Respiratory Medicines

Question 1

Describe the respiratory system structure

Answer 1

It can be divided into 2 cateogories: Upper (Structures in head and neck) and lower (Structures in chest cavity).

Some structures are air conducting passages: Nasal cavity, Pharynx, Larnyx (and epiglottis), Trachea, bronchi and Bronchioles.

Some are responsible for gas exchange: Respiratory bronchi and bronchioles and alveoli

Question 2

What is the purpose of the respiratory system?

Answer 2

To supply oxygen to body and remove CO2 from the tissues

Question 3

What is:

1. External respiration
2. Internal respiration
3. Cellular respiration

Answer 3

1. The exchange of gas from the external enviroment (lungs) and the internal enviroment (blood)
2. The exchange of gas between the blood and body cells
3. The oxidation of glucose to produce energy

Question 4

What are the types of respiratory diseases?

Answer 4

Bronchioitis - caused by a virus. Caused inflammation and congestion of airways

Intersital lung diseases - diseases of the lung which cause scarring of lung tissue (fibrosis) and lead to the lung tissue becoming rigid and therefore hard to breathe. Penuomoconiosis is an example of LF caused by inhalation of dust

Question 5

What do the following mean:

1. Obstructive
2. Restrictive
3. Parenchymal
4. Non-parenchymal

Answer 5

1. Diseases which make it hard to fully exhale air from lungs
2. Hard to fully expand the lungs
3. Diseases caused by the functional tissues of the lungs
4. Lung disease caused by conditions outwith the lungs

Question 6

What are the differences in symptoms and in terms of reversibility of Asthma and COPD?

Answer 6

Asthma is a reversible obstructive airway disease

COPD has limited reversibility due to change in lung structure over time. Therefore there is less reversibilty with perment decline in lung function

Question 7

What are the main classes of medication for COPD and Asthma?

Answer 7

• Relievers: Broncholdilators for acute symptomatic relief (SABA/SAMA, aminophylline)
• Preventers: Long acting bronchodilators (LAMA/LABA), MR aminophylline/theophylline, leukotrine receptor antagonists

Question 8

What is the mechanism of action of B-2 agonists?

What do they do?

Answer 8

Act onB-2 receptors on bronchial smooth muscle. Activate AC which catalyses the conversion of ATP to second messanger cAMP. caMP activates PKa which phospohyrylates MLCK and inhibits its action on MLC. Myosin and actin cannot interact so contraction inhibited.

Stimulates Beta2 receptors resulting in relaxation of bronchial smooth muscle. Often described to patients as “opening the airways”

Question 9

1. Examples of SABA?
2. Onset?
3. Duration of action?
4. Dose depends on?

Answer 9

1. salbutamol and terbutaline
2. rapid onset of action (15 minutes)
3. last for up to 4 hours.
4. Doses vary depending on the person’s age, response to treatment and the preparation prescribed.

Question 10

1. Examples of LABA
2. Duration of action -why?
3. How should they be introduced?
4. What forms are available?
   5.

Answer 10

1. Salmeterol, formoterol, vilanterol
2. Long-acting beta-2 agonists (LABAs) have prolonged receptor occupancy as they are elatively lipophilic so have a duration of action of 12 hrs.
3. A LABA should be introduced at a low dose and the effect monitored before considering a dose increase.
4. The drug is also available in combination with inhaled corticosteroids LAMA or both. Available as preventor of MART with ICS.

Important to watch licenced doses some inhalers are licenced for adults, some for adults and children -many strength combinations available.

Question 11

B-2 agonists:

1. Routes of administration?
2. Caution in patients with?
3. Side effects?
4. Drug interactions?

Answer 11

1. Inhalation(SABA/LABA), Nebulised, Oral and IV (SABA)
   
   • Inhaltion preferred - quick onset, targeted drug delivery and lower doses so less side effects.
   • Oral has greater first pass so larger doeses needed. Greater side effects - esp tremor
2. Cautions:
   
   • Hyperthyroidism - may stimulate thyroid activity
   • Diabetes - risk of ketoacidosis
   • CV disease - Arrythmias, alteration of HR/BP
   • Hypokalaemia
3. Side effects: tremor, palpitations, headache, mouth/throat dryness or irritation, cough, hoarseness,Hypokalaemia
4. Interactions: Diuretics, corticosteroids, theophylline, aminophylline, digoxin, gentamycin, insulin

Monitor K+ levels

Question 12

Signs of digoxin toxicity?

Answer 12

• Nausea
• Vomitting
• Loss of appitite
• drowsiness
• bradycardia
• visual defects

Question 13

What is the mechanism of action of Muscularinic antagonists?

Answer 13

Muscarinic antagonist (sometimes known as anticholinergics), block the binding of acetylcholine to muscarinic receptors inhibiting transmission of the parasympathetic system causing smooth muscle relaxation and dilatation of the airways.

Question 14

1. Examples of SAMA?
2. Time to reach max effect? What does this mean?
3. DOA
4. How often is it typically taken?

Answer 14

1. Ipratropium
2. It takes 30-45 minutes to reach maximum effect so is not suitable for rapid symptom relief as a single agent. It is often used in combination with salbutamol to increase bronchodilation.
3. Its effects last six to eight hours
4. it is generally used regularly three to four times a day.

Question 15

1. Examples of LAMA, their brand names and directions?
2. Benefits of LAMA?

Answer 15

1. Once a day:
   
   • Tiotropium (Spiriva)
   • Glycopyrronium (seebri)
   • Umeclidinium (incruse)
2. Twice Daily:
   
   • Aclidinium (eklira)

Sustained lung improvement and reduced frequecy of exacerbations using LAMA

Question 16

Muscularinic antagonists:

1. Routes of administation?
2. Caution in patients with?
3. Side effects?
4. Drug interactions?

Answer 16

1. Inhalation(SAMA/LAMA), Nebulised (SAMA)
2. Caution:
   
   • prostatic hyperplasia - worsened urinsty retention in elderly mean
   • CKD - stage 3 and above because of the risk of drug toxicity.
   • glaucoma - nebulized mist of antimuscarinic drugs can precipitate or worsen acute angle-closure glaucoma.
   • arrhythmias - greater risk or mortility
3. Side effects: Dry mouth, altered taste, nasal congestion, acute angle-closure glaucoma.
4. Interactions: no significant interactions.

Question 17

How doe methylxanthines work?

Answer 17

MOA: Not fully known!

1. Increases cAMP
2. Inhibits phosphodiesterases
3. Increases contractility of diaphragm

One theory on the action of this class is that they increase cyclic AMP levels. Increased levels of cyclic AMP leads to bronchodilation. They also non-selectively inhibit a group of enzymes called phosphodiesterases (PDEs), which appear to be involved in inflammatory processes in both asthma and COPD. Finally, the force of contraction of the diaphragm muscles are increased. This action appears to be due to enhanced calcium uptake through an adenosine-mediated channel

Question 18

1. Examples of methylxanthines and their routes of administration?
2. What is the therapeutic window?
3. What needs monitoring?
4. Why is it important to prescribe by brand

Answer 18

1. Oral: MR Aminophylline and Theophylline, IV: Aminophylline

Theophylline is given orally as sustained-release tablets and may be given by intravenous infusion (as aminophylline) in cases of life-threatening asthma.

1. A serum level of 10-20mg per litre is necessary to produce bronchodilation (the therapeutic window) but this gives little margin for error.
2. Patients whose condition is maintained on theophylline should have their serum levels checked annually and more often if something occurs to effect the stability of theophylline levels.
3. The absorption rates of different formulations vary, so it is important that this drug is prescribed by brand and patients are not switched from one brand to another which will destabilise serum levels.

Question 19

Methylxanthines:

1. Cautions in?
2. Side effects?
3. Interactions?

Answer 19

1. Use aminophylline and theophylline with caution in people with:
   
   • Cardiovascular disease, including cardiac arrhythmias.
   • Hepatic impairment.
   • Hyperkalaemia risk
   • Hypertension.
   • Hyperthyroidism.
   • Peptic ulcers.
   • Epilepsy
   • Older people - reduced renal excretion, comorbidities or more med usage
2. Sid effects: Nausea, Vomitting, Tremor, headache, palpataitions, arrythmias, CNS stimulation, convulsions.
   
   • Adverse effects can occur with therapeutic plasma aminophylline or theophylline concentrations of 10 mg/L to 20 mg/L. Both the frequency and severity of adverse effects increase when plasma concentrations of aminophylline or theophylline are above 20 mg/L.
3. Interactions:

• Beta-2 agonists, corticosteroids, diuretics — hypokalaemia may be potentiated. Check serum potassium levels regularly.
• Lithium — excretion of lithium may be altered. Check plasma lithium levels and alter dose if necessary.
• Fluvoxamine can raise the plasma level of theophylline. Avoid combination if possible, or halve the theophylline dose and monitor plasma levels.
• Plasma levels of theophylline altered by concomitant use of liver enzyme-inhibiting drugs such as verapamil, ciprofloxacin, fluconazole, erythromycin, clarithromycin, allopurinol, or cimetidine, or liver enzyme-inducing drugs such as primidone, phenobarbital, carbamazepine, phenytoin, ritonavir, rifampicin, or St John’s Wort.

Question 20

Before initating methylxanthines what monitoring is requied?

Answer 20

Before starting aminophylline or theophylline, check:

• Urea and electrolyte levels (paying particular attention to potassium levels)
• Liver function.
• Renal function

Question 21

Describe the monitoring of methylxathines in blood

Answer 21

Check drug plasma levels

Five days after starting oral treatment.

◦Routinely every 6–12 months. more regularly in older people or those with heart failure or hepatic impairment.

◦At least 3 days after any dose adjustments.

◦If an enzyme-inhibiting drug is prescribed (raises plasma levels) or if an enzyme-inducing drug is prescribed (lowers plasma levels).

◦If the person starts or stops smoking — a dose adjustment may be needed because tobacco can lower the plasma levels of aminophylline and theophylline.

Question 22

MOA of anti-inflammatory Corticosteriods?

Answer 22

The primary mechanism of action of corticosteroids is at the cellular level. These drugs bind to intracellular receptors, alter gene expression and ultimately regulate cellular processes. Their anti-inflammatory effect results from several different factors

MOA: Complex!

1.Inhibition of phospholipase, Arachidonic acid inflammatory mediators

2.Lymphocyte function altered

3.Alters permeability of vascular wall

1. The inhibition of phospholipase prevents the formation of arachidonic acid and subsequently inflammatory mediators.
2. Corticosteroids alter the function of lymphocytes. Inhibitis chemoattractant response after tissue injury - Retention of WBC in the lymphatic system limits their ability to migrate to the damaged tissue. Lymphocytic function is diminished.

Interleukin 1 (IL-1) which originates from macrophages and monocytes and tumor necrosis factor (TNF) which stimulates production of many inflammatory mediators are integral components to the cell mediated immune response to injury. The expression of these agents can be effectively inhibited by corticosteroids,

3. Corticosteroids also affect the permeability of the vascular wall. This membrane stabilization effect alters fluid shifts and decreases cellular and fluid movement from the vascular space. Lysosomal enzymes are also prevented from being released. The end result is alteration of fluid retention at the site of tissue damage.

Question 23

Examples of CCS and their routes

Answer 23

• Oral: Prednisolone
  
  • Lowest dose
  • Either short term for acute exacerbation of COPD or asthma of for long term maintaince
  • If maintaince a steriod card should be given
• IV: Hydrocortisone 100mg
  
  • Acute exacerbations asthma
  • Severe exacerbations asthma with oral route not available
• Inhaled: beclomethasone, Fluticasone, budesonide
  
  • Reduced side effects as locally acting
  • Quick onset

Question 24

Corticosteriods Oral:

1. Contradindications
2. Caurions

Answer 24

1. Active systemic infection - may mask symptoms of infection
2. Hepatic impairment — . Plasma concentrations of oral corticosteroids may be increased in hepatic impairment.

◦Psychiatric disturbance — monitor people with risk of mental health problems or a pre-existing mental health condition

◦Wounds — avoid corticosteroids for people who have wounds as they slow repair and healing, or use cautiously if this is unavoidable.

◦Pre-existing conditions, including heart failure, recent myocardial infarction, hypertension, diabetes mellitus, epilepsy, glaucoma, hypothyroidism, osteoporosis, obesity, or peptic ulceration. Monitor the person closely, as these conditions can be exacerbated by oral corticosteroids.

Question 25

CCS Oral:

Side effects

Answer 25

People receiving long-term oral corticosteroids (more than 3 weeks duration) and those needing frequent courses (3 or 4 per year) are at risk of systemic adverse effects, which are:

◦Endocrine — adrenal insufficiency, weight gain, and diabetes mellitus (new-onset, or worsening of blood glucose control in existing diabetes mellitus).

◦Gastrointestinal — peptic ulceration with perforation and haemorrhage, dyspepsia, abdominal distension, and oesophageal ulceration; especially in high-risk people.

◦Psychiatric — confusion, irritability, delusions and suicidal thoughts early in treatment and especially with high doses.

◦Musculoskeletal — osteoporosis and proximal myopathy.

◦Ophthalmic — glaucoma, cataract, blurred vision and other visual disturbances.

◦Cardiovascular — hypertension.

◦Skin — thinning of the skin, easy bruising, and delayed wound healing.

Question 26

CCS Oral drug interactions?

Answer 26

Many interactions including:

Anticoagulants.

Antiepileptics

Antidiabetic drugs —

Antifungals

Bronchodilators

Digoxin

Diuretics

Antiretroviral therapy (ART)

Live vaccines — live vaccines should be postponed for at least 3 months after high-dose corticosteroids are stopped

Nonsteroidal anti-inflammatory drugs — Nonsteroidal anti-inflammatory drugs may increase the risk of gastrointestinal bleeding and ulceration when they are given with corticosteroids.

To name but a few…see SmPC

Question 27

CCS: Inhalation

1. Caution?
2. Side effects

Answer 27

1. Untreated systemic infection
2. Local adverse effects of inhaled corticosteroids include:◦

Oral candidiasis, Candida Albican lives in the oral cavity. It is usually kept in check by other microbes. When you inhale ICS, some of the particles remain inside the oral cavity. Diminishing the immune response, thereby allowing the fungus to spread, causing an infection. It appears as white patches in the mouth, such as on your tongue. It can feel like you have a dry, cottony mouth, and the patches may seem to burn when you consume salty drinks or foods. it can be treated with medicines like Nystatin and fluconazole but can be avoided by advising patients to rinse their mouth with water or clean their teeth after using the steroid inhaler.

Dysphonia and hoarseness, especially in high doses. This can be caused by irritation of the mucous lining in the larynx, by “myopathy of laryngeal muscles,” or by laryngeal thrush. Regardless of the cause, this is one of the most common side effects of ICS. Some studies show that metered dose inhalers (MDI) have a higher risk for causing dysphonia than Dry Powder Inhalers (DPI). a spacer with an MDI will reduce this occurrence or switching to another inhaler product.

Question 28

CCS: inhaled

1. How to minimise risk?
2. Monitroing in children?
3. Interactions?

Answer 28

1. To minimize the adverse effects of inhaled corticosteroids: Ensure that the dose of inhaled corticosteroid is the lowest dose at which effective control of symptoms is achieved.
2. In children receiving prolonged treatment with a high-dose inhaled corticosteroid be alert to the symptoms of adrenal suppression, such as fatigue, weight loss, abdominal pain, headache, nausea and vomiting, especially during times of illness.
3. Monitor height regularly and accurately using a growth chart. Any reduction of growth rate should prompt a reduction in dose if possible, and/or referral to a paediatrician if needed.
4. Drug interactions are rare in people taking inhaled corticosteroids, because systemic corticosteroid concentrations are usually low. However, in people taking high doses of inhaled corticosteroids for prolonged periods, systemic corticosteroid concentrations may be high enough for interactions to become significant – would be as oral.

Question 29

CCS equivalent dose guidenlines read

Answer 29

ICS equivalence doses:

• https://www.sign.ac.uk/assets/sign158_categorisation_of_inhaled_corticosteroids-adults.pdf
• https://www.sign.ac.uk/assets/sign158_categorisation_of_inhaled_corticosteroids-children.pdf

https://www.nice.org.uk/guidance/ng80/resources/inhaled-corticosteroid-doses-pdf-4731528781

Question 30

Leukotrine recpetor antagonists:

1. MOA
2. Routes
3. CI and cautions
4. Side effects
5. Interactions

Answer 30

1. MOA: Binds with high affinity to cysteinyl leukotriene receptors (CysLT1) in the lungs inhibiting leukotriene mediated bronchoconstriction.
2. Routes: Oral only – tablets, granules and chewable tablets.
3. C/I and Cautions: None
4. Side effects: fever; gastrointestinal symptoms; headache; skin reactions; upper respiratory tract infection.
5. Interactions: Carbamazepine, Phenytoin, phenobarbital and rifampicin

Question 31

Links

Answer 31

http://Inhaler resistance chart

Inhaler techniques:

• https://www.asthma.org.uk/inhalervideos
• http://www.respelearning.scot/topic-3-treatment/inhalers

Determining suitable inhalers based on inspiration:

• Inhaler resistance chart
• https://www.youtube.com/watch?v=-n8MQUfjnEY