Respiratory Pharmacology Flashcards
<p>What is a cough?</p>
<p>A protective reflex that prevents lungs from aspiration. Common symptom of respiratory diseases</p>
<p>What is aspiration?</p>
<p>Process of drawing breath</p>
<p>What is a useless cough?</p>
<p>Persistent and unproductive --> dry cough</p>
<p>Should a useless cough be suppressed?</p>
<p>Yes</p>
<p>What are cough suppressants?</p>
<p>Antitussives</p>
<p>What are examples of useless coughs?</p>
<p>Asthma (worse in morning), oesophageal reflux, sinusitis</p>
<p>What is a useful cough?</p>
<p>Expels secretions and sputum --> productive</p>
<p>Should useful coughs be suppressed?</p>
<p>No as condition could get worse. Need to treat underlying condition</p>
<p>When should a useful cough be treated?</p>
<p>Only if exhausting and dangerous</p>
<p>What is an example of a useful cough?</p>
<p>Chest infection</p>
<p>Where does a cough originate?</p>
<p>From stimulation of structures innervated by the vagus nerve (including airways and distal oesophagus)</p>
<p>What are the 3 steps of the mechanism of a cough?</p>
<p>1. Cough receptors or lung irritant receptors detect stimuli
2. Sends to cough centre in medulla
3. Vagal stimulation leads to cough</p>
<p>On the afferent side, how can dry coughs be treated?</p>
<p>Reduce stimuli</p>
<p>What are linctuses?</p>
<p>Medicine to relieve cough --> coat mucous membrane with protective layer and soothes inflammation</p>
<p>Above the larynx, how can dry coughs be treated?</p>
<p>Linctuses</p>
<p>Below the larynx, how can coughs be treated?</p>
<p>1. Steam inhalation
| 2. Nebulised local anaesthetics</p>
<p>How can steam inhalation soothe a dry cough?</p>
<p>Makes environment warmer so more mucous secreted which provides protective layer to inflamed laryngeal membrane</p>
<p>How can nebulised local anaesthetics soothe a dry cough?</p>
<p>Inhibit sensory nerves in airways involved in cough reflex. Numb afferent receptors in larynx and trachea.</p>
<p>How can dry coughs be treated on the efferent side?</p>
<p>Medullary cough centre --> suppressed by antitussives
1. Opioids (codeine, methadone)
2. Non-opioids (dextromethorphan, noscapine)
3. Sedatives (diaphenhydramine)</p>
<p>What are side effects of opioids?</p>
<p>Sleepy, overdose</p>
<p>What are side effects of sedatives?</p>
<p>Make secretions very thick</p>
<p>How are productive coughs treated?</p>
<p>1. Expectorants
| 2. Mucolytics</p>
<p>What are 2 examples of expectorants?</p>
<p>1. Guaiphenesin
| 2. Ipecacuanha</p>
<p>What is effect of expectorants?</p>
<p>Increase volume of secretion to help bring up mucus (no added value)</p>
<p>What are 3 examples of mucolytics?</p>
<p>1. Acetyl cysteine
2. Carbocystine
3. Recombinant human DNA</p>
<p>When are mucolytics used?</p>
<p>Treat chronic conditions such as cystic fibrosis (very expensive)
Recombinant human DNA used in special circumstances</p>
<p>What is effect of mucolytics?</p>
<p>Decrease viscosity of sputum by breaking disulphide bonds</p>
<p>What is atelectasis?</p>
<p>A complete or partial collapse of the entire lung or area (lobe) of the lung. It occurs when the tiny air sacs (alveoli) within the lung become deflated or possibly filled with alveolar fluid</p>
<p>What should be asked about a cough in clinical scenario?</p>
<p>1. What type of cough? (useless or useful)
2. Should it be suppressed?
3. What is best treatment? (antibiotics, cough suppressants)</p>
<p>What are 4 likely causes of chronic coughs?</p>
<p>1. COPD
2. Bronchial asthma
3. Gastroesophageal reflux disease
4. Upper airways cough syndrome (post nasal drip)</p>
<p>What is bronchoconstriction?</p>
<p>Constriction of airways in lungs due to tightening of surrounding smooth muscle</p>
<p>How can inflammation lead to narrowing of lumen?</p>
<p>- Causes swelling of epithelium mucosa which leads to narrowing of lumen
- Release of inflammatory mediators leads to constriction of smooth muscle so lumen is compromised further (bronchoconstriction)</p>
<p>What are mucus plugs?</p>
<p>- Build up of mucus in airways
- Common after surgery (drugs make you breathe less deeply so normal secretions collect) or in people with CF and asthma</p>
<p>What are chronic obstructive lung diseases important causes of in adults?</p>
<p>1. Sickness absence from work
2. Reduced quality of life
3. Disability and hospital admissions</p>
<p>What are the 4 types of asthma?</p>
<p>1. Associated with allergic reactions
2. Not associated with specific allergens (intrinsic asthma)
3. Exercise induced asthma
4. Associated with COPD</p>
<p>What type of asthma is IgE mediated?</p>
<p>Type 1 - associated with allergic reactions</p>
<p>What are stages in allergen mediated asthma?</p>
<p>1. Antigen crosses epithelium and presented to T helper cells
2. Stimulates B cells to produce IgE
3. IgE antibodies combine with mast cells --> mast cell actication
4. Release of inflammatory mediators by mast cells (histamines)</p>
<p>What is result of inflammatory mediators?</p>
<p>Inflammation of mucosa, swelling of mucosa layer, constriction of smooth muscle --> BRONCHOCONSTRICTION</p>
<p>How can asthma be prevented?</p>
<p>1. Avoidance of antigen
| 2. Non-specific reduction of bronchial hyperactivity</p>
<p>How can non-specific reduction of bronchial hyperactivity be achieved?</p>
<p>1. Stopping cause (stop smoking, lose weight)
| 2. Pharmacological - corticosteroids</p>
<p>How do corticosteroids treat asthma?</p>
<p>• Considered most effective medications for controlling asthma when taken regularly
• Work continuously to reduce swelling of airways</p>
<p>What are sympathomimetics?</p>
<p>Produce physiological effects characteristic of the sympathetic nervous system by promoting the stimulation of sympathetic nerves.</p>
<p>How do sympathomimetics work?</p>
<p>Dilation of narrowed bronchi.
Mimicking of dilator neurotransmitter. Stimulation of enzyme adenylcyclase which increases production of cAMP. Relax bronchial smooth muscle, stabilise membrane of bronchial mast cell, increased bronchodilation.</p>
<p>How do methylxanthines work?</p>
<p>Direct acting bronchodilators</p>
<p>What are anticholinergics?</p>
<p>Blockers of contsrictor transmitter</p>
<p>How do anticholinergics work?</p>
<p>Block action of neurotransmitter acetylcholine at synapses. Inhibits parasympathetic nerve impulses by blocking binding of acetylcholine to its receptor in nerve cell.</p>
<p>How does acetylcholine play a key role in asthma?</p>
<p>Binds to muscarinic receptors, leading to bronchoconstriction, increased mucus secretion, inflammation and airway remodelling</p>
<p>How can mast cell stabilisers treat asthma?</p>
<p>Prevent release of inflammatory mediators (histamine)</p>
<p>What is effect of histamine</p>
<p>Contraction of smooth muscle, dilation of blood vessels which increases permeability and lowers blood pressure</p>
<p>How can leukotriene receptor antagonists treat asthma?</p>
<p>Anti-inflammatory bronchoconstriction preventors. They block the chemical reaction that leads to inflammation in airways</p>
<p>What are leukotriene receptor antagonists?</p>
<p>Class of oral medication that is non-steroidal
Anti-inflammatory bronchoconstriction preventors.</p>
<p>What is pulmonary oedema?</p>
<p>Fluid accumulation in the tissue and air spaces of the lungs. It leads to impaired gas exchange and may cause respiratory failure</p>
<p>How do corticosteroids act as anti-inflammatory?</p>
<p>1. Inhibition of influx of inflammatory cells after exposure
2. Reduced microvascular leakage (decrease oedema)
3. Inhibition of release of mediators (cytokines)
4. Inhibition of cyclooxygenase enzyme</p>
<p>How do corticosteroids reduce bronchial reactivity?</p>
<p>Reduce asthma exacerbations but not do not relax bronchial smooth muscle</p>
<p>What are adverse effects of long-term use of corticosteroids?</p>
<p>- Iatrogenic Cushing's Syndrome
- Inhibition of hypothalamic pituitary axis
- Oropharyngeal candidasis (mouth thrush) (inhalation)
- Hoarseness --> vocal cords (inhalation)</p>
<p>What are inhaled corticosteroids commonly called?</p>
<p>Brown inhalers</p>
<p>What are brown inhalers used to treat?</p>
<p>First line therapy --> mild to moderate asthma but not useful in acute severe asthma</p>
<p>What are oral corticosteroids used to treat?</p>
<p>Severe asthma (status asthmaticus)</p>
<p>How can you minimise oropharyngeal candidiasis and hoarseness?</p>
<p>Gargle and spit after every treatment</p>
<p>Why is administration of steroids better in morning?</p>
<p>Peak of endogenous ACTH (hormone that regulates cortisol levels)</p>
<p>Why is inhalational route less likely to develop side effects?</p>
<p>Up to 10x less dose of inhaled steroid compared to oral</p>
<p>What is a new glucocorticoid being used for asthma?</p>
<p>Cyclesonide</p>
<p>Why is cyclesonide better?</p>
<p>Prodrug - Only converted to active drug in bronchial epithelium. When absorbed in circulation, very tightly bound to proteins and therefore little effect on glucocorticoid receptors elsewhere (side effects minimum)</p>
<p>What is downside of cyclesonide?</p>
<p>Expensive</p>
<p>What is effect of mast cell stabilisers?</p>
<p>Inhibit release of mast cell mediators</p>
<p>How are mast cell stabilisers administered?</p>
<p>Inhalation and very poorly absorbed</p>
<p>Can mast cell stabilisers be used in acute bronchospasm?</p>
<p>No as no effect on bronchial smooth muscle so only useful if taken prophylactically</p>
Prophylactic –> prevents
<p>What are the main uses of mast cell stabilisers?</p>
<p>Allergic rhinitis, allergic conjunctivitis (drops)</p>
<p>What are side effects of mast cell stabilisers?</p>
<p>Throat irritation, cough, dermatitis, myositis, gastroenteritis</p>
<p>What are the 2 types of leukotriene pathway inhibitors?</p>
<p>1. Leukotriene synthesis inhibitors
| 2. Leukotriene receptor antagonists</p>
<p>Describe pathway of leukotriene that leads to bronchospasm</p>
<p>Leukotriene synthesised from arachidonic acid by 5 lipoxygenase
Leukotriene binds to receptor that initiates bronchospasm</p>
<p>How do leukotriene synthesis inhibitors work?</p>
<p>- Inhibit 5-lipoxygenase
| - Zileuton was discontinued due to liver toxicity</p>
<p>What forms of asthma can leukotriene receptor antagonists be used for?</p>
<p>1. Allergen induced asthma
2. Exercise induced asthma
3. Reduce frequency of exacerbations</p>
<p>Why are Leukotriene Receptor Antagonists good for children?</p>
<p>Given orally (not inhaler)</p>
<p>Are Leukotriene Receptor Antagonists effective in acute asthma?</p>
<p>No</p>
<p>What are the minor adverse effects of Leukotriene Receptor Antagonists?</p>
<p>Headache, gastritis, flu-like symptoms, CS syndrome</p>
<p>Which Leukotriene Receptor Antagonist is most commonly used and why?</p>
<p>Montelukast --> cheap</p>
<p>What is bronchal tone?</p>
<p>Determines lumen of airways (especially lower)</p>
<p>What is cAMP produced from? What is its effect?</p>
<p>Produced from ATP by adenyl cyclase and acts on bronchial smooth muscle, causing bronchodilation</p>
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<p>What is cAMP destroyed by?</p>
<p>Phosphodiesterase enzymes (PDE) to become AMP</p>
<p>What is effect of acetylcholine and adenosine?</p>
<p>Directly act on smooth muscle to cause bronchorestriction</p>
<p>What are 2 ways to cause bronchodilation?</p>
<p>1. Increase amount of cAMP
| 2. Reduce amount of acetylcholine and adenosine</p>
<p>What is effect of beta agonists on cAMP?</p>
<p>Stimulate adenyl cyclase enzyme, increasing cAMP production, causing bronchodilation</p>
<p>What is effect of theophylline on cAMP?</p>
<p>1. Inhibit phosphodiesterase enzyme so inhibit breakdown of cAMP, causing bronchodilation
2. Also inhibit adenosine</p>
<p>What is effect of muscarinic antagonists?</p>
<p>Inhibit action of acetylcholine, reducing bronchoconstriction</p>
<p>How do sympathomimetic agents act?</p>
<p>Via B2 adrenoreceptors. Selective B2 agonist agents.
| 1st line of therapy</p>
<p>What are sympathomimetic agents commonly known as?</p>
<p>Blue inhalers</p>
<p>Is Salmetrol a long or short-acting beta agonist?</p>
<p>Long acting (12-24 hours) --> LABA</p>
<p>What is a non-selective sympathomimetic agent and when is it used?</p>
<p>Adrenaline - used in emergency, as subcutaneous injection of micro-aerosol</p>
<p>Which sympathomimetic agent is most commonly used?</p>
<p>(Albuterol) Salbutamol</p>
What are side effects of selective B2 agonist agents?
Due to B2 receptors in heart, muscle and other tissues
Heart – palpitation, tachycardia, cardiac arrhythmias
Muscle – tremor
Others – restlessness, nervousness, hypokalaemia
<p>What are methylxanthines? What are 2 examples?</p>
<p>Direct acting bronchodilators
1. Theophylline
2. Aminophylline</p>
<p>How is theophylline administered? What is its effect?</p>
<p>Oral --> rapid and complete absorption
Inhibits PDE and adenosine</p>
<p>When is theophylline used?</p>
<p>Adjuvant therapy in asthma</p>
<p>What are side effects of methylxanthines?</p>
<p>o Palpitations, cardiac arrhythmia, hypotension
o Gastrointestinal irritation (increased acid production)
o Diuresis, hypokalemia
o Anxiety, headache, seizures</p>
<p>How is aminophylline administered? When is it used?</p>
<p>Intravenous
Used in severe asthma</p>
<p>What are anticholinergic agents commonly known as?</p>
<p>Green inhalers</p>
<p>How do anticholinergic agents work?</p>
<p>Inhibit muscarinic receptors (selective muscarinic antagonist agents)
This blocks binding of acetylcholine to its receptor (prevents bronchoconstriction)</p>
<p>How are anticholinergic agents administered?</p>
<p>Inhalation</p>
<p>When are anticholinergics used?</p>
<p>Adjuvant therapy in acute severe asthma, COPD</p>
<p>What do anti IgE monoclonal anitbodies do?</p>
<p>Inhibit binding of IgE to mast cells. Expensive.
Omalizumab</p>
<p>When are magnesium and ketamine used?</p>
<p>Patients who fail to respond to inhaled bronchodilators</p>