Disease (Cold)
A cold is a contagious disease. It affects the nose, sinuses, trachea, and windpipe.
Etiology
Cold is caused by viruses and spread by germs. Rhinoviruses are the most common cause. It occurs when a cold virus enters the body through the mouth or nose (Mayo clinic, n. d). Consequently, the virus spreads through droplets when an affected individual sneezes or coughs.
Impacts of the disorder on the body
The severe symptoms of a cold are evident after 2 to 3 days, including sore throat, runny nose, stuffy nose, sneezing, coughing, fever, and watery eyes. Although a normal cough is normal and healthy, one that persists for several weeks may or brings bloody and discolored mucus may signify a need for medical attention (Mayo Clinic, n. d). Coughs can cause dizziness, sleeplessness, vomiting, and urinary incontinence.
Codeine
Codeine is a drug-inducing pain reliever that treats coughs and colds. It belongs to a group of narcotic analgesics or pain medicines.
Mechanism of Action
Codeine, also called methyl morphine, is used for the symptomatic treatment of colds. It binds to the three main µ-opioid receptors to produce both euphoria and analgesia. When the opioids bind to the three receptors with G-proteins coupled with mu, delta, and kappa, a series of intracellular events occur. Consequently, it results in a limited intracellular cAMP, hyperpolarization of the neuronal cells, and less neurotransmitter release. The medicine usually suppresses the cough reflex by directly affecting the medulla’s cough center. Consequently, the enzyme called cytochrome P450 2D6 (CYP2D6), which usually shows genetic polymorphism converts codeine into morphine. Patients with ‘CYP2D6 ultra-rapid metabolizers easily convert codeine into morphine much faster, resulting in high levels of morphine in their blood. It sometimes leads to some toxic effects, including breathing difficulties. The activation of mu receptors in the midbrain and the nervous system is a dominant mechanism of opioid-induced analgesia.
Pharmacokinetics (ADME)
Absorption
Absorption occurs when codeine sulfate is absorbed from maximum plasma concentration (Cmax) and the gastrointestinal tract after approximately sixty minutes (Peechakara & Gupta, 2023). External factors such as food presence usually do not affect codeine absorption.
Distribution
Codeine has a volume of distribution of 3 to 6 L/kg. This suggests extensive tissue distribution.
Metabolism
Conjugation to morphine and N-demethylation to norcodeine causes codeine metabolization. P450 3A4 acts as the primary enzyme for transforming codeine to norcodeine.
Excretion
The kidney excretes the codeine. However, the kidney excretes 90 % of the changed and 10 % of unchanged codeine (Peechakara & Gupta, 2023). The time of codeine and metabolites is 3 hours.
Drug Interactions
There are drug interactions, disease interactions, and alcohol or food interactions. These interactions are highly beneficial, and as Fulton et al. (2019) note, the drug-drug interactions obscure the benefits of genotyping. One of the most common interactions is between tramadol and codeine used to treat severe pain. Although the analgesic impact of codeine and tramadol is highly variable, the two prodrugs are converted into active metabolites with a CYP2D6 gene, which is highly polymorphic. The metabolic activity, usage, and dosage are highly checked under strict regulations.
Regarding food-drug interaction, clinicians and physicians hold that some foods alter the body’s ability to utilize a particular food when taken simultaneously. Grapefruit juice highly interacts with codeine to reduce the analgesic property of the drug. In addition, Marijuana, when taken along with codeine drugs, increases the state of dizziness. When patients on codeine consume an alcoholic beverage, it adds to CNS’s depressant effect on codeine.
Numerous diseases interact with codeine. These include diarrhea, liver disease, alcohol intoxication, hypotension, urinary retention, seizure disorders, respiratory depression, arrhythmias, and gastrointestinal obstruction. Excessive dosage may exacerbate hypo perfusion and hypotension. When given by subcutaneous or intramuscular administration, impaired perfusion, and excessive taking may lead to incomplete drug absorption. In any case, it is highly recommended that the use of codeine or any other analgesic agent is contraindicated in infants. This is because agents may cross the immature blood-brain barrier to a greater extent than in adults.
Adverse effects
First, when codeine is used in large doses or for a long time, it becomes addictive. Thus, it easily causes mental or physical dependence. Physical dependence, if not considered, may result in withdrawal impacts when a person stops taking medicine. Other adverse effects of codeine administration include drowsiness, dizziness, and lightheadedness.
In most cases, people known to be hypersensitive to various opioids may exhibit cross-sensitivity to codeine. Opioids, including codeine sulfate, should be cautiously used in patients with chronic obstructive pulmonary disease or those with decreased respiratory reserve, hypercapnia, hypoxia, or pre-existing respiratory depression. In such patients, normal doses may result in decreased respiratory drive. Patients may consider alternative non-opioid analgesics. Codeine may be employed only under careful medical supervision.
Conclusion
Codeine is an important medicine for treating coughs and colds. Codeine is related to morphine, and long-term use of it may result in opioid dependence, abuse, and toxicity. It causes opioid addiction and dependence. When deciding to use it, a person should weigh its risks and benefits. Due to codeine’s greater applicability to real-world settings understanding the vital information about its interactions with drugs, diseases, and foods will guide therapeutic decisions. At the same time, clinicians and patients will remain vigilant to mitigate the adverse impacts of the drug.
References
Fulton, C. R., Zang, Y., Desta, Z., Rosenman, M. B., Holmes, A. M., Decker, B. S., … & Eadon, M. T. (2019). Drug–gene, and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. Pharmacogenomics, 20(06), 397-408.
Mayo Clinic (n. d). Common cold. https://www.mayoclinic.org/diseases-conditions/common-cold/symptoms-causes/syc-20351605
Peechakara, B. V., & Gupta, M. (2023). Codeine. https://www.ncbi.nlm.nih.gov/books/NBK526029/#:~:text=Mechanism%20of%20Action,-Classically%2C%20there%20are&text=Absorption%3A%20Codeine%20sulfate%20is%20absorbed,affect%20the%20absorption%20of%20codeine.
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