Introduction to Bronchodilators

Question 1

List all the types and subtypes of bronchodilators.

Answer 1

adrenergic bronchodilators (short vs long acting), anticholinergic bronchodilators, xanthine bronchodilators

Question 2

Describe the effects of the a receptors.

Answer 2

vasoconstriction, vasopressor

Question 3

Describe the effects of B1 receptors.

Answer 3

increased myocardial conductivity/HR/force of contraction

Question 4

Describe the effects of B2 receptors.

Answer 4

bronchodilation, inhibition of inflammatory mediator release, stimulation of mucociliary clearance

Question 5

Define isomers.

Answer 5

identical formula, different structures

Question 6

Describe the 2 spatial arrangements of bronchodilators and the receptors they are activeon.

Answer 6

S-epi: not active on B adrenergic receptors

r-epi: active on a/w B adrenergic receptors, producing bronchodilation

Question 7

List the steps involved in adrenergic bronchodilators B and A2 activation.

Answer 7

catecholamine attaches to receptors causing conformational change which decreases affinity of a subunit of G protein for GDP (replaced with GTP), a subunit dissociates and connects with adenylyl cyclase, this catalyses synthesis of second messenger cAMP, inactivates myosin light chain kinase (dereased intracellular calcium), smooth muscle relaxation

Question 8

Describe the mechanism of action of direct-acting adrenergic (sympathomimetic) bronchodilators.

Answer 8

mimic NE, bind to adrenoceptors

increased HR/BP, a/w smooth muscle relaxation, glycogenolysis, skeletal muscle tremor, CNS stimulation

Question 9

Describe the mechanism of action of indirect-acting adrenergic (sympathomimetic) bronchodilators.

Answer 9

increased accumulation of NE at synapse, lead to non specific adrenoceptor activity in the post-synaptic cell

Question 10

Describe the Keyhole Theory of B2 specificity.

Answer 10

addition of complex groupings to amine side chains increase B2 specificity (the larger the side chain attachment to a catechol base, the greater the specificity for B2 receptors)

allows sympathomimetic drug to conform more closely to B2 receptor on a/w smooth muscle (leads to activation of secondary messenger system and relaxation of smooth muscle)

Question 11

Catecholamine metabolism performed by monoamine oxidase (MAO) is carried out where? Describe the process.

Answer 11

in the neurons, oxidative deamination (removal of -NH2)

Question 12

Catecholamine metabolism performed by catechol-o-methyltransferase (COMT) is carried out where? Describe the process.

Answer 12

in non-neuronal tissues, methylation to the OH- at carbon 3

Question 13

What is the resulting product of catecholamine metabolism?

Answer 13

inactive on adrenergic receptors

Question 14

What is the duration of action of catecholamines/agonists?

Answer 14

up to 3 hours

Question 15

What is the major clinical indication of adrenergic bronchodilators?

Answer 15

presence of reversible airflow obstruction

Question 16

What is the major indication of short-acting agents?

Answer 16

acute reversible airflow obstruction in asthma or other obstructive a/w diseases

Question 17

What are the 3 major indications for long-acting agents?

Answer 17

maintenance bronchodilation, control of bronchospasm, and control of nocturnal symptoms

Question 18

Which receptors will be acted upon to achieve parasympathetic control/anticholinergic agents?

Answer 18

Muscarinic in a/w: M1 (nasal mucosa), M2 (heart), M3 (a/w smooth muscle), blood vessels

Question 19

What are muscarinic receptors blocked by?

Answer 19

atropine

Question 20

Anticholinergic (parasympatholytic) agents are known as what type of compounds? What is the mechanism of action? CNS effects? Systemic effects?

Answer 20

tertiary ammonium compounds

block muscarinic receptors, antagonize action of ACh

easily circulating and can cause CNS effects

poorly absorbed compounds in the bloodstream, less systemic effects

Question 21

Describe the mechanism of action of anticholinergic bronchodilators.

Answer 21

competitive antagonism of ACh at M3 cholinergic receptors, inhibits guanylyl cyclase which causes cGMP suppression

decreased cGMP prevents a/w smooth muscle contraction, glandular secretions, and histamine release

Question 22

Describe the steps involved in the M3 receptor blockade.

Answer 22

• ACh binds to M3 receptor, conformational change
• decreases affinity of a subunit of G protein
• a subunit dissociates, connects with phospholipase C
• increase synthesis of second messenger IP3 and DAG, increases cytoplasmic concentration of Ca (smooth muscle contraction/increased secretions)
• *anticholinergic
  bronchodilator administered
• blocks receptor and ACh cannot bind
• sequence of events that would normally cause smooth. muscle contraction is interrupted, resulting in smooth muscle relaxation

Question 23

List 3 specific indications for antimuscarinic/anticholinergic bronchodilators.

Answer 23

chronic bronchitis, emphysema, vagally, mediated asthma

Question 24

Describe the respiratory tract, CNS, eye, and CV effects relating to anticholinergics. Precautions?

Answer 24

resp - inhibits mucociliary clearance, relaxes a/w smooth muscle

CNS - restlessness, irritability, drowsiness, fatigue, mild excitement, *increased doses may lead to disorientation, hallucinations, or coma

eye - pupil dilation, blurred vision, *increased intraoccular pressure in glaucoma patients

CV - decreased heart rate

Question 25

Describe xanthines.

Answer 25

nitrogenous compound found in many organs and bodily fluids, alkaloids commonly used for their effects as mild stimulants and are used for the same reasons as bronchodilators

Question 26

Describe methylxanthines.

Answer 26

methylated drugs (+ CH3 group) derived from xanthines, additional methyl group to a substrate

Question 27

List the 6 general pharmacologic properties of xanthine bronchodilators.

Answer 27

CNS stimulation, cardiac muscle stimulation, diuresis, smooth muscle relaxation, peripheral and coronary vasodilation, cerebral vasoconstriction

Question 28

Methylxanthines promote and inhibit what? What types of patients? Delay release/formation of what?

Answer 28

promote relaxation of a/w smooth muscle and inhibit glandular secretions in cases of refractory asthma

patients who no longer respond to B2 agonists

delay release/formation of allergic mediators (histamine/leukotrienes)

Question 29

List the proposed mechanism of action in the inhibition of phosphodiesterase in xanthine bronchodilators.

Answer 29

inhibition of cAMP phosphodiesterase (PDE)

Question 30

Describe the mechanism of action behind inhibition of cAMP PDE.

Answer 30

*exact mechanism not known
PDE involved in hydrolysis of cAMP (allows for muscle contraction), increased intracellular cAMP induces bronchial relaxation (inactivates myosin light chain kinase and decreases intracellular Ca) and anti-inflammatory effects

Question 31

Describe the mechanism of action behind inhibition of adenosine in xanthine bronchodilators.

Answer 31

block a1 receptors that inhibit cAMP

adenosine stimulates A1/2 in target organs innervated by SNS (A1 = inhibition of cAMP, A2 = increases cAMP)

theophylline = inhibitor of A1/2 and block muscle contraction

A1 receptors are coupled with inhibition of adenoletcyclase and effects are opposite to those of B-adrenergic receptors

Question 32

List the proposed mechanisms of action(s) in the inhibition of adenosine in xanthine bronchodilators.

Answer 32

antagonism of adenosine, catecholamine release

Question 33

Describe the mechanism of action behind inhibition of adenosine via catecholamine release in xanthine bronchodilators.

Answer 33

possible production and release of endogenous catecholamine = bronchial relaxation

Question 34

List some clinical indications for xanthine bronchodilators.

Answer 34

considered 2nd or 3rd line agents in treatment of asthma/COPD
when patients stop responding to other bronchodilators
used to treat AOP

Question 35

What are the typical endings of muscarinic antagonists?

Answer 35

‘ium’

‘late’

Question 36

What are the typical endings of beta agonists?

Answer 36

‘ol’

Question 37

What are the typical endings of inhaled corticosteroids?

Answer 37

‘one’

‘ide’

Question 38

List the sequence for clinical use of bronchodilators for a patient with asthma.

Answer 38

ICS, LABA, LAMA

SABA prn

Question 39

List the sequence for clinical use of bronchodilators for a patients with COPD.

Answer 39

LAMA, LABA, ICS

SABA prn