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Flashcards in Pharmacology Deck (115):
1

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

M3

2

What does post-ganglionic stimulation of cholinergic fibres cause?

bronchial smooth muscle contraction
increased mucous secretion

3

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

false - causes relaxation by Nitric Oxide and Vasoactive intestinal peptide

4

Peptides involved in parasympathetic non-cholinergic fibres?

Nitric Oxide (NO)
Vasoactive Intestinal Peptide (VIP)

5

Which nerve provides parasympathetic stimulation to the airway smooth muscle?

Vagus - CN X

6

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

true

7

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

- 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

8

contraction stimulated by a1-adrenoceptors

vascular smooth muscle

9

relaxation stimulated by b2 adrenoceptors

bronchial smooth muscle

10

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

Gq/11

11

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

PLC, IP3, DAG

12

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

sarcoplasmic reticulum, IP3

13

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

ryanodine receptor

14

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

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

15

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

Calmodulin, MLCK, myosin, actin

16

What is calmodulin?

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

17

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

true

18

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

primary and secondary active transport

19

Primary Active Transport

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

20

Secondary Active Transport

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

21

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

adrenaline, Gs

22

Activation of the Gs protein stimulates the enzyme...

adenylate cyclase

23

adenylate cyclase produces _____ which is broken down by _____

cAMP, PDE

24

What does cAMP activate?

PKA

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