Addictive Medication David Cook University of Alberta.

Addictive Medication David Cook University of Alberta

The agenda this afternoon 1:45pm-2:30pmIntroduction to addiction, Opioids 2:30pm-2:45pmBreak 2:45pm-3:30pmBenzodiazepines 3:30pm-3:45pmBreak 3:45pm-4:10pmMethylphenidate etc 4:10pm-4:30pmQuestions

Some definitions Drug use taking something Drug use taking something Drug abuse taking something that results in negative consequences Drug abuse taking something that results in negative consequences Drug addiction continued drug use where it is blindingly obvious that drug use is causing problems with work, home, family life, friendships, spirituality etc. Drug addiction continued drug use where it is blindingly obvious that drug use is causing problems with work, home, family life, friendships, spirituality etc.

Abstinence syndrome (Withdrawal syndrome, previously called physical dependence) Abstinence syndrome (Withdrawal syndrome, previously called physical dependence) A situation in which the body has changed so that it behaves more normally in the presence of the drug than its absence. That is deprive the person of the drug and they get sick. A situation in which the body has changed so that it behaves more normally in the presence of the drug than its absence. That is deprive the person of the drug and they get sick. Tolerance Tolerance A situation where the user needs progressively more of the drug to get the same effect A situation where the user needs progressively more of the drug to get the same effect

There are reward pathways in the brain Stimulation of those nerves makes us feel good Stimulation of those nerves makes us feel good The pathway exists to reward us for actions that are good for the individual or the species (eating, sex etc.) The pathway exists to reward us for actions that are good for the individual or the species (eating, sex etc.) When we feel good we want to repeat the experience When we feel good we want to repeat the experience We easily become dependent on behaviours that stimulate this pathway (gambling, music etc.) We easily become dependent on behaviours that stimulate this pathway (gambling, music etc.)

The drugs simply activate the reward pathway! GABA (Alcohol, Benzodiazepines etc.) Opiods (Heroin etc.) Dopamine (Amphetamines and Cocaine) Acetylcholine (Nicotine) The drugs work at the most fundamental survival level The drugs work at the most fundamental survival level

Consequences of repeated drug use are: The pathway starts to turn itself off! Increased dose to obtain the same effect Reduction or absence in the effect of normal reward stimuli After abstention NOTHING activates the pathway! After abstention there will be an abnormal emphasis on getting the reward pathway working

Key point about brain chemistry Attempts to abstain from drugs are difficult because the user has rewired the brain. Expecting the user to be able to stop drug use and immediately regain normal attitudes is unrealistic. The healing process is real and may be prolonged. Attempts to abstain from drugs are difficult because the user has rewired the brain. Expecting the user to be able to stop drug use and immediately regain normal attitudes is unrealistic. The healing process is real and may be prolonged.

Narcotics, Opiates, Opioids, Narcotics is an old term for these drugs, often used for legal purposes Narcotics is an old term for these drugs, often used for legal purposes Opiates are compounds that are chemically related to morphine Opiates are compounds that are chemically related to morphine Opioids are ANY compounds that interact with the opioid receptor Opioids are ANY compounds that interact with the opioid receptor

Opium poppy Photo: Opium.Org Photo: CIA

Scraping off the resin Photo: CIA

Opium gum Photo: CIA

Heroin

Where does it come from?

Opium/Morphine/Heroin These are by far the best pain relieving drugs we have! These are by far the best pain relieving drugs we have! They have been known for more than 3000 years as agents that relieve pain, cough and diarrhoea They have been known for more than 3000 years as agents that relieve pain, cough and diarrhoea Addiction to the drugs has been known for almost as long as the pain relieving properties have been known Addiction to the drugs has been known for almost as long as the pain relieving properties have been known

Pain What causes it What causes it How the body responds to it How the body responds to it How we control it How we control it

Sir William Osler The greatest service a physician can render to his patients is in the alleviation of pain

Pain has two components: 1 The pain itself which results from nerves near the site of the pain transmitting information. The pain itself which results from nerves near the site of the pain transmitting information.

Brain? This is your big toe. You just stubbed me, you idiot!

There is a threshold Not all perceived touch is painful Not all perceived touch is painful Not all warmth is experienced as a burn Not all warmth is experienced as a burn Injury releases prostaglandins - chemicals that AMPLIFY the pain sensation Injury releases prostaglandins - chemicals that AMPLIFY the pain sensation If we block the production of prostaglandins, the pain will recede to levels that are not experienced as pain. If we block the production of prostaglandins, the pain will recede to levels that are not experienced as pain. This is how Aspirin and Tylenol work This is how Aspirin and Tylenol work

The second part is how the pain is interpreted. This is MUCH more complicated!

It hurts!

It hurts but its worth it!

It hurts but it is a profound religious experience

It hurts but it turns me on!

Pain is sensed by nerve endings Two sorts of pain fibres that carry messages to the central nervous sytem: Two sorts of pain fibres that carry messages to the central nervous sytem: A fibres very fast and trigger the reflex that makes us move away from the pain in less than 0.5 sec! A fibres very fast and trigger the reflex that makes us move away from the pain in less than 0.5 sec! C fibres are slower but convey it HURTS takes about 2 seconds C fibres are slower but convey it HURTS takes about 2 seconds Pain hits us twice! Pain hits us twice! Neuropathic pain arises from nerve damage Neuropathic pain arises from nerve damage

The fibres do NOT go straight to the brain They go to a part of the spinal cord that is called the Dorsal horn via the dorsal root ganglia. The dorsal horn They go to a part of the spinal cord that is called the Dorsal horn via the dorsal root ganglia. The dorsal horn Organizes the reflex motor response Organizes the reflex motor response Transmits the message to the brain that something painful has happened via the ASCENDING PATHWAYS Transmits the message to the brain that something painful has happened via the ASCENDING PATHWAYS Face and neck nerves go to the brainstem Face and neck nerves go to the brainstem

The dorsal horn can get confused The structure gets multiple inputs from different sites. Usually it can sort them out, but sometimes it makes a mistake. The structure gets multiple inputs from different sites. Usually it can sort them out, but sometimes it makes a mistake. Referred pain Referred pain It can also become sensitized chronic pain It can also become sensitized chronic pain

How is the information sent onwards? There are lots of chemical messengers in the dorsal horn. Opioid receptors block the transmission of information. There are lots of chemical messengers in the dorsal horn. Opioid receptors block the transmission of information. Thus drugs like codeine, morphine and Demerol have a direct pain-relieving effect Thus drugs like codeine, morphine and Demerol have a direct pain-relieving effect This is just part of the story This is just part of the story

The brain can modulate the pain sensation The brain sends DESCENDING nerves to the dorsal horn. The brain sends DESCENDING nerves to the dorsal horn. These nerves are only stimulated by very unusual situations, BUT if they are stimulated, they block the upward transmission of information. These nerves are only stimulated by very unusual situations, BUT if they are stimulated, they block the upward transmission of information. Opioid receptors are key Opioid receptors are key This is another way in which codeine etc work. This is another way in which codeine etc work.

How does the brain convert the information into pain We really dont know! We really dont know!

The drugs themselves High-potency, short acting Fentanyl (Sublimaze), Sufentanyl (Sufenta), Alfentanyl (Alfenta), Oxymorphone (Numorphan) Fentanyl (Sublimaze), Sufentanyl (Sufenta), Alfentanyl (Alfenta), Oxymorphone (Numorphan)Analgesics Morphine (MS-Contin), Heroin, Meperidine (Demerol), butorphanol (Stadol), hydromorphone (Dilaudid), Nalbuphine (Nubain) Morphine (MS-Contin), Heroin, Meperidine (Demerol), butorphanol (Stadol), hydromorphone (Dilaudid), Nalbuphine (Nubain) Orally active Codeine, Oxycodone (Oxycontin, Percodan, Percocet) Codeine, Oxycodone (Oxycontin, Percodan, Percocet) All agents except codeine require a triplicate prescription

Tylenol-3, 292 etc.

Percocet , Percodan , Oxycontin

Tylenol-3, 292 etc. Why? Peaceful pleasant mild heroin-like. Often arises from prescription Why? Peaceful pleasant mild heroin-like. Often arises from prescription Acute risks? Minimal, although combination with other drugs may cause problems Acute risks? Minimal, although combination with other drugs may cause problems Long term risks? Significant dependence that is difficult to shake. Constipation, difficulty in providing good pain management Long term risks? Significant dependence that is difficult to shake. Constipation, difficulty in providing good pain management Real risks? Dependence Real risks? Dependence

Opioid withdrawal Painful but not life-threatening Painful but not life-threatening Craving, Restlessness, increased pain sensitivity, nausea, cramps, muscle aches, sleeplessness, anxiety Craving, Restlessness, increased pain sensitivity, nausea, cramps, muscle aches, sleeplessness, anxiety Pupillary dilation, sweating, hair stands on end (cold turkey), increased heart rate, diarrhoea, fever Pupillary dilation, sweating, hair stands on end (cold turkey), increased heart rate, diarrhoea, fever Triggered by antagonists Triggered by antagonists

Issues around opioid use In-patient use is almost never responsible for addiction In-patient use is almost never responsible for addiction Outpatient use is a different story there are lots of excuses for long-term use Outpatient use is a different story there are lots of excuses for long-term use Things that are probably not helped a great deal include: Things that are probably not helped a great deal include: Fibromyalgia Fibromyalgia Low back pain Low back pain Headache Headache BUT there are a few conditions in which long-term opioid use may be the best option BUT there are a few conditions in which long-term opioid use may be the best option

Break time!

Anxiety and insomnia Anxiety is a useful thing, but may sometimes became disabling. Anxiety is a useful thing, but may sometimes became disabling. On the basis of the effects of drugs, presumably there are problems involving the GABA receptor system, but we are not really sure On the basis of the effects of drugs, presumably there are problems involving the GABA receptor system, but we are not really sure For most people the management of long-term disabling anxiety involves psychotherapy For most people the management of long-term disabling anxiety involves psychotherapy Drug use is usually a short-term solution only Drug use is usually a short-term solution only

Sleep We know a lot about sleep, but we still do not know how it works and why we need it We know a lot about sleep, but we still do not know how it works and why we need it Generally the body takes what sleep it needs Generally the body takes what sleep it needs A cycle starts in which something causes an interruption of normal sleep and this is followed by worry about sleep followed by further insomnia. A pattern of chronic arousal results. A cycle starts in which something causes an interruption of normal sleep and this is followed by worry about sleep followed by further insomnia. A pattern of chronic arousal results. Medication produces sleep, but it is not a normal sleep Medication produces sleep, but it is not a normal sleep

Non-drug management of sleep disorder Make sure that it it really is happening most insomniacs underestimate the time spent asleep Make sure that it it really is happening most insomniacs underestimate the time spent asleep Caffeine no caffeinated beverages after 2:00pm Caffeine no caffeinated beverages after 2:00pm Exercise Exercise Warm drink (not caffeinated!) Warm drink (not caffeinated!) Acceptance of changed sleep pattern Acceptance of changed sleep pattern Relaxation exercises Relaxation exercises Do not use bedroom for reading, TV etc Do not use bedroom for reading, TV etc Develop a routine Develop a routine

Sedative-hypnotic drugs Benzodiazepines:Valium, Librium, Ativan, Serax, Xanax, Lectopam, Versed, Tranxene, Dalmane, Mogadon, Restoril, Halcion Benzodiazepines:Valium, Librium, Ativan, Serax, Xanax, Lectopam, Versed, Tranxene, Dalmane, Mogadon, Restoril, Halcion Others: Imovane, Equanil, 282 MEPs Others: Imovane, Equanil, 282 MEPs All these drugs have the potential to cause addiction All these drugs have the potential to cause addiction

ALL SEDATIVE/HYPNOTICS All work at the GABA receptor and all create the following series of events: All work at the GABA receptor and all create the following series of events: Decreased anxiety Decreased anxiety Excitement/Disinhibition Excitement/Disinhibition Sedation Sedation Sleep Sleep Anesthesia Anesthesia Coma Coma Respiratory depression Respiratory depression Death Death

ALL these drugs Produce rebound insomnia Produce rebound insomnia Produce somnolence, impair driving and in overdose depress breathing. Produce somnolence, impair driving and in overdose depress breathing. Interact with alcohol and with each other to produce effects which are greater. Interact with alcohol and with each other to produce effects which are greater. Can impair memory, particularly in the elderly Can impair memory, particularly in the elderly Are relatively free of damage to heart, liver, blood pressure etc. Are relatively free of damage to heart, liver, blood pressure etc. Make it easier to survive anxiety and stress, at the cost of making everything bland. Make it easier to survive anxiety and stress, at the cost of making everything bland. Medically should only be used for longer than one month in rare cases. Medically should only be used for longer than one month in rare cases.

Other uses Sedation prior to surgery (no risk of addiction!) Sedation prior to surgery (no risk of addiction!) Sedation in the ER after stimulant overdose Sedation in the ER after stimulant overdose Clonazepam (Klonopin) is used in epilepsy and sometimes in mania all the benzodiazepines have some anti-seizure activity Clonazepam (Klonopin) is used in epilepsy and sometimes in mania all the benzodiazepines have some anti-seizure activity Chlordiazepoxide (Librium) is used to suppress withdrawal syndrome in alcoholics Chlordiazepoxide (Librium) is used to suppress withdrawal syndrome in alcoholics As muscle relaxants As muscle relaxants

Issues around benzodiazepine use The drugs are over-used, particularly in the long term management of anxiety The drugs are over-used, particularly in the long term management of anxiety They are sometimes used because the doctor feels a need to do something to alleviate the patient's distress; the patient may be better off to change their circumstances They are sometimes used because the doctor feels a need to do something to alleviate the patient's distress; the patient may be better off to change their circumstances Withdrawal is difficult use a physician, because seizures can occur Withdrawal is difficult use a physician, because seizures can occur The drugs do have a street value The drugs do have a street value

You deserve a break!

Stimulants - ADHD The drugs are methylphenidate (Ritalin, Concerta, Attendade, which is optically pure d- methylphenidate), amphetamines (Dexedrine, Adderal, not available in Canada since Feb 2005). The drugs are methylphenidate (Ritalin, Concerta, Attendade, which is optically pure d- methylphenidate), amphetamines (Dexedrine, Adderal, not available in Canada since Feb 2005). They are used for: They are used for: ADHD ADHD Narcolepsy Narcolepsy All have a street value All have a street value

ADHD Incidence is 3-5% in children. In about 80% of thes, problems continue into the teens, and about half have problems into adulthood. Incidence is 3-5% in children. In about 80% of thes, problems continue into the teens, and about half have problems into adulthood. If one plots activity vs number of children: If one plots activity vs number of children:

ADHD Poor attention span Poor attention span Opposition-defiance disorder Opposition-defiance disorder Conduct disorder Conduct disorder Often diagnosed by teachers Often diagnosed by teachers Often over-diagnosed Often over-diagnosed A child psychiatrist can make sensible decisions A child psychiatrist can make sensible decisions Resistance to authority is not, by itself a sign of ADHD Resistance to authority is not, by itself a sign of ADHD

ADHD The cause is largely unknown The cause is largely unknown There are significant differences in the brains of kids with ADHD There are significant differences in the brains of kids with ADHD Treatment tends to normalize the brain picture Treatment tends to normalize the brain picture About 95% of ADHD patients improve with medication About 95% of ADHD patients improve with medication There are strong opinions on the value of medication, often held by people with no experience of the condition and no knowledge of the literature. There are strong opinions on the value of medication, often held by people with no experience of the condition and no knowledge of the literature.

What do stimulants do? The help the patient to concentrate The help the patient to concentrate They improve tolerance for boredom and increase the chances of finishing a task They improve tolerance for boredom and increase the chances of finishing a task They do not help learning as such They do not help learning as such They improve relationships between the patient and his/her teacher, parents and peers They improve relationships between the patient and his/her teacher, parents and peers The medicine is usually well-tolerated The medicine is usually well-tolerated

Medication Complementary and alternative therapies have usually not been subjected to appropriate testing. Complementary and alternative therapies have usually not been subjected to appropriate testing. Behavioural therapy along with medication seems to give the best results, followed closely by medication alone. Behavioural or community psychotherapy or guidance are less successful. Behavioural therapy along with medication seems to give the best results, followed closely by medication alone. Behavioural or community psychotherapy or guidance are less successful. That said, there are plenty of things parents and others can do to help the child. That said, there are plenty of things parents and others can do to help the child.

Adverse effects Reduced appetite during the day, but no evidence of long-term growth retardation Reduced appetite during the day, but no evidence of long-term growth retardation Difficulty falling asleep (often resolved by using a lower dose) Difficulty falling asleep (often resolved by using a lower dose) VERY RARE cardiovascular problems, but the drugs do elevate blood pressure and heart rate. VERY RARE cardiovascular problems, but the drugs do elevate blood pressure and heart rate. Addiction rates in treated patients are lower than in untreated controls Addiction rates in treated patients are lower than in untreated controls In one study 25% of those receiving the drugs had diverted the material onto the street, at least once In one study 25% of those receiving the drugs had diverted the material onto the street, at least once

Addiction True addiction in people using the drugs for ADHD is very rare True addiction in people using the drugs for ADHD is very rare If the drugs are taken recreationally by someone who does not have ADHD, they have effects like amphetamines If the drugs are taken recreationally by someone who does not have ADHD, they have effects like amphetamines Ritalin used to be combined with the opioid pentazocine (Talwin) to give Ts & Rs or Poor mans heroin. Talwin is no longer widely available in an injectable form, but we still see this combination on occasion Ritalin used to be combined with the opioid pentazocine (Talwin) to give Ts & Rs or Poor mans heroin. Talwin is no longer widely available in an injectable form, but we still see this combination on occasion

Client issues around ADHD Make sure that the patient really does have ADHD Make sure that the patient really does have ADHD Support the use of stimulants if the child does have ADHD Support the use of stimulants if the child does have ADHD Make sure the drug is not being diverted Make sure the drug is not being diverted Key concepts in support of the patient include emotional support and praise, clear statements of the childs responsibility, and the establishment of routine. Key concepts in support of the patient include emotional support and praise, clear statements of the childs responsibility, and the establishment of routine. Good nutrition and healthy sleep patterns are important Good nutrition and healthy sleep patterns are important

Time for your questions on anything we have discussed!

Thanks, and bon voyage!

Addictive Medication David Cook University of Alberta.

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