drugs of abuse Flashcards
T/F: the use of illicit substances increases the risk for adverse consequences and drug interactions during anesthesia
TRUE
_______________ = psychological dependence
addiction
definition of addiction
compulsive drug use despite negative consequences
T/F: dependence equals addiction
false; dependence occurs with chronic exposure
which normally comes first, dependence or addiction?
dependence
___________________ is the primary target of addictive drugs
mesolimbic dopaminergic system
the mesolimbic pathway connects the _________________ (in the midbrain) to the _____________________
ventral tegmental area; nucleus accumbens
_________________ is where dopamine producing neurons are housed, and where large amounts of dopamine are released to the nucleus accumens and prefrontal cortex
ventral tegmental area (in the midbrain)
systemic administration of drugs of abuse –> the release of ____________
dopamine
the mesolimbic pathway is aka the ___________________
reward pathway
as a general rule, addictive drugs activate the __________________________
mesolimbic dopamine system
class of addictive substance is determined by _____________________
receptor
what are the three receptor types that addictive substances can act on to activate the mesolimbic dopamine system
- GCPR
which addictive drugs activate the mesolimbic dopaminergic system through GCPR ?
- opioids
what are the two way that addictive substances activate the mesolimbic dopaminergic system through GCPR
- target GABA neurons of the ventral tegmental area (VTA)
_________________ target Mu opioid receptors (MOR) on GABA neurons in the VTA; MORs are expressed on the ___________________ of these cells and the somatodendritic compartment on the ____________________ cells
opioids; presynaptic; postsynaptic
what is the major addictive mechanism of opioids on the presynaptic terminal of GABA neurons
G-protein (beta-gamma) inhibition of VG Ca channels (inhibiting the inhibitor –> excitation of dopamine neuron)
in dendrites mu opioid receptors activate _______________ channels –> _____________
K+; hyperpolarization (making it harder to respond to another stimulus)
together the pre and postysynaptic mechanisms of the Mu opioid receptors in the VTA –> ______________________
removal of inhibition of dopamine by GABA neurons
THC and other cannabinoids cause increased dopamine through _______synaptic inhibition of the _____________ receptor –> inhibition of ______________
pre; CBR1; GABA
Gama-hydroxybutyric acid (GHB) targets the ________________ receptors, which are located on both cell types; however, ______________ neurons are more sensitive to GHB than _______________
GABAb; GABA; dopaminergic
GHB will increases ______________ –> hyperpolarization of the GABA neuron
Cl
what is the clincial use of GHB
administered to pts with narcolepsy for high quality sleep
which addictive drugs work on ionotropic receptors to increase the release of dopamine
- nicotine
addictive drugs that work through ionotropic receptors work on _________________ neurons to increase release of ________________
dopaminergic & GABA; dopamine
which addictive substances –> addiction through primary actions on the dopamine transporter?
- cocaine
MOA of addiction from cocaine and amphetamines
- block the dopamine transporter –> blocking dopamine reuptake
T/F: cocaine and amphetamines effect the transporters of dopamine only
false; they affect dopamine primarily; but also other monoamines (NE and serotonin) issues with increased SNS when actively intoxicated with cocaine
hasish is __________x more potent than weed
3
benefits of cannabinoids
- increased appetite
___________________ is a FDA approved cannabinoid agonist in the US
dronabinol
________________ = older commercial THC analog recently reintroduced in the US for the management of chronic pain
nabilone
overall addictive potential of marijuana
2 (on 0-5 scale)
what is the psychoactive substance in cannabinoids
tetrahydrocannabinol (THC)
THC leads to _________________ with chronic use; but has a low risk for _______________
dependence; addiction
onset of smoking cannabinoids _____________; peak ______________
within minutes; 1-2 hours
_____________________ leads to euphoria, relaxation, feelings of well being, grandiosity, and an altered passage of time
cannabinoids
dose dependent perception changes of cannabinoids
- visual distortions
very high doses of cannabinoids can cause what rare effects
- visual hallucinations
withdrawal symptoms from cannabinoids would onset within ________________ hours from last use
24-72
withdrawal symptoms from cannabinoids
- restlessness
who is the MOST at risk for heroine use
18-25 year old caucasians in large metropolitan areas
heroine has an addiction score of ______________ on a 0-5 scale
4
_________________ is a semi-synthetic opioid agonist
heroine
metabolism of heroine
rapidly metabolized via biotransformation into mu-opioid agonist 6-monoacetylmorphine and morphine
smoking heroine has a _________________ delivery and ___________ bioavailability
rapid; low
tolerance of heroine leads to death from __________________
respiratory depression
heroine will cause a rush of ________________ followed by ______________ hours of sedation
euphoria; 2-4
IV dose of heroine:
5-10 mg
IV onset of heroine
3-5 seconds
smoking dose of heroin
15-25 mg
onset of heroin if smoked
5-15 seconds
IM/SubQ onset of heroin
5-10 min
insufflating (snorting) onset of heroin
2-10 min
PO onset of heroin
60-90 min
what is the typical dose of Lysergic Acid Diethylamide-25 (LSD)
20-30 mcg
LSD is what class of drug
ergot alkaloid
what is the MOA of LSD
- increases glutamate release in the cortex
onset of LSD
30 min
DOA of LSD
6-12 hours
T/F: LSD induces tolerance
TRUE
T/F: LSD stimulates dopamine release
FALSE
_______________ is psychotomimetic and neurotoxic, meaning it mimics the sx of psychosis
LSD
addiction score of LSD on a 0-5 scale
0
psychomimetic and neurotoxic sx of LSD
- depersonalization
somatic symptoms of LSD
- dizziness
MOA of amphetamines
inhibits vesicular transporters ability to store dopamine in the presynaptic terminal –> increase release of synaptic dopamine
route of methamphetamines
PO, IV, inhale, insufflate
onset of methamphetamines is route dependent, so onset ranges from ________ - _______
instant; 30 min
DOA of methamphetamines
4-8 hours
metabolism of methamphetamines
liver
excretion of methamphetamines
kidney
methamphetamines are __________________ via NMDA receptor _______________
neurotoxic; antagonism
methamphetamines indirect increased release of dopamine causes what s/sx
- euphoria
methamphetamines indirect release of NE causes what s/sx
- increased arousal
methamphetamines indirect release of serotonin would cause what s/sx
- hallucinations
withdrawal sx from methamphetamines
- dysphoria
bruxism is common with chronic _______________ users
methamphetamine
methamphetamines have an addictive score of _____________ on 0-5 scale
5
amphetamine pyschosis s/sx
- paranoia
onset of smoking cocaine
6-8 seconds
duration of action of smoking cocaine
20 min
IV onset of cocaine
15 seconds
Nasal onset of cocaine
5 min
duration of action of IV cocaine
30-60 min
duration of action of nasal cocaine
90 min
________________ = water soluble salt stimulant of the SNS that is highly addictive
cocaine
cycle experienced with cocaine use
- euphoria
effects that may occur with chronic use of cocaine
- loss of appetite
s/sx of OD of cocaine
- hyperthermia
uses of cocaine in clinical medicine
- local anesthetic
when you become sensitized to small doses of cocaine this describes __________________
reverse tolerance
withdrawal s/sx of cocaine
- dysphoria
metabolism of cocaine
- 90% metabolized by plasma cholinesterases (to inactive metabolites)
1/2 life of cocaine
30-90 min
cocaine metabolites are detected in urine testing up to __________ days after single use
6
urine test can detect urine cocaine metabolites ________________ days after high dose or long term use
10-20
central MOA of cocaine
- blocks reuptake of dopamine, 5-HT, and NE
peripheral MOA of cocaine
inhibits voltage gated sodium channels
what is a “speedball”
IV cocaine mixed with heroine
_________________ will foster the feelings of intimacy and empathy without impairing intellectual capacity
MDMA
MOA of MDMA
reverses monoamine transporters: 5-HT
onset of MDMA
30 min
DOA of MDMA
3-5 hours
you can have intracellular decrease of 5-HT for _____________ hours after 1 dose of MDMA
24
acute adverse effects of MDMA
- hyperthermia
using MDMA with other serotonin agonists will cause what s/sx
- mental status change
s/sx of withdrawal from MDMA
- depression lasting possibly serveral weeks
abuse of _________________ often causes pts to water board –> water intoxication which can cause hyponatremia, seizure, and death
MDMA
complications of IV drug abuse
- local infections/dificulty with access
complications of inhalational drug abuse
- cilia depletion
evidence of IV drug abuse (physical assessment)
- track marks
pupillary response with amphetamine use
mydriasis
pupillary reponse with opioid use
miosis
pupillary response with PCP abuse
nystagmus
lymphadenopathy can be a sign of _____________ drug abuse
IV
nasal perforation is a sign of ____________ abuse
cocaine
______________ abusers tend to be malnourished, while ____________ abusers tend to be well nourished
amphetamine; opioids
goals in management of pt who has a substance abuse d/o
- adequate pain control
recommendations for managing the substance abuse pt to meet anesthetic management goasl
- ketamine infusion
if you have a patient present for elective surgery and you think they are under the influence of illicit drug what should you do
cancel/delay until further patient evaluation can be performed
acute drug abuse –> elevated heart rates. what drugs should be avoided
- ketamine
issues/risks with anesthetic management in a heroin abuser
- PUD
anesthetic management recommendations for pt who abuses heroin
- regional
issues/risks of anesthetic management in methamphetamine abuser
- rhabdomyolysis
recommendations for anesthetic management of pts who abuse methamphetamines
- avoid neuraxial
issues/risks in anesthesia management in the pt who abuses cocaine
- increased SNS activity
recommendations for anesthetic management in the pt who abuses cocaine
- avoid long acting BB
anesthetic management for the pt who abuses MDMA
- beware of sympathomimetics (2/2 increased SNS)
acute use of marijuana is _______________ to anesthetic agents
additive
T/F: cannabinoids have a cross tolerance to anesthetic agents
TRUE
what are the 3 humoral systems used to manage hemodynamics?
- SNS
which SNS receptor is Gq coupled
alpha 1 (postsynaptic)
which SNS receptor is Gi coupled
alpha 2 (presynaptic)
alpha 1 receptor is Gq coupled meaning it activates ______________; causing _________ –> _______ + _______
phospholipase C; PIP2; IP3; DAG
alpha 2 receptor is Gi coupled meaning it inhibits _____________ –> inhibition of _______________
adenylyl cyclase; cAMP
B1 and B2 receptors are ______________ coupled meaning they activate ________ –> ___________
Gs; adenyl cyclase; cAMP
effects of alpha 1 stimulation
- vasoconstriction
effects of alpha 2 stimulation
- inhibits insulin release in the pancrease
effects of B1 stimulation
- chronotropy, dromotropy, and ionotropy
effects of B2 stimulation
- bronchodilation
what is the primary NT from postganglionic SNS nerve?
NE
the adrenal medulla releases 80% ________ and 20% __________
epi; NE
________________ is the final product in the synthesis of natural catecholamines
epi
describe the steps of SNS production of catecholamines
- tyrosine into SNS nerve
what is the rate limiting step for NE synthesis
tyrosine to L-dopa via tyrosine hydroxylase
__________% of NE is transported back into the nerve terminal via reuptake transport system
90
metabolism of NE that occurs in the cytoplasm of the axon is done via __________
MAO
metabolism of NE that occurs in the nerve junction is done via ____________
COMT
