Pharmacology Flashcards
What are the 3 main category of drugs used in asthma and COPD and what are their subcategories?
What are the advantages and disadvantages of inhalation administeration of drugs?
Direct effect on airways , particulary for Asthma and COPD
The major advvantage is that the doses are much more effective with a decrease risk of systemic side effects
Bronchodilators also have rapid onset when administered orally
Can be used in combination with other drugs to have synergistic effects (LABA and ICS)
Disadvantages are that a mucus plug or airway obstruction could block adminsteration
If in an intense asthma attack may be hard for someone to hold their breath
What are the advantages and disadvantages of oral route administeration of drugs?
Can be used if there is airway obstruction or patient is in servere asthma and cannot function properly enough to coordinate inhalation
Disad: dose much higher than the inhaled dose requuired to achieve same effect as inhalation.
There are also increase systemic side effects
What are the 3 types of bronchodilators?
B2 adrenergic agonists
Anticholinergic agents
Methylxanthines
What is the mechanism of action for B2 adrenergic agonists?
Action of B2 receptor Gs-adenylyl cyclase –> increases cAMP-PKA pathway which leads to relaxation via phosphorylative events
What are the 4 effects of B2 adrenergic agonists?
Prevents mediator release from mast cells
prevents microvascular leakage and thus decreases development of oedema
Enhances mucocillary clearance
Reduces neutrotransmission (inhibits ACh release)
What are the 2 types of B2 adrenergic agonists you can have?
SABA and LABA
Which bronchodilator is specifically best for treating acute severe asthma?
SABA
Why must SABA’s be used in moderation?
overuse of SABA will cause desensitisation of the receptors
Are LABA’s used in COPD and are they used in combination with other drugs?
yes they are used in COPD and can be used alone or with combination of anticholinergics or ICS
Are LABAs prescribed alone to treat asthma? and if so why or why not?
Should never be used alone!!!! Do not treat the underlying chronic inflammation, and this may increase the risk of life-threatening and fatal asthma exacerbations
always used in combination with ICS
What does comibining a LABA and ICS result in?
Increased synergistic actions in treatment for COPD and asthma
What are the adverse effects of B2 adrenergic agonists?
Muscle tremor from stimulation of B2 receptors in skeletal muscle
Tachycardia and palpitations from stimulation of atrial B2 receptors and myocardial B1 receptors
What are the 2 broad actions of B2 agonists?
Bronchodilation and stabilise the mast cells membrane (decrease oedema mucus etc)
What is the mechanism of action for muscarinic cholinergic antagonists?
Inhibit M3 – Gq –PLC receptor which inhibits IP3 (prevents the increase in intracellular calcium) and DAG from stimulating PKC which prevents stimulation of Calcium sensitisation latch bridge
Inhibits only ACh-mediated bronchoconstriction
Describe the effectiveness of muscarinic cholinergic antagonists in Asthma and COPD patients
Less effective as bronchodilators than B2 agonists (used as an addition to bronchodilator) so not as effective as beta 2 agonists
Effective or suprerior to B2 agonists in COPD
They decrease gas trapping and increase exercise tolerance. This is because they prevent relieve bronchoconstriction and bronchoconstriction is the only reversible symptom of COPD. B2 agonists are just unecessary as have extra effects of mast cells????
What are the adverse effects of muscarinic cholinergic antagonist? (x2)
Dry mouth and bitter taste of inhaled
What are the 2 broad effects of anticholinergics on airways?
Effect just the bronchioles which produce just bronchdilation and reduce mucus secretion
What is the mechanism of action for methylxanthines?
They bypass the action of extracellular receptors (adrenergic or cholinergic) and prevent the degradation of cAMP. –> results in smooth muscle and relaxation
What is the contraindication of methylxanthines (in regards to its mechanism of action
lacks specificity – smooth muscle cells are not the only ones to use cAMP as a 2nd messenger
Why are methylxanthines still used despite its adverse effects?
Used in developing countries because it is inexpensive
what are the adverse effects of methylxanthines
nervous system overstimulation
anxiety, nervousness nause, vomitting
Glucocorticoids potently suppress _______
inflammation
What are the effects of corticosteroids on the inflammatory processes? (x4)
Inhibit the production of factors that are critical in generating the inflammatory response
decrease release of vasoactive and chemoattractive factors
diminished sedcretion of lipolytic and proteolytic enzymes
Reduce expresssion of pro-inflammatory cytokines
What is the mechanism of action for corticosteroids?
Enter target cells and bind to glucocorticoid receptors (GR)
The GR complex moves into n ucleus and binds to target genes –> alters transcription of the gene
directly Inhibits acetylation and causes activates HDAC2 which causes deactylation
Why are corticosteroids not effective in COPD?
This is because they work by activating HDAC2 which causes deactylation of gene expression
However in COPD there is a decrease in HDAC2 int he first place.
What are the effects of the corticosteroids on the inflammatory cells in airways? (x4)
Decrease mast cell rupture
Decrease new antibody production
decrease activity of immune cells
decrease recruitment of inflammatory cells into airways
What are the synergistic effects of corticosteroids and B2 agonists?
Corticosteroid effects of B2 adrenergic responsiveness:
Increase strength of effects of B2 agonists on smooth muscle
Prevent and reverse B receptor densitiation
Increase transcription of B2 receptor gene
B2 agonists effects on corticosteroid responsiveness
B2 agonists also increase the action of GRs
Increase binding of GRs
What are the adverse effects of corticosteroids? (x3)
Susceptible to infection in the pharynx region due to supression of immune function
Controversy over whether it stunts growth in children
hoarse voice
Comment on the timing of effects of the corticosteroids
ICS inhibits the late phase and inhibits the increase of hyper-responsiveness
has no effect on early stage (which is stimulation of mast cell and chemotaxines release)
only effects when the mediators are released and epitihelial damage and inflammation starts occuring etc….
When is ICS given in asthma?
Give to people with persistent asthma
(basically anyone who needs to use B2 agonist inhaler for symptom control more than twice weekly)
When are systemic steroids give in asthma?
If lung function is below 30% predicted
When is ICS given in COPD patients?
Jokes lol, it never really is because it doesnt have much of an effect
COPD patients only occasionally respond to steroids –> these patients likely to have accompanying asthma
Explain the mechanism of action for leuktriene receptor antagonists
leukotrienes are produced by inflammatory cells, particulary mast cells and eosinophils
The airways have receptors for leukotrienes, if these bind they trigger smooth muscle contraction, mucus secretion and odema.
These drugs block the receptor and thus decrease these effects
What is the mechanism of action of monoclonal anti-IgE treatment?
Bind with free IgE and prevent these from binding with mast cells
used in severe atopic asthma
Whats a drug that is used commonly in severe atopic asthma?
monoclony anti IgE
Why is IV administeration of these asthmatic drugs bad?
Because increase number of systemic effects due to the increase abundance of these drugs in plasma
Why ICS not given on its own?
Because it only acts upon the late phase, I.E it doesnt relieve bronchospasm
Why is SABA first?
As they are quick acting relievers that are only meant to be used for asthma that is controlled and not persistent
Best for ‘sudden’ asthma
Describe the stepwise approach to asthma therapy
which medication is the colour white/blue or just blue?
SABA
which medication is the colour light blue/white
LABA
which medication is the colour red?
ICS/LABA combinations
Why are muscarinic cholinergic antagonists used adjutant in asthma?
Not as much research surrounding LAMA
