16 - Respiratory Pharmacology Flashcards

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1
Q

What is the pathophysiology behind asthma?

A
  • TH2 and eosiniphil driven inflammation resulting in mucosal oedema, bronchoconstriction, mucus plugging and bronchial hyperresponsiveness

- Chronic inflammatory, intermittent, reversible

  • Parasympathetic M3 causes bronchoconstriction
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2
Q

What does asthma control mean?

A
  • Minimal symptoms during day and night
  • Minimal need for reliever medication
  • No exacerbations
  • No limitation of physical activity
  • Normal lung function (FEV1 and/or PEF >80% predicted or best)
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3
Q

What should you check with a patient before you step them up or down the asthma treatment ladder?

A
  • Adherance
  • Inhaler technique
  • Eliminate trigger factors
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4
Q

What is the stepwise approach for the treatment of asthma?

A

- Step 1 – short acting β2 agonists as needed, consider low dose ICS

- Step 2 – regular low dose ICS

- Step 3

A. LABA + low dose ICS

B. LABA + ↑ dose ICS / stop LABA if no effect

- Step 4 – LABA + high dose ICS (can add LTRA/aminophylline)

- Step 5 – daily oral steroid + high dose ICS + consider others

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5
Q

Should you add LABA or LTRA after low dose ICS?

A

NICE suggests LTRA as this is cheaper but BTS/SIGN says LABA and most patients do end up on this

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6
Q

How do SABA’s act to help mild/intermittent asthma?

A
  • Bronchodilation by agonising beta-2 receptors
  • Gs protein so activate adenyl cyclase, and then PKA which phosphorylates myosin light chain kinase to inhibit smooth muscle contraction.
  • Also increases mucus clearance by action of cilia
  • Symptom relief by reversing bronchoconstriction, only use as required
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7
Q

What are some examples of beta agonists and when are they used?

A

SABA: as needed

LABA: add on therapy with ICS and p.r.n SABA. Can be used as a preventer before exercise to prevent exacerbations and improve lung function

(formoterol has rapid onset of action similar to salbutamol but long acting. More potent and efficacious than salmeterol)

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8
Q

What are some adverse affects that can occur when using B2 agonists and what drugs cannot be used alongside it?

A
  • May generate a tolerance if constantly using
  • Tachycardia
  • Palpitations
  • Anxiety
  • Tremor
  • Muscle cramps (LABA)
  • Increased renin and glycogenolysis so could raise b.p
  • Don’t use with beta blockers as may reduce effects of beta agonist
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9
Q

What should LABA always be taken with and why is it taken as a combined inhaler?

A

ICS - increased risk of death when prescribed alone

  • Adherance
  • Ease of use
  • Less prescriptions
  • Safer
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10
Q

When are inhaled corticosteroids added on to asthma treatment and what is their mechanism of action?

A
  • When reliever alone not sufficient and using more than 3 times a week or waking up with symptoms

- Reduces mucosal inflammation, widens aiway and reduces mucus to reduce symptoms, exacerbations and death

  • Lipid soluble so activate intracellular GC receptor alpha and cause gene activation of B2 receptors and inactivation of inflammatory mediators and cytokines
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11
Q

What are some side effects of ICS being used as a regular preventer therapy?

A
  • Can have local immunosuppressive action e.g oral candidiasis, hoarse voice
  • Pneumonia risk with COPD
  • Very few ADRs if taken correctly
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12
Q

What are some examples of ICS’s and what are their pharmacokinetic properties?

A
  • Poor oral bioavailability which is why little side effects and you inhale.
  • Slow dissolution in aqueous bronchial fluid but high affinity for glucocorticoid receptor
  • When inhaling some will go to stomach and some will sta in mouth
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13
Q

After a an ICS and a LABA have been added to an asthma treatment and this is still not controlling the patient’s condition, what can be added next?

A
  • Increase dose of ICS to medium by having two puffs a day
  • Add LTRA (montelukast)
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14
Q

What is the mechanism of action of leukotriene receptor antagonists like montelukast?

A

- Leukotrienes are released by mast cells/eosinophils, induce bronchoconstriction, mucus secretion and mucosal oedema and promote inflammatory cell recruitment through GPCR CysLT1

  • LTRAs block the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor
  • Only works in 15% of asthmatics
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15
Q

What are the side effects of using a LTRA?

A
  • No major drug interactions but:
  • Headache
  • GI disturbance
  • Dry mouth
  • Hyperactivity
  • Angiooedema
  • Anaphalyxis
  • Fever
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16
Q

How do long acting muscarininc antagonists (antimuscarinics) act as an addition controller therapy for asthma and what are the side effects of this drug?

A

- Tiotropium bromide and Ipratropium bromide

  • Selective for M3 (SAMA are less selective) and have anticholinergic effects but not as effective as beta agonists in dilating

- Dry mouth, urinary retention, dry eyes

  • Given in severe asthma and COPD
17
Q

How do methylxanthines work as a controller therapy for severe asthma and what are some of the side effects?

A
  • Theophylline oral or aminophylline IV in acute

- Adenosine receptor antagonist - inhibit phosphodiesterase and increase cAMP

  • Narrow TI and can cause arrhythmias so keep on ECG. Also have N+V and reflux
  • Metabolised by CYP450 so any inhibitors (e.g ciprofloxacin and erythromycin) will increase theophylline concentration
18
Q

When would you get a patient to take a high dose ICS?

A

When there are high levels of eosinophils in the sputum

19
Q

When are oral steroids used in asthma?

A
  • Post acute exacerbation for at least 5 days and 5-7 days in exacerbation of COPD
  • Prednisolone
  • Can be given with AntiIgE and AntiIL-5 monoclonal antibodies for steroid tapering
20
Q

When diagnosing a patient with asthma what should you give them apart from pharmacological agents?

A

- Self management plan for better day to day management and reduce exacerbations

  • Useful for children and carers
  • Instructions on when to step up and down. Need to review after exacerbation
21
Q

What are the characteristics of acute sever and life threatening asthma?

A
  • Only need one bold to be classed as life threatening
  • Fatal when CO2 starts to increase as patient is tiring. They need mechanical ventilation
22
Q

What is the treatment plan when someone presents with acute severe/life threatening asthma?

A

OSHIT ME

Oxygen: get them to 94-98%

Salbutamol: high dose nebulised oxygen driven

Hydrocortisone/Prednisolone: IV or oral

Ipratropium Bromide: nebulised SAMA not LAMA like tio.

Theophylline/Aminophylline: I.V if life threatening and no success with above

23
Q

What are the five tasks needed for management of stable COPD?

A
24
Q

What is the treatment plan when someone presents with an acute exacerbation of their COPD?

A

- Nebulised salbutamol and/or ipratropium

  • If hypercapnic or acidotic give air in nebuliser not oxygen

- Antibiotics

- Oral steroids: sometimes but not as effective as in asthma as not effective on neutrophils like eosinophils

  • Review chronic treatment and aciton plan
25
Q

What are the different inhaler options?

A
  • Pressured metered dose inhalers: slow breath in and hold. can be used with a spacer

- Breath actuated MDI: automatic actuation

- Dry power inhalers: fast deep inhalation

NEED THE RIGHT TECHNIQUE TO GET THE RIGHT PARTICLE SIZE AND RIGHT DEPOSITION

26
Q

How can you check someone is using the right inhaler technique?

A

In-check DIAL device measures inspiratory flow for different devices

27
Q

What is the difference between a metered dose and dry powdered dose inhaler?

A

(google more)

  • Dry powder has more pharyngeal deposition
28
Q

What antihypertensive drug should you not give to asthmatics?

A

Beta antagonists

29
Q

What drug can you give an asthmatic to reduce her coughing at night?

A
  • Make sure they’re taking ICS and reliever
  • Give muscarinic antagonist like montelukast as parasympathetics are more active at night causing the cough so this depresses this
30
Q

When prescribing ICS to COPD patients what risk do we need to be aware of?

A

High pneumonia risk as they are immunocompromised

31
Q

Why are inhalers prescribed by brand name not class like other drugs?

A

Patients may have incorrect inhaler technique with a different brand, even if same mixture in the inhaler

32
Q

What can help to improve a patient’s inhaler technique?

A

Spacer for MDIs gets it straight to lungs and not in mouth