Resp Flashcards
What are bronchodilators
Medications which relieve bronchoconstriction caused by conditions that affect air passageways and alveoli.
Alpha and beta adrenoceptors and muscarinic acetylcholine receptors (mAChRs) are…
G-protein coupled receptors
Alpha1 affect
Blood vessels, gut, liver, bladder, sweat glands, iris
Alpha2 affect
Presynaptically on all adrenergic nerve terminals, post-pancreas
Beta1 affect
Heart muscle, gut, juxtaglomerular apparatus
Beta2 affect
Bronchioles, skeletal muscle, pancreas, mast cells, liver, uterus
Beta3 affect
Adipose tissue, heart
Alpha1 receptors activate:
Phospholipase C (PLC) producing inositol trisphosphate (IP3) and diacylglycerol (DAG)
Alpha2 receptors inhibit
Adenylate cyclase thus decreasing cyclic adenosine monophosphate (cAMP)
All subtypes of beta receptors stimulate…
Adenylate cyclase thus increasing cAMP
Alpha1 receptor activation results in
Vasoconstriction, pupil dilation, decreasing peristalsis and decreasing voiding, sweating, hepatic glycogenolysis
Alpha2 receptor activation results in
Autoinhibition of transmitter release (NA and acetylcholine receptor release from autonomic nerves)
Beta1 receptor activation results in
Increased cardiac rate and force, relaxation of GI smooth muscle (decreasing peristalsis), renin release and lipolysis
Beta2 receptor activation results in
Bronchodilation, vasodilation, relaxation of uterine smooth muscle, hepatic glycogenolysis, increased insulin secretion, fine muscle tremor
Beta3 receptor activation results in
Lipolysis
Selective alpha1 agonists
Phenylephrine and oxymetazoline
Selective alpha2 agonists
Clonidine
Selective beta1 agonists
Dobutamine
Selective beta2 agonists
Salbutamol, formoterol, terbutaline and salmeterol used mainly in asthma
The drug class of choice for an immediate phase asthmatic attack and what does it do?
Beta2 adrenoceptor agonist- dilate the bronchi by a direct action on the beta2 adrenoceptors in the bronchial smooth muscle causing relaxation
What do beta2 adrenoceptor agonists inhibit
Inhibit mediator release from mast cells and decrease mucus production
What are the main short-acting drugs in the beta2 adrenoceptor agonist class?
Salbutamol and terbutaline
How are salbutamol and terbutaline administered?
Typically administered by inhalation (aerosol, powder, nebuliser) but can be given by IV in severe attacks
Characteristics of salbutamol and terbutaline:
Rapid onset of action, within a few minutes; effect lasts for 3-5 hours
Common AEs of salbutamol and terbutaline:
Fine muscle tremor, headache, palpitations, hypotension due to peripheral vasodilation, hypokalaemia, increase in BGL
How long do longer acting beta2 agonists (LABA) produce effects for
Up to 12 hours
E.g. of LABA
Salmeterol, formoterol/eformeterol
What are LABA used for
To improve resp function in patients with COPD
What drugs are not recommended for use in asthma and why?
Drugs acting on both beta 1 and 2 (e.g. adrenaline and isoprenaline) are not recommended for use in asthma as they may lead to cardio-acceleration, anginal attack and myocardial infarction (MI)
Beta antagonists (e.g. propranolol) can cause…
Wheezing in asthmatics (no effect on airway function in normal individuals) and can precipitate an acute asthma attack
How many muscarinic receptor subtypes have been identified?
Five
What does M1 act on
Act in the brain on higher cerebral function and peripherally on the parietal cells of the gastric mucosa to increase acid secretion
What does M2 act on
Act in the myocardium and decrease HR and the force of contraction
What does M3 act on
Affect exocrine glands and visceral smooth muscle, pupil constriction, increase gut motility and secretion of digestive juices, promote voiding and defecation as well as secretion from exocrine glands (lacrimation, salivation, sweating)
The physiological roles for which muscarinic receptors are unknown?
M4 and M5
M1, M3 and M5 receptors activate…
Phospholipase C, hence formation of two secondary messengers (IP3 and DAG) eventually leading to an intracellular increase of calcium and excitation
M2 and M4 receptors inhibit
Adenylate cyclase, thereby decreasing the production of the second messenger cAMP leading to inhibition
What are muscarinic receptor antagonists referred to as and why?
Generally referred to as parasympatholytic because they selectively reduce or abolish the effects of the peripheral nervous system (PNS)
What are the parasympatholytic effects muscarinic receptor antagonists have?
Inhibition of secretions- salivary, lacrimal, bronchial and sweat glands.
HR- modest tachycardia.
Eye- pupil dilation, unresponsive to light (blurred vision).
GI tract- reduced GI motility (constipation).
Other smooth muscle- bronchial, biliary, urinary tract smooth muscle dilation (bronchodilation, smooth muscle relaxation, decreased voiding).
CNS- high doses cause agitation and disorientation.
Muscarinic antagonists used specifically as an anti-asthmatic are:
Ipratropium (non-selective) and tiotropium (M3 receptor selective) by inhalation
Ipratropium and tiotropium side effects:
Dry mouth, urinary retention, facial flushing, constipation, pupil dilation
Ipratropium and tiotropium properties:
o Maximum effect is after 30 minutes
o Lasts 3-5 hours
o Can be useful as an adjunct to another therapy (when a beta2 agonist alone is inadequate) to help with bronchodilation and reduce mucus secretion
o Not absorbed well into circulation so there is minimal action on muscarinic receptors in locations other than the bronchi
What do ipratropium and tiotropium do?
These stop the activity of acetylcholine in the smooth muscle preventing contraction and producing relaxation
E.g. of anticholinergics:
Short-acting muscarinic antagonist (SAMA) and long-acting muscarinic antagonist (LAMA)
E.g. of SAMA
Inhaled ipratropium
What does SAMA do
Blocks the action of acetylcholine thereby inhibiting nerve impulses responsible for involuntary muscle movements and various bodily functions
What do LAMA do
Blocks the action of acetylcholine thereby inhibiting nerve impulses responsible for involuntary muscle movements and various bodily functions
E.g. of LAMA
Aclidinium, glycopyrronium (inhaled), tiotropium, umeclidinium
SAMA and LAMA mode of action
Blocks the action of acetylcholine in bronchial smooth muscle
SAMA and LAMA side effects
Dry mouth, throat irritation
E.g. of beta2 agonists
Short-acting beta agonists (SABA) and long-acting beta agonists (LABA)
For what and when are SABA used
To provide quick relief (rescue inhalant) of asthma symptoms, during periods of acute symptoms and exacerbations
E.g. of SABA
Salbutamol and terbutaline
For what and when are LABA used
Taken daily (maintenance inhalant) to relax the muscles lining the airways that carry air to the lungs, used to achieve and maintain prophylactic control of persistent asthma
E.g. of LABA
Formoterol, indacaterol, salmeterol, vilanterol
SABA and LABA mode of action
Both stimulate beta2 adrenergic receptors in the smooth muscle of bronchi and bronchioles. These receptors in turn stimulate the enzyme adenyl cyclase to increase production of cAMP which produces bronchodilation