Introduction to Bronchodilators Flashcards
List all the types and subtypes of bronchodilators.
adrenergic bronchodilators (short vs long acting), anticholinergic bronchodilators, xanthine bronchodilators
Describe the effects of the a receptors.
vasoconstriction, vasopressor
Describe the effects of B1 receptors.
increased myocardial conductivity/HR/force of contraction
Describe the effects of B2 receptors.
bronchodilation, inhibition of inflammatory mediator release, stimulation of mucociliary clearance
Define isomers.
identical formula, different structures
Describe the 2 spatial arrangements of bronchodilators and the receptors they are activeon.
S-epi: not active on B adrenergic receptors
r-epi: active on a/w B adrenergic receptors, producing bronchodilation
List the steps involved in adrenergic bronchodilators B and A2 activation.
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
Describe the mechanism of action of direct-acting adrenergic (sympathomimetic) bronchodilators.
mimic NE, bind to adrenoceptors
increased HR/BP, a/w smooth muscle relaxation, glycogenolysis, skeletal muscle tremor, CNS stimulation
Describe the mechanism of action of indirect-acting adrenergic (sympathomimetic) bronchodilators.
increased accumulation of NE at synapse, lead to non specific adrenoceptor activity in the post-synaptic cell
Describe the Keyhole Theory of B2 specificity.
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)
Catecholamine metabolism performed by monoamine oxidase (MAO) is carried out where? Describe the process.
in the neurons, oxidative deamination (removal of -NH2)
Catecholamine metabolism performed by catechol-o-methyltransferase (COMT) is carried out where? Describe the process.
in non-neuronal tissues, methylation to the OH- at carbon 3
What is the resulting product of catecholamine metabolism?
inactive on adrenergic receptors
What is the duration of action of catecholamines/agonists?
up to 3 hours
What is the major clinical indication of adrenergic bronchodilators?
presence of reversible airflow obstruction
What is the major indication of short-acting agents?
acute reversible airflow obstruction in asthma or other obstructive a/w diseases
What are the 3 major indications for long-acting agents?
maintenance bronchodilation, control of bronchospasm, and control of nocturnal symptoms
Which receptors will be acted upon to achieve parasympathetic control/anticholinergic agents?
Muscarinic in a/w: M1 (nasal mucosa), M2 (heart), M3 (a/w smooth muscle), blood vessels
What are muscarinic receptors blocked by?
atropine
Anticholinergic (parasympatholytic) agents are known as what type of compounds? What is the mechanism of action? CNS effects? Systemic effects?
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
Describe the mechanism of action of anticholinergic bronchodilators.
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
Describe the steps involved in the M3 receptor blockade.
- 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
List 3 specific indications for antimuscarinic/anticholinergic bronchodilators.
chronic bronchitis, emphysema, vagally, mediated asthma
Describe the respiratory tract, CNS, eye, and CV effects relating to anticholinergics. Precautions?
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
Describe xanthines.
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
Describe methylxanthines.
methylated drugs (+ CH3 group) derived from xanthines, additional methyl group to a substrate
List the 6 general pharmacologic properties of xanthine bronchodilators.
CNS stimulation, cardiac muscle stimulation, diuresis, smooth muscle relaxation, peripheral and coronary vasodilation, cerebral vasoconstriction
Methylxanthines promote and inhibit what? What types of patients? Delay release/formation of what?
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)
List the proposed mechanism of action in the inhibition of phosphodiesterase in xanthine bronchodilators.
inhibition of cAMP phosphodiesterase (PDE)
Describe the mechanism of action behind inhibition of cAMP PDE.
*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
Describe the mechanism of action behind inhibition of adenosine in xanthine bronchodilators.
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
List the proposed mechanisms of action(s) in the inhibition of adenosine in xanthine bronchodilators.
antagonism of adenosine, catecholamine release
Describe the mechanism of action behind inhibition of adenosine via catecholamine release in xanthine bronchodilators.
possible production and release of endogenous catecholamine = bronchial relaxation
List some clinical indications for xanthine bronchodilators.
considered 2nd or 3rd line agents in treatment of asthma/COPD
when patients stop responding to other bronchodilators
used to treat AOP
What are the typical endings of muscarinic antagonists?
‘ium’
‘late’
What are the typical endings of beta agonists?
‘ol’
What are the typical endings of inhaled corticosteroids?
‘one’
‘ide’
List the sequence for clinical use of bronchodilators for a patient with asthma.
ICS, LABA, LAMA
SABA prn
List the sequence for clinical use of bronchodilators for a patients with COPD.
LAMA, LABA, ICS
SABA prn
