W14 Cold Flu And Allergies

Question 1

Cold, flu objectives:
don’t need to memorise brand names unless in red font

● recognize key limitations and precautions of agents used to treat cold, flu, and/or allergies
● recommend supportive care treatment of cold, flu, and/or allergies considering patient-specific factors

Question 2

Common cold stats — just familiarise
Most common virus responsible?
Symptoms last?

Answer 2

● typically acute, self-limiting
● viral, mostly rhinovirus (not the flu /influenza), with no known definitive cure (yet)
● symptoms typically last 7-10 days, but can persist for longer (ie, lingering cough)
● incidence declines with increasing age
● a leading cause of missed work and school
● cough alone results in up to 30 million primary care visits per year
● national spending on OTC cough and cold medicine industry was >$8 billion a year in 2018, higher now

Question 3

Rhinitis: what is it?
Symptoms
Causes
Tx for both allergic and non-allergic?
Tx for allergic ONLY

Answer 3

= inflammation of the nasal mucosa

symptoms
● irritability
● hypersecretion
● obstruction
● post-nasal drip can manifest as throat irritation, cough

causes
● allergic (seasonal or perennial)
● infectious (viral, bacterial)
● non-allergic and non-infectious

for both allergic and nonallergic rhinitis
DADS
● avoiding irritants
● ⭐️ saline irrigation
● ⭐️ topical or oral sympathomimetics (x2 decongestants)
● ⭐️ topical anticholinergic

* patients should be instructed to use bottled distilled water, and/or boil tap water for at least 1-3 minutes in advance (and then cooled to room temp*

typically only for allergic rhinitis (limited utility if nonallergic)
CALM
● ⭐️ topical Corticosteroids
● ⭐️ oral and topical Antihistamines
● ⭐️ Mast cell stabilizers
● ⭐️ Leukotriene inhibitors
● immunotherapy

consider topical agents if symptoms are limited to the nasal passage, oral agents if more widespread; consider combining multiple agents with differing mechanisms of action

Question 4

sympathomimetics / decongestants

Answer 4

MOA:
ɑ agonism → vasoconstriction of arterioles in nasal mucosa → decreased swelling, fluid production

used for temporary relief of
● nasal/ear congestion
● rhinitis, post-nasal drip (often presents as throat pain, irritation)

adverse effects (oral > nasal)
● cardiac: hypertension, tachycardia, palpitations
● CNS: insomnia, restlessness, anxiety

precautions
● cardiovascular disease
● pregnancy (anything that vasoconstricts and compromises uterine bloodflow)
● topical agents - rhinitis medicamentosa; some systemic
exposure concerns - nasal or ophthalmic meds can absorb into the bloodstream in small amounts

Question 5

TOPICAL (nasal) sympathomimetics / decongestants 2
Precaution, what is Afrin addiction?
Counselling point?

Answer 5

phenylephrine and oxymetazoline (longer-acting)

precaution:
—⭐️rhinitis medicamentosa: aka rebound
congestion, ‘Afrin Addiction’

● prolonged use leading to tachyphylaxis and
severe rebound congestion when discontinued
● treatment options: discontinuation, ?intranasal corticosteroids and other agents listed in the following slides w/ different MOA’s

key counseling point:
—use for no more than 3 days (this is stated on the packaging)

available OTC

Question 6

ORAL sympathomimetics / decongestants — 2

Answer 6

pseudoephedrine
● often found in combination with antihistamines, as indicated by the “D” (for decongestant) in Zyrtec-D or Claritin-D
● ⛔️sold ‘behind the counter’ or in a secure location, max amount allowed per purchase and per individual per month (ID required)

phenylephrine (PE)
● in over 200 combination cold and flu medications (not sold on its own)
● not really effective!

available OTC

multiple studies, including some funded by the pharmaceutical companies that make cold/flu products with phenylephrine, show that it is no better than placebo. FDA is currently reviewing whether to keep it on the market

Question 7

topical (intranasal) anticholinergics
(Anti-muscarinic)

Answer 7

ipratropium bromide 0.03% or 0.06% Rx only

MOA:
—inhibits serous and seromucous gland secretions
labeled indications

● allergic/nonallergic perennial rhinitis
● seasonal allergic rhinitis
● rhinorrhea due to colds

for allergic rhinitis, less effective compared to
intranasal corticosteroids, so not typically first-line

Question 8

Allergic rhinitis
Pathophysiology

Answer 8

prevalence:
—affects up to 25% of the population, incidence increases in adolescence and peaks in the 30s-40s

pathophysiology
● IgE mediated (type I) reaction to an allergen
● late-phase or cellular reaction: release of cytokines and leukotrienes → chemotaxis of inflammatory cell (eosinophils), starts hours after initial sensitization and may last for up to 48 hours
● seasonal and/or perennial

Question 9

Allergic rhinitis
Allergens
s/s

Answer 9

allergens:
—typically environmental (pollen, mold spores, dander, tobacco smoke, car exhaust), foods, insect stings

s/sxs:
—clear rhinorrhea
—congestion, sneezing,
—itching, postnasal drip

not life-threatening, but can severely impact quality of life - functionality, energy levels, sleep quality, etc.

children - learning difficulty

Question 10

topical (nasal) corticosteroids
MOA
Which options, know the top 3
ADRs
Precautions

Answer 10

MOA:
↓inflammatory mediators and cytokines, ↓lymphocyte proliferation

highly effective for allergic rhinitis, possible utility for nonallergic rhinitis and polyps, requires up to 1 week of use for full effect

multiple options, all are equally effective
● ⭐️ fluticasone (Flonase®) - OTC
● ⭐️ triamcinolone (Nasacort® AQ) - OTC
● ⭐️ budesonide (Rhinocort® AQUA) - OTC
● mometasone (Nasonex®)
● and various others

adverse effects
—are mostly local (burning, stinging, dryness, epistaxis)

precautions
● local injury or respiratory infection
● glaucoma, cataracts

Question 11

Oral antihistamines
ΜΟΑ
Οreal: 1st gen and 2nd gen

Argument for 2nd gen anti-histamines

Answer 11

MOA:
—competes w/ histamine for H1 receptor sites on effector cells located in blood vessels and the respiratory tract

oral (many):
● 1st gen: ⭐️diphenhydramine (Benadryl®),
chlorpheniramine, and others
● 2nd gen: ⭐️ cetirizine (Zyrtec®) ⭐️,
levocetirizine (Xyzal®), ⭐️ loratadine
(Claritin®) ⭐️, desloratadine, fexofenadine (Allegra)
most are OTC

the argument for 2nd-gen antihistamines
● less lipophilicity = less adverse effects (anticholinergic effects, particularly sedation and next-morning ‘hangover’); we’ll review more anticholinergic SEs with inhaler meds
● longer duration of action, typically taken once-daily
● levocetirizine (R-enantiomer of cetirizine) - double the H1 receptor binding affinity so more potent, less sedating; Allegra is also generally considered to be less-sedating than Zyrtec and Claritin

Question 12

topical (nasal and ophthalmic) antihistamines

Answer 12

MOA:
—competes w/ histamine for H1 receptor sites on effector cells, which are located in blood vessels and the respiratory and GI tract

topical/nasal:
● ⭐️azelastine (Astepro®) ⭐️ - nasal, ophthalmic
● olopatadine (Pataday®) - nasal, ophthalmic
● cetirizine

the two pictured are OTC, the rest are Rx-only

Question 13

mast cell stabilizers —2
(these are also antihistamines - prevent histamine release, rather than blocking receptors)

Answer 13

MOA:
—inhibits histamine degranulation from mast cells

for preventive purposes - must be started prior to allergen exposure (ideally 1-2 weeks beforehand)

common examples:
● ⭐️ cromolyn (nasal spray, oral, oral inhalation, and ophthalmic drop)
● ⭐️ ketotifen (ophthalmic, oral)

cromolyn nasal spray and ketotifen eye drops are OTC
the rest are Rx-only

Question 14

Nasal spray administration
Just FYI

Answer 14

● prime before first use, or if not used in awhile
● clear nasal passages in advance (blow or rinse)
● spray tip should be inserted no more than ½ inch
into the nose
● leaning forward slightly, and pressing close the
nostril not being treated; some sprays require
gentle nasal inhalation
● spray away from the septum (ie, towards the ear)
to minimize adverse effects (esp epistaxis) and
ensure medication reaches the back of the nose;
easiest to hold w/ contralateral hand
● wipe and clean spray tip and recap after each use

Question 15

leukotriene receptor antagonist
MOA
Uses?
Which agent

Answer 15

MOA:
—inhibition of leukotriene, pro-inflammatory
chemicals that are particularly well-known in for their role
in the pathophysiology of asthma

⭐️montelukast (Singulair®) ⭐️ and zafirlukast (Accolate®) for…
● allergic rhinitis if refractory to other options, or if coexisting asthma
● maintenance therapy of asthma
● prevention of exercise-induced bronchoconstriction
● various allergy-related off-label uses

BBW posted in 2020: serious neuropsychiatric events
(agitation, aggression, depression, sleep disturbance,
suicidal thoughts)
Rx only

Question 16

Cough (Tussis)
Which is the only med that has been shown to decrease cough count, effort and frequency ?

Answer 16

note: despite widespread use, most antitussives lack strong evidence showing that they work better
than placebo, and there is a known placebo effect; only dextromethorphan has been shown to decrease cough count, effort, and frequency

Question 17

Guaifenesin
MOA
When is it indicated?
NOT indicated for?
Known brand names?

Answer 17

MOA:
expectorant - thins and loosens mucus, possible direct effects on respiratory epithelial cells and cough-reflex sensitivity

for short-term management of acute, ineffective, productive coughs only; NOT indicated for chronic cough d/t chronic
lower respiratory tract disease (COPD, smoker’s cough, asthma, etc.)

well-tolerated (few adverse effects)
OTC

available own its own (Mucinex®, Robitussin®) and in numerous combinations:
● w/ codeine
● w/ codeine and phenylephrine
● w/ dextromethorphan (DM)
● w/ hydrocodone
● and lots more

Question 18

other antitussives (cough suppressants)
for short-term treatment of productive and non-productive coughs
OTC
Tx
OTC topical agents

Answer 18

OTC
● dextromethorphan
● diphenhydramine

Rx only
● benzonatate
● promethazine
● codeine and other opioid derivatives

OTC topical agents
● menthol - activates nasal sensory afferents, in various cough and throat products
● benzocaine (Cepacol®, Chloraseptic®) - local anesthetic
● camphor (ie, Vicks®) - vapors help w/ cough and congestion

Question 19

dextromethorphan
MOA
ADR
Precautions

Answer 19

MOA:
—analogue of levorphanol (a codeine analog), acts
centrally on the medulla, increases cough threshold

adverse effects
● GI: nausea/vomiting, discomfort
● CNS: drowsiness, dizziness

precautions
● caution w/ other sedating drugs and alcohol
● must be >18yr to purchase d/t abuse (‘robotripping,’
‘skittling,’ etc.)
● overdose → euphoria, visual hallucinations, etc.,
effects are similar to PCP and ketamine
● serotonin reuptake inhibition = risk of serotonin
syndrome with other drugs of similar effect (ie,
antidepressants), contraindicated with MAO
inhibitors

available on its own (Delsym®) as well as in numerous combination products…
● guaifenesin-dextromethorphan (Robitussin DM, Mucinex DM)
● promethazine-dextromethorphan
● and tons more

Question 20

topical agents - benzocaine, menthol, camphor, etc.
Adverse affects to know

Answer 20

Benzocaine: methemoglobinemia

Camphor: if ingested, can cause severe CNS toxicity (incl. agitation, seizure, respiratory depression, coma)

Question 21

benzonatate (Tessalon®)
MOA
Age in kids
Route
ADRs

Answer 21

MOA:
—precursor to tetracaine, which has local anesthetic (numbing) effects on respiratory stretch receptors

for use in adults and children >10yo

gel caps must be swallowed whole (if chewed, contents can cause local numbness and choking hazard)

adverse effects are uncommon, but may
include:
● constipation
● dizziness
● fatigue
● stuffy nose
● nausea
● headache

overdose → local anesthetic toxicity incl seizures, coma, cardiac arrest (more to be covered in surgery module); recent increasing trends of this happening in children because the gel caps look like candy

Question 22

Promethazine

Answer 22

MOA:
—anticholinergic/antihistamine
→bronchodilates, reduces edema and congestion

note: first-generation antihistamines (ie, diphenhydramine) also work for cough because they penetrate the blood brain barrier and exert antihistaminic and antimuscarinic effects
on the medulla; second-gen antihistamines (ie, loratadine, cetirizine) do not have antitussive effects

adverse effects are the same as you’d expect
from other anticholinergics, esp drowsiness, dizziness

on its own (Phenergan®), promethazine is mainly used to treat nausea and vomiting

for cough and congestion, typically given in combination…
● w/ codeine
● w/ dextromethorphan
● w/ phenylephrine
● w/ phenylephrine and codeine
● etc

Question 23

Codeine
MOA
In combo with?
ADRs?
Precautions! Contraindicated in?

Answer 23

MOA:
—metabolized to morphine, acts centrally on the medulla, increases cough threshold

always in combination form, such as…
● promethazine-codeine
● guaifenesin-codeine (Robitussin AC®)
● hydrocodone-chlorpheniramine (Tussionex®)

(there’s also acetaminophen-codeine for pain)

adverse effects:
● nausea/vomiting
● sedation
● dizziness
● constipation

precautions
● contraindicated in children <12 yo
● elderly
● impaired respiratory function
● substance abuse - mixed w/ soda +/- candy to make ‘purple drank,’ ‘lean,’ ‘sizzurp,’ ‘syrup,’ etc.

Question 24

oral analgesics and antipyretics (anti-fever)

Answer 24

● aspirin - caution hypersensitivity and GI ulcers
● NSAIDs - caution hypersensitivity and GI ulcers, cardiovascular disease, pregnancy
○ one study found that patients who used NSAIDs during an acute respiratory infection tripled their risk of an acute myocardial infarction
● acetaminophen - caution exposure from multiple sources, liver injury if
overdose

Question 25

precautions in special populations
Which cold and flu meds to avoid for:
Pregnancy, HTN, CVD (3)
Children <2y.o

Answer 25

Question 26

herbals and supplements worth mentioning

Answer 26

Question 27

combo cold and flu products - don’t get them mixed up!

Answer 27

● Robitussin Maximum Strength
Cough and Chest Congestion DM =
guaifenesin + dextromethorphan

● Robitussin Maximum Strength
Nighttime Cough DM =
dextromethorphan + doxylamine

● Robitussin Children’s 12 Hour
Cough Relief Medicine =
dextromethorphan

● Robitussin Children’s Nighttime
Cough Medicine =
chlorpheniramine +
dextromethorphan

caution prescribing or recommending agents by brand name

if a patient shares that they tried a brand name agent, dig further to determine what active ingredients it contains so that your recommendation is well-informed

look out for potential overdose due to overlapping ingredients from multiple sources

Question 28

⭐️Know this BBWs for promethazine and codeine

Answer 28

Metabolised to morphine and causes respiratory distress
Absolute no-no in under 12
And post surgery