stimulants including khat.pptx

Editor's Notes

• #2: When to use pharmacological intervention in ?
• #5: Throughout his professional life, he was addicted to cocaine and later also to morphine,[4][5] which were not illegal during his time. As revealed by Osler's diary, Halsted developed a high level of drug tolerance for morphine. He was "never able to reduce the amount to less than three grains daily" (approximately 200 mg).[6] Halsted's addictions resulted from experiments on the use of cocaine as an anesthetic agent that he performed on himself
• #7: Erythroxylum coca Used in its raw form for more than 1500 years indigenous to South America, where the leaves of the shrub are chewed bylocal inhabitants to obtain the stimulating effects among mostly abused psychostimulant substance
• #8: Regular local anesthetics for eye surgery Was added in coca cola beverage 1976 –freebase developed 1980-crack popularized
• #10: Methods Cocaine can be snorted, injected, smoked or eaten. The level and length of the effects depend on how the drug was induced.
• #11: Cocaine hydrochloride salt:  80% less potent Water-soluble formulation  Can be ingested orally, intranasally, or intravenously Freebase cocaine – potent –free of the drug’s hydrochloride additive.converted to cocaine sulphate. Extremely potent Heat-stable formulation that can be smoked Very rapid onset of action  Extremely addictive Crack rock- produced by dissolving powdered cocaine in a mixture of water and sodium bicarbonate (baking soda) and boiled till it becomes solid -slid pieces -lethal
• #12: Most brain dopamine produced where? What aout ne and sero action? 1/MC) Projetcs VTA to pfc Regulates cognition ,emotions, affect and functioning. Associated with –sxs and depressive sxs of schizophrenia 2/ML Projects VTA to Nucleus accumbens in the limbic system Regulates rewards ,pleasure ,reinforcement, learning and conditioning and addiction systems. Substances enhance the reward system , Associated with +sxs of schizophrenia …. 3/NG Substantia nigra to stratium Regulate movement 4/tuberiinfundibular Hyphothalamus to pitotary Reguale prolactin prodaction As it is sympathomimtic nuerotransmittor….can act in adrenergic receptor (a and b)….so other effects (not related to z topic)Can also be converted to norepinephrine by catalase reaction by enzyme dopamine-beta hydrooxalase Cocaine targets the dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters blocking reuptake thereby increasing neurotransmitter levels within mesocorticolimbic circuits. These circuits include dopaminergic cells in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc) and prefrontal/orbitofrontal cortex (PFC). Both the VTA and NAc receive glutamaterigc inputs from the PFC. Neurons from the noradrenergic cell body region, locus coeruleus (LC), also project to the PFC and VTA significantly influencing cellular activity. The reinforcing effects of cocaine are generally attributed to increases in dopamine (DA) within limbic circuits. However, recent evidence indicates norepinephrine (NE) also plays an important role in the reinforcing effects of stimulants providing another possible therapeutic targe
• #13: binding in dopamine-rich brain regions,including the caudate-putamen and the VTA. Moderate levels of cocaine binding also occur in the substantia nigra, amygdala, hypothalamus, andlocus coeruleus. In humans, cocaine rapidly permeates the striatum, thenquickly redistributes out of it with a half-life of about 20 minutes. The timecourse of self-reported “high” closely follows this pattern of rapid uptake andclearance.Drug-related reinforcement is most strongly related to the dopaminergicprojections from the VTA to the nucleus accumbens. Cocaine administrationcauses transient increases in extracellular dopamine levels in these regions bybinding to the presynaptic dopamine transporter (DAT), thereby inhibitingdopamine reuptake
• #14: cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregulatory adjustments that mediate heat dissipation. Cns effects Cardiac Gi Generale
• #15: Aggressiveness, psychosis.
• #16: Cocaine is one of the most addictive drugs known to man. Those who use cocaine heavily or regularly find it extremely difficult to stop and often suffer through serious withdrawal symptoms such as:
• #17: It is a cns stimulant but used for ADHD! Amphetamines-like substances called in different names Dextroamphetamine(ice) Methamphetamine(crystal) mixed dextroamphetamine-amphetamine salt(crystalmeth) amphetamine-like compound methylphenidate(speed) Types of amphetamines Classical amphetamines :  Dextroamphetamine , methylphenidate , and methamphetamine Detected in routine urine  drug screening  (false positive  results may occur with the use of pseudoephedrine, bupropion , or beta-blockers ) Nonclassical amphetamines : chemically categorized as amphetamines , but clinically considered to be hallucinogens Substituted amphetamines  or “designer” drugs:  Includes MDMA  (“ecstasy ” or “party drug”) Not detected by urine  drug screening Bath salts: Synthetic cathinones (large family of amphetamine analogs)  Mechanism of action is similar to that of amphetamines . Prolonged duration of effect (days to weeks) Not detected in urine  drug screening
• #18: Amphetamine is one of the commonly used stimulants. Sinthesized from Chinese ephedra plant 1887- 1st synthesized 1930- for congestion, narcolepsy, post encephalitic parkinsonism, depression, 1914 -Used in WW II to fight fatigue and enhance performanceand lethargy. 1970s-US FDA–approvedindications for amphetamine Narcolepsy Obesity Depression and dysthymia Chronic fatigue syndrome Acquired immunodeficiency syndrome (AIDS) Cancer-related fatigue End-of-life care (depressive symptoms) Dementia Multiple sclerosis Fibromyalgia
• #19: Drug Alcohol Depend . 2021 Oct 1;227:108921.  doi: 10.1016/j.drugalcdep.2021.108921. Epub 2021 Jul 28. Methamphetamine use among American Indians and Alaska Natives in the United States Lara N Coughlin 1, Lewei Allison Lin 2, Mary Jannausch 2, Mark A Ilgen 2, Erin E Bonar 3
• #20: Although not as addictive ascocaine, amphetamines are nonetheless addictive drugs.Other amphetamine-like substances are ephedrine, pseudoephedrine, andphenylpropanolamine (PPA)
• #21: Classic and designer amphetamines are less addictive than cocaine. Amphetamine is a central nervous (CNS) system stimulant that functions by increasing the amounts of dopamine, norepinephrine, and serotonin (to a lesser extent) in the synaptic cleft through a variety of mechanisms. Amphetamine enters the presynaptic axon terminal through diffusion or uptake by the monoamine transporters DAT, NET, and SERT. Once inside the presynaptic terminal, amphetamine increases the amounts of monoamine neurotransmitters in the cytosol through the inhibition of vesicular monoamine transporter 2 (VMAT2) as well as through disruption of the electrochemical gradients necessary for vesicular transporter function. Amphetamine also inhibits the metabolism of monoamine neurotransmitters by inhibiting monoamine oxidase (MAO). At the same time, amphetamine stimulates the intracellular receptor TAAR1, which induces internalization or transporter reversal of DAT. The effects of TAAR1 on DAT may also extend to NET and SERT, although co-localization of TAAR1 with these two transporters has only been indirectly evidenced in studies thus far. The net result of this activity is increased efflux of dopamine into the synaptic cleft and reuptake inhibition in the synaptic cleft through DAT internalization and direct competition 
• #22: Amphetamine is a central nervous (CNS) system stimulant that functions by increasing the amounts of dopamine, norepinephrine, and serotonin (to a lesser extent) in the synaptic cleft through a variety of mechanisms. In addition to dopamine …..norepinephrine…. Norepinephrine is z 1 neurotransmitter used by z sypmathethic nurve system….in cns is linked to aruasal, alertness and attenction. Anlike epinephrine nor epinephrine more act on alpha receptors/vasoconstriction/inc BP. But may be converted to epi and act equally at a and b…(noreepi act on a1=vasocon. b1 =heart-tachy+arythmia.---inc.bp….due to inc.systolic and diastolic blood pressure they will be bradycardia(by Musca(m2).is nonselective a and b1 agonist! By different proposed mechanisms it acts on the affect aruasal ,cognition and attention of the brain
• #25: Why khat on cheeks? More than 40 alkaloids, terpenoids, flavonoids, sterols, glycosides, tannins, amino acids, vitamins and minerals. The khat phenylalkylamines comprise cathinone, cathine and norephedrine Cathinone is more potent than cathine Cathine converted to Cathinone will metabolized to norephedrine
• #26: Subst Abuse Rehabil . 2021 Aug 15;12:41-48.  doi: 10.2147/SAR.S324711. eCollection 2021. Prevalence of Khat ( Catha edulis) Chewing and Its Determinants: A Respondent-Driven Survey from Hossana, Ethiopia Riyaz Ahmad Rather 1, Solomon Berhanu 1, Lemma Abaynah 1, Mohammed Sultan 2 BMC Psychiatry . 2017 Apr 17;17(1):142.  doi: 10.1186/s12888-017-1284-4. Prevalence, withdrawal symptoms and associated factors of khat chewing among students at Jimma University in Ethiopia Tilahun Abdeta 1, Daniel Tolessa 2, Kristina Adorjan 3 4 5, Mubarek Abera Meta-Analysis  BMC Public Health . 2019 Feb 4;19(1):150.  doi: 10.1186/s12889-019-6495-9. Epidemiology of khat (Catha edulis) consumption among university students: a meta-analysis Getinet Ayano 1, Kalkidan Yohannis 2, Mebratu Abraha 3 Affiliations collapse Affiliations 1Research and Training Department, Amanuel Mental Specialized Hospital, POBOX: 1971, Addis Ababa, Ethiopia. [email protected]. 2Department of Psychiatry, Dilla University, Dilla, Ethiopia. 3Department of Psychiatry, Paulo's millennium medical college, Addis Ababa, Ethiopia   Review  PLoS One . 2018 Apr 12;13(4):e0195718.  doi: 10.1371/journal.pone.0195718. eCollection 2018. Prevalence and predictors of khat chewing among Ethiopian university students: A systematic review and meta-analysis Alemu Gebrie 1, Animut Alebel 2, Abriham Zegeye 1, Bekele Tesfaye 2 Subst Abuse . 2021 Mar 2;15:1178221821999079.  doi: 10.1177/1178221821999079. eCollection 2021. Khat Chewing Practice and Associated Factors among Medical Students in Gondar Town, Ethiopia, 2019 Tsegaye Adane 1, Walelegn Worku 1, Jember Azanaw 1, Lamrot Yohannes 1
• #28: Bath salts(synthethic cathinone)-very strong white powder eople typically swallow, snort, smoke, or inject synthetic cathinones.
• #29: Cathonine acts by increasing the realease of DAS and inhibition of norepi and sero. Cathonine is unstable
• #34: Schizophreniform psychosis paranoid delusions auditory hallucinations (frequently of a persecutory or threatening type) Consumption is ceased, resolution occurs 3–11 days but there is a tendency for the psychosis to recur if chewing is restarted. Manic psychosis grandiose delusions with flight of ideas and tangential thought processes, and a labile mood varying from euphoria to anger. subsides spontaneously within about 8 hours of chewing 3. Depression Arises on cessation of use. This has, on occasions, been associated with self-harm and suicide. Self-harm, suicide and violence Rare,documented during both chewing and the subsequent intoxication phase.
• #35: StUD is one the 10 class of drug disorder , as any SUD, indicating that the individual continues using the substance despite significant substance-related problems.
• #36: type of psychoactive substance that increases activity in the brain and cantemporarily elevate alertness, mood, and awareness. 
• #37: They generally follow the template for all substance usedisorders 
• #41: ………………………………. Stimulant withdrawal syndromes ……………………………………………………. A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine,or other stimulant use.B. Dysphoric mood and two (or more) of the following physiological changes,developing within a few hours to several days after Criterion A:1. Fatigue.2. Vivid, unpleasant dreams.3. Insomnia or hypersomnia.4. Increased appetite.5. Psychomotor retardation or agitation 
• #42: In early remission: After full criteria for stimulant use disorder were previouslymet, none of the criteria for stimulant use disorder have been met for at least 3months but for less than 12 months (with the exception that Criterion A4, In sustained remission: After full criteria for stimulant use disorder werepreviously met, none of the criteria for stimulant use disorder have been met atany time during a period of 12 months or longer (with the exception that CriterionA4, “Craving, or a strong desire or urge to use the stimulant,” may be met).  In a controlled environment: This additional specifier is used if the individual isin an environment where access to stimulants is restricted  in early remission in a controlled environmentor in sustained remission in a controlled environment). Examples of these environments areclosely supervised and substance-free jails, therapeutic communities, and locked hospital units. 
• #43: to control weight to improve performance in school, work, or athletics. For the treatment of attention-deficit/hyperactivity
• #49: While stimulant intoxication occurs in individuals with stimulant use disorders,intoxication is not a criterion for stimulant use disorder, which is confirmed by the presence of 2of the 11 diagnostic criteria for use disorder 
• #50: While stimulant intoxication occurs in individuals with stimulant use disorders,intoxication is not a criterion for stimulant use disorder, which is confirmed by the presence of 2of the 11 diagnostic criteria for use disorder
• #51: What is it? Specify ….the specific stimulant! Bradycardia is often present and is a reliable measure of stimulant withdrawal. Anhedonia and drug craving can often be present but are not part of the diagnostic criteria 
• #53: Delirium associated with stimulant use generally results from high doses of astimulant or sustained use, and so sleep deprivation affects the clinicalpresentation There is evidence either from history or physical or investigation findings 
• #54: The hallmark of SIPD is the presence of paranoid delusions and hallucinations(in 50%). Auditory hallucinations> visual and tactile. Rx for amphetamine-induced psychotic disorder is the short-term useof an antipsychotic medication such as haloperidol 2. SIMD includes the diagnoses of stimulant induced bipolar disorder and stimulant-induced depressive disorder, either ofwhich can begin during either intoxication or withdrawal. In general,intoxication is associated with manic or mixed mood features, whereaswithdrawal is associated with depressive mood features. 3. SIAD can occur during intoxicationor withdrawal. Stimulants can induce symptoms similar to those seen in panicdisorder and phobic disorders, in particular 4. SIOCD can occur during intoxication or withdrawal. After high doses of stimulants, someindividuals develop time-limited stereotyped behaviors or rituals (i.e., pickingat clothing, and arranging and rearranging items purposelessly) that share with OCD5. People sometimes use amphetamines as an antidote to the sexual side effectsof serotonergic agents such as fluoxetine, but stimulants are often misused bypersons to enhance sexual experiences. High doses and long-term use areassociated with erectile disorder and other sexual dysfunctions. 6. Stimulant-induced sleep disorder can begin during either intoxication orwithdrawal, and sleep dysfunction can vary depending on the onset. Stimulant intoxication -insomnia and sleep deprivation, stimulant withdrawal -hypersomnolenceand nightmares 
• #55: Cocaine and other substance abuse disorders are complex, involving biological systems as well as myriad social, familial, and environmental factors. Therefore, treatment of cocaine and stimulant abuse can be complex. As with any disorder, treatment strategies need to assess the biological, social, emotional, and pharmacological aspects of the individual's drug abuse. Behavioral therapies are often the only available effective treatment for many drug use problems, including cocaine use. Cognitive-behavioral treatment is a focused approach to helping cocaine abusers cut down or abstain, and remain abstinent, from abusing cocaine and other substances. The underlying assumption is that learning processes play an important role in the development and continuation of substance abuse. The same learning processes can be employed to help individuals reduce drug use and successfully cope with relapse. Cognitive-behavioral therapy aims to help patients recognize the situations in which they are most likely to use cocaine, avoid the situations when appropriate, and cope more effectively with a range of problems associated with drug abuse. CBT is also compatible with a range of other treatments, including pharmacotherapy. Another approach to treatment is harm reduction, whereby psychotherapeutic strategies are aimed at reducing the negative consequences associated with substance abuse without requiring the individual to commit to abstinence. Such an approach may eventually lead users to abstinence, and data shows that it often does, but its primary goal is to improve users' quality of life whether or not they are immediately willing to aim for abstinence Pharmacological Approaches There are no medications currently available to treat cocaine abuse specifically. Consequently, the National Institute on Drug Abuse (NIDA) is aggressively pursuing the identification and testing of new cocaine treatment medications. Several emerging compounds are being investigated to assess their safety and efficacy. Two medicines currently marketed for other conditions, topiramate and modafinil, have shown promise. Additionally, baclofen, a GABA-B agonist, has shown promise in a subgroup of cocaine addicts with heavy use patterns. Antidepressant drugs are of some benefit with regard to mood changes experienced during the early stages of cocaine abuse. Medical treatments are also being developed to deal with acute emergencies resulting from excessive cocaine abuse. Medications are sometimes used in combination with behavioral therapy. Disulfiram (a medication that has been used to treat alcohol abuse) in combination with behavioral treatment, has been successful in reducing cocaine abus Amphetamine The most effective treatments for amphetamine addiction are cognitive-behavioral intervention and contingency-management models. The Matrix Model, for example, is a comprehensive behavioral treatment approach that combines behavioral therapy, family education, individual counseling, 12-step support, drug testing, and encouragement for non-drug-related activities; it has been shown to be effective in reducing amphetamine abuse. Contingency management interventions, which provide tangible incentives in exchange for engaging in treatment and maintaining abstinence, have also been shown to be effective. There are no specific medications that counteract the effects of amphetamines or that prolong abstinence from and reduce the abuse of amphetamines. However, there are a number of medications that are FDA-approved for other illnesses that might also be useful in treating amphetamine addiction. Recent findings indicate that bupropion, the anti-depressant marketed as Wellbutrin, may reduce a methamphetamine-induced high as well as drug cravings elicited by drug-related cues. This medication and others are currently in clinical trials, while new compounds are being developed and studied in preclinical models.
• #56: reassurance; keep in safe and quiet environment.• Short-term use of sedatives to alleviate symptoms of anxiety and insomnia –benzodiazepines Stablization Iv line, cardiac monitoring ,O2 ,Measure core tempreture ,Head ct scan ,Evalue blood glucose, BUN, electrolye , ,Cbc ,urinalysis , coagulation profile Supportive measure Airway management ,Rapid rehaydreation ,Gastric decontamination if ingested , Assess psychological and neurological status Specific measures Agitation, anxiety ,hyperactivity , usualy controlled by enzadiazepines, diazepam is choice of drug Hyperthermia-should e talked with hypothermic blankets ,ice baths, dantrolene sodium infusion Tachycardia-amiodarone can be used Amphetamine indued chorea=diazepam and chloropromazine //// physiologic effects are not severe enough to require inpatient or residential drug withdrawal Most stimulant users do not come to treatment voluntarily. Their experience with the substance is too positive, and the adverse effects areperceived as duration is short as too minimal to warrant seeking treatment . ………….Supportive rx
• #57: In individual therapy - therapists should focus on the dynamicsleading to stimulant use, the perceived positive effects of the stimulant, and other ways to achieve these effects. Group therapy - often focus on discussions with other persons who use stimulants and on sharing experiences and effective coping methods. Family therapy- the way the patient’s past behavior has harmed the familyand the responses of family members to these behaviors, on the future and on changes in the family’s activities that may help the patient stay off the drug and direct energies in different directions. All this is for outpatient! Network Therapy. a specialized type of combined individual and group therapy designed to ensure greater success in the office based treatment of addicted patients.Network therapy uses both psychodynamic and cognitive-behavioral approaches to individual therapy while engaging the patient in a group support network. The group, composed of the patient’s family and peers, is used as a therapeutic network joining the patient and therapist at intervals in therapy sessions. The approach promotesgroup cohesiveness as a vehicle for engaging patients in this treatment ///The patient, peers, family and the therapists are part of the group./// Psychological intervention usually involves individual, group, and familymodalities. Individual therapy Motivational enhancement therapy (always) o Cognitive behavioral therapy o Interpersonal therapy (when indicated) 
• #59: Disulfiram Disulfiram (Antabuse®) is indicated for the treatment of alcohol use disorder however several randomized clinical trials have shown disulfiram decreases cocaine use [39]. Disulfiram and its metabolite diethyldithiocarbamate bind copper. Decreased copper levels inactivates copper-dependent enzymes such as dopamine-β hydroxylase (DβH) (Table 2), which converts DA to NE. DβH Inhibition increases DA and decreases the synthesis of NE [40]. Disulfiram also inhibits carboxylesterase and cholinesterase enzymes that metabolize cocaine thereby increasing plasma levels of cocaine [41]. Inhibition of DβH by disulfiram and subsequent decrease in central NE levels is likely responsible for its ability to decrease cocaine use [39]. Interestingly, a large clinical trial suggested that low doses of disulfiram (62.5mg and 124mg/day) increased whereas a higher dose decreased (250mg) cocaine use over time