Term
| Drug abuse affects our ability to ________ . |
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Definition
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Term
| How do drugs and addiction negatively impact our day-to-day lives? |
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Definition
Medical: neurotoxicity, AIDS, cancer, death, etc.
Economic: Loss of productivity, negatively impact our economy
Social Wellbeing: Homelessness, crime, violence |
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Term
| What two reasons cause people to take drugs? |
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Definition
1. To feel good- to have novel feelings, sensations, experiences
2. To feel better- to lessen anxiety, worries, fear, depression, etc. |
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Term
| What kind of disease is addiction? |
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Definition
| Addiction is a brain disease. |
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Term
| How do we characterize addiction? |
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Definition
| The continued abuse of drugs despite negative consequences. Chronic, potentially relapsing despite treatment. Compulsive behavior. |
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Term
| What are some factors of addiction? How do these complicate its treatment? |
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Definition
Factors: Genes/Biology, Environment, The drug used, brain mechanisms
They complicate addiction treatment because the feed back into each other and each piece is difficult to study/connect. |
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Term
| What does it mean to say drugs are "imposters" of brain messages? |
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Definition
| Drugs are exogenous chemical substances with a biological effect and are comparable to our brains endogenous chemicals. They bind to the same receptors. |
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Term
| Anandamide, an endogenous chemical, is similar to _________, an exogenous drug chemical. |
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Definition
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Term
| What is our brains "reward center"? Why is it termed such? |
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Definition
| The nucleus accumbens,because it receives dopamine from the ventral tegmental area (VTA). It is activated very early on in drug abuse/addiction and has a heavy association with dopamine. |
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Term
| What part of the brain is involved in inhibitory/impulse control? |
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Definition
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Term
| Why is the prefrontal cortex so susceptible to drug abuse? |
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Definition
| It takes a long time (20+ years) to develop and helps us assess risks. It is often damaged by drug use. It also receives dopamine from the nucleus accumbens . |
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Term
| What neurotransmitter pathway is mostly involved in drug abuse? Which is involved to a lesser extent? |
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Definition
| Dopamine. lesser is serotonin |
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Term
| What are some of the functions of the dopamine pathway? |
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Definition
| Reward, motivation, pleasure, euphoria, fine tuning of motor functions, compulsion, survival |
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Term
| How does dopamine released in the nucleus accumbens impact the PFC? |
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Definition
| The PFC lies downstream of the NA in the dopamine pathway so dopa produced within the NA may travel and end up in the PFC. |
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Term
| What natural rewards elevate our dopamine levels? How does this work? What happens when we introduce drugs to this system? |
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Definition
| Food, sex, etc. These natural rewards are important for staying alive. When we introduce drugs they "hijack" this system. |
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Term
| What effect does music have on our dopamine levels? |
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Definition
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Term
| How do we define tolerance? How does tolerance occur? |
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Definition
| When we no longer respond to the same initial dose. Tolerance occurs when we repeatedly expose ourselves to the same dose of drug, leading to a diminished response/effect. |
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Term
| What receptors in the brain are effected by repeated drug use? How are they impacted? |
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Definition
| The expression of dopamine D2 receptors is effected by repeated drug exposure. Over time, the receptor numbers are reduced. This leads to a loss of gray matter = loss of expression. |
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Term
| How is addiction similar to other diseases? |
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Definition
| It is preventable, treatable, changes our biology, and can last a lifetime if left untreated. |
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Term
| What organs exhibit lower expression in response to repeated drug use? |
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Definition
| The brain, the heart, etc. |
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Term
| How does drug abuse lead to morphological changes in brain structure? |
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Definition
| Certain drugs, like alcohol, can lead to degeneration of brain matter after prolonged use. The PCF is very susceptible to damage. |
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Term
| Why cant addicts "just quit"? (from a physiological standpoint) |
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Definition
| Addiction changes our brain circuitry over time. Our control circuitry become reduced while saliency (reward), memory,and drive are enhanced. Essentially addiction begins with normal thoughts and turns into addiction as these pathways become stronger, therefore creating patterns in the brain. |
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Term
| How does drug dependence effect homeostasis? |
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Definition
| Our body now considers the drug to be a part of our normal biology. This means that we do not feel "normal" without them. |
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Term
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Definition
| When our drug dependence is so severe that you feel ill without the drug. |
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Term
| What are some psychological withdrawal symptoms? Physical? |
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Definition
Psychological: Anxiety, restlessness, insomnia, depression
Physical: Sweating, tachycardia, tremors, nauseas, emesis |
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Term
| Going "cold turkey" from what kinds of drugs can lead to death by causing seizures? |
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Definition
| Benzodiazepines and alcohol |
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Term
| How does comorbidity impact the likelihood of drug abuse? |
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Definition
| Individuals with comorbidity (diagnosed mental disorders or predisposition to developing a mental disorder) have a higher risk of abuse. |
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Term
| What are some examples of co-morbid mental illness? |
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Definition
| Early physical/sexual abuse, witnessing violence, stress |
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Term
| True or False: Drug users have a higher risk of developing mental disorders. |
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Definition
| True, ex: psychosis, depression, anxiety, panic attacks |
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Term
| How does smoking play a role in alcoholism and other addictions? |
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Definition
| Once you are dependent on one substance, you are susceptible to other dependencies. Smoking epidemiology: normal pop = 23 %, alcoholics and other addicts = 90+ % |
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Term
| Approximately what percentage of people with diagnosed depression smoke? |
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Definition
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Term
| What is the genetic theory behind smoking and schizophrenia that explains why nearly 85% of schizophrenics are smokers? How does this exhibit reestablishment of normal expression? |
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Definition
They are likely self medicating because both acetylcholine (endo) and nicotine (exo) bind to the same receptor and activate it.
This established normal expression because nicotine fills the spot of the acetylcholine which is not being produced, therefore bringing said person to the levels of normal expression. |
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Term
| How many Americans were estimated to have a substance use disorder in 2015? |
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Definition
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Term
| What treatment approach is necessary for addiction? |
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Definition
| We must treat the whole person- pharmacologically (medications), behavior therapies, social services, medical services |
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Term
| What is "functional recovery" of an addict? |
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Definition
| It involves dopamine transporter recovery- improvement in expression of dopamine receptors (with prolonged abstinence). |
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Term
| What are some ways we can interact with addicts to help them recover? |
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Definition
| Show them love, patience, perseverance, active treatment and replacement of triggers. |
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Term
| Differentiate between opium, opiate, and opioid |
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Definition
Opium- fluid obtained from poppy plant
Opiate- substance derived from opium
Opioid-substance with morphine- like actions, but not derived directly from plant |
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Term
| What are the contents of poppy fluid? |
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Definition
Alkaloids, 20+
Morphine 4-21%
Codeine 1-25 % |
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Term
| What was the first "designer drug"? How was it made and what was its intended use? |
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Definition
| Diacetylmorphine (heroin) made by adding hydroxyl groups to a methyl group. intended to be used to block cough. |
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Term
| In what year was morphine isolated as the main active ingredient in opium? |
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Definition
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Term
| Explain the relationship between the civil war and opium use. |
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Definition
| During the civil war, opium was introduced via chinese workers. Additionally, the hypodermic needle was invented. Soldiers were treated during the war with morphine and many came home with addictions. |
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Term
| What was the first commercial product by Bayer? |
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Definition
| Heroin to treat cough- using it to cure opium and morphine dependence |
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Term
| What are our endogenous opioids? Give a brief description. |
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Definition
1. Beta- endorphin (or endomorphins) (runners high), natural pain killer and important for fight or flight
2. The enkephalins (met-enkephalin and leu-enkephalin),primarily in connections between neurons
3. Dynorphin- too much or too little will cause pain
4. Orphaning FQ
5. Endomorphins 1 +2- mu receptor endogenous ligands, no genetic code for these so we can't genetically manipulate them for study |
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Term
| Why is it problematic to chronically use opioids? |
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Definition
| Because they bind to our endogenous receptors and our body then shuts down production of our own chemicals, problematic when you don't have access to drugs anymore |
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Term
| What are the proteins of the genes that are precursors for the endogenous opioids? |
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Definition
1. Pro-opiomelanocortin POMC (beta- endorphin)
2. Proenkephalin (enkephalins)
3. Prodynorphin (dynorphin)
4. Pronociception/orhpanin FQ- orphanin |
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Term
| Explain how POMC serves as a precursor for Beta-endorphin. Why is this important for fight or flight? |
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Definition
When out body is under stress, an enzyme cleaves off beta-endorphin from the end of a POMC, creating a natural pain killer. (ex: in child birth)
This is important for fight or flight because the cleaving of beta-endorphin allows for production of cortisol 9stress steroid) which gets our hearts pumping and allows for the reaction. |
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Term
| Where do each of our endogenous opioids bind? Where do drugs bind? |
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Definition
1. Endomorphins, like beta-endorphin, (from POMC) bind at mu 1 +2.
2. The enkephalins (from proenkephalins) bind at delta
3. Dynorphins (coming from prodynorphins) bind at kappa
4. Drugs bind to all! |
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Term
| What is the main opiate receptor in the brain? What kind of binding can occur here? |
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Definition
Mu
Full stimulation (agonist), partial effect (partial agonist), block the effect (antagonist) |
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Term
| Explain activation of GPCR. |
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Definition
| GDP goes to GTP, activated. Alpha subunit breaks off of beta-gamma. Hydrolyzes GTP to GDP to switch off. |
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Term
| All opioids are couple to _________ ________ proteins. |
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Definition
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Term
| Why are opiates great for pain? |
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Definition
1. They block the transmission of pain (by blocking the passage of neurotransmitters along pain path).
2. Block the perception of pain
3. Block anxiety associated with pain |
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Term
| How does acute use of opioids block the release of neurotransmitters? |
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Definition
| When cAMP goes down (because opioid receptors are couples to adenylate cyclase via g proteins), calcium entry into cell is blocked. K+ leaves the cell, so it becomes hyper polarized and turns negative. Neurotransmitters are then blocked from release because of decreased calcium levels. |
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Term
| What are two effects of opioids that you don't really ever build tolerance to? |
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Definition
| Constipation and bradycardia |
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Term
| Which receptor is typically responsible for deadly side effects in overdose? |
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Definition
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Term
| What are the effects of mu 1, mu2, kappa, and delta? |
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Definition
Mu1: analgesia, euphoria
Mu2: constipation, respiratory depression. bradycardia
Kappa: spinal analgesia, miosis
Delta: Analgesia through enkephalins (connecting neurons) |
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Term
| What will be the pupil size in withdrawal or opioids? In overdose? |
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Definition
Withdrawal- pupil will be dilated
Intoxication/overdose- pin point pupils (miosis) |
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Term
| What can be given in opioid intoverdose that is fast acting? Is this an agonist, antagonist? How is it given? |
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Definition
| Narcan (naloxone), antagonist, given through IV and pushed every 2-3 minutes |
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Term
| Describe each kind of binding at opioid receptors and what drugs may bind in such a way. |
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Definition
1. Agonist- morphine like effect (heroin,morphine, methadone, codeine weak binding except for Fentanyl)
2. Partial agonist- weak morphine like effects with strong affinity (buprenorphine)
3. Antagonist- block you from getting high but no effect in absence of opiate (Naltrexone,naloxone) |
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Term
| Why would n opiate addict always choose heroin over morphine? |
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Definition
| Morphine crosses into blood brain barrier much slower |
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Term
| What is the active metabolite of morphine? What does this mean about the drug (to have a metabolite which remains active)? Why is this important to know |
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Definition
Morphine-6-glucuronide
This means it has a longer duration of action. It is important to know this because if youre treating someone who cant clear the metabolite well (due to medical issues like kidney failure), you may overdose them. |
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Term
| Why is codeine 10% as effective as morphine? |
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Definition
| It is metabolized into 10% morphine. |
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Term
| Why is codeine often paired with acetominophen or aspirin? |
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Definition
| Requires less opioid for pain relief and rids pain via two distinct mechanisms. |
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Term
| Why is heroin considered a prodrug? |
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Definition
| Because it is broken down into an active drug (morphine). |
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Term
| Describe tolerance. What are the two kinds of tolerance (loss of activation of G proteins) to opioids? Describe each. |
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Definition
Tolerance involves the uncoupling of G proteins from receptors and binding to others. Calcium levels are restored and pain is not blocked. You then need more drugs to block the pain and lower calcium levels. (shifting dose responses curve to the right)
1. Desensitization (uncoupling from g proteins and coupling to beta arrestion, receptors being taken down into membrane)
2. Down regulation (degradation of the receptors entirely) |
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Term
| What is the classic triad seen in opiate overdose? What should be given in case of overdose to send someone into withdrawal? |
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Definition
Miosis (kappa receptor). coma, respiratory depression (mu2)
Give Naloxone |
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Term
| True or False: Withdrawal and overdose symptoms are the same. |
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Definition
| False, they are opposites. |
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Term
| What are some opiate overdose symptoms? Withdrawal? |
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Definition
Overdose- Analgesia, euphoria, respiratory depression, constipation, hypothermia, relaxation
Withdrawal- pain and irritability, hyperventilation, dysphoria, depression, diarrhea |
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Term
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Definition
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Term
| How long does protracted opiate withdrawal last? |
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Definition
| Up to 9 months, with weight gain, menstrual irregularities, etc. |
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Term
| Discuss medications that can aid in opioid withdrawal: |
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Definition
1. Clonidine- antihypertensive
2. Buprenorphine- partial agonist
3. Methadone- longer acting, limits ups and downs
4. Hydromorphone (Dilaudid w/ no acetominophen, Palladone)- shorter acting and more seducing
5. Oxycodone- Oxycontin- Time released, percocet (combined with acetominophen) |
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Term
| Acetominohen is damaging to what organ at higher doses? |
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Definition
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Term
| What is the most potent and fat soluble opiate medication? Forms? |
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Definition
| Fentanyl- forms Sublimaze (iv), duragesic (patch), Actiq (lollipop) |
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Term
| What is iontophoresis and what is it used for? |
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Definition
| Low intensity electric current transport of fentanyl through skin and into systemic circulation (IONSYS) |
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Term
| What treatment therapy for opioids is based on agonist maintenance? |
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Definition
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Term
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Definition
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Term
| The oldest known sample of marijuana is 2700 years old. Was it found to be psychoactive? |
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Definition
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Term
| What percentage of Americans have tried marijuana before graduating high school? |
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Definition
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Term
| True or False?L Legalization of marijuana hasn't led to any increase of consumption. |
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Definition
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Term
| Why is marijuana effective in such small doses? |
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Definition
| We have endogenous receptors which the chemicals in marijuana bind to readily. (the endocannabinoid system) |
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Term
| Cannabinoid receptors are GPCRS. Are they inhibitory or stimulatory? What is the effect? |
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Definition
Inhibitory- inhibit adenylyl cyclase thus lowering cAMP and activating MAPK
--They calm things down |
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Term
| What are the two classical types of cannabinoid receptors? Describe each |
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Definition
1. CB1- "central" receptor, most abundant GPCR in the brain!
2. "peripheral" receptor, localizxed mainly in immune cells and lymphoid organs |
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Term
| What are our two endogenous neurotransmitters which bind to our endocannabinoid receptors? |
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Definition
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Term
| What makes our endocannabinoids different from other neurotransmitters? Explain. |
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Definition
| They are made on demand, not stored. When we need them, we make them. |
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Term
| Describe the production of endocannabinoids. |
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Definition
| They start with precursors in the membrane and on demand are synthesized by enzymes. (have membrane precursors!) |
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Term
| What kind of signaling do endocannabinoids do? Explain. |
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Definition
| Retrograde signaling. Action potential in pre synaptic travels down neuron, causes Ca2+ release and neurotransmitter release. Binds across synaptic cleft and creates neuronal activity. Once neuron activated, starts endocannabinoid synthesis on demand. Then they travel from post to pre and bind to CB1 to inhibit it. Once used, broken down. |
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Term
| What breaks down anandamide and 2-AG into arachidonic acid? |
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Definition
Anand is broken down by COX2 and FAAH
2-AG is broken down by MAGL |
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