PODA: Substance Abuse Flashcards
_________ is produced when there is a progressive pharmacological ADAPTATION to the drug resulting in tolerance
Dependence or physical dependence
This can be considered a form of MALADAPTIVE MEMORY….It is produced by REPEATED DRUG USE and leads progressively to compulsive out of control drug use
Addiction
Drug addiction causes brain reward circuits
TorF: most users with addiction potential do not develop a drug use disorder?
True
The likelihood of a person who uses drugs developing a substance abuse disorder depends on three things:
- The drug variables
- The Host variables
- The environment
THIS is defined as the ability of a drug to produce effects that will make the user want the drug again
REINFORCEMENT
Reinforcing properties of drugs are linked to their capacity to …
INCREASE neuronal activity in the brain REWARD AREAS
mesolimbic DA pathway
Cocaine, amphetamine, ethanol, opioids, cannabinoids, and nicotine INCREASE DA levels in the:
VENTRAL STRIATUM
specifically in the nucleus accumbens which causes euphoria
What factors affect drug variables?
- Speed and onset
- Availability
- Cost
- Purity/potency
- Route of administration
HOST variables that affects likelihood of substance abuse?
- Hereditary
- Metabolism of drugs
- Psychiatric symptoms
- Prior experiences or expectations
- Propensity for risk taking behaviors
Repeated dosing of a drug leads to a RIGHTWARD SHIFT in the dose-response curve can be defined as:
Acquired tolerance
This is acquired pharmacoKINETIC tolerance:
develops when the capacity to METABOLIZE or EXCRETE a drug INCREASES
Pharmacodynamic tolerance
this is due to NEURONAL ADAPTATION leading to REDUCE RESPONSE to the same concentration of drug
short term exposure vs long term exposure to drugs:
Short term: neuroadaptive changes in NT release due to DECREASE in receptor number or altered conductance of ion channels
Long term: neuroadaptive changes in GENE EXPRESSION relating to learning and memory
The need for a drug to be present at the site of action to maintain normal functioning
Dependence
What are the MOAs of ethanol?
- Increases Cl- conductance through GABAA receptors leading to hyperpolarization
- DECREASES Ca+2 conductance via NMDA receptors leading to hyperpolarization
MOLECULAR adaptation to chronic alcohol intake involves these mechanisms:
- Internalization and decreased expression of normal a1 subunit on GABAA receptors
- Increased surface expression of low sensitivity a4 subunits on GABAA receptors
- Increased phosphorylation of NMDA receptors containing high conductance NR2B subunits
During withdrawal, when the patient is in a dependent state, in the absence of alcohol, neuronal adaptation can lead to:
Generalized hyperexcitability of neurons
CNS excitation is demonstrated as anxiety, insomnia, delirium, and possibly seizures
TorF: rewarding effects of alcohol may be partially mediated by a direct action on cannabinoid receptors.
FALSE. rewarding effects of alcohol may be partially mediated by an INDIRECT action on cannabinoid receptors.
SE of Antabuse incl:
- Optic and PERIPHERAL NEUROPATHY
- drowsiness
- rash
- psychosis
- hepatitis(RARE)
- metallic taste
GIWA’s PP: (causes severe nausea, vomiting, flushing when consumed with alcohol which essentially requires strict abstinence from all alcohol)
MOA of Antabuse:
inhibits aldehyde dehydrogenase=increased acetaldehyde in the blood=producing an acute sensitivity to ethanol
Naltrexone:
- Opioid receptor antagonists that blocks endorphin activation properties of alcohol
- BETTER TOLERATED THAN DISULFIRAM
- SE: hepatotoxicity, nausea, insomnia
Acamprosate:
- competitive inhibitor of glutamate receptors and (GIWA): possibly inhibit GABA
- normalizes dysregulated neurotransmission associated with chronic alcohol intake
SE: GI upset, muscle or joint pain, headache, syncope, impotence, edema, palpitations, (GIWA): NAUSEA AND DIARHHEA
Chronic administration of BZD can induce DOWN-REGULATION of these pathways by neuroadaptation:
DOWN-REGULATION may be due to:
- uncoupling of BZD site from GABAA receptors
- CHRONIC ADMINISTRATION…down-regulation can leave the brain under-inhibited therefore increasing the possibility of seizures and delirium after abrupt withdrawal of BZD
The rewarding and addicting effects of BZD are presumed to be mediated by
a1 containing GABAA receptors expressed on neurons in the VTA
What receptor is the responsible for the reinforcing properties of opioids?
Mu receptor
What mechanism is involved in the neuroadaptation of opioids?
ACUTE USE of opioids leads to activation of mu-receptor resulting in G protein dependent ACTIVATION OF K+ channels and INHIBITION OF ADENYLYL CYCLASE ACTIVITY
molecular adaptation of opioids:
- phosphorylation of mu-receptor leading to receptor internalization and degradation
- DECREASED EFFICACY of mu-receptor signal transduction
- Hyperactivation of adenylyl cyclase signaling resulting in enhanced GABA release and to increase gene transcription via activation of transcription factors (such as cyclic AMP response element binding protein, CERB)
In opioid withdrawal
INCREASED GABA release, DECREASE DA = dysphoria and anhedonia(inability to feel pleasure)
Opioid withdrawal symptoms:
craving for opioid
restlessness
irritability
insomnia
anxiety
muscle aches
NVD
TorF: cocaine causes an initial euphoria
True.
What is the neuroadaptive result of ACUTE USE of cocaine?
- Inhibits DAT —> Increased synaptic DA—-> Increased activation of postynaptic DA receptors in the nucleus accumbens—-> feeling of euphoria and increased energy
- Increased synaptic DA—-> stimulation of presynaptic D2 receptors—->decreases DA synthesis
What is the neuroadaptive result of CHRONIC USE of cocaine?
- Increase expression of DAT
- Decreased postsynaptic DA receptors
- Presynaptic DA is depleted leading to dysphoria
What happens in neuroadaptive cocaine withdrawal?
*Decreased levels of DA—->decreased activation of postsynaptic DA receptors—> dysphoria and anhedonia
Cocaine produces a dose-dependent increase in _____ and _______.
HR and BP
as well as increased arousal and improved performance
Sleepiness is a symptom of cocaine withdrawal. TorF?
TRUE
Nicotine activates __________ receptors that are located centrally, peripherally, and at the _________
- Nicotinic ACh receptors
* neuromuscular junction
What is the MOA of nicotine?
- Activation of CENTRAL nicotinic receptors produces anxiolytic effects, increases arousal, and suppress appetite.
- Activation of PERIPHERAL nicotinic receptors increases blood pressure and stimulates smooth muscle contractions.
- Activation of the nicotinic receptors stimulates the
dopaminergic reward system.
TorF: Activation of postsynaptic nicotinic receptors on dopaminergic terminal facilitates the release of dopamine
False. Activation of PRESYNAPTIC nicotinic receptors on dopaminergic terminal facilitates the release of dopamine
TorF: nicotine binds predominately to nACh receptors in the CNS, primarily is the a4b2 nicotinic receptor in the VTA.
True
Nicotine withdrawal symptoms include:
Irritability, impatience, hostility, anxiety, dysphoria, restlessness, difficulty in concentrating, bradycardia, increased appetite or weight gain
BUPROPION acts by blocking:
NET and DAT
Uses of bupropion in the therapy of smoking cessation:
Improves abstinence rate among smokers
Used as an aid in smoking cessation therapy
Varenicline is a partial _______ agonist
Nicotinic
TorF: Varenicline reduces cigarette craving and improves long term abstinence rates
True
SE of CHANTIX
Insomnia, abnormal dreams,nausea,constipation
Acute use of amphetamine releases NE and DA from neurons, inhibits DAT leading to increased synaptic DA levels and increased activation of postsynaptic DA receptors in the nucleus accumbens; these effects cause euphoria and feeling of increased energy.
AMPHETAMINE= RELEASE NE AND DA + inhibits DAT——> postsynaptic DA activation ——-> euphoria and energy
TorF: Increased extra-synaptic DA also leads to stimulation of presynaptic D2 receptors which decreases DA synthesis.
True
During chronic exposure to amphetamine, expression of DAT _________ while the number of postsynaptic DA receptor __________, and presynaptic DA is depleted
INCREASE
DECREASE
During withdrawal decreased synaptic levels of DA (from reduced synthesis and increased clearance through DAT) causes decreased activation of postsynaptic DA receptors;
feeling of dysphoria, fatigue and anhedonia occurs
AMPHETAMINE WITHDRAWAL
TorF: Caffeine acts by blocking presynaptic adenosine receptors on dopaminergic and adrenergic terminals.
True
CANNABINOIDS
§ Mechanism of Action:
Act on G protein-coupled receptors:
- CB1-receptors are mainly found in the CNS
- CB2-receptors are found in the periphery
What are the two endocannabinoids?
Anandamide
2-arachidonoyl glycerol (2-AG)
In cannabinoids, tolerance is due to down-regulation of CB1-receptors and post-translational modifications that reduce signal transduction efficiency.
Cannabinoids
Tolerance and dependence of cannabinoids is due to
*stimulation of central corticotropin-releasing factor
systems in the amygdala
*Blockade of CB1-receptors with rimonabant can precipitate a
withdrawal system in chronic users.
TorF: LSD, psilocybin and mescaline are agonists at 5-HT2 receptors
True
TorF: LSD can precipitate schizophrenic attacks in susceptible patients
True
KETAMINE AND PHENCYCLIDINE Act by blocking
glutamate-activated NMDA receptor channels
TorF: ketamine can cause schizophrenia in susceptible patients
False: Phencyclidine can cause schizophrenia in susceptible patients
MDMA acts by
Act by causing 5-HT release into synaptic space, inhibition of 5-HT biosynthesis and blockade of SERT.
TorF: CNS depressant action of barbiturates are more widespread than BZDs making its withdrawal symptoms are severe and more dangerous.
True
