Module 3 - Sedative-Hypnotics PDF

MODULE 3- Sedative-Hypnotics Intro to Sedative-Hypnotic Agents - They are Central nervous system depressants. - Magnitude of Central nervous system depression produced by a drug at a particular dose, determines the effects that an agent produces. Low Dose...

MODULE 3- Sedative-Hypnotics Intro to Sedative-Hypnotic Agents - They are Central nervous system depressants. - Magnitude of Central nervous system depression produced by a drug at a particular dose, determines the effects that an agent produces. Low Dose High Dose Anti-anxiety Sedation Hypnosis (sleep) General Anesthesia Magnitudes of - treats anxiety - relieves - produces - induces general CNS depression disorders anxiety, drowsiness and anesthesia (generalized decreases aids in onset and (unconsciousness anxiety, and activity, maintenance without pain). obsessive moderate sleep. compulsive excitement, and disorder) calms an individual. Interactions between sedative-hypnotic agents with CNS depressants (alcohol, and antihistamines) are important and can be dangerous. Mechanisms of Action of sedative hypnotics - Most of the sedative-hypnotic drug classes decrease glutamate (excitatory neurotransmitter) induced nerve firing, by increasing inhibitory signaling. WITH sedative-hypnotics - Inhibitory signals from GABA neurons increase, and glutamate nerve firing decreases WITHOUT sedative hypnotics - Brain activity involves excitatory neurons, which release glutamate. Neurons fire when the excitatory inputs exceed inhibitory inputs. GABA signaling - GABA is the primary inhibitory neurotransmitter in the CNS. - Bonds to and selectively open chloride channels → chloride ions flow in and out when channels are open. - Chloride ions flow into postsynaptic neuron - Influx of chloride ions makes it hard for postsynaptic neurons to transmit incoming messages to other neurons, depressing CNS neuronal signaling. Drugs that bond to the chloride channel - Different sedative-hypnotics bind to a different site on the chlorine channel and enhance the inhibitory effect of GABA. - Results in an increase in synaptic inhibition and dampening of neuronal responses Benzodiazepines - Most widely prescribed drugs in the world Routes of Administration Mechanism of Action Therapeutic effects - Capsule or tablet - Activation of the - Relaxation, calmness - Some are intravenous benzodiazepine (decrease aggression), or intranasal use receptor increases the relief of anxiety or frequency of the tension. opening of the - Produces muscle chloride channel. relaxation and seizure-preventing effects. - Minimal suppression of REM-type sleep. Lethality of Benzodiazepines - Most involved in overdose - High therapeutic index= wide margin of safety (deaths from overdose are rare) - Death occurs following enormous dosages, rapid injection, or in combination with other sedating drugs Antidote for Benzodiazepines: Flumazenil (administered as an antidote during overdose)  - reverses effects in event of an overdose - Benzodiazepine receptor antagonist that blocks the effects of benzodiazepines Adverse effects of benzodiazepine use 1. Adverse effects of Short Term Benzodiazepine use Central Nervous System Breathing Motor coordination - Drowsiness, lethargy, - Respiratory - Moderate doses can fatigue, impairment of depression is observed impair motor thinking and memory following rapid coordination and - CNS depression intravenous driving. depends on the administration. - Patients taking them targeted therapeutic during the day should effect refrain from o[erating Ex. If the therapeutic goal is machinery. anti-anxiety, drowsiness may - Responses are be an adverse effect, but exaggerated as the would it be a therapeutic dose increases. effect if the goal was sedation? 2. Adverse effects of Long Term Benzodiazepine use - Some take large doses and have no evidence of major intoxication - Others show symptoms of chronic sedative-hypnotic intoxication (impaired thinking, poor memory and judgment, disorientation, in coordination and slurred speech. 3. Benzodiazepine use in special populations Pregnant people/Chestfeeding: Older adults - Benzodiazepines cross the placenta - Benzodiazepines can produce and distribute into the fetus. cognitive dysfunction in older adults.  - During the first trimester: results in - Should be used with caution at this small but significant risk of fetal age group. abnormalities. - Benzodiazepines are metabolized - Benzodiazepines are secreted into the slower in older adults than young milk, exposing nursing infants to adults leading to over-sedation,falls therapeutic or toxic doses of the drug and injury. and can result in sedation or death. Potential for misuse and SUD - Benzodiazepines can result in tolerance, withdrawal and addiction, - Misuse occurs in combination with alcohol which enhances CNS depression effects if both. Misuse potential Tolerance Withdrawal Addiction - Benzodiazepines - Tolerance - A mild but - May develop have weaker develops to the distinct in some reinforcing sedative effects and withdrawal individuals properties than impairment of can occur but not all. other drugs coordination, after - Inherent anxiolytic effects, therapeutic harmfulness is or euphoric effects. use exhibiting low and does not - the magnitude of anxiety, depress tolerance that headache and respiration at develops to insomnia. therapeutic benzodiazepines - Chronic use doses and does does not produce and sudden not often lead to clinical concerns. discontinuatio death on its own. - high degree of n leads to cross tolerance more extreme occurs among symptoms benzodiazepines, (agitation, and other seizures, and sedative-hypnotic paranoia)  drugs. - Occur less frequently than barbiturates How do benzodiazepines reduce an athlete's anxiety? - Benzodiazepines increase CNS depression in a dose dependent manner, therefore at low doses, they act as anti-anxiety agents. Barbiturates - Class of sedative hypnotics - Classified into their duration of action (1-2 days) or (3-8 hours) and (20 minutes) - Have been replaced by safer, more effective sedative hypnotics Routes of Administration: - Administered based on what they are treating. Ex. epilepsy (orally), anesthesia (intravenously) Mechanism of Action: - Activation of barbiturate receptor increases the duration of the chloride channel opening - Demonstrate full spectrum dose dependent CNS depression Anti-anxiety→ sedation→ hypnosis→ general anesthesia → death Therapeutic use: - Low doses= beneficial effects of tranquility and relaxation - Indice sleep if dose is sufficient - Ultra short and short acting barbiturates can be used to induce anesthesia - Some long acting agents can be used as antiepileptics Lethality: - Barbiturates have been replaced by newer and safer drugs because of their low therapeutic index - Lethal dose varies - Lethality due to depression of respiration is common Adverse effects of barbiturate use - They suppress REM-type sleep. 1. Short term use - Low doses result in mild euphoria and reduced interest in surroundings - Dizziness and mild impairment of motor coordination - Pleasurable state of intoxication and euphoria as the dose is increased - High doses depress the cardiovascular system, slowing the heart and lowering blood pressure. 2. Long term use - Chronic inebriation: memory, judgment and thinking impairment. - Individuals exhibit hostility and mood swings including depression. Potential for misuse and SUD - Used less frequently now - Illicit use problems continue Misuse potential Tolerance Withdrawal Addiction - Potential for - Tolerance - occurs after chronic - Addiction can misuse is equal can develop use result from to or greater than - High - symptoms include: regular use no alcohol degree of tremor, anxiety, matter the - Pleasurable cross weakness, and dose effects give a tolerance insomnia, as well as - Craving significant occurs postural hypotension. persists long degree of between - must be withdrawn after use has reinforcement barbiturates slowly under medical stopped - Inherent and other supervision.  harmfulness is sedatives high through injections due to the risk of death from respiratory depression or withdrawal. Comparisons: Benzodiazepines and Barbiturates Benzodiazepines Barbiturates Mechanism of action - Increases frequency - Increases the of opening the duration of the chloride channel opening of the chloride channel. Therapeutic uses - Acute anxiety states - Tonic-clonic (ie. grand - Sedation for minor mal) seizures, partial surgical procedures seizures. - Insomnia - Absence seizures, status epilepticus - Skeletal muscle spasms - Alcohol withdrawal Pharmacology - High therapeutic - Low therapeutic index index - Suppress REM sleep - Minimal suppression - Cause-dose dependent of REM sleep respiratory and - Decreased aggression, cardiovascular skeletal muscle depression relaxation - Lethality common,  - Has an anecdote: especially with Flumazenil alcohol - No antidote Misuse Misuse potential: low misuse Misuse potential equal to or potential and inherent greater than alcohol, and high harmfulness inherent harmfulness. Tolerance: Yes, develops to desired effects but not a Tolerance: yes problem clinically. Withdrawal: yes Withdrawal: yes, less Addiction: yes common than with barbiturates Addiction: Yes, in some cases Zopiclone and the Benzodiazepine-like drugs - Benzodiazepine-like drugs are another class of sedative hypnotics used to treat problems like anxiety or difficulty sleeping - BLD like zopiclone and zolpidem bind to a subset of the GABA receptors and cause sedation - They disturb sleep patterns (REM sleep) even less than benzodiazepines - These drugs should be used with caution in older adults \ Drugs that bind to the chloride channel Buspirone - Anxiolytic that doesn't act on the GABA receptor, but the serotonin receptor - Helps for generalized anxiety states - May be prescribed instead of a benzodiazepine or benzodiazepine-like drug. A1: zopiclone and the other benzodiazepine-like drugs have been shown to disturb skee patterns even less than the benzodiazepine. A2: Tolerance does not appear to be a problem for the clinical use of benzodiazepines, however it can develop to the sedative effects and impairment of coordination, the anxiolytic effect or the euphoric effects. Section 2- Alcohol Intro to alcohol - Alcohol (ethanol) is one of the 3 most used non medical drugs in Canada along with caffeine and nicotine. - Alcohol produces more health problems and death resulting in healthcare and social costs - Misuse and extensive use is due to the availability and permissive attitudes of society. ADME of alcohol 1. Absorption - Ethanol is absorbed rapidly by the stomach (20% is absorbed), and the upper small intestine (80% is absorbed). - Time from last drink to max blood alcohol concentration ranges from 30-90 minutes - Absorption rate is affected by Stomach emptying time or time required for alcohol to reach small intestine Ethanol [] is GI tract and presence of food 2. Distribution - Ethanol distributes throughout the entire total body water - Readily gains access to the brian and can cross the placenta and distribute throughout a developing fetus. 3. Metabolism: 4 main steps Alcohol dehydrogenase - Ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH) - Rate limiting step: speed of conversion sets the pace for the rest of metabolism Meos - Microsomal ethanol oxidizing system (MEOS) is part of the cytochrome P450 system - MEOS contributes to the metabolism of ethanol and the breaking down into acetaldehyde when ADH is at full capacity. Acetaldehyde dehydrogenase - Acetaldehyde is then converted to acetate by the enzyme aldehyde dehydrogenase (ALDH) Acetate - Acetate (acetic acid) further metabolized by a number of tissues into CO2 and water  - Both enzymes in the ethanol breakdown process show variation in the genes that code for ADH and ALDH - These genetic differences cause difference in the sped of breaking down alcohol - Rate of ethanol metabolism is unusual because it occurs at a constant rate regardless of the blood alcohol concentration (BAC). → about 120mg ethanol/kg body weight/hour 4. Excretion - Over 95% of ethanol in the body is eliminated by biotransformation, primarily in the liver and the remaining 5% is excreted in the breath, urine and sweat. Medical uses of ethanol - Alcohol sponge applied topically to treat fever - Skin disinfectant - Antidote in treatment of methanol (wood alcohol) poisoning - Hand sanitizer CNS effects of ethanol - Ethanol is classified as a general CNS depressant - CNS effects of ethanol are proportional to the blood alcohol concentration (BAC) - To convert BAC in mg/dL to a BAC represented as a percentage of weight/volume yoy move the decimal place 3 decimal pplaces to the left. - Ex. BAC of 100mg/dL is equal to 0.1g per 100 mL of blood or 0.1% weight/volume BAC and driving - In Canada for new drivers and drivers under the age of 22, a zero tolerance BAC applies. For all other drivers, having a BAC of 0.05% is a provincial offense, and having a BAC of 0.08% is a criminal offense. Mechanism of action of alcohol - Alcohol binds to the Cl ion channel and augments the GABA-mediated neuronal inhibition - Interaction of alcohol with the chloride ion channels on dopaminergic neurons in the reward areas of the brain, may explain the reinforcing effects of the drug. Effects of short- term use of alcohol Low doses (1-3 drinks) High doses (>5 drinks) Cardiovascular - Creates vasodilation - Depresses (flushing) of the cardiovascular system vessels to the skiing leading to alterations resulting in feelings of of the normal heart warmth rhythms Stomach - Leads to increased - Irritate stomach lining gastric secretion causing inflammation and erosion (gastritis) - Gastritis caused vomiting, abdominal pain and ulcers.  Liver - Occasional small - Alcohol binge will doses does not have a inhibit glucose significant effect on production and with the liver fasting can lead to low blood sugar Adverse effects of binge drinking 1. Memory Loss - Individuals lose memory of events that occurred when they were under the influence of alcohol. 2. Psychiatric effects - Heavy drinking leads to depression, irritability and over sedation - Negative moods can lead to self harm or acts of violence 3. Overdose - Excessive short term use can lead to overdose which suppresses respiratory use, and can induce a coma or death. Adverse effects of chronic high dose alcohol use 1. CNS - Alcohol damages axons of neurons within the brain, resulting in fewer connections between neurons which can decrease cognitive functioning affecting memory, judgment and thinking. (alcoholic dementia). 2. Cardiovascular - High chronic doses of alcohol can lead to alcoholic cardiomyopathy (destruction of or poor heart muscle). - Increased incidence of hypertension and stroke. 3. Liver - Chronic high doses leads to alcoholic liver disease which causes hospitalization and death Effects of alcohol use during pregnancy - Chronic use of high-dose ethanol can produce teratogenic effects in the embryo/fetus which can lead to Fetal Alcohol spectrum disorder (FASD) → group of conditions that  can occur in a person whose mother drank during pregnancy including fetal alcohol syndrome (FAS). Alcohol and drug interactions Alcohol use during drug therapy (effects of having a drug and ethanol in the body at the same time) - Ingestion of Ethanol and other CNS depressants leads to an additive or synergistic effect of CNS depression - Inhibition of metabolism of certain drugs (sedative hypnotics) Chronic use before drug therapy - Only occurs if there us no co-existing ethanol induced liver injury - Increases activity of metabolizing enzymes in the liver resulting in increased metabolism of certain drugs (sedative-hypnotics). Potential for Misuse and SUD Potential for Misuse Tolerance Cross tolerance Withdrawal Addiction - Misuse potential is - Tolerance does - cross tolerance occurs - Withdrawal - Compulsive moderate occur between ethanol and: produces desire to - Inherent harmfulness is - Tolerance 1. Sedative compensatory drink ethanol moderate develops during hypnotics excitation of exists the performance 2. General the CNS, and of tasks under anesthetics can create the influence - Higher dose of convulsions both these coma and drugs is possibly required to feel death. the effects. Drugs used to treat Alcohol use Disorder - Naltrexone (opioid antagonist is effective in the treatment of alcohol addiction).  - It diminishes the craving for ethanol and assists in the maintenance of abstinence, and blocks the activation of dopaminergic reward pathways in the brain. Summary Section 3: Cannabis Intro to Cannabis - Cannabis Sativa - 60 chemical compounds are found in Cannabis and are referred to as cannabinoids (CB) - 1-trans-delta-tetrahydrocannabinol (THC) is the most potent psychoactive agent in cannabis and accounts for most of its psychoactive effects. History of Cannabis 2700 BCE-1800 CE - Cannabis plants were used for manufacturing rope and for its mild intoxicating effects 1920s - Legislation that outlawed the use of cannabis was enacted and it is now known as a narcotic 1960’s - Use of cannabis increased from cold war and political and cultural climate change 1978 - The herbicide paraquat was under investigation by a USA-sponsored project in attempts of destroying the crop in mexico due to its ability to produce lung toxicity 1997 - Chargers were dismissed in relation to drug use - Canada changed the law allowing some uses of cannabis in the manufacturing of rope. Clothing and other hemp products 2005 - Health canada supported trials on the medical use of cannabis 2012 - Recreational use of cannabis was legalized in washington 2018 - Recreational cannabis became legal in canada Classification of Cannabis 1. Pharmacological  - Cannabis is classified as a CNS depressant, euphoriant and hallucinogen (hallucinogenic properties occur at high doses). 2. Legal - October 17th 2018, cannabis became legal in Canada. Administration of Cannabis - Cannabis is usually smoked or inhaled - Extracts containing concentrated amounts of cannabinoids typically in oil, which can be administered by vaping or oral consumption Mechanism of Action of Cannabis - THC binds specifically to receptors in the brain and spinal cord called type 1 cannabinoid receptors (CB) - Release of anandamide binds to the CB1 receptor inhibiting the release of excitatory neurotransmitters reducing cognitive function. Cannabinoid receptors 1. CB1 - THC is not an effective agonist but with a lot of receptors it does produce a response - CB1 receptors in the cerebral cortex mediate distortions of time, color, sound and taste. They also mediate the decrease in cognitive function and concentration - Receptors in the hippocampi may account for changes in memory and learning  - No CB1 receptors are present in the brain stem and don't suppress respiration. 2. CB2 - Receptors found outside of the CNS - Are not involved in psychoactive effects but may be involved in inflammation - Binding of THC to CB2 receptors on lymphocytes may explain immunosuppressive properties of THC. ADME of THC 1. Absorption - Inhaled: absorption is rapid from smoke, and onset is almost immediate with lasting effects of 3-4 hours. - Ingested: absorption of oral administration is slow and incomplete and onset of action is 30-60 minutes with less effects. 2. Distribution - THC rapidly distributes throughout the body especially to lungs, heart, brain and liver. - THC rapidly crosses placenta - THC is highly lipid soluble and will be stored in adipose tissues. 3. Metabolism - Metabolized slowly and metabolites can be measured in drug tests 4. Excretion - 30 minute half life, but elimination from adipose tissues may be longer. Effects of short term cannabis use CNS - Relaxation, drowsiness, euphoria, impaired motor coordination & increases appetite - As dose increases, a person may experience pseudo-hallucinations (person knows it’s a hallucination) Cardiovascular system - Increased heart rate - Increased blood flow to extremities  - Postural hypotension may occur (acute low blood pressure when standing or sitting up which can cause dizziness or fainting). GI tract - Increased appetite - Dryness of mouth and throat Other - Reduction of male sex drive - Disruption of ovarian cycle - Hangover when drug wears off Effects of Long term cannabis use Psychological Occasional low dose: no harmful psychological effects High doses: short term memory, lack of concentration. And loss of abstract thinking. - Amotivational syndrome → appears upon cessation of drug use Permanent effects: currently unknown. Cardiovascular - Cardiovascular effects are usually reversible - Changes in BP aren't serious, but increase of heart rate can be a problem for those with heart issues. - Respiratory - Bronchitis, asthma, sore throat, chronic irritation and damage to respiratory tract - Higher concentrations of tars and  carcinogens after long term use can be damaging. - Lung cancer and chronic obstructive pulmonary disease (COPD) Fertility Males: long term use can lead to decreased sperm Females: cycles can occur without ovulation Pregnancy: THC can freely cross developmental delays. Medical uses of Cannabis - Drugs that can bind to CB1&2 receptors that are less toxic than THC are to be developed. - Challenge for pharmacological use is deciphering between benefits and psychotropic effects Potential for Misuse and SUD 1. Tolerance Tolerance occurs to: - Psychoactive properties - Effects on cardiovascular system - Impairment of performance and cognitive function 2. Withdrawal - Sleep disturbance - Irritability - Loss of appetite - Nervousness$ - Mild agitation - Upset stomach - Sweating 3. Addiction - Addiction occurs especially for those who use cannabis to control psychological stress SUMMARY Section 4- Opioids Introduction to Opioids - Class of drug found in opium of the poppy plant - Produces morphine and codeine - Morphine is one of the most useful pharmacological drug but causes opioid use disorder (OUD) Classes of opioids 1. Endogenous Opioids - Opioids made in the body that exert analgesic effects - 3 families: enkephalins, endorphins and endorphins - Endogenous opioids affect the perception of pain and emotional response to pain → may influence mood 2. Natural Opioids Morphine - Binds directly to opioid receptors and is used clinically to treat severe acute and chronic pain and can cause euphoria Codeine - Codeine is converted to morphine in the body by live enzymes - Morphine is 10 times more potent than codeine - Found in tylenol 3  3. Semi-synthetic opioids → slightly altered versions of morphine that are chemically changed to obtain different pharmacological properties. Hydromorphone - Clinically used for analgesic (5x more potent than morphine) Diacetylmorphine - Brand name heroin, is used as an injectable opioid - Used as illicit use 4. Synthetic opioids - chemically synthesized to bind to the opioid receptor (designed to elicit similar properties as morphine) Fentanyl - 100 times more potent than morphine and was designed for treatment of severe acute and chronic pain. → contributes to OUD crisis Loperamide - Over counter drug that leverages constipation and diarrhea (side effects of opioid use) - The chemical structure allows very little to enter and remain in circulation but instead it stays in the intestine and is quickly metabolized → prevents illicit use. Methadone - Used for analgesia and can treat OUD - Prevents withdrawal symptoms Opioid Receptors - Locates in central and peripheral nervous systems - Located in GI tract and responsible for constipation caused by opioids 1. MU receptors - Present in brain and spinal cord - Mediate analgesic and are responsible for morphine-mediate depression of respiration in the brain stem. → difficult to obtain drugs with a separation between two responses - Receptors are involved in compulsive misuse of opioids 2. Kappa receptors - Involved in analgesia, dysphoria (state of uneasiness) and miosis (pinpoint pupils) 3. Delta - Involved in analgesic at spinal cord and brain - Modulate emotional response to opioids Mechanism of action of opioids Morphine and other opioids will block pain pathways in the spinal cord and brain and is primarily exerted through activation of mu opioid receptors. 1. Reduce Neurotransmitter release - Opioids prevent pain signals from traveling by reducing neurotransmitter release from presynaptic neurons and reducing the effect on the postsynaptic neurons 2. Reduce emotional reaction - Opioids reduce the emotional reaction to pain through modulation of the limbic system Short term effects of Opioids 1. Analgesia - Opioids lead to analgesia (loss of pain) , and indifference to pain - Loss of pain→ reduces intensity of pain and perception/no reaction to pain 2. Sedation and Hypnosis - Patients may be aroused but may experience drowsiness. Dreamy, mild dozing state - All opioid analgesics produce sedation 3. Suppression of Cough center - Suppression of the cough center in medulla prevents cough, and relieves coughs. 4. Respiratory depression  - Opioids suppress the respiratory center in the brainstem and the response to respiratory drive by carbon dioxide is stopped. Depression of respiration is the most important side effect of opioids and usually the cause of death. 5. Endocrine effects - Opioids reduce the release of the hormone that regulates the release of sex hormones from the hypothalamus - Drops of sex hormones and libido in men. 6. Miosis - Opioids cause constriction of the pupils (miosis) - All opioids that gain access to the CNS will cause pinpoint pupils 7. Heart rate and thermoregulation - Hgh doses of opioids can create an irregular heart rate, low body temperature, and cold and clammy school. 8. Decreased intestinal motility - Individuals will experience constipation Long term uses - Marked physiological deterioration or psychological impairment does not seem to occur with long-term use of opioids. Therapeutic uses of opioids - 3 main therapeutic uses 1. Relief of severe pain - Analgesic is the major use - Opioids can mitigate post-surgical pain and pain experiences by some terminally ill patients 2. Treatment of diarrhea - Loperamide is an over the counter opioid that is not analgesic and does not produce withdrawal - Controls diarrhea 3. Cough suppression  - Opioids are effective cough suppressants but better options with low misuse potential are available Opioids: potential for misuse Misuse Potential Risks of Injection Overdose - Most opioids have powerful - individuals who administer - overdose is a medical euphoric effects which leads drugs by injection are at emergency and overdose of to a large risk of misuse higher risk of infections at opioids can produce sites of injections and respiratory depression which Inherent harmfulness: internally. can cause death - Low moderate doses: not - HIV may be a result of - treatment consists of opioid high for morphine contaminated needles antagonists and support of - High doses: life threatening respiration and other vital → individuals are at risk the functions higher the dose because they - opioid antagonist naloxone are not sure what they are treats opioid overdose. An taking (lethal dose can be opioid antagonist is used to administered unknowingly). treat alcohol use disorder. Risk of OUD Tolerance Withdrawal Addiction - Tolerance occurs due - Opioid withdrawal is - Addiction occurs to to respiratory not life threatening euphoric effects depression and and manifests: analgesic effects. Restlessness, anxiety - Tolerance reverses in and insomnia a few days after use is Sweating, fever, chills discontinued Increased respiratory - Cross tolerance rate  between all opioid Cramping, retching analgesics occurs and vomiting proving they act on Diarrhea the same receptor. Symptoms are determined by particular drug, chronicity and pattern of use,daily dose, route of administration and whether other drugs are taken. Opioid use during pregnancy - Mother taking opioids during pregnancy is at risk of premature delivery and low birth weight. - At birth the baby undergoes termination of opioid exposure leading to specific withdrawal reactions: sleep problems, irritability and poor feeding. Treatment of OUD 1. Buprenorphine/Naloxone - Buprenorphine is a long acting synthetic opioid that binds to mu receptors → prevents withdrawal symptoms but decreasing euphoria and sedation - Naloxone injected: block opioid receptors causing withdrawal symptoms - Naloxone taken orally: naloxone is broken down before getting into circulation and has no significant effects 2. Methadone - Synthetic opioid that is effective following oral administration and has a longer duration of action - Misuse potential is lower - Removed potential risks of injections (taken orally) - Oral administration leads to a slower onset of pharmacological effects and less euphoria - Methadone is long acting and taken less often reducing misuse potential. SUMMARY