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DEENT Exam 2 > Lecture 2 > Flashcards

Lecture 2 Flashcards

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1
Q

What are associated with the release of histamines, serotonin, and prostaglandins?

A

Allergic conditions such as sinus drainage, hay fever, asthma, hives, eczema, contact dermatitis, food allergies and reactions to drugs

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2
Q

What are sometimes referred to as autocoids or local hormones?

A

histamines, serotonin, prostaglandins

because these substance do not come from a gland but travel a distance in the body

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3
Q

Where are basophils located?

A

basophils carry histamine in granules through the blood (to sites of injury)

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4
Q

Where are mast cells located?

A

in almost all tissues

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5
Q

What is the CNS’s role in histamine production?

A

Acts like a neurotransmitter instead of an autocoid.

Action - Neuroendocrine control, cardiovascular regulation, thermal and body weight regulation and sleep and arousal.

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6
Q

Where are enterochomaffin-like cells are where are they located?

A

they are located in the stomach and they activate acid production

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7
Q

What are the 4 histamine receptors and what are their post receptor mechanisms?

A

H1 (smooth muscle, endothelium, brain) - Gq: increase IP3, DAG
H2 (gastic mucosa, cardiac muscle, mast cells, and brain) - Gs: increased cAMP
H3 (Presynaptic autoreceptors in brain, myenteric, and other neurons) - Gi: decreased cAMP
H4 (Eosinophils, neutrophils, CD4 Tcells) - Gi: decreased cAMP

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8
Q

What are the functions of the H1 receptor?

A

mediates pain and itching, contraction of the bronchi, gut, uterus and iris, relaxation of small blood vessels causing vasodilation, contraction of endothelial cells causing edema, increases arachidonic add (AA) release and prostaglandin synthesis, increases the amount and viscosity of mucus from goblet cells, stimulates the cough reflex

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9
Q

The H1 receptor is similar to what receptor and has what role in allergies and inflammation?

A

45% similar to muscarinic receptor and 5-HT receptors.
The receptor has higher affinity for histamine than the H2 receptor.

Increased histamine release.
Increased adhesion molecules and chemotaxis.

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10
Q

What are the functions of the H2 receptor?

A

Increase gastric acid secretions, autoreceptor for histamine release in mast cells and basophils, relaxation of airway, uterine and vascular smooth muscle, positive inotropic and chronotropic

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11
Q

H2 receptors: allergy and inflammation

A

decreased eosinophil and neutrophil chemotaxis, decrease cytokine production

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12
Q

What are the functions of the H3 receptor?

A

sleep/wake cycle, energy and endocrine homeostasis, cognition and memory

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13
Q

H3 Receptor: allergy and inflammation

A

neurogenic inflammation, pro-inflammatory, prevents excessive bronchoconstriction

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14
Q

What is the function of the H4 receptor?

A

causes differentiation of myleoblasts

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15
Q

H4 receptor: allergy and inflammation

A

increases eosinophil chemotaxis

important in psoriasis

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16
Q

What are the two types of release?

A

degranulation and receptor mediated (antigen-mediated)

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17
Q

What are the primary cells involved in the immediate hypersensitivity reaction?

A

tissue mast cells and blood basophils

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18
Q

What is the process of antigen-mediated release or degranulation?

A

Antigen causes the generation of IgE.
IgE binds to the surface of mast cells or basophils.
Antigen bridges the IgE and increases calcium levels in the cell.
Exocytosis of contents (degranulation)

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19
Q

What can degranulation release?

A

histamine, kinins, serotonin, slow-reacting substance, prostaglandins, platelet activating factor

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20
Q

What are compounds and agents that release histamine?

A

Any thermal (ex. burn) or mechanical stress of sufficient intensity. (any injury)
Basic drugs and chemicals: morphine, codeine, d-tubocurarine, guanethidine succinylcholine and vancomycin
Venoms from stinging insects

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21
Q

What can cause red man syndrome?

A

vancomycin

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22
Q

What are the phases of an allergic reaction?

A

Sensitization phase: allergen stimulates IgE production
Early phase: re-exposure causes release of histamine and proteases from mast cells
Cellular recruitment: circulating leukocytes like basophils and eosinophils are recruited to release more inflammatory mediators
Late phase: After 2-4 hours, mucus hyper secretion occurs

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23
Q

What is the MOA of H1 antihistamines?

A

inverse agonist (not antagonist!) at the H1 receptor
binds and stabilizes the inactive state of the receptor
Can act as an antagonist at non-H1 receptor sites
Antihistamines has anticholinergic and other side effects because they bind to lots of receptors

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24
Q

What is the pharmacological effect of H1 antihistamines?

A

At the H1 Receptor: decreased redness, swelling, itching, sneezing, rhinorrhea, and whealing
A the nuclear factor: decreased antigen presentation, expression of cell-adhesion molecules, chemotaxis, and proinflammtory cytokines.
At the calcium-ion channels: decreased mediator release

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25
What are the side effects of the first generation antihistamines?
Sedation: central H1 receptors, readily cross thee BBB Paradoxical excitement in children Nervous system effects: disturbed coordination, decreased cognition Increased appetite Abuse potential (diphenyhdryamine and dimenhydriniate which may cause euphoria, hallucinations, and "getting high") Peripheral sodium channel blockade (good local anesthetic) Anticholinergic effects (Can't see, can't pee, can't spit, can't shit) Anti-SLUGE Cardiovascular effects: tachycardia Sensitivity reactions
26
What are the side effects of the second generation antihistamines?
No or low sedation Cardiovascular effects: (astemizole and terfenadine which are no longer on the market) cause most of the dangerous CV effects, changes in the electrical conductivity of the heart pacemaker cell can result in lethal tosades de points Food-drug interaction: 5 oz of orange, apple or grapefruit juice reduce serum levels of fexofenadine by 40%. separate by 2 hours
27
What are the uses of 1st and 2nd generation antihistamines?
``` Anti-allergy Uticaria(hives) Parkinson's disease and movement disorders Motion sickness/antiemetic action Dermal itching and pain Insomnia (1st gen) ```
28
What is Intranasal saline's formulation, products and MOA?
Formulation: isotonic or hypertonic Products: nasal spray, neti pot, bulb syringe MOA: unknown
29
What are the pharmacological effects of nasal saline?
improve mucus clearance, enhance ciliary beating, remove antigens and inflammatory mediators
30
What are the side effects of nasal saline?
``` burning or stinging of the nose Amoeba infection (do not use tap water) ```
31
What is the order of ability to cross the BBB of first generation antihistamines?
``` Diphenhydramine = promethazine = hydroxyzine chlorphenirmaine = dexchlorpheniramine ```
32
What are the antihistamines used for Parkinson's disease or movement disorders?
diphenhydramine, hydroxyzine, cyproheptadine, and promethazine
33
What antihistmaines can be used for motion sickness/antiemetic action?
Efficacy = scopolamine > promethazine > meclizine = cyclizine = dimenhydrinate
34
What antihistamines are used for insomnia?
All PM drugs, nytol, sominex, and sleepinal have diphenhydramine. Night-time Sleep-Aid and Unisom have doxylamine.
35
What are the secretory cells and what do they do?
Epithelial cells, goblet cells, and basal, cells. They secrete enzymes, IgA antibodies (special antibodies located in body secretions which kill things coming in), mucus (captures particles in the air before it reaches the lungs). Use anticholinergic to reduce vasodilatin and mucous secretion.
36
What do the cholinergic receptors do to the nasal mucosa?
PNS - ACh: Vasodilation Increases mucus secretion
37
What is the location of adrenergic alpha 1 and 2 receptors?
a1 is located in the blood vessels, vascular smooth muscles(bladder), heart, CNS, bladder neck, piloerector muscle, mucosal membrane. a2 is located in the mucosal membrane, vascular smooth muscle, pancreas, and CNS.
38
Where are the alpha 2 adrenergic receptors located?
mucosal membrane vasculature of the nasopharnyx, vascular smooth muscle, pancreas, CNS/peripheral NS
39
What decongestant has more alpha 2 selectivity than beta 1 selectivity?
Imidazoline.
40
Where are the beta 2 adrenergic receptors located?
respiratory, uterine, vascular smooth muscle, liver, eye
41
What is the MOA of decongestants?
Direct agonist- Binds to alpha nd beta receptors and initiate the transduction pathway. Indirect agonist - Cause the release of NE from the nerve terminal to produce an effect. Do not bind to alpha or beta receptors, bind instead to the nerve that releases the NT. Ex: cocaine, methamphetamines. Mixed Ex: Ephedrine and pseudoephedrine.
42
What is the pharmacological effect of decongestants?
Constriction of nasal vasculature. Reduced tissue swelling. INCREASED NASASL DRAINAGE -mucus flows out until the backflow of mucus is empty, then dry nose. Improved airflow through nasal passages. Reduce mucus secretions by decreasing blood flow to mucus glands.
43
What is phenylpropranolamine?
Off the market in US because of hemorrhagic stroke (used large quantities as diet aid) Main use: diet aid/appetite suppression
44
What is pseudoephdrine?
The gold standard a quarter as potent on the cardiovascular system and half as potent as bronchodilator as compared to ephedrine. Has far fewer side effects. Behind the counter status - used for making methamphetamine. Combat meth act - 146 30 mg tablets per day and 366 per month.
45
What antihistamines are used for insomnia?
All PM drugs, nytol, sominex, and sleepinal have diphenhydramine. Night-time Sleep-Aid and Unisom have doxylamine.
46
What are the functions of blood vessels in the nasal mucosa?
Warms and humidifies inspired air. | Provides nutrients to goblet glands (glands that produce the mucous)
47
What are the structures of the nasal mucosa?
Arteriovenous anastomoses arterioles and venules cavernous sinusoids
48
How do you make a nose less stuffy?
Shrink blood vessels with decongestants. Use antihistamines to decrease mucous production. Use combo for increased effect.
49
What are the secretory cells and what do they do?
Epithelial cells, goblet cells, and basal, cells. They secrete enzymes, IgA antibodies (special antibodies located in body secretions which kill things coming in), mucus (captures particles in the air before it reaches the lungs). Use anticholinergic to reduce vasodilation and mucous secretion.
50
What do the adrenergic receptors do to the nasal mucosa?
SNS - Epi, NE, ACh: Vasoconstriction Decreases mucus secretions
51
What is the location of adrenergic beta 1 and 2 receptors?
b1 are located in the heart and juxtaglomerular cells of kidney. b2 are located in the lungs, respiratory, uterine, vascular smooth muscle, liver(gluconeogenesis), and eye. We want drugs that are b2 selective to reduce effects on the heart.
52
Why do we want drugs that are more alpha specific than beta specific?
Less heart effects.
53
What are the approved FDA uses for decongestants?
nasal and Eustachian tube congestion (ears blocked - feels like they are filled with fluid). Cough associated with postnasal drip.
54
What are the phenylethylamines?
``` Epinephrine (multiple routes) Ephedrine (oral) Phenylpropanolamine (oral) Pseudoephedrine (oral) Phenylephrine (oral) ```
55
What is epinephrine?
Used in surgical procedures to decrease blood flow. Was used in asthma (Primatene mist and Bronkaid mist) Not commonly found in OTC decongestant products - not taken orally because it is broken down.
56
What is ephedrine?
It is off the market in US. Used to be used for asthma. Direct and indirect agonist.
57
What is phenylpropranolamine?
Off the market in US because of hemorrhagic stroke (used large quantities as diet aid) Main use: diet aid/appetite suppression
58
What is pseudoephdrine?
The gold standard a quarter as potent on the cardiovascular system and half as potent as bronchodilator as compared to ephedrine. Has far fewer side effects. Behind the counter status - used for making methamphetamine. Combat meth act - 146 30 mg tablets per day and 366 per month.
59
What is phenylephrine?
The replacement for pseudoephedrine. Least B activity of the pheynylethylamines. Little effect on heart rate and blood pressure under 25 mg. Therapeutic doses don't seem to be as effective as pseudoephedrine. 10 mg is too small of a dose. Extensively metabolized in the stomach.
60
What are the imidazoline products?
Naphazoline, Tetrahydrozoline, Xylometrazoline, and Oxymetazoline.
61
What receptors are imidazoline products specific for?
More specific for the a2 receptor than a1 and much more than B receptors. Fewer cardiac side effects.
62
What is the absorption for imidazolines?
Poor oral absorption (used topically or intranasal admin) | Absorbed systemically after topical application - overuse or high doses may cause some systemic side effects.
63
What are the side effects of phenylethylamine?
CNS: Nervousness, irritability, insomnia, athletic performance enhancement (prohibited in pro athletes) Cardiovascular: Increased BP, Increased HR and tachycardia, hypertension and ischema, hyperthyroidism (causes the heart to pump more with the higher thyroid hormone levels), diabetes mellitus (masks hypoglycemia) GI: decreased appetite GU effects: Bladder relaxation (beta receptors causes bladder to feel full, a1 will not allow urine to pass), difficulty in urination, prostatic hypertrophy. Eye: increased IOP in closed angle, increased IOP in others. Piloerection Rhinitis medicamentosa - rebound effect after using nasal spray - do not use more than 3-5 days Burning, stinging, nasal dryness, and sneezing. Damage to nasal septum with long term use. CNS depression - do not cause the excitement that phenylethylamines do
64
What do nighttime meds never have?
decongestants because they will keep you up. Daytime meds have decongestants.
65
How would you choose a drug based on PCOL properties?
Decongestants - constrict blood vessels and reduce mucus flow Prevent production of mucus. Antihistamines: prevent cause of mucus prevent production of mucus sedation Anticholinergic (don't give too many side effects) Prevent production of mucus anti-SLUDGE

DEENT Exam 2 (7 decks)

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