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Renal Exam > Respiratory Pharmacology > Flashcards

Respiratory Pharmacology Flashcards

1
Q

What two major drug categories do we use to treat asthma?

A

– Bronchodilators: treat the primary symptom of asthma, i.e bronchoconstriction
– Antiinflammatory agents: reduce the level of airway smooth muscle hyperresponsiveness resulting from airway inflammation.

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2
Q

What is cromolyn sodium?

A

Inhaled anti-inflammatory agent used in asthma to stabilize Mast Cell: Exact mechanism not known

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3
Q

When is cromolyn sodium used?

A

chronic control of asthma
Prophylaxis of bronchospasm
NOT FOR RESCUE
not used in USA

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4
Q

What are the three main classes of bronchodilators?

A

– β2 Adrenergic agonists (sympathomimetics)
– Theophylline (a methylxanthine)
– Anticholinergic agents (muscarinic receptor antagonists)

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5
Q

What are 2 Inhaled β2

agonists?

A

Albuterol &Salmeterol

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6
Q

Why are Albuterol & Salmeterol used in asthma?

A
  • bronchodilator treatment of choice in asthma
  • most effective bronchodilators
  • have minimal side effects when used correctly
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7
Q

What is the short acting beta-2 agonist?

A

Inhaled short-acting β2-selective agonists (SABA) (albuterol) have a duration of action (3-6 hours)

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8
Q

What is the long acting beta-2 agonist?

A

Inhaled long-acting inhaled β2
agonists (LABA) (salmeterol and formoterol) have longer duration of effect, providing bronchodilation and bronchoprotection for >12 hours

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9
Q

What is the MOA of beta-2 agonists?

A

directly stimulate β2
receptors in airway smooth muscle -> activation of the Gs
-adenylyl cyclase-cAMP-PKA pathway. PKA phosphorylates a variety of target substrates and Decrease calcium

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10
Q

What are some Other Effects of beta2 Agonists in Airways?

A

– Prevent mediator release from mast cells
– Prevent bronchial mucosal edema
– Enhance mucociliary clearance
– Reduce reflex cholinergic bronchoconstriction

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11
Q

What are some adverse effects of beta2 agonists?

A

muscle tremor, tachycardia, hypokalemia, restlessness, hypoxemia.

all are dose related and decreased risk with drug inhaltion

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12
Q

Which beta 2 agonist is a rescue medication?

A

albuterol: Onset of action w/i minutes after inhalation and lasts for `3-6 hrs

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13
Q

Which beta 2 agonist can improve asthma control?

A

Salmeterol: protect against bronchoconstriction > 12 hrs

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14
Q

Are beta2-agonists Safe?

A

Two randomized controlled safety trials found that LABAs were associated with three- to fourfold risks for asthma-related death

should not be the first medicine used to treat asthma should be added to the asthma treatment plan only if other medications do not control asthma, including the use of low- or medium-dose corticosteroids

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15
Q

Why do some patients have adverse events or effects when using inhaled beta-agonists?

A

49 different polymorphisms having been identified – importance of these polymorphisms remains controversial

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16
Q

What is the Methylxanthine used for asthma?

A

Theophylline (related to caffeine) - Oral - used in the treatment of asthma since 1930 still widely used in developing countries because it is inexpensive.

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17
Q

What is the MOA of Methylxanthine (Theophylline)?

A

nonselective phosphodiesterase (PDE) inhibitor (increased levels of cAMP and cGMP) & Adenosine receptor antagonism (adenosine helps release histamine and leukotrienes)

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18
Q

What are the side effects of Theophylline toxicity?

A
  • headache
  • palpitation
  • dizziness
  • nausea
  • hypotension
  • tachycardia
  • severe restlessness
  • agitation
  • seizures
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19
Q

How do Anticholinergics help with asthma?

A

– Relaxes airway smooth muscle

– Decreases mucus secretion

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20
Q

What is the MOA of Anticholinergics?

A

competitive antagonists of acetylcholine (ACH) binding to muscarinic cholinergic
receptors

ACH acts on bronchial smooth muscle muscarinic receptors to cause constriction and increased mucous secretion

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21
Q

What is the antiocholinergic drug we should know to treat asthma?

A

Ipratropium bromide

22
Q

What are some things we should know about Ipratropium bromide administration?

A
  • Inhaled
  • maximal responses develop over 30-90 min
  • Effects last for 4-6 hours
23
Q

What are some adverse effects of Ipratropium bromide?

A 
Predictable consequences of muscarinic receptor blockade
– Dry mouth
– Constipation
– blurred vision
– dyspepsia
– cognitive impairment

less when inhaled

24
Q

When is Ipratropium bromide indicated for asthma treatment?

A
  • effective in acute severe asthma but less effective than β2agonists.
  • In the acute and chronic treatment of asthma, have additive effect with β2 agonists and considered when control of asthma is not adequate with inhaled β2 agonists
25
Q

What is the major inhaled steroid we should know for asthma?

A

Beclomethasone

Most effective and most often prescribed ANTIINFLAMMATORY drugs for treatment of CHRONIC INFLAMMATION underlying asthma.

26
Q

How do steroids reduce inflammation?

A

activate the NF-kappa-B pathway

27
Q

Do steroids help with the airway constriction of asthma?

A

no direct effect on contractile responses of airway smooth muscle (early response), but
inhibits the late response (which may be due to an effect on macrophages, eosinophils, and airway wall edema) and also inhibits the increase in airway hyperresponsiveness

28
Q

Combination inhalers usually include what?

A

LABA agonist and a corticosteroid

convenient for patients, simpler, improved compliance

29
Q

What about systemic steroids?

A

Prednisolone and prednisone are the most common but Effect may take several days

indicated in acute asthma if lung function is <30% predicted and then usually IV therapy is needed

30
Q

What are side effects of systemic steroids?

A
  • cataract formation and osteoporosis
  • dermal thinning and skin capillary fragility
  • concern about the use in children because of growth suppression
31
Q

What are the side effects of inhaled steroids?

A
  • deposition of inhaled steroid in the oropharynx.
  • hoarseness and weakness of the voice due to atrophy of the vocal cords
  • occurs in up to 40% of patients
  • Particularly in patients who use their voices during their work (lecturers, teachers, and singers)
32
Q

When are inhaled corticosteroids used in asthma?

A

• first-line therapy for all patients with persistent asthma.
• started in any patient who needs to use a β2agonist inhaler for symptom
control more than twice weekly.
• effective in mild, moderate, and severe asthma and in children as well as adults

33
Q

What drugs modify leukotriene secretion?

A

zileuton & zafirlukast

34
Q

What is the MOA of zafirlukast?

A

antagonists of the cys-LT1

receptor

35
Q

What is the MOA of zileuton ?

A

5-lipoxygenase (5-LO) enzyme inhibitors (usually cleaves arachidonic acid into leukotrienes)

36
Q

How and when Leukotriene Antagonists administered?

A

oral administration

mild to moderate chronic asthma are indicated as an add-on therapy in patients who are not well controlled on ICS.

37
Q

What are the adverse effects of Leukotriene Antagonists?

A

considerably less effective than ICS in the treatment of mild asthma and cannot be considered the treatment of first choice

rare cases of hepatic dysfunction

38
Q

What is aspirin induced asthma?

A

Aspirin hypersensitivity: A small proportion (1–5%) of asthmatics become worse with aspirin and other COX inhibitors maybe due to shunting of AA into the leukotriene pathway

39
Q

How is COPD different than asthma?

A
  • Pattern of inflammation differs
  • affects small airways
  • airway closure on expiration, leading to air trapping and hyperinflation
40
Q

How is COPD treated?

A

based on increase severity of disease:

  1. stop smoking and management education
  2. bronchodilators
  3. inhaled steroids
  4. pulmonary rehabilitation
  5. oxygen
  6. surgery
41
Q

What about anticholinergics and COPD?

A

Anticholinergic drugs may be as effective as or even superior to β2 agonists

they reduce air trapping and improve exercise tolerance

42
Q

How are steroids used in COPD?

A

ICS alone should not be considered first-line therapy in stable COPD patients

for acute exacerbations, COPD is not generally responsive to ORAL corticosteroid therapy

43
Q

Why is azithromycin used in COPD?

A

are used to prevent and treat acute exacerbations of bronchitis (excessive cough and sputum secretions) that may be accompanied by bacterial infection

44
Q

What mucolytic can be used in COPD?

A

Inhaled N-acetylcysteine

45
Q

How does Inhaled N-acetylcysteine work?

A

– free sulfhydryl group opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity
– Side effects of bronchospasm so never give acetylcysteine by itself to asthmatics!!
– Best given with a bronchodilator like albuterol

46
Q

What are some therapies for cystic fibrosis?

A

– Antibiotics to preventing and controlling lung infections
– Anti-inflammatory medicines (inhaled or oral) to reduce swelling in airways due to ongoing infections.
– Inhaled bronchodilators to help open the airways, help loosen and remove thick, sticky mucus from the lungs
– Recombinant human deoxyribonuclease (rhDNAase, dornase alpha)
– Ivacaftor

47
Q

What is dornase alpha?

A

Genetically engineered version of naturally occurring DNAase

• Dornase alpha breaks down DNA

48
Q

How does dornase alpha help with CF?

A 
Infiltrating neutrophils release DNA which has high viscosity so dornase alpha breaks down DNA leading to:
– decreases viscosity
– facilitates sputum clearance
– improve lung function
– decreases frequency of infection
49
Q

What is Ivacaftor (kalydeco)?

A

increases chloride transport by potentiating the channel-open gating in 5% of cystic fibrosis patients with a G551D mutation

should be avoided in patients with serious hepatic dysfunction and is VERY expensive

50
Q

What is a problem with inhaled medications?

A

Inhalation therapy deposits drugs directly, but not exclusively, in the lungs.

Most material will be swallowed and absorbed, entering systemic circulation
after undergoing the first-pass effect in the liver

51
Q

What does the distribution of inhaled medication depend on?

A

Distribution between lungs and oropharynx depends mostly on the particle size and the efficiency of the delivery method

52
Q

What helps a lot with inhaled medications?

A

a spacer between the device and the person’s mouth

Renal Exam (22 decks)

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