Anticholinergics

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Anti-cholinergics Steroids

• By Jim Clarke

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Anticholinergic Bronchodilators

• Indications
• Used for the treatment of bronchoconstriction in
  COPD
• Is also available for the treatment of allergic
  rhinitis (nasal spray formulation)

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How Anticholinergics Work
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Vagal Triggers

• Irritant Aerosols
• Cold dry air
• Cigarette smoke
• Noxious fumes
• Histamines
• High airflow (in exercise)
• Persistent cough (upper airway inflammation)

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Vagally-Mediated Bronchospasm
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Anticholinergic Agents

• Ipratroprium Bromide (Atrovent)
• Atropine Sulfate
• Glycopyrrolate (Robinul)
• Oxitroprium bromide

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Effects of Atrovent
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Affects of Atropine
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Available Forms Characteristics
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Anticholinergic Use in COPD

• Appear to work better than Beta agonists for
  patient with emphysema-chronic bronchitis
• Also appears to be of some help in patients with
  severe long term asthma
• Acts mainly on larger, more central airways
• Has fewer side effects than beta agonists

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Anticholinergic Use in Asthma

• Not as widely used for tx of asthma
• Useful in tx of
• Nocturnal asthma
• Psychogenic asthma

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Combination Drugs

• New preparations mix albuterol and ipratroprium
  for maximum bronchdilation effect
• Combivent (MDI)
• Frequently - unit dose preparations of the above
  medications are given during the same nebulizer
  treatment

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Advantages of Combivent

• Patients can receive the benefits of taking two
  drugs at once
• Better bronchodilation with improved airflow
• Compliance is better since there is only 1 MDI vs
  2 separate MDIs

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Corticosteroids
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Physiology of Corticosteroids

• Secreted by the Adrenal gland
• inner zone or medulla produces epinephrine
• outer zone or cortex produces corticosteroids

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Products of Adrenal Cortex

• Mineral corticoids
• aldosterone
• Sex hormones
• Estrogens Androgens
• Glucocorticoids
• related to natural cortisol
• Referred to as corticosteroids or steroids

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General Action of Steroids

• Defined as anti-inflammatory agents used in the
  treatment and prevention of asthma and other
  conditions causing an exaggerated inflammatory
  response in the lung.
• Inflammation is defined as the response of
  vascularized tissue to injury

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Inflammation in Asthma

• New understanding of asthma defines it as a
  disease in which there is chronic inflammation of
  the airway wall, causing airflow limitation and
  hyperresponsiveness to a variety of stimuli
• Process is mediated by a variety of agents
• Mast cells eosinophils T lymphocytes
  macrophages

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Hallmark Signs of Inflammation

• Redness
• Local dilation of blood vessels
• Flare
• Reddish color several centimeters around the
  original injury site
• Wheal
• Local swelling, occurring in minutes

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Events at the Cellular Level

• Increased vascular permeability
• Exudate in surrounding tissues
• Leukocytic infiltration
• White cells are attracted to area
• Phagocytosis
• White cells and macrophages ingest foreign
  material

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Events at the Cellular Level

• Mediator Cascade
• Histamine other chemicals are released at
  injury site
• Inflammatory mediators are produced
• leukotrienes

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Early Phase Response

• After initial triggering event, there is mast c
  cell degranulation with release of variety of
  chemical mediators (histamine prostaglandin D2
  leukotrine C4)
• Early phase response is bronchospasm
• There is a resulting decrease in expiratory flows
  from the lungs

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Late Phase Response

• After 1-2 hours, mast cells mediators recruit
  eosinophils, basophils, etc. to the lung
• After 6-8 hours, inflammatory cells have migrated
  into the airway walls
• Mediators stimulate other vasoactive and
  bronchoactive agents that last up to 24 hours
  longer
• Primary agent is arachidonic acid

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Late Phase Culmination

• Increased mucus production
• Increased permeability of vessels causing mucosal
  edema of the airway
• Shedding of airway wall cells (desquamation)
• Goblet cell hypertrophy
• Thickening of epithelial basement membrane

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Primary Actions of Steroids

• Inhibits recruitment migration of inflammatory
  cells
• Act by inhibiting the production of arachidonic
  acid
• Induces gene expression for anti-inflammatory
  proteins and receptors
• Suppresses gene expression for pro-inflammatory
  proteins

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Other Steroidal Effects

• Improve responsiveness to Beta 2 agents
• Decreases the white cell response to chemotaxis
• This causes eosinophil counts to fall

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Corticosterods for Oral Inhalation

• Dexamethasone (Decradron)
• Beclomethasone (Vanceril Beclovent)
• Triamcinlone (Azmacort)
• Flunisolide (AeroBid)
• Fluticasone (Flovent)
• Budesonide (not yet available in U.S.)

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Side Effects

• Oral Candiasis or Thrush
• Rinse mouth after use to prevent
• Hoarseness
• Cough and actual bronchoconstriction
• Poor use leading to inadequate dosing

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Systemic Steroids

• Given orally (p.o.) I.V. or I.M.
• Oral forms reach peak action in as short as 1
  hour
• Some forms may remain available for up to 1-4
  weeks (I.M. I.V.)

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Examples of Systemic Steroids

• Hydrocortisone (Solu-Cortef)
• Methylprednisolone (Medrol Solu-Medrol
  Depo-Medrol)
• Prednisolone (Delta-Cortef)
• Dexamethasone (Decadron)

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Side Effects of Systemic Steroids

• Hypothalmic-Pituitary-Adrenal Suppression
• Immuno-suppression
• Psychiatric reactions (psychosis)
• Cataract formation
• Osteoporosis
• Fluid retention
• Hypertension

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More Side Effects!

• Peptic ulcer formation
• Dermatologic changes
• Thinning of skin
• Cushingoid appearance
• Retardation of growth (in children)
• Slowing of healing in adults
• Incrased glucose levels steroids diabetes
• Myopathy of skeletal muscle

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Nasal Sprays

• Nasalide (flunisolide)
• Beconase Vancenase (beclomethasone)
• Nasacort (triamcinolone)
• Rhinocort (budesonide)
• Flonase (fluticasone)
• Doses are typically 1-2 sprays/nostril 1-4
  times/day

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Indications for Steroid Use

• Control of Asthma
• It is NOT a rescue drug when given via MDI
• Treatment of other bronchospastic conditions not
  controlled by other therapy
• Control of seasonal allergic or non-allergic
  rhinitis
• Steroids have been widely used in COPD
• It is less clear if they actually help patients

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End of Week 5 - Monday