Module 2 Flashcards

Question

ANESTHESIA

Answer 1

* Loss of senstation * Protect from pain of surgery * Still surgical field * Anesthesiologists manage all non cutting elements of the patients care After reciving increasing roles in assessment and optimization of operation, post operative pain management, chronic pain, critical care and other area

Answer 2

* Indcues 5 physiological characteristics ○ Hypnosis - loss of consciousness ○ Amnesia - loss of memory ○ Analgesia - Loss of response to pain ○ Areflexia - loss of autonimic response ○ Relaxation - skeletal muscle relaxation * Ideal anesthic would induce quickly allowing prompt recovery after administration has stopped * Would also produce high therapeutic index and have no adverse effects * No agent can do this * General anesthetics are often used in combinations * CNS depressants * They are depressed reticualr activated system - bundle of nerve near the brainstem that filters uneccessary information from reaching the brain stem such as crow of talking people in the brain

Answer 3

* 2 main ideas are Faciilitation of gaba mediated inhibition receptor chloride channel ○ Strengths of the inhibitory function of GABA increasing CNS depression * Antagonism of glutamic acid and excitation of NMDA channel receptor ○ Decrease the excitation in CNS , enhancing the CNS depression * Ikely that general anesthetics function by combination of above mechanisms * In depth anesthesia dependnt on concentration of anesthetic in the CNS * Greater the concentration of angesthetic in the brain and spinal cord, the deeper the anesthesia * 2 main categories ○ Inhaled Intravenous

Answer 4

* Breathe them in * Drug reaches alveoli and is transffered to blood * Travels to brain * Increased pulmonary ventillation increases the speed of uptake * Liver metabolism is the primary route of elimination * Concentration that is required to prevent 5o% patients from responding to painful surgical stimulus with "gross purposeful" movements * Called Minimum alveolar concentration MAC * Represents a low potency of inhales anesthetic * 2 main types ○ Nitrous oxide N2O § Low potency and produces incomplete anesthesia § Has rapid and prominent analgesic effects § Minimum hypotension and respiratory depression occur with the use of these inhaled anesthetics ○ Volatile anesthetics, halothane isoflurane § Liquid at room temperature § Are aeroslized for inhalation § Potent drugs that produce unconcous and less degree of analgesia and muscle relxation Adverse effects of volatile anesthetics are decreased BP and decreased respiratory bronchial dillation also occur

Answer 5

* Go to blood * Travel to brain and exter effect * Also go to vital organs heart and brain * Also muscle and fat * Patient awakes after being given bolus of drug because redistribution of drug from brain to muscles and fat not by elimination in the body * Propofol ○ Most frequent form ○ Patients recover fast ○ Despite prolonged infusions ○ Extensive metabolism in liver and other organs ○ Ideal ambulatory anestehtics in addition to low dose can prevent nausea and vomitting common adverse effects is hypotension * Ketamine ○ Common general anesthetic used in hospital and often used in pediatric anesthia ○ Also a street drug ○ Causes hypertension and tachycardia but not usually apnea ○ Causes intracranial pressure ○ Most balanced anesthetic ○ Used to provide anthesthia for patient ○ Multiple drugs are used including inhaled, intravenous, and sedative hypnotic, opioid and nuromusclar blocking drugs to minimize unwanted adverse effects

Answer 6

* Loss of sensation that is confined to discrete area of the body * Local anesthetics not only block pain but also autonimic function temperature sensation light touch sensation and motor function * Therapuetic effect of local anesthethics can be terminated by systemic absorption, distribution and elimination * Recovery from local anesthesia is normal sponteansous, precitable and complete * Measning that no residual effects of local anesthetic remain after recovery * Locals are used for the following ○ Local infiltration anesthesia § Local anesthesia produced by injection of naestegtic solution in are aof terminal nerve endings ○ Spinal anesthesia § Solution is injected into spinal fluid ○ Epidurla anesthesia § Anesthestuc solution is injected into epidural space

Answer 7

* Allergy ○ Most allergies are not allergies to the anesthtic itself but due to the added preservatives to the solution ○ Sometimes reactiokn is mistermed allergy when it is additive physiological effect due to other drugs the patient is taking * Systemic toxcitiy ○ Occur from eccessively high BP levels ○ Associated with drug overdoses ○ All local anesthetics can produce sedation ○ Light headedness, visual and auditory disturbances and restlessness when the blood levels of the anesthetic are too higj * To prevent toxicity the dose of local anesthetic should be limited to below the known toxic threshold

Answer 8

* 5 criteria and 2 need to be met to be classifdied * Social impairments ○ Patient dose not fulfill major roles in their life ○ Peristent interpersonal and social problems ○ Occupatation or recreational activities may be reduced * Risky use ○ Use the substance in physically hazardous situations ○ Despite physiological or psychological problems caused by the susbtance * Impaired control ○ Persistent craving - addiciton * Tolerance ○ Individual may develop a tolerance to the drug * Withdrawal ○ If they stop using

Answer 9

* Genetic factors ○ Predispose someone to SUD ○ Mutations of dopinergic pathways may be associated with addiction * Pre existenting disorders ○ Disorder like Bipolar or depression ○ Or anxiety or schizo are at higher risk * Environment factors ○ Some environments can lead to SUD ○ Exposure to the drug in family or trauma or social groups ○ Genetic factors of spouses and sublings with SUD are at higher risk * Developmental factors ○ Some people are more vulnerable during certain timeframes of life ○ Adolsence and adulthood are the age groups primarily associated with initiation of SUD ○ Smoking usually begins before the age of 18 ○ 80% of those with alchol use disorder begin problematic use of alcohol before the age of 30 and illict dryg use of ten begins between 15 and 18 years of age

Answer 10

* Nature of drug ○ All drugs are natural reinforcers ○ Same as food and sex ○ Pleasureable effects produced increase probability that it will be taken again ○ Heroin and cocaine produce intensely pleasureable effects * Route of administration ○ Some routes have rapid administration ○ Greater potential for misuse than drugs that produce the effect more slowly ○ Drugs administered by sniffing inhaltion or intravenous are usually more prone to mususe than those taken orally * Amount/frequency ○ Greater the dose and frequency of use ○ The greater the potential for development of tolerance withdrawal and addiction ○ Occasional use of alchol in moderation will rarely lead to tolerance withdrawal or addiction ○ Frequent use will lead to thoose thinhs * Availability ○ Major factor in determining potential for misuse ○ More widespread a drug is the more likely it will be misused ○ Alchol is only moderate intrinsic misuse potential ○ Most used in psychoactive substance in socity ○ Because readily availabke ○ Heroin has a very high intrinsic misuse potential ○ Has posed a lower overral risk in NA as availability is controlled by law * Inherent harmfulness ○ Potential of drug to cause harm ○ If drug is a risk to health will not be widely available ○ Methyl alcohol iw widely available when consumed produces inebriating effects similar to ethyl which is the drinkable one ○ In small doses methyl can cause blindness and death which is why it is not widely misused despite being very avaiable

Answer 11

* State which repeated administration of given dose has less pharmacologocial effect * OR, state which the dose of a drug must be increased to obtain the same magnitude of pharmacological effect as was produced * * Drug tolerance is usually expressed as shortended duration of action * And a decreased magnitude of effect * Tolerance does not develop to all drugs * Drug tolerance is reversible upon discontinuation * Tolerance develops to the euphoria caused by heroin but not the constipating effects of it * Develops by 2 mechanisms * Metabolic tolerance ○ Increased elimination of the drug from the body usually due to increased metabolism * Cellular tolerance ○ Occurs via up or down regulation receptor systems ○ Under normal circumstances there is balance between receptor and activity and a cellular proccess ○ Repeated adminsitration can induce cellular tolerance ○ Normal regulatory mechanisms will increase or decrease the receptor population/transmitter release to maintain a set level of activity ○ The diagram is a concept of cellular tolerance

Answer 12

* Drug binds to receptor on cell membrane * Activates proccess within the cell * Then compares the current activity within the cell to the regular set point or the set level of activity that is nor,ally maintained within the cell * When the drug repeatedly bidns to a receptor, the genetic set point increases and cellular tolerance to that drug increases * When drug is administered increase in the observed cellular response * Now the receptor activation by both endogenous and exogenous transmitter with time the biological system accommodates the presence of the drug and the endogenous system Leaving the exogenous drug will need t be added to obtain the same response as occurred with the first dose as the endogenous susbstance is no longer present

Answer 13

* Occur between pharmacologically similar drugs * Defined as the resistance or tolerance to one drug becauses of the tolerance to a similar drug Person is tolerant to CNS depressant alchol they will also be tolerant to CNS depressant benzodiazepines even if they have never taken them before in their life

Answer 14

* Abnormal physiological state produced by repeated administration of a drug that leads to the appearance of withdrawal syndrom when the drug administratioon is discontinued or the dose is decreased * Severity of the withdrawal syndrome increases witj the speed of drug withdrawa; * AS the biological proccess that have accommodated ot the presence of the drug do not have the time to reverse themselves * The fear of withdrawa; is one factor that contributes to the continuing of the drug-taking behaviour * Withdrawal symptoms are usually the opposite to the effects of the drug * Withdrawal from amphetamine would manifest as sleepiness * The severity of the withdrawal symptom increases with the speed of the drug * Withdrawal, as there is not time for the biological processes that have accomodated to the presence of the drug to reverse themselves

Answer 15

* Impaired control manifests as emotional and mental preoccupation with the drugs effecst and by a persistenc craving for the drug with its effects * Regardless of the consequences this is commonly reffered to as addiction * In other words it’s a state of which abruptly stopping or reducing dose produces non physical symptoms * Can occur not only to drugs but gambling shopping video games * Drug addiction is used interchangably with SUD

Answer 16

* Dopamine increase ○ Suggests that commonly misused drugs increase dopamine in the reward system ○ Other neurotransmitter sytsems are involved in susbstance misuse but the increase in dopamine appears to be key component of the brains reward system * Effects on reward systems ○ Dopaminergic systems are also responsible for natural rewards such as food and sex Drugs associated with addiction such as cociaine cause an axagerrated increase in dopamine latering the communication of the brain

Answer 17

* Increased dopamine ○ Number of sustances can lead to increase in dopamine in the brain § CNS stimulants like cocaine, amphetamines, nicotine, caffeine § Opioids (Morphine heroin, oxycontin § Other drugs alchol cannabis * Produce novelty ○ Some drugs are addicitive becauset hey produce a novel feeling ○ In the person taking the drug ○ Some of these include Lysergic acid diethylamide LSD ○ And ecstasy MdMA 3,4-methylenedioxymethamphetamine * Reduce anxiety ○ Some drugs are addictive because the yreduce anxiety in a person taking the drug These drugs include CNS depressants such as benzodiazepines and barbiturates

Answer 18

* SUD can occur with medications used as perscribed or with musused of substances * Misuse is defined as using the drug in amounts or ways other than what was perscribed * Perscribed opioids for a long period of time will develop withdrawal and tolerance * These are physiological processes that occur due to the presence of the drug * Occurance of tolerance and withdrawal alone are not sufficient for diagnosis of SUD * If this individual also meets some of the criteria outlined for SUD * They would be classified as having a SUD therefore SUD can occur with perscription use of a drug * Individual can also develop SUD after misuing a susbstance or drug * If the individual is using the drug in ways or amounts other than what was prescribed, or against social norms, the potential for misuse of a drug varies and is unfluenced by a number of factors

Answer 19

* Dependent on balance of excitatory and inhibitory signals * Glutamate is the primary excitatory neurotransmitter * Gamma-aminobutric acid GABA is the primary inhibitor Balance between these 2 control and modify the activity of the brain

Answer 20

* Common disorders linked to excessive CNS excitation * Behavioural changes like stress reduction and physicxal exercise and medication such as * Relative hypnotic agents * Anti anxiety effect ○ Treat anxiety disorder as obsessive-compulsive disorder * Sedation ○ Relieve anxiety, decrase activity, moderate excitement, and generally calm the individual * Hypnosis ○ Produce drowsiness and aid in the onset of maintenance of sleep * General anesthesia ○ Induce general anesthesia - state of unconsciousness with the absence of pain sensation

Answer 21

* Generalized anxiety disorder * Obsessive compulsive disordere * Panic Disorder * Post traumatic stress disorder * Number of phobias * Class of drug controls CNS excitation * Reduce amount of glutamate induced neural excitation * Can increase gabag inhibtory effect in brain * Most sedative hypnotics work in this manner 1. Most brain activity involved excitatory neurons, the release the excitatory neurons release Glutamate which binds and activates glutamate receptor. Nuerons fire when excitatory input exceed inhibitory pulse 2. GABA binds to its receptor on chloride channel and initiates the inhibitory effect. Most sedative hypnotic agents will also bind to chloride channel and mimic the inhibitory effects of GABA. The increased inhibitory signals in the presence of sedative hypnotics agents slows excitatory CNS transmission 3. Inhibitory signals eventually exceed excitatory signals and the glutamate nerves cease to fire

Answer 22

* Group of drugs that have the same mechanism of action and smiliar pharmacological properties. Thiopental secobarbital and phenobarbital are all drugs that fall under barbiturate calss of drug

Answer 23

* Most sedative hypnotics work by increase GABA inhibitory signals * GABA binds to chloride ion channel on membrane of neurons un brain and spinal chord * Its binding causes the channel to open and chloride ions to flow into the cell * Sedative hypnotic agents also bind to chloride channel * Each class of agent binds to a different one * Result is an increase in synpatic inhibition and thus damepning of neuronal responses * Drugs that bind to the chloride channel enhance the inhibitory effect of GABA

Answer 24

* 3 main classes of sedative hypnotics ○ Benzodiapzepines ○ Barbiturates "z" drugs

Answer 25

* Widely perscribed drug in the world * 10% of canadians use thjem atleast once a year for medical reasons * They bind to the chloride channel at a different receptor than GABA called the benzodiazepine receptor * Upon binding benzodiapzepines increase the fequency of opening the chloride channel enhacning the efect of GABA and producing CNS depression

Answer 26

* Usually a capsule or tablet * Some are intrvaeneous * Dufferent durations of actions * Determined by rate of liver metabolism And formation or lack of formation of pharmacological active metabolites

Answer 27

* Different clinical effects depending on short term or long term use * Short term ○ Relaxation ○ Calmness relief of anxiety or tension ○ Adverse § Drowsiness § Lethary § Impairment of thinking and memory § Nausea § Constipation § Modterate doses can impair motor control and driving § Patients on these drugs should refrain from driving or operating machinery * Long term use ○ Some individuals can take large amounts for long periods of time without any major evidence of intoxication ○ While otherdemonstrate symptoms of chronic sedative hypnotic intoxication § Impaired thinking, poor memory and poor judgement § Disorientation, incoordinationm slurred speech

Answer 28

* Have an increased likelihood of producing adverse effects in 2 populations * Elderly and pregnant/breastfeeding individuals * Elderly ○ Can produce cognitive dysfunction which should be used with caution. Also they metabolize things much slower and lead to over sedation, falls and injury * Pregnant/breasfeeders ○ Freely cross the placenta ○ When administered in the first trimester ○ They are associated with a small but significant risk of abnormailities ○ They are also secreted in milk and exposure to nursing infants can result in death

Answer 29

* Commonly involved in overdoses * Wide margin of safety for these drugs * Means that deaths form them are rare * Death occurs following ingestion of a large dose or rapid injection of a large dose * With combination of drugs like CNS depressant drugs like alcohol * Flumazenil ○ Benzodiazepine receptor antagonist that blocks the effect of the benzodiazepine. As such can be ised as an antidote for benzodiazepine poisoning * Patterns of use ○ Most widely perscribed drugs ○ Disorder can develop from perscription or recreational use * Misuse potential ○ When taken alone have weaker reinforcing properties than barbiturates, alchol, or opioids, and stims ○ They inherent harmfulness is much lower ○ Benzos do not depress respiration at therapeutic doses ○ They are often taken with other CNS depressants or stims and can increase misuse potential * Benzodiazepine misuse disorder ○ High degree of cross toleerance among benzos and other sedative-hypnotics such as barbiturates, alcohol ○ They all modulate chloride ion channel in the CNS ○ Risk of withdrawal is low for short term use (few months) ○ If use is chronic (1 year or more) sudden discontinuation will lead to withdrawal § Agitation § Paranoia § Seizures § Delirium

Answer 30

* Potent CNS depressants and are classified according to duration of action ○ Long acting 1-2 days phenobarbital ○ Short acting 3-8 hours secobarbital ○ Ultrashort acting 20 minutes thiopental * Similar to benzos they bind to the chloride channel at a separate site than GABA - the barb receptor * Activation of the barb receptpr increases the duratrion of the chloride channel increasing the GABA effects * Duriation of action for barbs determine medical use * Ultra short are for anesthia for surgery * Short to mimmediate acting may be for sleep * Long acting is for pain/migraine relief

Answer 31

* Possess a low therapeutic index and supress REM-type sleep * Lethality is common especially when combined with alcohol * There is no antidote * Result can happen during barbiturate withdrawal * They have been replaced by newer drugs

Answer 32

* Limited * Since they have been replaced with safer alternatives * Ultra short acting is used to induce anesthesia and phenobarbital is an anti seizure * Patterns of use ○ Perscribed much less frequently than 50 years ago ○ Illict use is still a problem ○ Sometimes combined with heroin, amphetamines and alc * Misuse potential ○ Equal or greater to alcohol ○ Pleasurable effects give significant degree of reinforcement ○ Inherent harmfulness of the barb is very high and shuld be avoided * Barbiturate use disorder ○ Tolerance develops rapidly ○ Mood effects barbiturates ○ Within a few weeks of nightly administration yp;erance to the anticonvulsant action develops much more slowlu and dose not appear to be a major problem clinically ○ High degree of cross tolerance exists between barbs and other sedatives ○ Addiction to barbs can result from regular use ○ Cravings often last persist long after use has stopped ○ Withdrawal happens after chroni cuse ○ Symptoms appear as § Tremors § Anxiety § Weakness § Insominia § Later on progress to § Seizures § Delirium § Visual hallucinations ○ Withdrawal can be fatal and dependent individuals must be withdrawan slowly under medical supervision

Answer 33

* Zolpidem, Zopiclone * And similar drugs that begin with the letter Z * Subset of GABA receptors that cause sedation * They have advantahes over benzos * As a hypnotic they disturb sleep patterns REM sleep even less than benzodiazepines Drugs in this class appear to have more sedative effects as compared to aniolytic effects as with benzos these drugs should be used with caution to the elderly

Answer 34

Anxiety - Benzos are second line treatment * SSRIs are the first lone * Potential for over sedaion and cognitive impairment is set for benzos Insomnia * Z drugs * Short acting benzos * Deoressive nature of these drugs cause users to feel drowsy Seziures * Long Acting barbiturates * For partial seizures * Benzos for status epilepticus Skeletal muscle spasm * Benzos - relax smooth muscle in disoreders like cerebral palsy Alcohol withdrawal * Benzos * Cross tolerance with alc

Answer 35

* 1% of Canadians have reccurent sseizures - epilepsy * Cause half of the seizures to be unknown * Other half occur due to CNS trauma * Metabolic or toxic states (brain deprived of oxygen or inflammation of brain) or alcohol withdrawal 2 groups general and partial

Answer 36

* 40% of all seizures * Involve entire CNS * Airising in both cerebral hemispheres and accompanied by a loss of consciousness * Subdivided into several classes * Type of movement and duration of loss of consciousness that occur during the seizure * Recovery from generalied seizures can take anywhere from minutes to hours * Depending on the type of generalized seizure * The postital period which is the period of latered state of consciousness that occura immediately after seizure If oten accompanies by gradullay clearing delilrium

Answer 37

* The other 60% * Excitatory neurons in the CNS * They have more restricted synmptoms Motor distrubances, alterations of perception taste smell or behaviour ( violence, disrption of consciousness)

Answer 38

* Synchronous discharge my radiate to involve surrounding areas * Of the brain * Extend of the involvement of the brain determines the classification and charactersitics of the seizures * Major exitctaory neurotrabsmitter in the CNS is glutamate * Major inhibitor is GABA * If exitatory glutamate input excees the inhibitory GABA inputt he neurons in the CNS will fire and most exitatory neurons in the CNS are glutamatergic neurons Seizures result from synchronous discharge of exitatory neurons in the CNS, then seizures must involve glutamatergic neurons

Answer 39

* Not completely effective * 65% of people have complete comtrol of their seziures and 32% suffer from seizures are not able to find relief * Increaseing inhibitory input to the neuron to supress firing ○ Accomplished by increasing GABA activity in the brain ○ Few common antoconvulsants that act by increasing GABA activity are valproate, phenobarbital and benzos * Blocking eletcrical activity of the nerve to slow nerve impulses ○ Block sdoium channels ○ Which slow the conduction of nerve impulses ○ Work by blocking nerve impulse transmission are lamotringe and valproate * Decrease excitatory transmission ○ Accomplished by decreasing the release of glutamate in the synapse ○ Lamotrigene act in this manner In addition to blocking sodium channels

Answer 40

* Most anti seizure drugs have similar pharmacokinetics * Since they all have to be able to cross the blood brain barrier * Absorption of these drugs is 80-100% from oral * They are cleared by the liver primarily * The anticonvulsant depends on the type of seizure * Drugs used for partial seizures are essential the same for all types of partial seizures * Drugs used for generalized ones are likely to be determined by the individual seizure type * Use of a single drug is often preferred especially in patients who are not severly affected * For patients with hard to control seizures many drugs may be used

Answer 41

* They are all similar and generally dose related and transient * CNS ○ Sedation ○ Tremor ○ Ataxia ○ Cognitive and visual impairment * GI ○ Nausea ○ Vomitting ○ Diarrahea * Hepatic ○ Elevated hepatic enzymes ○ Generally asymptomatic ○ Period of monitoring liver function is required * Immune system ○ Benign skin rashes occur in 5 to 20% of patients on anticonvulsants ○ Severe and potentially fatal skin hypersensitivity reactions can also occur as such ○ Presence of an anticonvulsant induced skin rash should prompt drug discontinuation * Adverse effecst to them should be minimized by starting with low doses * Slowly increase the dose * Dividing the dose of the drug with meals the classic anticonvulsants such as valporate are generally associated with more adverse effects than newer agents such as lamotrigine

Answer 42

* Most induce biotransofmraiton enzymes * Metabolism of concurrently adminsitered drug is increased * Resulting in decrease of duration of action of concurretnt drugs * Lead to a loss of therapeutic effect of concurrently administered drugs unless approporaye dosage adjustments are made

Answer 43

* Decrease CNS activity * Rarely lethal * Most dangerous effect of overdose is respiratory depression * Can be potentiated by other CNS depressants such as alcohol * Overdose treatment consists of supportive therapy As efforts to hasten the removal of the drug are usually ineffective

Answer 44

* Withdrawal of anticonvulsants does occur * Severity depends on the drug being withdrawn * Can increase frequency and severity of seizures Prudent to hradually discontinue the drug

Answer 45

* Reactive ○ Secondary depression ○ Most common type ○ Accounts for 60% of all cases ○ Occurs in response to real stimuli ○ May resolve sponteanously or through treatements * Major depression (endogenous) ○ 25% of all depression ○ Recurs throughout life ○ Distrubances in sleep, hunger and appetite ○ Loss of pleasure in most activities ○ Decrease in sex drive ○ Mental slowness ○ According to current evidence it is a genetuically determined biochemical disorder ○ Causes an inibility to cope with stress ○ Usually respind to antidepressant therapy * Depression associated with bipolar disorder ○ Accounts for 10-15% of all depression ○ Mood stabilizer is used to minimize atypical shifts in mood associated with this disorder ○ Deoression is sometimes managed with antidepressants although variable success

Answer 46

* Depressed mood for atleast 2 weeks * And a loss of interest in pleasure in activities * Associated with significant morbidity and mortality and is one of the most common causes of diability * Diagnosis relies on interveiw * Amine hypothesus ○ Depression may be due to a reduction in activity of one or more neurotransmitter systems in the CNS * Neurotropic hypothesis ○ Depression may be due to a loss of neurptrophic support characterized by a decrease in neurogenesis and synpatic connectivity * Neuroendocrine hypothesus ○ Depression may be due to an abnormality in hormones affecting mood

Answer 47

* Depression results form a deficiency of excitatory neurotransmitters in the CNS ○ Norepinephrine ○ Serotonin ○ Dopamine * Serotonin reuptake transporters SERT and norepinephrine uptake transporters NET remove their respective neurotransmitters from synapses * Terminating their action * Enzyme monoamine oxidase A MAO-A inactivates the neurotransmitters and they cannot be repackaged into vessicles * The amine hypothesis theorizes thtai n depression levels of release neurotransmitters fall below nromal levels leading to impaired neuronal function * Manifests as a lack of exictattion of neurosn and depression * Amine hypothesis is incimplete * Many studoes show that function or levels of norepinephrine or serotonin or dopamine are not decreased in depressed patients * However all current effective antidepressant drugs increase the amount of these neurotrabsmitters

Answer 48

* Depression is associated with reduced neurotrophic support * Refers to the grwoth and inter connectivity of neurons * This hypothesis stheprizes that reducing in nerve growth and inter connectivity neurons * Theorizes a reducting in nerve growth factors are responsible for a loss of neural plasticity and neurogenesis * Antidepressants stim neurogenesis and synaptic connectivity in cortical areas of the brain * Brain derived neuro trophic factor BDNF is a protein required for neural growth and axon sprouting within the nervous system * Changes in trophic factors such as BDNF is thought to play major role in development of major depression * Reduced interconnectivity between neurons resulting from reduced levels of BDNF leads to reduced neural activity and hence depression * Antidepressants appear to reverse thus process * Much evidence supports this but not all does * This is being widely investigated

Answer 49

* Abnormality in hormones which affect mood * Theory primarily focuses on changes within and interactions between the nervous and endocrine system * Major depression is associated with changes in a variety of hormones * Major depression is associated with increased cortisol levels * Well known endogenous elevation of cortisol is associated with mood symptoms similar to these seen in major depression * Up to 25% of depressed patienst have abnormal thyroid function * Known as hyperthydroidsim and characterized by depressive symtoms * Sex steriods are also implicated in major depression As estrogen deficiency in females and test deficiency in males are thought to be associated with depression

Answer 50

* Pathophysiology of depression can be explained by integrating all 3 theories * Amino neurotorphic and neuroendocrine * They are not miutally exclusive * But linked * Chronic stim of monoamine receptpr appear to increase synthesis of BDNF Evidence suggests that binding of cortisol to receptor in brain may decrease synthesis of BDNF

Answer 51

* Work in 1 of 3 ways * Block neurotransmitter reuptake systems ○ TCAs, SSRI, SNRIs * Block neurotransmitter metabolism thereby increasing the amount of neurotransmitter released ○ MAOi * Number of different antidepressants exist that may be persecibed to treat depression * Each target a different mechanism of action * All have common goal increase neurotransmitter in synaptic cleft * Maximal beneficial effecrs of antidepressants are often not seen until 4-6 weeks after initiation of therapy For each of the 3 antidepressant mechanisms various types of antidepressants are classified under these categories

Answer 52

* First antidepressants * They are a 3 ringed nucleus * Inhibit reuptake transporters of both serotonin and norepinephrine * Into the presynaptic axon causing an increased ocnentration of trhese neurotransmkitters are present in the synpatic cleft * Most common adverse effects that limit therapeutic usefyllness of TCAs an other receptor system which do not cobtriubute to efficacy but toxicity ○ Anticholinergeic effects - Dry moith, urinary retention constipation, and blurred vision ○ Antiadrenergic effects ○ Antihistaminic actions ○ Block NA Channels ○ Weight gain These drugs are effective antidepressants they have a number of adverse effects are generally only used when other drugs Fail to control depressio

Answer 53

* Intropduced in the 80s * Most widely used class of drug for depression * Relatively selective for blocking serotning transpoprter protein in the presynaptic terminal * Have much less effect on autonomic nervous system than the TCAs and therefore have less toxcity than thhe TCAs SSRI cause nausea headache and nervousness and insomnia * High incidence of sexial dysfunction with SSRI * They are much safer than TCA in even of over dose

Answer 54

* Decreased metabolism ○ SSRIs inhibit CYP450 enzyme metabolism of concurrently administered drugs is altered ○ Lead to drug toxcicity or loss of drug efficiacy ○ Some have minimal inhibition while others have major interactions * Serotnin syndrome ○ Occur due to concurrent use of multiple drugs that increase serotonin ○ Monoamine oxidase inhibitors are major culprit ○ TCAs and nother drugs increase serotonin also contribute ○ Serotonin syndrome is characterized by muscle rigitidy, elevated body temp and mental statis change ○ Syndrome can lead to coma and death

Answer 55

* Block transporters for both serotonin and norepinephrine * Have fair good safety profiles * Unlike TCAs these drugs do not have effects at autonomic and histaminic receptors * These agents share the same adverse effects as SSRI * These drugs have some adverse effects attributed to norpinephrine including an increasei n blood pressure and heart rate * Depressed patients may respond to this class of antidepressant and do not respond to SSRIs

Answer 56

* 2 MAOs exist * Designated as MAO A and MAO B * MAI A is enzyme responsible for metabolism of norpinephrine, serotonin and tyramine * MAO-B is more selective for metabolism of dopamine * Blocking major metabolic pathways for the monoamine neurotransmkitter * MAO inhibitor allow more amines to accumulate in the presynpatic stores * Resulting in more to be released when the nerve impulses reach the presynpatic neuron * Adverse effects include ○ orthostatic hypertension ○ Agitation ○ Insomnia

Answer 57

* MAO inhibitors are perscribed * Patients must be warned for the drugs interact with many other drugs * Over the counter and with tyramine containing foods * And can cause hypertensive crsis * Use of TCA, SSRI, or dextromethorphan is a patient taking mao inhibitor to wear off before switcjing to a new medication * This proccess usually takes several weeks MAOIs are considered second line drugs and are used when therapy or other drugs have failed

Answer 58

* Newer type of antidepressant that inhibits the activation of A2 receptors * A2 receptors are loacted on the presynaptic neuronal membrane are autoreceptors meaning that activation of the receptor inhibits the release of neurotransmitter form the presynaptic neuron * Drugs that block A2 autoreceptors remove this negative feedback loop * Allowing the presynaptic neuron to release moreneurotransmitter into synpatic cleft * Mritzapine is an example of an antidepressant that is an antagonist A2 recetors Also a potent antagonist for a1 and muscarinic receptors which contribute to adverse effects

Answer 59

1. Reduce the patient’s mood to a “normal” range with antipsychotic medications such as haloperidol, chlorpromazine, or new atypical antipsychotics. 2. Stabilize the patient’s mood within “normal” range with a mood stabilizer.

Answer 60

reduce psychotic symptoms caused by a variety of disorders, including bipolar disorder, schizophrenia, and drug-induced psychoses. You will learn about three classes of antipsychotics: 1. Phenothiazine antipsychotics PHAR 370 Module 03 Section 04 Page 2 of 6 2. Haloperidol 3. Atypical antipsychotics

Answer 61

primarily due to antagonism of dopamine receptors in different regions of the CNS Antagonism of dopamine receptors in the mesolimbic and mesofrontal regions of the brain helps to alleviate some of the symptoms associated with psychosis, such as unusual or bizarre behaviour, thought disorder, and delusions * Adverse Effects: * Antagonism of dopamine receptors in the nigrostriatal system of the brain results in extrapyramidal movement disorders. These include: o tremor o rigidity of limbs and slowing of movement o reduction in spontaneous activity o dystonia (involuntary muscle spasms) o akathesia (anxiety, restlessness, and repetitive purposeless action) o Tardive dyskinesia is a serious movement disorder that can occur and is characterized by involuntary movements of the face, tongue, trunk, and limbs, and can be severely disabling. This adverse effect may limit the therapeutic use of these drugs. * Antagonism of dopamine receptors in the hypothalamus will result in excess release of prolactin. o In females, this will result in the flow of milk from the breast and menstrual changes o In males it will cause sexual dysfunction Phenothiazine antipsychotics can also antagonize other receptors in the brain. Blockade of Cholinergic (muscarinic) receptors: * Therapeutic effects: Reduction of extrapyramidal adverse effects. PHAR 370 Module 03 Section 04 Page 3 of 6 * Adverse effects: Blurred vision, dry mouth, constipation, difficulty urinating. Blockade of Histamine Receptors: * Adverse effects: Sedation, drowsiness, and weight gain. Blockade of α-adrenoceptors: * Adverse effects: Postural hypotension, dizziness, reflex tachycardia

Answer 62

Like the phenothiazines, haloperidol competitively blocks dopamine receptors. Therefore, haloperidol has very similar pharmacological effects to the phenothiazines. The sedative and hypotensive actions observed with haloperidol are less than that observed with phenothiazines, but it has a high propensity for producing extrapyramidal movement disorders. It is considered a useful alternative for patients who do not respond to or cannot tolerate phenothiazines

Answer 63

Atypical antipsychotics, or second-generation antipsychotic agents, produce less extrapyramidal side effects. It is thought that these second-generation antipsychotics have a dual action by blocking dopamine and serotonin receptors. A large number of second-generation antipsychotics are on the market. Some examples are clozapine, risperidone, and olanzapine. Prominent side effects of the second-generation antipsychotics are: weight gain, increased risk of developing diabetes, and sudden cardiac death due to an abnormality in the rhythm of the heart.

Answer 64

schizophrenia * delusions and aggression associated with dementia in the elderly * autism spectrum disorder * developmental disorder * posttraumatic stress disorder (as an alternate to antidepressants) * obsessive compulsive disorder * borderline personality disorder

Answer 65

Mood stabilizers are the second category of drugs used to treat bipolar disorder. They are commonly used to prevent the mania (highs) and depression (lows) associated with bipolar disorder. Two categories of drugs commonly used as mood stabilizers are lithium carbonate, and anticonvulsants

Answer 66

Lithium carbonate is a mood-stabilizing agent used to prevent mood swings in patients with bipolar disorder. It is also used to treat mania. The mechanism of action of lithium has not been resolved. Two possibilities are currently under investigation: 1. Effect on electrolytes and ion transport. PHAR 370 Module 03 Section 04 Page 5 of 6 2. Effect on second messengers that mediate transmitter action. The evidence appears to be the strongest for the second possibility.

Answer 67

A period of two to four weeks of lithium administration may be required for lithium to have a full therapeutic effect. Acutely, manic patients often require temporary treatment with an antipsychotic drug, such as haloperidol, or an anti-anxiety drug, such as a benzodiazepine. The body eliminates lithium as if it were sodium. As such, increased sodium intake increases lithium excretion. In addition, lithium has a narrow therapeutic index. Therefore the safety and efficacy of lithium is enhanced by monitoring serum lithium concentration. Measurements should be made approximately 12 hours after the last dose

Answer 68

Tremor, thirst, excessive urination, edema, and weight gain may persist for the duration of treatment. * Confusion and loss of muscle coordination. * Mild hypothyroidism. * Toxic kidney effects are observed in some individuals treated chronically with lithium, but are uncommon. * When taken during pregnancy, it can, as a rare event, cause cardiac malformations in the fetus

Answer 69

Lithium was once the drug of choice for long-term maintenance to prevent both manic and depressive episodes in patients with bipolar disorder, however, the side effects and toxicities are relegating it to second-line therapy. Interestingly though, of all medications with demonstrated efficacy for treatment of bipolar disorder, lithium has the greatest efficacy for prophylaxis of future manic and depressive episodes. Furthermore, lithium is the only medication that has demonstrated a reduction in suicidality among bipolar patients.

Module 2 Flashcards

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