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anticholinergic Flashcards

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1
Q

What is the Clinical Indications for Use of anticholinergic?

A
  1. COPD maintenance
    - -> via Inhaled anticholinergic bronchodilator

2.COPD with airflow obstruction
–> Inhaled for combined anticholinergic and β
agonist bronchodilators

  1. Allergic and non allergic perennial rhinitis
    - -> Anticholinergic Nasal spray (itrapromium bromide)
  2. cardiac medication
    - ->Intravenous anticholinergic (atropine sulfate)
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2
Q

what is the effect of anti-cholinergic?

A
  • increase HR
  • pupil dilation
  • drying of upper airway
  • reduced tearing
  • urinary retention
  • constipation
  • reduced mucociliary action
  • Inhibit bronchoconstriction
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3
Q

What is the normal result of activation of the cholinergic pathway?

A

if M3 receptor is stimulated by ACh or drug
- Results in increased intracellular Ca++
and bronchoconstriction,
mucous & histamine release

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4
Q

What is the action of anti cholinergic?

A

inhibits the pathway of parasympathetic receptors

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5
Q

What structure or form does anti-cholinergic drug come in

A

Tertiary , Quaternary forms

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6
Q

what is the characteristics of tertiary anti-cholinergic drug ?

A

Easily absorbed in the bloodstream

Cross the blood brain barrier

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7
Q

what is the characteristics of Quaternary forms anti-cholinergic drug ?

A
  • Poorly absorbed in the bloodstream or central
    nervous system
  • Better for inhalation
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8
Q

What is an advantage of Quaternary forms anti-cholinergic drug ?

A
  • doesnt cause any systemic effect
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9
Q

example of tertiary anti-cholinergic drug ?

A

Atropine and scopolamine

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10
Q

function of scopolaminne?

A

treat motion sickness and postoperative nausea and vomiting

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11
Q

What is the Pharmacological Effects of Tertiary ammonium compound effects?

A
  • Respiratory tract
  • Central nervous system
  • Eyes
  • Cardiac
  • Gastrointestinal
  • Genitourinary
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12
Q

What is the Pharmacological Effects of Tertiary ammonium compound effects?

A

Side effects are localized to the site of drug

exposure

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13
Q

What is the relationship between parasympathetic tone and bronchdilation

A

inverse relationship

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14
Q

What is the mechanism of action of anti-cholinergic

A

it blocks ach from attaching to the muscarnicic receptor

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15
Q

What factor causes Vagally mediated reflex bronchoconstriction

A 
Irritant aerosols
cold air
high airflow rates
smoke,
fumes
histamine release
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16
Q

How does these factors cause bronchoconstriction

A

Afferent impulse to CNS –> reflex cholinergic
efferent impulse –> constriction of airway smooth
muscle –> mucus and cough

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17
Q

What structures carry out the effects of the stimulation of PNS

A

airway epithelium
submucosal glands
smooth muscle
mast cells

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18
Q

What is the effect of stimulationn of PNS in airway?

A

increase bronchomotor tone

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19
Q

What are the 3 Muscarinic Receptor Subtypes?

A

M1, 2, 3

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20
Q

the function of M1?

A

Parasympathetic post ganglia

  • Facilitate neurotransmission and bronchoconstriction
  • Cause secretion and rhinitis in the nose
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21
Q

the function of M2?

A
  • Inhibit continued use of acetylcholine

* Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for M1 and M3

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22
Q

the funciton of m3?

A
  • Smooth airway muscle and submucosal glands
  • Cause bronchoconstriction
  • Cause secretion and rhinitis in the nose
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23
Q

What does nonspecific blockade?

A

the drug action isn’t specific to any receptor subtype?

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24
Q

what is an example of nonspecific blockade

A

ipratropium

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25
what is the effect of blocking M3?
improve airflow because: * Reduces bronchoconstriction * Reduces pulmonary secretions * Reduces histamine release
26
What is the side effect of anticholinergic?
``` – Dry mouth (most common) – Coughing due to dryness – Mydriasis (eyes should be protected) – SVN (make sure drug is contained and dont come in contact with patient face): also pharyngitis, dyspnea, flulike symptoms, bronchitis, upper respiratory infection ```
27
which anticholingeric is used in asthma patient?
Tiotropium ® Respimat **Anti muscarinics not superior to β agonists for asthma
28
when is Tiotropium ® Respimat used for asthma?
- Nocturnal asthma - Psychogenic asthma - Asthmatics being treated for another condition with β blockers - An alternative to theophylline - In acute/severe episodes not responding to β agonist - use with SABA for AE asthma due to its synergistic , e.g. combivent`
29
When is Spiriva Respimat indicated?
Indicated as add on treatment to high dose ICS&LABA in patients with severe persistent symptoms and have experienced an exacerbation in the previous year
30
how does Spiriva Respimat help with symptoms?
improved dyspnea QofL scores spirometry lung deflation
31
how can Tiotropium be given for asthma
Combivent (combined with SABA) nebuilzer *usually given after b-agonist as it has rapid onset
32
What is an example of Quarternary drug?
atrovent
33
what is the drug structure of atropine sulfate
tertiary amine derivative of | atropine
34
how is atropine sulfate delivered?
nebulized and parenteral | administration
35
when is atropine sulfate indicated?
mostly used as IV cardiac drug | Effect => ↑ HR (vagal blockade)
36
what is the drug structure of glycopyrrolate
quaternary amine compound
37
when is glycopyrrolate indicated?
- NM blockage reversal - drying agent used pre -intubation to reduce secretion - used in OR to wake patient up due to similar effect to atropine
38
what is the drug structure of ipratropium bromide | Atrovent
quarternary amine derivative of atropine | non selective anti muscarinic
39
What is ipratropium bromide | Atrovent effect?
local effects on large diameter, central | airways
40
the onset, peak and duration of ipratropium bromide | Atrovent
onset: 5- 15 min; peak: 1 -2 hrs (slower than SABA) duration: 4 - 6 SAAC
41
What is the indication of ipratropium bromide | Atrovent
bronchodilator therapy for COPD or Asthma in Acute Resp.distress
42
the precaution of ipratropium bromide | Atrovent
not as rapid a response for acute bronchospasm as SABA glaucoma, urinary retention
43
adverse effect of atrovent
bad taste dry mouth eye problems headache
44
what is the Route/dose/frequency of atrovent?
1. inhaled via nebulizer OR nubules - -> 1-2 mls of 250 mcg/mL in 3 mls N/S - ->prn 2. pMDI -->20 mcg/puff --> 4-8 puffs prn for acute exacerbations of Asthma and COPD with salbutamol
45
what is the drug structure of tiotropium bromide Spiriva
quaternary amine derivative of atropine
46
characterisitc of spiriva?
similar to ipratropium, but long acting | receptor selectivity M1 , M3
47
the onset, peak and duration of spirivia?
* onset: 30 min; * peak: 3 hrs * duration: 24 hrs
48
indication of spirivia?
``` - Long term maintenance of bronchodilation due to COPD - bronchodilation; good for moderate to severe COPD ```
49
contraindication of spirivia?
lactose intolerance 18yrs+ Not for acute bronchospasm
50
Route/dose/frequency of spirivia
inhaled - ->DPI Handihaler - 18mcg - once daily - ->SMI Respimat - once daily q a.m.
51
What other drug can atrovent or LAMA be combined with
another LABA Tiotropium- Olodaterol / Inspiolto ®
52
dose/frequency of inspiolto?
SMI: 2.5μg OD via respimat
53
what is the brand that combine ipratropium and salbutamol together?
Duoneb, combivent respimat
54
what is the dosage of duoneb?
0.5 mg ipratropium and 2.5 mg salbutamol
55
what is the dosage of respimat?
20 μg ipratropium and 100 μg salbutamol/puff qid
56
What is the indication of LAMA?
same as with Tiotropium
57
What is the risk of LAMA
Risk: paradoxical bronchospasm
58
What is an example of LAMA?
glycopyrronium - seebri aclidinium bromide - genuair / Tudorza umeclidinium - Ellipta
59
dose/frequency of glycopyrronium?
Seebri® Breezhaler® 59mcg/puff
60
What is the effect of Seebri® Breezhaler®
- Reduced breathlessness - Improved dyspnea - delay moderate or severe exacerbation - Use less rescue medication
61
dose/frequency of aclidinium bromide?
BID 400mcg
62
What is advantage of aclidinium bromide
Very low and transient systemic exposure --> reduce potential side effects Potent antagonist for all muscarinic receptors
63
What is soime LABA/LAMA combination?
Aclidinium/Formoterol : Duaklir® Genuair® | umeclidinium / vilantero : Anoro ®Ellipta
64
dose/frequency of Aclidinium/Formoterol?
DPI 400 μg/12μg per inhalation bid
65
What is umeclidinium bromide
a LAMA Long Acting Once Daily Dosing TX of bronchoconstriction of airflow obstruction
66
dose/frequency of umeclidinium bromide?
Incruse® Ellipta | DPI: 62.5 μg/inhalation, once daily
67
dose/frequency of Anoro ®Ellipta?
62.5 μg umeclidinium & 25 μg vilanterol/puff | OD
68
What is the triple therapy in canada?
TRELEGY ELLIPTA - fluticasone furoate 100mcg - umeclidinium 62.5mcg - vilanterol 25mcg **addition of an ICS to LAMA+LABA
69
indication of triple therapy
- long term, once daily - maintenance treatment of chronic obstructive pulmonary disease - for frequent or severe AECOPD who symptoms cannot be controlled by LAMA+LABA
70
what is a Phosphodiesterase-4 Inhibitor?
Roflumilast, Daxas®
71
indication of Phosphodiesterase-4 Inhibitor?
anti-inflammatory therapy for COPD - for frequent or severe AECOPD who symptoms cannot be controlled by triple therapy*** - reduce the number of flare-ups or worsening of COPD symptoms (exacerbation). - patients with severe and very severe airflow limitation caused by excessive airway secretions linked to chronic bronchitis
72
dose/frequency of Roflumilast?
tablet, oral 500mcg OD
73
What is the MOA of PDE4?
PDE4 is expressed in - airway smooth muscle, - pulmonary nerves - proinflammatory - immune cells. *contribute to asthma inflammation
74
What is the action of Roflumilast | (Daxas®)?
``` inhibits PDE 4 targeting 3 componenets of COPD: - bronchoconstriction mucus - hypersecretion - airway remodelling ```
75
What is the precautions of Roflumilast | Daxas®
- not recommended for patients with primary emphysema - Roflumilast is not a bronchodilator and should not be used for treating sudden shortness of breath.
76
dose/frequency of Roflumilast | (Daxas?
500 mcg | OD, PO
77
what is the side effect Roflumilast | (Daxas?
N&D, headaches, tremors, weight loss
78
What is the contraindication of Roflumilast 500mcg
Cannot be used under 18, pregnant liver function problems
79
what is Xanthines
- central ventilatory drive stimulant - respiratory muscle strength & endurance
80
what is the indication of Xanthines
1. apnea of prematurity - -> caffeine citrate (safer, higher therapeutic 2. COPD - ->Theophylline: alternative to β 2 agonist and anticholinergics - ->Not used in acute exacerbations 3. use in asthhma - -> Theophylline: maintenance therapy if persistent asthma despite β 2 , ICS - -> a weaker bronchdilator than beta 2 - -> use late in ER treatment of asthma
81
what is exampe of Xanthines?
methylxanthines - ->Theophylline - ->Theobromine - ->Caffeine
82
Wat is the effect of Xanthines
``` • CNS stimulation • Cardiac muscle stimulation • Diuresis • Bronchial, uterine, and vascular smooth muscle relaxation • Theophylline is generally classified as a bronchodilator • Peripheral and coronary vasodilation • Cerebral vasoconstriction -->Used in headache remedies ```
83
Wat is te MOA of xanthines
• Smooth muscle relaxation via inhibition of phosphodiesterase (?) • Antagonism of adenosine receptor (?) • Enhancement of catecholamine release (?)
84
Wat is te lung effect of xantines?
* bronchodilation * increase resp muscle strength * increase resp muscle endurance * central ventilatory drive
85
wat is te cardiac effect of xantines
increase cardiac output decrease pulm vascular resistance increase myocardial perfusion in ischemia
86
what is the route/dose of xantines
theophylline, Theo dur IV 0.8 and 1.6 mg/ml in 5% dextrose Tabs 400 and 600 mg tabs (slow release)
87
wat is te terapeutic range of xantines
55 -110 m mol/L dangerous if above: 20 mcg/L 110 mmol/L usually toxic
88
What is te side effect of xantines?
CNS anxiety, dizziness, headache, restless, insomnia, irritability, seizures GI nausea/vomiting, diarrhea , anorexia, Renal excessive diuresis CVS palpitations, arrhythmias, tachycardia, hypertension/hypotension
89
what increase Conditions that increase theophylline levels:
``` Viral hepatitis Left ventricular failure corticosteroids alcohol beta blockers propranolol renal failure ```
90
Wat decrease theophylline levels:
Smoking Isoproterenol IV barbiturates Benzodiazpines Valium
91
When is xanthines used in asthma?
Only after other relievers and controllers have | failed
92
When is xanthines used in COPD?
If ipratropium bromide and β 2 agonist fail to | provide control
93
what does mast cell and basophils release
leukotrienes (LT)
94
wt is the function of leukotrienes
tpotent broncho constrictors and stimulate other cells to cause: - Airway edema - Mucus secretion - Ciliary beat inhibition - Recruitment of other inflammatory cells
95
What is an example of Antileukotriene Agents | LTRA
Zafirlukast Accolate ® | Montelukast Singulair ®
96
Dose/frequency/route of accolate?
Oral 20mg Dosage | BID
97
onset,peak, duration of accolate?
onset: 30 min peak: 3-4 hr ; duration 12 hr
98
What is te side effect of Antileukotriene
* Headache * Infection * Nausea * Diarrhea * Pain
99
Dose/frequency/route of Montelukast Singulair?
for children Oral Dosage chewable or granules 4mg (2-5yrs), 5mg (6- 14yrs) adult 10 mg
100
onset,peak, duration of Montelukast | Singulair?
Onset 30 min ; peak 3- 4 hr duration 24 hours OD
101
What is the advantage of Antileukotriene in treating asthma?
- safe, with few side effects | - effective for patient wit aspirin sensitivity and exercise induced asthma
102
What is the disadvantagge of Antileukotriene
- systemic drug exposure, not limited to lung | - unknown long term toxicitity
103
What is severe asthma?
“Asthma which requires treatment with : - high dose ICS and a second controller for the previous year, or - systemic corticosteroids for 50% of the previous year to prevent it from becoming ‘uncontrolled’ or - which remains ‘uncontrolled’ despite this therapy
104
How to define uncontroll asthma
Poor symptom control - ACQ consistently >1.5 - ACT <20 - child asthma control test cACT ) <20 Frequent severe exacerbations Two or more systemic steroid bursts (≥3 days in the previous year Serious exacerbations - hospitalisation, - intensive care stay - mechanical ventilation Airflow limitation FEV 1 <80% predicted of personal best
105
what is difficult to treat asthma?
Difficult to treat asthma can be hard to control despite high intensity asthma medications, due to: Poor medication adherence Poor inhaler technique Ongoing exposure to sensitising or irritant agents Comorbidities (rhinosinusitis, obesity, GERD, obstructive sleep apnoea) Incorrect diagnosis confounded with upper airway dysfunction, cardiac failure or lack of fitness Psychosocial issues
106
What is thhe problem with severe asthma compared to normal asthma population
Have higher morbidity rates | Are at increased mortality risk
107
Wat is a biologic
A pharmaceutical product that is produced by biotechnology, generated by lviing cells
108
Wat are the examples of biologic
- growth factors - antibodies - clotting factors - antibody factor - recmobinant proteins
109
What is te characteristic of Severe eosinophilic asthma
Severe eosinophilic asthma is characterised by persistent eosinophilic airway inflammation, and includes disease that is driven by either allergic or non allergic triggers 1,2
110
Wat is the problem wit eosinophilic
Eosinophils are a source of a wide variety of | cytokines and other mediators
111
Wat are 2 But inflammatory infiltrating eosinophils tat are recruited into te lung
Type 1: Homeostatic regulatory eosinophils type 2: Inflammatory infiltrating eosinophils
112
Wat does Eosinophil activation leads to production ?
IL 5
113
wat is the function of IL 5
IL-5 has a direct effect on eosinophil growth, activation and surviva
114
Wat are examples of anti IgE
Xolair® Omalizumab | --> a Monoclonal Antibody
115
Wat is Omalizumab
is a subcutaneously injected monoclonal | antibody.
116
indication of omalizumb?
1. treatment of moderate to severe asthma in adults and adolescents 12 years of age and older who have a positive skin test - or reactivity to a perennial aeroallergen 2. treating seasonal allergic rhinitis
117
Whats te MOA of omalizumb
MOA: drug blocks the binding of IgE to mast cell --> causing reduction of mediators that can be released in allergic response
118
dose/form of omalizumb
reconstituted and has a concentration of 150mg/1.2ml once mixed. Dosing is q2 - 4 wks, depending of serum IgE level
119
clincal use of omalizumb
a prophylactic agent used in moderate to severe persistent asthma It may allow reduction of asthmatic rescue agents. It may allow reduction of high dose ICS or prevent an increase in the dose of inhaled corticosteroids.
120
what is te contraindication of omalizumb
1. not indicated for acute relief or rescue therapy 2. not a replacement for ICS 3. not optimal as monotherapy in persistent asthma.
121
Wat is Il-5 inibitors for
Three drugs targeting IL 5 or its receptor have been developed to treat severe eosinophilic asthma.
122
What are some example of iL-5 ?
mepolizumab NucalaTM reslizumab CinqairTM benralizumab Fresenra TM)
123
indication of iL5
- inadequately controlled severe asthma with high dose inhaled corticosteroids - (ICS) and an additional asthma controller(s) & (e.g. LABA) + -have a blood eosinophil count of ****≥150 cells/mL) at initiation of treatment OR 300 cells/mL in the past 12 months
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