The opioids and heroin. Dr Deny Susanti

Transcription

1 The opioids and heroin Dr Deny Susanti

2 Opioids Introduction Opiates, sometimes referred to as narcotics, are a group of drugs which are used medically to relieve pain, but also have a high potential for abuse. This group of drugs includes opium, morphine, heroin, and codeine. Other opiates, such as meperidine (Demerol), are synthesized or manufactured. Opium come from Papaver somniferum (poppy plant), native to Middle East in the areas that border the Mediterranean Sea The poppy plant is the source of a type of drug called opiates Opium is the dried sap produced by the poppy plant.

3

4 Opium resists poison and venomous bites, cures chronic headache, vertigo, epilepsy, asthma, coughs, jaundice, analgesic etc. Heroin can be a white or brownish powder which is usually dissolved in water and then injected. Sometimes opiates with legal medicinal uses also are abused. They include morphine, meperidine, paregoric (which contains opium), and cough syrups that contain codeine [a synthetic narcotic, such as dextromethorphan].

5 How are opiates use? Swallowed Dissolve in water and injected Sniff Inhaled the fumes from the heated powder There are a number of synthetic opiates which are used as painkillers such as pethidine and methadone which is often prescribed for heroin and opiate addiction. Opiates-the name given to the active narcotic analgesics in opium and to the derivatives that can be synthesized from them. Opioids-usually reserved for totally synthetic morphine-like drugs, example of opioid are Demerol, Talwin and methadone

6 How nerve cells respond to opiate? Within the limbic system, brainstem and spinal cord, there are places on certain nerve cells that recognize opiates. When stimulated by opiates, these sites -- called opiate receptors -- trigger responses in the brain and body. There are 3 types of opioid receptors in human : μ (mu) : mediate the euphoria and physical dependence to opioid δ (delta) κ (kappa)

7 Opiates Act on Many Places in the Brain and Nervous System The limbic system controls emotions. Opiates change the limbic system to produce increased feelings of pleasure, relaxation and contentment. The brainstem controls things your body does automatically, like breathing or coughing. Opiates can act on the brainstem to stop coughing or slow breathing. Source: NIDA The spinal cord transmits pain signals from the body. By acting here, opiates block pain messages and allow people to bear even serious injuries.

8

9 The synapse and synaptic neurotransmission Source: NIDA Vesicle containing dopamine, move toward the presynaptic membrane as an electrical impulse arrives at the terminal. Once inside the synaptic cleft, the dopamine can bind to specific proteins called dopamine receptors on the membrane of a neighboring neuron.

10 Dopamine neurotransmission Source: NIDA After the dopamine binds, it comes off the receptor and is removed from the synaptic cleft by uptake pumps that reside on the terminal. This process is important so that not too much dopamine is left in the synaptic cleft at any one time.

11 Dopamine and the production of cyclic AMP Source: NIDA When dopamine binds to its receptor, another protein called a G-protein moves up close to the dopamine receptor. The G-protein signals an enzyme to produce cyclic adenosine monophosphate (camp) molecules inside the cell. camp controls many important functions in the cell including the ability of the cell to generate electrical impulses.

12 Localization of opiate binding sites When a person injects morphine, it travels quickly to the brain. The opiates bind to opiate receptors that are concentrated in areas within the reward system (VTA, nucleus accumbens, caudate nucleus and thalamus). Indicate that the action of opiates in the thalamus contributes to their ability to produce analgesia.

13 Opiates binding to opiate receptors in the nucleus accumbens: increased dopamine release Source: NIDA Three neurons participate in opiate action: the dopamine terminal, another terminal (on the right) containing a different neurotransmitter (probably GABA ), and the post-synaptic cell containing dopamine receptors. opiates bind to opiate receptors on the neighboring terminal and this sends a signal to the dopamine terminal to release more dopamine.

14 Increased camp produced in post-synaptic cell Source: NIDA Since there is more dopamine released, there is increased activation of dopamine receptors. This causes increased production of camp inside the post-synaptic cell, which alters the normal activity of the neuron

15 opiate binding in nucleus accumbens and activation of the reward pathway Source: NIDA As a result of opiate actions in the nucleus accumbens, there are increased impulses leaving the nucleus accumbens to activate the reward system. Continued use of opiates makes the body rely on the presence of the drug to maintain rewarding feelings and other normal behaviors. The person is no longer able to feel the benefits of natural rewards (food, water, sex) and can't function normally without the drug present.

16 Action of morphine and opiates Pain relief potent Addition potential high Respiration Cough reflex Peristalsis Constipation GI secretion Pupil of eye constricted Euphoria

17 Pharmacokinetic Opiates are readily absorbed from the gastrointestinal tract, nasal mucosa and lungs. Once in the bloodstream, opioids are distributed throughout the body and accumulation in the kidney, lungs, liver, spleen, digestive tract, muscle and brain. Most opiate drugs are rapidly metabolized in the liver and excreted by the kidney. Excretion of opiates is fairly rapid, with 90% excretion within a day after taking the drug. However, traces of morphine may remain in urine for 2-4 days after use

18 The commonly abused opioids are all metabolised principally in the liver and the metabolite are then excreted renally. Heroin is unusual in that the molecule itself has no intrinsic action at opiate receptor, all its actions are due to its 2 main metabolites: 6-monoacetyl-morphine morphine Heroin is rapidly deacetylated in the liver, kidney, blood, brain and other tissues to form these metabolites, such as that it has an average half life of only 3 min Morphine is converted to a range of metabolites in the liver and has an average half life of about 3 hours. The 2 most important metabolites are formed by conjugation: morphine-3- glucoronide and morphine-6-glucoronide (5% of metabolite, but more potent opioid agonist than morphine)

19

20 Heroin is rapidly deacylated to 6-monoacetylmorphine and then to morphine

21 Basic elements of morphine metabolism

22 Comparison of the major opiate drugs Generic name Brand name Potency Duration of action Morphine hours Heroin hours Codeine hours Methadone Dolophine hours Potency estimates are presented relative to an effective dose of morphine

23 Effect of administration and withdrawal of opiate drugs Administration Decreased body temperature Decrease blood pressure Pupil constriction Drying of secretion Constipation Decrease sex drive, impotence Respiratory depression Analgesia Euphoria Withdrawal Increase body temperature Increase blood pressure Pupil dilation Tearing, runny nose Diarrhea Spontaneous ejaculation/orgasm Yawning Pain Depression/anxiety

24 Heroin

25 Introduction Heroin is a synthetic opiate drug that is highly addictive. It is made from morphine Heroin usually appears as a white or brown powder or as a black sticky substance, known as black tar heroin. First synthesized from morphine in 1874, heroin was not extensively used in medicine until the early 1900s. Commercial production of the new pain remedy was first started in 1898.

26 How is Heroin Abused? Heroin can be injected, snorting/sniffed, or smoked Injecting is the use of a needle to release the drug directly into the bloodstream. Snorting is the process of inhaling heroin powder through the nose, where it is absorbed into the bloodstream through the nasal tissues. Smoking involves inhaling heroin smoke into the lungs. The street name of heroin: Big H, Blacktar, Brown sugar, Dope, Horse, Junk, Mud, Skag, Smack.

27 What are its short-term effect? The short-term effects of heroin abuse appear soon after a single dose and disappear in a few hours After an injection of heroin, the user reports feeling a surge of euphoria ("rush") accompanied by a warm flushing of the skin, a dry mouth, and heavy extremities. Other heroin effects include dizziness, feeling as though the body has become heavy and the person cannot move, nausea a change in skin temperature begin to feel tired though the world no longer exists around them their ability to function both mentally and physically will decrease

28 What are its long-term effects? damage the nervous system can cause short and long term harm to the respiratory and cardiovascular systems collapsed veins infection of the heart lining and valves abscesses and cellulites liver disease pulmonary complications

29 How Does Heroin Affect the Brain? Heroin enters the brain, where it is converted to morphine and binds to receptors known as opioid receptors. Heroin overdoses frequently involve a suppression of respiration. With regular heroin use, tolerance develops. This means the abuser must use more heroin to achieve the same intensity of effect. Eventually, chemical changes in the brain can lead to addiction.

30 What Other Adverse Effects Does Heroin Have on Health? Heroin abuse is associated with serious health conditions, including fatal overdose, spontaneous abortion, infectious diseases, including HIV/AIDS and hepatitis. Chronic use of heroin leads to physical dependence, a state in which the body has adapted to the presence of the drug. If a dependent user reduces or stops use of the drug abruptly, they may experience severe symptoms of withdrawal.

31 Major withdrawal symptoms peak between 48 and 72 hours after the last dose and typically subside after about a week Withdrawal symptoms can begin as early as a few hours after the last drug administration, include restlessness muscle and bone pain insomnia diarrhea and vomiting cold flashes with goose bumps ( cold turkey ) kicking movements ( kicking the habit ) severe craving for the drug

32 Typically, a heroin abuser may inject up to four times a day. Intravenous injection provides the greatest intensity and most rapid onset of euphoria (7 to 8 seconds), while intramuscular injection produces a relatively slow onset of euphoria (5 to 8 minutes). When heroin is sniffed or smoked, peak effects are usually felt within10 to 15 minutes.

33

34 What Treatment Options Exist? A range of treatments exist for heroin addiction, including medications and behavioral therapies. Treatment begins with medically assisted detoxification, to help patients withdraw from the drug safely. Medications such as clonidine and, now, buprenorphine can be used to help minimize symptoms of withdrawal.

35 Medications to help prevent relapse include: Methadone reducing the desire for other opioid drugs while preventing withdrawal symptoms Properly prescribed methadone is not intoxicating or sedating, and its effects do not interfere with ordinary daily activities. Buprenorphine Naltrexone It is an opioid receptor blocker and effective in highly motivated patients. It should only be used in patients who have already been detoxified in order to prevent severe withdrawal symptoms. Naloxone is a shorter acting opioid receptor blocker, used to treat cases of overdose

36 Methadone maintenance In 1964, Drs. Vincent Dole and Marie Nyswander began their pioneering research with transitioning heroin and morphine addicts to methadone Their work indicated that methadone was an effective alternative to heroin or morphine because it did not cause wild mood swings or euphoria yet would satisfy the craving for narcotics

37 Opiate Addiction Tolerance to and physical dependence on heroin, morphine, codeine and the synthetic opioids can develop upon continued administration of these drugs The addiction depends on many factors: The individual The specific opiate used The size of the dose The frequency of administration The route of administration

38 Aspect of the heroin withdrawal syndrome Hours since last heroin dose Sign and symptoms 0-8 No withdrawal sign and symptoms 8-12 Yawning, runny nose, tearing of the eyes, sweating Perhaps a restless sleep (yen) lasting for several hours, addict awakes unrefreshed and miserable Intensification of misery, loss of appetite, nausea, vomiting, diarrhea, irritability, gooseflesh Peak syndrome: all the preceding sign plus violent yawning, muscle twitching (kicking habit), severe sneezing, weakness, depression, intestinal spasm, back pain, alternate chills and flushing, ejaculation in men, orgasm in woman, abnormal white cell count and acid-base balance

39 Tolerance Repeated administration of an opioid over period of a few week will reduce the respiratory, depressant, analgesic and euphorigenic effects initially produced by the drug.

40 How Widespread is Heroin Abuse? Monitoring the Future Survey According to the 2007 Monitoring the Future survey, there were no significant changes since 2006 in the proportion of students in 8th, 10th, and 12th grades reporting lifetime, past-year, and pastmonth use of heroin overall. Heroin Use by Students, 2007: Monitoring the Future Survey 8 th grade 10 th grade 12 th grade Life time 1.3% 1.5% 1.5% Past year Past month

41 National Survey on Drug Use and Health (NSDUH) According to the 2006 National Survey on Drug Use and Health, the number of current (past-month) heroin users in the United States increased from 136,000 in 2005 to 338,000 in The corresponding prevalence rate increased from 0.06 to 0.14 percent. There were 91,000 first-time users of heroin aged 12 or older in 2006, down from 108,000 reported in Among persons aged 12 to 49, the average age at first use of heroin was 20.7 years.

42 Deaths from Narcotic Analgesics in the 1999 DAWN Report

43

44