Exam I Flashcards
Nicotine: 2nd line drugs for smoking cessation include:
- Combination (nicotine + buproprione)
- Clonidine
- Nortriptyline
What are 1st line therapy drugs?
- Nicotine replacement (patch, gum, vaping)
- Buproprione (anti-depressant)
- Varenicline (nicotinic receptor agonist)
Nicotine: After smoking, nicotine can reach the brain in about 10 seconds. It acts by acting on ______ inc. dopamine release and eliciting positive reinforcement (reward, relaxation).
nACh receptors
- nACh-R’s become desensitize (inactivated)
- upregulation of receptors
- inc. need
NOTE: withdrawal occurs when there is no nicotine
Nicotine: True/False - In the absence of nicotine, patient’s can undergo withdrawal symptoms including irritability, restlessness and increased craving (inc. desire to smoke)
True
Nicotine: 1 cigarette is equivalent to about ~10 puffs, meaning a person can receive ~10 positive reinforcements. Thus, > 5 ciggies/day can lead to dependence.
Dopamine is released in the ____, which is regulated by presynaptic nAChRs.
nucleus accumbens
*Nicotine activates nAChRs in the Ventral tegmental area
Nicotine: True/False - Treatment of tobacco dependence shoud address the physiological and the behavioral aspects of dependence
True
Physiologic:
- -addiction to nicotine
- -meds for cessation
Behavioral:
- -habit
- -behavior change program
Nicotine: Nicotine is an alkaloid obtained from the leaves of Nicotiana species.
It is a prototype agonist that stimulates different nAChRs (non-specific).
Nicotrine replacement therapy is approved (FDA) for smoking cessation. What are its actions?
- dec. withdrawal symptoms
- -irritability, anxiety, concentration, inc. appetite - decreases craving
- -long term benefit
*nasal sprays = most efficacious
Nicotine: Nicotine is metabolized by the liver into a long-acting metabolite (cotinine).
What is the risk for individuals who are poor metabolizers?
Inc. risk of addiction
NIcotine: Adverse effects of nicotine (esp. high dose) include Nausea, Insomnia and Headache.
What are adverse effects of vaping?
coughing, pulmonary disease
Nicotine: What are drug interactions and contraindications of nicotine use?
- Interactions
a. avoid smoking – N/V, tachycardia, nicotine overdose - Contraindications
- -pregnancy, lactating
- -pulmonary diseases
Nicotine: _____ is FDA approved as a monotherapy for smoking cessation.
It releives symptoms of nicotine withdrawal and craving, and also improves long term abstinence
Buproprion
- dec. weight gain after cessation
- also used in MDD
Nicotine: Buproprione acts by inhibiting both ____ and _____, thereby increasing dopamine and NE. This leads to relief of symptoms.
It also acts by inhibiting _____, whih aids its function as an anti-depressant and in efficacy as a smoking cessation agent.
- Inhibits DAT and NET
2. Inhibits different nAChRs
Nicotine: Buproprione acts by inhibiting both ____ and _____, thereby increasing dopamine and NE. This leads to relief of symptoms.
It also acts by inhibiting _____, whih aids its function as an anti-depressant and its efficacy as a smoking cessation agent.
- Inhibits DAT and NET
- Inhibits different nAChRs
DAT: dopamine transporter
Nicotine: Contraindications to use of Buproprione include:
- Epilepsy
- Bipolar disorder
What are Interactions?
- Drugs that modify CYP enzyme
(e. g. MAO inhibitors) = increase the risk of hypertension.
Nicotine: ______ is FDA approved as monotherapy for smoking cessation. It acts by decreasing nicotine reward.
It relieves symptoms of nicotine withdrawal and craving, with higher efficacy thatn bupropion or NRT.
Veranicline (Chantix)
Nicotine:
- Nicotine binds __1___ nicotinic receptors promoting DA release.
- During smoking cessation, there is NO dopamine release
- Varenicline (partial agonist) binds ___1___ nAChRs with higher affinity than nicotine. This permits inhibition of nicotine binding, while activating nAChRs.
alpha 4 Beta 2 receptors
less DA release than nicotine
Nicotine: Varenicline has minimal liver metabolism and is excreted in the urine.
Side effects include:
- N/V
- Insomnia
- Potential psychiatric effects (black box)
What are contraindications?
- Kidney disease (renal metabolism)
- Psychiatric conditions
- Pregnant/Lactating women
- -potential risk
Nicotine: 2nd line therapies for nicotine addiction include:
- Bupropioe + Nicotine patch
OR buproprione + varenicline - Nortriptyline
- Clonidine
_____ has a higher clinical efficacy than monotherapy as it provides sustained release. This therapy is most often used when monotherapy fails (heavy smokers)
Combination therapy (patch + buproprion)
Nicotine: 2nd line therapies for nicotine addiction include:
- Bupropion combined with nicotine patch or varenicline
- Nortriptyline
- Clonidine
Combination of bupropion and Varenicline has been shown to have a higher clinical efficacy than monotherapy.
*See slide 29
Nicotine: 2nd line therapies for nicotine addiction include:
- Bupropion combined with nicotine patch or varenicline
- Nortriptyline
- Clonidine
_____ is an NE transporter inhibitor (NET inhibitor) that is used when 1st line treatments fail or are contraindicated. It minimizes withdrawal symptoms, but is not FDA approved. It is effective in smokers w/out depression.
Nortriptyline
MOA: NE transporter; NET inhibitor
- effective in smokers w/out depression
- can be combined with nicotine patch
Nicotine: 2nd line therapies for nicotine addiction include:
- Bupropion combined with nicotine patch or varenicline
- Nortriptyline
- Clonidine
____ is very effective during the first stage of withdrawal. It minimizes withdrawal symptoms (from several addictive drugs, including nicotine). It however, does not improve craving
Clonidine
MOA: a2-agonist
*does not treat addiction (does not improve craving)
Nicotine: Which of the following is an adverse effect of Clonidine (anti-HTN)?
a. Dry mouth
b. Sedation
c. Weight gain
d. Dizziness
A and B
*hypotension
Cx: CV disease, pregnancy
Nicotine: Which of the following is an adverse effect of Nortriptyline (anti-depressant)?
a. dry mouth
b. sedation
c. hypertension
d. dizziness
Weight gain, dizziness, HTN
Cx: CV disease
Addiction Medicine: Addiction is a genetic, biological disease, NOT a moral failure.
Addiction may occur via many different substances including:
- Stimulants
- Depressants
- Hallucinogens
List examples of stimulants
- Cocaine
- Nicotine (deadliest in the world)
- Caffeine (most abused substance)
- AMphetamine and Methamphetamine
Addiction Medicine: Addiction is a genetic, biological disease, NOT a moral failure.
Addiction may occur via many different substances including:
- Stimulants
- Depressants
- Hallucinogens
Depressants include _____, opoids, benzos, and marijuana
a. alcohol
b. topiramate
c. caffeine
d. biotin
alcohol
*MJ - depressant/hallucinogen
Addiction Medicine: Addiction is a genetic, biological disease, NOT a moral failure.
Addiction may occur via many different substances including:
- Stimulants
- Depressants
- Hallucinogens
True/False - Hallucinogens include LSD, Xtacy, Pilocybin and Phencyclidine (PCP, Angel dust)
True
Addiction medicine: Mechanisms of use include:
- Nasal inhalation
- Ingestion (MJ brownies)
- Sublingual (acid - LSD)
- Injection (inc. risk transmission with HIV)
- Smoking
- Transdermal/mucosal
True
Addiction medicine: There are 3 broad categories associated with addiction
- Intoxication
- Withdrawal
- Dependence (“Use” Disorder)
____ occurs when the patient exhibits symptoms that are a direct physiologic effect of the chemical on a receptor. It is time limited (goes away) and occurs within hours of ingestion.
Intoxication
Addiction medicine: There are 3 broad categories associated with addiction
- Intoxication
- Withdrawal
- Dependence (“Use” Disorder)
_____ occurs when the px exhibits symptoms consistent with dysregulated numbers of receptors in relation to the availability of the substance. It can miserable, and deadly, and is often the reason people continue to use.
Withdrawal
Addiction medicine: There are 3 broad categories associated with addiction
- Intoxication
- Withdrawal
- Dependence (“Use” Disorder)
____ is characterized by long-standing use. It involves maladaptive behaviors (despite negative consequences). Individuals are normally “addicted” at this point.
“Use” Disorder
*previously dependence
Addiction medicine: Physicians are given the authority to prescribe controlled meds by the _______ agency and the __________. This authority comes as part of an agreement to abide by good medicine and to be responsible (safe use)
Drug enforcement agency (DEA) and OK Bureau of Drugs and Narcotics (OBN)
- obtain after get medical license (PGY2)
- must pay regular fee
Addiction med: True/False - Physicians must have continuing medical education every 2 years on “proper prescribing” to maintain their medical license.
True
*yearly for opoids
Addiction med: List the schedule I and schedule II drugs
- Schedule 1
- -most potential for abuse/dependence + no medicinal qualities
- -Heroin, LSD, MJ, ecstasy, peyote - Schedule II
- -high potential + some medicinal qualities
- -vicodin, cocaine, caffeine, meth, oxycontin, adderal - Schedule III
- -moderate potential + acceptable medicinal qualities
- -require prescription
- -tylenol with codeine, ketamine
Addiction med: True/False - Controlled substances should almost always be used within their FDA indication and doses. It is possible to prescribe off label with a compelling reason, however, all prescriptions should be based on sound evaluation and Dx.
Physicians must demonstrate good vigilance
True
- risk vs. benefit
- shift based on change in clinical status or new info
Addiction med: Which of the following is true about proper prescribing?
a. should evaluate functional outcome (drugs promote ability of the px to function)
b. should be evaluating objective evidence
c. should be monitoring
d. not required to use within FDA indications
A-C
Addiction med: Forms of monitoring include:
- Checking Urine Drug Screens
- Checking PMP (prescription monitoring program)
- Document, Document (risks vs. benefits)
True/False - Positive results of other substances in the urine is important as well as negative results (as it may indicate px is not using the drug - may be selling)
True
Addiction med: Forms of monitoring include:
- Checking Urine Drug Screens
- Checking PMP (prescription monitoring program)
____ should be done every time a controlled substance is written. It must be done every 6 months
PMP
Addiction med: Which of the following is a red flag of addiction?
a. taking more than prescribed
b. taking routinely despite being prescribed prn
c. continued use outside of the prescribed window
d. admittance that they want to stop, but cannot
all of the above
*unsuccessful Tx programs (meetings, hospitalizations)
Addiction med: Which of the following is NOT a red flag of addiction?
a. small jobs/panhandling to get the next dose
b. criminal activity
c. excessive time incapacitated from the dose
d. excessive violence following consumption
D
*A-C = other red flags
Addiction med: True/False - Other red flags of addiction include:
- Missing work, deadlines due to intoxication/hungover
- Termination/dismissal from school
- Change in roles at home due to lack of responsibility
- Arguments with friends and family about use/consequences, but uses anyway
True
- legal problems due to use
- withdrawal from gatherings (holidays)
- withdrawal from social groups
- unemployment
Addiction med: True/False - Red flags of addiction may also go so far as to include reckless driving/driving under the influence, using heavy machinery, or altered ability to supervise children.
True
Addiction med: Red flags of addiction may also be associated with:
- overdose with continued use
- failure to adhere to physician recommendations to cease use
- failure to adhere to recommendations by a mental provider
- contraction of hepatitis, HIV, liver failure, or endocarditis as a direct consequence of using
True
- need for inc. doses due to tolerance
- transition to stronger formulations
Addiction med: Red flags of addiction may also be associated with:
- overdose with continued use
- failure to adhere to physician recommendations to cease use
- failure to adhere to recommendations by a mental provider
- contraction of hepatitis, HIV, liver failure, or endocarditis as a direct consequence of using
True
- need for inc. doses due to tolerance
- transition to stronger formulations
- need for inc. amounts of substance to achieve intoxication
- no effect from what is being taken
Addiction med: Social signs of addiction include:
- Personality changes
- Unusual favors
- Secretive
- Stealing
List examples of each
- Personality
- -angry, irritable, defensive, demanding, selfish - Unusual favors
- -housing, transportation, borrow money - Secretive
- -territorial about personal space, vague about details, absent for long periods of time - Stealing
- -petty crimes (small items), assist others in access to one’s house
Neuro of Addiction: Addiction is a brain disease whose visible symptoms are bad/altered behaviors. It is biologically based on 3 things:
- Activation of the reward circuit
- Alteration of receptor densities (upreg/downreg)
- Alteration of NT levels
True/False - Drug abusers tend to have altered brain structures (resembling traumatic brain injury). Often they lose the capacity to experience pleasure
True
Neuro of Addiction: Addiction is a brain disease whose visible symptoms are bad/altered behaviors. It is biologically based on 3 things:
- Activation of the reward circuit
- Alteration of receptor densities (upreg/downreg)
- Alteration of NT levels
____ is the area of the brain that is involved in a feedback loop of reinforcement. It involves the nucleus accumbens and the ventral tegmental areas of the brain
Reward circuit
- Involves: Food, Sex, Social interaction, Drugs
- involves hippocampus = memories
Neuro of addiction: True/False - THe reward circuit tells the individual what to repeat in order to obtain reward. It builds pathways and connections that remain.
Drugs take advantage of and exaggerate this system
True
- brain myelinates from back to front
- initial drug use sends small messages, but inc. use/concentrations leads to stronger signals (inc. receptor numbers)
Neuro of addiction: What is the mechanism of withdrawal?
receptor dysregulatin
Neuro of addiction: True/False - The brain has many receptors for opoids. An overdose occurs when there is too much of an opois (e.g. heroin, oxycodone) that fits into too many receptors slowing the CNS and decreasing breathing
True
- how long it binds
- efficacy/potency
- morphine is standard measure
Neuro of addiction: Dependence can occur within 2 weeks. Dependence is highly influenced by strength of the drug and tolerance.
Tolerance occurs by
downregulation (degradation) of receptors (desensitized)
*it then takes more substance to produce the same analgesic effect as when first established
Neuro of addiction: Treatment of addiction involves treating its biological basis (because it is a medical problem).
True/False - Standard therapeutics involve treatment towards medication. In other words, detox the patient first (get them through withdrawal period) and then provide long-term treatment/long term abstinence.
True
Neuro of addiction: Addiction is created by the science of the substance and all individuals are at risk, though some are at higher risk than others due to personality and genetics.
True/False - The only factor that causes addiction is exposing the brain to an addictive substance (causing dopamine surge
True
NOTE: Physician controls the volume (treatment); assume 10% of meds will be abused
Opoids: List the 3 opoids receptors found in the CNS
- Mu
- Kappa
- Delta
Opoids: Opoids act as agonists at the opioid receptor. They consist of two types:
- Opiates (non-synthetic opoids)
- Opoids (synthetic opoids and opiates)
Opoids receptors are present due to three naturally ocurring peptides (endorphins). List them
- Beta-endorphin
- Enkephalins
- Dynorphins
Opoids: Which of the following is an opoid?
a. Morphine
b. Heroine
c. Codeine
d. Lithium
A-C
-oxycodone, meperidine, pentazocine, hydromorphone, hydrocodone, methadone, levo-alpha-acetylmethadol, buprenorphine
Opoids: ______ is synthetically derived from morphine. It has a rapid onset of action and a very short half life.
It is most often used intravenously, but there is increased intranasal and smoking of this drug (higher availability of purer drug)
Heroin
*different color compounds based on climate
Opoids: ____ is a semi-synthetic compound derived from thebaine (found in opium – refined). It is a prescription opoid prescribed for treatment of acute and chronic pain.
Oxycodone
*immediate/extended releasde - oxycontin
Opoids: ____ is a form prescription pain medicine that is currently used to treat 5HT syndrome (other med interactions).
It should not be used for more than 48 hours.
Meperidine
*benefit in CNS (chemo rigors) and bowel obstruction
Opoids: ______ was the first agonist-antagonist. It works at both mu and kappa receptors. It is often mixed with Naloxone to prevent euphoria
a. Pentazocine
b. Methadone
c. Hydromorphone
d. Hydrocodone
Pentazocine
*not widely used
Opoids: _____ is one of the stronger analgesics that is used for moderate to severe pain. It may be administered IV, PO, nasally and/or rectally
a. Codeine
b. Morphine
c. Hydromorphone
d. Pentazocine
Hydromorphone
Opoids: ____ is a prescription drug frequently used for minor pain. It is often mixed with acetaminophen.
It is highly abused (OK’s poison!)
a. Hydrocodone
b. Methadone
c. Levo-acetyl-methadol
d. Meperidine
Hydrocodone (Lortab)
Opoids: ____ is a long acting synthetic that is used mainly as maintenance Tx for heroin addiction.
It is also used in chronic pain, but should NOT be used in opoid naiive patients, as it will cause respiratory depression
Methadone
- high risk overdose
- administered every morning
Opoids: ____ is a long acting, synthetic compound that is similar to methadone.
It was FDA approved for Tx of heroin addiction. However, post-marketing surveillance led to a black box warning. It is no longer available in the U.S.
Levo-alpha-acetylmethadol
Opoids: ______ is a partial agonist at mu and kappa, but an antagonist at delta. It is often mixed with naloxone.
It is used to treat pain and is a pillar of treatment for opoid use disorder
Buprenorphine
Opoids: Buprenorphine is a partial agonist of the mu receptor with high receptor affinity. Thus, it will displace most full mu agonists (e.g. heroin).
True/False - Buprenorphine has slow mu receptor dissociation. Thus, it will remain on the receptor for a long time, preventing the binding of full agonists
True
- short analgesic effects
- really good drug to fight addiction
Opioids: Which is true about partial Mu agonists?
a. results in high level of abuse
b. activates mu at lower levels
c. relatively less reinforcing (less reward circuit activ.)
d. includes buprenorphine
B-D
*less abuse
Full agonist: highly reinforcing, high abuse; morphine, methadone, codiene, fentanyl, heroine, codones…
NOTE: hydrocodone equiv. to morphine (slide 20)
Opoids: There are 12 criteria for the diagnosis of opioid use disorder:
- Opioids taken in larger amounts or over a longer period of time than intended
- There is persistent desire or _______ efforts to cut down or control opoid use
- There is a great deal of time spent performing activities necessary to obtain the opioid, use the opioid, or recover from its effect.
- _______, or a strong desire or urge to use opioids
- unsuccessful
4. craving
Opioids: There are 12 criteria for the diagnosis of opoid use disorder:
- recurrent opioid use resulting in a failure to fulfil major role obligations at work, home or school
- continued use despite having persistent or recurrent social or interpersonal problems due to opioids
- Important social, occupational, or _______ activities are given up or reduced due to opioid use
- recurrent use in situations where it is physically ______
- Continued use despite knowledge of having a persistent, recurrent physical or psych problem associated with the substance
- recreational
8. hazardous
Opioids: Tolerance and Withdrawal are also part of the criteria involved in diagnosing “Opioid Use Disorder.”
- _______ is defined as either a need for markedly inc. amounts to achieve intoxication/desired effect, OR a markedly diminished effect with continued use of the same amount.
- ______ is either characteristic opoid withdrawal syndrome OR when opioids are taken to relieve or avoid withdrawal symptoms.
- Tolerance
- –does NOT apply when taken under medical supervision - Withdrawal
- -does NOT apply w/ medical supervision
*tolerance and withdrawal = physiologic dependence
Opioids: What is the purpose for treating Opioid Use disorder?
a. prevent death
b. prevent morbidity
c. manage withdrawal
d. pharmacologic management
all of the above
- non-pharmacologic management
- prevent public health morbidity
Opioids: True/False - Prevention of death involves
- education about risk behavior
- administration of naloxone (narcan) rescue kits
- avoid co-prescribing (opioids and benzos)
What are examples of education about risky behavior?
- mixing opioids with other meds/alcohol
- use of dangerous opioids (fentanyl/carfentanyl)
*test strips - determine if purely fentanyl
Opioids: Naloxone is a full opioid antagonist that can be used to rapidly reverse opioid overdose. However, it is important to be cautious of the short half-life
True
*lazarus effect
Opioids: True/False - Co-prescribing opioids with other depressants (BZD, OH, sleep aids) is extremely dangerous and should be avoided. It is important for physician’s to check the PMP for other meds the patient may be taking
True
**100% higher incidence of overdose when opioid is taken with Benzo
Opoids: With regard to preventing morbidity, ______ is the outcome of interest, NOT reduction of pain.
Furthermore, needle use is a public health emergency. There are programs (needle exchange, methadone clinics) that have been proven to reduce incidence of HIV and Hep C (harm reduction)
Functionality
Opoids: A patient presents with complaints of GI distress (N/V, diarrhea, cramping), lacrimation, goosebumps and pupillary dilation.
You suspect
Opioid withdrawal
*piloerection
Opioids: Which of the following is a method for management of opioid withdrawal?
a. slow taper of opioid
b. treat symptoms (anti-emetic/anti-diarrheal)
c. clonidine
d. buprenorphine (tapered)
all of the above
*cold turkey – not recommended (leading cause of overdose)