Qurat Mansoora 100301323 Sean Forrester BIOL3020

1. Qurat Mansoora100301323Sean ForresterBIOL3020 Heroin

2. Background information • Very addictive and illegal! • Belongs to the opioid family - Derived from the opium poppy (Papaver somniferium) - Semi-synthesized from morphine providing a stronger and more immediate effect. • Pain reliever and cough suppressant http://upload.wikimedia.org/wikipedia/commons/8/87/Opium_poppy.jpg

3. Also known as… • Street Names: - Black Tar, Mud, Smack, Junk, China White, Mexican Brown, Horse, H, Skag, Dope= • Diacetylmorphine: the International Nonproprietary Name • Diamorphiane: the British Approved Name; legally prescribed drug

4. Formation • The -OH group of morphine is replaced by –OCH3 producing codeine • Both –OH groups of morphine replaced by –OCOCH3 produces heroin • Morphine • Codeine • Heroin

5. So what’s the difference? • Morphine: - used for medicinal reasons- prescribed pain killer • Heroin: - illegal to manufacture, possess, or sell- used as a pain-killer as well as a recreational drug- highly addictive! Pure Heroin • White powder • Has a bitter taste http://www.pbs.org/wnet/wideangle/shows/centralasia/images/heroin5.jpg

6. production • The opium gum is converted to morphine in labs near the fields and to heroine in labs near the producing countries. • The dealers then dilute it with sugars, starch, or powder milk prior to selling • Sometimes quinine is also added to imitate the bitter taste so the user is unable to tell the quantity of heroin in the sample. http://www.spiegel.de/img/0,1020,817155,00.jpg

7. Intake techniques • Can be mixed with other narcotics for various effects • Sniffed, snorted or smoked for high purity • Powder form can be heated to melt and then injecting the liquid form into veins using a syringe- 3-5 times more potent than the powder form. • Easily overdosed and can lead to death • Possible transmission of HIV and other diseases due to the sharing of needles [1-3] http://www.russianspy.org/wp-content/uploads/2006/11/heroin.jpg http://i.current.com/images/asset/889/022/26/PN7mpv.jpg

8. Heroin on the streets • Varies in color from white to dark brown due to additives or impurities left from the synthesis process • Comes in granule, powder, solution, or pill forms • The dealers then dilute it with sugars, starch, or powder milk prior to sellingso the user is unable to tell the quantity of heroin in the sample • Sometimes quinine is also added to imitate the bitter taste. http://upload.wikimedia.org/wikipedia/commons/archive/5/5b/20070725121556!Heroin_asian.jpg

9. Pathophysiologicalimmediate results • After intake, heroin crosses the blood-brain barrier:- Converts into morphine by removal of the acetyl groups • Binds quickly to µ,κ, or δ opioid receptors- µ: results in analgesia, euphoria, CNS depression, respiratory depression, and miosis- Κ and δ: also analgesia but kappa receptors are mostly found in the spine. • Feeling of a quick surge of pleasure targeted in the gut • “High” or a “rush” • Pain relief [2,3]

10. Overall effects • The intensity dependant on dose of heroin is taken in and therefore how quickly the heroin enters the brain and binds to the µ-opioid receptors • Warm flushing of the skin • Dry mouth • Extremities feel heavy • Nausea and Vomiting • Several hours of drowsiness • Clouded mental function by effect on the CNS • Slows the heart as well as breathing Flushing of the skin http://www.vlib.us/medical/HMSO/skin1.jpg

11. Central nervous system • Alters the Paleomammalian brain • Manipulates emotions with increased feelings of pleasure and euphoria • Blocks pain signals transmitted by the spinal cord • Changes the brain stem • Controls reflexes • Slows down breathing [2,3]

12. Extended long-term effects • Addiction • Increased tolerance • Physical dependence • Euphoric reward decreases • Need higher doses for the same effect • Increased repetition • Severe shortening of breath or suffocation

13. Withdrawal symptoms • Increase in intensity and occur more often • Restlessness • Insomnia • Muscle and bone damage • Can cause death to the fetus of a pregnant user [2-4] • Major affect on gastric movements • Cold sweats • Quivers • Nail biting • Yellowing and darkening of the nails

14. Mechanism • Endogenous Substance: • The natural neurotransmitters are endorphins • Used to combat pain • Endorphins production reduced when present • Difference- Endorphins: naturally produced by the body and are quickly broken down after they are released; - Heroin: more addictive; stays in the body for a longer period of time • Reduced endorphin production creates strong dependence on heroin [5]

15. Mode of action • Mimicry of Endorphins: • Heroin is first converted into morphine then mimics endorphins, creating a sense of well-being • Direct agonist that directly binds to the µ-opioid receptor and activates it • Mimics and substitutes for endorphins • Leads to increases in dopamine release in the limbic system • Increased dopamine concentration produces the “high” [6]

16. Incentive • Pleasurable sensation from heroin occurs due to the reward centre being stimulated • Dopamine: Key neurotransmitter in the reward system • Three types of neurons are involved in the reward process: • Endorphin neurons • GABA neurons • Dopamine neurons [4,5,7]

17. Dopamine GABA Electric Signal Inhibitory Signal µ-OpioidReceptors GABA Receptors GABA Neuron 2. Neurotransmitter GABA inhibits the release of dopamine µ-Opioid Receptors Dopamine intercepted No reward Dopamine Neuron 1. Normally, Dopamine is released continuously (Normal Conditions) Incentive

18. GABA Neuron Dopamine 2. When bound, the opioid receptors prevent electric signals from releasing GABA [5,7] Inhibitory Signal Electric Signal µ-Opioid Receptors Endorphin GABA not released GABA GABA Receptors Endorphins immediately begin dissociating and break down after being bound to opioid receptors Endorphin Neuron Dopamine free to proceed to target 1. Electrical signal is applied on an endorphin neuron, the vesicles are exocytosed and are able to bind to the µ-opioid receptors on the GABA neuron [5] µ-Opioid Receptors Dopamine Neuron 3. Inhibition of GABA allows the dopamine neuron to release dopamine, resulting in the feeling of pleasure and well-being [5,7]. Incentive

19. Dopamine Inhibitory Signal Electric Signal Endorphin µ-Opioid Receptors Dopamine Neuron Endorphin Neuron The dopamine neuron possesses µ-opioid receptors. Binding inhibits dopamine from reaching its target. Endorphins can therefore produce stimulatory and inhibitory effects [5].

20. Dopamine GABA Neuron Inhibitory Signal µ-Opioid Receptors Electric Signal Endorphin Neuron Morphine Endorphin GABA not released GABA GABA Receptors Dopamine free to proceed to target µ-Opioid Receptors Heroin converts into morphine and mimics the endorphins by binding tightly to the µ-opioid receptors. As the GABA supply decreases, dopamine is more free to proceed to its target and stimulate pleasurable reward [5,7]. Dopamine Neuron (Heroin Conditions) Reward

21. Morphine also binds to µ-opioid receptors of the dopamine neuron, decreasing inhibition of dopamine activity • However, the release of dopamine is independent as it is not being inhibited or intercepted by the inhibitory signals due to the binding of morphine to the GABA neuron µ-opioid receptors [7]

22. Morphine µ-opioid Receptors Endorphin P Substance Prevention of P Substance release P Neuron Morphine: competitive agonist as it binds to receptors on the P neuron, blocking the release of more P substance (pain signals) [5,7] Endorphin Neuron Adjacent Neuron Receptors Adjacent Neuron Morphine also acts as a competitive antagonist as it will also block the receptors on the adjacent neuron from receiving P substance [5,7]

23. Morphine eventually dissociates from receptors and slowly breaks down • Difference:- Endorphin: short term effect; dissociate almost immediately; quick break down- Heroin: longer lasting; stays bound for a longer period of time

24. Fatal effects • Heroin can easily lead to overdose and can most dangerously cause suffocation • Can severely affects breathing rhythm- neurons regulating breathing patterns also possess µ-opioid- morphine acts like an antagonist, inhibiting signal transmission to the breathing muscles and slowing down the breathing • An overdose can cause lungs to collapse and therefore prevent all breathing causing suffocation [2-5]

25. Other physiological effects • Heroin contracts the pupils to as small as less than one millimete • Many areas in the gastro-intestinal tract contain many opioid receptors • Heroin inhibits bowel activity leading to constipation • The vomiting centre is stimulated by heroin • The cough centre is suppressed by heroin • After continuous use, ability to feel pleasure is reduced or terminated if heroin is not taken often • Body has reduced or complete inability to release dopamine in a natural way [2-5]

26. treatment • OPIOID AGONISTS • Methadone: standard drug treatment for heroin addicts • Mimics morphine • Binds to and activates the same µ-opioid receptors as heroin/morphine, and produces the same cellular effects as heroin/morphine • PRO: more sterile, no crime or violence involved, reduces relapse • CON: still harmful! • Levomethadyl Acetate Hydrochloride (LAAM) produces effects similar to methadone in the brain and to reduce relapse • Longer duration of action than methadone [8]

27. OPIOID ANTAGONISTS • Naloxone • Reduces heroin craving post-withdrawal • Induces rapid detoxification in heroin addicts • Naltrexone • similar to naloxone, but is longer-acting • Nalmefene • Most effective since block more µ-opioid receptors • Buprenorphinemimics the brain’s natural neurotransmitters, resulting in gradual reduced withdrawal • Partial agonist • Acts as both an opioid agonist and antagonist[8]

28. References [1] Clatts MC, Giang LM, Goldsamt LA, Yi H. 2007. Novel Heroin Injection Practices: Implications for Transmission of HIV and other Bloodborne Pathogens. American Journal of Preventive Medicine; 32(6): 226-233. [2] Michels II, Stöver H, Gerlach R. 2007. Substitution treatment for opioid addicts in Germany. Harm Reduction Journal; 4: 5. [3] Jaffe JA and Kimmel PL. 2006. Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review. Clinical Journal of the American Society of Nephrology; 1: 655-667. [4] Lenoir M and Keiflin R. 2006. Heroin Addiction: Anticipating the Reward of Heroin or the Agony of Withdrawal. The Journal of Neuroscience; 26(36): 9080-9081 [5] Belgraver M, Erkamp B, Dragutinovic, Kerssemakers R. 2007. Heroin and the Brain. Jellinek Preventie Amsterdam: http://www.eztest.com/web/index.php?option=com_wrapper&Itemid=39 [6] Terenius L. 1997. Opioid Peptides and Receptors in Drug Abuse. Department of Clinical Neuroscience; 11: 171-176. [7] Yao L, McFarland K, Fan, Peidong, Jiang Z, Inoue Y, Diamond I. 2005. Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior. Proceedings of the National Academy of Sciences of the United States of America; 102(24): 8746-8751. [8] Wasilow-Mueller S and Erickson CK. 2001. Drug Abuse and Dependency: Understanding Gender Differences in Etiology and Management. Journal of the American Pharmaceutical Association; 41(1): 78-90.