Introduction to Biological Psychology Part III Chapter 6 Psychopharmacology How do Drugs Work on the Brain

i 237 . HOW DO DRUGS WORK ON THE BRAIN ?

Bryan Singer Learning Objectives To gain knowledge and understanding of how drugs enter the body and the time course of their effects To gain a basic understanding of how general classes of drugs interact with neurons to alter their function .

238 Having learnt about how neurons in the brain communicate , let now consider how drugs can affect their function . In a fictional example , Sam has both high cholesterol and attention hyperactivity disorder ( To help alleviate their symptoms , the prescribes them to lower their cholesterol , while a psychiatrist prescribes to help improve their attention . Both and are considered drugs . Researchers who design drugs and investigate how they act on the body are often called ( they study pharmacology ) While a general pharmacologist might explore the use of or , someone who researches might be more interested in understanding how can reduce symptoms of . These scientists don just develop drugs or observe changes in symptoms after administration they also ask various other questions ! For example , a may consider the following ' What parts of the brain does a drug act on ?

Does a drug have its effect because it interacts with a receptor type ?

How does the administration of a drug impact brain biology ?

After a drug is taken , how long do its effects last ?

Can a drug chemical structure be changed so that its i 239 effects can be prolonged ?

Would taking medicine in a certain way ( oral nasal ) Exercise improve the drugs ability to act on the brain ?

Could brain biology explain why there is individual can you think variation in the capacity of of other drugs to ameliorate certain conditions ?

questions thata Building on your knowledge of neurobiology , this chapter will explore the concepts needed to investigate ?

understand how a might approach addressing these questions . Classifying drugs Before exploring how drugs act on the body and brain , we need to clarify how we refer to different drugs it can be confusing because certain compounds can go by different names . For example , a may describe as a ( or a ) a reuptake inhibitor . In contrast ,

240 a chemist might refer to the drug by its chemical structure . Furthermore , might be prescribed by a psychiatrist as Ritalin and referred to by the UK government ( 2022 ) as a Class controlled substance ( which has severe penalties for illegal possession and intent to supply ) While the following is likely not an exhaustive list of methods to categorise drugs , they can broadly be referred to in the following ways ' Source ' Chemical structure ' Relative mechanism of action in the brain ' Therapeutic use or effect ' Marketed names ' Legal or social status We will now focus on three of these categories that you are likely to encounter in your studies of biopsychology . by source

241 Fig . poppy , with milky latex sap oozing from a recent cut Drugs come from Various places some are naturally occurring , while others are created in the laboratory . Cocaine ( is an example of a naturally occurring drug 242 i because it is directly extracted from the leaves of the coca plant . Opium is also naturally occurring , taken from the unripe seed pods of the opium poppy . In other words , all the molecules that give cocaine and opium their psychoactive properties are already present in the plant itself . drugs are chemically derived from naturally occurring substances . An example of a drug is heroin ( a molecule of morphine , the main active ingredient of opium ) The drug lysergic acid ( is also , originally derived from the grain ergot Fungus . Finally , some drugs are entirely synthetic , made from start to in the laboratory . Methadone , amphetamine , and ( or ecstasy ) are all examples of synthetic psychoactive substances . Relative mechanism of action in the brain We will discuss the details of how drugs might act in the brain in the pharmacodynamics section ( Section ) For now , it essential to understand that certain drugs can have very similar molecular targets in the brain .

243 I ) oo ( mu Fig . Similar chemical structures for different opioids For example , opium ( natural ) heroin ( and methadone ( synthetic ) all act on opioid receptors in the brain . Therefore , these drugs might be considered variations on a theme . Despite their overall affinity for binding to opioid receptors , it important to remember that the biological and psychological effects may still differ . There are different types of opioid receptors ( and these might be differentially located across the brain ) and certain opioid drugs might bind to some of these receptors more readily than others . These drugs may also differ in terms of how quickly they reach the brain after being administered , as well as how fast they are eliminated from the body ( see , below ) It also crucial to remember that the brain does not express opioid receptors with the sole purpose of mediating the effects of drugs like methadone or heroin . The body already has

244 endogenous opioids circulating in regions of the nervous system these molecules play essential functions , like enabling us to feel pain and pleasure and helping to regulate our respiration ( Le et , 2009 Corder et , 2018 ) In contrast , drugs are exogenous compounds that originate outside the human body . Therapeutic use or effect Drugs can also be according to their biological , behavioural , or psychological effects . Drugs that target opioid receptors treat pain and are therefore called . Drugs that excite the central nervous system ( and make us more alert are called stimulants ( cocaine , amphetamine , nicotine ) In contrast , substances with the opposite effect are ( alcohol , Some types of hallucinogens ( mescaline , psilocybin ) and psychotherapeutics ( antidepressants like and ) are drugs that alter psychological states . It is also possible that some drugs can fall under different categories or are otherwise unclear what type they belong to . Ecstasy ( has a chemical structure like the stimulant amphetamine , yet it also can have hallucinogenic effects . Ecstasy is also sometimes referred to as an because of the emotional state of relatedness , openness , or sympathy that it can create ( Nichols , 2022 ) For all of these drugs , the effects and potential

I 245 therapeutic use depend on how much and by what method they are administered .

246 I Absorption Metabolism Lumen Mucosa Fig . Overview of is a of pharmacology that studies how drugs 247 are absorbed by the body , distributed , and ! excreted from the body . Thinking about the journey a drug goes on may be helpful to understand these concepts . A drug might first enter the body from a variety of routes . Nicotine , For example , could be smoked in a cigarette or taken via a patch applied to the skin . For this module , the effects of nicotine that we are most interested in studying are those happening in the brain . We will review how drugs like nicotine get to the brain . Finally , you will learn how drugs , as well as their metabolites , can be removed from the body in urine .

248 Fig . Time course of drug effects . parameters ( maximum serum concentration area under the curve clearance ) highest level ( Next , during the elimination phase , the concentration of Based on the example timeline shown ( left ) for nicotine , we can plot the concentration of a drug in the body ( Figure ) When a drug is initially administered , the concentration in the body increases ( absorption phase ) Then , at a particular ( the reaches its concentration the drug in the body decreases this happens because the drug is both and excreted . At some point , the level of the drug decreases so that it is half the value of the amount of time it takes to reach this point is the drug life (

I 249 Absorption and distribution Several factors how quickly a drug is taken up ( absorbed ) by the body . Perhaps the most obvious is how the drug is administered . Several and invasive methods for drug administration are shown in Table .

250 Method Administration Oral Sublingual Nasal Rectal Transdermal Inhalation Into the mouth Under the tongue Absorption through blood capillaries lining nasal cavities Like oral , but can be done in unconscious individuals because it doesn require swallowing On the skin via a patch Into the lungs , which have a large surface area and are highly In Methods of Drug Subcutaneous Intramuscular Intravenous Epidural Under the skin , but not into the muscle Into the muscle Directly into the vein , so directly into the body bloodstream Into the space between the dura mater and vertebrae , used in spinal anaesthesia Injections methods primarily used in animal ( in rodent model of mental health ) Intraperitoneal Intracranial Injection into the peritoneal cavity surrounding the intestines Injection into either the tissue ofa brain region or ventricle since these drugs are injected into the brain , they do not need to access the body circulatory system

251 Table . Routes of administration With so many injection methods , how is the best method for delivering a drug determined ?

It turns out that there are many factors that decision . Intravenous ( IV ) infusions might be the quickest to enter the body , but a drug administered via this route might have the shortest length of action in the body ( a short quickly into and out of the body ) So , an IV administration of an analgesic might lead to rapid pain relief , but the effect might not last for long . Plus , some people are afraid of needles , and training is required to administer IV injections . Thus , IV injections do not allow patients to care for themselves independently .

252 I LOGY Plasma Concentration of Drug as a Function of Response Time Route of administration oral IM ( intramuscular ) IV ( intravenous ) Plasma Concentration of Drug Time Fig . On this graph , represents the time at which a drug dose is administered . The curves illustrate how plasma concentration of the drug changes over intervals of time ( ti through ) As the graph shows , when a drug is administered intravenously , the concentration peaks very quickly and then gradually decreases . When drugs are administered orally or intramuscularly , it takes longer for the concentration to reach its peak . Perhaps on the opposite end of the administration spectrum from IV injections are oral administrations . Most individuals can swallow medications , so this method ensures a level of independent care . Unlike IV administration , however , drugs do not immediately enter the bloodstream when taken

253 orally . Therefore , the desired effects of medications swallowed are slower than drugs administered through IV injections . Further complicating this is that drugs taken by the oral route are absorbed through the gastrointestinal system , and not by the mouth . This has two primary consequences . First , drugs can initially be destroyed by stomach acids , limiting the maximum effect a drug can have ( for a medication , might be higher after IV than after oral administration ) Furthermore , the stomach environment is constantly changing ( especially after meals ! impacting how much of the drug eventually reaches other parts of the body . Also , after exiting the stomach , drugs enter the liver , where they undergo metabolism this can further destroy orally administered medications , reducing the concentration of the drug that reaches the rest of the body . That said , some medications ( are designed in a certain way so that a person initially swallows an inactive ( 2010 ) When the undergoes metabolism , it is converted into the active drug ( the amphetamine ) that can later impact brain function . A few other vital implications of drug administration routes impact how quickly and for how long drugs have their effect . If a drug is administered into an area of the body with a large surface area and a high level of blood circulation ( the lungs ) then the drug can enter the bloodstream quicker and be faster at having its desired impact . In contrast , a drug would be much slower to act , and potentially work for a longer duration ,

254 if it first needs to cross several cell layers before eventually arriving at a blood vessel ( transdermal delivery ) Furthermore , depot binding might occur if drugs become sequestered into inactive sites of the body where there are no receptors for them to bind to ( in fat stores ) these fat stores may slowly release a drug or its metabolites , further prolonging their actions on the body . If not injected via the IV route , drugs can be slow to enter the circulatory system because they need to pass through various membranes before entering the bloodstream ( stomach , capillaries , While some endogenous compounds have the luxury of helper proteins designed to transport the molecule across the membrane , exogenous drugs usually do not have this mechanism . Instead , drugs most often from high areas of concentration to lower regions ( via their concentration gradient ) and eventually cross membranes they encounter simply through passive diffusion . Since our body membranes are made of lipids ( a lipid ) the ability of drugs to pass through membranes is determined by their lipid solubility and ionisation .

I 255 MEMBRANE ' SIZE OF DRUG OF LIPID SOLUBILITY MOLECULE MOLECULE OF MOLECULE . Fig . Drugs passing through membranes , most drugs are either weak acids or bases . When a drug is dissolved in a solution , it becomes ionised ( charged ) The more a drug is ionised , the less it becomes , decreasing its ability to cross cell membranes . In general , drugs that are acids are less ionised in more acidic solutions , while drugs that are bases are less ionised in more basic solutions . So , for example , the drug aspirin is a weak acid . If aspirin is taken orally in a tablet , it goes to the stomach . The stomach is strongly acidic ( so aspirin remains primarily in its form . Because it is and thus

256 soluble , aspirin can pass through the stomach lining and enter a blood vessel . Blood , however , is slightly basic ( this would result in aspirin becoming ionised , making it less likely to leave the vessel because it more challenging to cross membranes ( it now less ) The situation where a drug is stuck in a compartment because it is highly ionised and low in lipid solubility is called ion trapping ( Ellis and Blake , 1993 ) Concentration gradients can rectify ion trapping the high concentration in one bodily compartment compared to a neighbouring compartment can encourage the drug to move across membranes to the lower concentration region . Various formulas are used to calculate drug diffusion but are beyond the scope of this module . Finally , for drugs to enter the brain , as you ve read about elsewhere , they must first cross the barrier ( Drugs that are can most easily pass through the . So , for example , because heroin is more than morphine , it can more quickly pass through the and arrive in the brain ( et , 2020 ) Therefore , heroin tends to be faster acting than morphine this may contribute to its addictive qualities . Patients use prescribed medications to improve mental health because the drugs impact brain function . However , as described above , delivering drugs directly to the brain is challenging . Because drugs spread across our body via the bloodstream , they act in the periphery before reaching the brain this can lead to unwanted side effects . Thus , part of the

257 job of a is to develop medications that can improve mental via their actions on the brain while minimising undesirable and unwanted effects . Metabolism and excretion We have already discussed one way of drugs pass metabolism in the liver , where enzymes can break down medications into simpler compounds . Through , the liver can metabolise drugs so that they are more ionised this causes them to lose their lipid solubility , further preventing them from crossing the to enter the brain . Finally , drugs are primarily excreted by the body via the kidney ( urine ) but other excretion products include bile , faeces , breath , sweat and saliva . Special enzymes in both the blood and the brain can also break down drugs . For example , when in the brain , heroin can be into morphine . This raises an important example drugs can be into molecules that are also biologically active . While morphine and heroin might have similar effects , the metabolites of other drugs can have opposing effects . For example , alcohol is into acetaldehyde via the alcohol dehydrogenase enzyme ( Figure ) If acetaldehyde accumulates in the body , it can make a person feel sick . Acetaldehyde itself is by aldehyde dehydrogenase into acetic acid . There are drugs for alcohol use disorder that block aldehyde dehydrogenase (

258 I thereby resulting in increased levels in the body ( et , 1997 ) Because the effects of are unpleasant , it is believed that the administration of this drug might prevent people from drinking alcohol in the first place . While this might sound useful , compliance with this treatment is often an issue ( et , 2016 ) AD Ethanol Acetate ( NAD 02 mop mo Fig . Metabolism of alcohol Finally , there is also individual variation in metabolism , For example , there might be sex differences in levels of certain enzymes . Women may have lower levels of gastric alcohol dehydrogenase than men so for a given dose of alcohol , more alcohol enters the bloodstream ( et , 1990 ) There is also individual adaptation chronic drinkers have higher levels of alcohol dehydrogenase . In this example , someone with an alcohol use disorder might need more alcohol

I 259 than someone else to achieve the desired effects of alcohol this is an example of tolerance resulting from a state of enzyme induction ( increased rate of metabolism due to enhanced expression of genes for enzymes tolerance is discussed again later in this chapter ) Age also impacts metabolism older individuals have reduced liver function , and this might lead to exaggerated alcohol effects ( Meier , 2008 ) Finally , genetics can impact metabolism as well some individuals have a polymorphism in the gene encoding aldehyde dehydrogenase lack of this enzyme means there a greater accumulation of acetaldehyde and thus more of its unpleasant effects ( Agarwal , 1987 ) Pharmacodynamics While focuses on how a drug spreads across the body and is eliminated , pharmacodynamics studies the effect a drug has once it reaches its target in the body . So , while explains how a drug eventually passes through the to get to the brain , pharmacodynamics describes what type of receptor a drug binds to in the brain and what consequence this has on neuronal signalling . Notably , while this example discusses a drug targeting a receptor , medicines can interact with many different types of molecules in the brain , impacting brain function in numerous ways . The below gives a few examples of how a drug can affect synaptic transmission . Once again , it crucial to recognise that

260 I drugs are acting on cellular mechanisms that already exist to help us survive . For example , nicotine binds to an receptor that usually binds the neurotransmitter acetylcholine . This particular receptor also binds nicotine , so we call it the nicotinic acetylcholine receptor . vane mans or we A was me us am or use In non ulna or ' A ' shine so we A mam ma scams Fig . Sites of drug action Agonist drugs and curves Throughout this and future modules , you will learn about many different types of drugs and their impact on brain biology . For now , we will focus on two general kinds of drugs

261 and antagonists that bind to receptors . Receptors are molecules that a drug ( or an endogenous ) bind to and initiate a biological effect . Receptor is a very general term we often think of receptors as proteins that are inserted into the membrane of cells , but this does not have to be the case ( receptors can also be in the cytoplasm , for example ) Some examples of where receptors can be located are shown in Figure . For example , receptors can be found on neurons ( nicotinic acetylcholine receptors ) and on synaptic terminals ( known as , which help regulate neurotransmitter release , the dopamine receptor ) Drugs are often not limited to binding one particular receptor they are often considered dirty , binding to multiple types of receptors to varying degrees across the body . This is one reason why drugs often have unwanted side effects . Second generation antipsychotic medications are notorious for impacting multiple types of receptors , and this may be why there is individual variation in their tolerability ( et , 2019 ) Drugs that are considered can bind to a receptor and initiate some type of biological effect , such as turning on an intracellular cascade of signalling events . Because of this , we often think of as working via a mechanism inserting a drug into a receptor enables events to occur ( see Figure , top ) It is critical to recognise that drugs tend to bind to receptors weakly and can rapidly dissociate from the receptor . Therefore , the acute impact drugs have is

262 reversible , This is important because when a drug is no longer bound to a receptor , the endogenous for that receptor can once again bind . ma ox I mane we mama Iu mama Fig . Interactions between drugs or and their receptors How much biological impact a drug has on the brain is , in part , dependent upon the number of receptors that are available to bind the drug . Therefore , increasing the number of drug molecules in the brain will also increase the probability of binding to a receptor . While larger doses of a drug can have a more impact on biology , there is always a limit . The maximum effect of a drug is achieved when the drug is continuously bound to all receptors that is , a drug reaches its

263 maximal effect when all receptors are occupied this is known as the law of mass action and can be described by a ' EFFECT ( 36 OF 10 1000 10000 DRUG CONCENTRATION Figure curve As you can see from Figure above , curves have a typical . They are usually plotted with a logarithmic function of dose of drug administered on the axis and a measured response on the . Looking at the , you can see that at some point , increasing the dose of the drug no longer produces a bigger response at this point ( known as effective dose 100 , the drug is occupying all of the available receptors and therefore is having its maximum effect . Another important point on the graph is the for

264 I the drug . is a measure representing the dose that produces half of the maximal effect . Alternatively , can characterise the amount of a drug that produces an effect in half of the population to which it was administered . Finally , it is also crucial to remember that most medications have various effects on the body and can even interact with multiple receptors . Binding to Receptor A might impact pain perception , while binding to Receptor might impact blood pressure . If Receptor is more prevalent than Receptor A , then the dose required to affect blood pressure maximally would be higher than that to alter pain perception . Accordingly , there would also be a different value for each response . Drugs often have side effects that are either undesirable or dangerous curves can also be used to characterise these effects . For example , one unwanted effect of a drug is sedation . The dose of the medicine that produces this effect in 50 of subjects is referred to as the toxic dose 50 ( Using this information , doctors can calculate a margin of safety , known as the therapeutic index ( or therapeutic window ) which indicates how much the dose of a drug may be raised safely . Just as drugs might have multiple desirable effects , there may also be numerous toxic effects , each with a different . Finally , in the therapeutic index formula , can be substituted with the lethal dose 50 ( which is the dose of a drug that can kill 50 of subjects .

265 Comparing curves of agonist drugs Up until now , we have primarily discussed the efficacy of drugs the maximum effect they can produce . Drugs also differ in potency how much medication is needed to produce an effect . Figure shows curves for three opioid drugs with similar , morphine , and codeine can all effectively reduce pain . However , different doses of these drugs are required to relieve pain a higher concentration of codeine is needed for pain relief than morphine . Because of this , the of each of these drugs are also different . Drugs with a lower are considered more potent than drugs with a higher . CURVES FOR ?

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um i vo we near I MAXIMUM ' a Man I i Qe i OVEN , You i as av nos me is i A is i am . rows , am A as sci ME NE was Figure . Comparing efficacy and potency of analgesic drugs 266 The also displays the curve for aspirin , a drug that can be used to reduce pain . Not only is a higher dose of aspirin required to reach similar levels of pain relief compared to opioids like morphine , but pain can also not be entirely relieved by any close of aspirin . So , aspirin is both less potent and less for relieving pain than morphine . There are likely several reasons For these differences in potency between drugs . For example , the are likely different between medications if one drug has an enhanced ability to cross the , then more molecules of that drug will bind receptors , and that drug will have supreme efficacy . In addition , some drugs might have a greater for receptors than other drugs a drug with higher affinity will likely stay bound to the receptor For a more extended period and thus keep on having an effect . Differences in the efficacy of drugs likely signify that those medications work through different mechanisms . While both morphine and aspirin relieve pain , morphine works by binding opioid receptors , and aspirin instead the enzyme . Antagonist drugs Agonist drugs binding to receptors can cause a biological response as such , they are said to have intrinsic activity . In contrast , antagonists bind to receptors and counteract either an agonist or endogenous effect on a receptor .

267 Therefore , one can measure the effectiveness of an antagonist by observing how its administration impacts the curves of agonist drugs . Unlike agonist drugs that follow a lock and key mechanism to initiate biological effects ( Figure , top row ) it may be helpful to imagine an antagonist as a key that into a lock but does not turn ( Figure , bottom row ) awe AGONIST RECEPTOR INTERACTION no ANTAGONIST INTERACTION Figure . Action of agonist drugs ( top ) and competitive antagonists ( bottom ) There are a couple of categories of antagonists that you should be familiar with ( Figure ) Competitive antagonists bind to the same site on a receptor as an agonist or endogenous

268 . Because of this , this type of antagonist compete with the endogenous for available binding sites . Therefore , a higher dose of the agonist drug would need to be administered to the presence of an antagonist this would shift the of the agonist curve to the right . Theoretically , if there is so much agonist that absolutely no antagonist molecules can bind to a receptor , and if the agonist occupies all available receptors , then the agonist can reach the same as in the absence of an antagonist .

269 A ) COMPETITIVE no 90 ID OR CONCENTRATION ) NONCOMPETITIVE ANT AGONIST nu 10 . OR CONCENTRATION Figure Competitive ( A ) noncompetitive ( antagonists 270 I Unlike competitive antagonists , bind to a different part of a receptor than an agonist or endogenous therefore , they do not compete for binding . In effect , antagonists make receptors unavailable for agonist drug action . While antagonists still shift the curves of to the right ( Figure ) they can also decrease the maximum possible effect an agonist or endogenous has ( they reduce the ED 100 ) Because antagonists bind to different receptor sites as agonist drugs , simply increasing the dose of an agonist can not overcome this blockade . When discussing , we mentioned that most drugs form weak bonds with receptors . This means that the effects of the drug are reversible because the drug can easily dissociate from a receptor . Most antagonist drugs work similarly , and their interaction with receptors is temporary . However , the effects of some antagonist drugs are they form a bond with receptors . One example of such an antagonist is ( from banded krait venom ) which blocks acetylcholine receptors at neuromuscular junctions . This can result in paralysis , respiratory failure , and death . However , there is a hypothetical scenario to overcome the effects of irreversible antagonists synthesising new receptors . Suppose enough new receptors are formed and become functional , and the irreversible antagonist is no longer in the system ( it has been eliminated via urine ) In that

271 case , these new receptors can begin to restore biological function ( when they bind or endogenous ) Other types of There are three other types of agonist drugs you may encounter in your studies . First , indirect ( or ) can bind to a different receptor part than a ( regular ) Full agonist or endogenous . These indirect help full , or endogenous , have their full effects . are an example of an indirect agonist because they bind to receptors , and they enhance the channel conductance when ( the endogenous ) is also attached . Second , partial bind to the same receptor site as agonist drugs , but they have low efficacy ( Figure ) Therefore , a drug as a partial agonist is relative the response to a partial agonist must be less than the maximum response produced by a Full agonist . Importantly , when both full and partial are administered simultaneously , they compete for the same receptor binding site . In this scenario , because the partial agonist is less effective at producing a biological response , it the effect of the Full agonist . In other words , it is impossible For the body to produce a full response to the agonist because partial ( which are less efficacious ) occupy the sites . Such an effect can be overcome by increasing the dose of a full agonist ,

272 allowing it to the partial agonist for binding to receptor sites . Because of these effects , partial are sometimes called mixed drugs . Full 75 Percent 50 Response From 25 Neutral antagonist Inverse agonist Figure . Agonist comparison The type of drug we will discuss is the inverse agonist . Some receptors in the body have substantial endogenous activity , even when are not bound to them . This observation breaks the general rule that receptors have no activity when they are not bound to a . Inverse reduce this spontaneous activity , resulting in a descending curve ( Figure ) Although their mechanism is complex , some alkaloids are considered inverse . alkaloids bind to

273 receptors at the same site as . While facilitate chloride conductance through the receptor channel and decrease anxiety , alkaloids have the opposite effects when administered ( Evans , 2007 ) The effects of these inverse lead some people to call them . By contrast , drugs that are competitive antagonists at the receptor do not the receptor function on their own , but instead block the ability of full , partial , or inverse to alter the receptor activity . Effects of repeated drug use If an individual is repeatedly administered a dose of an agonist drug , then the ability of the drug to exert effects on the body might change . If the drug effects get smaller , this is known as tolerance . So , if an individual has developed tolerance to a particular drug , then the dose of the drug might need to be increased so that the drug is still efficacious . Sometimes , drug effects get bigger and bigger with repeated administrations this is known as or . Because drugs can have multiple effects on the nervous system and behaviour , some drug responses may undergo tolerance , while others are . For example , repeated administration of amphetamine can result in tolerance to the effects of the drug , but

274 I to psychomotor or impacts . Exercise To help you think about these concepts , try drawing curves for the development of tolerance and . Remember that , with tolerance , more drug is required to get the same effect In contrast , with less drug is needed to get the same effect . Because certain drugs target similar receptors in the nervous system , sometimes happens , where one drug also reduces the effects of another drug . For example , alcohol drinkers might be less affected by since the impact of both types of drugs are dependent upon transmission and the expression of receptors ( Le et , 1986 ) Mechanisms underlying drug might be a bit less studied than tolerance . One example , however , of is the ability of certain drugs ( like amphetamine ) to increase levels of the neurotransmitter dopamine across

LOGY 275 administrations ( Singer et , 2009 ) You will learn more about drug tolerance and when studying addiction . Summary Key Takeaways Multiple classification systems for drugs exist involves the absorption , distribution , and elimination of drugs from the body Pharmacodynamics involves how drugs interact with receptors and alter the functional state of the receptor . In this chapter , you have learned about different categories of drugs and how they impact the body through and pharmacodynamic processes ( Figure ) Entire modules are often devoted to pharmacology , and many of the concepts we described can be further

276 I Via mathematical formulas , allowing for precise drug comparisons . As you study different psychiatric conditions and their biomedical treatments , be sure to refer to this chapter to help you understand how medications can be used for many individuals to improve mental wellbeing , body sin and . ma Compliance and , i , me ( body . and of his elimination of . in ii We . pharmacological ! Ii ) Physiological ( age renal ( an Pathological ( mmy . mi ( iii ) Genetic ' my i ) in ( in ) Fig Summary of factors influencing drug action References Corder , Castro , 2018 ) Endogenous and exogenous opioids in pain . Annual of , 41 ,

277 Ellis , Blake , 1993 ) Why are drugs so variable in their efficacy ?

A description of ion trapping . of the , 52 , Evans , A . 2007 ) Pharmacology of the , a partial inverse agonist at the benzodiazepine site of the A receptor neurochemical , neurophysiological , and behavioral effects . Drug , 13 ( di , Terpin , Lieber , 1990 ) High blood alcohol levels in women . The role of decreased gastric alcohol dehydrogenase activity and metabolism . The New England journal of , 322 ( NE , Agarwal , 1987 ) Polymorphism of aldehyde dehydrogenase and alcohol sensitivity . Enzyme , 37 ( Hagi , Kane , 2019 ) effectiveness of oral generation antipsychotics in patients with schizophrenia and related disorders a systematic review and of direct comparisons . 18 (

278 , 1986 ) Tolerance to and among ethanol , pentobarbital and . Pharmacology , and , 24 ( Le , Becker , 2009 ) Reward processing by the opioid system in the brain . 89 , 2010 ) a stimulant for the treatment of in children and adults . 15 , Meier , 2008 ) Age , alcohol metabolism and liver disease . Current in and Metabolic Care , 11 ( 2016 ) Current and mechanisms of action in the treatment of alcohol dependence . 49 ( Nichols , 2022 ) How the name for a novel class of psychoactive agents originated . Frontier in , 13 , Doke , 2020 ) Effects of drugs of abuse on the barrier

279 A brief overview . Frontier in Neuroscience 14 , Singer , Li , 2009 ) changes in dendritic morphology in rat forebrain correspond to associative drug conditioning rather than drug sensitization . 65 ( 10 ) UK Government ( 2022 ) List of most commonly encountered drugs currently controlled under the misuse of drugs legislation . Accessed 13 Dec 2022 ) government , Johnson , Mays , 1997 ) Inhibition of aldehyde dehydrogenase by and its metabolite methyl sulfoxide . Pharmacology , 53 , 96 )

280 About the Author Bryan Singer UNIVERSITY OF in Bryan Singer is a lecturer in the School of Psychology at the University of ( Brighton , UK ) Bryan lab is part of the highly collaborative Behavioural and Clinical Neuroscience group . He is the Director of the Addiction Research and Intervention Centre ( and a member of Neuroscience . Bryan also has an Associate role at The Open University ( UK )