Term
| How are respiratory dysfunctions classified? |
|
Definition
1. classic lung disease
2. centrally-mediated respiratory dysfunction |
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Term
| Name 4 classic lung diseases |
|
Definition
Asthma
COPD
Pulmonary Oedema
Cystic Fibrosis |
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Term
| Name 3 centrally-mediated respiratory dysfunctions |
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Definition
Premature birth
Opioid intoxication
Rett syndrome |
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Term
| What is bronchial asthma? |
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Definition
| a chronic inflammatory disease of the airways that causes acute bronchospasm and dyspnea |
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Term
| What happens during an asthma attack? |
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Definition
| smooth muscle cells in the bronchial walls contact, constricting the airways making breathing difficult |
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Term
| What happens during chronic asthma? |
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Definition
| the airway walls become inflamed |
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Term
| Name some common triggers for asthma attacks |
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Definition
| allergens, rapid changes in temperatures, drug side-effects and exercise |
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Term
| What are the symptoms of asthma |
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Definition
| feeling of breathlessness, a tight chest, wheezing and coughing (especially at night) |
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Term
|
Definition
| measuring the FEV1:FVC ratio (Tiffeneau test) and/or bronchoscopy |
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Term
| What is asthma treatment based around? |
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Definition
| relieving an ongoing attack and/or preventing subsequent attacks |
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Term
| Which drug is used to treat bronchoconstriction in asthma? |
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Definition
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Term
| How do β2 Adrenoceptor Agonists act? |
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Definition
| via the activation of G protein-coupled receptors and an increase in [cAMP] in airway smooth muscle cells (i.e. they mimic the bronchodilator effect of sympathetic stimulation) |
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Term
| How does an increase in cAMP stop muscle contraction? |
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Definition
1. cAMP inhibits the enzyme myosin light chain kinase (MLCK)
2. MLCK phosphorylates myosin in smooth muscle, which initiates the process of muscle contraction.
3. Therefore inhibition of MLCK reduces the force of contraction of bronchial smooth muscle, resulting in bronchodilation. |
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Term
| How are short-acting β2 Adrenoceptor Agonists administered? |
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Definition
| via an inhaler or nebulizer, a route of administration which ensures rapid delivery of the drug to it’s desired site of action and minimises side-effects |
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Term
| What are the adverse effects of short-acting β2 Adrenoceptor Agonists? |
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Definition
| include muscle tremor and hypokalaemia and, when taken in excessive amounts, tachycardia |
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Term
| Name short-acting β2 Adrenoceptor Agonists |
|
Definition
| salbutamol and tertbutaline |
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Term
| Name long-acting β2 Adrenoceptor Agonists |
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Definition
| salmeterol and isoproterenol |
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Term
| What are long-acting β2 Adrenoceptor Agonists used to treat? |
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Definition
- these are intended for long-term prevention of attacks, rather than acute relief, as they usually have a delayed onset of action (>15 mins)
- Particularly useful for treating nocturnal asthma |
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Term
| What are the actions of anticholinergics? |
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Definition
| Muscarinic receptor antagonists (MRAs) cause bronchodilation by binding to muscarinic receptors on airway smooth muscle cells and thereby preventing the action of acetylcholine released from parasympathetic nerves |
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Term
|
Definition
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Term
| Are MRAs completely effective? |
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Definition
| MRAs do not prevent all types of bronchospasm, but are particularly effective against irritant-induced attacks |
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Term
| Are MRAs selective? What are the effects of this? |
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Definition
- currently available MRAs do not discriminate between M1, M2 and M3 receptors
- it is likely that blockade of M2 receptors on cholinergic presynaptic terminals may reduce their effectiveness |
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Term
|
Definition
short-acting: atropine, ipratropium bromide and oxitropium bromide
longer-acting: tiotropium bromide |
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Term
| How are MRAs administered? |
|
Definition
| by inhalation to speed up their onset of action, and to reduce their systemic adverse effects |
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Term
|
Definition
| When inhaled, they are poorly absorbed into the pulmonary circulation, do not cross the blood-brain barrier and have few adverse effects |
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Term
| When does max bronchodilator through MRAs occur? |
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Definition
| after around 30 mins and the effects last for around 5 hours (short-acting) and 15 hours (longer-acting) |
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Term
| Which diseases do MRAs treat? |
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Definition
| after around 30 mins and the effects last for around 5 hours (short-acting) and 15 hours (longer-acting) |
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Term
| How can coffee/tea be used to treat asthma? |
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Definition
| Coffee and tea contain naturally-occurring xanthines such as caffeine and theobromine, and it has long been known that drinking strong coffee can relieve the symptoms of asthma |
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Term
| Describe the mechanism of action of xanthines |
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Definition
| They act by inhibiting phosphodiesterase enzymes in airway smooth muscle: these enzymes are involved in the metabolism of cAMP, so inhibition leads to increases in [cAMP], which inhibits MLCK and produces smooth muscle relaxation |
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Term
| Name the main xanthine and its administration |
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Definition
| The main xanthine used clinically is theophylline, given orally usually in the form of a ‘slow-release’ preparation to overcome its short biological half-life (it is rapidly metabolised) |
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Term
| What is the issue with xanthines as bronchodilators? |
|
Definition
| they have a very narrow therapeutic window: plasma concentrations of <10 μg/mL are generally ineffective, but concentrations >20 μg/mL are associated with adverse effects |
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Term
| What are the adverse effects of MRAs |
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Definition
| nausea, cardiac arrhythmias and convulsions, and drug interactions can also be problematic |
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Term
| What drug is used in the treatment of asthma to prevent subsequent inflammation? |
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Definition
| Most anti-inflammatory drugs (AIDs) and are therefore classed a prophylactic antiasthma drugs |
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Term
| Why can't AIDs treat acute attacks? |
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Definition
| they do not cause bronchodilation |
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Term
| What type of AIDs are best for the treatment of the chronic inflammatory process underlying asthma? |
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Definition
|
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Term
| How do glucocorticosteriods act? |
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Definition
| they inhibit inflammatory cell infiltration into the airways and reduce oedema formation by acting on the vascular endothelium |
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Term
| Name some examples of glucocorticosteriods |
|
Definition
| beclometasone and budesonide |
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Term
| What combination of drugs are commonly found in inhalers today |
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Definition
| glucocorticosteroid and a long-acting β2 agonist |
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Term
|
Definition
Chronic bronchitis and emphysema
often occur together (particularly in heavy smokers) |
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Term
| How can genetics increase susceptibility |
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Definition
| Susceptibility may be increased by a genetic deficiency in the enzyme α1 antitrypsin |
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Term
| What is COPD associated with? |
|
Definition
| with the excessive production of sputum, a chronic cough and breathlessness on exertion |
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Term
| How does COPD obstruct airways? |
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Definition
| Airway obstruction is the result of luminal narrowing and mucus plugs, which may lead to secondary respiratory infection |
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Term
| What does chronic bronchitis cause? |
|
Definition
| alveolar hypoventilation, hypercapnia and hypoxia (although some patients hyperventilate to reduce the degree of hypoxia) |
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Term
| What is emphysema associated with? |
|
Definition
| the destructive loss of alveolar structures and a consequent chronic impairment of gas exchange |
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Term
| Describe emphysema treatment |
|
Definition
| There are no drugs available to prevent or reverse emphysema, and the prognosis is very poor for patients with this condition |
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Term
| Describe chronic bronchitis treatment |
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Definition
| Treatment of chronic bronchitis involves the use of bronchodilators, mucokinetic drugs and antibiotics |
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Term
| Describe bronchodilator therapy in chronic bronchitis |
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Definition
| Bronchodilator therapy is essentially the same as for the treatment of asthma : mainly β2 agonists, muscarinic antagonists (particularly useful, as they also inhibit mucus secretion) and xanthines |
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Term
| What drugs affect the mucus? |
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Definition
| Mucokinetic drugs act by reducing the viscosity of mucus: N-acetylcysteine and ambroxol act by breaking the disulphide bonds that hold mucus glycoproteins together |
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Term
| What other drugs are used in COPD treatment? |
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Definition
| Antibiotics are often prescribed to combat the secondary bacterial infections colonising the sputum |
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Term
| Describe pulmonary oedema |
|
Definition
| by an abnormal build up of fluid within the alveolar space, leading to a shortage of breath, cough and impaired gas exchange |
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Term
| What causes pulmonary oedema? |
|
Definition
|
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Term
| How is pulmonary oedema diagnosed? |
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Definition
| Diagnosis may be based on ECG, heart sounds and measurement of PaO2 |
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Term
| What are the aims of treating pulmonary oedema? |
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Definition
| Treatment is based on reducing blood volume (to reduce blood pressure and thereby reduce the hydrostatic pressure forcing fluid out of the pulmonary capillaries, and to reduce cardiac work), improving cardiac function and administration of O2 |
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Term
| Which drugs reduce blood volume and how? |
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Definition
| Diuretics (e.g. furosemide) act to increase urinary fluid loss (and thereby reduce blood volume) by inhibiting the reabsorption of water and electrolytes in the loop of Henle |
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Term
| Which drugs improve cardiac function and how? |
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Definition
| Drugs used to improve cardiac function include the cardiac glycosides (e.g. digoxin) phosphodiesterase inhibitors (e.g. inamrinone) and β1 agonists (e.g. dobutamine) |
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|
Term
|
Definition
| Cystic fibrosis is an inherited disease, developing in early childhood and affecting the airways (and ducts of various organs) |
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|
Term
| What defect causes cystic fibrosis? |
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Definition
| The primary defect is a mutation in specific proteins essential for Cl- efflux from the cells within the lung |
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Term
| What does the defect result in? |
|
Definition
The defect results in thick and viscous secretions in ducted organs, including the airways of the lung
This gives rise to poor ventilation of the affected areas, and subsequent bacterial infection results in irreversible lung damage (bronchiectasis) |
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|
Term
| What is the life expectancy of those with cystic fibrosis? |
|
Definition
| People with cystic fibrosis have a markedly reduced life expectancy, but it can be significantly extended by aggressive treatment with drugs and physical therapy |
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Term
| What are the aims of cystic fibrosis treatment? |
|
Definition
(1) Thinning secretions, thereby keeping the airways as clear as possible and
(2) Combating opportunistic infections |
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Term
| Name 5 drugs that are used |
|
Definition
Muscarinic antagonists (e.g. atropine)
Expectorants (e.g. glyceryl guaiacolate)
Mucolytic agents (e.g. N-acetylcysteine)
Agents that break down DNA tangles (e.g. recombinant DNAases given by aerosol) |
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|
Term
| How do muscarinic antagonists treat cystic fibrosis? |
|
Definition
| Muscarinic antagonists (e.g. atropine) reduce mucus secretions |
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|
Term
| How do expectorants treat cystic fibrosis? |
|
Definition
| Expectorants (e.g. glyceryl guaiacolate) increase the fluidity of secretions and thereby increase the productivity of coughing |
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Term
| How do mucolytic agents treat cystic fibrosis? |
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Definition
| Mucolytic agents (e.g. N-acetylcysteine) decrease the viscosity of secretions |
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Term
| How do agents that break down DNA tangle treat cystic fibrosis? |
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Definition
| Agents that break down DNA tangles (e.g. recombinant DNAases given by aerosol) have recently shown to be effective |
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Term
| How do antibiotics treat cystic fibrosis? |
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Definition
| Antibiotics (e.g. gentamycin) are used to treat bacterial infections (pneumonia is particularly common) |
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Term
| What causes opiod intoxication? |
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Definition
| Opioid intoxication can occur either as a consequence of drug abuse (e.g. heroin) or as a result of accidental overdose of opioid painkillers |
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|
Term
| What are the effects of opiod intoxication? |
|
Definition
- centrally-mediated depression of respiration
- The underlying mechanism is related to stimulation of μ opioid receptors |
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|
Term
| Describe the opiod mechanism |
|
Definition
These G-protein-coupled receptors, the activation of which inhibits adenylate cyclase
This decreases [cAMP], once consequence of which is decreased neuronal excitability |
|
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Term
| Where are μ opioid receptors located? |
|
Definition
| The μ opioid receptor is abundantly expressed in neurones within the respiratory control centres of the pons and medulla |
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|
Term
| How can opioid intoxication lead to respiratory arrest in overdose situations? |
|
Definition
| opioid intoxication depresses respiratory neuronal excitability and depresses ventilation |
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|
Term
| How is opiod intoxication treated? |
|
Definition
| The preferred treatment of accidental opioid overdose is to administer the opioid antagonist naloxone, which blocks the opioid receptors and reverses the effect of the opioid |
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|
Term
| What are the effects of naloxone? |
|
Definition
- blocks the opioid receptors and reverses the effect of the opioid
- reverses the analgesic effect of opioids |
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|
Term
| Therefore, when should a different treatment be used? |
|
Definition
| when this analgesic effect must be maintained (e.g. when using high doses of morphine for pain relief in cancer patients) |
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|
Term
| What receptor is co-expressed with the opioid μ receptor in the same neurones? |
|
Definition
| The serotonin receptor 5-HT4(a) and the 2 receptors act in a mutually antagonistic manner |
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|
Term
| What does stimulation of 5-HT4(a) receptors cause? |
|
Definition
| Stimulation of 5-HT4(a) receptors activates G proteins which stimulate adenylate cyclase, increasing [cAMP] |
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Term
| What does administration of a 5-HT4(a) agonist cause? |
|
Definition
| Administration of a 5-HT4(a) agonist will counteract the opioid-induced respiratory depression without counteracting the analgesic effect (because the receptors don’t co-express in the neurones responsible for the analgesic effects of opioids) |
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|
Term
| How effective are 5-HT4(a) agonists? |
|
Definition
| The use of 5-HT4(a) agonists (e.g. mosapride) has shown promise in animal studies but not, as yet, in human trials |
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