PHARM: Basics of Pulmonary Pharmacology Flashcards
True or false: the lung is more permeable to macromolecules than any other portal.
TRUE! IT is even more permeable to small molecules than the GI tract
What is one of the major issues with the delivery of inhaled corticosteroids?
Deposition of a significant portion of the drug dose in the oral cavity –> thrush
How can you minimize thrush due to inhaled corticosteroids?
Use a spacer or rinse mouth after use
Lipid soluble compounds are absorbed via what route?
transcellular route (dissolve in the lipid bilayer)
Lipid insoluble compounds are absorbed via what route?
paracellular (pass through intercellular tight junctions)
Do ionized molecules have faster or slower absorption?
slower (because they have more interactions with the proteins and lipids that line the pore.
For molecules above 1000 D, what is the most important factor for absorption rate?
molecular weight (and ionization)
For molecules 100-1000 D, what is the most important factor for absorption rate?
Degree of ionization (the less ionized, the faster absorption)
What are the 3 major lung issues that require pharmacological treatment?
Inflammation
Infection
Transformation
What is interesting about mucolytics?
they never enter the body, but rather they break up the physical structure of mucus making it easier to be expectorated
How do vasoconstrictors help the upper respiratory tract? What receptors to they act upon?
alpha-1 agonists that relieve congestion by relieving nasal congestion
Which will produce more rapid relief for asthma: a beta-agonist or a corticosteroid?
Beta-agonist (controls smooth muscle directly) will provide more immediate relief while anti-inflammatory drugs may have same effect eventually over time by controlling inflammation
What are the 3 major issues we are concerned about with anticancer drugs?
1) Toxicity
2) Resistance
3) Duration of clinical effect
What two drug classes are used to control bronchospasm?
Beta-2 agonists
Muscarinic antagonists
True or false: the SNS directly innervates bronchial smooth muscle.
FALSE: the SNS does not directly innervate bronchial smooth muscle but can modulate the activity of the PNS via hetero-receptors
What class of drugs is contraindicated in asthma due to effect on receptors in the airway?
Nonspecific beta blockers (P-T olols) are contraindicated!
What is the major role of M1 receptors in the airway?
- Transduce vagal signals to sub-mucosal glands and airway smooth muscle
- Increase glandular secretions in nasal mucosa
What is the role of M2 receptors in the airway?
they are pre-synaptic inhibitory autoreceptors!
What happens if ACh binds to M-3 receptors in the airway?
bronchoconstriction and mucus secretion
What happens if ACh binds to M-2 receptors in airway smooth muscle?
they oppose the increase in cAMP production produced by Beta-2 adrenergic stimulation
What is the “Jekyll and Hyde” aspect of muscarinic antagonists?
M3 antagonism inhibits bronchial smooth muscle, but antagonism of M2 could actually lead to increased release of Ach from the pre-synaptic membrane (and cause contraction)
What is the name of the selective M-1/M-3 antagonist?
tiotropium
Anticholinergic drugs have what effect on glandular secretions?
dries and thickens them!
What drug has a very similar anticholinergic activity with respect to secretions (dries them)?
1st generation antihistamines
What drugs have cholinergic activity with respect to secretions (increases them)?
acetylcholinesterase inhibitors and marijuana (these prevent the almost-immediatedegradation of Ach)
What is albuterol?
beta-2 selective agonist
What is the major response to the administration of albuterol?
relaxation of bronchial smooth muscle and bronchodilation
Albuterol is only effective against what phase of asthma?
the early (bronchospastic) phase… it does nothing for the late (inflammatory) phase
Beta-2 agonists may cause bronchoconstriction via what mechanism?
increasing PNS (bronchoconstrictive) tone
Activation of beta-2 receptors on mast cells lead to what?
reduction of histamine release
Beta-agonists have what effect on cilia?
increase beat frequency of cilia and facilitate mucociliary clearance
Beta-agonists have what effect on vascular endothelial permeability?
decrease microvascular leakage
At high concentrations, beta2 agonists have what effect on the heart?
Stimulation, prolongation of QT interval (especially in presence of hypokalemia)
How do beta2 agonists lead to QT prolongation and tremor?
stimulate skeletal muscle Na/K ATPase to increase intracellular K+ and decrease serum K+
Beta-2 receptors use what type of GPCR?
Gs
If you too frequently stimulate your beta-2 receptors, what might happen?
internalizaiton and loss of physiologic function (“tolerization”)
How might corticosteroids help with beta-2 agonist “tolerization”?
they transcriptionally upregulate the expression of beta-adrenergic receptor to renew the response to beta2-agonist inhaler treatment
