Upper Respiratory Dr. Roane EXAM I Flashcards
Compartments of the Upper Respiratory Tract
-Nose and Nasal Cavity
-Sinuses
-Connections: Eustachian tube to the middle ear
Nasolacrimal ducts to the eye
-Mouth
-Pharynx
-Larynx (covered by the epiglottis)
Pharynx and Larynx share a pathway (food and air)
Compartments of the Lower Respiratory Tract
-Trachea
-Primary bronchi
-Lungs
Function of the Upper Respiratory Tract
-Warm and moisten incoming air
-Trap inhaled particles
-Front line of immunological defense
-Olfaction (smell)
Function of the Lower Respiratory Tract
-Ventilation (moving air in and out - Ribcage, Diaphram)
in the Alveoli: Gas exchange
O2 to the blood
CO2 out of the blood
Pathophysiology of the Upper Respiratory Tract
Allergies
Infections
What are the obstructive disorders?
Which part of the lung is affected?
-Obstruction: something is in the way
-Asthma, COPD, Bronchiectasis (inflammation of the walls of the bronchi (branches))
-Compromised exhalation !!!
–> Lower Respiratory tract
What are the restrictive disorders?
Which part of the lung is affected?
elastic lung tissues (contracts, expands) is compromised by diseases:
-Fibrosis (thickening of the air sacs in the lungs), Sarcoidosis (autoimmune),
-Compromise inhalation !!!
Others:
–> Lower Respiratory tract
Other Pathophysiologies of the lung
-Silicosis (caused by fine sand)
-Black lung (in mine worker)
-Cystic fibrosis (inherited)
-Pulmonary hypertension
-Infections
What is the physiologic equation important for Lower Respiratory conditions?
-Poiseuille’s Law (Flow of fluids)
-Relation between Flow and change in pressure, the radius of the tube, length, and viscosity
Which factor in Poiseuille’s equation is critical?
-Radius (diameter to the 4th power)
-small changes in the radius result in big changes in flow
Equation #2 important for Lower Respiratory conditions?
-Ficks Law of Flux
-How fast a substance (gas, drug molecule) can move across a barrier
Factors Fick’s equation
What is important regarding to Lower Respiratory conditions
Flux = (C1-C2)PSA/D
-C1-C2 (concentration difference) - movement from high to low
-Permeability
-surface area
-D distance across the barrier
-Changes in thickness of the wall !!!
Where are the Turbinates and what is its function?
-in the Sinuses
-increases the surface area inside the folds of the tissue
What are the benefits of an increased surface area in the turbinates?
-inhaled air is exposed to more tissue
-more junk can be caught in the mucus
What are the bone-forming tissues posturing into the breathing passage and the spaces between those, called?
Bone-tissue:
Superior concha
Middle concha
Inferior concha
Space between concha:
Superior meatus
Middle meatus
Inferior meatus
What are large spaces with narrow passages inside the nasal cavitiy?
-Sinuses
Examples:
-Frontal Sinus (above the eyebrow)
-Sphenoidal Sinus (in the back)
Where is the Maxilla sinus located?
Behind the cheekbone?
What causes pain in a sinus infection?
-Bacterial growth cause recrution of immune cells (neutrophils, macrophages)
-Filled space and included openings
-Swelling, increased pressure in an inelastic space
What is the function of alpha-agonists when exposed to tissues?
Vasoconstriction of blood vessels
What are the characteristics of the nasal cavity?
-lined with a thick mucosal cell layer
-rich blood supply (epistaxis)
-Large surface area: slows airflow, warms incoming air; mucosa traps microbes
-rich in immune cells: innate immunity
What types of fluids are secreted in the nasal cavity?
-Serous fluid: watery
-Mucus: thick and slimy
-vascular exudate from dilated blood vessels
Where are fluids in the nasal cavity produced?
-most come from exocrine glands and goblet-like mucous cells
-1L per day
What promotes fluid secretion in the nasal cavity?
Histamines -> binding to muscarinic receptors
What are the effects of the H1 Histamine receptors?
-Sneezing, itching
-fluid secretion
-Vasodilation
DRUG TARGET
What are the effects of the M3 muscarinic receptors?
Stimulate serous and some mucus secretion
DRUG TARGET
What are the effects of the Alpha (a1) receptors?
-Stimulate Vasoconstriction
-countering the histamine effect, but are NOT part of an allergic response
DRUG TARGET
What are the effects of the Leukotriene (LT-D4) receptors?
-Similar to H1
-Sneezing, itching
-fluid secretion
-Vasodilation
DRUG TARGET
How does an allergic reaction develop?
-Allergen binds to IgE (IgE sits on mast cells)
-Degranulation and release of mast cell mediators (histamines, prostaglandins, leukotrienes, and more)
What are the effects of mast cell mediators released after Degranulation?
-Stimulation of sensory nerve endings -> Sneezing and Itching
-Stimulation of mucous glands inducing hypersecretion -> Rhinorrhea
-Acting on blood vessels -> Vasodilation -> Tissues swell up -> Congestion
What does atopic disorder mean?
-IgE response to an allergen (antigen, normal part of the environment)
-caused by an allergen that not everyone would respond to (only those allergic will respond)
Effects of Histamines and other mediators
Increase nasal fluid production and cause severe
vasodilation
-Blocks airways (stopped up/runny nose)
-cause itchy, watery eyes* (composition of the tear depends on the stimulus - tears from crying due to sadness are different)
-Can create a sinus headache
-Facilitate sneezing
What are the Histamine receptors involved in allergic diseases?
H1 - H4 Receptors
Which cells responsible for acid secretion contain H2 receptors?
H2 receptors on Parietal cells -> gastric acid secretion
H2 blockers decreasing acid secretion are specific to H2 receptors -> they DON’T help with allergic reactions in the nose (H1)
Which histamine receptor is associated with the function of the sleep cycle?
H3 Receptor
Benadryl is often used to help with sleep
Histamine receptor associated with cytokine production, adhesion molecule production, vasodilation, bronchoconstriction, allergy, and inflammation
H1 Receptor
Histamine receptor associated with Immunomodulators, Chemotaxis, Degranulation, Ca release from ER
H4 receptor
Future research targets
H1-H4 receptors
-Wakefulness
-Appetite/body weight (why pts. on atypical
antipsychotics gain weight)
-Psychosis and a variety of mental disorders
Question
Does Histamine behind unspecifically to different types of H receptors (H1, H2, H3, H4)
Classes of older Gen Antihistamines
-Ethanolamines
Diphenhydramine and Doxylamine
-Propylamines
Chlorpheniramine
Brompheniramine
-Piperazines
Meclizine (Bonine for motion sickness)
Hydroxyzine
What are the side effects associated with older Antihistamines?
Drowsiness
-> probably caused by blocking H1 receptors and/or 5-HT receptors in the brain
Histamines helps to in keeping people stay awake during the day
-f.e. Hydroxyzine sedative, anxiety before surgery
Examples of Antihistamines with different effects
-Hydroxyzine: Anxiety
-Dimenhydrinate (Dramamine) an antihistamine for nausea
-Cyproheptadine: appetite stimulator
What other receptors are blocked by Antihistamines?
Muscarinic receptors
Muscarinic effects: Parasympathetic: Urinating, nasal mucus secretion, salvation,…
-> Antimuscarinic effects: difficulty urinating in men with benign prostatic hyperplasia (BPH)
Which Antihistamine binds to different histamine receptors and has multiple effects?
Promethazine (Class: Phenothiazines)
-Antihistaminic (allergy symptoms)
-Anticholinergic (helps with diarrhea)
-Antidopaminergic (Anti-nausea and potentiates narcotic effects - make pain meds work better)
-Anti-alpha receptor effects in the CNS (sedation)
Why are 2nd Gen Antihistamines more successful than the 1st Gen Antihistamines?
-more specific to H1 and lower CNS penetration (less drowsiness)
-2nd Gen: Loratidine, Certirizine
-3rd Gen: Desloratadine, Fexofenadine
How is Desloratdine different from Loratidine?
Desloratadine is an active metabolite of Loratidine
-metabolized by CYP3A4 or 2D6
-more effective in people no-function CYP2D6 allele
-more hydrophilic, less CNS effect
-increases the effect of isotretinoin (for acne)
Which initial Antihistamine was withdrawn from the market?
-Terfenadine (Seldane)
-due to fatal arrhythmias secondary to prolonged QTc interval
-> the active metabolite (CYP3A4) Fexofenadine is not toxic
Levocetirizine (Xyzal) (l-isomer) is more active than its isomer Cetirizine (Zyrtec)
T or F
True
Effect of Alpha-1 agonist and where is it used for treatment
-Vasodilation causes a stuffy nose
Alpha-1 Agonist binds to Alpha-1 receptor -> Vasoconstriction
Alpha-1 Agonist - Decongestant
-Ephedrine
-Phenylephrine
-Pseudoephedrine (1 CH3 away from methamphetamine)
-Naphazoline (mostly ophthalmic – “gets the red out”)
-Oxymetazoline (12 hour due to enzyme resistance)
What might happen if alpha-agonists are taken periodically or systemic (oral)
-periodically: Tachyphylaxis (decrease in response), rebound stuffy nose
-systemically (oral): Vasoconstriction -> raises blood pressure
What does the “D” indicate in Combination products?
Decongestants (alpha agonist)
-often in antihistamine products
What is the MOA of Leukotriene inhibitors?
Antagonist (Blockage) of the LTD4 receptors
LTD4 (inflammatory mediator) mediates vascular permeability, mucus secretion, attracts other immune cells -> ALLERGY reaction
-f.e. Monteklust (Singulair)
BOXED WARNING: neuropsychiatric signs
AVOID in patients with a psychiatric history
MOA of Glucocorticoids
-f.e. Fluticasone converted to Cortisol
Cortisol binds to the cytosolic receptor and moves to the nucleus -> together with a co-factor it represses transcription in immune cells (in other cells f.e. fat cells it can activate transcription)
-> IMMUNOSUPPRESSIVE
Why should patients on Glucocorticoids not discontinue the drug abruptly?
Negative Feedback loop of Glucocorticoids -> suppressing CRH and ACTH -> in the Hypothalamus pathway -> low levels of natural cortisol
-adrenal deficiency -> stopping the glucocorticoids abruptly will result in the patient having insufficient steroids in the body -> fatigue, muscle weakness, weight loss
What does the BLACK BOX WARNING
-avoid in patients with mental disease, if they have mild allergic reactions
-For allergic rhinitis: only use if patients can’t tolerate other allergy medicines
NEED TO KNOW
-Identify the Gen by the name
-Function of the H receptors
1-anti allergic
2-gastric acid
3-drowsiness
-LTD4 receptors - BLACK BOX WARNING
-Function of Glucosteorides
