Pharmacology

Question 1

what does stimulation of cholinergic postganglionic fibres do to ASM

Answer 1

M3 muscarinic Ach receptors cause ASM to contract increased mucus secretion on goblet cells

Question 2

what do non cholinergic postganglionic fibres do to ASM

Answer 2

muscle relaxation

mediated by Nitric oxide and VIP

Question 3

What does the sympathetic division do to ASM

Answer 3

no direct effect, but causes release of adrenaline into system which binds to beta 2 adrenoceptors to relax ASM cells, decrease goblet cell secretion and increase activity of mucociliary escalator

Question 4

smooth muscle contraction in heart is regulated by

Answer 4

alpha 1 adrenoceptor

Question 5

Describe the chain of events which cause ASM contraction

Answer 5

IP3 allows calcium entry to cell to phosphorylate MLC to MLCK and allows sliding of actin and myosin for contraction

Question 6

How is ASM relaxed

Answer 6

Adrenaline binds to B2 adrenoceptors to produce cAMP and inhibit MLCK. dephosphorylates MLC by myosin phosphatase

Question 7

What is asthma

Answer 7

recurrent and reversible obstruction to airways in response to substances that are not necessarily noxious

Question 8

what are causes of asthma

Answer 8

allergens

cold air, environmental pollutants, dust and smoke

Question 9

What is asthma an onset of and what can it involve

Answer 9

Acute, intermittent attacks of bronchoconstriction

involves pathological changes to bronchioles form longstanding inflammation

Question 10

What are the long term consequences of asthma

Answer 10

hyperplasia and hypertrophy of smooth muscle
Oedema
Sub epithelial fibrosis
epithelial damage that exposes sensory nerve endings
increased secretion of mucus

Question 11

airway resistance is increases. how does this affect FEV1 and PEFR

Answer 11

Decreased FEV1 and peak expiratory flow rate (PEFR)

Question 12

how is bronchial hyperresponsiveness caused

Answer 12

increased airway sensitivity due to exposure of sensory nerve endings
Inflammation induced by release of peptides by these endings

Question 13

What is hyperreactivity

Answer 13

excessive response made due to presence of sensitive stimuli

Question 14

What is hypersensitivity

Answer 14

more prone to abnormal respons in presence of particular antigen

Question 15

how is hyperreactivity diagnosed

Answer 15

Administration of spasmogens to test spasm of bronchioles

Mannitol, histamine, methacholine

Question 16

How many phases does an asthma attack have and what are they

Answer 16

2
Immediate bronchospasm
Delayed inflammatory response

Question 17

what reaction does a nonatopic individual have to an allergen

Answer 17

TH1 response with Immunoglobulin G

Question 18

what response does an atopic asthmatic individual have presented with an allergen

Answer 18

TH2 response with IgE

usually a poor prognosis

Question 19

how does atopic allergic asthma develop

Answer 19

dendritic cell presents allergens antigens to CD4 T cell
proliferates to TH0 cell and then a TH2, producing a cytokine environment
TH2 promotes proliferation of B cells by IL-4, proliferating to plasma cells secreting IgE

Question 20

What does IgE in an asthmatic do

Answer 20

IgE, IL-4, IL-13 cause calcium entry into mast cells which causes histamine and leukotrine release
Prostaglandins released which attract other inflammatory cells

Question 21

what two part of asthma should be treated in consideration with drug prescription

Answer 21

drugs that treat the acute asthma phase as well as long term immune and inflammatory treatment

Question 22

2 rough classes of drugs in asthma treatment

Answer 22

Relievers

Preventors

Question 23

How do B2 adrenoceptor agonists work?

Answer 23

increases cAMP so phosphorylates myosin phosphatase to inhibit MLCK and relaxes smooth muscle

Question 24

Names of 3 SABA drugs and their adverse effects

Answer 24

Salbutamol
Albuterol
Terbutaline
Few adverse effects noted, except fine tremor, tachycardia and cardiac dysrythmia due to presence of B2 adrenoceptors on cardiac muscle

Question 25

how are SABA administered and what do they do

Answer 25

Usually inhaler to minimize systemic effect rapid acting on bronchial smooth muscle, reduced constriction as well as decreasing mediator release from mast cells and increasing mucus clearance

Question 26

Name of LABAs

Answer 26

formoterol | salmeterol

Question 27

What are LABA most used for?

Answer 27

not great for acute bronchospasm but used in nocturnal treatment Add on therapy, not monotherapy

Question 28

What must a LABA always be administered with?

Answer 28

Glucocorticoid

Question 29

true/false - beta blockers are safe for use with SABA/LABA

Answer 29

false - it is contraindicted due to risk of bronchospasm. beta blockers are B2 adrenoceptor antagonists

Question 30

Why is isoprenaline redundant for use in asthma

Answer 30

it is non selective between B2-adrenoceptors and cardiac B1-adrenoceptors so can increase heart rate

Question 31

What do cysteinyl leukotrine receptor antagonists act on

Answer 31

competitively on CysL1 receptor to inhibit it

Question 32

what are cysteinyl leukotrines derived from and what do they do

Answer 32

Derived from mast cells | Increase smooth muscle contraction, mucus secretion and oedema

Question 33

name of CysLT1 receptor antagonist and how they are used

Answer 33

monteleukast zafirlukast add on with other medications by oral route not recommended for relief of acute phase asthma

Question 34

Name 2 Methylxanthines

Answer 34

theophylline | aminophylline

Question 35

What are xanthines believed mechanism of action?

Answer 35

inhibits PDE so prevents breakdown of cAMP and so cAMP continues to stimulate pathway that relaxes ASM

Question 36

Xanthines are used in combination with ____

Answer 36

B2-adrenoceptor agonists and glucocorticoids

Question 37

What do xanthines do?

Answer 37

can be bronchodilators at high dose anti inflammatory mediation by mast cell inhibition increased mucus clearance

Question 38

true/false - xanthines have a large window of therapeutic treatment with little contraindication

Answer 38

False- narrow range | severe contraindication in use with antibiotics like CYP450s

Question 39

How do xanthines improve lung ventilation

Answer 39

increase diaphragmatic contractility and reduce fatigue

Question 40

What are the two types of steroid hormones synthesised by the adrenal cortex

Answer 40

glucocorticoids | mineralocorticoids

Question 41

What are glucocorticoids and what is the main one in man

Answer 41

corticosteroids which regulate decrease of inflammatory and immunological responses Hydrocortisone

Question 42

what are mineralocorticoids and what is the main one

Answer 42

Corticosteroids which regulate the retention of salt and water by the kidney aldosterone

Question 43

true/false - inhaled glucocorticoids are given for acute bronchoconstriction

Answer 43

fasle - they do not have any bronchodilator effect and are given as a prophylaxis by inhalation

Question 44

3 types of glucocorticoids and how are they administered

Answer 44

beclometasone budesonide fluticasone administered by inhaler in metered dose

Question 45

glucocorticoids signal by _____ receptors

Answer 45

nuclear

Question 46

glucocorticoids combine with what receptor in the cytoplasm to translocate to the nucleus

Answer 46

GRa

Question 47

what happens to glucocorticoids in the nucleus

Answer 47

monomers assemble into homodimers and bind to glucocorticoid response elements in promoter region

Question 48

transcription of genes can be ...

Answer 48

transactivated or transrepresed

Question 49

How do glucocorticoids affect transcription of inflammatory genes besides transrepression

Answer 49

deacylation of histones, condensing them and preventing them from being transcribed

Question 50

Name a chromone and its frequency and means of use

Answer 50

sodium chromoglicate | used infrequently, and in prophylaxis by inhalation

Question 51

what phase of asthma can chromones treat and who is it effective in

Answer 51

both phases, but can take weeks to work | more effective in children and young adults

Question 52

what is omalizumab?

Answer 52

a monoclonal antibody treatment of asthma, binds IgE with Fc to prevent attachment to mast cell receptors

Question 53

How do muscarinic ACh receptor antagonists work

Answer 53

antagonists of M3 receptor activation - prevents binding of ACh which causes bronchoconstriction

Question 54

What does M1 do

Answer 54

facilitates fast neurotransmission mediated by ACh

Question 55

what does M2 do

Answer 55

inhibitory autoreceptor - reduce ACh release

Question 56

What does M3 do

Answer 56

Present on ASM and mediates contraction in response to ACh binding

Question 57

Why are broad spectrum muscarinic antagonists not useful and name one

Answer 57

they inhibit all muscarinic receptors in the body. Atropine

Question 58

Name SAMA

Answer 58

ipratropium | non selectively blocks M1,2,3

Question 59

name 4 LAMAs

Answer 59

Tiotropium Glycopyrronium Aclidinium Umeclidinium

Question 60

describe how SAMA/LAMAs are administered, adverse effects and their action mechanism

Answer 60

``` Inhalation Little adverse effect due to quaternary ammonium group delayed onset bronchodilator decrease mucus secretion they do little to stop COPD progression ```

Question 61

Why are selective muscarinic antagonists that bind selectively to M3 better than iprotropium

Answer 61

they prevent the unwanted block of M2, which helps to block the release of ACh

Question 62

true/false - a beta agonist and muscarinic antagonist are better in combination than either drug alone

Answer 62

true

Question 63

why are LABA/LAMA combinations logical

Answer 63

they work in opposite yet complementary ways to relax smooth muscle

Question 64

Name a PDE4 inhibitor and how they work

Answer 64

Rofumilast | Inhibits PDE4 to suppress inflammatory and immune cells to suppress inflammation and emphysema

Question 65

when would a glucocorticoid be administered with a beta agonist and LAMA/LABA and how could they be administered

Answer 65

eosinophilic COPD | Potentially administered separately or in triple inhaler

Question 66

when might a glucocorticoid not work in a patient with eosinophilic COPD

Answer 66

Oxidative/nitrative stress - chronic inhalation of cigarette smoke

Question 67

What is rhinitis and how could it be caused

Answer 67

Acute or chronic inflammation of nasal mucosa | Can be allergic, non allergic or mixed

Question 68

How can allergic rhinitis be classified and what does it strongly resemble in terms of similarity

Answer 68

Seasonal Perennial Episodic Linked to asthma

Question 69

What type of rhinitis involves allergic and non allergic compounds

Answer 69

occupational

Question 70

How is non allergic rhinitis classed as such and what are its causes

Answer 70

it isnt involved with IgE dependent events | Infectious, hormonal, vasomotor, NARES, drug induced

Question 71

What rhinitis can corticosteroids be used and which ones are used

Answer 71

SAR and PAR | Prednisolone (oral), beclometasone, fluticasone

Question 72

How do antihistamines treat allergic rhinitis and which are used

Answer 72

competitive agonists to H1 receptor, reduce effects of mast cell derived histamine Cetirizine, Loratidine, fexofenadine

Question 73

What muscarinic antagonist can be used and how does it stop rhinorrhoea

Answer 73

Iprotropium | Prevents binding of ACh which causes watery secretion from glands

Question 74

what drug used in rhinitis treatment stabilises mast cells and is not as effective as a corticosteroid

Answer 74

Sodium cromoglicate

Question 75

CysLTR antagonists

Answer 75

reduce effect of CysLTs Oral route for asthma and allergic rhinitis montelukast

Question 76

Vasoconstrictors

Answer 76

Mimic effect of noradrenaline to vasoconstrict vessels | Oxymetazoline