Specific Substances

Substance pharmacology principles

Rapid onset generally associated with greater
reinforcement (inhalation, intravenous)
Tolerance can develop at the level of
metabolism (eg cytochrome enzymes) and
also CNS neuroadaptation
Additive effects of combined intoxication
increases risk of complication and death
 Alcohol Pharmacology
Non-specific and complex neurobiologic
mechanism
Does not bind directly to a receptor
Overall CNS depression
Indirectly potentiates GABA transmission
Relatively high concentrations for intoxication
Enzymes become saturated
Elimination kinetics are linear: ~ 10-20mg/dL/h
 Cannabis forms & administration
Marijuana, hashish, hash oil

Pharmaceutical delta-9-THC: dronabinol

(Marinol)
Synthetic cannabinoids: K-2, spice

Smoked/vaporized/inhalation, oral
 Cannabis pharmacology
Multiple active cannabinoids with delta-9-THC
the most psychoactive in marijuana
Binds to cannabinoid receptors (CB1 is
primary CNS receptor)
CB1 primarily pre-synaptic axon terminals,
with multiple CNS effects
THC binds to adipose tissue so elimination is
very gradual, occurring over days/weeks
 Sedative-hypnotics, anxiolytics
Benzodiazepines: anxiolytics, sedatives
Lorazepam (Ativan)
Clonazepam (Klonopin)
Alprazolam (Xanax)
Diazepam (Valium)
Oxazepam (Serax)
Hypnotics Z drugs for sleep
Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunesta)
Barbiturates
Phenobarbital
Butalbital (in Fioricet)
 Benzodiazepine pharmacology
Agonist at the GABA-A receptor: benzodiazepine
complex
Chloride ion influx hyperpolarization, thereby inhibiting
Similar effects, differences in onset of action and
metabolism/elimination
Cross-tolerance with alcohol and other sedative
hypnotics
Reinforcing for people with anxiety or SUD
Overdose: respiratory depression synergistic with
alcohol, opioids
 Hypnotic z-drug pharmacology
Also bind BZ receptor on GABA-A receptor
complex, but favorably bind to alpha-1
Alpha-1 selective GABA-A agonists more effect
for sedation (and memory impairment)
Less effect on anxiety, so generally less
reinforcing
Similar effects, differences in onset of action
and elimination
 Barbiturate pharmacology
Similar to BZ, Agonist at the GABA-A receptor
More often used in anesthesia
Less frequently prescribed now due to
respiratory depression with overdose
 Stimulants
Amphetamines
amphetamine (Adderall)
dextroamphetamine (Dexedrine)
Methamphetamine (Crystal Meth)
methylphenidate (Ritalin, Concerta)
Cocaine
 Stimulants: forms and administration
Amphetamines
Prescription: oral, intranasal
Methamphetamine: oral, intranasal, smoked
Methylphenidate Prescription: oral, sniffed/snorted
 Cocaine
Derived from cultivated coca plant
Forms and administration
Intranasal powder form
Inhaled crack or freebase
Intravenous (speedball when combined with
opioid)
Elimination half-life is short, ~ 1hour
 Stimulant pharmacology
Stimulate dopaminergic VTA neurons in
reward circuitry
Often highly reinforcing with strong trigger by
cues
 Opioids
Opiates: opium, morphine, codeine
Semi-synthetic
heroin (the first)
oxycodone-APAP (Percocet)
oxycodone (Oxycontin)
hydrocodone (Vicodin)
hydromorphone (Dilaudid)
Buprenorphine-naloxone (Suboxone)*
Naloxone and naltrexone**
Synthetic
methadone
meperidine (Demerol)
Fentanyl
Tramadol
Propoxyphene
 Opioids form and administration
Prescription oxycodone: oral, intranasal,
injected
Fentanyl IV anesthesia, transdermal patch,
synthetic injected
Heroin- intranasal, injected (can be inhaled)
Buprenorphine-naloxone (Suboxone)
Naltrexone and naloxone
 Fentanyl
Prescription fentanyl
Synthetic illicit derivatives
Much more potent than heroin
When mixed with heroin, increases risk of
death by overdose
 Opioid pharmacology
Bind to opioid receptors (mu, delta, kappa)
Mu agonist inhibits GABAergic neurons in VTA
(which tonically inhibit DA release)
Pain
Tolerance
Dependence
References for Specific Substances
American Psychiatric Press Textbook of
Substance Abuse Treatment, 5th ed, 2015.
Toxidromes and Withdrawal
Syndromes

Images / Slides compiled by David

Marcovitz, M.D.
10/11/15
 Toxidromes
A Toxidrome is basically a toxic syndrome associated with a
particular substance, often used to describe when a
substance is a poison or is simply taken in overdose.

The diagnosis may be assisted by:

Pupillary findings
Neuromuscular abnormalities
Mental status alterations
Skin findings
Bowel Sounds
VS abnormalities, Temp, BP and HR alterations, RR changes

Source: UpToDate, General approach to drug poisoning in adults/

Please focus on
these three
toxidromes
(opioids,
cocaine,
sedative-
hypnotic). The
third are
similar to
EtOH. The
next slide has
more detail
but the
important
thing is to
know the big
picture.

Source:
http://sketchymedicin
e.com/2012/01/toxidr
omes/
Though its difficult to make a general
rule, the slide below in blue
demonstrates nicely that toxidromes
and withdrawal syndromes often
involve opposite physiologic effects,
with constipation in opiate use and
diarrhea in opioid withdrawal being a
simple example.
Again just a
nice pictorial
about opioid
withdrawal
and the
expected
physiologic
signs and
symptoms as
well as their
time course

Source: Elsevier
Netterimages.com/
Please note that
while Ativan and
diazepam can be
used to assist
with alcohol or
benzodiazepine
withdrawal,
Librium is also a
common choice.

Source:
http://sketchymedicine.co
m/
TOXIDROMES
 Toxidromes
A 21-year-old male patient is dropped off at an
emergency department. The patient is agitated, believes
computers in the ED are flashing messages at him, and
says "I need my knife to protect myself." Which of the
following substances is most likely to be found on urine
toxicology?
A. Marijuana
B. Alcohol
C. Amphetamine
D. Heroin
E. MDMA
 Toxidromes
A 26-year-old patient is brought to the emergency
department due to psychomotor retardation,
drowsiness and slurred speech. On physical
examination the patient peoples are noted to be
constricted. Intoxication with which of the following
substances most likely?
Alcohol
Opioids
Cocaine
Amphetamines
Benzodiazepines
WITHDRAWAL
 Withdrawal syndromes
A patient with a history of heavy alcohol use presents to the emergency
department with a two day history of confusion. The patient is also on long-
term olanzapine treatment for schizoaffective disorder. The patient describes
visual and auditory hallucinations, is disoriented to place and time, and
cannot sustain attention. Temperature of 100.3F (37.9C,) heart rate 119
BPM, blood pressure 136/102 mmHg, and diffuse tremulousness are evident.
All laboratory values are within normal limits except for the
electroencephalogram (EEG) which shows low voltage fast waves
superimposed on slow waves. Which of the following diagnoses is most
likely?
delirium associated with alcohol withdrawal
neuroleptic malignant syndrome
alcoholic hallucinosis
korsakoff psychosis
serotonin syndrome
 Withdrawal syndromes
A patient with a 20 year history of alcohol use
has a seizure 12 hours after stopping drinking. A
typical feature of epileptic activity in this
situation is:
A. focal onset
B. multiple episodes
C. long duration
D. occurrence after 72 hours
 Withdrawal syndromes
A 41-year-old patient presents to the emergency
department with a blood alcohol concentration of 0.4
to 5 g/dL. The patient stuporous, the pulse of 70 spied
beats per minute and the blood pressure is 110 over 70
mmHg. There are no other drugs and abuse detect in
the blood or urine. Which of the following would be
the most immediate clinical concern?
seizures
liver failure
violent behavior
respiratory failure
Delirium tremens