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REVATHI.G, M.PHARM., PHARMACEUTICAL CHEMISTRY
ASSISTANT PROFESSOR, DEPT. OF PHARMACEUTICAL CHEMISTRY,
SHRI VENKATESHWARA COLLEGE OF PHARMACY
Current strategy of magazine report about Opioid
dependence ….
First half of 2018, nearly 63% of opioid
overdose deaths in the United States also
involved → cocaine, methamphetamine or
benzodiazepines, signaling the need to
address polysubstance use as part of a
comprehensive response to the opioid
epidemic.
▪ Individuals knowingly combine or co-use opioids with stimulants or depressants, an additional
and growing concern is the adulteration of other drug supplies with fentanyl.
▪ Increase in opioid use evolves → increase in polysubstance use - how different substances
interact may inform strategies that help prevent overdose?
▪ Strengthening policy efforts → continuum of prevention, harm reduction, and treatment to
address the risks of polysubstance use can slow the rates of drug overdose deaths in US
Statistics Report For Opioids
Overdose
Benzodiazepines Cocaine
• POLYSUBSTANCE USE:
➢ More than one drug is used or misused over a defined period of time
➢ From either the intentional use of opioids with other drugs or by accident, such as if
street drugs are contaminated with synthetic opioids.
➢ Fentanyl - highly potent synthetic opioid→ identified as a driver of overdose deaths
involving other opioids, benzodiazepines, alcohol, methamphetamine, and cocaine.
➢ 2 classes of drugs frequently co-used with opioids: depressants and stimulants.
➢ Medical uses for some drugs in these classes → high potential for misuse.
➢ Mixing opioids—which are depressants—with other depressants or stimulants, either
intentionally or unknowingly, → rising number of opioid overdose deaths (more than
doubled since 2010).
➢ Efforts to reduce opioid overdose deaths - strategies to prevent, mitigate, and treat
the use of multiple substances.
Introduction
➢ DRUG → Any substance, natural or artificial, other than food, that by its
chemical nature alters structure or function in the living organism
➢ DRUG DEPENDENCES → As per WHO, is a state, Psychic and sometimes
physical in which the user has a compelling desire to continue taking the
drug either to experience its effects or to avoid the discomfort of its
absence. A person may be dependent on more than one drug.
➢ DRUG ADDICTION → Is a state of periodic or chronic intoxification
produced by the repeated consumption of a drug (natural or synthetic).
➢ DRUG ABUSE → Consumption of a drug apart from medical need or in
unnecessary quantities. Majority drugs of abuse are the agents that act on CNS –
→ profound effects on mood, feeling & behaviour.
➢ DRUG MISUSE → Use of drugs for purposes or conditions for which they are
unsuited or even in appropriate use but in improper dosage.
➢ DRUG HABITUATION → condition resulting from the repeated consumption of a
drug
➢ DRUG TOLERANCE → State of decreased responsiveness to the pharmacological
effect of a drug resulting from a prior exposure to that drug or to be related drug
As per the definition by WHO, is a state psychic and sometimes physical in
which the user has a compelling desire to continue taking the drug either to
experience its effects or to avoid the discomfort of its absence.
Drug dependence is a general term in which a person may be dependent on
more than one drug.
It has 2 distinct and independent components:
Psychologic Dependence Physical Dependence
MECHANISM OF DRUG DPENDENCE
Psychologic Dependence
➢ Condition characterized by an emotional or mental drive to continue
taking a drug, whose effects the user feels to maintain his sense of
well being
➢ Varies with individual and with drug
➢ Desire to continue taking the drug
→ psychic craving or compulsion
➢ User behaviour termed as → drug – seeking behaviour
Physical Dependence
➢ State that manifests itself by intense physical disturbances when the
administration of the drug is suspended
➢ It is altered or adaptive physiological state produced in an individual by
the repeated administration of a drug.
WITHDRAWAL OR ABSTINENCE
SYNDROME
Prolonged use of drugs
Physical dependence induced
Drug abruptly discontinued or action diminished by administration of
specific antagonist
Physical depence manifests itself as intense physiological disturbances
Termed as Withdrawal or Abstinence syndrome
Degree of physical dependence measured by severity of withdrawal
symptoms
CLASS OF DRUGS USED FOR DRUG ABUSE AND
THEIR EFFECTS
DRUG PSYCHOLOGICAL DEPENDENCE PHYSICAL DEPENDENCE
1. NARCOTICS
Opiates
Strong,develops rapidly Early development, which
increases with increase in dose
2. GENERAL DEPRESSANTS
Alcohol & Barbiturates
Mild to strong, develops slowly Develops slowly but to marked
degree
3. HALLUCINOGENS
Marijuana
Variable None
4. CNS STIMULANTS
Amphetamine and Cocaine
Mild to strong Low degree
2 Major Treament
DETOXIFICATION
Freezing Body From ADR
Done by stopping drug and taking medical treatment for withdrawal symptoms
Takes 10-21 days depends on → severity of problem
Followed by long-term treatment otherwise relapses very common
REHABILITATION OF PATIENT
Part of long-term treatment
Depends upon patient needs;
After detoxification, psychotherapy, Behaviour therapy
DETOXIFICATION
❑Process of abolishing a substance of dependence from the
body in a way which does not hinder the body’s physiology.
❑Detoxification often takes a couple of days and half a month
to finish, which is contingent upon the substance being
abused, the seriousness of reliance and the help accessible to
the client.
Progression of liver disease in
chronic alcoholism
REHABILITATION OF PATIENT
➢ Part of long-term treatment
➢ Depends upon patient needs;
➢ After detoxification, psychotherapy, Behaviour therapy
✓ Self help groups like;
✓ Alcohol anonymous (AA)
or
✓ Narcotic Anonymous (NA) → treatment of drug dependence
✓ Public should be educated about ADR of all drugs
✓ Need Constant monitoring for High risk drugs and should have adequate
facilities
Government control
(Recent Act)
➢ Narcotic Drugs and psychotropic substances Act, 1985 is now in force which
has replaced the opium Act,1857, the opium Act,1878 and the Dangerous Drugs
Act 1930.
✓ It prescribes a punishment of rigorous imprisonment of 3 years to 10 years
and fine of Rs.1 lac for trafficking in narcotic and psychotropic drugs.
✓ Maximum Punishment- 20 years and fine Rs. 2 Lacs
✓ Punishment upto 30 years and Rs.3 Lacs for repeated offences
Important drugs of abuse and their
treatment are;
1. Narcotic Analgesics → Opiates
2. General Depressants→ Alcohol and Barbiturates
3. Hallucinogens
4. CNS Stimulants
1. Narcotic Analgesics
❑Opiates: (Morphine and Heroin)
✓ Mostly commonly addicts use→ heroin, morphine, pethidine, methadone
✓ Heroin is a drug of preference
✓ Chronic opiate abuse results in;
✓Physical dependence
✓Development of tolerant state
✓Manifested by decreased sensitivity to the opiate and increased sensitivity to
antagonists
❑Medical Complications of opiate abuse include:
✓Constipation
✓Swelling of hands
✓Feet scalp
✓Eyelids
✓Biliary hypertension
✓Pulmonary edema
✓pin-point pupils
✓Impotence in male
✓Viral hepatitis due to contaminated needle
Withdrawal Symptoms
✓Abrupt cessation of Morphine or heroin shows abstinence
syndrome → varies with individual.
✓Unpleasant, they are never fatal in healthy diet
✓It begins at 8 hr, after last dose & repeat every 32-72 hrs.
✓First yawning, rhinorrhoea , crying and sweating are seen
✓At 20 hr. Sweating, Chills and gooseflesh appear.
✓At 24-48 hr, nausea, vomiting, diarrhoea, hypertension and fever
are seen.
✓Complaints of severe cramps may lasts upto a week
✓Sleep disturbances and anxiety may persists for weeks or months.
Treatment of Opiate Dependence
• Dosage reduction with appropriate psychotherapy and social
counselling being undertaken
• Involves methadone maintenance
• Gradually increasing dose of methadone as heroin is
withdrawn 30 mg which is safe and efective dose for hard core
addicts.
• Dosage level is stabilised at less than 100 mg daily
• Dependence on methadone → consequence of treatment but
withdrawal symptoms are mild.
General Depressants
• ALCOHOL
Alcoholism → behavioural disorder state resulting due to persistent and excessive use of alcohol.
CAUSES:
Physical disability
Impaired emotional
Occupational
Interpersonal adjustment
Alcohol addiction→ include both tolerance and dependence
As tolerance develops→ person comsumes progressively increasing amount of alcoholto achieve the
same state of psychological reinforcement previously induced by smaller doses of alcohol →
dependences develops slowly
Medical complications
1. Malabsorption
2. Gastritis
3. Cirrhosis
4. Alcoholic hepatitis
5. Fatty liver
6. Chronic diarrhoea
7. Beriberi
8. Cutaneous ulcers
9. Delirium tremens
10. Conculsive
11. Alcoholic myopathy
12. Hyper or hypoglycemia
Withdrawal Symptoms
• After cessation of alcohol ingestion, withdrawal symptoms vary from
hangover to delirium tremens.
• After around 6-8 hr. of stopping the alcohol, withdrawal symptoms
start with sweating, insomnia, headache, muscle twitching,
tachycardia, cramps, diarrhoea, vomiting and agitation in most cases.
• Symptoms reduce after 40-50 hrs of cessation
• After 2 to 3 days → hallucinations, disorientation, seizures and
delirium occurs.
Treatment of Alcoholism
• To overcome nutritional deficiencies → vitamin B mainly
thiamine and nicotinic acid.
• IV fluid and electrolyte replacement
• Sedatives like chlordiazepoxide, diazepam and
chlormethiozole may be given
• Supportive psychotherapy
• Drugs like →Disulfiram dose of 0.5mg / day with
metronidazole and calcium carbimide
BARBITURATES
❑ Many patients start barbiturates for insomnia and using the drug in
progressively increasing doses.
❑ The results in persistent self-medication at a higher dose. This abuse of
barbiturates may develop into physical dependence.
❑ Dependence on large doses of sedative and hynotics is more common in
women of middle age.
Medical complications:
▪ Chronic abuse of barbiturates include
▪ impairment of psychomotor functions,
▪ altered sleep pattern,
▪ impaired pshychomotor skills,
▪ folate deficiency,
▪ rickets in children and
▪ osteomalacia in adults
Withdrawal symptoms:
✓ Nausea, vomiting, weakness, dizziness, visual hallucinations,
anorexia, insomnia, weight loss, hypotension, anxiety,
muscle twitching, EEG abnormalities etc.
✓ Recovery occurs after several weeks.
Non substitutive treatment is recommended:
# Gradual withdrawal of the drug over a period of ten days to
three weeks.
# This is with the aim to minimize the withdrawal symptoms.
# If the dose taken daily by the person is known then the dose
is reduced at the rate of 10% a day.
ANTIDOTE → Naloxone / naltrexone
Hallucinogens:
❖ Its a drug that acts on the central nervous system to produce a state of
perception of objects with no reality or of sensations with no external cause.
❖ Lysergic acid diethylamide (LSD), mescaline psilocybin and psilocin and
marijuana are hallucinogens.
❖ The hallucinogens are also referred to as Pshychotomimetics and
Psychotogens.
❖ Psychotomimetics means the effects produced by the hallucinogens , mimic
the naturally occurring psychoses.
❖ Psychedelics is a drug which is self-administered for its capacity to reliably
cause marked changes in mood, judgement and perception that are not or
cannot be experienced, except in dreams.
eg: Atropine and scopolamine
❖ Lysergic acid diethylamide is a most common hallucinogen of abuse 20-25μg
of LSD may produce effects in susceptible individuals and may last for 8-
12hr.
❖ The major effects of LSD abuse include blurred vision, altered shapes and
coloures, great heightening of colour intensity, colours are seen, sounds may
be heard distortion of space, hallucinations.
❖ Dizziness, muscular weakness, increased heart rate, dry mouth, nausea,
vomiting, tremors are experienced.
❖ Psychological changes show altered moods, euphoria, decreased ability to
concentrate, tension, anxiety etc.
• Treatments:
➢ For patients taking LSD include supportive environment
and anti-anxiety and sedative drugs.
➢ Prolonged pshycotic complications like schizophrenia may
be treated with drug like chlorpromazine.
Hospital and clinical pharmacy - D.Pharm

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Hospital and clinical pharmacy - D.Pharm

  • 1. REVATHI.G, M.PHARM., PHARMACEUTICAL CHEMISTRY ASSISTANT PROFESSOR, DEPT. OF PHARMACEUTICAL CHEMISTRY, SHRI VENKATESHWARA COLLEGE OF PHARMACY
  • 2. Current strategy of magazine report about Opioid dependence …. First half of 2018, nearly 63% of opioid overdose deaths in the United States also involved → cocaine, methamphetamine or benzodiazepines, signaling the need to address polysubstance use as part of a comprehensive response to the opioid epidemic. ▪ Individuals knowingly combine or co-use opioids with stimulants or depressants, an additional and growing concern is the adulteration of other drug supplies with fentanyl. ▪ Increase in opioid use evolves → increase in polysubstance use - how different substances interact may inform strategies that help prevent overdose? ▪ Strengthening policy efforts → continuum of prevention, harm reduction, and treatment to address the risks of polysubstance use can slow the rates of drug overdose deaths in US
  • 3. Statistics Report For Opioids Overdose Benzodiazepines Cocaine
  • 4. • POLYSUBSTANCE USE: ➢ More than one drug is used or misused over a defined period of time ➢ From either the intentional use of opioids with other drugs or by accident, such as if street drugs are contaminated with synthetic opioids. ➢ Fentanyl - highly potent synthetic opioid→ identified as a driver of overdose deaths involving other opioids, benzodiazepines, alcohol, methamphetamine, and cocaine. ➢ 2 classes of drugs frequently co-used with opioids: depressants and stimulants. ➢ Medical uses for some drugs in these classes → high potential for misuse. ➢ Mixing opioids—which are depressants—with other depressants or stimulants, either intentionally or unknowingly, → rising number of opioid overdose deaths (more than doubled since 2010). ➢ Efforts to reduce opioid overdose deaths - strategies to prevent, mitigate, and treat the use of multiple substances.
  • 5. Introduction ➢ DRUG → Any substance, natural or artificial, other than food, that by its chemical nature alters structure or function in the living organism ➢ DRUG DEPENDENCES → As per WHO, is a state, Psychic and sometimes physical in which the user has a compelling desire to continue taking the drug either to experience its effects or to avoid the discomfort of its absence. A person may be dependent on more than one drug. ➢ DRUG ADDICTION → Is a state of periodic or chronic intoxification produced by the repeated consumption of a drug (natural or synthetic).
  • 6. ➢ DRUG ABUSE → Consumption of a drug apart from medical need or in unnecessary quantities. Majority drugs of abuse are the agents that act on CNS – → profound effects on mood, feeling & behaviour. ➢ DRUG MISUSE → Use of drugs for purposes or conditions for which they are unsuited or even in appropriate use but in improper dosage. ➢ DRUG HABITUATION → condition resulting from the repeated consumption of a drug ➢ DRUG TOLERANCE → State of decreased responsiveness to the pharmacological effect of a drug resulting from a prior exposure to that drug or to be related drug
  • 7.
  • 8. As per the definition by WHO, is a state psychic and sometimes physical in which the user has a compelling desire to continue taking the drug either to experience its effects or to avoid the discomfort of its absence. Drug dependence is a general term in which a person may be dependent on more than one drug. It has 2 distinct and independent components: Psychologic Dependence Physical Dependence
  • 9. MECHANISM OF DRUG DPENDENCE
  • 10. Psychologic Dependence ➢ Condition characterized by an emotional or mental drive to continue taking a drug, whose effects the user feels to maintain his sense of well being ➢ Varies with individual and with drug ➢ Desire to continue taking the drug → psychic craving or compulsion ➢ User behaviour termed as → drug – seeking behaviour
  • 11. Physical Dependence ➢ State that manifests itself by intense physical disturbances when the administration of the drug is suspended ➢ It is altered or adaptive physiological state produced in an individual by the repeated administration of a drug.
  • 12. WITHDRAWAL OR ABSTINENCE SYNDROME Prolonged use of drugs Physical dependence induced Drug abruptly discontinued or action diminished by administration of specific antagonist Physical depence manifests itself as intense physiological disturbances Termed as Withdrawal or Abstinence syndrome Degree of physical dependence measured by severity of withdrawal symptoms
  • 13. CLASS OF DRUGS USED FOR DRUG ABUSE AND THEIR EFFECTS DRUG PSYCHOLOGICAL DEPENDENCE PHYSICAL DEPENDENCE 1. NARCOTICS Opiates Strong,develops rapidly Early development, which increases with increase in dose 2. GENERAL DEPRESSANTS Alcohol & Barbiturates Mild to strong, develops slowly Develops slowly but to marked degree 3. HALLUCINOGENS Marijuana Variable None 4. CNS STIMULANTS Amphetamine and Cocaine Mild to strong Low degree
  • 14. 2 Major Treament DETOXIFICATION Freezing Body From ADR Done by stopping drug and taking medical treatment for withdrawal symptoms Takes 10-21 days depends on → severity of problem Followed by long-term treatment otherwise relapses very common REHABILITATION OF PATIENT Part of long-term treatment Depends upon patient needs; After detoxification, psychotherapy, Behaviour therapy
  • 15. DETOXIFICATION ❑Process of abolishing a substance of dependence from the body in a way which does not hinder the body’s physiology. ❑Detoxification often takes a couple of days and half a month to finish, which is contingent upon the substance being abused, the seriousness of reliance and the help accessible to the client.
  • 16. Progression of liver disease in chronic alcoholism
  • 17. REHABILITATION OF PATIENT ➢ Part of long-term treatment ➢ Depends upon patient needs; ➢ After detoxification, psychotherapy, Behaviour therapy ✓ Self help groups like; ✓ Alcohol anonymous (AA) or ✓ Narcotic Anonymous (NA) → treatment of drug dependence ✓ Public should be educated about ADR of all drugs ✓ Need Constant monitoring for High risk drugs and should have adequate facilities
  • 18. Government control (Recent Act) ➢ Narcotic Drugs and psychotropic substances Act, 1985 is now in force which has replaced the opium Act,1857, the opium Act,1878 and the Dangerous Drugs Act 1930. ✓ It prescribes a punishment of rigorous imprisonment of 3 years to 10 years and fine of Rs.1 lac for trafficking in narcotic and psychotropic drugs. ✓ Maximum Punishment- 20 years and fine Rs. 2 Lacs ✓ Punishment upto 30 years and Rs.3 Lacs for repeated offences
  • 19. Important drugs of abuse and their treatment are; 1. Narcotic Analgesics → Opiates 2. General Depressants→ Alcohol and Barbiturates 3. Hallucinogens 4. CNS Stimulants
  • 20. 1. Narcotic Analgesics ❑Opiates: (Morphine and Heroin) ✓ Mostly commonly addicts use→ heroin, morphine, pethidine, methadone ✓ Heroin is a drug of preference ✓ Chronic opiate abuse results in; ✓Physical dependence ✓Development of tolerant state ✓Manifested by decreased sensitivity to the opiate and increased sensitivity to antagonists
  • 21. ❑Medical Complications of opiate abuse include: ✓Constipation ✓Swelling of hands ✓Feet scalp ✓Eyelids ✓Biliary hypertension ✓Pulmonary edema ✓pin-point pupils ✓Impotence in male ✓Viral hepatitis due to contaminated needle
  • 22. Withdrawal Symptoms ✓Abrupt cessation of Morphine or heroin shows abstinence syndrome → varies with individual. ✓Unpleasant, they are never fatal in healthy diet ✓It begins at 8 hr, after last dose & repeat every 32-72 hrs. ✓First yawning, rhinorrhoea , crying and sweating are seen ✓At 20 hr. Sweating, Chills and gooseflesh appear. ✓At 24-48 hr, nausea, vomiting, diarrhoea, hypertension and fever are seen. ✓Complaints of severe cramps may lasts upto a week ✓Sleep disturbances and anxiety may persists for weeks or months.
  • 23. Treatment of Opiate Dependence • Dosage reduction with appropriate psychotherapy and social counselling being undertaken • Involves methadone maintenance • Gradually increasing dose of methadone as heroin is withdrawn 30 mg which is safe and efective dose for hard core addicts. • Dosage level is stabilised at less than 100 mg daily • Dependence on methadone → consequence of treatment but withdrawal symptoms are mild.
  • 24. General Depressants • ALCOHOL Alcoholism → behavioural disorder state resulting due to persistent and excessive use of alcohol. CAUSES: Physical disability Impaired emotional Occupational Interpersonal adjustment Alcohol addiction→ include both tolerance and dependence As tolerance develops→ person comsumes progressively increasing amount of alcoholto achieve the same state of psychological reinforcement previously induced by smaller doses of alcohol → dependences develops slowly
  • 25. Medical complications 1. Malabsorption 2. Gastritis 3. Cirrhosis 4. Alcoholic hepatitis 5. Fatty liver 6. Chronic diarrhoea 7. Beriberi 8. Cutaneous ulcers 9. Delirium tremens 10. Conculsive 11. Alcoholic myopathy 12. Hyper or hypoglycemia
  • 26. Withdrawal Symptoms • After cessation of alcohol ingestion, withdrawal symptoms vary from hangover to delirium tremens. • After around 6-8 hr. of stopping the alcohol, withdrawal symptoms start with sweating, insomnia, headache, muscle twitching, tachycardia, cramps, diarrhoea, vomiting and agitation in most cases. • Symptoms reduce after 40-50 hrs of cessation • After 2 to 3 days → hallucinations, disorientation, seizures and delirium occurs.
  • 27. Treatment of Alcoholism • To overcome nutritional deficiencies → vitamin B mainly thiamine and nicotinic acid. • IV fluid and electrolyte replacement • Sedatives like chlordiazepoxide, diazepam and chlormethiozole may be given • Supportive psychotherapy • Drugs like →Disulfiram dose of 0.5mg / day with metronidazole and calcium carbimide
  • 28. BARBITURATES ❑ Many patients start barbiturates for insomnia and using the drug in progressively increasing doses. ❑ The results in persistent self-medication at a higher dose. This abuse of barbiturates may develop into physical dependence. ❑ Dependence on large doses of sedative and hynotics is more common in women of middle age. Medical complications: ▪ Chronic abuse of barbiturates include ▪ impairment of psychomotor functions, ▪ altered sleep pattern, ▪ impaired pshychomotor skills, ▪ folate deficiency, ▪ rickets in children and ▪ osteomalacia in adults
  • 29. Withdrawal symptoms: ✓ Nausea, vomiting, weakness, dizziness, visual hallucinations, anorexia, insomnia, weight loss, hypotension, anxiety, muscle twitching, EEG abnormalities etc. ✓ Recovery occurs after several weeks. Non substitutive treatment is recommended: # Gradual withdrawal of the drug over a period of ten days to three weeks. # This is with the aim to minimize the withdrawal symptoms. # If the dose taken daily by the person is known then the dose is reduced at the rate of 10% a day. ANTIDOTE → Naloxone / naltrexone
  • 30. Hallucinogens: ❖ Its a drug that acts on the central nervous system to produce a state of perception of objects with no reality or of sensations with no external cause. ❖ Lysergic acid diethylamide (LSD), mescaline psilocybin and psilocin and marijuana are hallucinogens. ❖ The hallucinogens are also referred to as Pshychotomimetics and Psychotogens. ❖ Psychotomimetics means the effects produced by the hallucinogens , mimic the naturally occurring psychoses. ❖ Psychedelics is a drug which is self-administered for its capacity to reliably cause marked changes in mood, judgement and perception that are not or cannot be experienced, except in dreams. eg: Atropine and scopolamine
  • 31. ❖ Lysergic acid diethylamide is a most common hallucinogen of abuse 20-25μg of LSD may produce effects in susceptible individuals and may last for 8- 12hr. ❖ The major effects of LSD abuse include blurred vision, altered shapes and coloures, great heightening of colour intensity, colours are seen, sounds may be heard distortion of space, hallucinations. ❖ Dizziness, muscular weakness, increased heart rate, dry mouth, nausea, vomiting, tremors are experienced. ❖ Psychological changes show altered moods, euphoria, decreased ability to concentrate, tension, anxiety etc.
  • 32. • Treatments: ➢ For patients taking LSD include supportive environment and anti-anxiety and sedative drugs. ➢ Prolonged pshycotic complications like schizophrenia may be treated with drug like chlorpromazine.