ANTINAUSEANTS AND ANTIEMETIC AGENTS-

• Nausea and Vomiting


  The act of emesis and the sensation of nausea that accompanies it generally are viewed as protective reflexes that serve to rid the stomach and intestine of toxic substances and prevent their further ingestion
• Vomiting


  1. Pre-ejection phase (gastric relaxation and retroperistalsis)

  2. Retching (rhythmic action of respiratory muscles preceding vomiting and consisting of contraction of abdominal and intercostal muscles and diaphragm against a closed glottis)

  3. Ejection (intense contraction of the abdominal muscles and relaxation of the upper esophageal sphincter)
• Vomiting


  • Accompanied by multiple autonomic phenomena including salivation, shivering, and vasomotor changes
  • During prolonged episodes, marked behavioral changes including lethargy, depression, and withdrawal may occur
• Emesis center


  Coordinated by a central emesis center in the lateral reticular formation of the mid-brainstem adjacent to both the chemoreceptor trigger zone (CTZ) in the area postrema (AP) at the bottom of the fourth ventricle and the solitary tract nucleus (STN) of the vagus nerve
• Chemoreceptor trigger zone (CTZ)


  Monitors blood and cerebrospinal fluid constantly for toxic substances and to relay information to the emesis center to trigger nausea and vomiting
• Emesis center inputs


  • Gut, principally by the vagus nerve (via the STN) but also by splanchnic afferents via the spinal cord
  • Cerebral cortex (particularly in anticipatory nausea or vomiting)
  • Vestibular apparatus (in motion sickness)
• Emesis center outputs


  Nuclei responsible for respiratory, salivary, and vasomotor activity, as well as to striated and smooth muscle involved in the act
• CTZ receptors


  High concentrations of receptors for serotonin (5-HT3), dopamine (D2), and opioids
• STN receptors


  Rich in receptors for enkephalin, histamine, and ACh, and also contains 5-HT3 receptors
• A variety of neurotransmitters are involved in nausea and vomiting, and an understanding of their nature has allowed a rational approach to the pharmacological treatment of nausea and vomiting
• Disorders of the respiratory system

  • Respiratory tract infections
  • Allergic disorders
  • Inflammatory disorders
  • Conditions that obstruct airflow (e.g. asthma and chronic obstructive pulmonary disease, COPD)
• Drugs acting on the respiratory system

  • Bronchodilators
  • Corticosteroids
  • Cromoglycates
  • Leukotriene receptor antagonists
  • Antihistamines
  • Cough preparations
  • Nasal decongestants
• Asthma


  A chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells
• Asthma


  • Causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning
  • Associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment
  • Causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli
  • The condition of a patient's asthma may change depending on the environment, activities, and other factors
• Aerosol delivery of drugs


  • Topical application of drugs to the lungs can be accomplished by use of aerosols
  • Produces a high local concentration in the lungs with a low systemic delivery, thereby significantly minimizing systemic side effects
• Devices for aerosol therapy

  • Metered-dose inhalers
  • Nebulizers
• Metered-dose inhalers


  • Cheaper and portable
  • Require hand-breathing coordination
• Nebulizers


  • Do not require hand-breathing coordination
  • Can be delivered by facemask to young children or older patients who are confused
• Dry-powder inhalers


  • Use lactose or glucose powders to carry the drugs
  • Require a relatively high airflow to suspend the powder properly
  • The dry powder can be irritating when inhaled
  • Storage in areas with wide temperature fluctuations or high humidity can impair their performance
• Cough


  A useful physiological mechanism that serves to clear the respiratory passages of foreign material and excess secretions
• Centrally active antitussive agents

  • Reduce the frequency or intensity of coughing
  • The cough reflex is complex, involving the central and peripheral nervous systems, as well as the smooth muscle of the bronchial tree
• Centrally active antitussive agents

  • Opioid analgesics (codeine and hydrocodone)
  • Nonopioid agents
• Codeine


  • Used widely owing to its high oral/parenteral potency ratio
  • Orally, codeine at 30 mg is approximately equianalgesic to 325 to 600 mg aspirin
  • Combinations of codeine with aspirin or acetaminophen usually provide additive actions, and at these doses, analgesic efficacy can exceed that of 60 mg codeine
• Oxycodone


  • Used widely in combination with aspirin or acetaminophen
  • Available in a sustained-release formulation for chronic pain management (OXYCONTIN)
  • Subject to widespread abuse leading to serious consequences, including death
• Expectorant


  • Any agent which dissolves thick mucus and is usually used to help relieve respiratory difficulties
  • Does so by hydrolyzing glycosaminoglycans, tending to break down/lower the viscosity of mucin-containing body secretions/components
• Mucolytic agent


  • Helps bring up mucus and other material from the lungs, bronchi, and trachea
  • Example: guaifenesin which promotes drainage of mucus from the lungs by thinning the mucus and also lubricates the irritated respiratory tract
• Sometimes the term "expectorant" is incorrectly extended to any cough medicine
• Expectorants increase bronchial secretions and mucolytics help loosen think bronchial secretions
• Expectorant

  A mucolytic agent or expectorant is any agent which dissolves thick mucus and is usually used to help relieve respiratory difficulties. It does so by hydrolyzing glycosaminoglycans, tending to break down/lower the viscosity of mucin-containing body secretions/components.
• Expectorant

  An expectorant (from the Latin expectorare, to expel from the chest) is a medication that helps bring up mucus and other material from the lungs, bronchi, and trachea.
• Example of expectorant

  • guaifenesin which promotes drainage of mucus from the lungs by thinning the mucus and also lubricates the irritated respiratory tract
• Expectorants

  Increase bronchial secretions
• Mucolytics

  Help loosen think bronchial secretions
• Expectorants

  Reduce the thickness or viscosity of bronchial secretions thus increasing mucus flow that can be removed more easily through coughing
• Mucolytics

  Break down the chemical structure of mucus molecules. The mucus becomes thinner and can be removed more easily through coughing
• Chronic Obstructive Pulmonary Disease (COPD)

  • Umbrella term for various conditions characterized by limitation of airflow that is not reversible
  • Chronic airflow limitation caused by a mixture of small airway disease and parenchymal destruction
  • Airflow limitation is often progressive
  • Associated with an abnormal inflammatory response of lungs to noxious substances
  • PREVENTABLE and TREATABLE disease
• Emphysema

  Destruction of the gas exchanging surfaces of the lung (alveoli)
• Chronic bronchitis

  Presence of cough and sputum production for at least 3 months in each of two consecutive years
• Risk factors for COPD

  • Genes
  • Exposure to particles (tobacco smoke, occupational dusts, indoor air pollution, outdoor air pollution)
  • Lung Growth and Development
  • Oxidative stress
  • Gender (appears to be related to cigarette use?)
  • Respiratory infections
  • Socioeconomic status
  • Nutrition
  • Comorbidities (e.g. asthma)
• Asthma

  Eosinophilic inflammation