Pharmacotherapy of the Upper Airway

Question 1

Glucocorticoids are our best ____ agents

Answer 1

Anti-inflammatory

Question 2

For treating colds and allergies, what is the major target?

Answer 2

Blood vessels

Question 3

What do allergies increase and what happens from this?

Answer 3

Histamine. This causes vasodilation so you get bigger vessels that are leaky–this causes congestion and runny nose.

Question 4

For colds, what is increased and what does this cause?

Answer 4

Viral inflammation increases bradykinin. Bradykinin causes runny and stuffy nose (via blood vessels).

Question 5

What would blocking histamine receptors help against?

Answer 5

Allergies

Question 6

Would blocking histamine receptors do anything against colds? If not, what should be done?

Answer 6

No, colds are not mediated through histamine, they are mediated through bradykinin. We don’t have direct bradykinin inhibitors so in order to counteract bradykinin’s vasodilation, we need to stimulate a1 receptors to vasoconstrict.

Question 7

True or False: bradykinin can cause cough

Answer 7

True. It can stimulate sensory receptors that signal the cough center in the CNS. This is why ace inhibitors can cause cough.

Question 8

Antihistamines are primarily used to treat ____ ____

Answer 8

allergic rhinitis

Question 9

Decongestants (vasoconstrictoors) are primarily used to treat _____ and ____

Answer 9

allergic rhinitis and viral cold infections

Question 10

What’s the difference between 1st generation and 2nd generation anti-histamines?

Answer 10

They are both equally effective at blocking H1 histamine receptors but they block the receptors at different locations. Thus, they have different uses and side-effects associated with them.

Question 11

For treating allergies, do we typically inhibit the release of histamines or inhibit the receptors from receiving the histamines?

Answer 11

We inhibit the receptors. The histamines have already been released.

Cromolyn is a mast cell stabilizer that can prevent the release of histamine but in allergy treatment the histamines have been released already so we target the receptors.

Question 12

How do beta adrenergic agents (epinephrine, isoproterenol) affect mast cells?

Answer 12

They reduce the release of mast cell contents. This may be a small anti-inflammatory effect you get from LABA for asthma or epinephrine in anaphylactic shock.

Question 13

What is the pathophysiology of histamine in…

cardiovascular

GI

lungs

neuro

Answer 13

Histamine stimulates H1 receptors on endothelial cells which increases NO.

In the cardiovascular system, this causes vasodilation of the arterioles which can lead to hypotension, nasal congestion, reflex tachycardia, increased capillary permeability which can cause edema, shock, rhinorrhea, and hives.

Histamine stimulates H2 receptors which cause cardiac stiulation and vasodilation.

In the GI tract, histamine stimulates H1 receptors which cause contraction of smooth muscle (cramping) and H2 receptors which increase gastric acid secretion.

In the lungs, histamine can cause bronchoconstriction which is a hyperactive response in asthma.

In neurons, histamine can stimulate sensory nerve endings which can cause pain and/or itching.

Question 14

What is an anaphylactic reactions, what causes it, and how is it treated?

Answer 14

Anaphylactic reactions are caused by histamine plus other mediators released from mast cells and present with urticaria, abdominal carmps, laryngospasm, bronchospasm, decreased blood pressure, and shock.

Anaphylactic reactions are treated by epinephrine (to reduce release of mast cell contents).

Antihistamines are effective to add on to epinephrine treatment but are not sufficient alone for treatment.

Question 15

Which generation of antihistamines is selective for blocking peripheral H1 receptors?

Answer 15

2nd generation.

2nd generation antihistamines are selective for H1 receptors in the periphery (but not in the brain)

Question 16

Which generation of antihistamines has additional blocking actions at non-H1 receptors?

Answer 16

1st generation antihistamine agents

Question 17

True or False: Both generations of antihistamines block H1 receptors equally well

Answer 17

TRUE

Question 18

Do antihistamines block reversibly or irreversibly?

Answer 18

Reversibly

Question 19

Answer 19

B. Hypertension

C. Bronchodilation

Question 20

Answer 20

B. Epinephrine

D. Albuterol

Question 21

What does blocking muscarinic receptors do?

Answer 21

Sedation (lower level of sedation in 2nd gen. bc they are highly H1 selective and less CNS penetrative)

Prevention of nausea-vomiting

Block secretions

Question 22

What are some side effects of blocking muscarinic receptors?

Answer 22

Urinary retention, blurred vision, dry mouth, constipation

(no pee, no see, no spit, no shit)

Question 23

Antihistamines can block sodium channels. What does this block do?

Answer 23

Local anesthetic action via block of Na⁺ channels involved in action potential generation. Most often used topically

Question 24

Antihistamines can block a1-adrenergic receptors. What does this block do?

Answer 24

This blocks vasoconstriction and can cause orthostatic hypotension in susceptible individuals.

E.g. promethazine

Question 25

For allergic reactions (rhinitis-urticaria) would you use 1st or 2nd generation antihistamines?

Answer 25

Either. They both do H1 receptor block

Question 26

For cough suppression, what channel do you need to block and what generation antihistamine would be used?

Answer 26

Na⁺ channel block which can be done by 1st generation antihistamines.

Question 27

For suppressing motion sickness, which receptor(s) do you need to block and what generation antihistamine can be given for this?

Answer 27

You need to block H1 and muscarinic receptors to interrupt the visceral afferent pathway to vestibular nucli. You do this by giving a 1st generation antihistamine.

2nd generation doesn’t get into the brain so you can’t use that… also 2nd generation are selective for H1 and don’t do much to muscrinic receptors.

Question 28

Do 1st or 2nd generation histamines penetrate into the CNS?

Answer 28

1st generation

Question 29

For suppressing nausea-vomiting of pregnancy, which receptors need to be blocked and which antihistamine generation can be given to do this?

Answer 29

H1 and muscarinic receptors by 1st generation antihistamines.

Question 30

Antihistamines can be used as a sleep aid for insomnia. Which receptors need to be blocked for this effect and which generation antihistamine does this?

Answer 30

H1 and muscarinic receptor block. This is done with 1st generation antihistamines.

Question 31

True or False: onset for antihistamines is slow

Answer 31

False! It’s rapid

Question 32

True or False: corticosteroids are very effective at treating allergic disorders quickly

Answer 32

False. While corticosteroids are very effective at treating allergic disorders, the onset of action is slow (on the order of days).

This is because they need to go into the nucleus to change transcription.

Question 33

Answer 33

C. Overuse associated with rebound congestion

F. More effective than pseudoephedrine for viral cold symptoms

Question 34

What are side effects of antihistamines?

Answer 34

Sedation (prominent with 1st generation agents like diphenhydramine and minimal with 2nd generation bc it doesn’t cross the blood brain barrier)

Antimuscarinic action (dry mouth, urinary retension, constipation, blurry vision)

Paradoxical excitation (most patients will experience sedation but occasionally you see excitability. weird.)

Postural hypotension (from a1 block- more with promethazine)

GI effects (loss of appetite, nausea/vomiting - taking with food or water eliminates this effect)

Question 35

Answer 35

B. Dry mouth

F. Drowsiness

Question 36

Name 3 first-generation antihistamines

Answer 36

1. Dimenhydrinate
2. Diphenhydramine
3. Meclizine

Question 37

Name 3 second-generation antihistamines

Answer 37

1. Cetirizine
2. Fexofenadine
3. Loratadine

Question 38

Of the 3 first-generation antihistamines, which gives the least drowsiness?

Answer 38

Meclizine

Question 39

What are antiemetic effects?

Answer 39

An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer.

Question 40

Are 1st or 2nd generation antihistamines used for antiemetic effects?

Answer 40

1st generation

Question 41

Are 1st generation or 2nd generation antihistamines longer acting?

Answer 41

2nd generation antihistamines

Question 42

While all first-generation antihistamines have antiemetic effects, which is most commonly used for its antiemetic ability?

Answer 42

Meclizine. Meclizine has the least sedative effects and most antiemetic effects.

Question 43

Answer 43

C. 2nd generation agents are not effective in the OTC treatment of insomnia

F. 1st generation agents are effective in the OTC treatment of insomnia

Question 44

What receptor(s) do decongestants target?

Answer 44

alpha 1 receptors in vessels

Question 45

What are 4 cold symptoms and how do rhinoviruses cause these symptoms?

Answer 45

The viruses attach to respiratory cells which generates inflammatory mediators including bradykinin. Bradykinin causes the cold symptoms:

1. Pain (via activation of nociceptors)
2. Nasal stuffiness (via dilation of blood vessels)
3. Nasal fluid hypersecretion (via increased capillary permeability plus parasympathetic reflex mechanisms)
4. Cough (via activation of irritant sensory receptors)

Question 46

True or False: Mast cell mediators (histamine) have a major role in the viral inflammatory response.

Answer 46

False. They have a minor role in the viral inflammatory response (colds)

Question 47

What’s the mechanism for topical decongestants?

Answer 47

They stimulate alpha 1 receptors of nasal blood vessels that are dilated by histamine or bradykinin. This causes vasoconstriction which promotes drainage and improves breathing.

Question 48

What are side effects of topical decongestants and why are patients prone to developing these effects?

Answer 48

Topical decongestants cause a prompt effect relative to oral decongestants which can lead to tendency of overuse. When you vasoconstrict too much, you decrease flood flow and oxygenation of tissue causing tissue damange and inflammation. Patients usually think that the medication used to work but stopped working so they try using more and more of it which actually makes the problem worse causing rebound congestion (rhinitis medicamentosa) due to ischemia-local irritation.

Question 49

Name 2 topical decongestants and what the differences are between the two

Answer 49

1. Phenylephrine (neosynephrine) is the most effective agent, is shorter in duration, and may produce marked irritation in some
2. Oxymetazoline (Afrin) is longer acting (6-12 hr duration); used twice/day, and limits rebound congestion.

Question 50

Does phenylephrine or oxymetazoline have a higher likelihood of causing rhinitis medicamentosa?

Answer 50

Phenylephrine

Question 51

What’s the mechanism of action for oral decongestants?

Answer 51

Oral decongestants stimulate alpha1 receptors of nasal blood vessels dilated by histamine or bradykinin which causes vasoconstriction. The decongestants are delivered via systemic circulation to the nasal vascular bed. Oral decongestants are less intense but have a longer duration of action compared to topical.

Question 52

What are side effects for oral decongestants?

Answer 52

Systemic actions can cause headaches, nausea, dizziness, and increased BP-palpitations (chronic high doses)

Question 53

Name 2 oral decongestants and describe the difference between the them

Answer 53

1. Pseudoephedrine (Sudafed) is the safest and most effective of oral agents. When pseudoephedrine passes through the liver, it is not metabolized by MAO.
2. Phenylephrine (sudafed PE) is less safe orally because when it passes through the liver it is metabolized by hepatic MAO which causes variable interpatient blood levels. The duration of this drug is about 4 hours. (remember, phenylephrine is very effective to take topically though)

Question 54

Answer 54

A. Effective against rhinorrhea and congestion due to allergies

E. More reliable oral bioavailability than phenylephrine

H. Increases neuronal release of NE

Question 55

Antihistamines are great for ____ rhinitis but not ____ rhinitis

Answer 55

allergic, viral

Question 56

If a patient has high BP, should you avoid giving them oral or topical decongestants?

Answer 56

Avoid giving oral decongestants (e.g. pseudoephedrine) to patients with high BP or cardiovascular problems because one of the side effects is increased BP and palpitations.

If a patient’s HTN is controlled, a dose of pseudoephedrine here and there won’t hurt them but don’t give chronically.

Question 57

True or False: Decongestants do very little for cough.

Answer 57

True. Decongestants are for runny and stuffy noses

Question 58

What are antitussive agents used for?

Answer 58

They are used to reduce the frequency of cough, especially dry, non-productive cough. Excessive coughing can be discomforting and self-perpetuating.

Question 59

What is the mechanism of action for antitussive agents? What are some antitussive agents?

Answer 59

Antitussive agents have both central and peripheral actions.

The most effective agents are agonists at endogenous u-opioid receptors to depress the cough center in the brain stem.

Diphenhydramine is generally less effective, as it works through antihistaminic and/or local anesthetic actions.

Codeine, hydrocodone, and hydromorphone are opioid drugs (controlled substances) and are effective antitussives at lower doses.

Dextromethorphan (Robitussin DM) is the most commonly used OTC cough suppressant. It has variable effectiveness. It is an opioid agonist but does not depress respiration or predispose to addiction (only l-isomers do this). Mild adverse effects include drowsiness and GI upset. 15-30mg suppresses cough while 500-1500mg is drug abuse (“robo tripping”)

Diphenhydramine (a 1st generation antihistamine) can also be safe and somewhat effective as an antitussive. It has a greater propensity for side effects (sedation, anti-muscarinic effects) than dextromethorphan.

Benzonatate is a top 100 drug. Tetracaine (local anesthetic) congener.

Question 60

What are the most common adverse effects of antitussive agents?

Answer 60

Nausea, drowsiness, constipation, and (less commonly) allergic reactions

Question 61

True or False: When opioid drugs should only be given short term

Answer 61

True. You don’t want to build physiological or psychological dependence

Question 62

What are guidelines for treatment for acute cough due to common cold in adults?

Answer 62

1st generation antihistamine/decongestant (e.g. brompheniramine/pseudoephedrine)

Naproxen (TID x 5 days) blocks inflammation that stimulates cough afferents

Question 63

What are guidlines for treatment of cough in adults with upper airway cough syndrome (postnasal drip)?

Answer 63

1st generation antihistamine/decongestant (e.g. brompheniramine/pseudoephedrine)

Question 64

Answer 64

C. An NSAID like naproxen may be of benefit in coughs due to common cold viruses