About Codeine:

• Codeine is a painkiller. It's used to treat pain, for example after an operation or an injury. It's also used for long-standing pain when everyday painkillers, such as aspirin, ibuprofen and paracetamol, haven't worked.
• It works in the central nervous system and the brain to block pain signals to the rest of the body. It also reduces the anxiety and stress caused by pain.
• Codeine is also used to treat diarrhoea.
• Codeine is available on prescription. It comes as tablets, a liquid to swallow and as an injection. Codeine injections are usually only given in hospital.
• You can buy lower-strength codeine from a pharmacy. It comes mixed with paracetamol (co-codamol) or with aspirin (co-codaprin) or with ibuprofen (Nurofen Plus).
• You can also buy codeine from a pharmacy as a syrup (linctus) to treat dry coughs.

When codeine blocks the pain, there are other unwanted effects - for example slow or shallow breathing. It also slows down digestion, which is why codeine can cause constipation.

Key Facts:

• Codeine works by stopping pain signals from travelling along the nerves to the brain.
• The most common side effects of codeine are constipation, feeling sick (nausea) and feeling sleepy.
• It's possible to become addicted to codeine, but this is rare if you're taking it to relieve pain and your doctor is reviewing your treatment regularly.
• It may be best not to drink alcohol while taking codeine as you're more likely to get side effects like feeling sleepy.

Do not give codeine to children under 12 years old. Only give codeine to children aged 12 to 18 years if everyday painkillers like paracetamol and ibuprofen haven't worked.

How much will I take?

• Codeine can be taken by adults and children aged 12 years and older.
• Codeine comes as:
  • Tablets - these contain 15mg, 30mg or 60mg of codeine
  • A liquid that you swallow - this contains 25mg of codeine in a 5ml spoonful
  • Cough syrup - this contains 15mg of codeine in a 5ml spoonful
  • An injection (usually given in hospital)
• You might only need to take codeine for a few days.
• Sometimes, you may need to take codeine for longer. But usually a different medicine will be prescribed for long term pain or diarrhoea, especially if you have side effects like constipation.

Important: Do not take more than 4 doses of codeine in 24 hours if you're: a child (aged 12 to 18 years) or taking a 60mg dose

Codeine:
https://www.nhs.uk/medicines/codeine/

Codeine is an opioid medicine (sometimes called an opiate). It is used to treat mild-to-moderate types of pain. It can be particularly useful when painkillers such as paracetamol and ibuprofen have not been effective. It works by binding to certain tiny areas, called opioid receptors, in your central nervous system (brain and spinal cord). This leads to a decrease in the way you feel pain and your reaction to pain. Codeine is available on a prescription from a doctor.

Codeine is also contained in a number of combination medicines, some of which can be bought over-the-counter, without a prescription, in pharmacies. You should not drink alcohol while you are taking codeine. Codeine is likely to affect your reactions and ability to drive. You will not be given codeine for longer than is necessary. This is because when you take codeine repeatedly over a period of time and then stop taking it, it can cause withdrawal symptoms. Codeine is normally prescribed for short periods of pain. If you take it over a longer period of time, your body can become used to it and it will not work as well.

Excerpt from patient.info:
https://patient.info/medicine/codeine-for-pain-relief

Some people may find that codeine doesn't relieve their pain. That's because the body must first convert codeine into morphine, and some people lack the gene responsible for that conversion. Also, not everyone's liver processes codeine at the same rate. Therefore, people whose bodies break down codeine quickly may need higher doses than usual or more frequent doses to relieve their pain. And people who process codeine slowly might need lower doses of codeine than usual.

Excerpt from Everyday Health:
https://www.everydayhealth.com/drugs/codeine

Codeine is part of a group of drugs known as opioids. Opioids interact with opioid receptors in the brain and elicit a range of responses within the body, from feelings of pain relief, to relaxation, pleasure and contentment. Codeine is used to provide relief from a number of conditions, including: Mild to moderate pain, Severe pain (when combined with aspirin or paracetamol), Dry irritating cough, Diarrhoea, Cold and flu (when combined with antihistamines and decongestants).

Some people misuse codeine by intentionally taking more than the recommended dose to get high, or as an act of self-harm.

Codeine is usually swallowed and comes in different forms, including: Tablets, Capsules, Suppositories, Soluble powders and tablets, Liquids.

Excerpt from Alchohol and Drug Foundation:
https://adf.org.au/drug-facts/codeine/

Codeine is an opiate used to manage mild to moderate pain severe enough to require an opioid. Codeine is a selective agonist for the mu opioid receptor and has an affinity to delta and kappa-opioid receptors. In some countries, this drug is regulated under various narcotic control laws, because its chronic use can cause physical dependence. In others, it is available without a medical prescription in combination with paracetamol.

Codeine:
https://drugs.ncats.io/drug/UX6OWY2V7J

Codeine is an opioid found naturally in Papaver somniferum, the opium poppy. It's somewhat misleading to call it an opioid since codeine primarily functions as a prodrug, offering little of its own activity. Morphine seems to be its primary active metabolite. Its name comes from the Greek word "kodeia," which means "poppy head." Medically, codeine is used as an analgesic, antitussive, and antidiarrheal. It's also taken recreationally, often at higher doses.

Evidence supports the existence of codeine's analgesic effects in minor to moderate pain, yet the drug usually doesn't make a lot of sense compared to other analgesics. It's primarily a prodrug, with its most relevant metabolite being morphine. In which case, there's a good argument in favor of simply using morphine itself. Using codeine means administering an unknown dose of morphine since that metabolic pathway varies between people. If people don't generate enough morphine, they may receive little to no benefit. And if they generate too much, severe negative effects could be more likely. When looking at codeine from a purely efficacy-focused perspective, it doesn't make much sense. But because of its widespread availability and unjustifiably good reputation, it's one of the world's most popular analgesics. In cases where it works, the drug can dull pain sensation to the extent that it becomes bearable and sometimes barely noticeable.

The Drug Classroom:
https://thedrugclassroom.com/video/codeine/

Codeine is a narcotic pain-reliever and cough suppressant similar to morphine and hydrocodone. Moreover, a small amount of codeine is converted to morphine in the body. Codeine binds to receptors in the brain (opioid receptors) that are important for transmitting the sensation of pain throughout the body and brain. Codeine increases tolerance to pain, decreasing discomfort, but the pain still is apparent to the patient. In addition to reducing pain, codeine also causes sedation drowsiness and depresses breathing. Codeine frequently is combined with acetaminophen (Tylenol) or aspirin for more effective pain relief. The FDA approved codeine in 1950.

Codeine is habit forming (addictive). Mental and physical dependence can occur but are unlikely when used for short-term pain relief. Using codeine during pregnancy can cause opioid withdrawal syndrome in the newborn, which may be life-threatening if not treated. Alcohol and other sedatives such as alprazolam (Xanax) can produce further brain impairment and even confusion when combined with codeine. Therefore, alcohol and other sedatives should not be used when taking codeine.

Excerpt from Medicinenet:
https://www.medicinenet.com/codeine/article.htm

Codeine is a naturally-occurring opioid substance of the morphinan class found in extracts of the poppy Papaver bractreatum. Members of this group produce effects such as sedation, cough suppression, and euphoria. Codeine is the second most predominant alkaloid in opium (up to three percent). Although codeine can be extracted from natural sources, a semi-synthetic process is the primary source of codeine for pharmaceutical use.

Codeine is currently the most widely used opiate in the world, and is one of the most commonly used drugs overall. It is one of the most effective orally administered opioid analgesics and has a wide safety margin.

Recreationally, it is usually purchased over the counter within painkillers that mix it with other more toxic substances. Codeine is available within pharmacies across the world in a variety of forms which combine it with other products which are dangerous or even fatal to consume at higher dosages. This is done to act as a deterrent to prevent their recreational use.

Excerpt from psychonautwiki.org:
https://psychonautwiki.org/wiki/Codeine

Codeine is considered a 'weak' opioid pain medication. It is in the same family of medicines as opioid pain medications and drugs such as morphine, oxycodone and heroin. In the body codeine is converted into morphine, which is thought to be responsible for almost all of the pain relieving effects of codeine.

UNSW Australia National Drug and Alcohol Research Center (PDF 2 pages):
https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/NDA073%20Fact%20Sheet%20Codeine%20update.pdf

UNSW Australia National Drug and Alcohol Research Center (PDF 41 pages):
https://www.tga.gov.au/sites/default/files/presentations-codeine-scheduling-workshops-perth-30-november-2017-sn.pdf

Codeine Sulfate (codeine)

Side Effects:
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
RxList
Codeine Sulfate (codeine): https://www.rxlist.com/codeine-sulfate-drug/patient-images-side-effects.htm
Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.
Call your doctor at once if you have: noisy breathing, sighing, shallow breathing, breathing that stops during sleep; a slow heart rate or weak pulse a light-headed feeling, like you might pass out confusion, unusual thoughts or behavior feelings of extreme happiness or sadness seizure (convulsions) problems with urination low cortisol levels - nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness
Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.
Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.
Long-term use of opioid medication may affect fertility (ability to have children) in men or women. It is not known whether opioid effects on fertility are permanent.
Common side effects include: feeling dizzy or drowsy constipation nausea, vomiting, stomach pain
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Codeine

Duration: Codeine is a weaker opioid used to treat mild to moderate pain and to relieve cough. In many countries it is available over the counter in combination with paracetamol, which can easily be extracted to retrieve near-pure codeine. For this reason, it is used widely as a recreational opioid. It is metabolised into morphine in the body at a rate of 5% mg for mg.
Route	Onset	Duration	After Effects
Tripsit Factsheets
Codeine Basic Information: http://drugs.tripsit.me/codeine
All ROAs:	30-45 minutes	3-6 hours	1-12 hours
Avoid: People seeking codeine experiences from medications that contain acetaminophen (paracetamol) may be putting themselves at risk for acetaminophen-related complications such as liver damage.
Marquis: Very dark purple
Effects: Euphoria, Dry Mouth, Mood lift, Itchiness, Relaxant, Constipation, Pupil constriction, Analgesia.
Warning: You must only use this drug orally due to the risk of severe immune system responses. It needs to pass through the liver to be activated anyway so IV, nasal, plugging etc do not offer an advantage

Liver:
Codeine, like other opioids, has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.

Codeine Hepatotoxicity:
Despite wide use for many years, codeine has not been linked to serum enzyme elevations during therapy and there have been no convincing cases of idiosyncratic acute, clinically apparent liver injury attributed to its use.

E Liklihood score: E (unlikely cause of clinically apparent liver injury).

Codeine Overview:
https://www.ncbi.nlm.nih.gov/books/NBK548359/

Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of codeine in the pediatric population. It should not be used in children younger than 12 years of age.

Safety and efficacy have not been established.

Codeine sulfate tablets should not be used to relieve pain after surgery removal of tonsils or adenoids in any children 12 to 18 years of age. Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of codeine in the elderly. However, elderly patients are more likely to have confusion and drowsiness, and age-related lung, liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving codeine in order to avoid potentially serious side effects.

Other Interactions:

• Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease (adrenal gland problem)
• Alcohol abuse, history of
• Brain problems (eg, tumor, increased intracranial pressure)
• Breathing or lung problems (eg, chronic obstructive pulmonary disease [COPD], cor pulmonale, hypoxia, sleep apnea)
• Depression, history of
• Drug dependence, especially narcotic abuse or dependence, or history of
• Enlarged prostate (BPH, prostatic hypertrophy)
• Head injuries
• Hypothyroidism (an underactive thyroid)
• Kyphoscoliosis (curvature of spine that can cause breathing problems)
• Mental health problems, history of
• Obesity (overweight)
• Problems with passing urine
• Stomach or digestion problems - Use with caution. May increase risk for more serious side effects

• Breathing problems (eg, asthma, hypercapnia), severe
• Respiratory depression (hypoventilation or slow breathing)
• Stomach or bowel blockage (including paralytic ileus) - Should not be used in patients with these conditions

• Hypotension (low blood pressure)
• Pancreatitis (swelling of the pancreas)
• Seizures, history of - Use with caution. May make these conditions worse

• Kidney disease
• Liver disease - Use with caution. The effects may be increased because of slower removal of the medicine from the body

Codeine (Oral Route):
https://www.mayoclinic.org/drugs-supplements/codeine-oral-route/description/drg-20074022

Breastfeeding:
Summary of Use During Lactation:

Maternal use of codeine during breastfeeding can cause infant drowsiness, central nervous system depression and possibly even death, with pharmacogenetics possibly playing a role.

Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral codeine to 2 to 4 days at a low dosage with close infant monitoring, especially in the outpatient setting.

If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

Excessive sedation in the mother often correlates with excess sedation in the breastfed infant.

Following these precautions can lower the risk of neonatal sedation.

Numerous professional organizations and regulatory agencies recommend that other agents are preferred over codeine or to avoid codeine completely during breastfeeding; however, other opioid alternatives have been studied less and may not be safer.

Drug Levels:
Propoxyphene is metabolized to active norpropoxyphene (25%) and to several inactive metabolites.

Norpropoxyphene has a 30 to 36 hour half-life.

The oral bioavailability of norpropoxyphene is unknown. Propoxyphene is available in 2 salt forms: 65 mg of the hydrochloride form is equivalent to 100 mg of the napsylate.

Effects on Lactation and Breastmilk:

Narcotics can increase serum prolactin.

However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider:

• Acetaminophen
• Butorphanol
• Hydromorphone
• Ibuprofen
• Morphine
• (Antitussive) Dextromethorphan

Codeine Drug Levels and Effects:
https://www.ncbi.nlm.nih.gov/books/NBK501212/

New Zealand Rivotril Data Sheet (PDF 10 pages):
https://medsafe.govt.nz/profs/Datasheet/c/CodeinePhosphatePSMtab.pdf

Erowid Experience Vault:
https://erowid.org/experiences/subs/exp_Codeine.shtml

Codeine (1,400 threads):
https://drugs-forum.com/forums/codeine.161/

It is reported that Elvis was found with ten times the standard amount of codeine in his body. He was also reportedly addicted to a variety of substances, such as diazepam, methaqualone, phenobarbital, ethchlorvynol and ethinamate. The toxicology report concluded, at the time, that 'the strong possibility is that these drugs were the major contribution to his demise'. But modern medical advancements now suggest that his underlying heart problems were exacerbated by the heady concoction of drugs found in his system - but they were not a direct cause.

Excerpt from Metro:
https://metro.co.uk/2017/08/16/how-did-elvis-presley-die-myth-and-legend-explored-as-the-king-is-remembered-40-years-on-6850638/

FDA Codeine Sulfate Tablets (PDF 13 pages):
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022402s000lbl.pdf

Janssen Tylenol with Codeine Monograph (PDF 39 pages):
https://www.janssen.com/canada/sites/www_janssen_com_canada/files/prod_files/live/twc2n3_cpm.pdf

Electronic Medicines Compendium Codeine Package Leaflet (PDF 2 pages):
https://www.medicines.org.uk/emc/files/pil.2375.pdf

Important Information:
You should not use codeine if you have severe breathing problems, a blockage in your stomach or intestines, or frequent asthma attacks or hyperventilation.

Codeine can slow or stop your breathing, and may be habit-forming. MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription.

Codeine is not for use in anyone under 18 years old.

Taking codeine during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Fatal side effects can occur if you use codeine with alcohol, or with other drugs that cause drowsiness or slow your breathing.

Do not drink alcohol. Dangerous side effects or death could occur.

Codeine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Interactions:

Drug Interactions (448) Alcohol/Food Interactions (1) Disease Interactions (17)

What other drugs will affect Codeine?
You may have breathing problems or withdrawal symptoms if you start or stop taking certain other medicines. Tell your doctor if you also use an antibiotic, antifungal medication, heart or blood pressure medication, seizure medication, or medicine to treat HIV or hepatitis C.

Opioid medication can interact with many other drugs and cause dangerous side effects or death.

Be sure your doctor knows if you also use:

• cold or allergy medicines, bronchodilator asthma/COPD medication, or a diuretic ("water pill")
• medicines for motion sickness, irritable bowel syndrome, or overactive bladder
• other narcotic medications - opioid pain medicine or prescription cough medicine
• a sedative like:
  • Valium - diazepam
  • alprazolam
  • lorazepam
  • Xanax
  • Klonopin
  • Versed
  • others
• drugs that make you sleepy or slow your breathing - a sleeping pill, muscle relaxer, medicine to treat mood disorders or mental illness
• drugs that affect serotonin levels in your body - a stimulant, or medicine for depression, Parkinson's disease, migraine headaches, serious infections, or nausea and vomiting

This list is not complete. Other drugs may interact with codeine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

A total of 448 drugs are known to interact with Codeine.

• 116 major drug interactions
• 329 moderate drug interactions
• 3 minor drug interactions

Codeine Drug Information:
https://www.drugs.com/codeine.html

Drugs.com Codeine Monograph:
https://www.drugs.com/monograph/codeine-phosphate.html

Tylenol with Codeine (acetaminophen/codeine phosphate)

Maximum Dosage:
Prescribers Digital Reference
Prescribers Digital Reference Tylenol with Codeine No.3 and Tylenol with Codeine No.4 Drug Summary: https://www.pdr.net/drug-summary/Tylenol-with-Codeine-acetaminophen-codeine-phosphate-277
NOTE: For combination products containing acetaminophen, total daily intake of acetaminophen from all sources should be considered and may be the dose-limiting consideration for acetaminophen; codeine products.
Adults:	Acetaminophen 4,000 mg/day PO; codeine 60 mg/dose PO; some clinicians have recommended the following maximum dosages: for pain, codeine 360 mg/day PO; as an antitussive, codeine 120 mg/day PO.
Geriatric:	Acetaminophen 4,000 mg/day PO; codeine 60 mg/dose PO; some clinicians have recommended the following maximum dosages: for pain, codeine 360 mg/day PO; as an antitussive, codeine 120 mg/day PO.
Adolescents:	Safety and efficacy have not been established.
Children:	12 years: Safety and efficacy have not been established.
Children:	1 to 11 years: Use is contraindicated.
Infants:	Use is contraindicated.

codeine (Rx)

Black Box Warnings:
codeine (Rx): https://reference.medscape.com/drug/codeine-343310
Opioid analgesic risk evaluation and mitigation strategy (REMS) Drug exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death; assess each patient's risk prior to prescribing drug, and monitor all patients regularly for the development of these behaviors and conditions To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers Healthcare providers are strongly encouraged to: Complete a REMS-compliant education program Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist Consider other tools to improve patient, household, and community safety Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with therapy Monitor for respiratory depression, especially during initiation of therapy or following a dose increase Respiratory depression and death reported following tonsillectomy and/or adenoidectomy in patients that appeared to be rapid metabolizers of codeine due to CYP2D6 polymorphism Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children Life-threatening respiratory depression and death have occurred in children who received codeine; most of reported cases occurred following tonsillectomy and/or adenoidectomy and many of the children had evidence of being ultra-rapid metabolizers of codeine due to a cytochrome P450 (CYP) 2D6 polymorphism Avoid use of in adolescents 12-18 years of age who have other risk factors that may increase their sensitivity to respiratory depressant effects of codeine Neonatal Opioid Withdrawal Syndrome Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts; if opioid use is required for a prolonged period in a pregnant woman, advise patient of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of CYP3A4 inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors with codeine are complex; use of CYP3A4 inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors with drug requires careful consideration of effects on parent drug, codeine, and active metabolite, morphine Risks from concomitant use with benzodiazepines or other CNS depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death Reserve concomitant prescribing of with benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate Limit dosages and durations to minimum required Follow patients for signs and symptoms of respiratory depression and sedation

US National Library of Medicine Dailymed Codeine Sulfate Drug Label Info:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5819bdf7-300e-45b8-8f3a-447b53656293&audience=consumer

Experiences with Codeine
Forum (4355 posts):
https://healthunlocked.com/codeine

User Reviews Codeine Sulfate Oral Webmd:
https://www.webmd.com/drugs/drugreview-7420-codeine-sulfate-oral.aspx?drugid=7420&drugname=codeine-sulfate-oral

IMPORTANT WARNING:
Codeine may be habit forming. Take codeine exactly as directed. Do not take more of it, take it more often, or take it in a different way than directed by your doctor. Codeine may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. The risk that you will develop breathing problems may be higher if you are an older adult or are weak or malnourished due to disease. Codeine should never be used to treat pain or a cough in children younger than 18 years of age. Taking certain medications during your treatment with codeine may increase the risk that you will experience breathing problems or other serious, life-threatening breathing problems, sedation, or coma. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment.

Medlineplus Codeine:
https://medlineplus.gov/druginfo/meds/a682065.html

Codeine:

In 2013, about 361,000 kg of codeine were produced while 249,000 kg were used, which made it the most commonly taken opiate.

• An opiate
• Used to treat pain, coughing, and diarrhea
• It is typically used to treat mild to moderate degrees of pain

  Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

• It is generally taken by mouth
• It typically starts working after half an hour, with maximum effect at two hours
• Its effects last for about four to six hours
• Common side effects include vomiting, constipation, itchiness, lightheadedness, and drowsiness
• Serious side effects may include breathing difficulties and addiction
• Its use as of 2016 is not recommended in children
• Discovered in 1832

Codeine works following being broken down by the liver into morphine; how quickly this occurs depends on a person's genetics

GENERIC NAME: PAPAVERINE
BRAND NAME: Pavabid
This medication is used to increase blood flow throughout the body, including the heart and the brain. Papaverine is a vasodilator. It works by relaxing the muscles in the blood vessels.Papaverine is also an antiarrhythmic medication that treats certain abnormal heartbeats (ventricular arrhythmias). It works by blocking the abnormal electrical activity in the heart so a normal heart beat can return. It may also help the heart beat better by increasing the blood flow to the heart.

Excerpt from Medicinenet:
https://www.medicinenet.com/papaverine-oral/article.htm

Papaverine belongs to the group of medicines called vasodilators. Vasodilators cause blood vessels to expand, thereby increasing blood flow. Papaverine is used to produce erections in some men with erectile dysfunction. When papaverine is injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection. Papaverine injection should not be used as a sexual aid by men who do not have erectile dysfunction. If the medicine is not used properly, permanent damage to the penis and loss of the ability to have erections could result.

Geriatric:
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. Although there is no specific information comparing the use of papaverine for erectile dysfunction in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems - These conditions increase the risk of bleeding at the place of injection

• Liver disease - Papaverine can cause liver damage when it is given in ways that allow it to get into the bloodstream (by mouth or by injection into a muscle, a vein, or an artery); when papaverine is given by intracavernosal injection, liver damage is much less likely because the medicine enters the bloodstream very slowly

• Priapism (history of)
• Sickle cell disease - Patients with these conditions have an increased risk of priapism (erection lasting longer than 4 hours) while using papaverine

Papaverine (Injection Route):
https://www.mayoclinic.org/drugs-supplements/papaverine-injection-route/description/drg-20065314

Papaverine:

• An opium alkaloid antispasmodic drug
• Used primarily in the treatment of visceral spasm and vasospasm (especially those involving the intestines, heart, or brain), and occasionally in the treatment of erectile dysfunction. It is also used in the treatment of acute mesenteric ischemia
• Discovered in 1848

While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic morphine-like compounds

https://en.wikipedia.org/wiki/Papaverine

Noscapine's cough-suppressing capability was discovered in 1930. The drug was also found to be a potential oncology therapy during preclinical trials, where it exhibited less impact on healthy cells than currently available chemotherapy.

New natural techniques for the production of this medicine are necessary as currently opium poppy is the only feasible source but is limited by expensive controls and regulations. Noscapine obtained from the plant also takes a year to reach maturation stage, while the newly bioengineered yeast only needs three to four days as there are three separate sections of the noscapine biosynthesis pathway incorporated into a single yeast strain. Researchers used the CRISPR gene-editing tool to reconstruct the genes and allow them to better work with each other, increasing the production of a chemical in the yeast that ensures robust production of the drug. Smolke noted: "We're no longer limited to what nature can make. We're moving to an age where we can borrow nature's medicine-manufacturing processes and, using genetic engineering, build miniature living factories that make what we want."

Excerpt from Pharmaceutical Technology:
https://www.pharmaceutical-technology.com/news/stanford-university-devises-new-way-make-noscapine-drug/

Noscapine:

Also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane

• A benzylisoquinoline alkaloid
  

  Benzylisoquinoline Alkaloids:
  https://en.wikipedia.org/wiki/Benzylisoquinoline

• It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential.
• This agent is primarily used for its antitussive (cough-suppressing) effects.
• Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics
• First isolated in 1817

Recreationaly the effects, beginning around 45 to 120 minutes after consumption, are similar to dextromethorphan and alcohol intoxication

https://en.wikipedia.org/wiki/Noscapine

Isoquinoline alkaloids:

• Natural products of the group of alkaloids
• Chemically derived from isoquinoline
• They form the largest group among the alkaloids
• The isoquinoline alkaloids are primarily formed in the plant families of Papaveraceae, Berberidaceae, Menispermaceae, Fumariaceae and Ranunculaceae.

  The opium poppy, which belongs to the Papavaraceae family, is of great interest, since the isoquinoline alkaloids morphine, codeine, papaverine, noscapine and thebaine can be found in its latex.

Isoquinoline alkaloids can be further classified based on their different chemical basic structures. The most common structural types are the benzylisoquinolines and the aporphines. According to current knowledge, a total of about 2500 isoquinoline alkaloids are known nowadays, which are mainly formed by plants.

EMPIRIN TABLET
GENERIC NAME: Aspirin
Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions such as arthritis. Aspirin is known as a salicylate and a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking a certain natural substance in your body to reduce pain and swelling. Your doctor may direct you to take a low dose of aspirin to prevent blood clots. This effect reduces the risk of stroke and heart attack. If you have recently had surgery on clogged arteries (such as bypass surgery, carotid endarterectomy, coronary stent), your doctor may direct you to use aspirin in low doses as a "blood thinner" to prevent blood clots.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-6185/empirin-oral/details

FIORINAL
GENERIC NAME: Butalbital-Aspirin-Caffeine
This combination medication is used to treat tension headaches. Aspirin helps to decrease the pain from the headache. Caffeine helps increase the effects of aspirin. Butalbital is a sedative that helps to decrease anxiety and cause sleepiness and relaxation.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-15819/fiorinal-oral/details

TYLENOL
GENERIC NAME: Acetaminophen
This drug is used to treat mild to moderate pain (from headaches, menstrual periods, toothaches, backaches, osteoarthritis, or cold/flu aches and pains) and to reduce fever.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-7076/tylenol-oral/details

BAYER ASPIRIN, EASPRIN, ECOTRIN
GENERIC NAME: ASPIRIN
Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions such as arthritis. Aspirin is known as a salicylate and a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking a certain natural substance in your body to reduce pain and swelling. Consult your doctor before treating a child younger than 12 years.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-1082-3/aspirin-oral/aspirin-oral/details

SK APAP CODEINE TABLET
GENERIC NAME: ACETAMINOPHEN CODEINE
This combination medication is used to help relieve mild to moderate pain. It contains an opioid (narcotic) pain reliever (codeine) and a non-opioid pain reliever (acetaminophen). Codeine works in the brain to change how your body feels and responds to pain. Acetaminophen can also reduce a fever.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-57815/sk-apap-codeine-oral/details

FDA Fiorinal with Codeine (PDF 37 pages):
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019429s040lbl.pdf

Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of acetaminophen and codeine combination oral suspension in children younger than 3 years of age.

Safety and efficacy have not been established.

No information is available on the relationship of age to the effects of Tylenol with codeine tablets in the pediatric population.

Use of acetaminophen and codeine combination oral solution or tablets is not recommended in children younger than 12 years of age.

Safety and efficacy have not been established.

Acetaminophen and codeine combination should not be used to relieve pain after surgery to remove tonsils or adenoids in any children.

Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of acetaminophen and codeine combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney, heart, or lung problems, which may require caution and an adjustment in the dose for patients receiving acetaminophen and codeine combination.

Other Interactions:

• Cabbage
• Ethanol
• Tobacco

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease (adrenal gland problem)
• Alcohol abuse, history of
• Brain tumor
• Breathing problems (eg, chronic obstructive pulmonary disease [COPD], cor pulmonale, hypoxia, sleep apnea)
• CNS depression
• Drug abuse or dependence, or history of
• Enlarged prostate
• Head injuries
• Hypothyroidism (underactive thyroid)
• Increased pressure in the head
• Mental illness, history of
• Obesity (overweight)
• Problems with passing urine
• Weakened physical condition - Use with caution. May increase risk for more serious side effects

• Allergy to sulfites
• Asthma - Acetaminophen and codeine combination tablets contains sodium metabisulfite, which can cause allergic reactions in patients with these conditions

• Asthma, acute or severe
• Respiratory depression (serious breathing problem)
• Stomach or bowel blockage (eg, paralytic ileus)
• Surgery (eg, nasopharyngeal tonsils, tonsils) - Should not be used in patients with these conditions

• Kidney disease
• Liver disease - Use with caution. The effects may be increased because of slower removal of the medicine from the body

Acetaminophen And Codeine (Oral Route) (APAP wCodeine | Capital wCodeine | Pyregesic-C | Tylenol wCodeine | Tylenol wCodeine 3 | Tylenol wCodeine 4 | Tylenol with Codeine No 3 | Vopac):
https://www.mayoclinic.org/drugs-supplements/acetaminophen-and-codeine-oral-route/description/drg-20074117

Also known by the genericised trade name eucodeine, and the salt name also sometimes given as methobromide, this drug was first synthesized in Austria-Hungary in 1903. As it is a bromide in addition to a codeine salt, it has a dual mechanism of action and is indicated for pain with insomnia or nervousness and violent coughing. It is used in a different way than basic salts of codeine like the phosphate or hydrochloride owing to its dual action, it is considered to be a different drug related to codeine rather than merely a salt of it in many contexts.

US Pharmacopeial Convention Codeine-N-Oxide (PDF 7 pages):
https://cymitquimica.com/pdf-viewer?file=https://static.cymitquimica.com/products/45/pdf/sds-1143802.pdf#page=1&zoom=auto,-16,850

Codeine N-oxide is an alkaloid from Papaver somniferum (opium poppy). It was studied as a potential pharmaceutical drug and is considerably weaker than codeine. Codeine-N-oxide (genocodeine) is an active metabolite of codeine.