Lecture 12- Over the counter drugs - Allergy and Insomnia Flashcards
____ are caused by the hypersensitivity of the immune system to typically harmless substances in the environment.
Allergies
Symptoms of allergies include?
- red eyes
- itchy rash
- sneezing
- runny nose
- shortness of breath
- swelling
The mechanism of allergies involve ____ ____ ____ (IgE). ____ cells react inappropriately to an allergen to produce IgE antibodies against the allergen. Antibodies bind to the receptors on mast cells or on ____phils. Subsequent exposure to the allergen triggers release of inflammatory chemicals such as ____.
Immunoglobin E antibodies; B cells; basophils; histamine.
How many classes of histamine receptors are there?
4
* H1: allergic inflammation
* H2: gastric acid secretion
* H3: neurotransmission
* H4: immunomodulation
Which H receptors play a predominant role in allergic response?
H1
H____ receptors are located in smooth muscles, on vasuclar endothelial cells, in the heart, and in the nervous system.
H1
Drugs that interfere with histamine signaling in the brain will have symptoms associated with disrupted ____ or ____.
wakefulness; drowsiness
Histamine H1 receptors occur throughout the brain, with particularly high density in regions involved in ____ and ____ (thalamus, cortex and noradrenergic, serotonergic and dopaminergic nuclei)
arousal and waking
Which neurotransmitter is important in the wake-promoting system?
histamine
____ readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in ____; it also supresses activity in the ____.
drowsiness; nTS
Drugs with high affinity will have ____ EC50.
low EC50 as the drug concentration required is less to occupy effectors.
____ and ____ have similar affinities to the H1 receptor, so you need relatively high doses of ____ to block ____ effects.
Diphenhydramine; histamine
What is an example of first generation antihistamines?
Diphenhydramine
High effinity = ____ Ki
low
What is Ki?
concentration needed to displace 50% of the ligand.
pKi is the ____ ____ of Ki (like pH). A drug with a high affinity will have a ____ pKi (low ki)
negative log; high pKi
First generation antihistamines bind with relatively high affinity to ____ ____ receptors which have anticholinergic effects. This can lead to side effects such as ____ ____, ____ and ____.
muscarinic cholinergic; dry mouth; constipation and confusion.
____ develops rapidly to the sedative effects of diphenhydramine.
tolerance.
Diphenhydramine also decreases the quality of sleep (____ time in REM and ____ time in light sleep)
less;more
Which generation antihistamines have higher selectiviery for the H1 receptors?
Second generation.
Second-generation anti-histamines have poor ____ ____ ____ permeability, so they lack the sedative effects.
Blood-brain barrier
Which generation of anti-histamines have longer duration of action?
Second generation.
____ is an H1 receptor antagonist in the second generation anti-histamines.
Cetirizine
Which of the following drug, Diphenhydramine or cetirizine, have a longer duration of action?
cetirizine (24 hours) while diphenhydramine is 4-6hours.
____ is an inverse agonist at the H1 receptor of the second generation anti-histamines.
Loratadine.
Loratadine is mostly bound to ____ ____ (i.e, albumin). The ____ however are not active.
plasma proteins; protein
When loratadine is given orally, rapid ____ ____ ____ converts loratadine into _____.
first pass metabolism; desloratidine, therefore loratadine is a prodrug.
When loratadine is given orally, rapid ____ ____ ____ converts loratadine into _____.
first pass metabolism; desloratidine, therefore loratadine is a prodrug.
Which of the following drug, loratadine or desloratadine, has a longer duration of action?
desloradatine.
____ (1/2) generation OTC anti-histamine drugs have ____( high/low) selectivity for the H1 receptor (off-target side effects) and penerate the blood-brain barrier, so they are ____ (sedative/non-sedative).
1; low; sedative
____ (1/2) generation OTC anti-histamine drugs have ____( high/low) selectivity for the H1 receptor (off-target side effects) and have poor penetration the blood-brain barrier, so they are ____ (sedative/non-sedative).
2; high; non-sedative.
First generation antihistamines are marketed for ____, ____, ____, and ____ whereas second generation anti-histamines were devleoped to isolate and optimize the anti-allergy effects.
allergy, insomnia, cough and cold.
