OTC Pharmacology

Question 1

What do decongestants do?

Answer 1

Alpha-1 adrenergic receptor agonists and/or indirect sympathomimetics (release NE)
Act in the nasal mucosa to produce vasoconstriction

Question 2

What are examples of decongestants? (3)

Answer 2

Ephedrine
Pseudoephedrine
Phenylephrine

Question 3

What is ephedrine?

Answer 3

Natural product, directly stimulates alpha-1 adrenergic receptors to cause vasoconstriction and beta-adrenergic receptors.
Enhances release of NE from sympathetic neurons.

Question 4

What is pseudoephedrine?

Answer 4

Stereoisomer of ephedrine and less potent
Directly stimulates alpha-1 adrenergic receptors, causing vasoconstriction and has some direct stimulation of beta-adrenergic receptors

Question 5

What is phenylephrine?

Answer 5

Selective alpha-1 adrenergic agonist

Question 6

What is the major AE of topical decongestants?

Answer 6

Rebound congestion which can be worse than the original congestion

Question 7

What are examples of antitussives?

Answer 7

Dextromethorphan and codeine.

Opioids are also potent antitussives but are not first line

Question 8

How do expectorants work? What is an example?

Answer 8

Thought to stimulate olfactory tract secretions, increasing fluid and decreasing mucous viscosity.
Ex. Guaifenasin. Not much evidence that it does anything, but not much evidence that they’re harmful either.

Question 9

How is histamine released during an allergic reaction?

Answer 9

Antigens interact with IgE antibodies on the surface of mast cells.
IP3 is produced, which increases intracellular calcium.
Calcium interacts with vesicles and facilitates release of stored histamine

Question 10

What does activation of H1 and H2 receptors lead to?

Answer 10

Arterial dilation
Smooth muscle constriction
Increased capillary permeability–> extravasion of fluid and edema

Question 11

What is the difference between first and second generation antihistamines?

Answer 11

Second generation antihistamines:
- do not cross the blood brain barrier
- have less affinity for muscarinic receptors
- longer half lives
First gen:
- block muscarinic receptors, resulting in anticholinergic side effects

Question 12

Define eicosanoids vs autocoids

Answer 12

Eicosanoids: lipid signaling molecules related to or derived from arachidonic acid
Autocoids: substances that act locally to modulate the activity of tissues

Question 13

What are prostanoids?

Answer 13

Derived from COX and other enzyme that convert arachidonic acid to PGH2 and then into prostanoids
Some are also produced from linoleic acid.

Question 14

What are leukotrienes?

Answer 14

Derived from HPETE, which is converted into leukotrienes by enzymes

Question 15

What happens during acute inflammation?

Answer 15

• Release of local inflammatory mediators and accumulation of neutrophils
• Swelling to bring plasma into the area to dilute present toxins and bring antibodies, complement and initiate blood clotting to prevent spread to other parts of the body.
• Increased blood flow to bring oxygen and nutrients to cells responsible for inflammation

Question 16

What happens during chronic inflammation?

Answer 16

Accumulation of additional blood cells, including macrophages and others

Question 17

Which compounds directly stimulate sensory pain neurons and which reduce the threshold at which neurons will fire?

Answer 17

Directly stimulate: histamine, bradykinins

Reduce threshold: histamine, prostaglandins

Question 18

How does acetaminophen exerts its antipyretic effects?

Answer 18

Inhibits COX in the thermoregulatory centre

Inhibit synthesis/release of PGE2 in the thermoregulatory centre of the anterior hypothalamus

Question 19

What are the three indications for NSAIDs?

Answer 19

Pain
Inflammation
Fever

Question 20

How do NSAIDs exert their effects?

Answer 20

Inhibit COX to prevent conversion of arachidonic acid to PGH2, preventing prostaglandin production

Question 21

Compare ibuprofen and naproxen

Answer 21

Naproxen has a longer half life than ibuprofen (14h vs 2-4h)

naproxen is very slightly COX-1 selective, while ibuprofen is almost equally selective for COX1 and 2

Question 22

How do corticosteroids exert their effects?

Answer 22

Target the first enzyme in the arachidonic acid cascade, phospholipase A2.
This shuts down all arachidonic acid products
Also have additional anti-inflammatory and immunosuppressant effects

Question 23

How do PPIs exert their effects?

Answer 23

Structurally related to H2 histamine receptor antagonists

Question 24

What are drug interactions to be concerned about when using PPIs?

Answer 24

Some anti-platelet medications and kidney adverse effects

Question 25

What were H2 receptor antagonists used for? How do they work?

Answer 25

To suppress acid production in the GI tract before PPIs were developed Block H2 receptors on parietal cells in the stomach

Question 26

What do bismuth containing compounds do?

Answer 26

Coat erosions and ulcers Stimulate prostaglandin production Stimulate mucous and bicarbonate secretion Decreases GI secretions to treat diarrhea Direct antimicrobial effects, including H. pylori

Question 27

How does sucralfate work?

Answer 27

It's a sucrose salt plus aluminum hydroxide that forms a viscous substance that coats ulcers in acidic environments

Question 28

Does dextromethorphan act through opioid receptors? What enzyme is it metabolized by? What is a drug interaction?

Answer 28

No-- acts centrally to elevate threshold for cough Metabolized by 2D6 inhibitors Risk of serotonin syndrome with MAOIs

Question 29

What is an example of a drug that stimulates histamine release

Answer 29

Acetylcholine | Non-immunologic histamine releasors (ex. opioids, some food components)

Question 30

Describe the distribution of H1 receptors

Answer 30

Widely distributed in the CNS and periphery, particularly on smooth muscle and endothelial cells

Question 31

Describe the distribution of H2 histamine receptors

Answer 31

Gastric parietal cells

Question 32

Describe the distribution of H3 and H4 histamine receptors

Answer 32

H3: Autoreceptors on histamine containing neurons H4: On white blood cells, play a role in inflammation and allergy

Question 33

What promotes acid secretion in the stomach?

Answer 33

Muscarinic, histamine and gastrin receptors promote the activity of the proton pump. We can block these receptors (ex. by prostaglandins) to stop proton pump activity (or can block proton pump itself)

Question 34

Describe the effect of PPIs vs H2 histamine blockers on stomach acidity?

Answer 34

PPIs: way better at reducing acid secretion throughout the day, H2 blockers: mostly good for nocturnal acid secretion

Question 35

Which receptors are involved in nausea and vomiting?

Answer 35

``` M1 muscarinic receptors H1 histamine receptors NK1 neurokinin receptors 5-HT3 serotonin receptors D2 dopamine receptors ```

Question 36

What are additional treatments for nausea and vomiting?

Answer 36

Cannabinoids Benzodiazepines Phenothiazines

Question 37

How much evidence exists for using cannabis to treat nausea and vomiting?

Answer 37

Little to none, but some evidence that it's effective for chemotherapy induced vomiting

Question 38

How do opioids treat diarrhea?

Answer 38

mu receptor agonists reduce the tone of the GI smooth muscle

Question 39

Describe melatonin 1 and 2 receptors

Answer 39

Melatonin 1 receptors: coupled to G-alphai and thought to promote sleep when activated Melatonin 2: Gq-coupled, thought to serve a coordinating function in the light-dark cycle