Dependence/Physical dependence Produced when there is progressive pharmacological adaptation to the drug
resulting in tolerance
Dependence can occur with the use of: 1. Opioids
2. B blockers
3. Antidepressant
4. Benzodiazepines
5. Stimulants
Appearance of withdrawal symptoms Cardinal sign of physical dependence
Addiction compulsive, out-of-control drug use
Tolerance The most common response to repetitive use of the same drug can be defined
as reduction in response to the drug after repeated administrations
Innate tolerance Refers to genetically determined lack of sensitivity to a
drug the first time that it is experienced.
Acquired tolerance Can be divided into three major types—pharmacokinetic, pharmacodynamic,
and learned tolerance—and includes acute, reverse, and cross-tolerance
Pharmacokinetic or dispositional tolerance Refers to changes in the distribution or metabolism of a drug after repeated
administrations, such that a given dose produces a lower blood concentration
than the same dose did on initial exposure. The most common mechanism is
an increase in the rate of metabolism of the drug.
Pharmacodynamic tolerance Refers to adaptive changes that have taken place within systems affected by
the drug so that response to a given concentration of the drug is altered
(usually reduced)
Learned tolerance Refers to a reduction in the effects of a drug due to compensatory
mechanisms that are acquired by past experiences. One type of learned
tolerance is called behavioral tolerance
Conditioned tolerance (situation-specific tolerance) Develops when environmental cues or situations consistently are paired with
the administration of a drug
Acute tolerance Refers to rapid tolerance developing with repeated use on a single occasion,
such as in a “binge.”
Sensitization or reverse tolerance Refers to an increase in response with repetition of the same dose of the drug
Cross-tolerance Occurs when repeated use of a drug in a given category
confers tolerance not only to that drug but also to other drugs in
the same pharmacological category.
Detoxification A form of treatment of drug dependence that involves giving gradually
decreasing doses of the drug to prevent withdrawal symptoms, thereby
weaning the patient from the drug of dependence.
Sensitization An increase in response with repetition of the same dose of the drug. It results
in a shift to the left of the dose-response curve
Reverse tolerance or sensitization Can occur with stimulants, such as coccaine or amphetamine
Physical dependence A state that develops as a result of the adaptation (tolerance) produced by a
resetting of homeostatic mechanisms in response to repeated drug use
Withdrawal syndrome The appearance of this when administration of the drug is terminated is the
the only actual evidence of physical dependence
2 origins of withdrawal syndrome 1. Removal od the drug of dependence
2. CNS hyper-arousal owing to readaption to the absence of the drug
dependence
CNS depressants 1. Ethanol
2. Benzodiazepines
3. Barbiturates and older sedatives
4. Nicotine
5. Opioids
ETHANOL Heavy use causes development of tolerance and physical dependence
sufficient to produce an alcohol withdrawal syndrome when intake is stopped
Ethanol Impairs recent memory and, in high doses, produces phenomenon of
“blackouts”
Ethanol Classifed as a depressant because it produces sedation and sleep
ETHANOL INTERVENTIONS Detoxification
Short acting benzodiazepines can be used at a dose of OXAZEPAM
15-20mg every 6-8 hours according to the stage and severity of
withdrawal
For severe cases Hydration and electrolytes; vitamins, especially high-dose THIAMINE (Vitamin
B1)
Have been shown to be effective in alcohol withdrawal but not CARBAMAZEPINE
as well as benzodiazepines
Blocks aldehyde dehydrogenase, the second step in ethanol DISULFIRAM
metabolism, resulting in the accumulation of acetaldehyde,
which produces an unpleasant flushing reaction when alcohol is
ingested
Another FDA-approved medication for alcoholism is a ACAMPROSATE
competitive inhibitor of the N-methyl D-aspartate (NMDA) type
glutamate receptor
The drug appears to normalize the dysregulated Acamprosate
neurotransmission associated with the chronic ethanol intake
and thereby to attenuate one of the mechanisms that lead to
relapse
BENZODIAZEPINES Most commonly prescribed medications worldwide
Benzodiazepines Used mainly for the treatment of anxiety disorders or insomnia
BENZODIAZEPINE INTERVENTION Long t1/2 benzodiazepine during detoxificaiton
Useful in treatment of overdose and reversing the effects of FLUMANEZIL
long-acting benzodiazepines used in anesthesia
It has been used experimentally in the treatment of persistent Flumazenil
withdrawal symptoms after cessation of long-term
benzodiazepine treatment
NICOTINE The most dangerous dependence-producing drug
Nicotine Absorbed readily through skin, mucous membranes, and lungs
Pulmonary route Produces discernible CNS effects in as little as 7 seconds
With 10 puff per cigarette The one-pack-per-day smoker reinforces the habit 200 times daily
NICOTINE INTERVENTION Nicotine replacement therapy
With prescription NICOTROL inhaler and nasal spray
Without prescriptions NICORETTE gum and others
COMMIT lozenges and others
The sustained-release preparation of this antidepressant BUPROPION
improves abstinence rates among smokers and remain a useful
option
A partial agonist at the a4B2 subtype of the nicotinic VARENICLINE
acetylcholine receptor, improves abstinence rates but has also
been linked to risk of developing suicidal ideation
BARBITURATES AND OLDER SEDATIVES Treatment of abuse and addiction should be handled similarly to interventions
for the abuse of alcohol and benzidiazepines
OPIOID Used primarily for the treatment of pain
Opioid Should never be withheld from patients with cancer out of fear of producing
addiction
OPIOID INTERVENTIONS
Transfer to a prescription opioid medication and then gradual Change the patient from a short-acting opioid, such as HEROIN, to a long-
dose reduction acting one such as METHADONE (initial dose: 20-30mg; reduction rate: 20%
daily)
An a2 adrenergic agonist that decreases adrenergic CLONIDINE
neurotransmission from the locus ceruleu
Acting upon distinct receptors but by cellular mechanisms that Clonidine
mimic opioid effects, can alleviate many of the symptoms of
opioid withdrawal, but not the generalised aches and opioid
craving
Activation of the endogenous opioid system without medication 1. Acupuncture
2. Transcutaneous electrical stimulation
PSYCHOSTIMULANTS 1. Cocaine
2. Amphetamine and related agents
3. Caffeine
4. Cannabinoids (Marijuana)
5. Psychedelic agents: LSD, MDMA (Ecstasy), Phencyclidine
CAFFEINE A mild stimulant, the most widely used psychoactive drug in the world. It is
present in softdrinks, coffee, tea, cocoa, chocolate, and numerous prescription
and over-the-counter drugs
Tolerance occurs rapidly to the stimulating effects of caffeine Thus, a mild withdrawal syndrome has been produced in controlled studies by
abruptly discontinuing the intake of as little as two cups of coffee per day
Caffeine withdrawal symptoms Feelings of fatigue and sedation
Higher doses of caffeine Headaches and nausea
MARIJUANA Most commonly used illegal drug in the U.S.
Marijuana abuse and addiction No specific treatments. Heavy users may suffer from accompanying
depression and thus may respond to antidepressant medication
Psychedelic agents 1. Indoleamines
2. Phenethylamines
Indoleamine 1. LSD
2. DMT
3. Psilocybin
Phenethylamines 1. Mescaline
2. DOM
3. MDA
4. MDMA
Indoleamine and Phenethylamines Both groups have a relatively high affinity for 5HT2 receptors, but they differ in
their affinity for other subtypes of 5HT receptors
LSD Interacts with most brain 5HT receptors as an agonist/partial agonist and
elicits sensory distortions (especially visual) and hallucinations at doses as
low as 1 µg/kg
LSD The most potent hallucinogenic drug, more than 3000 times more potent than
mescaline; “bad trip”
MDMA (Ecstacy) and MDA Phenylethylamines that have stimulant as well as psychedelic effects
Phencyclidine Developed originally as an anesthetic in the 1950s and later was abandoned
because of a high frequency of postoperative delirium with hallucinations
