Colds/allergies Flashcards
What are the three main approaches a drug can take to treat a congested nose?
- Sympathomimetic drugs
- Increase or mimic (nor)adrenergic transmission
- Antihistamine
- H1 (not H2) receptor antagonists
- Other
- Not recommended
What causes rhinitis?
Vasodilation and edema
What causes rhinorrhea?
Mucus secretion
Why does vasodilation cause a blocked nose?
Nasal cavity made up of erectile tissue, but can only expand inwards due to bone structure
Tissue expands inwards, circumference closes, increased airway resistance
How do sympathomimetic nasal decongestants work?
Act on sympathetic alpha1 or alpha2 receptors (either will cause vasoconstriction and alleviate rhinitis)
True/False? Sympathomimetic drugs work on all three problems associated with rhinitis (vasodilation, edema, mucus secretion)
False, only vasodilation
What is the difference between a direct and an indirect sympathomimetic? Name an example drug for each
Direct (Phenylephrine): acts directly on alpha1/2 receptor to cause vasoconstriction
Indirect ([pseudo]ephedrine/PPA): acts on NA terminal to release NA, which then acts on alpha receptors
What do alpha1 receptors do when stimulated?
G-Protein coupled cascade involving Protein Kinase C, IP3, Activated Ca-dependent kinase
End result is vasoconstriction
What do alpha2 receptors do when stimulated?
G-Protein coupled receptor cascade involving decreased cAMP, decreased PKA, adenylate cyclase
True/False? There is no cure for the common cold
True/False? There is no cure for the common cold
Zinc kind of helps but there are too many side effects
Why do some places ban the sale of pseudoephedrine?
Because you can make meth out of it
Name the two direct and indirect (4 total) decongestants and how they’re applied
Direct:
- NA, adrenaline (n/a)
- Phenylephrine (oral + topical)
Indirect:
- Pseudoephedrine (oral)
- PPA (oral topical)
What is rebound withdrawal?
Nasal resistance shoots up during chronic decongestant use (use decongestants acutely only)
What are the different routes of decongestant administration, and which is most effective?
Inhaler
Syrup
Nasal Spray
Nasal spray is best, Syrup is less effective but lasts longer, inhaler is just bad
Why would someone administer decongestants orally instead of nasally?
To unblock the Eustachian tubes (local administration does not pass systemically)
Which anticongestant does not work when adminstered orally?
Phenylephrine (doesn’t work reliably)
How does PPA increase Blood Pressure?
It is an indirect agonist
Stimulates Beta1 receptors on the heart
Stimulates Alpha1 receptors in vessels*
*might have affinity for alpha 1 (increases bp but doesn’t effect heart
Phenylephrine was ineffective - why?
Acts on alpha1 receptors, however… reflex bradycardia? Something else?
Why was PPA banned?
Stroke (hemorrhagic)
Heart attack
(young women would take megadoses to lose weight)
What can direct alpha1 receptor stimulation cause (4)
- hypertension
- Stroke
- insomnia/nervousness
- Loss of appetite
In what context would a2 agonists be better than a1 agonists? What happens if this is not the case?
Better safety profile, as effective - Apply topically to nose
But also used in autoreceptors in important places - if leaked into periphery, dangerous inhibition
What is hay fever?
Seasonal allergic rhinitis
How do allergies work?
eg pollen enters system, specific antibodies are produced, antibodies attach to mast cells, pollen attaches to mast cells on subsequent exposure, mast cells release inflammatory mediators, allergic reaction is triggered
How do mast cells illicit an allergic response? (2 ways)
- Releasing histamine which acts on H1 receptors
- Releasing inflammatory mediators which act on (among other things) leukotriene receptors
True/False? Leukotriene receptor antagonists are as effective as H1-blockers for allergic rhinitis
True/False? Leukotriene receptor antagonists are as effective as H1-blockers for allergic rhinitis
Which histamine receptor is associated with allergenic symptoms? (H1/H2)
Which histamine receptor is associated with allergenic symptoms? (H1/H2)
H2 is associated with ulcers (found in gut)
What is the difference between the two generations of H1 receptor blockers? Name two examples of each
1st Generation: sedating
- Diphenhydramine (benadryl)
- Chlorpheniramine
2nd Generation: non-sedating
- Terfenadine
- Hismanal
Should you take an antihistamine if you have a cold? Why/why not?
No, different system affected, no clear effect
During a cold, kinin levels increase but not histamine levels
Why is terfenadine non-sedating?
Drug doesn’t reach brain in concs sufficient enough to cause sedation (but saturates periphery)
Drug still gets into brain, just not enough to make you sleepy
How do we know it wasn’t a matter of getting the dose right for terfenadine not causing sedation?
Complete saturation was observed in periphery
Why doesn’t terfenadine cause sedation when it reaches the brain?
Acts competitively on the brain (if it reaches the brain)
designed NOT to reach brain
What is the differnce in response cuve for chlorpheniramine and terfenadine?
Chlorpheniramine: Rapid onset, reversible
Terfenadine: slow onset, irreversible(?)
What are spare receptors?
Receptors that are not bound to drug when cell is exhibiting maximum response
Why does terfenadine not have a standard dose/response curve?
It occupies spare receptors
Is terfenadine sedating?
No
What are terfenadine’s heart interactions?
Certain drugs/grapefruit can pause terfenadine metabolism, and too much terfenadine can act on the heart and cause ventricular arrhytmia
What are possible side effects of H1 antagonists? (6)
- Muscarinic block (dry mouth, alleviates motion sickness)
- Na Channel block (local anesthetic)
- Alpha1 block (postural hypotension)
- Competition for hepatic microsomes (drug interactions)
- Allergies (some people are allergic to the drug)
- CNS H1 block (sedation)
What are possible side effects of second generation H1 antagonists?
- Competition for hepatic microsomes (drug interaction)
What is a new type of drug that’s more effective than antihistamines?
Glucocorticosteroid inhalers (not immediate, slow onset)
Are antihistamine drugs 100% effective? Why/Why not?
No, because mast cells release lots of other “inflammatory mediators”
What is a scatchard plot?
Plot of bound/unbound ratio over drug conc
