codeine and pseudoephedrine

Action and Spectrum

Actions and spectrum: 

codeine: 

• Action: codeine is an opioid analgesic (pain reliever) and antitussive (cough suppressant). 
• Spectrum: It is primarily used for the relief of mild to moderate pain and for the suppression of non-productive cough. codeine acts by binding to opioid receptors in the central nervous system, which helps to alleviate pain and suppress coughing. 

pseudoephedrine: 

• Action: pseudoephedrine is a sympathomimetic decongestant. 
• Spectrum: pseudoephedrine works by constricting blood vessels and reducing swelling in the nasal passages, thereby relieving nasal congestion. 
• pseudoephedrine is commonly used for temporary relief of nasal congestion associated with the common cold, allergies, and sinusitis. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

codeine 

• Confusion, false well being, lightheadedness, paradoxical CNS stimulation, weakness, dizziness, headache, malaise, restlessness 
• Anorexia, vomiting, nausea, xerostomia 
• Ureteral spasm, decreased urination 
• histamine release, Blurred vision 
• Bradycardia, tachycardia, hypotension 
• Urticaria, rash 
• Increased LFTs 
• Dyspnea

>10% 

codeine 

• Constipation 
• Drowsiness 

Frequency not defined 

pseudoephedrine 

• Restlessness 
• Nausea 
• Insomnia 
• Tremor 
• Vomiting 

codeine (serious) 

• Seizure, With excessive doses 
• Respiratory depression 
• Hypotension, With IV use 
• Anaphylactoid reaction (rare) 

Black Box Warning

Black Box Warning: 

codeine and pseudoephedrine do not have specific black box warnings. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity or allergic reactions to codeine or any opioid analgesics. 
• Respiratory depression: codeine should be avoided or used with caution in individuals with respiratory depression, acute or severe bronchial asthma, or hypercapnia. 
• Paralytic ileus: codeine should not be used in patients with paralytic ileus. 
• Severe hypertension: pseudoephedrine should be used with caution or avoided in patients with severe hypertension or uncontrolled hypertension. 
• Severe coronary artery disease: pseudoephedrine should be used with caution or avoided in patients with severe coronary artery disease.

Caution: 

• CNS depression: codeine may cause drowsiness, dizziness, and impaired cognitive and motor function.  
• Dependence and addiction: codeine is an opioid and may lead to psychological and physical dependence with prolonged use. Caution should be exercised in individuals with a history of substance abuse or addiction. 
• CNS stimulation: pseudoephedrine can cause nervousness, restlessness, and insomnia. Caution should be exercised in patients with anxiety disorders, insomnia, or other conditions where central nervous system stimulation may be problematic. 
• Urinary retention: pseudoephedrine can exacerbate symptoms of urinary retention in patients with underlying conditions such as enlarged prostate or bladder outlet obstruction.

Comorbidities: 

• Cardiovascular conditions: Both codeine and pseudoephedrine can potentially increase blood pressure and heart rate. Individuals with pre-existing cardiovascular conditions, such as hypertension, coronary artery disease, arrhythmias, or history of stroke, may need close monitoring and adjustment of their medication regimen. 
• Respiratory conditions: codeine can suppress respiratory function, which may be of concern in individuals with respiratory conditions like asthma, COPD, or other respiratory disorders. pseudoephedrine, on the other hand, can stimulate the respiratory system. 
• Liver or kidney impairment: Both codeine and pseudoephedrine gets metabolized and eliminated by the liver and kidneys. Individuals with impaired liver or kidney function may require dosage adjustments or closer monitoring to prevent potential adverse effects or accumulation of the medications. 
• Thyroid disorders: pseudoephedrine can stimulate the release of norepinephrine, which can affect thyroid hormone levels. Individuals with thyroid disorders, such as hyperthyroidism, may require careful monitoring when using pseudoephedrine. 
• Prostate enlargement: pseudoephedrine can potentially worsen urinary symptoms in individuals with benign prostatic hyperplasia (BPH) or prostate enlargement. It is important to use caution and monitor for any worsening of urinary symptoms in such individuals. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Yes (codeine); Yes (pseudoephedrine)  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

codeine is an opioid analgesic that acts as a prodrug and is converted to its active form, morphine, by the liver. codeine relieves mild to moderate pain by binding to opioid receptors, reducing the perception of pain signals. codeine also has antitussive (cough suppressant) properties by acting centrally in the brainstem to reduce the cough reflex. 

pseudoephedrine is a sympathomimetic amine that acts as a nasal decongestant. It works by stimulating alpha-adrenergic receptors in the blood vessels of the nasal passages, leading to vasoconstriction and decreased nasal congestion.

pseudoephedrine reduces nasal congestion by constricting blood vessels in the nasal mucosa, thereby reducing swelling and promoting nasal drainage. pseudoephedrine can also have systemic effects due to its sympathomimetic activity. It can increase heart rate and blood pressure and may have mild bronchodilator effects.  

Pharmacodynamics: 

codeine: 

• Opioid receptor agonist: codeine binds to and activates opioid receptors in the central nervous system, primarily the mu-opioid receptors. This activation leads to analgesic effects and the suppression of cough reflex. 
• Analgesic effects: codeine’s analgesic effects are mediated by the activation of mu-opioid receptors, resulting in the modulation of pain perception and transmission. 
• Antitussive effects: codeine acts centrally to suppress the cough reflex by inhibiting the cough center in the brainstem. 

pseudoephedrine: 

• Alpha-adrenergic agonist: pseudoephedrine stimulates alpha-adrenergic receptors, particularly the alpha-1 receptors, causing vasoconstriction. 
• Nasal decongestant effects: pseudoephedrine’s primary action is on the blood vessels in the nasal passages. By constricting these blood vessels, it reduces swelling and congestion, leading to nasal decongestion. 
• Systemic effects: pseudoephedrine can have additional systemic effects due to its sympathomimetic activity. It can increase heart rate and blood pressure and may have mild bronchodilator effects. 

Pharmacokinetics: 

codeine: 

• Absorption: codeine is well-absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours. 
• Distribution: codeine is distributed throughout the body, including the central nervous system. It crosses placenta and gets excreted into breast milk. 
• Metabolism: codeine undergoes extensive metabolism in the liver by the enzyme CYP2D6 into its active metabolite, morphine. Genetic variations in CYP2D6 activity can affect codeine metabolism and efficacy. 
• Excretion: codeine and its metabolites are primarily excreted in the urine. Approximately 10% of codeine is excreted unchanged, while the majority is eliminated as metabolites. 

pseudoephedrine: 

• Absorption: pseudoephedrine is well-absorbed after oral administration, with peak plasma concentrations achieved within 1-2 hours. 
• Distribution: pseudoephedrine is widely distributed throughout the body, including the central nervous system. 
• Metabolism: pseudoephedrine undergoes minimal metabolism in the liver, primarily through oxidation. The major metabolite, norpseudoephedrine, is pharmacologically inactive. 
• Excretion: pseudoephedrine and its metabolites are primarily excreted in the urine. Approximately 55-70% of a pseudoephedrine dose is excreted unchanged within 24 hours. 

Adminstartion

Administration: 

codeine/pseudoephedrine is usually taken orally with or without food. The dose and frequency of administration will depends on the specific condition being treated, the formulation of the medication, and the individual’s age and weight. 

It is important to follow the prescribed dosage and should not exceed the recommended dose to avoid potential side effects or overdose. codeine may be available in combination with other medications, such as acetaminophen or cough suppressants. In such cases, it is necessary to follow the instructions for each active ingredient. 

pseudoephedrine is often available as a single-ingredient product or as part of combination medications for cold and sinus symptoms. In the case of combination products, it is necessary to follow the instructions for each active ingredient and be aware of any duplicate dosing. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: codeine and pseudoephedrine 

Pronounced: (koh-deen- soo-doh-eh-fed-rin) 

Why do we use codeine and pseudoephedrine? 

• Pain relief: codeine is an opioid analgesic that is used to relieve pain. It is often prescribed for conditions such as dental pain, postoperative pain, or pain associated with injuries. 
• Cough suppression: codeine is also used as an antitussive to suppress coughing. It is commonly found in cough syrups and other over-the-counter cold and flu medications. 
• Nasal congestion relief: pseudoephedrine is a decongestant that helps alleviate nasal congestion caused by colds, allergies, or sinusitis. It acts by narrowing the blood vessels in the nasal passages, reducing swelling and congestion. 
• Sinus pressure relief: pseudoephedrine can also help relieve sinus pressure and pain associated with sinusitis or allergies. 
• Eustachian tube congestion relief: pseudoephedrine may be used to relieve congestion in the Eustachian tubes, which can help with ear discomfort or pressure changes due to altitude or congestion.