Buprenorphine

• euphoriafeelings of joy and happiness,
• reduced anxiety,
• relaxation ².

• drowsiness,
• confusiontrouble focusing, slow or disorganised thinking, poor short-term memory, unsure of time or place, or having difficulty following a conversation,
• disorientation ².

• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More – 30 – 60 minutes,
• sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More – 40 – 80 minutes ⁵, 30 – 60 minutes ⁶.
• all ROA’sroute of administration - where the drug gets into your body – 60 – 90 minutes ⁷.

• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More – 4 – 8 hours,
• sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More – 4 – 8 hours ⁵, 1 – 4 hours ⁶.

• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More – 8 – 14 hours,
• sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More – 10 – 18 hours ⁵.
• all ROA’sroute of administration - where the drug gets into your body – low hours ⁷,
• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More (low dose) – 8 – 12 hours,
• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More (high dose) – 24 – 72 hours ⁶.

• insufflatedInsufflating, commonly referred to as snorting, is a method of drug administration where powdered substances are inhaled through the nose. More – 1 – 3 days,
• sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More – 1 – 3 days ⁵,
• all ROA’sroute of administration - where the drug gets into your body – 1 – 16 hours ⁷.

Buprenorphine is a synthetic opioid analgesicpain relieving and thebaine derivative, with a longer duration of action than morphine. Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the CNSthe Central Nervous System, upon which certain drugs act. Its primary actions of therapeutic value are analgesiadecreased pain awareness. More and sedationthe state of being relaxed or sleepy because of a drug More. Buprenorphine may increase the patient’s tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesiadecreased pain awareness. More, alterations in mood, euphoriafeelings of joy and happiness and dysphoriaexperiencing little or no joy in their life, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Pharmacological effects peaks at 15 minutes and persists for 6 hours or longer when given intramuscularly. When given intravenously, the time to onset and peak effect are shortened ³.

31% bioavailability (sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More). Sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More absorption is also dependent on pH. The length of time the tablet is under the tongue has little effect on absorption. Although buprenorphine is rapidly absorbed from the oral mucosa, the absorption into the systemic is slower. The time to reach peak plasma concentration (Tmaxthe time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. More) varies between individuals (range of 40 minutes to 3.5 hours). How buprenorphine is formulated does not affect this pharmacokinetic parameter. It also undergoes extensive first-pass metabolism and as a consequence, has very low oral bioavailability. Coadministration with naloxone does not effect the pharmacokinetics of buprenorphine ³.

• oral 22%,
• sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More 30%,
• intramuscular 90% – 100% ⁷.

Hepatic. Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation. The N-dealkylation pathway is mediated by cytochrome P-450 3A4 isozyme. Norbuprenorphine, an active metabolite and has one-fifth of the pharmacologic activity of the parent compound, can further undergo glucuronidation ³.

• IVintravenous More administration, 0.3 mg = 1.2 – 7.2 hours (mean 2.2 hours),
• Sublingualthe delivery of medication beneath the tongue, allowing for rapid absorption into the bloodstream. More administration = 37 hours ³.

Buprenorphine, like morphine and other phenolic opioid analgesics, is metabolised by the liver and its clearance is related to hepatic blood flow. It is primarily eliminated via faeces (as free forms of buprenorphine and norbuprenorphine) while 10% – 30% of the dose is excreted in urine (as conjugated forms of buprenorphine and norbuprenorphine) ³.

LD50the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals. The LD50 is one way to measure the short-term poisoning potential (acute toxicity) of a material in rats 3.1511 mol/kg ³.

Tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More to many of the effects of buprenorphine develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 – 7 days for the tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More to be reduced to half and 1 – 2 weeks to be back at baseline (in the absence of further consumption). Buprenorphine presents cross-tolerance with all other opioids, meaning that after the consumption of buprenorphine all opioids will have a reduced effect ⁵.

Buprenorphine’s analgesicpain relieving effect is due to partial agonist activity at mu-opioid receptorsnerve endings that sense changes in the body More. Buprenorphine is also a kappa-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. The binding to the mu and kappa receptorsnerve endings that sense changes in the body More results in hyperpolarization and reduced neuronal excitability. Furthermore, buprenorphine slowly dissociates from its receptor. This observation would account for the longer duration of action compared to morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence. Its receptor fixation half life is 40 minutes which is significantly longer than morphine (milliseconds) ³.

• physical euphoriaan intense feeling of pleasure and well-being More,
• pupil constriction,
• appetite suppression,
• cough suppression,
• orgasm suppression,
• pain relief,
• respiratory depressionslowing the drive and effectiveness of breathing More,
• sedationthe state of being relaxed or sleepy because of a drug More,
• constipationmeans that you're not passing stools regularly or you're unable to completely empty your bowels. More,
• decreased heart rate,
• difficulty urinating,
• dizziness,
• itchiness,
• nausea ⁵.

• cognitive euphoriastate of intense well-being, happiness, and excitement More,
• anxiety suppression,
• decreased libido ⁵.

• internal hallucinationsbest described as the perception of imagery and scenes which are experienced exclusively within a layer in front of one's open or closed eye vision and not seamlessly within the external environment around oneself. At lower levels, internal hallucinations begin with imagery which does not take up the entirety of one's visual field and is distinctively separate from its background. These can be described as spontaneous moving or still images of scenes, concepts, places, and anything one could imagine. They are manifested in varying levels of detail, ranging from ill-defined and cartoon-like in nature to completely realistic and beyond realism through seemingly impossible, non-euclidean geometric forms. They rarely hold their form for more than a few seconds before fading or shifting into another image. More ⁵.

• blurred vision,
• confusiontrouble focusing, slow or disorganised thinking, poor short-term memory, unsure of time or place, or having difficulty following a conversation,
• difficult or troubled breathing,
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position,
• drowsiness,
• irregular, fast, slow, or shallow breathing,
• cyanosisbluish tinge to fingers and lips, caused by inadequate blood supply,
• pinpointthe pupils are very small. More pupils,
• relaxed and calm feeling,
• sleepiness,
• unusual tiredness or weakness ⁸.

• euphoriafeelings of joy and happiness,
• sedationthe state of being relaxed or sleepy because of a drug More,
• pain relief,
• elevated mood,
• overall feeling of contentedness ⁶.

• pupillary dilation ⁶.

• dysphoric mood,
• piloerectiona reaction of the sympathetic nervous system that causes hair follicles to stick up from the skin. More,
• nausea,
• vomiting,
• diarrhoeaWhere you frequently pass watery or loose faeces,
• muscle aches/cramps,
• yawning,
• lacrimationcrying more tears than is normal. More,
• mild fever,
• rhinorrhoeaa runny nose. More,
• insomniadifficulty in going to sleep or in getting enough sleep,
• craving,
• sweating,
• distress/irritability ⁶.

• fever,
• irritability,
• muscle aches,
• sleeping difficulties,
• nausea,
• vomiting,
• constipationmeans that you're not passing stools regularly or you're unable to completely empty your bowels. More ⁹.

• tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More,
• accidents,
• constipationmeans that you're not passing stools regularly or you're unable to completely empty your bowels. More,
• overdose ².

• dependence,
• respiratory problems,
• if injected – damage to veins and circulation ².

• Ketamine – Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspirationvomit being inhaled into the lungs, a potentially life-threatening condition More if they are not placed in the recovery position.
• MXE – This combination can potentiate the effects of the opioid.
• DXM – CNSthe Central Nervous System, upon which certain drugs act depression, difficult breathing, heart issues, hepatoxicrelating to or causing injury to the liver. More, just very unsafe combination all around. Additionally if one takes dxm, their tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More of opiates goes down slightly, thus causing additional synergistic effectsan effect arising between two or more agents, entities, factors, or substances that produces an effect greater than the sum of their individual effects More.
• Cocaine – Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulanta drug that acts on the Central Nervous System, increasing some rates of function such as heart-rate wears off first then the opiate may overcome the patient and cause respiratory arrestRespiratory arrest is caused by airway obstruction, decreased respiratory drive, or respiratory muscle weakness. More.
• Alcohol – Both substances potentiate the ataxialoss of motor coordination More and sedationthe state of being relaxed or sleepy because of a drug More caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspirationvomit being inhaled into the lungs, a potentially life-threatening condition More from excess. Memory blackouts are likely.
• GBL / GHB – The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspirationvomit being inhaled into the lungs, a potentially life-threatening condition More is a risk if not placed in the recovery position.
• Tramadol – Concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergisticallyThe effect arising between two or more agents, entities, factors, or substances that produce an effect greater than the sum of their individual effects. More present.
• Benzodiazepines – CNSthe Central Nervous System, upon which certain drugs act and/or respiratory-depressant effects may be additively or synergisticallyThe effect arising between two or more agents, entities, factors, or substances that produce an effect greater than the sum of their individual effects. More present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspirationvomit being inhaled into the lungs, a potentially life-threatening condition More is a risk if not placed in the recovery position. Blackouts/memory loss likely ⁷.

• PCP – PCP can reduce opioid tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More, increasing the risk of overdose,
• Nitrous oxide – Both substances potentiate the ataxialoss of motor coordination More and sedationthe state of being relaxed or sleepy because of a drug More caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspirationvomit being inhaled into the lungs, a potentially life-threatening condition More is a risk if not placed in the recovery position. Memory blackouts are likely.
• Amphetamines – Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulanta drug that acts on the Central Nervous System, increasing some rates of function such as heart-rate wears off first then the opiate may overcome the patient and cause respiratory arrestRespiratory arrest is caused by airway obstruction, decreased respiratory drive, or respiratory muscle weakness. More.
• MAOIsMAOIs may be used to treat the symptoms of depression. More – Coadministration of monoamine oxidase inhibitors (MAOIsMAOIs may be used to treat the symptoms of depression. More) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresisexcessive sweating, hyperpyrexiaan excessive elevation of body temperature above the average normal temperature. More, flushing, shivering, myoclonusa brief, involuntary twitching of a muscle or group of muscles. More, rigidity, tremor, diarrhoeaWhere you frequently pass watery or loose faeces, hypertensionhigh blood pressure, tachycardiarapid pulse rate, seizuresthe outward effect can vary from uncontrolled jerking movement (tonic-clonic seizure) to as subtle as a momentary loss of awareness More, and coma. Death has occurred in some cases ⁷.