now that we are done covering the recreational stimulants we will now move to the opposite category the recreational depressants depressants are the yin to the stimulant Yang activating the parasympathetic nervous system and causing feelings of relaxation and sedation rather than the manic energy bursts of stimulants we'll go over three main classes of recreational and depressants alcohol benzo isipin and opiates in addition we'll briefly cover how to treat issues like addiction and overdose related to each drug class we'll start with alcohol the second most commonly used psychotropic substance in the world just after caffeine onethird of the world's population consumes alcohol on a regular basis whether in the form of beer wine mixed drink or Liquors alcohol acts primarily by altering the lipid Bayer surrounding the Gaba receptor which changes its confirmation and enhances Gaba Transmission in addition alcohol interacts with serotonin dopamine all three glutamate receptors in various ion channels however all you really need to know at this level is that it works primarily on Gaba the fact that alcohol is legal in the United States and many other countries does not mean that it is somehow more benign than illicit drugs in fact on the scale of all psychoactive substances alcohol is among the highest in terms of lethality and moderately high for dependence and abuse potential this serves to underscore the point that legality does not equal safety and vice versa this chart put up by the World Health Organization should really drive the point home unlike the previous chart this one shows actual harm done by each drug taking into account the number of people using them given the widespread use of alcohol it gets the number one spot by a mile surpassing even heroin and crack cocaine although on a perad basis it's definitely less harmful than those drugs alcohol intoxication is graded by blood alcohol content initially users will experience some mild Euphoria and relaxation as intoxication increases the depressant effect of alcohol becomes clear and users become increasingly sedated with slurred speech delayed responses and reaction times axic walking and movements and emotional libility with further intoxication users become confused disoriented and experience the classic room spinning with subsequent nausea and vomiting past the blood alcohol content of 3 severe stuper and Consciousness respiratory depression and potentially even death can occur following the first rule of neurotransmission what goes up must come down or in this case what goes down must come back up rebounding from a depressed state users experience a feeling of anxiety and activation with many finding it difficult to sleep in more severe cases patients can develop seizures and Vital sign instability owing to overactivation of the sympathetic nervous system this can lead to significant morbidity and mortality and before the Advent of modern medicine patients in severe alcohol withdrawal had a 35% chance of dying two quick clinical pearls related to alcohol first alcohol causes liver damage and this can be recognized by a greater increase than than alt you you can remember this by thinking of a and the letters in the word wasted second long-term alcohol use can cause a deficiency of thiamine or vitamin B1 you can remember this Association by thinking of a drunk man slurring the phrase I'm sorry thomine a drunken stuper if you make the I into a one you can remember that thomine is vitamin B1 as well because of the significant morbidity and mortality associated with it let's spend a few more moments going over alcohol withdrawal in more detail remember that as stated before withdrawal from a depressant such as alcohol is much worse from a clinical standpoint than withdrawal from a stimulant there are some clinical diagnoses that are associated with alcohol withdrawal that we need to go over the most feared complication of alcohol withdrawal is delirium tremin also known as DTS delirium tremin typically occurs in patients with a long history of chronic alcoholism and even with medical treatment is associated with a 5 to 15% risk of death often due to status epilepticus indor cardiovascular collapse about 2 to 3 days after the last drink patients with DTS experience significant shaking of the body hallucinations extreme Vital sign instability and seizures you need to be able to recognize this clinical picture as it requires a prompt response you can remember this using the Demonic DTS are hell D for delirium or the significant confusion and agitation that accompanies DTS t for Tremor s for sympathetic overactivation resulting in Fever hypertension tachicardia and teyia H for hallucinate ations primarily visual e for elevated ESR L for Luc cytosis and the second L for lfts use this pneumonic to rapidly recognize the clinical picture as these patients need to be in the ICU for closer monitoring you should be assessing for DTS on a daily basis while taking care of any patient detoxing from alcohol the treatment for DTS and for severe alcohol withdrawal in general is benzo aines while it is seemingly counterintuitive to treat Gaba withdrawal by giving a drug that activates gab it even more the use of a controlled taper allows for a slower safer return to Baseline rather than the erratic and extreme swings in physiology seen in unopposed withdrawal you can see that in this graph where the Blue Line shows what happens in unopposed alcohol withdrawal whereas the green line shows a steady more controlled return to Baseline seen with benzo aine treatment The Secret of successful treatment is to give as many benzo aines as it takes to suppress symptoms in the first 24 hours then taper off by about 10 to 20% each day one last note on alcohol withdrawal there is another clinical syndrome known as alcoholic hallucinosis that is easily confused for delirium tremens as both occur during alcohol withdrawal and both are characterized by an altered sensorium however it's important to distinguish between the two as alcoholic hallucinosis is much more benign than DTS the key feature is that alcoholic hallucinosis has no Vital sign instability making it much safer than DTS make sure you know how to distinguish between these two syndromes given the high addictive potential of alcohol as well as its effect not only on an individual's Health but also on the Public's Health from such activities as drunk driving we must briefly discuss the pharmacologic treatment strategies for alcohol abuse and dependence the first drug used to treat alcohol dependence is a camper Sate brand named cerol a camper state is like alcohol in that it agonizes Gaba and antagonizes glutamate but it does so in a much gentler way allowing those with neuronal degeneration from chronic alcohol abuse to live more easily without alcohol the benefits are only modest however and most data seem to indicate that long-term outcomes are not necessarily different between those receiving a camper Sate and those in normal support groups for this drug just know that it is used to treat those suffering from alcohol addiction I try to remember this Association by thinking of someone getting far away from The Temptations of alcohol by going camping and trying to live off the land for a bit go camping with a camper sate the next drug dulam brand named antibus is a bit more high yield than a camper Sate and gets tested more often dulam uses the psychological principle of positive punishment to decrease drinking behavior let's go over the mechanism in some more detail first when you drink alcohol the ethanol gets converted in your body to acetal deide on its own acet alide is toxic to the body causing nausea vomiting flushing of the skin tachicardia shortness of breath and generally feeling ill however under normal conditions nearly all of the acetal theide is quickly converted to acetate by the enzyme acetal theide dehydrogenate acetate is much more easily excreted by the body and does not produce any of the effects that acetal does leaving you able to enjoy your drink in peace however what dulum does is to block the second step in this process by inhibiting acetal dehydrogenase this causes the ethanol to be converted entirely to acetal deide rather than acetate leading to a rapid increase in acet alide which as you'll remember leads to uncomfortable symptoms such as vomiting and headache if you felt that way whenever you drank you would probably give up alcohol very quickly although honestly many patients just end up stalking dulam and staying on the alcohol so it really requires a very motivated person to comply with this type of treatment one high yield tidbit is that metronidazol an antibiotic used to treat ciff and other infections has a similar effect to daol Fram when taken with alcohol obviously this is something you want to counsel patients on so they know to avoid alcohol while a metronidazol and for about 48 hours after completing treatment I remember this Association by thinking of a drunk guy on a Metro Subway to remember the link between drinking and metronidazol there are other modalities for treating alcohol dependents the most famous of these is AA or Alcoholics Anonymous which uses peer support and Boundary setting to encourage abstinence from alcohol while AA is the most famous there are many other psychological treatments for alcohol dependence including the Psychotherapy CBT the efficacy of these therapies is controversial but research seems to indicate that most successful outcomes occur when the treatments are matched to Patient preferences so so it's worth discussing all the options available to see if there are any that the patient prefers we already covered benzo isipin under the anxiolytic section but it's worth taking a moment to consider that benzo and barbituates as well have no less of an abuse potential just because you can prescribe them indeed benzo aines are among the most frequently abused drugs of any kind prescription or not mechanistically when you prescribe so in benzos you're basically prescribing them alcohol with a somewhat cleaner pharmacologic profile so please weigh the risks and benefits before starting a patient on them remember from our previous discussion that the effects of benzo isipan intoxication are all about relaxing the central nervous system shuts down and muscles and clench like alcohol marked a taxia can occur one feature of benzo is a intoxication that is easily abused is its propensity to cause Amnesia in fact the date rape drug known as roipnol or rufies which is slipped into drinks with the purpose of causing the victim to forget the details of the event is actually a benzoa aine albe it one that is not approved for medical use in the United States stes the clinical picture of benzo opine withdrawal is everything you would expect knowing that withdrawal often produces the opposite effect of intoxication it is characterized by increased cognitive awareness anxiety and panic attacks physiologically sleep becomes more difficult and Vital Signs often resemble the effects of the sympathetic nervous system such as tachicardia and tnia in severe cases seizures can develop requiring ICU care while not as deadly as alcohol withdrawal withdrawal from benzo de isipin is still a serious event and require is close monitoring similarly to alcohol the treatment for benzo desine withdrawal is a controlled benzo disine taper to allow for a safe return to Baseline benzo aine overdose while not as uniformly fatal as barbit overdose is still a dangerous situation so knowing how to handle it in an emergency setting is important for patients who have overdosed on benzo diazines there's a Treatment available which antagonizes Gaba known as flumazenil brand named anate it is indicated for acute benzo P toxicity you can remember that flumazenil is related to benzos by the Aza in its name and you can also remember that it is an antagonist by thinking of the nil at the end of the name nil means nothing so flaz and nil turns benzos into nothing the last General category of recreational depressants we will cover are the opiates which like benzo isipin are dually categorized as both prescription drugs as well as recreational drugs while our discussion will mostly focus on dietal morphine more famously known as heroin keep in mind that what we are discussing applies largely to prescription opiates like morphine as well dietal morphine or heroin is your classic opiate narcotic heroin has the same binding affinity for the opioid receptor that prescription drugs such as morphine do and indeed some European countries allow prescription heroin and even prefer it to Morphine due to its lesser side effect profile compared with other opiates heroin and morphine seem to be the most capable of inducing a feeling of euphoria which makes them especially prone to abuse even though their analgesic effects are on the Lower Side compared with Sentinel or diloted the intoxication picture for heroin is straight out of the Armed Chinese man demonic analgesia respiratory depression meiosis Euphoria drowsiness and constipation meiosis or pinpoint pupils is a particularly high yield sign to note but you should know this whole slide cold in terms of withdrawal heroin is your classic cold turkey situation pyo erection as pictured here is fairly specific for heroin withdrawal in the context of drug use two other famous side effects diarrhea and dilated pupils should make sense as they are the opposite of the constipation and pupilary constrictions seen in heroin intoxication a quick note for boards black tar heroin a form of cheaply produced heroin traded by Mexican cartels has an association with botulism that you should know as far as boards are concerned just think black tar heroin equals botulism finally we will cover the treatment strategies used for opiate detoxification and treatment of opiate overdose like Suboxone for stimulants and flumazenil for benzos medications exist to help reverse the effects of these drugs two exist for opiates naloxone and nxone both of these work as competitive antagonists at opioid receptors but differ primarily in terms of Half-Life no loxone has a quick halflife and is used for acute management of opiate overdose whereas nxone has a longer halflife and is used on an outpatient basis for chronic dependence treatment I remember the uses of nil oxone and nxone by thinking of nail oxone and nail treone these two Dougs are the nail and the coffin of opiate dependence to differentiate between the two I focus on nxone and nxone like PA oxetine I think of a fast oxin which reminds me of the fast halflife of nxone and using it in a more acute Sense on the other hand when thinking of Naltrexone I think of a long Trek which reflects the reality that treating opiate dependence is a long journey which is where Naltrexone comes in just as a quick review from the section on analgesics methadone buprenorphine and tanol all of which are agonists or partial agonists at the opioid receptor are also used to treat opiate dependents in the United States feel free to watch the lecture on analgesics again for further review okay almost done take a break for now