Substances of Abuse/Addiction Seminar 4-6 PDF

Substances of abuse/addiction Alcohol Nicotine Legal Most problematic in normal population Marijuana Amphetamines Heroin Cocaine Many of these are illegal or obtained illegally Steroids Ecstasy Benzodiazepines Alcohol In...

Substances of abuse/addiction Alcohol Nicotine Legal Most problematic in normal population Marijuana Amphetamines Heroin Cocaine Many of these are illegal or obtained illegally Steroids Ecstasy Benzodiazepines Alcohol In everyday use, alcohol usually refers to drinks such as beer, wine, or spirits containing ethyl alcohol Alcohol acts on the CNS and can cause changes in mood, emotions, behaviour and consciousness Alcohol is rapidly absorbed from the small bowel via portal circulation (around 80%), and stomach (around 20%). Alcohol is water soluble, and little or no alcohol enters fatty tissue. Alcohol is rapidly distributed throughout the body water accumulating in tissues with high water content. Alcohol readily crosses blood-brain and placental barriers. It reaches the brain within five minutes of ingestion, with blood concentrations peaking between 30 to 90 (typically 45) minutes. Health and medical complications Body system Complication Gastrointestinal Cirrhosis of liver. Hepatitis. Gastritis. Pancreatitis. Gastrointestinal haemorrhage. Malnutrition. Weight loss. Malabsorption. Cardiovascular Cardiac arrhythmias. Cardiomyopathy. Hypertension. Neurological Blackouts. Convulsions. Peripheral neuropathy. Acute confusional states. Head injuries. Long-term brain damage. Depression. Respiratory Pneumonia. Aspiration of vomitus while intoxicated. Reproductive Males: Hypogonadism – loss of libido, impotence, loss of secondary sexual characteristics, enlarged breasts. Females: Hypogonadism – loss of libido, menstrual irregularities, loss of secondary sexual characteristics. Musculoskeletal Gout Other Increase in cancers – particularly mouth, oesophagus, liver and colon. Increased risk of alcohol-related trauma. Increased risk of self-harm and suicide. Burden of disease - Australia Image:https://www.abc.net.au/news/2014-07- 31/alcohol-related-deaths-australia-2010/5637156 Burden of disease - Australia Safe alcohol use The National Health and Medical Research Council (NHMRC) Australian guidelines to reduce health risks from drinking alcohol (2009), recommend: For healthy men and women, drinking no more than two standard drinks on any day reduces the lifetime risk of harm from alcohol-related disease or injury. For healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol related injury arising from that occasion. Parents and carers should be advised that children under 15 years of age are at the greatest risk of harm from drinking and that for this age group, not drinking alcohol is especially important. For young people aged 15–17 years the safest option is to delay the initiation of drinking for as long as possible. For women who are pregnant or planning a pregnancy, not drinking is the safest option. For women who are breastfeeding, not drinking is the safest option. Standard drink A standard drink is a unit of measurement. In Australia, a standard drink is any drink containing 10 grams of alcohol, regardless of container size or alcohol type (e.g beer, wine, spirit). alcoholthinkagain.com.au/Alcohol-Your-Health/What-is-a-Standard-Drink Standard drinks - Beer Standard drinks- Wine Standard drinks - Spirits Metabolism of ethyl alcohol More than 90% of the ethyl alcohol that enters the body is completely oxidized to acetic acid in the liver by alcohol dehydrogenase (ADH). The remainder of the alcohol is not metabolized and is excreted either in the sweat, urine, or given off in one’s breath. This is the basis of the breathalyser test and is the reason one can smell alcohol on the breath of someone who has been drinking recently. Blood alcohol concentration Blood alcohol concentration (BAC) refers to the amount of alcohol present in the bloodstream. A BAC of 0.05% (point 0 five) means that there is 0.05 grams of alcohol in every 100 millilitres of blood.  Blood alcohol concentration Ethyl alcohol distributes in the body in proportion to the water content in the particular tissue. Ethyl alcohol crosses with water into the blood stream, therefore the process of distribution of alcohol is rapidly speeded up. The more one drinks, the more alcohol would be in the blood. Blood alcohol concentration Brick, J., & Erickson, C. K. (2012). Drugs, the brain, and behavior : The pharmacology of abuse and dependence. Retrieved from http://ebookcentral.proquest.com Blood alcohol concentrations Alcohol and the adult brain Source http://www.kickoff.net.au/Alcohol.html Alcohol and the CNS Image: http://comprar-en-internet.net/worksheets/brain-parts-and-functions-worksheet.html Alcohol and neurotransmitters Four of the most important neurotransmitters with respect to alcohol are Glutamate – Ethyl Alcohol inhibits NMDA glutamate receptors, thus diminishing the excitatory actions of glutamate. Gamma aminobutyric acid (GABA) – ethyl alcohol facilitates the action of GABA the major inhibitory neurotransmitter in the brain. Dopamine – interacts with the reward system. Serotonin – plays a role in reward pathway and mood. Alcohol addiction – the reward system Image: Page 1210. Craft et al., (2019) The reward system is comprised ventral tegmental area, extended amygdala and the nucleus accumbens within that appear to be important in the reinforcing (rewarding) properties of a variety of drugs including alcohol. Addiction 1. Drug stimulates an increase in dopamine signalling from the ventral tegmental area (VTA) to the nucleus accumbens. 2. The nucleus accumbens “perceives” this dopamine signal and measures the “goodness” of the agent or the natural reward based on the size of the dopamine release. 3. Glutamate projections from the nucleus accumbens instruct the prefrontal cortex to remember the environment and behaviours which lead up to the occurrence of the “goodness”. 4. In addiction, excess signalling of glutamate neurons in the prefrontal cortex stimulates the nucleus accumbens, triggering drug-seeking behaviours at the expense of naturally rewarding or good behaviours. Image: Page 1210. Craft et al., (2019) Alcohol addiction A modified reward process where by drinking alcohol provides an overall positive effect (euphoria or decrease in an unpleasant situation). This is coupled with those vulnerable individuals with a pattern of diminishing or ignoring the negative impacts of overconsumption - the hangovers, loss of memory, fights, violence and arrests. The less vulnerable individual equates heavy alcohol consumption as overall unpleasant as a result of the negative effects outweighing the positive. Alcohol addiction Alcohol addiction takes place primarily through two means. Positive reinforcement Represents an environmental situation in which a rewarding stimulus or experience increases the chances that the individual displays a certain response. Negative reinforcement Refers to an increase in behavioural patterns, such as alcohol ingestion, if the behaviour facilitates the individual to circumvent or avoid an aversive stimulus (symptoms of withdrawal). Banerjee, N. (2014). Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. Indian journal of human genetics, 20(1), 20. doi: 10.4103/0971-6866.132750 Alcohol & Mental Health People with mental health problems are at increased risk of experiencing problems relating to alcohol (people with both anxiety and depressive disorders have four times the rate of alcohol dependence). People diagnosed as having an alcohol dependence problem are also more likely to suffer from other mental health problems. - There is a high correlation between alcohol dependence and Posttraumatic Stress Disorder (PTSD). Alcohol use at well above low-risk levels is itself a causal factor in a number of mental health conditions. Alcohol and Mental Health. Australian Government. https://www.therightmix.gov.au/assets/factsheets/DVA0007_6_Alcohol_Mental_H ealth_v4.pdf Alcohol & Mental Health Drinking above the levels set in the Guidelines can lead to poorer outcomes for people who have mental health problems. In particular, people who are depressed and sometimes drink excessively are at much greater risk of self-harm and suicide, especially if they also drink regularly above guideline levels. Depression can be made worse by drinking excessively and can also be a consequence of dependent drinking patterns. While alcohol may bring some relief from anxiety or stress in the short term, it can worsen anxiety in the longer term, especially with binge drinking. Alcohol use above low-risk levels is associated with poorer outcomes for people suffering from schizophrenia. Alcohol can cause disrupted sleep, and interfere with the effect of medications. Alcohol can interact in harmful ways with most of the medications prescribed for mental health problems, even at low-risk levels of drinking (1–2 standard drinks). (Alcohol and Mental Health. Australian Government. https://www.therightmix.gov.au/assets/factsheets/DVA0007_6_Alcohol_Mental_Health_v4.pdf Neuroadaptation Neural adaptations to alcohol underlie the production of alcohol tolerance and the associated symptoms of withdrawal. Following cessation of alcohol the brain attempts to compensate for ethanol which influences normal functioning by altering the number or function of the receptors. The brain attempts to counteract the depressant effect of ethyl alcohol by increasing the activity of the glutamate system and decreasing the activity of the GABA system. Through neuroadaptation the brain is able in many instances to up-regulate (increase) or down-regulate (decrease) its function to compensate for the presence or absence of ethanol. Alcohol withdrawal syndrome Most people experience alcohol withdrawal syndrome 4-6 hrs after ingestion Typically known as “hangover” Nausea and vomiting Gastritis Headache Fatigue Sweating and thirst Cause of symptoms is unclear but is attributed to Restlessness dehydration, Irritability hypoglycaemia, and the ‘shakes’ accumulation of lactic acid Vasomotor instability and acetaldehyde in the blood If a person drinks at levels that put them at short-term harm… Source from: https://admin.americanaddictioncenters.org/wp-content/uploads/2015/10/alcohol-withdrawal.png Alcohol withdrawal Source: What is the Timeline for Alcohol Withdrawal. Origins Behavioural HealthCare. https://www.originsrecovery.com/timeline-alcohol-withdrawal/ Alcohol withdrawal Source: What is the Timeline for Alcohol Withdrawal. Origins Behavioural HealthCare. https://www.originsrecovery.com/timeline-alcohol-withdrawal/ Alcohol withdrawal Source: What is the Timeline for Alcohol Withdrawal. Origins Behavioural HealthCare. https://www.originsrecovery.com/timeline-alcohol-withdrawal/ Alcohol withdrawal This is only a rough timeline and it is important to note that withdrawal symptoms may vary from person to person. Use a rating scale to determine overall severity rather than rely on stages as a framework for understanding withdrawal. Withdrawal can commence between 6-24 hours after the last drink and can occur before the blood alcohol level is than females Individual differences – idiosyncratic Medications Anticonvulsants – contraindicated. Generally, doses are reduced and ceased prior to ECT Benzodiazepines - increase threshold (should be avoided or at least minimised) Seizure threshold increases throughout a course of ECT, due to the anticonvulsant nature of ECT. EEG monitoring EEG monitors brain activity during ECT - waveform. Standard practice in Australia since mid-1990s. EEG readout alongside pulse and motor response provides information obtaining to the adequacy of a seizure. EEG monitoring The EEG used in ECT is a four- lead monitor. This provides a waveform for each hemisphere of the brain. Two leads are placed on the forehead of the patient. EEG Monitoring The other two leads are placed on the mastoid process. The red lead on the forehead correlates with the black lead on the mastoid to provide an electrical waveform for the brainwave activity of that hemisphere. Side effects Common side effects include: Headache: caused by propofol and ictal activity. Muscle Soreness: caused by suxamethonium. Memory Dysfunction: Most patients have some degree of memory dysfunction lasting up to months post-treatment. Generally, patients are disorientated post-treatment. Side effects Rare side effects include: Post-ictal Delirium Treatment-induced mania in BPAD patients Dislocation and Fractures Skin burns Death: as the development of arrhythmia or respiratory depression. Treatment of side effects Common side effects such as muscle and jaw pain and headache – treated with an analgesic agent - Paracetamol,- generally given prior to treatment. Mania can be treated by closer observations onward (change of treatment setting may be necessary). Continuing ECT is normal treatment. Delirium needs to be identified quickly to reduce the risk to patients. Is treated with sedation such as Midazolam. In case of an emergency situation (i.e.. asystole) usual hospital policy and standards need to be maintained. Complications - prolonged seizures When a seizure is still continuing at 90 seconds of EEG readout the treatment needs to be aborted. The anesthetist should be informed at this point to end the seizure through pharmacological means. Either propofol or midazolam are acceptable drugs to use to end a seizure. Long seizures are associated with a worsening of cognitive side effects. Complications - cardiovascular Abnormal and unwanted cardiovascular responses can include asystole post-stimulus and the development of cardiac arrhythmia. ECG is carefully monitored by medical staff throughout ECT delivery to monitor for signs of these. ECT and medications Most drugs are continued throughout the course of ECT. Exceptions anticonvulsant medication and benzodiazepines. Anti-Depressants; There is a general consensus that most anti- depressants should be stopped before a course of ECT. They may need to start again near the end of a course for maintenance reasons. Anti-Psychotics; are generally maintained throughout ECT and are believed to have minimal effect on ECT. Clozapine has been associated with low seizure thresholds. Lithium; Can be continued throughout the course but should be withheld the night before and morning of treatment. There is an increased risk of toxicity and cognitive side effects.  Antipsychotics Target Dopamine (D2) receptors but also interact with other dopamine receptors (D1, D3, D4, and D5) Many antipsychotics also block Serotonin 5Ht2A and 5Ht2c receptors may antagonize other receptors Alpha1 – adrenoceptors Histamine H1 receptors These effects do not influence their antipsychotic properties but can produce side effects  Antipsychotics Often classed into two groups – Atypical or Typical, however this is an arbitrary classification (not related to chemical structure or side effect profile) Atypical (2nd Generation) Typical (1st Generation) Clozapine Haloperidol Olanzapine Chlorpromazine Risperidone Zuclopenthixol Quetiapine Flupenthixol Ziprasidone Fluphenazine Arapiprazole Trifluperazine Amisulphride Pericyazine Paliperidone Droperidol Antipsychotics – side effects Common Side effects Anticholinergic effects (Due to blockade of cholinergic receptors) Blurred vision Dry Mouth Constipation Urinary hesitancy or retention Sedation (Due to blockade of H1 histamine receptors) Orthostatic Hypotension (Due to blockade of alpha receptors) Extrapyramidal effects (Due to blockade of dopamine receptors) Antipsychotics – side effects Extrapyramidal effects (EPSE) Dystonias Muscle spasms of the face, tongue, neck, and jaw Hyperextension of neck and trunk and arching back Drug-Induced Parkinsonism Shuffling gait, drooling, tremor, increased rigidity, Bradykinesia, Akinesia Akathesia Subjective motor restlessness, inability to stand or sit still, need to move around, often agitated Tardive Dyskinesia Abnormal involuntary movements of the mouth, face, tongue, and sometimes head, neck, trunk, or limbs Antipsychotics – side effects Endocrine effects - Hyperprolactinemia Gynacomastia, galactorrhoea, amenorrhoea, anovulation, impaired spermatogenesis, decreased libido, impaired sexual arousal, impotence, and anorgasmia Metabolic effects – Metabolic Syndrome Abnormal glucose tolerance, increased serum lipids, and weight gain Neuroleptic Malignant Syndrome (rare) Coarse tremor, catatonia, Fever (>38oC), muscle rigidity, altered consciousness, autonomic instability (tachycardia, tachypnoea and urinary & fecal incontinence), Increased serum creatine kinase and leucocytosis Cardiac Changes Prolonged QTc interval – life-threatening arrhythmias (torsades de pointes) Antidepressants Classed according to action Monoamine oxidase inhibitor (MAOI) Tricyclic Antidepressant (TCA) Selective Serotonin Reuptake Inhibitor (SSRI) Serotonin and noradrenaline reuptake inhibitor (SSNRI) Tetracyclic antidepressants (TeTCA) Others Noradrenaline reuptake inhibitor (NRI) Reversible MAOI Monoamine oxidase inhibitors (MAOI) Bind irreversibly to monoamine oxidase (enzyme) which is responsible for the breakdown of the biogenic amine neurotransmitters – Noradrenaline, dopamine, and serotonin MAOI’s include Phenelzine (Nardil ®) Tranylcypromine (Parnate ®) MAOI – side effects Common Orthostatic hypotension Weight gain Sleep disturbances Agitation Impotence Rare Image:http://clearevroisal.ml/952595-maoi-and- low-tyramine-diet-cheeses.html Hypertensive Crisis (potentially fatal) Usually related to foods containing tyramine (or drug interactions). Need to avoid tyramine-containing foods e.g. cheese, yeast, broad beans, salami, sour cream, and red wine etc. Reversible MAOI Competitively and reversibly inhibits type-A monoamine oxidase (enzyme) which decreases the metabolism of Noradrenaline, dopamine and serotonin and therefore increases the concentration of these neurotransmitters in the CNS Reversible MAOI - Moclobemide (Aurorix) less sedating and less toxic than MAOI low tyramine diet not usually required Less likely to cause sexual dysfunction Common side effects include Nausea, dry mouth, constipation diarrhoea, anxiety, restlessness, insomnia, dizziness and headache Tricyclic antidepressants (TCA) Block the reuptake of noradrenaline and serotonin into the presynaptic terminals Also block other receptors - Alpha1 adrenergic, histaminergic, cholinergic and serotonergic receptors TCAs include Amitriptyline Clomipramine Dothiepin Doxepin Imaprimine Nortriptyline Trimipramine TCA- side effects Side effects related to the effect the medication have on receptors Alpha1 adrenergic – Orthostatic Hypotension Histaminergic - Sedation Cholinergic – Anticholinergic effects (dry mouth, blurred vision constipation, urinary retention/hesitancy Cardiovascular effects Slowed cardiac conduction, T wave flattening or inversion, arrhythmias, and sinus tachycardia Cardiovascular toxicity (the leading cause of death in overdose) Metabolic and endocrine effects Hyperglycaemia, gynecomastia (males) and enlarged breasts and galactorrhoea (females) Selective Serotonin Reuptake Inhibitors (SSRI) Selectively block the reuptake of serotonin into the pre- synaptic cleft – thus increasing serotonin levels SSRI’s include Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline SSRI – side effects Common Nausea, diarrhoea, tremor, agitation, headache, sweating, insomnia, drowsiness, weight loss or gain, sexual dysfunction, rhinitis Rare Serotonin Syndrome – due to increased serotonin concentration in the synapse which leads to hyperstimulation of 5Ht receptors Triad of abnormalities Cognitive effects – mental confusion, hypomania, hallucination, agitation Autonomic effects – fever, hypertension, tachycardia, nausea Somatic effects – muscle twitching, hyperreflexia Serotonin & Noradrenaline Reuptake Inhibitors (SNRI) Selectively block the reuptake of serotonin and noradrenaline into the pre-synaptic cleft – thus increasing serotonin and Noradrenaline levels SNRIs include Venlafaxine Desvenlafaxine Duloxetine SNRI – side effects Common lossof appetite, weight, and sleep, drowsiness, dizziness, fatigue, headache, nausea/vomiting, sexual dysfunction, and urinary retention plus anxiety, mildly elevated pulse, and elevated blood pressure due to noradrenaline blockade Rare Serotonin Syndrome Sedatives Benzodiazepines promote the binding of GABA (which is inhibitory) to the GABAA receptor which opens GABA- activated chloride ion channels – which reduces the firing rate of neurons (*NB Benzodiazepines do not substitute GABA, i.e. they are not GABA-receptor agonists) Sedatives Benzodiazepines (BDZ) Very short acting (Midazolam, Triazolam) Short acting (Alprazolam, Oxazepam, Temazepam) Medium acting (Bromazepam, Lorazepam) Long acting (Clonazepam, Diazepam, Flunitrazapam, Nitrazepam) Non-Benzodiazepines (Non-BDZ) (Zolpidem, Zopiclone, Buspirone, Promethazine) Benzodiazepine antagonist (Flumazenil) Sedatives – side effects Common Light headedness, Drowsiness, Memory loss, hypersalavation, over sedation, Slurred speech and ataxia Infrequent Headache, disorientation, confusion, vertigo, hypotension, euphoria, paradoxical excitation, anxiety Withdrawal Anxiety, insomnia, nightmares, irritability, dysphonia, sweating, hallucination, tremors, tachycardia, hypertension, psychosis, seizures Mood stabilizers Lithium is the only specific anti-mania drug  Reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission  Neuroprotective effects - preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala Narrow therapeutic range Lithium – side effects Common Metallic taste, diarrhoea, epigastric discomfort, polyuria, weight gain, oedema, skin reactions, hypothyroidism Infrequent Neurogenic diabetes insipidus with polydipsia and polyuria Rare Hyperthyroidism Toxicity Extreme thirst, frequent urination, nausea and vomiting, anorexia, diarrhoea, drowsiness, ataxia, tinnitus, blurred vision, dysarthria, course tremor Mood Stabilizers Others Sodium Valproate Carbamezapine Lamotrogine Topramate Levatiracetam Olanzepine Quetiapine Anticonvulsants Mode of action Enhance GABA inhibition (e.g. benzodiazepines) or inhibit GABA transaminase (Vigabatrin, Tiagabine, and Topiramate) Inhibit sodium channel function to stabilize the cell membrane (Phenytoin, Carbamazepine, Sodium Valproate, and Lamotrigine) Inhibit calcium channel function or ‘calcium conductance’ (Ethosuximide) Raise brain levels of GABA (Gabapentin) Anticonvulsants Medication Type of seizure Carbamazepine (Tegretol) Tonic-clonic, simple or complex partial Clonazepam (Paxam; Rivotril) Absence, myoclonic Ethosuximide (Zarontin) Absence Gabapentin (Neurontin) Tonic-clonic, simple or complex partial Lamotrigine (Lamictal) Tonic-clonic, simple or complex partial, Absence, Myoclonic Phenabarbitone (Phenobarb) Myoclonic Phenytoin (Dilantin) Simple or complex partial Sodium Valproate (Epilim; Valpro) Tonic-clonic, simple or complex partial  Common antiepileptic medication choices for seizures Seizure Type Commonly Prescribed Antiepileptic Medications focal seizures carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, sodium valproate, topiramate, lacosamide, zonisamide generalised tonic clonic seizures carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, sodium valproate, topiramate, lacosamide, zonisamide absence seizures ethosuximide, lamotrigine, sodium valproate myoclonic, tonic and atonic seizures clobazam, clonazepam, lamotrigine, levetiracetam, sodium valproate, topiramate infantile spasms prednisolone, vigabatrin, ACTH, nitrazepam neonatal seizures phenobarbitone, phenytoin, clonazepam, levetiracetam, topiramate https://www.rch.org.au/neurology/patient_information/antiepileptic_medications/ Anticonvulsants Common side effects Behavioural altered mood, drowsiness, dizziness, sedation Cognitive confusion, impaired memory, poor concentration ECT and medications Thyroxine; should be continued and is safe to give prior to treatment. Thyroxine has been found to reduce post-ECT amnesia. Cardiovascular agents; Drugs that affect the heart should be given through a course of ECT and are safe to give prior to treatment. Standard vital observations need to be maintained. Nicotine replacement therapy