today we're going to be talking about benzodiazapines and some alternatives to benzo benzodiazapines and also General anesthetics these are all sedative hypnotic drugs some of which are used to alleviate anxiety others of which are used to uh induce general anesthesia I want to first talk about uh a basic introduction to Benz of aspine these are all what we call anxiolytic drugs that is they are used to treat anxiety or to alleviate anxiety they are the most commonly prescribed psychotropic drugs uh importantly keep in mind psychiatrists write less than 20% of us prescriptions in this class of drugs most of these drugs are prescribed by physicians Family Physicians General Practitioners Internal Medicine doctors Etc important to understand that this class of drugs these benzidines work very quickly to alleviate anxiety in fact they work instantly they are for treatment of acute anxiety we've already talked about selective serotonin repic Inhibitors and related drugs that can be used to treat chronic anxiety but these take several weeks to um take effect so for immediate relief of anxiety we often turn to the benzodiazapines now they are not without their problems but they can be used safely and effectively for treatment of occasional and uh for immediate relief of anxiety uh another alternative for treating anxie is of course cognitive behavioral therapy very effective but it may take months but tends to have a longer lasting effect after it's finished whereas the Bodines tend to be a temporary fix so what are they used for these Bodines obviously to alleviate anxiety they can also be used as an anti-convulsant to treat epilepsy they're often used in alcohol detoxification to keep people from getting uh the shakes or having seizures they are used as sedative hypnotics to treat insomnia they are used as Central muscle relaxants to treat spasticity particularly valum uh and they are also used as potentiation of the central nervous system depressants and anesthesia so wide variety of uses for this class of drugs of course we're going to turn first to talking about the pharmacokinetics the dosage in halflife varies significantly for the 12 drugs that are available in the United States their potency varies uh and it really depends on the goal of treatment as to which of these might be the most effective most of these are lipid soluble and thus must be taken orally the exception to the rule is medam or vered it is the only completely water soluble benzodiazapine most of the rest of them must be taken orally they are injectable versions of Valium and Adavan that are intramuscular but mostly these are taken orally now drugs like ad or Xanax and Adavan are sometimes abused and people will crush them and snort them which is uh does absolutely nothing uh but have a placebo effect because in order for a drug to be administered intranasally it has to be water soluble and these drugs are not at all water water soluble so we'll talk more about drugs of abuse as we move later on but these drugs are I do have potential for abuse and certainly have potential for addictive properties um again only mazam diazapam and lorazapam are injectable mazam is only available as an injectable uh it's primarily an intravenous drug it's always used under Physicians Care and it's almost always used uh in an anesthesia setting um some of these drugs do have active metabolites which will increase their effect of halflife and we'll talk more about that diazapam or Valium has a long halflife it's active metab like nordam has an even longer halflife and in older adults these are even longer uh so it's important to understand that there are a variety of actions involved in these benodin so this is a a good overview of the short intermediate and long acting Bodines mazalan which is also known as versed is again primarily used in anesthesia settings uh triazolam or houseon is often used uh to treat insomnia these are not used to alleviate anxiety m maasim is used to alleviate anxiety in a surgical setting but not um not in an outpatient setting uh the intermediate acting benzidines include alpram which is Xanax um lopan which is Adavan and of course there are some others to aipan Etc the longer acting benzidines are also uh used significantly for alleviating anxiety including Librium Clon aipan which is clopen chlorate which is transene and Dian which is Valium there are of course flaz of Pam and others these are the ones that are used most often to give you an idea about their halflife the short acting benzos like maasam and triazolam have about a two and a half hour half life uh Al praam or xanax has about a 12-h hour half life um compare that to to Clon a pen or Clon has a pan Which has a 30-hour half life um again really depends on what the goal is uh for treatment of these drugs now for someone who wants a very short acting help them get to sleep but not necessarily stay asleep triaz Lam or even alaz Lam is probably a good choice somebody wants to try to stay asleep for more significant amounts of time something like clopin is probably a better choice um provided uh they don't mind being having a hard time waking up really just depends on how people um respond to these uh transan or kopan has to First be metabolized in Nord diazapam and nor diazapam has a 60h hour half life uh it's important to understand these have uh very very significant effects in the elderly that are very different from um healthy adults healthy younger adults um the elderly have a reduced ability to metabolize uh particularly the longer acting benzodiazapine elimination the elimination halflife for diazapam and its metabolite nor diazapam is 7 to 10 days so one dose of valum is going to take a week to get to get rid of half of um so that's really a significant problem for older adults um for short Ting um benos the dosage for an older adult is about half what you would give a younger adult there are of course significant side effects for these drugs they can be demented remember these drugs have significant effects on memory and older adults that tend to mimic dementia uh they can be depressive and there is an increased rate of fall and hip fracture associated with use of these drugs in older adults so there is um significant risk in prescribing these to an older adult in fact very few um responsible Physicians will give these to an older adult who's not under someone else's care uh again all of these have very similar pharmacological effects all benzidines are pure Gaba agonists they fully facilitate Gaba binding at low doses they will moderate anxiety agitation and fear actions by actions on receptors in the Amala the insula and the orbital frontal cortex again uh these are reducing neural firing and those areas responsible for our Primal emotions like fear and anxiety and so they really are effective at those treatments uh as we've Ted already these drugs do have significant amnesic properties and can result in cognitive confusion this is primarily due to effects in the hippocampus and cortex and finally if as I mentioned some of these drugs can be used as muscle relaxers those qualities are due um to both the anotic properties and to gther receptors in the spinal cord and brain ST which will help release those plasticity uh issues in uh muscles there are a variety of clinical uses for these drugs the current clinical uses include of course treatment of debilitating anxiety treatment of insomnia treatment of muscle spasm intention uh intentional Anor gr Amnesia in clinical settings particularly for Conscious Sedation symptomatic treatment of panic attacks non-specific treatment of anxiety that may accompany other psychological disorders and treatment of alcohol dependence now the problem is you might create a new dependence so uh there is that problem there are of course some important limitations for these drugs they do have clear amnesic effects there is the potential for Rebound which increases anxiety and insomnia which can complicate withdrawal they can be addicting addicting drugs characterized by physical and psychological dependence this is particularly problematic in patients with alcohol and substance abuse problems as uh single agents they are not effective in treating comorbid depression these are not anti-depressants although there is a belief that kipin is anti-depressive it really has not been demonstrated to be so it is uh anti-anxiety drug but it is not an anti-depressant drug um they can make chronic pain worse they carry potential for lethality and overdosage particularly when combined with alcohol or opioids which we'll talk about later on importantly benzo Pines even at low normal clinical doses impure real world driving performance 1 milligram of Al Proline which is annx impaired driving similar to a blood alcohol content of 0.15 uh I can tell you that's a pretty large dose of ZX uh this is a drug I take on occasion for anxiety and to help sleep I take a quarter milligram um a milligram I would be asleep all day so not only wouldn't impair my driving it would impair my ability to be awake um so that's a pretty heavy dose but they do impair driving uh it appears that women are more affected by the side effects uh cognitive side effects for thanx and our men and there were significant detrimental effects in driving memory and in trying to divide attention amongst tasks it's important to understand there are some significant cognitive effects of these drugs there are of course well indicated and valid current uses often times these are used as pre-anesthetic medications for Sedation and to induce Amnesia again sometimes these are used for intentional drug induced anterior grade Amnesia and perhaps for acute treatment of debilitate debilitating anxiety um you will of course accept the accompanying cognitive and psychomotor impairments to deal with that acute treatment of anxiety but not for chronic treatment of anxiety um there are of course significant side effects associated with these drugs including sedation drowsiness Axia lethargy mental confusion motor and cognitive impairments disorientation sled speech Amnesia or dementia and of course these were traditionally hypnotics that is the idea is that you could be hypnotized more likely under the influence of these drugs there are of course physical and psychological dependence issues especially in those with substance abuse disorders importantly these drugs are associated with possible fetal fetal abnormalities and what's critical for you to understand here is that some can affect chromosomes in both sperm and ovam so birth defs can be caused by use for mother or father so if you and this is particularly true for mazlan or reset so if you're undergoing an outpatient procedure using the daam said you want to avoid any reproductive activity for the week following uh that drug because these are fairly long-lasting side effects so you want to carefully talk about that with your doctor and of course there are significant interactions with alcohol and other sedatives uh that can be both dangerous and clearly affecting cognitive functioning uh this is of course a class of drugs which has some potential for abuses obviously this is not something we want to use as a long-term treatment of life's anxieties um treatment of drug induced REM rebound and insomnia can be problematic um because you end up sort of creating a longer term cycle there of course uh date rap drugs one of the ban drugs in the United States FL trapan roit uh is basically know as a date rape drug uh long-term treatment of alcohol withdrawal just creates a new Addiction obviously people will self-medicate for psycholog iCal distress with these and we obviously want to avoid using the long acting bodas Pines on the elderly there are of course advantages and disadvantages to using bodas Pines and thinking about these for an individual are important uh these are very safe drugs they have low toxicity unlike barbits or alcohol they can be used safely they don't induce metabolic enzymes so don't accelerate their own metabolism so tolerance isn't generated they act on uh central nervous systems uh perer organs and liver are not impaired so this is a central nervous system drug disadvantages to using these drugs are of course they can be amnesic uh tolerance can develop in the brain that is the brain just doesn't respond as much as much like alcohol tolerance there is a the potential for dependency and for withdrawal particularly in people who are using them long term and of course they are potentially uh abused as well obviously they will also potentiate other stive hypnotics and so she never be used in combination with other stive hypnotics so while we mentioned this a number of times I want to spend a little bit of time talking about the uh effects of Bodines on memory and I see if May typo here but we'll live with it all benzines have the potential to cause temporary Andor great Amnesia um and that's something uh to keep in mind that all of these drugs can have this effect uh this is primarily for what we call episodic memory that is memory for what your life episodes are so what did you do yesterday what you do the day before what did you study last night all of these drugs have that effect so if this is a drug that you have available you want to make sure you're not combining that with your studying because that they do have significant reductions in upside M performance that are not State dependent okay um now obviously this Amnesia can be useful for presurgical preparations again there are some things in surgery that are oftentimes unpleasant and um this can really help a patient if they don't have to remember the trauma of that surgery um they may not be a problem this law temp Amnesia may not be a problem if they're taken for sleep because people are asleep anyway we're going to talk about issues with the um bzras here in a minute in which people don't remember doing things like eating or going to the store or that sort of thing which they're awake but don't have any memory for um importantly high anxiety itself May worsen memory so I'm very anxious um people benzo daes may not be amnesic so that could be a problem obviously in a surgical setting so really have to be very careful about these effects um interestingly there is a study I read recently about people with red hair that is real red hair uh there's something about their genotype which makes them uh much faster at metabolizing these drugs so drugs like mazan which are used in anesthesia people with red hair have to be given twice as much anesthesia to get the same effect so there are some important individual differences in how these drugs um fect people so what's happening here well of course we know Gaba is known to inhibit long-term potentiation in the hippocampus which is that neural process believed to be responsible for memory consolidation primarily these drugs have an effect on what we call explicit memory that is memory for conscious experiences or conscious memory for experiences we also have what's called implicit memory which is an unconscious form of memory and maaslin doesn't affect that but it does affect our conscious memory and again critically people are unaware of their effects on memory and that's some research that we've done uh in my uh past finally combined with aloh qualities have a severe effect on memory um my friend Mariam mitzer at John Hopkins has done some really interesting work with lorazapam and zanam that show when combined with alcohol they have a really wall up on memory so try not to make that combination the last thing I want to mention is there is an interesting drug called flanel and flanel will completely block the benzodiazapine receptor and in fact will completely reverse any effects of benzodiazapine that was given prior to flanel this is one of the things that makes use of benzodiazapines in a clinic so safe and the reason why medam is such a safe drug to give because you can completely reverse the action of maasam by introducing plone so it's a completely reversible uh drug so it's pretty remarkable in that way so that's a quick review of benzodiazapines I want to turn next to talk about what are called nonbenzodiazepine benzodiazapine receptor Agonist or bzras um generally these drugs are not anxiolytic most will actually bind to that Gava receptor again much like um benzodiazapines they're actually are benzidine receptor agonists so the Boost the functioning of bodzin then boost Gaba and there are currently three of these on the market zulm which is ambian uh zapon which is Sonata and uh Lunesta quick um introduction to these drugs Ambien has half life of about two to two and a half hours very difficult to overdose on Ambien and just be very sleepy for a long time um you really want to try to limit your use of this drug because it does have some very weird side effects um often times people will hallucinate when they're under the influence of Ambien um it's the reason I don't take it um and there are of course significant potential for um people to do things while they're under the influence of these drugs that they don't remember so that's ambian Sonata has a very short half life less than an hour can be used on short notice it's non addictive so somebody needs to quickly get to sleep but needs to be able to be awake in a couple of hours this is a drug that will work for that Lunesta is similar to zulm and traditional benzo Dianes has a much longer halflife um there is an increased RIS risk of nextto day sedation that is people having sort of a lunessa hangover um and so this is a long-term use for treating insomnia um but certainly not something you want to take if you need to be functional in just a few hours because this is a much longer longer lasting um halflife um as I mentioned there is the potential uh for doing things while you're sleeping including sleep driving so in 2017 the FDA required that all stive hypnotics used to induce or maintain sleep must warn of the risk of sleep driving people will drive while not fully awake and have no memory of the event um they will also make phone calls prepare and eat food um Etc people will wake up the next day and half the foods out of the refrigerator and they'll have no they'll think somebody broke into their house um importantly Blood Bubbles of drug sufficient to block memory um can happen in the absence of a sleep state so that is you can get to the point where memory's blocked but not be to the point where you're sleeping so it's important to understand are actually awake they call it sleep driving but they're not asleep they just don't remember it okay um I think it's important to have a full understanding of the drugs because they're used so much they're prescribed so often they more than likely somebody you know takes one of these so it's really important to understand the risks and benefits of these drugs okay let's now turn and talk about General anesthetics um obviously these aren't drugs that are ever used or abused but they are certainly used in a clinical setting um they are central nervous system depressants they will produce unconsciousness for surgery they can be administered through inhalation through or through uh injection some of the inhaled anesthetics are subject to abuse so nitrous oxide for example which is oftentimes used as the dentist um is a drug of abuse in fact um it's problematic because Nitric nitrous oxide is also used to charge things like whipped cream containers and so people will abuse them through whippet um can be very dangerous to do so um all of these involve some sort of Gaba agonism there are Ultra short short acting barbits like cyop pentanol or brevital peral which is Dian is another uh very short acting um Gaba Agonist all of these involve facilitation of Gaba receptors they have no analgesic or usually no euphor activity their onet is usually immediate and so these are used as anesthetics because they can be administered patients asleep within moments um and they wear off relatively quickly uh particularly the injected versions the uh inhaled anesthetic like hopane much more difficult to to regulate so uh these are are where most of the um anesthesia drugs are turning uh ketamine is another general anesthetic drug it's used primarily in Veterinary um Administration this induces induces both unconsciousness and Amnesia the problem is this can be particularly uh dangerous it's also very unique it induces both analesa and psychedelic hallucinations this is why it's often a drug of abuse in fact usually what's how it's abused is the liquid version of ketamine that would be used to inject the animal is um set out to dry uh and essentially the dissolved ketamine inside the liquid suspension uh becomes a powder and it's then snorted uh unlike other anesthetics does not reduce blood pressure so this can be important for critically ill surgery patients if somebody is uh very sick and already has low blood pressure a ketamine is probably worth exploring its use but it does have very psychedelic properties we'll talk more about that when we talk about the psychedelics um finally we've already talked a little bit about the serotonin receptor agonists as anxiolytics don't want to visit that in any more detail because we spent a lot of time on that with anti-depressants but we do understand that anxiety may result in part from defects and serotonin transmission and all six clinically available ssor antidepressants are widely prescribed for anxiety disorders and are actually considered to be the first choice of drugs for long-term anxiety thank you very much we will turn next to talk about natural remedies