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Respiratory Pharmacology Flashcards

1
Q

Boothe - Clinical Pharmacology

A

Respiratory Pharmacology - Drugs Affecting the Respiratory System

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2
Q

What are bronchodilator?

A

Drugs that reverse smooth muscule contraction of the bronchioles. by increaseing cAMP and decreasing cGMP or decreasing Ca2+.

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3
Q

How do B-agonists result in bronchodilation?

A

Promote bronchodilation regardless of cause.
Activation of adenylyl cyclase and then production of cAMP –> protein kinases –> bronchodilation.

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4
Q

What are the additional effects of B agonists?

A

Increased mucocillary clearance (due to decreased fluid viscosity, due to increased movement of chloride and water into the lumen) and increased cilliary beat frequency.
enhance vascular integrity, inhibit MCT and basophil mediator release

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5
Q

What may occur with repeated doses of B agonists?

A

Desensitiation via reduced receptor number and receptor internalisation.
This may cause patients to increase dosage to confur desired clinical response which may mask worsening or severe disease

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6
Q

What may be the concern utilising non selective B agonists for bronchodilation?

A

May have adverse cardiac affects and may contribute to airway constriciton - this may be reduced by aerosolising these drugs as only B2 receptors appear to line the airways

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7
Q

What is the MOA of theophyiline

A

non-specific inhibition of phosphodiesterases and increased cAMP and therefore activation of phosphokinases –> not completely understood.
Likely to cause bronchodilation and anti-inflammatory

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8
Q

Is theophylline stronger or weaker than B agonists

A

Weaker - however also results in increased mucocilliary clearance and reduced MCT degranulation and reduced cytokine production
Importantly may increase respiratory muscle strenght

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9
Q

How can theophylline be give?

A

Oral or IV

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10
Q

What is the difficulty of dosing oral slow release theophylline?

A

Markedly differing bioavailability and absorption time making dosing very difficult

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11
Q

When should theophylline be dosed in cats

A

More bioavailable in the evening - weird

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12
Q

What are some adverse reactions to theophylline?

A

CNS aggitation, GI upset, diuresis, tachycardia
When given rapidly IV may result in hypotension, nausea, tremors, respiratory failure

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13
Q

What may drug interaction may incrase the risk of theophylline toxicity

A

Fluroquinalone administration. Reduce metabolism and clearance –> increase toxicity

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14
Q

How will atropine influence the respiratory tract

A

May cause bronchodilation –> however MAY also cause broncho-constriciton.
Decrease mucocilliary clearance and reduce fluid flux into secretion

Bad side effects pretty much outway any potential benefit

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15
Q

What is cromolyn

A

A calcium channel blocker that stops mast cell degranulation

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16
Q

Why are glucocorticoids the cornerstone of treating inflammatory lung disease?

A

Anti-inflammatory effects as well as permmisive effects on beta receptors mediating bronchodilation

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17
Q

How are glucocorticoids of often administered in respiratory disease and does increasing dose increase efficacy

A

Inhaled or oral and no

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18
Q

When should systemic and inhalaed steroids be used

A

in uncontrolled disease or disease so severe that steroids unlikely to get to the small airways

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19
Q

How do leukotrienes effect the respiratory system and what drugs may be used to inhibit this

A

potent causes of oedema, inflammation, bronchoconstriciton
Drugs: LT synthesis inhibitors or LT-receptor antagonists ( more effective)

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20
Q

When may leukotriene inhibition be utilised

A

none have ever been studied in dogs and cats
Used in humans in mild cases - in addition to steroids or as sole agents
Offer mild anti-inflammatory and mild bronchodilation

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21
Q

Discuss NSAIDs and asthma

A

Not a lot of evidence but may shunt AA towards the lipoxygenase pathway and make things worse. But no one knows with newer nsaids

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22
Q

What is the goal of anti-tussive therapy?

A

Decrease the frequency and severity of the cough without impairing mucocilliary defences

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23
Q

What causes a cough

A

chemoreceptors and stretch receptors, commonly caused by bronchoconstriciton
decreased airways size causes increased air velocity to irritate stretch receptors

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24
Q

Where can a cough be supressed

A

peripherally - removing secretion with expectorants or mucolytics
inducing bronchodilation
blocked centrally in the cough centre (medulla)

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25
How do opioids function as antitussives?
depress the cough center.
26
What are common cough suppressant opioids
codiene and butorphanol
27
What are mucokinetic drugs
The facilitate the removal of secretions from the resp tree. They can increase cilliary beatting or decrease mucous viscosity
28
How can viscosity be reduced?
hydration, increasing pH, rupturing sulfide bonds
29
Is nebulisation very effective
It's efficacy is controversial
30
How does bromhexine function as a mucolytic?
decreases the formation of mucous secreting glands in the entire body
31
For mucolytic effects does NAC have to be inhaled?
No can just be oral - decrease incidence of bronchoconstriciton so should always be preceded by a bronchodilator
32
What are expectorants
Drugs used to increase the fluidity of resp secretions
33
What are two posible respiratory stimulants?
Caffeine and doxapram
34
What 3 characteristics determine the amount of inhalled drug reaching the airways
anatomy, ventilation and aerosol characteristics
35
What aerosol characteristics will affect drug delivery
diameter, size, mass, solution vs suspension, electrical charge
36
What sized particles are best at penetrating the small airways
1.5um or less
37
What are the two types of nebuliser?
Jet and ultrasonic (can get to smaller particle sizes)
38
How often do we clean our nebulisers?????
39
Why are spacers used
To reduce the need for hand breath co-ordination. increases penetration and results in a more uniform particle size
40
When nebulising a drug what is a dosing rule of thumb?
Take the systemic dose and dilute it to allow nebulisation for 30 mins
41
SPECIFIC DISEASE THERAPY
42
WHat is recommended for tracheal collapse
Cough suppressants, mukokinetics may be helpful, steroids may aid in reduction of airway inflammation caused by cyclic coughing, bronchodilators may be beneficial, may be reasonable to supplement glucosamine and chondoitin
43
What management is recommended in acute asthma
oxygen, sedation, steroids, parenteral B agonists --> aminophylline IV if fail to respond to B agonists (2-5mg/kg SIV
44
Why may bronchodilators result in worsened V/Q mismatch
Will often cause widespread pulmonary vasodilation resulting in perfusion of poorly ventilated areas
45
What is the mainstay of canine bronchitis treatment?
Bronchodilators, cough suppressants and steroids only if inflammation shown or suspected and not often needed long term
46
WHat suppliment may be helpful in medically managing chylothorax
Rutin - a non-anticoagulant coumarin a flavone benzo-gamma-pyrone plant fruit extract from brazil. Helps stimulate macrophage removal of proteins and decreases oncotic flux into the effusion.
47
Padrid -Small Animal Clinical Pharmacology
Drugs used in the management of respiratory diseases
48
What secondary messenger is associated with bronchodilation and what is associated with bronchoconstriction
cAMP - bronchodilation cGMP - bronchoconstriction reciprocal - increase in one = decrease in the other
49
At least how many Ach responsive receptors exist in the feline airway? And how far down do they go?
At least 5. All the way down to the alveoli
50
What are Ach respiratory mechanisms mediated by?
cGMP, 1,4,5-triphosphate (ITP) and diacylglycerol (DAG), Ca2+ influx
51
Are canine airways more or less responsive than feline airways?
canine airways are more responsive than feline airways to acetylcholine. However, canine airways (in relation to their body surface area) are enormous compared with feline airways and changes in bronchomotor tone in dogs result in relatively trivial clinical changes compared with the cat
52
What are the three types of bronchodilators?
β-receptor agonists, methylxanthine derivatives and anticholinergics.
53
How do b-agonists result in bronchodilation?
- Mediated not only through increasing cAMP concentrations but also - Activation of large-conductance calcium-activated potassium channels. Activating this channel allows an extracellular potassium efflux, increase in transmembrane potential and hence a reduction in calcium influx through the voltage-dependent L type calcium channels, thus resulting in bronchodilation
54
What are the several effects of methylxanthines?
They relax smooth muscle, particularly bronchial smooth muscle, stimulate the central nervous system and are weakly positive chronotropes and inotropes, as well as mild diuretics.
55
How does theophyline cause bronchodilation?
MAYBE - inhibition of phosphodiesterases with a resultant increase in intracellular cAMP, direct and indirect effects on intracellular calcium concentration, uncoupling of intracellular calcium concentration and muscle contractile elements and competitive inhibition of adenosine receptors HOWEVER - no one actually knows
56
Atropine
Not really discussed in depth - authors only recommended use is pre-treat asthmatic cats before airway sampling
57
How long before inhaled fluticasone becomes clinically effective?
1-2 weeks due to large molecule size and slow mucosal penetration
58
Where may anti-tussives act?
peripherally to bronchodilate to reduce cough stimuli peripheral nervous system central nervous system Most effective anti-tussives act to increase the cough threshold
59
how does Dextromethorphan hydrobromide cause cough suppression?
a semisynthetic derivative of opium that acts centrally to elevate the cough threshold.
60
How does codeine cause cough suppression?
Probably codeine specific receptors as has low opioid affinity
61
How do mucolytics function?
general, mucolytic drugs act by altering mucus structure through changes in pH, direct proteolysis and/or disruption of disulfide bond linkages
62
How do mucolytics function?
general, mucolytic drugs act by altering mucus structure through changes in pH, direct proteolysis and/or disruption of disulphide bond linkages
63
How does bromhexine act as a mucolytic?
Increases lysosomal activity --> this enhances hydrolysis of mucopolysaccaride polymers. HOWEVER - less effective in inflammatory mucous as viscosity is largely dependent on the amount of DNA present in these instances
64
NAC MOA?
Breaks down disulfide bonds and is not affected by the presence of DNA - however, is very irritant to the resp epithelium - limiting its use
65
Discuss the use of guaifenisin as an expectorant
Dose needed is likely the same as the emetic dose - lower doses probably do nothing

Respiratory (3 decks)

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