Dr G. - Alcohol and Substance Abuse

What are the symptoms seen in a person going through an opioid OD?

Sedation (“nodding”), respiratory depression, pinpoint pupils, blue lips and nails

The routes of administration for naloxone for opioid OD are via ____________ and _________________. MOA? Do we need a prescription for naloxone (Narcan)?

• intranasal, IM

• Naloxone instantly reverses opioid overdoses by blocking the opioids from interacting with the mu receptors.

If there is no response to Narcan in ____ minutes, you can administer another dose. It wears off in ____ minutes.

• three

• 30-90 minutes

List the FDA-approved treatments for opioids dependence and its MOA.

• Naltrexone: opioid antagonist

• Methadone: opioid agonist (helps with withdrawal symptoms, can be abused, ADR QT prolongation)

• Suboxone: buprenorphine + naloxone (sublingual).

• Buprenorphine is a partial agonist and antagonist, naloxone is an antagonist.

• Naloxone is not absorbed well sublingually. If the patient tries to abuse it by crushing it for IV, the naloxone will act as an antagonist to block the buprenorphine.

• Subutex: buprenorphine without naloxone

Name the antidepressant FDA-approved for smoking cessation.

Bupropion

Name the drug of abuse that can be “cooked” from OTC pseudoephedrine (Sudafed). 

Methamphetamine

What is considered “legally drunk” DUI blood alcohol concentration (BAC) in California?

• 0.08%- regular drivers

• 0.04%-commercial license drivers

List the treatments for alcohol w/d (inpatient) and rationale for their use.

• BZDs: preferred treatment for withdrawal symptoms with cross-tolerance with alcohol through modulation of GABA receptors. Most commonly used are BZDs with longer half-life: chlordiazepoxide (Librium), diazepam (Valium). Lorazepam (Ativan) is for patients with liver impairment.

• In situations of severe withdrawal sxs, large doses of BZDs can be required, and phenobarbital can be used in these cases.

• Adjunct treatment with clonidine is sometimes used for hypertension and to calm the sympathetic nervous system.

• Thiamine (B1) 100 mg is given to avoid Wernicke Korsakoff syndrome.

• A banana bag has IV fluids containing vitamins and minerals. The bags typically contain MVI, thiamine (B1), folic acid (B9), and magnesium sulfate, usually used to correct nutritional deficiencies or chemical imbalances in the body.

Wernicke Korsakoff syndrome is secondary to chronic alcohol abuse, is due to which vitamin deficiency? Prevention consists of supplementation of the depleted vitamin at what daily dose for about how long (days/weeks/months/years)?

• B1 (Thiamine), 100 mg for months

• Alcohol abuse decreases vitamin B1 (thiamine), which results in Wernicke Korsakoff syndrome. Wernicke encephalopathy has a sxs of confusion, ataxia, nystagmus; if untreated, can lead to Korsakoff psychosis characterized by memory loss, confabulation, and occasionally hallucinations (visual).

List the brand/generic name and MOA of the 3 FDA-approved treatments for alcohol use disorder. Indicate if they help with alcohol craving:

Brand	Generic	MOA	Targets Cravings
	Disulfiram	Inhibits aldehyde dehydrogenase --> accumulation of acetaldehyde --> deters alcohol use	No effect
Revia	Naltrexone PO	Blocks mu receptor --> decreases rewarding effects of alcohol use --> reduce cravings	X
Vivitrol	Naltrexone IM
Campral	Acamprosate	blocks NMDA receptors --> restoring GABA and glutamate balance	X

What is the most beneficial therapy for alcohol use disorder to attain long-term sobriety?

Alcoholics Anonymous (AA)

What is the MOA of flushing in some Asians after intake of alcohol AKA “Asian Flush”?  Describe the Antabuse reaction.

• Many Asian populations (30-50%) lack aldehyde dehydrogenase (acetaldehyde metabolizer). Acetaldehyde cannot be converted to acetate by aldehyde dehydrogenase.

• Disulfiram blocks aldehyde dehydrogenase causing drinkers to experience a similar unpleasant sensation when they drink.

How does Pepcid help with people with aldehyde dehydrogenase deficiency?

Which of the following are dissociative psychedelics drugs?
(Dissociation from environment or self in a dream-like state or trance)

1. Phencyclidine (PCP) (AKA Angel dust)

2. Ketamine (AKA vitamin K)

3. High doses of dextromethorphan

All of the above

Dextromethorphan at large doses used recreationally (300 to > 1500 mg), dextromethorphan N-methyl-d-aspartate (NMDA) receptors, producing dissociative effects similar to those of phencyclidine and ketamine.

Chronic alcohol abuse can induce CYP2E1 enzyme. What is the effect the metabolism of acetaminophen?

• APAP with the toxic metabolite of NAPQI can be damaging to the liver if used more than 4 grams a day

• If the pt has been drinking alcohol the max dose should NOT be > 2 gm/day (increased risk of hepatotoxicity). Chronic alcohol use induces the CYP2E1 enzyme that converts acetaminophen to the NAPQI

Your patient is taking Percocet 2T q6hr after surgery. In addition, she takes Tylenol extra strength 2T q 12 hr for pain relief for over 6 months. Any issue in this case?

Percocet 2TQ6 hr = APAP 2.6/day + 2 gm OTC = 4.6 gm/day

ABOVE THE APAP LIMIT/DAY for adults

Is naloxone effective in treating other types of overdoses other than opioids?

No

Can pregnant patients with opioid OD be given naloxone?

Yes

Which medication is FDA-approved for AUD and OUD?

Naltrexone (Revia)

What is Vivitrol and its indication?

naltrexone monthly IM injection for opioid & alcohol use disorders

What is the difference between Suboxone and Subutex? Why is naloxone added in Suboxone?

• Both have buprenorphine.

• Suboxone has buprenorphine and naloxone

What are the FDA-approved treatments for OUD?

• Buprenorphine. buprenorphine/naloxone

• Methadone

• Naltrexone

• Naloxone

What is the street name for MDMA (3,4-methylenedioxy-methamphetamine)? 

• Ecstasy

• 5-HT and oxytocin

What neurotransmitters imbalance causes alcohol withdrawal symptoms?

Glutamate and GABA

What are the symptoms of alcohol w/d (AIMS)?

• Anxiety

• Insomnia

• Muscle tremor

• Seizures

• Increase BP

The most commonly used benzodiazepines with longer half-lives are chlordiazepoxide (___________) and ___________ (Valium). Use ___________ (___________) for patients with liver impairment.

• Librium

• Diazepam

• Ativan (lorazepam)
  
  

__________________ syndrome can be seen in babies with mothers with alcohol use disorder. What are sxs of FAS?

• Fetal alcohol syndrome

  • Sx:

    • facial: small eye openings, smooth philtrum, thin upper lip

    • seizures, delayed speech, cognitive issues, behavioral problems, vision/hearing problems, heart/kidney defects, finger/limb deformities

Which OTC drug is abused in supratherapeutic doses to act on the mu opioid receptors (AKA poor man’s methadone)?

• Loperamide - usually anti-diarrheal agent but when used in very high doses is used in OD

What is Kratom? Is this abused? MOA?

• Kratom is an evergreen treat native to SE Asia

• is abused just as morphine, heroin, others

• MOA: it contains alkaloids that interact with opioid receptors in the brain → sedation, pleasure, decreased pain

Delirium tremens usually peaks around day 5 after alcohol cessation. What are the usual treatments for DTs?

• 2-3 days after alcohol. Peak at day 5, lasts up to 7 days

• Symptoms: agitation, disorientation, tachycardia, HTN, fever, diaphoresis, tremor

• Banana bag: Folic acid, thiamine, multivitamins, magnesium

• BZDs and phenobarbital in inpatient settings

Substance abuse frequently coexists with and complicates other psychiatric disorders, and it is a common and often unrecognized cause of physical morbidity. Intravenous drug abuse is a major factor in the spread of ____ and ____.

• HIV and Hep C

What are the most abused drinks in college students?

• Alcohol, coffee

Which of the following is a rescue drug for opioid OD?

Naloxone

Naltrexone is FDA-approved for which disorders?

• AUD

• OUD

Your patient is doing well on naltrexone but often misses their daily doses. What can you recommend?

Vivitrol (naltrexone) IM injection monthly

What is the most common ADR for Campral (acamprosate) for the treatment of AUD? Management?

• Diarrhea

  • Use lower therapeutic doses (333mg 2T po TID to 1T po TID)

Which class of medications contributes to the most fatalities with OD? Name the drug with most OD death.

Synthetic opioids (ex Fentanyl)

The most likely cause of opioid OD fatalities is from ___________________

Respiratory depression (stop breathing) → death

Higher risk of respiratory depression from opioid OD is higher with concurrent use of what other meds?

• BZDs (alprazolam, diazepam, etc)

• Gabapentin

Explain why it takes approximately 3 weeks for Valium (diazepam) to be cleared from the body?

It is a long acting benzo