Pharm I Flashcards
What are some advantages to pulmonary delivery of drug?
The lung is more permeable to macromolecules and even more permeable to small molecules than the GI tract and has extremely fast onset of action
What are some disadvantages to pulmonary delivery of drug?
-inhaled corticosteroids can deposit a
significant portion of the drug dose in the oral cavity, with opportunistic infections
like candidiasis arising from diminished immune function.
Acidic powders are
also a concern for the integrity of tooth enamel.
What routes do drugs take for absorption in the lung?
para and trans-ceullar
How are lipid-soluble drugs absorbed?
They can dissolve in the lipid bilayer and are absorbed trans-cellularly
How are insoluble drugs absorbed?
para-cellularly via aqueos pores in the tight junctions
T or F. The less ionized a molecule, the faster its absorption rate
T. because it forms fewer interactions with the proteins and lipids lining the pore
What are the three major categories of disease that require treatment of the lung?
- inflammation
- infection
- cancer
What types of inflammation diseases require lung treatment?
- asthma
- COPD
- allergic rhinitis
- cystic fibrosis
What are some classes of drugs that act in the upper respiratory tract?
- mucolytics
- vasoconstrictors
- antihistamines
- drugs acting in the CNS cough center
What are some major uses of antihistamines?
- allergic rhinitis
- hay fever
What is the major use of vasoconstrictors in the URT?
permit someone to breath more easily, by
relieving nasal congestion.
What is ivacaftor?
Recently gained approval as the first in a new class of CTFR (cystic fibrosis transmembrane conductance regulator) potentiators.
What part of the ANS dominates lung function?
PNS, it provides direct innervation of smooth muscle and glandular tissue
T or F. In humans, bronchial smooth muscle has no direct neural connection from the SNS
T. SNS activity can only modulate the activity of the PNS via hetero-receptors
What other way can the SNS affect the lung?
beta-2 receptors can respond to circulating Epinephrine or to exogenous drug treatment
What classes of drugs can be used to control bronchospasm in asthma?
B2 adrenergic agonists and muscarinic anatgonists
What is the role of muscarinic M1 receptors?
They transduce vagal signal to both sub-mucosal glands and the airway smooth muscle AND increase glandular secretions in nasal mucosa
What is the role of muscarinic M2 receptors?
they are inhibitory auto receptors on the pre-synaptic membrane of PG fibers AND are found in bronchial smooth muscle where they oppose the increase in cAMP produced by B2 adrenergic stimulation
What is the role of muscarinic M3 receptors?
promotes bronchoconstriction of airway smooth muscle and mucus secretion
How do non-selective drugs, like atropine and ipratropium affect the lungs?
they non-selectively antagonize M-2 and M-3 receptors equally well
How does blockade of the M2 auto-receptors affect the release of endogenous Ach?
it increases the release, which serves to partially offset any bronchodilatory drug effects. (So the non-selective nature is not good)
How selective is Tiotropium?
it is selective for M1 and M3 receptors
T or F. Tiotropium has a longer duration of action than other muscarinic antagonists
T. But a slower onset of effect
How would anticholinergic drugs affect glandular secretions?
it dries them and potentially thickens them
What other drugs have anticholinergic activity and thus induce drying of secretions?
1st gen antihistamines
What are the 1st generation antihistamines?
- Chloropheniramine
- Doxylamine
- Diphenhydramine
What kinds of drugs potentiate cholinergic activity?
Acetylcholinestase inhibitors
What are some Acetylcholinestase inhibitors?
- Neostigmine
- Edrophonium
What are some off-label uses of marijuana?
- anorexia
- cachexia
- glaucoma
- N/V
What effect does marijuana have on secretions?
increases them
Where are B2 receptors most common?
the lungs (70-80%)
What is the main effect of albuterol on the lungs?
bronchodilation and relaxation of smooth muscle and most effective against early (bronchospastic) response to inhaled antigens
T or F. Albuterol is ineffective against late (inflammatory) phase of inhaled antigen
T.
Are B2 agonists all good?
No, some with M-2 agonizing action have the potential to produce bronchoconstriction by increasing PNS tone
How does B2 stimulation affect mast cells?
reduces histamine release
How does ANS stimulation affect mucocilliary clearance?
Goblet cells and submucosal glands primarily receive PNS innervation but circulating epinephrine can give SNS effects
What do a-agonists do to mucocillary clearance?
increase fluid secretion volume
What do B-agonists do to mucocillary clearance?
- increase glycoprotein composition
- increase beat frequency of cilia to promote more clearance
How do B-agonists affect micro-vasculature?
They decrease microvascular leakage which reduces airway obstruction in asthma
T or F. B2 receptors exist in the heart
T. Some
At high conc, how do B2 agonists affect the heart?
- CV stimualtion
- QT prolongation, especially in hypokalemia
- widening pulse pressure
- arterial dilation in coronary, pulmonary, and skeletal muscle
One of the classical adverse effects that a patient who has taken too much beta-2 agonist
might display is a twitching or fasciculation of skeletal muscle. Why?
B2 stimulation increases Na/KATPase activity which increases intracellular K+
What are some DD interactions with B2 agonists?
- TCAs
- MAOIs
- Saquinavir
- Loop and thiazide diuretics
- Non-specific Beta-blockers
What are some common TCAs?
- amitriptyline
- Despiramine
Why are TCAs a potential DD interaction with B2 agonists?
block reuptake of drug
What are some common MAOIs?
- selegilene
- rasagilene
Why are MAOIs a potential DD interaction with B2 agonists?
they block metabolism of amines by monoamine oxidase-B
Why are Saquinavir and loop/thiazide diuretics potential DD interactions with B2 agonists?
they promote hypokalemia, QT prolongation, and arrhythmia
Both muscarinic and beta-adrenergic receptors are G protein-coupled receptors. M1 and
M3 are coupled to stimulatory ____ signaling,
Gq
What GCPR does M2 receptors work with?
Gi (inhibitory)
What GCPR does B2 receptors work with?
Gs mediated
Too frequent stimulation of B2 receptor causes what?
Too frequent a
stimulation of the beta-receptor leads to internalization and loss of physiologic function.
How are corticosteroids used in asthma treatment?
they transcriptionally upregulate the expression of the beta-adrenergic
receptor, leading to renewed response to the beta-2 agonist inhaler treatment.
