Lecture 9 - Drugs & Allergy Flashcards
List some Allergic Disorders that we discussed
- Allergic Rhinitis (hay fever)
- Allergic Conjunctivitis (pink eye)
- Atopic Dermatitis (eczema)
- Urticaria (hives)
- Asthma (inflammation of airways)
- Anaphylaxis (multi-organ allergic reaction)
Define what an allergy is
- Inflammatory disorder (hyper immune response to allergens)
- Maladaptive immune system response creating memory to antigens
Maladaptive
not providing adequate or appropriate adjustment to the environment or situation
What are the key players/immune cells involved in allergic reactions?
- IgE
- mast cells
- basophils
- eosinophils
- dendritic cells
- T-cells (Th1&2)
- B-cells
- plasma cells
What are mast cells?
Tissue cells of the immune system found in loose connective tissue, organs, vasculature, nerves, skin, respiratory tract, etc.
Where are mast cells not present?
in epidermal cells, CNS, gastric mucosa
What do mast cells store?
Store histamine, interleukins, proteoglycans (ex. heparin) and various enzymes in their granules at cytoplasm
When are mast cell granules released?
they are released upon stimulation an allergen; degranulation
What does mast cell degranulation cause?
- increased blood flow and permeability of blood vessels (i.e. inflammation and swelling)
- contraction of smooth muscles (ex. bronchial muscles)
- increased mucous production & fluid secretion
What allergy symptoms do histamine and prostaglandin cause?
- tickling
- itchiness
- nose rubbing
- allergic salute
What allergy symptoms do histamine and leukotrienes cause?
- sneezing
- runny nose (mucosal secretion)
- post nasal drip
- throat clearing
What allergy symptoms do histamine, leukotrienes, bradykinin, platelet activating factor (PAF) cause?
- nasal congestion
- mouth breeding
- stuffy nose (mucosal edema)
- snoring
Histamine is an autacoid. What does autacoid mean?
self relief
Where is histamine stored?
-stored in tissue mast cells and blood basophils
What is histamine released by?
- antigens; allergic responses (immediate hypersensitivity)
- drugs; morphine, succinylcholine, radio contrast media
- insect venoms
- physical factors; scratching, cold
How many H (histamine) receptors are there?
4
Which H receptor is the most important for allergic disorder and is the classic target for “antihistamines”?
H1
What does binding to the H1 receptor cause?
- contraction; gastric and respiratory smooth muscle (H1)
- vasodilation (H1 and H2)
- increased vascular permeability (H1)
- pruritis “itching” (H1)
- increased bronchial secretions and viscosity (H1)
- bronchoconstriction
What does binding to the H2 receptor cause?
- receptor stimulation mediates gastric acid secretion (H2)
- receptor blockage decreases gut acidity (ranitidine)
What does binding to the H3 receptor cause?
- cholinergic neurotransmission (airway)
- negative feedback mechanism; inhibit histamine, NE and acetylcholine release
What does binding to the H4 receptor cause?
chemotaxis of mast cells, eosinophils, neutrophils. Cytokine release from T and dendritic cells
What happens when histamine is pricked onto skin?
It produces a triple response:
1 - RED area at site of injection (vasodilation)
2 - WHEAL replaces red area - edema
3 - bright red FLARE - indirect vasodilation (axonal reflex)
Allergic rhinitis is known as ?
hay fever bitches
List some symptoms of allergic rhinitis
-rhinorrhea (runny nose), plugged nasal passages, itching (eyes, nose and throat) tearing, fatigue, headache
List 2 branches of allergic rhinitis
1: Seasonal (airborne pollen)
2: Perennial (animal dander, mold, dust, etc.)
___% of patients with rhinitis present with asthma
40
__% of asthmatics experience rhinitis
70
Allergic Rhinitis prevalence in North America = ___%
20
3 treatment options for AR are?
- Avoidance
- Pharmacotherapy
- Immunotherapy
What pharmacological options are available for the treatment of AR?
- antihistamines
- intranasal glucocorticoids
- leukotriene modifiers
- decongestants
- mast cell stabilizers
- anticholinergic
- anti-IgE therapy
- systemic steroids (not preferred)
List some antihistamines
- chlorpheniramine
- diphenhydramine
- cetirizine
- loratidine
- fexofenadine
List an intranasal glucocorticoid
-fluticasone
List a leukotriene modifier
-montelukast
List some decongestants
- phenylephrine
- pseudoephedrine
List a mast cell stabilizer
-cromolyn sodium
List an anticholinergic
-ipratropium
List an anti-IgE therapy
-omalizumab
What is Immunotherapy?
allergen specific immunotherapy
What is the action of antihistamines?
block H1 receptor
What kind of symptom relief do we see with antihistamines for the treatment of AR?
- decreased itching
- decreased vascular permeability
- decreased bronchial secretions
- relaxation of bronchial smooth muscle
- decreased cough receptor stimulation
List some 1st gen AH
- diphenhydramine
- chlorpheniramine
Side effects/other actions of 1st gen AH
- sedation
- anticholinergic effects (dry mouth, constipation, dry eyes)
- anti-emetic
List some 2nd gen AH
- cetirizine
- loratidine
List the 3rd gen AH
fexofenadine
What are the administration routes of antihistamines?
- Oral (allergy)
- Intranasal (allergy)
- Intravenous (used only later in anaphylaxis but benefit ?)
Half-lives of antihistamines?
Variable: 8-24 hours
Are antihistamines present in breast milk?
Yes - the conc in plasma = conc in breast milk
When is the optimal time to take antihistamines?
Best if given before an anticipated allergic reaction
**Remember, antihistamines do not get rid of existing released histamine, only prevent further histamine from binding to H1 receptors.
Most antihistamines are metabolized by ______ enzymes
CYP 3A4
Knowing that antihistamines are metabolized by CYP 3A4, what is a beverage that you would suggest patients stay away from when taking them?
grapefruit juice as it may block metabolism
What is the indication for antihistamines?
- DOC for mild to moderate rhinitis
- relieves sneezing, itching, nasal discharge and ocular symptoms (itching, tearing, erythema)
- may be given with decongestant (i.e. pseudoephedrine)
- best for exudative allergies (hay fever)
For seasonal mild AR, recommend ??
1st, 2nd, or 3rd generation AH
What do you recommend for severe AR
intranasal glucocorticoid (ex. fluticasone)
Adverse effects of 1st gen AH?
-anticholinergic (dry mouth, dry eyes, constipation) , somnolence (sleepiness/drowsiness), problems with cognition, learning and memory, psychomotor, etc.
Who are 1st gen AH approved for?
Anyone over 2
*Use limited for children under 6
Which gens of AHs are safe in pregnancy?
2nd and 3rd gen
Would you recommend a 1st gen AH in pregnancy?
No - recommend a 2nd or 3rd gen instead
Adverse effects of 2nd and 3rd gen AH’s?
- penetrate brain poorly
- sedation is NOT an issue (except maybe a little with cetirizine)
Fexofenadine is free of _____
sedation
Is cetirizine safe in children?
You bet your ass it is :D
Intranasal 2nd or 3rd gen AH = ____ onset
rapid
Give an example of an intranasal 2nd or 3rd gen AH
azelastine
Fluticasone is an example of ??
an intranasal glucocorticoid
Is fluticasone for prevention or treatment?
BOTH
Does increasing dose of fluticasone increase benefits?
No - it increases side effects and not benefits
Effective dosing of fluticasone?
once daily
Fluticasone:
May take _____ to be maximally effective
7 days
Fluticasone:
Could cause ___
epistaxis (nose bleed)
What do systemic glucocorticoids have effects on?
growth, bone density, cataract formation, intraocular pressure
Where do corticosteroids act?
- Act on phospholipase A2 so prevents formation of Arachidonic acid
- Acts on protein synthesis so prevents synthesis of COX1 and COX2
When are leukotrienes released?
During allergic inflammation by mast cells, eosinophils, basophils, inflammatory cells
What are leukotrienes involved in?
Infiltration of inflammatory cells, mucous secretion, but also affect airway (bronchiolar) constriction
Give an example of a leukotriene receptor antagonist
montelukast
What kind of symptom relief does montelukast provide?
- modest relief of congestion, itching, discharge
- less effective than intranasal glucocorticoids
- normally used with antihistamine or intranasal glucocorticoid
MOA of Montelukast?
block leukotriene receptor
Phenylephrine is a ______
decongestant
Phenylephrine is a __________ agonist
alpha 1
MOA of phenylephrine (decongestant)?
-increased vasoconstriction, reduced nasal swelling
SE of phenylephrine (decongestant)?
insomnia, nervousness, headache, palpitations, HTN, urinary retention
*nasal decongestants have WAY LESS side effects
Why should you only use phenylephrine for less than 3 days?
potential rebound congestion
How does chromoly sodium work?
It is a mast cell stabilizer:
-Inhibits mast cell degranulation and release of mediators
Why are mast cell stabilizers not really helpful?
MUST BE GIVEN BEFORE EXPOSURE
-hard to do
How does Ipratropium work?
It is an anticholinergic:
- Reduces mucus secretion
- No effect on inflammation
- No relief of sneezing, itching or congestion
When is Ipratropium v useful?
if primary symptom is nasal discharge
SE of Ipratropium?
Other anticholinergic effects:
-urinary retention, dry eyes, dry mouth
When is Ipratropium not recommended?
-caution in glaucoma and prostatic hypertrophy
Omalizumab is a _________
anti-IgE antibody
Describe the administration and MOA of Omalizumab
- given SC, selectively binds human immunoglobulin E (IgE)
- prevents IgE binding to cells and reduces free IgE in serum
When are oral glucocorticoids recommended?
- oral administration of glucocorticoids is last resort due to major side effects
- intranasal is best choice
chart on slide 29 = good stuff
cool
Describe Allergen Specific Immunotherapy
- SC allergen immunotherapy
- administer increasing doses of a solution of allergens SC to which patient is shown to be sensitive (skin tests)
- may also be given SL
- build up period…weekly then monthly injections for years, dose increased until fewer symptoms with natural exposure
- once desired dose is established, there is monthly maintenance
- administered over 3-5 years
- benefit may continue when this therapy is discontinued
Indications of Immunotherapy
- IgE in the serum or skin sensitivity to allergen (cat, pollen, dog, etc)
- poor pharmacotherapy response or side effects
- patient preference
When should you avoid Immunotherapy?
severe asthma, CV disease, high dose B blockers, do not initiate during pregnancy
