Drugs 101

Allergy
Adverse reaction to harmless material
Allergy requires prior exposure

• Immune system responds to something

– Epitopes of molecules from pathogens
• Immune system “remembers” that material
– Memory cells
• Subsequent exposure produces reaction
– Protection from pathogens
– Allergy to harmless material
Hay fever is a reaction to pollen
Cold-like symptoms
Some people get a geographic tongue
Atopic dermatitis from surface exposure
Contact dermatitis from irritants

• Hand washing makes it worse

• Common with industrial powders
Exposure to large amounts of powder
Contact dermatitis from immune reaction
Immune reactions at the site of contact
Urushiol produces the reaction

OH
OH
Latex from rubber tree sap
Latex gloves and condoms
Nickel is a common allergen
Nickel alloys are common
Many piercings made of stainless steel
Allergies to henna tattos on skin
Dust allergies are common
Mattresses can contain large amounts of
droppings
Allergies to pets
Most reactions are to pet saliva
Mold and fungi produce many allergies
Food can give allergy or intolerance

• Allergy
– Immune system reacts to the food
• Intolerance
– Substances in food produce adverse reaction
Food intolerance affects about 30 % of adults
Lactose intolerance is inability to digest lactose
Bacteria digest food instead
Lactase is available as a supplement

OH
HO OH OH HO OH
O O HO O
HO O O HO OH HO OH
HO OH OH
OH OH
OH
Lactose
Headaches from food
Spices can irritate stomach
Food allergies affect about 4 % of adults
Common food allergens
Signs of food allergy – bags under eyes
Signs of food allergy – dark under eyes
Peanut allergy common in North America
Peanut allergy rare outside North America
Peanut free schools common only in North
America
Spider and insect bites can give strong reactions
Rare allergies - allergy to sunlight
Aquagenic allergy – allergy to water
20th Century disease – “allergy” to man-made
substances
Allergy is a disease of the developed world

• Rates have doubled since 1980

Hay fever was a rare condition in 1900
Peanut free schools only in last 30 years
Are we exposed to more substances?
Industrial pollution more common in developing
world
Most allergies involve natural substances
Hygene hypothesis for allergy
Immunization and antibiotics reduce infection
rates
Children in daycare less likely to be allergic
Children in large families have less allergies
East Berlin had poor health care and lots
of pollution
West Berlin had good health care and
was less polluted
More allergies in West Berlin
Some kids tend to have fewer allergies
Some kids have more allergies
Allergy requires prior exposure

• Involves immune system memory

• Hypersensitivity on 1st exposure
– Unknown previous exposure
Mast cells display IgE antibodies
Allergin contacts the IgE molecules
Mast cell degranulation releases histamine
Histamine produces allergy symptoms
Managing allergy

• Avoidance
• Antihistamines
• Decongestants
• Immune modulators
• Immunotherapy
Allergy tests look for reactions
Avoidance best for food allergy

• Difficulty may be finding out what to avoid

• Processed foods contain variable
ingredients
Tracking down food allergy - logbook
Antihistamines are often taken

Diphenhydramine
Antihistamines are histamine antagonists
Messenger Messenger binding
changes receptor
shape

Receptor

Receptor
Membrane Membrane
Cell Cell

Second messenger

Drug stops normal

Drug binding does message
Drug
not change Messenger
receptor shape
Receptor

Receptor

Receptor
Membrane Membrane Membrane
Cell Cell Cell

Second
messenger not
released
Diphenhydramine is in Benadryl

Diphenhydramine
Generic versions are available
Diphenhydramine makes you sleepy
Chlorpheniramine is in Chlor-Tripolon

• Side effect is drowsiness

Cl

N
Chlorpheniramine is in cold medications
Antihistamines reduce nausea

Diphenhydramine (anithistamine)
8-chlorotheophyliine (stimulant)
 First generation antihistamines can enter
the brain

Cl

N
 Loratadine is a second generation
antihistamine

Cl

O O
Loratadine does not enter the brain

Cl

O O
Loratadine
Body converts Loratadine to Desloratadine

Cl Cl

N N
metabolism

N N
H
O O

Loratidine Desloratidine
(Claritin)
Desloratidine is in Aerius

Cl
N

N
H
Seldane contained terfenadine

OH
First non-drowsy antihistamine (1985)

OH
Drug-drug interactions with Ketoconazole
Terfenadine is activated in the body

OH OH

Liver
OH
N N
O

OH OH

Fexofenadine
Allegra contains fexofenadine

OH

OH
N
O

OH
 Reactine contains cetirizine

Cl

N O
O
OH
Various generations of antihistamines

• First generation (drowsiness)

– Diphenhydramine (1940’s, Benadryl, generic
available)
– Chlorpheniramine (1940’s, Chlor-Tripolon, generic
available)
• Second generation (non-drowsy)
– Loratadine (1989, Claritin, generic available)
– Desloratadine (2002, Aerius, generic available)
• Third generation (non-drowsy)
– Fexofenadine (1996, Allegra, generic available)
– Cetirizine (1996, Reactine, generic available)
Buyer beware! Price for 100 tablets
Benadryl (Dipheniramine) $32.45
Life-Brand Dipheniramine $44.95
Claritin (Loratadine) $63.32
Life-Brand Loratadine $81.23
Kirkland Loratidine $9.12

Aerius (Desloratidine) $83.30

Life-Brand Desloratadine $71.98
Allegra (Fexofenadine) $68.95
Life-Brand Fexofenadine $61.96
Reactine (Cetirizine) $62.05
Life-Brand Cetirizine $56.23
Fewer pills makes product look cheaper
Buying in bulk is best value
Pseudoephedrine for decongestion
Steroid decongestants (prescription)

Glucocorticoid agonists
- Suppress inflammation
Steroid decongestants (OTC)
F

O S
HO OH

F
O
F
Anaphylaxis is very serious
Epi-Pen for strong allergic reactions
Know how to use it
Epi-pen price extortion

• More than $600 US for 2 injectors

• Wholesale price of the drug is $2.50
Drug pricing based on cost of alternate
treatments
• Cost of the drug is not based on the cost
of manufacture
– old, off patent drug
• Cost is not based on cost of research
– old drug + old technology
• Rationale is that $600 US is cheap
compared to the cost of anaphylaxis
– Hospital costs in thousands
– Ambulance costs in thousands
– Costs of death or disability
Many other drugs are priced this way (US
pricing)
• Harvoni
– Hepatitus C
– $94, 500 per patient (3 months)
• Daraprim
– Parasitic infections
– $750 per pill
• Cost to manufacture: less than $1 per pill
• Emflaza
– Duchenne muscular dystrophy
– $89, 000 per year
Up to 50 % of allergies progress to asthma
Original drugs targeted nerve signals
Salbutamol targets nerves to bronchii
OH
H
N
Brain HO

HO
OH
HO NH2
Spinal cord

HO

Organ Sympathetic
Fight or Flight

Organ Parasympathetic
maintenance
O
N
O
Salbutamol is a selective adrenaline agonist
Messenger Messenger binding
changes receptor
shape

Receptor

Receptor
Membrane Membrane
Cell Cell

Second messenger

Drug Drug binding

changes receptor
shape
Receptor

Receptor
Receptor
Membrane Membrane
Cell Cell

Second messenger
Adrenaline agonists open airways in the lungs
High doses will stimulate the heart
OH
H
N
Brain HO

HO
OH
HO NH2
Spinal cord

HO

Organ Sympathetic
Fight or Flight

Organ Parasympathetic
maintenance
O
N
O
Over use caused heart attacks
Flovent inhaler delivers measured doses
Can use steroid decongestants
Leukotrienes associated with asthma

OH
- Related to prostaglandins CO2H
CO2H lipoxygenase
- Stimulate mast cells
S
Cys
Singulair is a leukotriene antagonist
Messenger Messenger binding
changes receptor
shape

Receptor

Receptor
Membrane Membrane
Cell Cell

Second messenger

Drug stops normal

Drug binding does message
Drug
not change Messenger
receptor shape
Receptor

Receptor

Receptor
Membrane Membrane Membrane
Cell Cell Cell

Second
messenger not
released
Singulair is very effective
Persistence pays off

• Identify the allergen

– Avoid it when you can
• Try antihistamines
– First, second or third generation
– Experiment and see which works best for you
• Prescription steroids
Various generations of antihistamines

• First generation (drowsiness)

– Diphenhydramine (1940’s, Benadryl, generic
available)
– Chlorpheniramine (1940’s, Chlor-Tripolon, generic
available)
• Second generation (non-drowsy)
– Loratadine (1989, Claritin, generic available)
– Desloratadine (2002, Aerius, generic available)
• Third generation (non-drowsy)
– Fexofenadine (1996, Allegra, generic available)
– Cetirizine (1996, Reactine, generic available)