Cough

PMPR 3270 – Nonprescription Pharmacotherapy, Natural

Medicines, and Self-Care I

Adam C. Welch, PharmD, MBA, FAPhA

 Allergies Colds Cough
INCS Antihistamine Mast Cell Decongestants Counter- Anesthe Expectorant Anti-
Stabilizer irritants tics tussive

Dietary Supplements Dietary Supplements Dietary Supplements

 Learning Objectives
• Compare and contrast nonprescription
treatment options for the cough
• Formulate a drug therapy plan for a patient
with coughing
• Identify risks of nonprescription cough and
cold medication
 How We Cough

https://youtu.be/usAqJoVYVSc
 Classifying Coughs
Acute Subacute Chronic

< 3 weeks 3-8 weeks > 8 weeks

Viral, upper respiratory Post infectious, Drug induced, cancer

tract infection, some pertussis, bacterial induced, GERD, COPD,
asthma sinusitis, some asthma smoking, some asthma
 Acute Cough Duration
Literature
• Any cough
– Mean duration 17.8 days
• Productive cough
– Mean 13.9 days
• Nighttime cough
– Mean 10.4 days

Survey of 493 adults in Georgia

– Mean 7.2-9.3 days

Ann Fam Med 2013;11(1):5-13.

 Coughs
• Productive: a process when coughing that expels
mucus from the lungs. AKA wet, chesty.
– Effective when excretions are expelled
– Ineffective when excretions are difficult to expel

• Although not a reliable indicator, mucus color and

smell may indicate presence of bacteria

• Nonproductive: serve no physiologic purpose. AKA

dry, hacking.
– Due to infections, gastroesophageal reflux disease
(GERD), medications, among others.
 Complications of Cough
• Exhaustion
• Insomnia
• Pain
• Hoarseness
• Incontinence
• Rib fractures (rare)
• Dysrhythmias (rare)
• Stroke (rare)
 ACE Inhibitor Induced Cough
Drug Incidence Withdrawal
• Dry, unproductive cough Benazepril 1.2%
that is persistent and often Captopril 0.5-2%
Cilazapril 3.2%
worse at night. Delapril 12.3% 4%
• Thought to be due to Enalapril 10%
Fosinopril 2-10%
accumulation of bradykinin Lisinopril 3.5%
• Often seen with initiation of Moexipril 6% 1%
Perindopril 7-12% 1-3%
therapy or dose change Quinapril 1-4%
– Similar symptoms seen at all Ramipril 3-12% 4%
Spirapril 0.9-4%
dose levels of lisinopril Trandolapril 3-4% 0.1%

Source: Micromedex
 Treatment Goals
• Reduce the number and severity of
coughing episodes
• Prevent complications
• Remedy underlying condition
 Nonpharmacologic
• Humidified air
• Lozenges
• Elevate head during sleep
• Stay hydrated
 Pharmacologic Therapy
• Expectorants
• Antitussives
• Dietary Supplements
 Expectorant vs Mucolytic
Expectorant Mucolytic
• Increase mucin secretion • Reduces viscosity of mucus
• Increase mucus hydration • Dissociated the disulfide bonds
– Yields a larger volume of in mucin
mucus
• Large mucus easier to expel • N-acetylcysteine,
via cough carbocysteine
• Guaifenesin, potassium citrate
Elasticity – ability to return
to normal shape after Viscosity – resistance to flow
deformation

Respiratory Care May 2014, 59 (5) 788-789

 Expectorant
• Guaifenesin (Mucinex, Robitussin)
– Children and adults 2 yrs and older

Mechanism
• Stimulates respiratory tract to increase fluid and
decrease viscosity of bronchial secretions

• Larger volume of mucus allows ineffective coughs

to be more productive
 Guaifenesin Dosing
• Adults:
– 200-400mg immediate release every 4 hours
• Max 2400mg/day
– 600-1200mg sustained release every 12 hours
• Max 2400mg/day

• Children:
– 6-11 years 100-200mg every 4 hours
• Max 1200mg/day
– 4-6 years 50-100mg every 4 hours
• Max 600mg/day
 Quick Question
• How much guaifenesin is in a teaspoon of
Robitussin?
A. 100mg
B. 400mg
C. 600mg
D. 1200mg
 Guaifenesin
• Adverse effects
– Not typically observed
– Nausea
– Vomiting

• Patient education
– Take with a full glass of water
 Oral Antitussives
• Dextromethorphan
– Delsym, DM
• Codeine
– AC
• Diphenhydramine
– Benadryl
A Quick Note on Antihistamines
• 1st generation antihistamine
• Sedative and anticholinergic properties
• May have central cough suppressant activity
– Specific to diphenhydramine

• Chlophedianol
– Alkylamine antihistamine with antitussive effects
– Used for nonproductive coughs
– May cause nausea, dizziness, drowsiness
 Dextromethorphan
• Mechanism
– Works centrally (in the medulla oblongata) to
elevate the threshold for coughing
– Treats nonproductive coughs
– Coughs with chemical or mechanical irritation
to the to the respiratory tract
 Dextromethorphan
• At normal doses, dextromethorphan has
minimal activity as:
• Analgesic
• Sedative
• Respiratory depressant
• Addictive properties
 Dosing
Dextromethorphan hydrobromide Dextromethorphan polistirex
• Adults • Adults:
– 30mg every 6-8 hours – 60mg every 12 hours
• Max 120mg/day • Max: 120mg/day
• Children • Children:
– 6-12 yr: 10mg every 4 – 6-12 yr: 30mg every 12 hrs
hours • Max 60mg/day
• Max 60mg/day – 4-5 yr: 15mg every 12 hrs
– 4-5 yrs : 5mg every 4 hours • Max 30mg/day
• Max 30mg/day
 Dextromethorphan Interactions
• Avoid in patients taking MAOI
– Not to be used within 14 days of stopping an
MAOI
• Evidence exist but not as strong for other
antidepressants
– Risk for serotonin syndrome
 Serotonin Syndrome
• Can be mild to life threatening and occur shortly after
serotonergic load (eg. from drug interaction)

• Symptoms:
– Clonus (repeated muscular spasms)
– Overresponsive reflexes
– Mild fever
– Hypertension
– Tachycardia
• Complications:
– Seizures
– Risk for bleeding
– Multi-organ failure
Dextromethorphan Adverse Effects
• Nausea
• Vomiting
• Dizziness
 General Cough - Warnings
• Excessive phlegm
• Chronic cough
• Cough lasting more than 7 days
 Codeine
• Mechanism
– Works centrally (in the medulla oblongata) to
elevate the threshold for coughing
– Good for nonproductive coughs
– Coughs with chemical or mechanical irritation
to the to the respiratory tract
 Codeine C-V at OTC doses
• To be sold without a prescription as a
controlled substance
– Must include one or more non-codeine
products
– Limits to 200mg codeine per 100mL
 Codeine Adverse Effects
• Adverse Effects
– Constipation
– Respiratory depression
– Dizziness
– Hypotension

• Metabolized by CYP2D6 to morphine

• Doses 500mg-1000mg may lead to fatal levels of

respiratory depression

https://cpicpgx.org/guidelines/guideline-for-codeine-and-cyp2d6/
https://youtu.be/Rv0Rb7w1u2A
https://cpicpgx.org/guidelines/guideline-for-codeine-and-cyp2d6/
Consumed at high doses (Robo-trippin) for
euphoric and hallucinogenic effects
www.whatisdxm.com
 Dextromethorphan Limits

TN law limits sale of dextromethorphan to

adults 18 years and older
(or emancipated minors)
 Dosage (maximum daily dosage)

Drug Adults/Children ≥12

Children 6 to <12 Years Children 2 to <6 Yearsa
Years
Codeineb-d 10–20 mg every 4–6 5–10 mg every 4–6 1 mg/kg/day PRN in 4
hours PRN (120 mg) hours PRN (60 mg) equal divided dosages
or by average body
weight

Dextromethorphan 10–20 mg every 4 hours 5–10 mg every 4 hours 2.5–5 mg every 4 hours
hydrobromideb or 30 mg every 6–8 or 15 mg every 6–8 or 7.5 mg every 6–8
hours PRN (120 mg) hours PRN (60 mg) hours PRN (30 mg)

Diphenhydramine HClb,c 25 mg every 4 hours 12.5 mg every 4 hours 6.25 mg every 4 hours
PRN (150 mg) PRN (75 mg) PRN (37.5 mg)

Guaifenesinb 200–400 mg every 4 100–200 mg every 4 50–100 mg every 4

hours PRN (2.4 g) hours PRN (1.2 g) hours PRN (600 mg)

OTC Handbook, Table 12-3.

https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm
 Varying Recommendations
FDA
• Does not recommend OTC
cough and cold products in
children younger than 2
years
CHPA
• Revised labeling of OTC
cough and cold products
• “Do not use” in children
younger than 4 years

2 4
https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm
https://www.chpa.org/PediatricCC.aspx
 Dietary Supplements
• Honey
• Eucalyptus
 Honey
• Mechanism
– Unknown
– May increase salivation
• Calm sensory nerves
– Antibacterial or anti-inflammatory effects
• Dosing
– 2.5 – 10mL orally, usually at bedtime
• Adverse Effects
– Gastrointestinal upset
– Nervousness
– Insomnia
 Honey
• Efficacy
• Subjective questionnaire on cough
frequency
– N=154
• -1.05 (95% CI, -1.48 to -0.62)
– N=300
• -1.85 (95% CI, -3.36 to -0.33)
 Avoid Honey in Infants
Honey should not be used in children less
than 1 yr for risk of botulism

Honey may be contaminated from

agricultural pesticides or Clostridium
botulinum spores
 Eucalyptus
• Oil has been used for antitussive properties
related to bronchitis.

• Adverse Effects
– Stomach pain
– Burning
– Muscle weakness

• Harmful if ingested or applied topically at full

strength.
 Chest Physicians in 2017
• In Adults, CHEST suggests until they have been
shown to make cough less severe or resolve sooner
– Against the use of OTC cough and cold medicines
– Against the use of NSAIDS

• Pediatrics (1-18)
– Honey (>1yr) may be better than
• Placebo
• Diphenhydramine
• Nothing
– Honey is not better than Dextromethorphan (>2yr)
– Avoid codeine-containing products (respiratory distress)

Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS. Pharmacologic and nonpharmacologic

treatment for acute cough associated with the common cold: CHEST Expert Panel report.
Chest 2017;152(5): 1021-37. DOI: http://dx.doi.org/10.1016/j.chest.2017.08.009
• Risks outweigh benefits in children
younger than 18 years for use of cough
and cold medications containing codeine
or hydrocodone
• Healthcare professionals should reassure
patients that cough due to cold or URI is
self-limiting
– If cough treatment is necessary, [use non-
opioid products]
https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm
 Pregnancy Resources
• Websites & electronic resources:
– www.motherisk.org
– https://mothertobaby.org
– www.infantrisk.com
• Mommymeds app for Mothers
• InfantRisk Center for Health Care Providers
– LactMed: https://www.ncbi.nlm.nih.gov/books/NBK501922/?report=classic
LexiComp© Pregnancy & Lactation database
– Micromedex® Pregnancy and Lactation sections
• Reference books:
– Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and
lactation. 11th ed, 2017.
– Hale TW. Medications and Mother’s Milk. 17th ed, 2017.

Source: Dr. Larissa Bossaer

 Cases

Allergies, Cold, Cough

 QuEST - SCHOLAR
• Quickly and accurately assess the patient
– Symptoms, Characteristics, History, Onset,
Location, Aggravating Factors, Remitting Factors
(Medications, Allergies, Coexisting conditions)
• Establish if patient is candidate for self-care
• Suggest appropriate self-care therapy
• Teach the patient on medication action and
what to expect
 26 yr Male
• Symptoms
– Nasal congestion
– Rhinorrhea
– Cough
• What else do you need to know?
 16 yr Female
• Symptoms
– Fever (101.2)
– Muscle pain
– Headache
– Cough
• What else do you need to know?
 45 yr Female
• Symptoms
– Runny nose
– Cough
– Itchy eyes
• PMH
– Hypertension on three medications
• What else would you need to know?
 References
• Levitzky MG. Nonrespiratory functions of the lung, chapter 10, In: Pulmonary Physiology 8th ed. 2013;
McGraw-Hill.
• Tietze K. Coughs. Ch 12. In Krisky et al. Handbook of nonprescription drugs, 19th ed. 2017; American
Pharmacists Association.
• Irwin RS et al. Overview of the management of cough: CHEST guideline and expert panel report. Chest
2014; 146(14): 886-889.
• Pratter MR. Cough and the common cold : ACCP evidence-based clinical practice guidelines. Chest
2006; 129(1 suppl): 72s-74s.
• Bolser DC. Cough suppressant and pharmacologic protussive therapy ACCP evidence-based clinical
practice guidelines. Chest 2006; 129(1 suppl): 238s-249s.
• Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and
adults in community settings. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.:
CD001831. DOI: 10.1002/14651858.CD001831.pub5.
• DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 193270,
Serotonin syndrome; [updated 2015 Apr 03, cited place cited Feb 9 2017]; [about 7 screens]. Available
from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=193270. Registration and login
required
• Crews et al. Clinical pharmacogenomics implementation consortium guidelines for cytochrome P450 2D6
genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95(4):376-82.
• Oduwole O, Meremikwu MM, Oyo-Ita A, Udoh EE. Honey for acute cough in children. Cochrane
Database of Systematic Reviews 2014, Issue 12. Art. No.: CD007094. DOI:
10.1002/14651858.CD007094.pub4.