MP324 - PHARMACOLOGY

Question 1

short-acting B2 adrenoceptor agonists

Answer 1

salbutamol
piralbuterol
levalbuterol

Question 2

mechanism of action of B2 adrenoceptor agonists

Answer 2

• function via a cyclin AMP-dependent relaxation of smooth muscle
• Ins(1,4,5)P3 receptor in the sarcoplasmic reticulum
• may be inactivated by protein kinase A (less calcium is released, inhibits contraction)

Question 3

function of stimulating adenylyl cyclase

Answer 3

this enzyme catalyses the formation of cyclic AMP

cAMP then activates protein kinase A

Question 4

actions of protein kinase A

Answer 4

inhibit MCLK
promote calcium efflux
inhibit the MPK pathway by phosphorylating and inhibiting Raf-1 kinase

Question 5

mechanism of action of long-acting B2 adrenoceptor agonists

Answer 5

have lipophilic groups attached which interact with exo-sites on the receptor

Question 6

problem with B2 adrenoceptor agonists

Answer 6

desensitisation

however less with salmeterol because partial agonist

Question 7

3 mechanisms of desensitisation

Answer 7

• phosphorylation of the occupied receptor by B-adrenoceptor kinase (B-ARK)
• internalisation of the receptor
• phosphorylation of the occupied receptor by protein kinase B (negative feedback)

Question 8

corticosteroids

Answer 8

beclamethasone
budesonide
fluticasone
mometasone
ciclesonide

Question 9

mechanism of action of corticosteroids

Answer 9

• dampen inflammation
• used as prophylactic therapy

Question 10

standard oral steroid

Answer 10

prednisolone

Question 11

intravenous steroids

Answer 11

hydrocortisone
methylprednisolone

Question 12

glucocorticoid effect on mediators

Answer 12

blocked/inhibited mediators:
- PAF
- LTB4
- PGD2
- Histamine

Question 13

steroid side effects

Answer 13

• weight gain/water retention
• mood changes
• increased appetite
• sweating/rashes
• shortness of breath
• sleep problems/moon face

Question 14

leukotriene inhibitors

Answer 14

zafirlukast
montelukast

Question 15

leukotriene B4

Answer 15

neutrophil chemoattractant

Question 16

leukotriene C4 and D4

Answer 16

cause bronchoconstriction
increased bronchial reactivity, mucosal oedema and mucous hypersecretion

Question 17

montelukast unique side-effects

Answer 17

eosinophilia
Churg Strauss syndrome (eosinophil granulomatosis in small vessels)

Question 18

xanthines

Answer 18

theophylline
emprofylline

Question 19

mechanism of adenosine receptor antagonists

Answer 19

block the inhibitory action of adenosine upon adenylyl cyclase (via its receptors), and allow intracellular cAMP to accumulate and promote relaxation

Question 20

mechanism of phosphodiesterase inhibitor

Answer 20

blocks reduction in intracellular cAMP and relax smooth muscle; increase catecholamines release

Question 21

effects of theophylline in asthma

Answer 21

• smooth muscle relaxation
• inhibit anaphylactic release of mediators
• suppress oedema
• central stimulation of ventilation

Question 22

problems with xanthines

Answer 22

• doses should be low to avoid gastro-abdominal problems
• CNS stimulation is a problem when maintenance administration is increased too quickly
• toxicity is a risk of seizures and arrhythmias

Question 23

oral theophylline most serious side-effects

Answer 23

anorexia
vomiting
mild CNS stimulation

Question 24

problems with xanthines through IV routes

Answer 24

increase arrhythmia, palpitations, and tachycardia at doses above 30mg/L

Question 25

long-acting B2 adrenoceptor agonists

Answer 25

salmeterol formoterol

Question 26

clinical efficacy of SABA (salbutamol)

Answer 26

- onset of action is within 3 minutes - peak activity after 2.5 hours - duration of action is between 4-6 hours

Question 27

clinical efficacy of LABA (salmeterol vs formoterol)

Answer 27

- option for patients that are symptomatic despite regular SABA use - both are lipophilic, but the water solubility of formoterol lets it diffuse rapidly to the B2AR and cause bronchodilation in between 1-3 min - salmeterol has longer onset of action

Question 28

side effects of SABAs

Answer 28

tachycardia/palpitations tremor hypokalemia headache

Question 29

short-acting muscarinic antagonists (SAMAs)

Answer 29

ipratropium bromide

Question 30

mechanism of action of SAMAs

Answer 30

- blocks all muscarinic receptors without sub-type selectivity - onset of action within minutes - peak activity between 1-2 hours - duration of action approximately 4 hours

Question 31

long-acting muscarinic antagonists (LAMAs)

Answer 31

tiotropium

Question 32

mechanism of action of LAMAs

Answer 32

- binds to M1-M3 receptors and is 10x more potent than SAMAs - dissociates slowly from M1 and M3 receptors - dissociates relatively rapidly from M2 receptor (kinetic selectivity) -onset occurs within 30 min - peak activity at 3 hours - duration of action over 24hours

Question 33

why are muscarinic receptors a good target

Answer 33

parasympathetic activity mediates both bronchial smooth muscle contraction and the release of mucus into the airway lumen through stimulation of muscarinic receptors

Question 34

location of M1 receptors

Answer 34

expressed in peribronchial ganglia

Question 35

location of M3 receptors

Answer 35

bronchial smooth muscle cells

Question 36

location of M2 receptors

Answer 36

post ganglionic parasympathetic nerve and act as auto receptors

Question 37

adverse effects of muscarinic antagonists

Answer 37

associated with its anti-cholinergic activity - dry mouth - exacerbation of narrow-angle glaucoma and myasthenia gravis (autoimmune disease)

Question 38

oxygen therapy reduces...

Answer 38

- haematocrit - pulmonary artery pressures - rapid eye movement related hypoxemia