1. Mechanism of habituation
Dr. S. Parasuraman M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University,
Bedong 08100, Malaysia.
2. • Variables factors simultaneously influence the
likelihood that a given person will become a drug
abuser or an addict.
• These variables can be organized into three
categories:
– agent (drug)
– host (user)
– environment
Mechanism of habituation
3. • Drugs vary in their capacity to produce immediate
good feelings in the user.
• Drugs that produce intensely pleasant feelings
(euphoria) are more likely to be taken repeatedly.
•
• Reinforcement refers to the capacity of drugs to
produce effects that make the user wishing to take
them again.
• Stronger the reinforcement, the drug produces, the
greater is the likelihood for the drug to be abused.
Agent (Drug) Variables
4. • Reinforcing increase neuronal activity in brain.
• Cocaine, amphetamine, ethanol, opioids,
cannabinoids, and nicotine all reliably increase
extracellular fluid dopamine levels in the ventral
striatum.
• Serotonin, glutamine, norepinephrine, opiates, and
g-aminobutyric acid (GABA) are also involved in
mediating the reinforcing effects of drugs.
Agent (Drug) Variables
5. • In general, effects of drugs (pharmacokinetic and
pharmacodynamic effects) vary among individuals.
• Genetics (polymorphism of genes that encode
enzymes) plays major role in drug absorption,
metabolism, and excretion and in receptor-
mediated responses.
• Genetic factors contribute to different degrees of
reinforcement or euphoria observed among
individuals.
Host (User) Variables
6. • Children of alcohol abuse Innate tolerance to alcohol
may contribute to the development of alcoholism innate
tolerance increases vulnerability to alcoholism, impaired
metabolism (alcohol, metabolized by alcohol
dehydrogenase), due to mutation in ALDH2 gene poor
metabolizer.
• Poor metabolizer (alcohol) excess accumulation of
acetaldehyde after the ingestion of alcohol These people
experience a very unpleasant facial flushing reaction 5 to 10
minutes after ingesting alcohol.
Host (User) Variables
7. • Taking drugs may be seen initially as a form of rebellion
against authority.
• Other factors like pleasure, diversion, or income are
particularly important in communities where educational
levels are low and job opportunities scarce.
Environmental Variables
8. • Tolerance can be defined as the reduction in response to the
drug after repeated administrations.
Pharmacological Phenomena
Tolerance
• Drug (dose) increases ↑ --- drug effect ↑
• Repeated drug administration tolerance
• Thus a higher dose is required to produce the same
effect that was once obtained at a lower dose.
Example:
Diazepam produces sedation at
doses of 5 to 10 mg in a first-time
user repeated user may required
several hundreds of milligrams to
produce desired effect (due to
development of tolerance)
10. • Pharmacokinetic tolerance: changes in the distribution
or metabolism of a drug after repeated administrations.
• Eg. Antihypertensive agents, barbiturates. Barbiturates
stimulate the production of higher levels of hepatic
CYPs (enzyme induction), causing more rapid removal
of barbiturates from the circulation results in
reduction of drug in systemic circulation.
Types of tolerance
11. • Pharmacodynamic tolerance: Adaptive changes that
have taken place within systems affected by the drug.
• Eg.: drug induced changes in receptor density or
efficiency of receptor coupling to signal-transduction
pathways.
• Behavioral/ Learned tolerance refers to a reduction in
the effects of a drug due to compensatory mechanisms
that are acquired by past experiences. Eg.: repeated
experiences to function normally despite a state of
intoxication (alcoholism).
• High levels of intoxication behavioral alteration
physical and psychological defect will be observed.
Types of tolerance
12. • Reverse tolerance: A drug user may actually become
more sensitive to a drug when that drug destroys brain
tissue and make it less enjoyable. Eg.: MDMA,
cocaine, amphetamine
• Acute tolerance:
– Also known as tachyphylaxis.
– Immediate tolerance to the effect of a drug as the body
adapts to it.
– Example, a single dose of most hallucinogens causes a
reduced effect if the drug is taken. Eg.: hallucinogen,
psilocybin, LSD-25.
Types of tolerance
13. • Inverse tolerance: Repeated use of some drugs can
suddenly cause a increased sensitivity to it, as the brain
antcipates and enhances its effects. Eg.: Long-term
marijuana or cocaine
• Conditioned tolerance:
– Also known as situation-specific tolerance.
– develops when environmental cues such as sights, smells, or
situations are consistently paired with the administration of a
drug.
– When a drug affects homeostatic balance by producing
sedation and changes in blood pressure, pulse rate, gut
activity, etc.,.
Types of tolerance
14. • Physical dependence is the physiological adaptation of
the body to the presence of an agent.
• Abrupt discontinuation or dosage reduction of chronic
use of a drug results negative physical symptoms of
withdrawal.
• Eg.: naloxone, pentazocine
Physical Dependence
15. • Physical dependence is the physiological adaptation of
the body to the presence of an agent.
• Abrupt discontinuation or dosage reduction of chronic
use of a drug results negative physical symptoms of
withdrawal.
• Eg.: µ-opioids, all GABA agonists, gabapentin,
neuroleptic, antidepressants, androgenic-anabolic
steroids, glucocorticoids, naloxone, pentazocine
Symptoms Physical Dependence
16. • Symptoms which may be experienced during
withdrawal or reduction in dosage include increased
heart rate and/or blood pressure, sweating, and
tremors. More serious withdrawal symptoms such as
confusion, seizures, and visual hallucinations indicate a
serious emergency and the need for immediate medical
care.
• Abrupt withdrawal from opioids can cause an
extremely physiologically and psychologically painful
withdrawal that is very rarely fatal in patients of
general good health and with medical treatment. Acute
withdrawal of opioid causes hypertension, arrhythmia,
constant diarrhea and vomiting.
Withdrawal Syndrome
17. • Methadone used for heroin withdrawal treatment
• Opioid acts – 4to 6 hr
• Methadone acts – 24-36 hr
• Methadone has ability to eliminate cravings
• Its also act μ (mu) and NMDA receptor
• Used for treatment of heroin withdrawal
• Heroin withdrawal can be treated by
– Methadone maintenance therapy (MMT)
– Buprenorphine therapy
– Buprenorphine + naloxone therapy
– Behavioral therapy
How methadone will work?
18. • patient under treatment for a medical disorder who has
become "addicted" to the available prescribed drugs.
• Addiction leads to conception of excess dose, out of
control.
• An example would be a patient with chronic pain,
anxiety, or insomnia who begins using the prescribed
medication more often than directed by the physician.
• If the physician restricts the prescriptions, the patient
may begin seeing several doctors without the
knowledge of the primary physician.
• Such a patients may need emergency admission in
hospital.
Medical addict
