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PHRM 211 > Lecture 5 > Flashcards

Lecture 5 Flashcards

1
Q

Obstruction of airway flow in asthma is due to 3 things

A

airway inflammation
bronchial hyperresponsiveness
smooth muscle constriction

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2
Q

Asthma is

A

chronic long term inflammatory condition affecting the upper airways in the lungs

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3
Q

asthma is characterized by

A

reversible bronchoconstriction and SOB

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4
Q

COPD is

A

a chronic progressive respiratory disease

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5
Q

COPD causes

A

irreversible restricted airflow and breathing problems

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6
Q

restricted airflow is due to

A

destruction of parts of the lung including alveoli.
mucus blocking the airways
inflammation and swelling of the airway lining.

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7
Q

is COPD curable?

A

Not curable, but can be managed by medications.

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8
Q

benefits of inhaled drug deposition

A
  • effective use of smaller dose
  • lower incidence of unwanted systemic effects
  • rapid onset of action
  • controlled delivery
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9
Q

Name two common short acting beta agonists

A

salbutamol and terbutaline

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10
Q

name two common LABA

A

sameterol, formoterol

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11
Q

MOA of B2 agonists

A
  1. B2 agonists bind and stabilize the receptor in the activated stage.
  2. activates adenylate cyclase, increases generation of cAMP from ATP
  3. cAMP inhibits Ca, hyperpolarizes smooth muscle cells = bronchodilation
  4. cAMP also activates protein kinase A, incrasing protein phosphorylation, regulates smooth muscle tone, = bronchodilation
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12
Q

what happens with frequent use of B2 agonists

A
  1. enhance inflammatory pathways, downregulation of B2receptors and tolerance to bronchodilator effects
  2. receptors desensitize rapidly, so B2 agonists do not reduce airway inflammation.
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13
Q

SABA onset of action

A

5 minutes

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14
Q

SABA peak effect (max bronchodilation)

A

15-30 minutes

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15
Q

how long do SABA bronchodilation effect last until

A

2-6 hours

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16
Q

How are SABAs administered

A

Inhalation, salbutamol sometimes given with IV infusion.

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17
Q

When should SABAs be used and why

A

intermittently or as needed

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18
Q

LABA duration of action

A

up to 12 hours, more lipophilic than SABAs and bind to the lipid of the smooth muscle cell membrane.

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19
Q

Which LABA has slower onset compared to others

A

salmeterol

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20
Q

low efficacy agonist LABA

A

salmeterol (60% partial agonist activity)

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21
Q

high efficacy agonists LABA

A

formoterol and Indacaterol - full agonist activity

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22
Q

should LABAs be used alone in asthma

A

NO! should be used as an add on to ICS to control persistent symptoms in adults. It reduces the risk of exacerbations compared to ICS alone

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23
Q

should LABAs be used alone in COPD

A

Can be used alone or in combo with CIS or LAMA

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24
Q

what do LABAs do alone in COPD

A

improve symptoms and exercise tolerance by reducing both air trapping and exacerbations.

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25
Q

ADRs of B2 agonists

A

muscle tremors, restlessness, headache, arrythmias and tachycardia. Hypokalemia in high doses

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26
Q

LABAS AND SABAS should be used with

A

Inhaled Corticosteroids for anti-inflammatory therapy

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27
Q

2 steps of Glucocorticoid receptors

A
  1. bind GS and GR undergoes confirmational change, ebcomes activates and dissociates from multi-protein complexes
  2. GR transolcates into the nucleus and regulates gene expression.
28
Q

Which enzyme moves a gene to the active stage

A

histone acetyltransferases

29
Q

which enzyme silences the genes

A

histone deacetylases

30
Q

what genes do GCS turn on/off

A

Switch ON anti-inflammatory gene expression
Switch OFF inflammatory gene expression

31
Q

Do CS have any benefit in the initial stages

A

NO, not in an acute attack bc they are NOT bronchodilators just anti-inflammatory agents.

32
Q

what do CS enable in asthma

A

less frequent use of bronchodilators

33
Q

List 4 common systemic corticosteroids

A

prednisone, prednisolone, methylprednisolone, hydrocortisone

34
Q

Name 6 inhaled corticosteroids

A

Beclomethasone, budenoside ciclesonide, fluticasone, mometasone, triamcinolone

35
Q

When should ICS be used for asthma

A

drug of choice for regular controller therapy, should be used regularly

36
Q

side effects local of ICS

A

hoarseness (dysphonia) caused by drug deposition on vocal cords
throat irritation
coughing
thrush

37
Q

ICS prolonged use SE

A

increased pneumonia risk
cataracs
HPA axis supression
osteoporosis
growth restriction
skin thinning/bruising

38
Q

benefits of LABA ICS therapy

A

adding a laba to an ICS is more effective than doubling ICS dose which also limits risk of side effects.

39
Q

what does the M3 receptor in the airways do

A

bronchoconstriction, increased bronchial secretions

40
Q

name a SAMA

A

ipratropium

41
Q

name a LAMA

A

Tiotroprium

42
Q

SAMA onset of action, peak, duration of action

A

15 mins, peak at 1-2 hours, duration of action 5-6 hours

43
Q

Ipratropium SE

A

metallic/bitter taste when inhaled

44
Q

LAMA MOA

A

functionally selective for M3 receptors due to faster disassociation from M2

45
Q

Onset, peak, duration of action

A

30 mins, 3-4 hours, 24 hours

46
Q

what is the dosing of a LAMA

A

once daily dosing

47
Q

SE LAMA

A

dry mouth, tachycardia, urinary retentoin

48
Q

why is tiotropium better than ipratropium?

A

more specific, longer duration of efficacy

49
Q

are antimuscarinics more or less effective as bronchodilators than b2 agonists

A

less

50
Q

role of antimuscarinics in COPD

A

release of ACh causes vagally-mediated bronchospasm, major reversible component of COPD

51
Q

LABA + LAMA combo therapy

A

additive bronchodilator effect, not synergistic

52
Q

PDE’s roles

A

hydrolyze cAMP and cGMP, hence they deactivate their cAMP/cGMP mediated effects

53
Q

which PDE is important for anti-inflammatory stuff

A

PDE 4

54
Q

methylxanthines are ?

A

PDE inhibitors

55
Q

Methylxanthines act to relax airways by

A

inhibit PDEs
Antagonize Adenosine receptors
activation of histone deacetylases

56
Q

how do methylxanthines work on adenosine recepors

A

adenosine causes bronchocontriction and inflammation. Methylxanthines inhibit the receptors thus causing bronchodilation and anti-inflammatory effects

57
Q

name two methylxanthines

A

theophylline and aminophylline

58
Q

PDE4 inhibitor

A

roflumilast

59
Q

Indication of Roflumilast

A

Patients with COPD with chronic bronchitis , with frequent exacerbations

60
Q

can roflumilast be used alone

A

NO! only has anti-inflammatory effects, doenst work for relief of acute symptoms.

61
Q

what is Roflumilast CI in

A

patients taking theophylline because it reduces roflumilast clearance

62
Q

Leukotrienes are a family of ______

A

inflammatory lipid mediators

63
Q

leukotrienes cause

A

narrowing and swelling of the airways in the lungs

64
Q

name two leukotriene receptor antagonists

A

Montelukast and Zafirlukast

65
Q
A

PHRM 211 (25 decks)

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