anticholinergic Flashcards
What is the Clinical Indications for Use of anticholinergic?
- COPD maintenance
- -> via Inhaled anticholinergic bronchodilator
2.COPD with airflow obstruction
–> Inhaled for combined anticholinergic and β
agonist bronchodilators
- Allergic and non allergic perennial rhinitis
- -> Anticholinergic Nasal spray (itrapromium bromide) - cardiac medication
- ->Intravenous anticholinergic (atropine sulfate)
what is the effect of anti-cholinergic?
- increase HR
- pupil dilation
- drying of upper airway
- reduced tearing
- urinary retention
- constipation
- reduced mucociliary action
- Inhibit bronchoconstriction
What is the normal result of activation of the cholinergic pathway?
if M3 receptor is stimulated by ACh or drug
- Results in increased intracellular Ca++
and bronchoconstriction,
mucous & histamine release
What is the action of anti cholinergic?
inhibits the pathway of parasympathetic receptors
What structure or form does anti-cholinergic drug come in
Tertiary , Quaternary forms
what is the characteristics of tertiary anti-cholinergic drug ?
Easily absorbed in the bloodstream
Cross the blood brain barrier
what is the characteristics of Quaternary forms anti-cholinergic drug ?
- Poorly absorbed in the bloodstream or central
nervous system - Better for inhalation
What is an advantage of Quaternary forms anti-cholinergic drug ?
- doesnt cause any systemic effect
example of tertiary anti-cholinergic drug ?
Atropine and scopolamine
function of scopolaminne?
treat motion sickness and postoperative nausea and vomiting
What is the Pharmacological Effects of Tertiary ammonium compound effects?
- Respiratory tract
- Central nervous system
- Eyes
- Cardiac
- Gastrointestinal
- Genitourinary
What is the Pharmacological Effects of Tertiary ammonium compound effects?
Side effects are localized to the site of drug
exposure
What is the relationship between parasympathetic tone and bronchdilation
inverse relationship
What is the mechanism of action of anti-cholinergic
it blocks ach from attaching to the muscarnicic receptor
What factor causes Vagally mediated reflex bronchoconstriction
Irritant aerosols cold air high airflow rates smoke, fumes histamine release
How does these factors cause bronchoconstriction
Afferent impulse to CNS –> reflex cholinergic
efferent impulse –> constriction of airway smooth
muscle –> mucus and cough
What structures carry out the effects of the stimulation of PNS
airway epithelium
submucosal glands
smooth muscle
mast cells
What is the effect of stimulationn of PNS in airway?
increase bronchomotor tone
What are the 3 Muscarinic Receptor Subtypes?
M1, 2, 3
the function of M1?
Parasympathetic post ganglia
- Facilitate neurotransmission and bronchoconstriction
- Cause secretion and rhinitis in the nose
the function of M2?
- Inhibit continued use of acetylcholine
* Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for M1 and M3
the funciton of m3?
- Smooth airway muscle and submucosal glands
- Cause bronchoconstriction
- Cause secretion and rhinitis in the nose
What does nonspecific blockade?
the drug action isn’t specific to any receptor subtype?
what is an example of nonspecific blockade
ipratropium
what is the effect of blocking M3?
improve airflow because:
- Reduces bronchoconstriction
- Reduces pulmonary secretions
- Reduces histamine release
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
which anticholingeric is used in asthma patient?
Tiotropium ® Respimat
**Anti muscarinics not superior to β agonists for
asthma
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`
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
how does Spiriva Respimat help with symptoms?
improved dyspnea
QofL scores
spirometry
lung deflation
how can Tiotropium be given for asthma
Combivent (combined with SABA)
nebuilzer
*usually given after b-agonist as it has rapid onset
What is an example of Quarternary drug?
atrovent
what is the drug structure of atropine sulfate
tertiary amine derivative of
atropine
how is atropine sulfate delivered?
nebulized and parenteral
administration
when is atropine sulfate indicated?
mostly used as IV cardiac drug
Effect => ↑ HR (vagal blockade)
what is the drug structure of glycopyrrolate
quaternary amine compound
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
what is the drug structure of ipratropium bromide
Atrovent
quarternary amine derivative of atropine
non selective anti muscarinic
What is ipratropium bromide
Atrovent effect?
local effects on large diameter, central
airways
the onset, peak and duration of ipratropium bromide
Atrovent
onset: 5- 15 min;
peak: 1 -2 hrs (slower than SABA)
duration: 4 - 6
SAAC
What is the indication of ipratropium bromide
Atrovent
bronchodilator therapy
for COPD or Asthma
in Acute Resp.distress
the precaution of ipratropium bromide
Atrovent
not as rapid a
response for acute
bronchospasm as
SABA
glaucoma, urinary
retention
adverse effect of atrovent
bad taste
dry mouth
eye problems
headache
what is the Route/dose/frequency of atrovent?
- inhaled via nebulizer OR nubules
- -> 1-2 mls of 250 mcg/mL in 3 mls N/S
- ->prn - pMDI
–>20 mcg/puff
–> 4-8 puffs prn for acute exacerbations of
Asthma and COPD with salbutamol
what is the drug structure of tiotropium
bromide
Spiriva
quaternary amine derivative of atropine
characterisitc of spiriva?
similar to ipratropium, but long acting
receptor selectivity M1 , M3
the onset, peak and duration of spirivia?
- onset: 30 min;
- peak: 3 hrs
- duration: 24 hrs
indication of spirivia?
- Long term maintenance of bronchodilation due to COPD - bronchodilation; good for moderate to severe COPD
contraindication of spirivia?
lactose intolerance
18yrs+
Not for acute bronchospasm
Route/dose/frequency of spirivia
inhaled
- ->DPI Handihaler
- 18mcg
- once daily
- ->SMI Respimat
- once daily q a.m.
What other drug can atrovent or LAMA be combined with
another LABA
Tiotropium- Olodaterol / Inspiolto ®
dose/frequency of inspiolto?
SMI: 2.5μg OD via respimat
what is the brand that combine ipratropium and salbutamol together?
Duoneb, combivent respimat
what is the dosage of duoneb?
0.5 mg ipratropium and 2.5 mg salbutamol
what is the dosage of respimat?
20 μg ipratropium and 100 μg salbutamol/puff
qid
What is the indication of LAMA?
same as with Tiotropium
What is the risk of LAMA
Risk: paradoxical bronchospasm
What is an example of LAMA?
glycopyrronium - seebri
aclidinium bromide - genuair / Tudorza
umeclidinium - Ellipta
dose/frequency of glycopyrronium?
Seebri® Breezhaler®
59mcg/puff
What is the effect of Seebri® Breezhaler®
- Reduced breathlessness
- Improved dyspnea
- delay moderate or severe exacerbation
- Use less rescue
medication
dose/frequency of aclidinium bromide?
BID 400mcg
What is advantage of aclidinium bromide
Very low and transient systemic exposure
–> reduce potential side effects
Potent antagonist for all muscarinic receptors
What is soime LABA/LAMA combination?
Aclidinium/Formoterol : Duaklir® Genuair®
umeclidinium / vilantero : Anoro ®Ellipta
dose/frequency of Aclidinium/Formoterol?
DPI
400 μg/12μg per inhalation
bid
What is umeclidinium bromide
a LAMA
Long Acting Once Daily Dosing TX of
bronchoconstriction of airflow obstruction
dose/frequency of umeclidinium bromide?
Incruse® Ellipta
DPI: 62.5 μg/inhalation, once daily
dose/frequency of Anoro ®Ellipta?
62.5 μg umeclidinium & 25 μg vilanterol/puff
OD
What is the triple therapy in canada?
TRELEGY ELLIPTA
- fluticasone furoate 100mcg
- umeclidinium 62.5mcg
- vilanterol 25mcg
**addition of an ICS to LAMA+LABA
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
what is a Phosphodiesterase-4 Inhibitor?
Roflumilast, Daxas®
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
dose/frequency of Roflumilast?
tablet, oral
500mcg
OD
What is the MOA of PDE4?
PDE4 is expressed in
- airway smooth muscle,
- pulmonary nerves
- proinflammatory
- immune cells.
*contribute to asthma inflammation
What is the action of Roflumilast
(Daxas®)?
inhibits PDE 4 targeting 3 componenets of COPD: - bronchoconstriction mucus - hypersecretion - airway remodelling
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.
dose/frequency of Roflumilast
(Daxas?
500 mcg
OD, PO
what is the side effect Roflumilast
(Daxas?
N&D, headaches, tremors, weight loss
What is the contraindication of Roflumilast 500mcg
Cannot be used under 18,
pregnant
liver function problems
what is Xanthines
- central ventilatory drive stimulant
- respiratory muscle strength &
endurance
what is the indication of Xanthines
- apnea of prematurity
- -> caffeine citrate (safer, higher therapeutic - COPD
- ->Theophylline: alternative to β 2 agonist and anticholinergics
- ->Not used in acute exacerbations - 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
what is exampe of Xanthines?
methylxanthines
- ->Theophylline
- ->Theobromine
- ->Caffeine
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
Wat is te MOA of xanthines
• Smooth muscle relaxation via inhibition of
phosphodiesterase (?)
• Antagonism of adenosine receptor (?)
• Enhancement of catecholamine release (?)
Wat is te lung effect of xantines?
- bronchodilation
- increase resp muscle strength
- increase resp muscle endurance
- central ventilatory drive
wat is te cardiac effect of xantines
increase cardiac output
decrease pulm vascular resistance
increase myocardial perfusion in
ischemia
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)
wat is te terapeutic range of xantines
55 -110 m mol/L
dangerous if above:
20 mcg/L
110 mmol/L usually toxic
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
what increase Conditions that increase theophylline levels:
Viral hepatitis Left ventricular failure corticosteroids alcohol beta blockers propranolol renal failure
Wat decrease theophylline levels:
Smoking
Isoproterenol IV
barbiturates
Benzodiazpines Valium
When is xanthines used in asthma?
Only after other relievers and controllers have
failed
When is xanthines used in COPD?
If ipratropium bromide and β 2 agonist fail to
provide control
what does mast cell and basophils release
leukotrienes (LT)
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
What is an example of Antileukotriene Agents
LTRA
Zafirlukast Accolate ®
Montelukast Singulair ®
Dose/frequency/route of accolate?
Oral 20mg Dosage
BID
onset,peak, duration of accolate?
onset: 30 min
peak: 3-4 hr ;
duration 12 hr
What is te side effect of Antileukotriene
- Headache
- Infection
- Nausea
- Diarrhea
- Pain
Dose/frequency/route of Montelukast Singulair?
for children
Oral Dosage
chewable or granules 4mg (2-5yrs),
5mg (6- 14yrs)
adult 10 mg
onset,peak, duration of Montelukast
Singulair?
Onset 30 min
; peak 3- 4 hr
duration 24 hours
OD
What is the advantage of Antileukotriene in treating asthma?
- safe, with few side effects
- effective for patient wit aspirin sensitivity and exercise induced asthma
What is the disadvantagge of Antileukotriene
- systemic drug exposure, not limited to lung
- unknown long term toxicitity
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
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
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
What is thhe problem with severe asthma compared to normal asthma population
Have higher morbidity rates
Are at increased mortality risk
Wat is a biologic
A pharmaceutical product that is produced by biotechnology, generated by lviing cells
Wat are the examples of biologic
- growth factors
- antibodies
- clotting factors
- antibody factor
- recmobinant proteins
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
Wat is the problem wit eosinophilic
Eosinophils are a source of a wide variety of
cytokines and other mediators
Wat are 2 But inflammatory infiltrating eosinophils tat are recruited into te lung
Type 1:
Homeostatic regulatory eosinophils
type 2:
Inflammatory infiltrating eosinophils
Wat does Eosinophil activation leads to production ?
IL 5
wat is the function of IL 5
IL-5 has a direct effect on
eosinophil growth, activation and
surviva
Wat are examples of anti IgE
Xolair® Omalizumab
–> a Monoclonal Antibody
Wat is Omalizumab
is a subcutaneously injected monoclonal
antibody.
indication of omalizumb?
- 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
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
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
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.
what is te contraindication of omalizumb
- not indicated for acute relief or rescue therapy
- not a replacement for ICS
- not optimal as monotherapy in persistent asthma.
Wat is Il-5 inibitors for
Three drugs targeting IL 5 or its receptor
have been developed to treat severe
eosinophilic asthma.
What are some example of iL-5 ?
mepolizumab NucalaTM
reslizumab CinqairTM
benralizumab Fresenra TM)
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
