2. Anticholinergic Bronchodilators

Question 1

what are the two autonomic nerve fibers?

Answer 1

cholinergic fibers and adrenergic fibers

Question 2

what are the two main autonomic neurotransmitters? which autonomic nerve fiber are they released by?

Answer 2

acetylcholine released by cholinergic fibers and norepinephrine (noradrenaline) released by adrenergic fibers

Question 3

1. what is the parasympathetic system responsible for?
2. which region of the spinal cord is it innervated by?
3. describe the length of the pre and post ganglionic fibers, are they short or long?

Answer 3

1. “rest and digest” response
2. craniosacral region
3. long pre ganglionic and short postganglionic

Question 4

1. why must the body oppose the parasympathetic system? (hint: 1 answer)
2. what do drugs do when they block the parasympathetic system? (hint: 1 answer)
3. what are the drugs called that block the parasympathetic system? (hint: 3 answers)

Answer 4

1. to counteract effects of the sympathetic system
2. cause relaxation of airway smooth muscle
3. anticholinergics or antimuscarinics, parasympatholytics, parasympathetic antagonists

Question 5

anticholinergic drugs will oppose the parasympathetic responses, what does the acronym SLUDGE stand for?

Answer 5

S = salivation 
L = lacrimation 
U = Urination 
D = defecation 
G = gastrointestinal motility 
E = excretions

Question 6

what other sympathetic responses do anticholinergics inhibit? (hint: 4 answers)

Answer 6

• bronchoconstriction
• decreased HR
• miosis (constriction of pupil)
• contraction (thickening) of lens

Question 7

1. where are M1 receptors found? what do they facilitate?

2. where are M2 receptors found? what do they inhibit?

Answer 7

1. parasympathetic nerve ganglia, facilitate cholinergic neurotransmission and bronchoconstriction
2. cholinergic nerve endings, inhibit further acetylcholine release from postganglionic neuron

Question 8

where are M3 receptors found? what do they cause? what do they stimulate?

Answer 8

found on airway smooth muscle, cause bronchoconstriction and stimulation of mucus glands (exocytosis)

Question 9

1. what is the vagally-mediated reflex triggered by?
2. what are some of the triggers? (hint:4 answers)
3. which cranial nerve is this bronchoconstriction reflex associated with? what does this control?

Answer 9

1. nonspecific stimuli
2. irritant aerosols, cold dry air, inflammatory mediators and pathogens/allergens
3. cranial nerve 10 (vagus nerve), controls innervation of the heart, lungs, GI tract

Question 10

1. what is the mechanism of action of anticholinergic drugs?
2. what does this inhibit? what does this suppress?
3. what does this prevent?

Answer 10

1. competitive antagonism of Ach at M3 - muscarinic cholinergic receptors
2. inhibits guanylyl cyclase –> cGMP suppression
3. decrease cGMP prevents: airway smooth muscle contraction, glandular secretions, histamine release

Question 11

what are antimuscarinic bronchodilators effective in treating? (hint: 3 answers)

Answer 11

• chronic bronchitis
• emphysema
• vagally-mediated asthma

Question 12

1. what are the tertiary ammonium compound prototypes for current anticholinergic inhaled therapy for managing?
2. what are the 2 naturally occurring belladonna alkaloids?
3. what do these compounds differ by?

Answer 12

1. managing asthma and COPD
2. atropine and scopolamine
3. oxygen molecule bridging carbon-7

Question 13

1. where are the tertiary compounds absorbed? where are they widely distributed?
2. can they cross the blood brain barrier? what does this cause?

Answer 13

1. in the bloodstream, distributed throughout the body

2. yes! causing significant systemic side effects

Question 14

which organs/organ systems are affected by tertiary ammonium compounds? (hint: 6 answers)

Answer 14

• respiratory tract
• CNS
• eyes
• cardiovascular
• gastrointestinal
• genitourinary

Question 15

1. what are the respiratory tract effects of tertiary ammonium compounds?
2. what are the CNS effects?
3. what can increasing doses lead to?

Answer 15

1. inhibits mucociliary clearance and relaxes airway smooth muscle
2. restlessness, irritability, drowsiness, fatigue, mild excitement
3. disorientation, hallucinations or coma

Question 16

1. what are the eye effects of tertiary compounds?

2. cardiovascular effects?

Answer 16

1. pupil dilation, blurred vision, increased intraocular pressure in glaucoma pts
2. decrease in HR with small doses and an increase in HR with large doses

Question 17

1. what are the GI effects of tertiary compounds?

2. what are the GU effects?

Answer 17

1. mouth dryness, dysphagia, decrease GI motility

2. inhibition of urinary sphincter leads to: urinary retention and male impotency

Question 18

1. are Quaternary ammonium compounds absorbed in the body?
2. do they cross the BBB? what does this cause?
3. where are they not rapidly removed from?

Answer 18

1. poorly absorbed in the bloodstream
2. no! causing less systemic side effects (wider therapeutic margin)
3. not rapidly removed from aerosol deposition site

Question 19

1. ipatropium bromide (atrovent) is what class of medication?
2. what type of derivative is this med? potent or nonpotent?
3. onset of action? peak? duration?
4. what does ipatropium lack? where is this med most effective in the respiratory tract?

Answer 19

1. SAMA
2. atropine derivative, potent bronchodilator
3. 15 mins, 1-2 hrs, 4-6 hrs
4. lacks selectivity for muscarinic recptors, most effective on large diameter proximal airways

Question 20

1. what does ipatropium (atrovent) minimize compared to atropine? what does this result in?
2. what are the methods of delivery for ipatropium? including dose.

Answer 20

1. minimizes adverse side effects compared to atropine, resulting in: decrease drying secretions, decrease ocular effects and CNS effects
2. MDI (20 mcg/puff), inhaled solution (0.2 mg/ml) or premixed nebules (500 microg)

Question 21

1. what is the onset of action for anticholinergics (SAMA)? beta agonists (SABA)? (very general)
2. peak effect?
3. duration?
4. presence of a tremor?
5. decrease in PaO2?
6. tolerance?
7. sit of action?

Answer 21

1. slightly slower for anticholinergics, faster for beta agonists
2. slower for anticholinergics, faster for beta agonists
3. anticholinergics longer and shorter for beta agonists
4. none for anticholinergics, present with beta agonists
5. none for anticholinergics, yes for beta agonists
6. none for anticholinergics, yes for beta agonists
7. larger/central airways for anticholinergics and central/peripheral airways for beta agonists

Question 22

1. is tiotropium (spiriva) a potent or nonpotent bronchodilator?
2. onset of action? peak? duration?
3. what is tiotropium good at versus ipatropium? what does this mean?

Answer 22

1. potent bronchodilator
2. 30 mins, 1-3 hours, 24 hours
3. good selectivity for M3 muscarinic receptors meaning, dissociates from M1,M2,M3 receptors at different rates

Question 23

1. what is tiotropium (spiriva) available as?
2. what dosing improves treatment compliance?
3. what is the dosing for a DPI? what type of DPI is normally used? what is deposition dependent on?

Answer 23

1. MDI or DPI
2. once daily dosing
3. 18 microg/inhalation, capsule for handihaler device, deposition dependent on inspiratory effort

Question 24

1. what is the MDI device for tiotropium (spiriva)? how does this improve compliance?
2. what are the two doses available?
3. what dose is recommended for COPD maintenance?
4. what dose is recommended for asthma maintenance?

Answer 24

1. respimat - improved compliance through ease of use
2. 1.25 mcg/actuation OR 2.5 mcg/actuation
3. 2 puffs (5.0 mcg) OD
4. > 12 years = 2 puffs (2.5 mcg) OD

Question 25

1. what type of med is Umeclidinium (Incruse)? 2. does it act locally or systemically? what does this cause? duration of action? 3. what does this med inhibit? 4. what delivery device is available for this med? how often should it be taken?

Answer 25

1. LAMA 2. locally to produce prolonged bronchodilation, 24 hour duration of action 3. competitively inhibits binding of Ach at M3 receptors on airway smooth muscle 4. DPI - take once daily via Ellipta

Question 26

1. what type of med is Aclidinium Bromide (Tudorza)? 2. what population of patients is this med for? 3. duration? how often is this taken? what type of device is used? 4. what is this med not used for? (hint: 3 answers)

Answer 26

1. LAMA 2. long term maintenance in COPD patients 3. 12 hours, taken BID, Genuair device 4. not used for acute deterioration, not used in patients with glaucoma or urinary retention

Question 27

1. what type of drug is Glycopyrronium (Seebri)? 2. what type of patients is this med intended for? 3. duration? how often should this be taken? onset? 4. what is the treatment not used for?

Answer 27

1. LAMA 2. long term maintenance of COPD patients 3. 24 hours, taken OD, 5 minutes 4. not for acute deterioration

Question 28

1. what does salbutamol + ipatropium (combivent) combine? 2. what is this med available as? 3. what is the common delivery device used? include dosage.

Answer 28

1. combines short acting B2 agonists and antimuscarinic effects (SABA + SAMA) 2. MDI, inhalational solution, and fixed dose drug in unit dose vials (UDV's) 3. respimat - 20 mcg of ipatropium and 100 mcg salbutamol per actuation

Question 29

1. what does Vilanterol + Umeclidinium (Anoro) combine? 2. what is the only population this drug is designed for? how often is it taken? 3. what type of delivery device is used?

Answer 29

1. combinees long acting B2 agonist and antimuscarinic effects (LABA + LAMA) 2. long term maintenance therapy for COPD only, taken once daily 3. DPI - Ellipta

Question 30

1. how do we monitor ongoing effectiveness of treatment? | 2. what does long term effectiveness rely on?

Answer 30

1. ongoing respiratory assessment --> RR/pattern, breath sounds before/after treatment, assess WOB - monitor flow rates --> peak flow meters, bedside spirometry - monitor ABG and/or pulse oximetry 2. relies on good bedside education

Question 31

1. what is a xanthine? | 2. what is a methylxanthine? list examples

Answer 31

1. nitrogenous compound found in many organs and bodily fluids (blood and urine) 2. methylated drug (CH3 + group) derived from xanthines (caffeine, theophylline and theobromine)

Question 32

1. what do methylxanthines promote? (hint: 2 answers) 2. what is epinephrine fast asthma? 3. what do methylxanthines delay? which mediators?

Answer 32

1. relaxation of airway smooth muscle and inhibit glandular secretions in cases of refractory asthma 2. patients no longer respond to B2 agonists 3. delay release/formation of allergic mediators (histamine and leukotrienes)

Question 33

1. what additional benefits do methylxanthine bronchodilators provide? 2. what is methylxanthine known as?

Answer 33

1. increased CO2 sensitivity in medullary respiratory centres leading to increase alveolar ventilation and increase diaphragmatic responses 2. known as a respiratory stimulant

Question 34

what are the proposed mechanisms of action of methylxanthines? (hint: 3 answers)

Answer 34

1. inhibition of cAMP phosphodiesterase --> increase intracellular cAMP induces bronchial relaxation and anti-inflammatory effects 2. antagonism of adenosine --> block A1 receptors that inhibit cAMP 3. Catecholamine release --> possible production and release of endogenous catecholamines causing bronchial relaxation

Question 35

what are the clinical indications for using methylxanthine bronchodilators (2 answers)

Answer 35

1. second/third line of treatment for COPD and asthma | 2. treat apnea of prematurity in neonates (caffeine citrate - Cafcit)

Question 36

what are the general pharmacologic properties of methylxanthines? (hint: 6 answers)

Answer 36

- CNS stimulation - cardiac muscle stimulation - diuresis - smooth muscle relaxation - peripheral and coronary vasodilation - cerebral vasoconstriction

Question 37

1. what type of med is theophylline? 2. what is special about this drug? 3. is the therapeutic margin narrow or large? 4. what degrades theophylline? 5. what are the routes of administration?

Answer 37

1. xanthine bronchodilator 2. only xanthine derivative with practical therapeutic value 3. narrow therapeutic margin, must monitor serum concentrations carefully 4. hepatic enzymes 5. orally, rectally and IV

Question 38

1. what factors enhance theophylline clearance? | 2. what factors inhibit theophylline clearance?

Answer 38

1. cigarette smoking, certain drugs (corticosteroids, B agonists, benzodiazepines) 2. liver disease, alcoholism, CHF, certain drugs (Ca 2+ channel blockers, leukotriene modifiers, some diuretics, vaccinations)

Question 39

1. what are some signs of toxic effects of theophylline? (hint: 10) 2. what are the signs of severe toxicity? (hint: 2)

Answer 39

1. nausea/vomiting, gastric bleeding, decrease BP, increase HR, palpitations, increase RR, headache, dizziness, agitation 2. seizures and arrhythmias

Question 40

1. what is aminophylline? 2. what is the solubility of this med? what is it ideal for? 3. what is this drug designed to treat? 4. what else can this drug be used for? what does this stimulate?

Answer 40

1. theophylline (85%) dissolved in solvent 2. water soluble, ideal for IV administration 3. treat status asthmaticus (acute bronchoconstriction/life threatening) 4. cheyne-stokes breathing (stimulate central respiratory control centers)

Question 41

1. what is the goal for combining xanthine bronchodilators? 2. what can this help to minimize? 3 what do fixed dose combinations lack? 4. what are the 4 component drugs?

Answer 41

1. goal - drug synergism 2. minimize amount of theophylline and unwanted side effects 3. lack versatility 4. theophylline, ephedrine, CNS depressants and expectorants