrenoceptors on goblet cells
  • increased mucociliary clearance mediated by b2-adrenoceptors on epithelial cells
  • vascular smooth muscle contraction mediated by a1-adrenoceptors
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8
Q

contraction stimulated by a1-adrenoceptors

A

vascular smooth muscle

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9
Q

relaxation stimulated by b2 adrenoceptors

A

bronchial smooth muscle

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10
Q

Activation of the M3 receptors leads to activation of which G protein?

A

Gq/11

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11
Q

Gq/11 activates ____ which converts PIP2 to ____ and ____

A

PLC, IP3, DAG

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12
Q

IP3 stimulates calcium release from the _______ _______ via the ____ receptor

A

sarcoplasmic reticulum, IP3

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13
Q

Calcium induced calcium release is mediated by which receptor in smooth muscle?

A

ryanodine receptor

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14
Q

Cellular depolarisation causes the closure of voltage gated calcium channels - true or false?

A

false

causes VGCC to open and allow calcium to influx allowing contraction of the smooth muscle

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15
Q

Calcium binds and activates _______, this allows the subsequent activation of _______. Active MLCK allows phosphorylated ______ cross bridge binding to ______ via the breakdown of ATP

A

Calmodulin, MLCK, myosin, actin

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16
Q

What is calmodulin?

A

calmodulin is a cytoplasmic Ca receptor which undergoes a conformational change when bound to Ca

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17
Q

In the presence of high IC Ca, the rate of phosphorylation exceeds the rate of dephosphorylation of MLCK by myosin phosphatase - true or false?

A

true

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18
Q

How is IC calcium removed from the cell for smooth muscle relaxation?

A

primary and secondary active transport

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19
Q

Primary Active Transport

A

utilises energy in the form of ATP to drive a process of moving the ion from a low concentration to a high concentration

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20
Q

Secondary Active Transport

A

utilises energy from another process where the energy is not required to move another ion i.e. a symporter

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21
Q

In order to counteract the action M3 causing contraction, _______ activates b2 adrenoceptors which activates the G-protein ___.

A

adrenaline, Gs

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22
Q

Activation of the Gs protein stimulates the enzyme…

A

adenylate cyclase

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23
Q

adenylate cyclase produces _____ which is broken down by _____

A

cAMP, PDE

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24
Q

What does cAMP activate?

A

PKA

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25
PKA phosphorylates and stimulates MLCK - true or false?
false | PKA phosphorylates and thus inhibits MLCK
26
PKA phosphorylates and stimulates...
myosin phosphatase
27
Overall, activation of PKA causes what?
bronchial smooth muscle relaxation
28
cAMP is degraded to what by PDE?
5'AMP
29
What is the incidence of Asthma in industrialised countries?
5-10%
30
How can asthma be defined?
recurrent and reversible obstruction to airways in response to substance or stimuli that are not necessarily noxious and do not normally affect non-asthmatics
31
Examples of asthma attack causes
``` Allergens Exercise Respiratory Infections Smoke Dust Pollutants Weather ```
32
Asthma is not just bronchospasm, it is....
intermittent attacks of bronchoconstriction; tight chest, wheezing, difficulty in breathing and coughs
33
Pathological changes that occur in the bronchioles of chronic asthmatics as a result of long standing inflammation (5)
- increased mass of smooth muscle (hyperplasia/trophy) - accumulation of interstitial fluid - increased secretion of mucous - epithelial damage exposing sensory nerve fibres - sub-epithelial fibrosis
34
Airway narrowing due to inflammation and bronchoconstriction increases the ______ _______ and decrease the ____ and _____
airway resistance, FEV1, PEFR
35
Which fibres are exposed in chronic asthma?
c-fibres
36
What are the components of hyper-responsiveness in asthma?
hypersensitivity and hyperreactivity
37
Which substance can be used to provoke asthma via H1 receptors?
histamine
38
Which substance can be used to provoke asthma via M3 receptors?
methacholine
39
What type of reaction is the early phase asthma attack?
type I hypersensitivity (bronchospasm)
40
What type of reaction is the late phase asthma attack?
type IV hypersensitivity (bronchospasm and inflammatory)
41
What response is normal following exposure to an allergen?
low levels of Th1 involving IgG and macrophages
42
Cell-mediated response following exposure to an allergen
low levels Th1 IgG Macrophages
43
Preferred allergen response pathway in asthmatics
Th2 anti-body mediated response
44
Antigen presenting cell presents allergen to ____ T cells which differentiate into ___ cells.
CD4+, Th0
45
In asthmatics, Th2 cells activate ____ cells which mature into ______ cells which secrete ____.
B, Plasma, IgE
46
What do Th2 cells secrete that enhances the B cell response?
IL-4
47
What interleukin do Th2 cells secrete to activate eosinophils?
IL-5
48
IL-13
activates mast cells which express IgE receptors in response to ILs
49
IL4
activates B cells and also mast cells to express IgE receptors
50
Cells which have IgE receptors to help activate them
eosinophils and mast cells
51
During activation, IgE receptors dimerise and allow Ca entry into the mast cells - true or false?
true
52
Mast cells release...
preformed histamine and other agents including leukotrienes LTC4 and LTD4. Substances (PAF and LTB4, PGDs) that attract pro-inflammatory mediators and cells
53
Leukotrienes cause...
airway smooth muscle contraction
54
Cells that cause inflammation in asthma
mononuclear cells | eosinophils
55
Key cells in the immediate phase of an asthma attack
mast cells and mononuclear cells
56
mast cells and mononuclear cells produce
- spasmogens, CysLTs, Histamine -> bronchospasm | - chemotaxins and chemokines -> late phase
57
Late phase asthma attack involves...
infiltration of cytokine releasing Th2 and monocytes, activation of inflammatory cells in particular eosinophils
58
During the late phase, mediators and CysLTs cause ______ _______, hyper-responsiveness, bronchospasm, ________, cough and ________.
airway inflammation, wheezing, mucous
59
During the late phase, eosinophils and major basic and cationic proteins cause epithelial damage, ______ _______, hyper-responsiveness, bronchospams, wheezing, ______ and mucous
airway inflammation, cough
60
Step 1 Asthma treatment
SABA
61
Step 2 Asthma treatment is given when...
SABA use is more than once daily
62
Step 2 asthma treatment
regular ICS
63
Step 3 Asthma treatment
Add LABA with ICS If LABA is not effective increase ICS dose, discontinue LABA If still not adequate consider other therapies i.e. monteleukast or theophylline
64
Step 4 asthma treatment
persistent poorly controlled, increase ICS and add 4th drug i.e. Monteleukast, theophylline, oral b2-agonist
65
Step 5 asthma treatment
introduce oral glucocorticoid and refer to specialist
66
B2-adrenoceptor agonists act as phsyiological ______ of all spasmogens.
antagonist
67
b2 agonists activate Gs --> AC which converts ATP to _____ which activates _____
cAMP | PKA
68
Types of b2-agonist
SABA, LABA, ultra long acting
69
Examples of SABA
salbutamol tertabutaline albuterol
70
SABAs are the _____ line treatment in ______, _________ asthma and are used as relievers when ______
first, mild, intermediate, required
71
SABAs are usually administered orally or nebulised - true or false?
false | usually in MDI, oral and IV or nebulised is used in severe and life-threatening asthma
72
Overall effects of SABAs (3)
bronchial smooth muscle relaxation increased mucus clearance decreased mediator release from mast cells and monocytes
73
Adverse effects of SABAs
fine tremor tachycardia cardiac dysrhytmia hypokalaemia
74
Examples of LABAs
Salmeterol | Formoterol
75
What are LABAs not recommended for?
acute relief of bronchospasm | monotherapy
76
Why are LABAs not recommended for monotherapy?
desensitisation to b-agonist by reducing the number of receptors
77
Examples of CysLT1 Receptor Antagonists
Monteleukast | Zafirlukast
78
LTC4, LTD4 and LTE4 are derived from ______ cells and infiltrate inflammatory cells causing smooth muscle ______, mucous _______ and _______.
mast, contraction, secretion, oedema
79
Examples of xanthines
theophylline and aminophylline
80
Suggested mechanism of action of methylxanthines
inhibition of PDE III and IV
81
What sort of mechanisms are exhibited by methylxanthines?
bronchodilator and anti-inflammatory
82
Theophylline activates HDAC which may ______ the activity of glucocorticoids
potentiate
83
Adverse effects of methylxanthines
``` dysrhythmias seizures hypotension nausea vomiting GI upset Headache ```
84
Reason for methylxanthines being problematic
drug interactions involving CYP450s, particularly antibiotics that inhibit CYP450
85
Glucocorticoids are produced in the ______ ________ of the adrenal cortex
zona fasiculata
86
Glucocorticoids are essential in regulating: (5)
``` decreased inflammatory responses decreased immunological responses increased liver glycogen deposits increased gluconeogenesis increased glucose output from the liver ```
87
Main mineralocorticoid
aldosterone
88
Site of production of mineralocorticoids
zona glomerulosa
89
Action of glucocorticoids
anti-inflammatory
90
In particular glucocorticoids decrease the formation of....
Th2 cytokines
91
Glucocorticoids prevent the production of IgE and influx of...
eosinophils and mast cells
92
common side affects of inhaled glucocorticoids
hoarse and weak voice, thrush
93
When might oral prednisolone be given?
when there is an exacerbation or severe asthma
94
Cromones are often described as _____ ____ ______ even though this is not their mechanism of action. An example is _______ _______
mast cell stabilisers | sodium cromoglicate
95
cromones are more effective in...
children and young adults
96
sodium cromoglicate is used to reduce _____ phases of an attack but efficacy may take several weeks to develop a block to _____ ______ attack
both. | late phase
97
Monoclonal antibodies used in asthma
IgE - Omalizumab | IL-5 - Mepolizumab
98
Preferred pharmacological target in the treatment of COPD?
M1 and M3 muscarinic receptors
99
Why is it preferable to avoid M2 receptors in the treatment of COPD?
the M2 receptor is a auto-regulatory receptor which provides negative feedback when stimulated.
100
Which immune cells are activated in COPD?
neutrophils, CD8 T cells and macrophages
101
SAMA examples
ipratropium & oxitropium
102
LAMA examples
tiotropium & aclidinium
103
Route of administration for SAMA and LAMA and why?
inhalational to avoid blocking systemic parasympathetic nervous system
104
B-adrenoceptor agonists used in COPD?
salbutamol, salmeterol, formoterol
105
Rofumilast
PDE4 selective inhibitor which suppresses inflammation and emphysema
106
Rhinitis or Rhinorrhoea may be allergic or non-allergic - TRUE or FALSE?
true
107
in allergic rhinitis, what mediators may be released that contribute to the inflammatory response?
IgE, cysLTs, histamine, tryptase, prostaglandins,
108
non-allergic causes of rhinitis
infection, hormonal, vasomotor, non-allergic rhinitis with eosinophilia syndrome, medications
109
treatment targeting inflammation in rhinitis?
glucocorticoids
110
glucocorticoids used in rhinitis?
beclometasone | fluticasone
111
treatments targeting receptors in rhinitis?
H1 receptor antagonists, CysLT1 receptor antagonists
112
H1 receptor antagonists used in rhinitis
fexafenadine citerizine loratidine
113
CysLT1 receptor antagonists used in rhinitis?
montelukast
114
oxymetazoline is used as...
a selective a1 adrenoceptor agonist for vasomotor rhinitis
115
indications of using oxymetazoline
can only be used for a short time because of rebound increase in congestion upon discontinuation

Y1 Respiratory (20 decks)

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