PHAR 100 Module 2: Drug Misuse and Addiction PDF

MODULE 2- DRUG MISUSE AND ADDICTION SECTION 1- SUBSTANCE USE DISORDER What is SUD? - Substance Use disorders - When an individual meets a minimum of 2 criteria, the SUD is considered severe. 1. Social Impairments - Persistent social or interpersonal problems that affect the fulfillment of...

MODULE 2- DRUG MISUSE AND ADDICTION SECTION 1- SUBSTANCE USE DISORDER What is SUD? - Substance Use disorders - When an individual meets a minimum of 2 criteria, the SUD is considered severe. 1. Social Impairments - Persistent social or interpersonal problems that affect the fulfillment of major roles at school,work,home,etc. 2. Risky Use - Uses the substance in physically hazardous situations - Uses despite physiological or psychological problems it causes 3. Impaired Control - Persisted craving for substance (addiction) 4. Withdrawal - Experiences withdrawal syndrome when stopped using the drug 5. Tolerance - The individual develops tolerance to the substance Addiction - Emotional and mental obsession with drug’s effects that cause impaired control - Stopping usage results in non-physical syms. Dopamine Hypothesis Explains addiction through hypothesis Dopamine increase Effect on reward systems - Hypothesis suggests that commonly - Dopaminergic systems are responsible for misused drugs increase dopamine in natural rewards like food and sex reward systems in brain (limbic system) - Responsible for stimulus related rewards (video games, gambling etc.) - Drugs associated with addiction increase dopamine alerting communication with the brain. Characteristics of Addictive Drugs - Addictive drugs are split into 3 categories based on their effects 1. Increase Dopamine - Certain drugs influence brain reward systems: Central Nervous System Stimulants: Cocaine, Amphetamines, Nicotine, Caffeine Opioids: Morphine, Heroin Ocycodone (Other drugs like cannabis and alcohol) 2. Produce Novelty - Produce a novel feeling in the individual Drugs include: Lysergic acid and diethylamine (LSD), Ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) 3. Reduce Anxiety - Drugs include CNS depressants: Benzodiazepines, Barbiturates Drug Withdrawal - Appearance of withdrawal syndrome after the discontinuation or decrease in dosage of a drug - Produces an abnormal physiological state - Severity of withdrawal syndrome increases with the speed of drug withdrawal as the biological processes that have accommodated the drug don't have enough time to reverse themselves. Drugs and their withdrawal symptoms - Withdrawal symptoms are usually opposite to the effects of the drug 1. Stimulant Drugs: eg. Cocaine and amphetamines Sleepiness, muscle pain. Anxiety, tremors, low mood, suicidal ideations,, cardovascular problems 2. Opioids: eg. heroin, morphine, oxycodone Sweating, muscle aches, agitation, diarrhea, abdominal cramping, vomiting Drug tolerance - Defined as the state in which repeated administration of a given dose of a drug had progressively less pharmacological effect, or a state in which the dose of a drug must be increased to obtain the same magnitude of pharmacological effect as was produced by the original drug dose. - Biological system accommodates the presence of the drug as indicated by the shift in the dose response curve. - Expressed as a shortened duration of action and a decreased magnitude of effect  - Drug tolerance is reversible upon drug discontinuation. Cross Tolerance - Resistance or tolerance to one drug because of the resistance or tolerance to a pharmacologically similar drug Factors influencing SUD 1. Genetic Factors - Genetic mutation in dopaminergic pathways in the brain, associated with addiction confer an increased risk of SUD 2. Pre-existing disorders - Individuals with major affective disorder (anxiety, depression, etc) are at higher risk. 3. Environmental factors - Exposure to environments that promote drug use family dynamics, trauma alter the risk of SUD - Siblings and spouses of those with SUD have a higher risk associated with it. 4. Developmental factors - Individuals are more vulnerable during certain developmental timeframes - Adolescence and early adulthood are the age groups primarily associated with the initiation of SUD. Stigma of SUD - People with SUDs have been stigmatized not only by society in general but also by medical professionals. - To help remove stigma, alternate language can be used. Abuser, Addict Druggie or Junkie → Person with SUD Abuse→Use/misuse Clean→ In recovery/not currently using Harm reduction - An approved to reduce and prevent the negative consequences of substance use and improve health without judgment in 2 ways: 1. Health Harms - Goal to decrease morbidity (transmission of blood borne) and morality (overdose and secondary to associate morbidity)  2. Societal Harms - Decrease lost productivity, of children and criminal activity 3. Supervised injection sites Prescription Use vs Misuse of substances - Misuse is defined as using a drug in ways or amounts other than what was prescribed or against social norms. - when simply using a drug and then experiencing withdrawals, e cannot classify this as a SUD unless other criteria for a SUD are outlined. Potential for misuse of drugs - Misuse potential refers to the tendency of a specific drug to be misused. - Five factors affect this: 1. Nature of the drug - Effects produced by drugs increase the probability of it to be taken again - Natural reinforcers → heroin and cocaine produce intense pleasurable effects 2. Route of administration - Drugs administered through rapid routes of absorption, and that give rapid effected have a larger misuse potential - Siffing, inhalation, intravenous injection 3. Amount/Frequency of use - Greater dose and frequency increases potential of tolerance, withdrawal, and addiction (continued misuse) - Frequent alcohol use can lead to the development of these factors 4. Availability - More widespread a drug is the more it is used 5. Inherent harmfulness - Potential of the drug to cause harm - The more harmful it is it will be used less. Drug classes: Tolerance, withdrawal, and addiction Drug class Tolerance Withdrawal Addiction Opioids (morphine, Yes Yes Yes codeine, heroin) CNS depressants Yes Yes Yes (ethanol, sedative-hypnotics) CNS stimulants Yes Yes Yes (amphetamines, cocaine)  Hallucinations (LSD) Yes No Yes Cannabis (THC) Yes Yes Yes What is tolerance best defined as? - A state in which repeated administration of a given dose of drug has progressively lower pharmacological response. Which class of drugs is thought to result in addiction but no withdrawal? - Hallucinogens SECTION 2- AMPHETAMINES AND COCAINE - Reflect on similarities and differences Amphetamines - Controlled substances in Canada - Widespread misuse - Drug class includes: amphetamine, dextroamphetamine, and methamphetamine Related compounds: 1. Methylphenidate (ritalin) → used to treat ADHD 2. MDMA (ecstasy) → derivative of methamphetamine and is often misused (causes neuronal damage and death) Chemistry: - Synthetic organic compounds have similar structure to endogenous neurotransmitters norepinephrine and dopamine. - Synthesized fast resulting in elicit manufacturing Pharmacology of amphetamines - Increase excitation by increasing dopamine or norepinephrine in the synaptic cleft - Amphetamines are substrates for the dopamine transporter, meaning amphetamines compete with dopamine for dopamine transporter. This means that there is a build up of dopamine in the neuron and it must exit in a reverse manner out of the synaptic cleft, therefore increasing CNS excitation. CNS effects of amphetamines  1. Decreased threshold for transmitting sensory input to the cerebral cortex leading to CNS excitation → overstimulation, dizziness, restlessness, mild confusion, tremor, and rare instances usually with high dosage can cause panic and psychosis 2. Feeling of Euphoria and Reward 3. Temperature regulation and feeding center modifications leading to appetite suppression 4. Increase in aggressive behavior and mood swings Increased CNS excitation can lead to increased alertness, feeling of power, reduced fatigue, increased responsiveness, and may result in increased heart rate and blood pressure. Other effects of amphetamines 1. Effects of short-term use - Chest pain (angina, heart attacks) - Cardiovascular collapse → severe low blood pressure - Increased respiratory rate - *overdose may result in a seizure, high fever or stroke 2. Effects of long-term use - Chronic sleeping problems - Poor appetite - Anxiety, repetitive behavior, psychoses, aggressive behavior - Elevated blood pressure and abnormal cardiac rhythm 3. Concurrent drug-use - Drug use with other drugs at the same time may result in drug-drug interactions, misusing additional drugs and potential SUD’s Therapeutic use of amphetamines 1. Narcolepsy: chronic sleep disorder 2. Drug therapy can calm hyperactivity and improve attention and control enhancing task completion and scholastic/occupational performance. Ritalin can be used to treat these disorder Amphetamines: Potential for Misuse and SUD - Amphetamines produce euphoria and are effective CNS stimulants and are therefore widely misused. Potential for Misuse Potential for SUD - Extremely high because amphetamines Tolerance: develops to euphoria, and mood and methamphetamine produce powerful elevating effects, anorectic effects (substance euphoria producing loss of appetite), cardiovascular and - Water soluble salt forms of the drug allow respiratory stimulatory effects. And lethal effects for large doses that are readily injectable of drugs. → does not develop to therapeutic  resulting in quick and intense response. effects or drug induced psychosis. - Inherent harmfulness is due to their long term toxicities however it doesn't deter Withdrawal: Stopping use can result in mood misuse. depression that include profound, prolonged sleep, huge appetite, lack of energy and fatigue. Addiction: Administered to produce a rush, and these effects act as rewards for those taking the drug and become used to those effects. If the drug is not available it results in panic. Pharmacology of Cocaine - Cocaine is classified pharmacologically as a local anesthetic and CNS stimulant - Cocaine is classified as a narcotic and is the most popular recreational drug next to alcohol, caffeine, and cannabis. - Similar to amphetamines in its acute effects and pattern of toxicity Duration of Action: shorter duration of action usually less than an hour, compared to amphetamines at 12 hours. Routes of Administration: sniffed or smokes, while amphetamines are administered intravenously Mechanism of action of cocaine - Cocaine causes generalized CNS stimulation in a dose dependent manner (more cocaine=more CNS stimulation) 1. Reuptake inhibition - Cocaine inhibits the reuptake of primarily dopamine and serotonin into the presynaptic neuron. 2. Postsynaptic neuron activation - Increases concentration of these neurotransmitters in synaptic cleft , which increases the activation of the postsynaptic neuron’s receptors. Therapeutic Use of cocaine - Local anesthetic for mouth and throat - No longer widely used as better local anesthetics have been developed that have similar chemical structure but do not create the potential of misuse and SUD. Effects of Long term use of cocaine - Toxic psychosis (paranoia) - Hallucination or sensation of insects crawling under skin - Impaired sexual function - Permanent brain damage and impairment of neuronal function can occur - High BP and irregular heart rhythm - Changes to nasal mucosa as drug is sniffed Using alcohol and cocaine at same time can create a reaction that forms an active metabolite called cocaethylene. → it temporarily increases the euphoria experienced but also dangerously increases BP, violent thoughts and poor judgment. Cocaine: Potential for misuse and SUD - Widely misused and is often used concurrently with other types of psychoactive drugs. Potential for misuse Potential for SUD - One of the highest misuse liabilities Tolerance: tolerance develops towards mild amongst all drugs. elevating effect not psychotic effect. Tolerance - Due to euphoria which is reached rapidly does not develop to hallucinatory and behavioral by injecting the drug or smoking the form effects like amphetamines. of cocaine that has a lower melting point making it easier to smoke. Withdrawal: similar to this associated with - Inherent harmfulness: those who take amphetamines. cocaine experience physical and - mood depression that include profound, psychological deficits but do not appear to prolonged sleep, huge appetite, lack of deter misuse. energy and fatigue. Addiction: addiction can occur and results from the pleasurable and rewarding effects. Amphetamines Cocaine Quiz answers 1. Administration of amphetamines can result in insomnia due to their excitatory effect on the CNS 2. Cocaine inhibits the reuptake of dopamine and serotonin increasing their concentration in the synaptic cleft. SECTION 3: Introduction to nicotine and caffeine Cost of Tobacco to society - Each year, 48,000 canadians die from tobacco use - Social and economic cost is about 16 billion per year in canada ADME (pharmacokinetics) of nicotine - Nicotine is found in tobacco (responsible for smoking addiction) 1. Absorption: - Nicotine exists as very small particles and are absorbed rapidly when inhaled. - Absorbed from the GI tract, oral mucosa, and across the skin. - Dose absorbed can be controlled by the depth of inhalation and by frequency of smoking 2. Distribution: - Nicotine is distributed through the body and rapidly to the brain  3. Metabolism - Nicotine is rapidly metabolized through the liver 4. Excretion - Metabolites are excreted in the urine→ half life in body is about 2 hours Mechanism of Action of Nicotine - Nicotine stimulates nicotinic receptors at synapses→ similar to acetylcholine - Activation of receptors increase psychomotor activity, cognitive function, attention and memory. - Large doses can cause agitation, tremors, and seizures. - Effects in CNS are mediated by nicotinic receptor mediate release of dopamine and serotonin. Smoking in the 60’s - Use of tobacco products increased from the 1940’s until the 1970’s as it was considered “cool” smoke Therapeutic uses of Nicotine - Used in gum, transdermal patches or buccal spray - These attempt to maintain the blood nicotine levels and satisfy nicotine cravings. Short-term effects of smoking - Mild euphoria, enhanced arousal, increased concentration, and sense of relaxation → increase in heart rate and blood pressure and may suppress appetite. - Non regular smoker→ dizziness, headache nausea, vomiting, abdominal cramps. → smoke may trigger coughing or gagging. Long term effects of smoking - Tobacco contains carbon monoxide, carcinogenic aromatic hydrocarbons , tars and products of combustion. Cardiovascular disease Lung disease Cancer - Smoking has a higher - Smokers syndrome → - 30% of all cancers are  risk of cardiac caused difficulty breathing, estimated to be caused death. wheezing, chest pain, by cigarette smoke. - Long term respiratory congested lung and - Increases risk of lung, and carcinogenic effects increased lung oral, cavity and throat, are related to products infections. bladder and uterus of combustion. - Increased risk of cancer. - Nicotine has been linked emphysema and other to cardiovascular forms of chronic disease. obstructive lung disease. - Carbon monoxide rescues capacity of the red blood cells to carry oxygen → increase incidence of atherosclerosis and formation of thrombi Other effects of smoking - Exposure to passive smoke is associated with risk of cardiovascular disease and cancer. - Passive smoke increases the risk of bronchitis, pneumonia, asthma and sudden infant death syndrome. During pregnancy smoking can cause being small for gestational age and being born preterm. Nicotine: Potential for misuse and SUD 1. Tolerance - Most smokers keep nicotine blood levels at a certain range (30 to 40 nanograms/milliliter). 2. Withdrawal - Withdrawal results in irritability, restlessness, anxiety, insomnia, fatigue, and inability to concentrate. 3. Addiction - Occurs and manifests an extreme urge to smoke Pharmacology of Caffeine - Found in coffee, tea, and chocolate and over the counter stimulants, analgesic, and diuretics (substances that increase urine production and the excretion of water from the body through the kidneys). - Lethal dose of caffeine is 10g of caffeine for the average adult. ADME of caffeine 1. Absorption - Caffeine is rapidly and completely absorbed - Blood levels of caffeine are significant at 30 minutes and peak at 2 hours after ingestion 2. Distribution - Caffeine distributes to all parts of the body and freely crosses into the brain and placenta.  3. Metabolism - Genetics determines rate of metabolism and excretion of caffeine - Rapid and slow metabolizers. 4. Elimination - Half Life can be from 2.5 - 10 hours. Mechanism of caffeine - 100-250mg of caffeine, increases mental performance and motor activity while decreasing drowsiness and fatigue. Short term effects of caffeine 1. CNS - Increases mood and reduces fatigue - Caffeine produces nervousness and can interfere with sleep. - High doses produce irritability, nervousness, a rambling flow of thoughts and speech and psychomotor agitation. 2. Cardiovascular - Caffeine constricts cerebral blood vessels (useful during a headache) , increases peripheral blood flow and stimulates cardiac muscle (heart rate is increased) - High doses causes a rapid and irregular heartbeat 3. Respiration - Caffeine causes mild stimulation of respiratory rate and a relaxation of bronchial smooth muscle - Caffeine stimulates breath in preterm newborn as it helps their immature brain and lungs to remember breath. Long term effects of caffeine - Restlessness - Nervousness - Insomnia - Increased urinary output  - Gastric upset - Rambling speech and thought No definite link between caffeine consumption and disease states. Effects of caffeine in special circumstances - Drinking caffeine while smoking and during pregnancy 1. Caffeine and smoking - Cigarette smoke increases the metabolism of caffeine, and so the duration of action of caffeine is shortened in smokers. - Smoking cessation should prompt decreases caffeine intake 2. Caffeine and pregnancy - Caffeine is not associated with fetal abnormalities - Metabolism of caffeine slower in pregnant people, extending duration of caffeine and remains in the body two times longer in the second trimester and 3 times longer in the 3rd trimester. - Pregnant people decrease intake to avoid feeling unwell. Caffeine: Potential for misuse and SUD - Potential for misuse and SUD is low Potential for misuse Potential for SUD - Misuse potential is low Tolerance: - Euphoria experiences is mild in intensity - Advice suggests a tolerance does develop - Low to moderate intake of caffeine each to caffeine day does not appear to be associated with Withdrawal: adverse events - Abrupt cessation of caffeine intake will - Larger doses result in result in mild withdrawal like headache, irritability,nervousness, insomnia, and fatigue, and drowsiness irregular rhythm of the heart. Addiction: - Mild addiction can occur Amphetamines Cocaine Nicotine Caffeine SECTION 4 - INTRO TO PERFORMANCE ENHANCING DRUGS History of Drugs in sports 1950’s - Era of performance drugs began - Use of amphetamines and anabolic steroids - Used lots until the sports regulatory bodies banned these substances 1976 - First steroid testing occurred at montreal olympics → 11 athletes tested positive 1988 - Canadian Ben johnson was stripped of his gold medal in 1988 after a positive steroid test 1999 - World drug anti-doping agency was established in 1999 - Responsible for anti-doping policies in sports and countries 2007 - US athlete Marion Jones admitted to drug use and was sentenced to prison for perjury in 2007\ 2012 - Lance armstrong, Tour de France winner was stripped of his 7 titles for having an elaborate doping scene 2016 - Russian athletes were banned for doping scandal from 2016 olympics 2019 - State run doping got russia banned from olympics and major sporting events Classes of drugs used in sports 1. Amphetamines Q: Given the physiological effects of amphetamines, why do you think they are used in sports? Endurance Speed - Amphetamines allow athlete near - 14/15 swimmers were faster and 73% of exhaustion to continue runners improved their times. → large doses of amphetamines can lead to fatal increases in blood pressure (tolerance develops quickly) Anabolic steroids - Most commonly used banned drug in sports - Used to increase muscle mass, and strength in a large variety of sports, including football, wight lifting, running and gymnastics - Synthetic anabolic steroids are typically used in sports performance→ reduce androgenic effects but maintain anabolic effects. - Anabolic steroids stimulate growth of muscle tissue 1. Anti-catabolic  - Anabolic steroids produce an anti-catabolic response, which blocks the action of using protein from muscles to fuel training, which allows athletes to maintain muscle mass. 2. Anabolic - Anabolic effects result in protein production - Greater effects at high dosages by athletes - Protein supplementation is required. 3. Motivation - Motivational responses also contribute to the overall effect. Anabolic steroids can produce aggressive behavior (roid rage) → beneficial for most sports Effects of anabolic steroids 1. Low to moderate doses - Modest effects on average adult - Effect in inexperienced weightlifters is less than a good exercise program 2. Large doses (in athlete at peak of training) - In combination with a diet high in protein, it leads to increase in body mass, body weight, and strength. Toxicities of anabolic steroids 1. Mood swings - Chronic use is associated with aggressive behavior and mood swings 2. Severe Acne - Chronic use leads to development of severe acne on both the face and body 3. Cardiovascular disease - Anabolic steroids increase the plasma levels of low density bad cholesterol (lipoproteins) and decrease the levels of high density good cholesterol. 4. Altered liver function - Associated with altered liver function such as: hepatitis, liver failure, and liver cancer. 5. Reduced Testosterone levels - Steroids block the release of gonadotropin releasing hormone leading to a reduction in testosterone levels and sperm production → can lead to infertility, reduced libido and impotence - Low basal testosterone levels→ synthetic anabolic steroids produce androgenic effects such as increased facial and body hair, lowered voice, enlarged clitoris, increased libido and amenorrhea (absence of menstruation). Benzodiazepines - Used to combat insomnia and anxiety in elite athletes - For a good night sleep→ allows them to recover faster from intense training - Impaired psychomotor coordination and focus at higher doses → can cause benzodiazepine use disorder Blood Doping and erythropoietin - Used for performance enhancement in sport - EPO stimulates body to make more RBC’s - Blood doping is the reinfusion of the athletes own RBC’s Detection of Blood doping and erythropoietin use 1. Blood doping - Can be detected by measuring the age of the red blood cells 2. Erythropoietin - Can be detected by testing urine for the presence of recombinant erythropoietin Diuretics - Drugs that enhance the excretion of salt and water through kidneys - These drugs are used right before a competition to reduce body water and allow athletes to perform in lower weight classes. - Toxicities: excess electrolyte and water depletion (blood pressure drop, and kidney failure) Why Ban performance- enhancing drugs - 192 substances are banned in athletic competitions 1. Athlete protection - Must be protected - Athletes under pressure ignore their own health - Coaches can coerce the athlete to use performance enhancing drugs 2. Unfair advantage - Training and diet cannot match effects of drugs