Jan.

30, 2007
 Sample questions have been posted
 When go into eCollege, go to week 4
o Lecture
o Test
o Self-check
o 5 or 6 question to direct you on what you need to know for the test
o The ones people notoriously forget to look over
 each lecturer makes questions on their section
 questions for Dr. Laic’s section are straight from the notes
 Adverse Drug Effect Reporting website
o From Health Canada
o End of second lecture
o Address opens up small powerpoint presentation
 One test question will come from here
o Log onto main page for health Canada
o Table of contents on Left hand side
o Click on ‘Reporting Adverse Effects’
o New page that comes up will be a huge text article on all things you can
report
o Within text will find ‘Medeffects’ and click on that
o Will be within first or second paragraph
o Table of contents on right hand side of screen
o Click on ‘Learning Centre’
 Questions
o Were put on doc sharing, but will be changed to eSnips
o Presented groups – please post your questions on eSnips and your soft-
copy of your presentations
 Cases
o Will be handed back prior to being handed out the second round of cases
o

Drugs acting on the Respiratory System (This section is not on the exam this Thursday)
 Objectives
o Brief review on how we will look at drugs for the rest of the year
 The Respiratory System (not in note package)
o Tracheobronchial tree bathes in mucus-containing fluid
o Composed of : mucoproteins, proteins, fat, mucopolysaccharides
o Function: warm/moisten inspired air and trap foreign airborne particles
o Normal mucus secretions are 95% water (to maintain this need regular
proper hydration and regular maintained humidity of inspired air)
o Ca++ ions contribute to viscosity of sputum
 Seen in cystic fibrosis
o Yellow/green discolouration due to infection/stagnation of secretions
  Infection can be part of copper, pulled out from immune system
response
 DNA strands from broken down phagocytes
o Mucous produced from 3 sources
 Goblet cells, bronchial glands, serous transudate from mucosal
vasculature
• See in bronchitis – a large about of goblet cells and a large
amount of mucous
o Drug therapy wants to stimulate a greater volume of
secretion (more watery and less viscus)
o If going to take a drug that increases the amount of
secretion, need to stimulate the coughing reflex or
mechanically suck out the mucous
o Body makes approx 100ml/day
 Classification of Drugs used for Respiratory Tract disorder
o Anti-inflammatories
 Glucocorticoids
• Most commonly used
o Bronchiodilators
 Comparing the two drugs w.r.t their benefit and costs
o Anti-tussives
 Used to stop coughing
 A lot of controversy with Dextromethorphan
o Expectorants
 Most common overthecounter medication is guaifenesin
 Drugs affecting Respiratory Tract Fluid
o Anti-mucokinetic agents
 Atropine
• Parasympathetolitic
o Mucokinetic agents
 Increase the amout of mucous we are producing and increasing the
productiveness of cough
 Guaifenesin
• Works by stimulating the vagus nerve
 Menthol/camphor/lemon oil - mostly used as steam/vapour
inhalation
 Ipechacuanha
• Used with the vomiting centre
• Used in gastric reflux via vagus nerve
• Also controls cough reflex
 KI
• Water saline aerosols
 o Important regulatory agents to stimulate
expectoration
o Mucolytic agents
 Help break down/liquefy the mucous
 Given in aerosol form
 Agents that help cleave disulfide bond
 The Cough Reflex
o Receptors detect changes in tension and sends afferent signals to cough
centre (medulla) and cough centre sends efferent signals to diaphragm and
respiratory muscles to produce cough
o Anti-tussives anesthetize the afferent signal
o Some directly work in the medulla
 The 2 functions of coughing
o Gets rid of accumulated fluid and accumulated cells from the airway
o Clears and protects from microorganism proliferation
o Abnormal cough
 Suppress cough
o Narcotic Drugs
 Opiates most effective in suppressing cough
 Out of the opiates, codeine is the most effective anti-tussive
compared to its analgesic effect
 The drugs are primarily pain killers
 For it’s coughing anti-tussive effects need only a fraction of what’s
given in analgesic effect
 Less risk of side-effects less risk of toxicity
 The exact mechanism isn’t known
 Greatest risk factor
• Respiratory depression
• Tolerance and dependence
 Dextromoethorphan
• Considered to be the most widely used anti-tussive agent
• Not necessarily the strongest
o Non-Narcotic Drugs
 Diphenhydramine
• Benadryl
• Anti-tussive b/c works directly with anti-cough centre
 Guraifenesin
• Used to make things less sticky
• Sinusitis – b/c of protyolitic/disulfide bond cleaving
capability
 Rhinitis
o Allergic rhinitis
 Can be seasonal/non-seasonal
  Treated with some sort of anti-histamine or glucocorticoid
o Viral rhinitis
 From cold/flu
 Have general malaise/discomfort
 Drugs used to treat Rhinitis
o Anti-histamines
 Especially with allergic rhinitis
 Diphenhydramine
o Coriticosteroids
 To treat inflammation in the nose
 Most effect anti-inflammatory drugs for rhinitis
 Can be given in burst therapy (high dosage for short amount of
time)
o Alpha-adrenergic agonists
 Help decrease fluid loss from arterioles, so constrict them
 Less fluid leaking out, less resistance in the area
 Aerosol
 Oral
• Takes longer for action to happen and get longer action
• If take orally risking systemic effects
o Cromolyn
 Can be used prophylactically before allergy season
 Usually gluco-corticoids are first used, but if can’t handle them use
Cromolyn
o Ipratropium
 Anticholenergic
 Atrovent
 Rhinorrhea aspect of rhinitis
 Usually used for asthma
 Asthma Development
o Diagram
 Top left corner IgE flags
 Allergen comes in
 Flaged by IgE
 IgE sends signal to the cell for mediators to be released
 Also releases lipid mediators
• AA
• Prostoglandins
• And other immune system mediators
o Diagram
 Flow chart of AA production and prostaglandin production
 Inflammation within the airway
 Asthma Pathology
 Diagram
o Hallmark for Asthma is Bronchial hyperactivity to endogenous and
exogenous stimuli
o Hyperactivity is amplified by the fact that there is chronic inflammation
o Two big problems
 Chronic inflammation
 Hyperactivity
 Diagram
o Variety of different factors that can trigger degranulation and histamine
release
o B-adrenergic agents – will come up again
o Even after mast cell degranulation person can still experience asthma
attacks
 Asthma Pathology
o It’s shortness of breath happens two times
 Early/immediate
• Major concern is sudden immediate bronchoconstriction
• Will respond very well to bronchodilators
 Late/prolonged
• Sustained bronchoconstriction
• Not mediated by the same factors as early phase –
cytokines
• Increasing the hypereactivity of the bronchi
• Starts with too many eosinophils
 Asthma Facts
o Expiratory wheeze – hallmark expiratory measure
o Nearly 70% of asthma-related deaths occur at night
 Parasympathetic mode
 No one answer – controversial
 Asthma Population
o Treatment always same – improving quality of life by decreasing the
amount of acute attacks
 Drug treatment of Asthma (not in note package)
o Short-term RELIEVERS (bronchodilators)
o Long-Term CONTROLLERS (anti-inflammatory agents)
o Studies indicate that asthmatic bronchospasm may be effectively treated
by drugs with different modes of action, including:
 Inhaled Drug Delivery Methods
o Drug in solution
 In very small, air-suspended solution
o Inhaler
 Problem
• Aerosol propellant used is a CFC
 o Increase risk of hypoxemia and arrhythmia
o Now slowly being replaced with safer HFA
(hydrofluoroalkanes)
o Turbuhaler
 Don’t need propellant
 More complicated
o Nebuliser
 Can put other drugs in there, so used in hospitals
 Anti-inflammatory drugs
o Glucocorticoids
 Serious drugs, so used for serious situations
 Have greatest potential to cause adverse reactions
 Limited to inhaled use
 Beclomethasone, Budesomide, Fluticasone, Triamcinolone
• Children can get spacer that will help propel deeper in
respiratory tract, if stays in mouth get risk of thrush
• Fluticasone – preferred for children b/c only needed bid
• Used for preventing
 Burst
• Short duration, so no access to pituitary-adrenal
o Mast Cell Stabilizers
 Cromolyn Sodium
• Autocoids – leukotrienes and prostaglandins
• Used in prevention treatment of asthma
• Pharmacokinetics
o Oral bioavailability 1%
 Means you have to take more to get a
therapeutic level in the body
 The amount of drug you take orally only 1%
will get into blood to have an effect
 Less drug is getting into the body to cause
an effect
• Considered nontoxic b/c of pharmacokinetic factors
• Most of the side-effects are local – within respiratory tract
o Leukotriene Inhibitors
 Montelukasts
• Used for mild to moderate treatment of asthma
• Considered an alternate choice for treatment
• Can take orally
• Highly plasma protein bound
o Watch out for interactions!!!!
o Short half-life so studies haven’t showed any drug
interactions
 • Highly Metabolized by CYT P450
o Uh Oh!!! Watch out for interactions again!!!!
• Cascade effects in the body last longer, so only need one
dose of the drug
• Don’t need as much of a dose of a bronchodilator
 Bronchodilators
o B2-Adrenergic Receptor Agonists
 IV magnesium was used prior to this, to relax the smooth muscle
 So for asthma patients, Mg may be something you want to consider
 Sympathomimetic agents
 Increase in cAMP
• cAMP is the pivotal molecule here
• causes a cascade of reactions
• lowers intracellular Ca++ and muscle relaxes
 Selective B2 Receptor Agonists
• Select specifically to lower respiratory tract
• So NO muscle relaxation in cardiac muscle (B1 receptor)
• Used in acute attacks
• Albuterol (Ventaline)
• Salmeterol (Cerevent)
o Muscarinic receptor antagonist
 Ipratropium (adravent)
• Stops Ca++ from pbeing released via IP3 system, and
minimizes the amount of bronchoconstriction seen in late
stage asthma
• Primarily used in COPD
o More effective than B2-agonists
• Combination therapy
o Not used as primary therapy but as cocktail of drugs
o Theophylline
 Falls into same category as caffeine
 Similar reaction as you would see with coffee
 Cascade of many different reactions and actions
 More cAMP more relaxation of the muscle
 Not as prominent in its therapeutic dosage as it should be
• Only 10-20% of this inhibition occurs from the free drug in
the body
• What is the other 90% of the drug doing?
o Produces block in adenosine receptors
o Influences Ca++ receptors
 PK
• Phosphodiesterase enzyme inhibition
 • Less used now
• Little first pass effect
o Bioavailablity is higher
• Has very narrow therapeutic index
o Toxicity is very close to therapeutic index
 Nausea, vomiting
 Interactions
• With some antibiotics
 Naturopathic Considerations
• Diet influenced theophylline as well
•
o Ipratropium
o Theophylline