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Applied Pharmacology > Resp > Flashcards

Resp Flashcards

1
Q

Beta-2-agonists - Indications

A
  1. Asthma = short acting (SABAs) are used to relieve breathlessness. Long acting (LABAs) are used mainly in stage 3 of Tx in chronic asthma but must be given alongside ICS
  2. COPD = SABA are used to relieve breathlessness whilst LABAs are used as an alternative option/second line therapy of COPD.
  3. Hyperkalaemia = nebulised Salbutamol (SABA) can be used as an additional Tx for urgent treatment of high serum K+ concentration.
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2
Q

Where are B2 receptors found

A

B2 receptors are found within smooth muscle on airways/bronchi, GI tract, uterus and blood vessels.

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3
Q

What is the MOA of B2-agonists in asthma and COPD?

A

The B2-receptors are G-coupled protein receptors and so once activated by ligand binding they trigger a cascade which leads to smooth muscle relaxation.
This will relieve any constiction in the airways which then improves airflow through them relieving any breathlessness.

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4
Q

What is the MOA of B2-agonists in Hyperkalaemia?

A

B2-agonists stimulate Na+/K+ ATPase pumps on the cell surface membrane and this causes more K+ to move out from the extracellular surface and into the intracellular compartment hence making it useful in the treatment of hyperkalaemia but they shouldn’t be used on their own for this.

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5
Q

What are the side effects of B2-agonists?

A
  1. common flight or fight effects such as tachycardia, palpitations anxiety and tremor.
  2. Increased serum glucose through the promotion of glycogenesis
  3. can increases lactate levels at high doses
  4. LABAs can cause muscle cramps.
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6
Q

What are contraindications for B2-agonists?

A
  1. CVD as side effect of tachycardia may provoke angine or arrhythmias.
  2. LABA cannot be used if the patient is not on ICS
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7
Q

What are important interactions of B2-agonists that you should be aware of?

A
  1. Beta-blockers reduce the effect of B2-agonists.
  2. High dose nebulised B2-agonists with theophylline and corticosteroids can lead to hypokalaemia (serum K+ should be monitored)
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8
Q

Give examples of SABAs and LABAs?

A 
SABAs = salbutamol and terbutaline
LABAs = salmeterol and formoterol
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9
Q

What are indications for anti-muscarinics?

A
  1. COPD = SAMAs/short acting are used to relieve breathlessness due to things like exertion or acute exacerbation. LAMAs used to prevent breathlessness and exacerbations.
  2. Asthma: SAMAs are used as adjuvant therapy to relieve breathlessness during acute exacerbations alongside SABAs. LAMAs are added to high-dose ICS and usually step 4 of asthma management
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10
Q

What is the MOA for bronchodilator anti-muscarinics?

A

They bind to the muscarinic receptors and act like a competitive inhibitor of acetylcholine.
Stimulation of the muscarinic receptor usually stimulates parasympathetic ‘rest & digest’ effects.
Therefore, blocking the receptor, anti-muscarinics have the opposing effects - reducing smooth muscle tone (relaxing the airways)

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11
Q

What are examples of these bronchodilator anti-muscarinics?

A 
SAMA = ipratropium,
LAMA = tiotropium, glycopyrronium, aclidinium
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12
Q

How are antimuscarinics used in CVS and GI?

link to the indications?

A

As blockade of muscarinic receptors leads more flight and fight effects - it increased heart rate and conduction
It reduces smooth muscle tone and peristaltic contractions.
It reduces secretions from glands in the respiratory tract and the gut.

Therefore they can be used in severe/symptomatic bradycardia to increase HR, used in IBS for their antispasmatic effect.

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13
Q

Give examples of anti-muscarinics used for CVS/GI purposes

A
  • Atropine (first line bradycardia)
  • Hyoscine butylbromide (first-line in IBS)
  • Glycoppyronium
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14
Q

What are the side effects of bronchodilator anti-muscarinics?

A

Adverse effects are uncommon in inhaled antimuscarinics because they are metabolised rapidly.

  1. dry mouth
  2. irritation of respiratory tract with nasopharyngitis, sinusitis and cough
  3. GI disturbance such as constipation
  4. urinary retention
  5. blurred vision & headaches
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15
Q

What are contraindications for antimuscarinic bronchodilators?

A
  1. Angle-closure glaucoma - has to be used very cautiously as it can lead to a dangerous rise in intraocular pressure.
  2. Arrhythmias
  3. urinary retention.
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16
Q

What interactions do anti-muscarinic bronchodilators have?

A

Very low systemic absorption = no significant interactions.

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17
Q

What are the indications for Inhaled Corticosteroids/Glucocorticoids?

A
  1. Asthma = treat airway inflammation and control symptoms when they are not being well controlled by SABAs
  2. COPD = control symptoms and prevent exacerbations in patients with severe airflow obstruction on spirometry and/or recurrent exacerbations - ICS usually are prescribed in combination of LABAs or LABA bronchodilators.
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18
Q

What is the MOA of ICS?

A

The corticosteroid passes through the plasma membrane and act as a ligand, binding to cytoplasmic receptors,
This forms a corticosteroid-receptor complex which translocates to the nucleus to modify the transcription of large numbers of genes.

This modification of gene expression = Pro-inflammatory interleukins, cytokines and chemokines are downregulated whilst anti-inflammatory proteins are upregulated. Therefore, reducing mucosal inflammation, widen airways and reduced mucus secretion thus improving the symptoms and reduced exacerbations in asthma and COPD.

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19
Q

What are the side effects of ICS?

A
  1. Oral candidiasis/thrush = due to the immunosuppressive effect
  2. Hoarse voice
  3. may increase the risk of pneumonia in COPD
  4. less common due minimal amount getting absorbed in the blood but rarely can lead to systemic side effects if given at a high dose - includes adrenal suppression, growth retardation (in children) and osteoporosis.
20
Q

What are the contraindications for ICS?

A
  1. COPD patients with a Hx of pneumonia - cautious if given at high doses
  2. Children who are more susceptible to growth suppression
21
Q

What are examples of ICS?

A
  1. beclomethasone
  2. budenoside
  3. fluticasone
22
Q

What are the indications for Oxygen?

A
  1. Hypoxaemia = to increase oxygen delivery to tissues
  2. Pneumothorax = to accelerate reabsoprtion of pleural gas
  3. Carbon monoxide (CO) poisoning = reduce the half life of carboxyhaemoglobin.
23
Q

What is the MOA of Oxygen for each of these indications?

A

In Hypoxaemia, supplemental oxygen will increase the partial pressure of oxygen in alverolar gas and this increases the amount and rate of diffusion into the blood. This results in an increased delivery of oxygen to tissue hence resolving the hypoxia.

In Pneumothorax, oxygen has additional effect of reducing the fraction of nitrogen in the alveolar air. Due to pleural air mainly consisting of nitrogen it increases the rate of reabsorption of pleural air.

In Carbon monoxide poisoning, the Oxygen competes for binding sites on haemoglobin and thereby shortens the half life of carboxyhaemoglobin allowing haemoglobin to carry more oxygen to tissues.

24
Q

What are the side effects of giving supplemental oxygen?

A
  1. most commonly side effects are related more to the delivery device e.g. discomfort of a facemask
  2. lack of water vapour leads to dry throat - improved by humidification.
  3. hyperoxaemia may be harmful
25
Q

What are the contraindications for giving supplemental oxygen?

A
  1. chronic Type 2 Resp failure = e.g. severe COPD
    when exposed to high inspired oxygen concentations, the finely balanced adaptive state in response to the patients hypoxemia and hypercapnia is disturbed resulting in a rise in CO2 partial pressure. This can potentially lead onto respiratory acidosis, depressed consciousness and worsened tissue hypoxia.
  2. fire risk if exposed to heat source or naked flame - oxygen accelerates combustion.
26
Q

What are the indications for anti-histamines?

A
  1. Allergies/hay-fever = first-line treatment
  2. Pruritus (itching) and Uticaria (hives) = relieves itchy skin and hives from insect bites, drug allergies and infections (e.g chicken pox)
  3. Anaphylaxis = used as adjunctive treatment often after administering adrenaline & other life-saving measures
  4. Nausea and vomiting = H1-receptor antagonists and antiemetics.
27
Q

What is the MOA of anti-histamines in most indications?

A

Histamines are released from storage granules in mast cells as a result of antigen binding on IgE cell surfaces. Usually, the histamine will bind to H1 receptors inducing Type 1 hypersensitivity which involves increased capillary permeability, oedema formation, vasodilation and erythema. It also relieves itches due to sensory nerve stimulation.

Anti-histamines antagonise H1-receptors. Blockade prevent the downstream effects.

28
Q

What is the MOA of anti-histamines in anaphylaxis?

A

In anaphylaxis there is widespread histamine release which produces generalised vasodilation and vascular leakage with consequent hypotension. Essentially produces a very exaggerated allergic response.
Usually, anti-histamines are too slow to cope with the histamine release and so adrenaline is given as first line Tx.

29
Q

What are the side effects of antihistamines?

A 
first gen anti-histamines (chlorphenamine) cause sedation/drowsiness. Histamine binding to H1 receptors in the brain usually contribute to wakefullness but blockade removes this effect.
second gen (ceterizine & loratadine) do not cross the blood-brain barrier and tend not to have sedative effects.
30
Q

What are the contraindications of anti-histamines?

A

sedative first gen anti-histamines should be avoided in severe liver disease as they may precipitate hepatic encephalopathy.

31
Q

What are examples of antihistamines?

A

chlorphenamine (first gen)

ceterizine, loraditine fexofenadine (second gen)

32
Q

What are the indications of Leukotriene receptor antagonists?
how do the indications differ in different age groups?

A

Asthma

In adults : considered as an add-on therapy for asthma when ICS & LABA aren’t controlling symptoms

Children 5-12yrs: as an alternative to LABAs of add-on to ICS

Children under 5: as first-line preventative therapy for asthma where ICS are contraindicated.

33
Q

What is the MOA for LTRAs ?

A

Leukotrienes are produced by mast cells and eosinophils and activate the G-coupled leukotriene receptor = CysLT1
This activates a cascade leading to inflammation and bronchocontriction.

LTRA reduce inflammation and bronchoconstriction in asthma by blocking CysLT1 and dampening the inflammatory cascade.

34
Q

What are the side effects of LRTAs?

A

generally well tolerated
most common = headaches and abdo pain (mild)

increased rate of URTI
Hyperactivity and reduced ability to concentrate

35
Q

What are contraindications of LRTAs?

A

Only give LRTAs if the asthma is incompletely controlled with ICS, LABAs.

36
Q

What are the interactions of LRTAs?

A

No important drug interactions

37
Q

What are the indications for theophylline?

A

asthma

usually in uncontrolled/chronic asthma

38
Q

What is the MOA for theophylline?

A

Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction.

39
Q

What are the side effects of Theophylline?

A
  1. anxiety/palpitations
  2. arrhythmias
  3. seizures
  4. dizziness
  5. GI discomfort diarrhoea & vomiting) GORD
  6. headaches
40
Q

What are contraindications of theophylline?

A
  1. cardiac arrhythmias or cardiac disease esp if elderly
  2. Epilepsy
  3. fever
  4. HTN
  5. Peptic ulcer
  6. Risk of hypokalaemia
  7. thyroid disorder
41
Q

What are the interactions of theophylline?

A

smoking increases theophylline clearance - increased doses may be required.

42
Q

Mucolytic - Examples

A
  • Carbocisteine

- Acetylcysteine

43
Q

Carbocisteine - Indications

A

COPD

Cystic Fibrosis

44
Q

Carbocisteine - Contraindication

A
  • active peptic ulceration.
  • asthma or respiratory failure.
  • pregnant or breastfeeding.
45
Q

Carbocisteine - Caution

A

People with a history of peptic ulceration or those taking concomitant medications known to cause gastrointestinal bleeding.

46
Q

Carbocisteine - Interaction

A

antitussives and/or substances that dry out secretions (atropinic) is not rational.

47
Q

Carbocisteine - Side Effects

A
  • Skin reactions including Stevens-Johnson syndrome and erythema multiforma.
  • GI bleeding and vomiting.

Applied Pharmacology (11 decks)

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