Drug Cocktails

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Alcohol

Booze, ethyl or ethanol, adult beverage, brew, brewski, liquor, drink, shot, sauce, rot gut, hooch, giggle juice, moonshine, jello shots, wobbly pop

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Interaction

a) As a CNS depressant, oxycodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as alcohol. Combined use of opioids and alcohol may lead to sedation and respiratory depression. A study found that alcohol increased oxycodone induced respiratory depression in opioid-naive patients.

b) Oxycodone 10 mg in combination with ethanol produces greater abuse liability-related subjective effects than either substance alone in narcotic naive adult subjects. The effect was confined to lower doses of ethanol (0.3 g/kg). Somewhat surprisingly, psychomotor and cognitive performance was unaffected by combination oxycodone and alcohol use over either drug alone. They may detected impairment if higher doses of ethanol had been tested, but whether an opioid combined with a higher dose of ethanol would result in greater impairment is open to question.

c) A study found that the median time to maximum concentration of extended-release oxycodone with sequestered naltrexone (Troxyca ER, formerly known as ALO-02) was decreased from 12 hours to 8 hours when this formulation was administered with 40% ethanol. AUC increased by 13% and the maximum concentration increased 37%. No changes were seen with 20% ethanol compared to water.

d) A study found regular alcohol consumers (daily intake: 20-40 g) required higher concentrations of related opioid alfentanil than individuals who were lifelong abstainers or only drank alcohol occasionally (<60 g per year).

Mechanism

a) Additive CNS depression effects.

d) Chronic consumption of alcohol can produce substances (tetrahydropapaveroline and salsolinol) that act like opioid agonists, potentially inducing tolerance to opioids.

Significance

a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

b) Oxycodone in combination with low dose ethanol may increase the abuse liability over either drug alone.

c) Alcohol may compromise the extended release profile of some oxycodone formulations, such as Troxyca ER. The Troxyca ER approval was cancelled by the US FDA in May 2018. This product is not available in Canada.

d) Regular alcohol consumption may result in opioid tolerance and higher than expected opioid dose requirements.

Serious Risk for Harm

Oxycodone and alcohol are both 'CNS depressants' which means they slow the brain. Oxycodone is a strong opioid can cause sleepiness, dizziness and confusion. Alcohol can make this worse, and make it more dangerous to drive or do activities that require alertness and attention. Mixing oxycodone with alcohol may cause dangerously slowed breathing, and even death.

Think First

Chronic alcohol use can increase your tolerance to opioids, including oxycodone. Tell your doctor if you drink alcohol regularly.

Tobacco

smokes, butts, cigs, cigars, darts, stogies, cancer sticks, chew, dip

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Interaction
A prospective study including 848 patients undergoing surgery compared opiate use during the first 72h after surgery. Male smokers required more opiate analgesics compared with male non-smokers and past-smokers. Male smokers also reported more pain on day 1 after surgery.

A study involving 7 women during caesarean recovery found that weight adjusted morphine use over 24h was 1.8mg/kg in smokers and 0.64mg/kg in non-smokers. Another study also found increased morphine requirements in smokers.

Mechanism
Nicotine in cigarettes may blunt a patient’s pain perception (potentially by increasing plasma beta-endorphins), thus increasing baseline patient analgesia prior to hospitalization (which may then ceased upon admission to hospital).

Significance
Knowledge of patient’s current smoking status upon hospitalization or prior to surgery may help optimize initial pain management following a surgical procedure.

Think First

Smoking cigarettes regularly could change the amount of opioid painkillers (like oxycodone) required for pain control. On-and-off cigarette smoking could make pain relief from use of opioids inconsistent.

Caffeine

coffee, java, joe, soda, pop, tea, energy drinks (Red Bull®, Monster®, Rock Star®, Amp®, NOS®, Full Throttle®, 5-hour Energy Drink®, Beaver Buzz®), chocolate, cocoa

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Interaction
No information currently available.

Unknown Dangers

Unknown dangers.

Cannabis/ Hash

Marijuana, mary jane, BC bud, blunt, chronic, J, jay, joint, hemp, pot, grass, herb, 420, dope, THC, weed, reefer, ganja, gangster, skunk, hydro, hash oil, weed oil, hash brownies, grease, boom, honey oil, K2, spice, poppers, shatter, budder

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Interaction
a) Tetrahydrocannabinol (THC), the main active ingredient in cannabis, releases endogenous opioid peptides dynorphin A, to enhance action of related drug morphine in the spinal cord, indicating a synergistic interaction between the endogenous opioids and cannabinoid system.

A study in 21 patients maintained on stable doses of morphine sustained-release or oxycodone sustained-release taken twice daily found that inhaled vaporized cannabis (900 mg once on day one, three times daily on days 2-4, and once on day 5) did not change the AUC of either opioid. Pain scores were decreased by an average of 27% but this was only statistically significant for morphine.

b) As a CNS depressant, oxycodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as cannabis.

Mechanism
a) The authors postulate that a cannabinoid receptor linked to the endogenous opioid system may exist.

b) The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

Significance
a) Discovery of these receptors may be important in future treatments of pain. Cannabis may improve pain and reduce opioid requirements, but more data is required.

b) Concomitant use of opioids and cannabis is not advisable. It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

Serious Risk for Harm

Oxycodone and cannabis are both 'CNS depressants', which means they slow the brain. Mixing oxycodone with cannabis may cause slowed breathing, and even death. Oxycodone is a strong opioid and can cause sleepiness, dizziness and confusion. Cannabis can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Cocaine/ Crack

coke, snow, flake, nose candy, blow, lady white, stardust, rock, crystal, bazooka, moon rock, tar

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Interaction
A retrospective study found that mechanically ventilated trauma patients who had used cocaine before admission had similar opioid requirements to those who had a negative urine drug screen for cocaine.

Unknown Dangers

Unknown dangers.

Opioids

codeine, Tylenol #3®, cody, meperidine, Demerol®, DXM, dextromethorphan, robo, skittles, morphine, morph, monkey, methadone, bupe, sub, or dollies, oxycodone, Oxycontin®, hillbilly heroin, OxyNeo®, OC, oxy, roxy, percs, fentanyl, Sublimaze®, Duragesic®, china white, hydrocodone, Hycodan®, Vicodin®, suboxone®, buprenorphine, vike, heroin, H, horse, junk, smack, brown sugar, black tar, down, china white, purple drank, W18, carfentanil, elephant tranquilizer, loperamide, lope, lean

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Interaction
ALL OPIOIDS: a) As oxycodone is an opioid itself, concomitant use with another opioid would result in additive effects including adverse/toxic effects. As a CNS depressant, morphine has the potential to enhance the adverse or toxic effects of other CNS depressants, such as other opioids.

Combined use of multiple opioids may lead to sedation and respiratory depression. It can also increase the risk for opioid overdose, which may be fatal (symptoms may include decreased level of consciousness and pinpoint pupils, slowed breathing and heart rate, sometimes to a stop, blue lips and nails due to insufficient oxygen in the blood, seizures and muscle spasms).

b) Concomitant use of oxycodone and opioids increases the risk of secondary constipation, potentially leading to hemorrhoids, rectal prolapse, and fecal impaction.

c) Opioids that are agonist/antagonists (buprenorphine, butorphanol, nalbuphine, pentazocine) may precipitate opioid withdrawal if given to patients maintained on oxycodone.

MORPHINE: A 43-year-old woman developed consciousness disorder and respiratory insufficiency during treatment with oral sustained-release oxycodone and patient-controlled analgesia (PCA) with morphine.

REMIFENTANIL: A study in 45 patients found that intra-operative remifentanil (mean infusion rate 300 ng/kg/min; a relatively large dose) did not alter pain scores or oxycodone consumption post-op.

Mechanism
ALL OPIOIDS: a) Additive CNS and respiratory depressant effects.

b) Opioids can cause constipation. The effect may be additive with multiple opioids.

c) The partial agonist/antagonist will not have the same effect as a pure agonist, such as codeine, and this could precipitate withdrawal symptoms.

MORPHINE: A large morphine dose, combined with the ongoing delivery of oxycodone from a sustained-release preparation was the likely cause of this near fatal opioid overdose.

Significance
ALL OPIOIDS: a) Concomitant use of multiple opioids is unusual. It would be important to monitor the patient for any excessive CNS depression. It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

It is important to warn patients to avoid using combinations of opioids if not being monitored closely. Inform patients who use combinations of strong opioids of the signs of opioid overdose, and how they or people around them can get help (by contacting emergency services, or administering naloxone (Narcan) if available).

b) Encourage patients to exercise regularly (ideally 30-60 minutes of aerobic exercise at least 5 times weekly) if possible, maintain a fibre intake of 25-30 grams/day, and not ignore the urge to defecate. Supplementary use of laxatives such as PEG 3350 may be necessary if it has been more than 3 days since they have had a bowel movement, or if constipation has become a chronic condition. Attempt to use the lowest effective dose of each agent to minimize this adverse effect.

Serious Risk for Harm

Oxycodone and opioids are 'CNS depressants' which means they slow the brain. Mixing oxycodone with opioids may cause dangerously slowed breathing and even death. Together they also cause sleepiness, dizziness, confusion and make it more dangerous to drive or do activities that require alertness and attention.

Think First

Taking oxycodone can make you constipated. Other opioids can make this worse. To help keep your bowels moving properly, try to exercise for 30 to 60 minutes 5 times a week, eat high fibre foods (for example, whole grains and fruits like bananas and kiwi fruit), and don’t “hold it in” when you need to use the washroom.

See your pharmacist, nurse or doctor for advice about laxatives if constipation becomes problematic for you (for example, pain with bowel movements or more than 3 days between bowel movements).

Think First

BUPRENORPHINE, BUTORPHANOL, NALBUPHINE, PENTAZOCINE: Taking these opioids with oxycodone can make oxycodone not work as well as expected. It could also give you symptoms of opioid withdrawal.

Amphetamines/ Stimulants

uppers, ecstasy, E, X, Molly, mesc, XTC, love drug, MDA, MDE, Eve, MDMA, adam, disco biscuit, bennies, black beauties, Dexedrine®, Adderall®, dexies, Ritalin®, speed, crystal, meth, ice, glass, crank, tweak, cat, qat, kat, khat, bath salts, Ivory Wave, Vanilla Sky, Cloud 9

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Interaction
a) Dextroamphetamine and methylphenidate have been shown to increase the analgesic effects of the related drug morphine. Dextroamphetamine (0.215 mg/kg) combined with low-dose morphine (0.15 mg/kg) increased the analgesic effect and antagonized respiratory depression of morphine for more than five hours. Dextroamphetamine combined with high-dose morphine (0.3 mg/kg) was unable to completely reduce the respiratory depressant effect, and some residual effects of morphine persisted at 23 hours.

Methylphenidate reduced the sedative effects of opioids in 28 chronic cancer pain patients and increased analgesic effects.

b) A retrospective study found that mechanically ventilated trauma patients who had used amphetamines before admission had similar opioid requirements to those who had a negative urine drug screen for amphetamines.

Significance
a,b) Combination dextroamphetamine-morphine has been shown to provide increased analgesia with fewer side effects while increasing the analgesia-to-respiratory depression ratio. Combination methylphenidate-morphine has been shown to provide increased analgesia with reduced sedation. This combination may be useful in the post-operative setting. However, the study described in b) shows that this may not always be the case, and it may not be appropriate to empirically reduce analgesic doses in patients using amphetamines.

Think First

For some medical reasons your doctor may prescribe you oxycodone and an amphetamine or stimulant together, but using amphetamines or stimulants without your doctor knowing is a risk.

Phencyclidine/ Ketamine

PCP, angel dust, PeaCe Pill, rocket fuel, love boat, embalming fluid, elephant tranquilizer, hog, illy, wet, wet stick, dipper, toe tag, cadillac, snorts, or surfer, Special K, vitamin K, CVR, cat tranquilizer, cat valium, jet, kit kat, Ketalar®

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Interaction
KETAMINE: a) As a CNS depressant, oxycodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as ketamine. Combined use of opioids and ketamine may lead to sedation and respiratory depression.

b) Various studies have investigated the use of adjunctive ketamine peri-operatively or post-operatively. Some of the studies have found that ketamine reduces intra-operative opioid requirements, post-op pain and opioid consumption, and post-op nausea and vomiting. However, other studies have not found statistically significant differences for these results.

c) A review found that ketamine may be effective as an alternative or adjunct to opioids for acute pain in the emergency department when patients do not respond to conventional therapies.

PHENCYCLIDINE: No information currently available.

Mechanism
KETAMINE: a) Additive CNS depressant effects.

Significance
KETAMINE: a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

b,c) Ketamine may be effective as an adjunctive analgesic for post-op pain and to reduce post-op nausea/vomiting, as well as for acute pain. However, the evidence is still conflicting. The current studies did not report an increase in serious adverse effects with the combination.

Serious Risk for Harm

KETAMINE: Oxycodone and ketamine are 'CNS depressants' which means they slow the brain. Mixing oxycodone with ketamine may cause slowed breathing, and even death. Together they also cause sleepiness, dizziness, confusion and make it more dangerous to drive or do activities that require alertness and attention.

Unknown Dangers

PHENCYCLIDINE: Unknown dangers.

LSD/ Hallucinogens

acid, blotter, cartoon acid, hit, purple haze, trip, white lightning, raggedy ann, sunshine, window-pane, microdot, boomers, buttons, mesc, peyote, salvia, morning glory seeds, flying saucers, licorice drops, pearly gates, magic mushrooms, shrooms

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Interaction
No information currently available.

Unknown Dangers

Unknown dangers.

Benzodiazepines

benzos, downers, tranquilizers, tranks, Ativan®, Halcion®, Klonopin®, Rivotril®, Restoril®, Serax®, Valium®, Xanax®, Rohypnol® (roofies, rope, the forget or date rape pill)

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Interaction
ALL BENZODIAZEPINES: a) As a CNS depressant, oxycodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as benzodiazepines. Combined use of opioids and benzodiazepines may lead to sedation and respiratory depression.

b) Benzodiazepines have been implicated in the sudden death of patients who abuse opioids.

c) A study found that in chronic pain patients, benzodiazepine use was associated with increased self-reported pain severity and use of higher doses of opioids. Some data shows that diazepam may increase pain scores in patients taking related medication morphine. Alternatively, midazolam appears to reduce the dose of related medication morphine required for post-op analgesia.

DIAZEPAM: Related drug morphine delayed the absorption of diazepam.

Mechanism
BENZODIAZEPINES: a) Additive CNS depressant effects.

b) Additive CNS depression resulting in respiratory depression and coma is likely a factor.

DIAZEPAM: Opioids delay gastric emptying and therefore reduce the absorption rate of diazepam.

Significance
a,b) While concomitant use of opioids and benzodiazepines may be clinically appropriate in some situations, it is important to monitor the patient for excessive CNS and/or respiratory depression.

It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

c) Whether these results generalize to oxycodone is unknown.

DIAZEPAM: Whether this effect generalizes to oxycodone is unknown.

Serious Risk for Harm

Oxycodone and benzodiazepines are 'CNS depressants' which means they slow the brain. Mixing oxycodone with benzodiazepines may cause slowed breathing and even death. Together they also cause sleepiness, dizziness, confusion and make it more dangerous to drive or do activities that require alertness and attention.

There are medical reports of deaths in patients who use opioids and benzodiazepines together.

Think First

Opioids may slow down the absorption of benzodiazepines after you take them. This means the benzodiazepine would take longer to work and may not work as well as expected.

Think First

Doctors sometimes prescribe opioids like oxycodone and benzodiazepines together, but this is done carefully in a medical setting with close monitoring.

References

[+]

also see MORPHINE

Creekmore FM, Lugo RA, Weiland KJ. Postoperative opiate analgesia requirements of smokers and nonsmokers. Ann Pharmacother 2004; 38: 949-53.  [PubMed Citation]

Lemmens HJ, Bovill JG, Hennis PJ, et al. Alcohol consumption alters the pharmacodynamics of alfentanil. Anesthesiology 1989; 71: 669-74.  [PubMed Citation]

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2021; August 22, 2021.

Malhotra B, Matschke K, Wang Q, et al. Effects of Ethanol on the Pharmacokinetics of Extended-Release Oxycodone with Sequestered Naltrexone. Clin Drug Investig 2015; 35: 267-74.  [PubMed Citation]

Preston CL (Ed), Stockley’s Interactions Checker. [online] London: Pharmaceutical Press. (accessed on August 22, 2021).

Therapeutic Research Center. Natural Medicines [Internet]. Somerville (MA): Oxycodone; [cited August 24, 2021].

van der Schrier R, Roozekrans M, Olofsen E, et al. Influence of Ethanol on Oxycodone-induced Respiratory Depression. Anesthesiology. 2017; 126 :534-42.  [PubMed Citation]

Welch SP, Eads M. Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Res 1999; 848: 183-90.  [PubMed Citation]

Zacny JP, Guttierez S. Subjective, psychomotor, and physiological effects of oxycodone alone and in combination with ethanol in healthy volunteers. Psychopharmacology 2011; 218: 471-81.  [PubMed Citation]

The Drug Cocktails website – “Facts for Youth about mixing Medicine, Booze and Street Drugs” (the “Site”) has been developed as a resource for youth and staff within Children’s & Women’s Health Centre of British Columbia Branch (C&W) for Provincial Health Services Authority and its branch agencies (PHSA)(C&W and PHSA together the “Societies”). There are support systems at the Societies which may not exist in other clinical settings and therefore adoption or use of this manual is not the responsibility of the Societies. Agencies other than the Societies should use Cocktails as a guideline for reference purposes only. The contents of this website were current at the time of development in July 2013. The Societies are not responsible for information that has changed after that time, whether incorporated into the Site or not.

The Site contains best practice knowledge, but practice standards may change as more knowledge is gained. Decision making in a specific context remains the responsibility of attending professionals. Nothing on the Site should in any way be construed as being either official or unofficial policy of the Societies.

Contact information and links to websites contained on the Site are provided for convenience only. The Societies cannot guarantee that the information, links or content from these links remain current. Providing a contact or link does not mean that the Societies endorse the views, products or services that may be offered via the link. The Societies assume no responsibility or liability arising from any error in, or omission of, information or from the use of any information, link, contact, opinion, advice or similar, provided on the Site.

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oxycodone

References

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