1-Drugs PDF

Topic #1 - Drugs Tricky Topic Video - Drug Mechanisms Psychotropic/Active : Act on the brain to affect menta...

Topic #1 - Drugs Tricky Topic Video - Drug Mechanisms Psychotropic/Active : Act on the brain to affect mental state by influencing neurotransmitter signaling Neuronal Com Review. - Action Potential triggered by postsynaptic neuron NT's are contained in vesicles in the axon terminal When AP reaches the terminal vesicles fuse W/ cell membrane NT to enter an causing synaptic clefts and it can interact w/ recep. On the post synaptic neuron Excitatory = depolarization Specific effect of NT the #-type of Nis-receptors Involved is dependent - a on Two Major Drug Types (2 classes of pschotropics). 1 Receptor agonist. 2 Receptor Antagonist receptor (Acts against activation) ↳ Activate the receptor - Inhibit Activation of the Recep Effect Full > 1 [10 Receptor Agonists : Act most similarly to NT's (Activate) ↳ SimilarStructure to NT's Partial ↳ more into synaptic cleft + binds with Postsyn. recep. ↳ ↑ [3 = ↑ receptor binding/activation (Even when no NT present Inverse > - ↳ 10 % Full Agonist Agonist that triggers level of response of normal Ap (max "40mV) (100% activation) : ↳ morphine Partial Agonist Agonist that fall between 0-100 % of recep activation (ex buprenorphine :.. ↳ AP may not be triggered In verse Agonists : Inverse eff. on recep , negative response 20 % (hyperpolarization occurs) Receptor Antagonist : Inhibit recep activation ↳ Binds to receps. in Syn Cleft to inactivate them. (less recep for NT to bind to : less NT's active " as Antag. ↑ , More receps are inactivated (if high enough NT can no longer trigger an AP in the neuron ( Competitive Struct. Similar to NT butCan't : cause activation (NT can't bind/act. recep) ex. naloxone Non competitive binds to an allosteric site : - changes binding site -NT can no longer bind ex. CBD Reversible Only temporarily shortly after : binds to recep , dissociate from recep binding Irreversible : Permanent bond w/recep · completely inactivating it , only way to regain receptor function is by replacing recep. ↳ ex. naloxazone  Terminating response to NTs Enzymatic breakdown-enzymes - deconstruct the NT /must constantly prod replacement NTs to keep functioning) Reuptake NT from to be reused transporters) - - Syn. Cleft is taken back to presynaptic neuron (using mem. Reuptake inhibitors ↳ Group of compounds that act as antagonists for membrane transporters that allow neurons to be reused Competitive and Non, In both NT is cleared from the synapse at a lower rate = ↑ [NT] in syn cleft - SSRI's : Primarily inhibit reuptake of serotonin + used to treat depression by prolonging presence of serotonin Textbook Reading - Chapter 39 (Drugs + Altered Consciousness) Physical dependence changes : in normal bodily functions , withdrawal from Lrug upon cessation of use Psychological dependence : emotional need for the drug+ used to relieve psychological distress Tolerance : linked to psych dependence when of the drug to achieve eff prev exp at lower doses · , a person requires more+ more.. Drug Withdrawal : () symptoms exp when drug. use is discontinued Lopp of the effects of the drug) Drug Categories Stimulant (THR : , BP, Temp ↑ alertness euphoria, ↓app. , ↑ agitation paranoia, hallucinations , psych add , , ,. Yes amphetamines (Adderall) methamphetamines MDMA (Molly/Ecstasy ↳ ex. Cocaine , , , Sedatives/Hypnotics : ↓HR, BP ↑ Relax , inhibitions , , induce sleep motor disturbance , , mem loss ↓ , Resp. Rate , Psych. Add Les ↳ ex. Alcohol barbiturates (Secobarbital pentobarbital) , , , Benzodiazepines (Xanax) Opiates ↓ pain : , pupil dilation to gut motility ↓ , , Resp Function euphoria sleepiness, dth. , ,. due to Resp depression Psych Add Yes. , Fentanyl Morphine Oxycodone ↳ ex. Opium , Heroin , , , , Vicoden , methadone , other prescription pain relievers Hallucinogens : ↑ HR + BP, Percept changes. based on strain , method of ingestion + indu. differences , Psych. Add Yes. ↳ ex. Marijuana , LSD , Peyote , mescaline, DMT dissociative , anesthetics including Ketamine + PCP Depressant : drug that tends toSuppress (NS activity ↳ includes alcohol barbiturates , , benzodiazepines Lagonists of the GABA NT system) Methamphetamine : in its smokable form crystal meth is highly addictive (reaches brain quickly to prod euphoria) reuptake of dopamine ↳ block + stimulates it's release Euphoric High : feelings of intense elation + pleasure especially , in those who smoke or inject the drug Opiod - : Category that includes heroin , morphine , codeine, methadone that↓ pain E Methadone : synthetic opiod that is less euphorigenic than heroin and similar drags Codeine : Opioid with relatively low potency often prescribed for minor pain Lecture Notes Addiction : chronic disease characterized by repeated periods of drug craving , intoxication bingeing , withdrawal Substances of abuse are either stimulants or depressants of the CNS dev ↳ approx. 10 % of recreational drug users. drug addiction/dependence ↳ Worldwide legal drugs like alcohol + tobacco are the main cause of drug-related ↳ An alcohol is the most harmful of all lowest harm drugs, hallucinogens produce a ↳ In alcohol harm to others exceeds harm to self Sites of drug Action in the Brain Dopamine : Key NT connected to action of many drugs ↳ Rewarding eff - of drugs are linked to mesolimbic dopaminergic pathway (VTA Nac) + ↳ Many drugs avail. of brain Dz (dopamine) receptors (may explain tolerance) Drug Mechanisms Most drugs Agonist of NT (mimic NT) are or antagonists (Block NT) Some drugs ↳ interfere w/NT transporters w/ enzymes involved NT degradation or in synthesis or Altered consciousness Psychoactive drugs change : conscious experience , Tolerance after prolonged use Physical dependence : Withdrawal Psychological dependence Addiction Compulsive : use despite (*) consequences Routes of Administration Most drugs absorbed through capillaries in : Lungs marijuana/nicotine/cocaine / Fentanyl - Intestines-Ecstasy/alchol Intravenous-Heroin Intranasal - Cocaine ↳ Psychoactive drugs act centrally - must cross blood-brain barrier (BBB) ↳ BBB is of blood vessels brain composed special cells that line in the  Reward + Reinforcement ReinforcesStrengthen behavior : - Positive Reinforcement : addition of desirable stimulus ↑ response - Negative Reinforcement : Removing an undesirable stimulus ↑ response Types of Reinforcers Natural reinforcers : Food , Water , Sex-Have Survival value , Responding ↓ when satiety is reached Not-so Natural : Psychostimulants (cofe, speed) , Alcohol Addiction as a learning disorder Addition a "high jacking" of brain processes for reward-based learning Operant : (t Reinforcement : euphoria , I reinforcement = Withdrawal ↳ Smoking behaviour modeled from peersa Classical cond of drug eff. US and drug cues (S Why does Addictive State Persist ↳ Withdrawal symptoms disappear after a few days Depending ↳ on drug type physiological withdrawal symptoms duration Can vary ↳ Drug abusers easily relapse after withdrawal has long disappeared ↳ Drug-associated stimuli in the ehurm. can trigger relapse Psychostimulants - Caffeine Nicotine , , Cocaine , Amphetamine + derivatives (methamphetamine - Ecstacy) What , , Mephedrone Stimulants - diff. mechanisms Caffeine - Adenosine receptor antagonist Nicotine - cholinergic nicotinic receptor agonist Cocaine Monoamine - reuptake inhibitor Amphetamine - dopamine releasers (methamphetamine) what-weak dopamine releaser monoamine , reuptake inhibitor Methamphetamine Vs Cocaine. Meth highly dopamine releaser which↑ is neurotoxic cytosolic + cellular dopamine (3 transporters - with by interacting a I cell membrane synaptic) degradation + and with enzymatic and synthetic pathways - Cocaine inhibits reuptake of dopamine which the eff of signaling of this NT & the synapse Note : Cocaine is also a local anesthetic (Blocks Na channels) cause of burns in crash cocaine smokers , ↳ Regu high temps to become volatile+ causes numbness of the lips  Depressants Alcohol : health benefits w/ light moderate use - Most studies disagree ↳ Tumors of oral cavity, pharynx , larynx oesophagus liver, , , colorectum + breasts associated with alcohol consumption Smoking + Drinking have synergistic effect on cancer Sedatives Benzodiazepines : most common , Act as GABA agonists Opiates : Pain ↑ mood , , morphine , codeine , heroin , Oxycodone Inhalants : ex. acetone Opiates Opium extracted from the poppy Papaver Somniferum : has been used for thousands years Morphine Named after Morpheus greek god of dreams, : isolated in 1806 Heroin : chemically diacetylation 1898 synthesized by morphine in ↳ Opioid therapeutics are the most effective analgesics available , medically first used to treat dysentry ↳ All Opioid receptors mediate analgesia ↳ N receptors involved in reward 8 in emotions, stimulation , is triggering dysphoria Self Administration Primates - Cocaine Self-Administration produces characteristic pattern of drug administering + breaks when the drug produces convulsions - When given free unlimited access to morphine/heroin a person/monkey's daily intake ↑ slowly wo periods of abstinence Q Flupentixol (dop recep blocker) doses ↑ and in high doses ↓ but has little eff - in low Self-administration on heroin s-ad. -. cocaine. Lesion of the mesolimbic of 6-PHDA ↓ cocaine but not heroin self-administration dopamine system - Drugs + Neuronal Plasticity - Chronic cocaine ↑ dendritic branching + spine density in the nucleus accumbens (NA) and medical prefrontal cortex (MPFC) - Chronic morphine ↓ spine density and dendritic branching in the same structures Opioid Overdose + Psychological Tolerance Example of behavioural tolerance and classical conditioning - - Animals given daily small doses of heroin had a higher survival of lethal doses /similar in humans) ↳ Mice will switch easily into opioid administration in homecage us outside cage Alcohol Approx ppl worldwide abuse alcohol - 100m - Sdrinks for men/4 24 considered harmful/binge drinking women over a period are Abuse/dependence twice - as common in men as in women Higher in European countries lower in Asia - Most long-term Brain - alcoholics show cognitive impairment and damage Alcohol Metabolism - Majority metabolized in the liver - Metabolism of ethanol is constant w/tine-arTong person (Oml pure ethanol/hour Zhus to metabolize ~ I drink DNA damage due to alcohol No alc. dehydrogenase in brain but alc can be. metabolized by catalase and cytochrome PYSO ZE2 Both reactive O species produced by ↳ cytochrome + acetaldehyde can induce DNA damage ↳ these it's believed up of a hangover is the build Fetal Alcohol Spectrum Disorder (FASD) - caused by maternal alcohol consumption during pregnancy - Pre and postnatal growth deficiencies small brain, facial anomalies , (NS dysfunction , - Binge drinking is more harmful than chronic exposure Alcohol and Dementia Risk of dementia is ↑ for abstinent as well as those who consume more than 14 alcohol units /week Alcohol Mortality , and Cancer - Any dose of alcohol is connected to↑ risk of cancer Drinking (1 drink/day is associated w/ ↓ overall mortality + cardio-related mortality - Many researchers disagree with benefits Hallucinogens Marijuana : Cannabis sativa plant , THC , Endocannabinoids Memory impairment Medicinal , , uses LSD : Lysergic acid diethylamide - IS or acid , Profound effects on perception Psychopharmacological Effects of Hallucinogens ↳ Produce altered states of consciousness but at doses that are not toxic to mammalian tissues ↳ do not induce drug dependence or addiction + are not considered reinforcers ↳ effects are unpredictable and depend on expectations of user ↳ Motivation for taking them is usually not connected to reward but to curiosity History of Cannabis - One of oldest psychotropic drugs known to humanity - Most widely used group of illicit drugs Two Main preparations derived from marijuana and hashish - -> viscous resin of the plant Chinese Emperor Shen Nung 1st to have BC prescribed the properties theraputic 2733 - + uses in Acute Effects Locomotion ↓ locomotor activity : Cognitive Slowed Cognitive processing ↓ ST Memory, ↓ inhibitory control , ↓ sustained (3 , Perfo : , ↓ visuospatial processing Cardiovascular ↑ HR BP : , Immune system : suppresses immune function (CB2) Eye : ↓ intraocular pressure Temp : ↓ Body Temp Anti-nausea/appetite stimulation : used clinically Anti convulsant: Used to treat muscle spascity Pain : Analgesic