Psychiatry Flashcards
Define tolerance and withdrawal
Tolerance (needing higher amounts of the substance to achieve the desired
effect or experiencing diminished effects when repeating the same dose)
Withdrawal (a substance-specific syndrome occurring when a patient stops or reduces heavy/prolonged substance use)
(It is possible to have a substance use disorder without having phys- iological dependence (i.e., without having withdrawal or tolerance))
A 56 yo business executive is 1 day out from an uncomplicated cholecystectomy for symptomatic cholelithiasis. The nurse notices a significant variation in his VS compared to what was measured in the PACU. HR is 153 bpm, BP is 170/105. He has tremors and has been feeling nauseous. He is given a beta blocker for symptomatic relief. 24 hrs later he begins to describe a feeling of bugs crawling under his skin, appears delirious, and has a mild fever. He begins to have generalized tonic-clonic movements of his hands and legs. What is the next best step in the management of this patient?
a. IV Lorazepam therapy.
b. IV Phenobarbital therapy.
c. A 4-6 week course of Bupropion.
d. Referral for Alcoholics Anonymous counseling.
The best answer is A, Lorazepam therapy. This patient has gone into delirium tremens. He deserves a benzodiazepine.
(You should watch out for this specific scenario on the shelf/Step 2)
This is alcohol withdrawl - give short acting benzo like lorazepam iv; don’t give bupropion may make sxs worse; phenobarbital not first line - try benzo first
MOA for benzodiazepine in treating delirium tremens
increases frequency of chloride channel opening which hyperpolarizes neurons (via GABA receptor)
(Ie., work by potentiating the effects of gamma-aminobutyric acid (GABA))
(Facilitate GABA action by frequency of Cl– channel opening (“frenzodiazepines” increase frequency). )
Alcohol effects on GABA and glutamate receptors?
Alcohol activates GABA, dopamine, and serotonin receptors in the CNS. It inhibits glutamate receptor activity and voltage-gated calcium channels. GABA receptors are inhibitory, and glutamate receptors are excitatory; thus, alcohol is a potent CNS depressant.
Most adults will show some signs of intoxication with BAL ——— and obvious signs with BAL
———mg/dL.
> 100
> 150
Tx alcohol intoxication:
- Monitor: Airway, breathing, circulation, glucose, electrolytes, acid–base status.
-Give parenteral thiamine (to prevent or treat Wernicke’s encephalopathy) and folate. Remember thiamine must be given before glucose, as it’s a necessary cofactor for glucose metabolism.
Ethanol, along with methanol and ethylene glycol, can be a cause of ——— acidosis.
anion gap metabolic
Confabulation—inventing stories of events that never occurred—is often associated with
Korsakoff’s “psychosis,” or alcohol-induced neurocognitive disorder
(Patients are unaware that they are “making things up”)
What are the typical features of Wernicke’s encephalopathy?
The classic triad is confusion (altered mental status), ataxic gait, and oculomotor findings (typically nystagmus or gaze palsies).
A 42-year-old man has routine surgery for a knee injury. After 72 hours in the hospital he becomes anxious, flushed, diaphoretic, hypertensive, and tachycardic. What most likely accounts for this patient’s symptoms? Treatment? What are you most concerned about?
Dx: Alcohol withdrawal
Tx: Benzodiazepines (chlordiazepoxide [Librium] or lorazepam [Ativan] are considered the drugs of choice)
Concerns: Seizures, delirium tremens, autonomic instability, and cardiac arrhythmias. Remember that alcohol withdrawal can be fatal.
Signs and symptoms of alcohol withdrawal syndrome include
insomnia, anxiety, hand tremor, irritability, anorexia, nausea, vomiting, autonomic hyperactivity (diaphoresis, tachycardia, hypertension), psychomotor agitation, fever, seizures, hallucinations, and delirium tremens
Alcohol withdrawal induced seizures are treated with
benzodiazepines
Long-term treatment with anticonvulsants is not recommended for alcohol withdrawal seizures.
Delirium tremens is a dangerous form of alcohol withdrawal involv- ing ——— and treated with ———
Sxs: mental status and neurological changes; Symptoms include disorientation, agitation, visual and tactile hallucinations, and autonomic instability (increase in respiratory rate, heart rate, and blood pressure)
(It carries a 5% mortality rate but occurs in only 5% of patients that experience EtOH withdrawal. Patients often require ICU level of care)
treatment: supportive care and benzodiazepines
Timing of minor alcohol withdrawal sxs (ie Tremulousness, mild anxiety, headache, diaphoresis, palpitations, anorexia, gastrointestinal upset; normal mental status)
6-36 hours
Timing of seizures with alcohol withdrawal
6-48 hours
Definition and timing of alcoholic hallucinosis following alcohol withdrawl
Alcoholic hallucinosis=Visual, auditory, and/or tactile hallucinations with intact orientation and normal vital signs
12-48 hours (.5-2 days)
Definition and timing of delirium tremens following alcohol withdrawl
Definition: Delirium, agitation, tachycardia, hypertension, fever, diaphoresis
Timing: 48-96 hours (2-4 days)
Tx delirium tremens
Benzodiazepines (lorazepam, diazepam, or chlordiazepoxide)
Parenteral thiamine, folic acid, and a multivitamin to treat nutritional deficiencies (“banana bag”)
Alcoholic Ketoacidosis: Defintion
Hallmark is ketosis without hyperglycemia and a negative alcohol level
Frequently seen in the setting of alcohol cessation after an alcohol binge secondary to protracted vomiting and lack of oral intake
(Alcoholic ketoacidosis stems from the patient’s inability to ingest, absorb and utilize glucose from their diet. The vomiting and nausea prevent adequate solute intake from the gastrointestinal tract. The alcohol further depresses gluconeogenesis in the body and keeps blood sugar levels low. An anxiety state and alcohol withdrawal further exacerbate the patient’s ability to eat. The lack of nutrients other than alcohol causes the formation of ketones and elevated gap ketoacidosis in the absence of diabetes.)
Alcoholic Ketoacidosis: lab findings and treatment
Laboratory studies reveal a high anion gap metabolic acidosis, ketonemia, and low levels of potassium, magnesium, and phosphorus
Treatment consists of hydration with D5NS, and replacing electrolytes.
Lab findings suggestive of excessive long-term alcohol use
AST:ALT ratio ≥2:1 and elevated GGT
(they take a few weeks to return to normal during abstinence)
At-risk or heavy drinking for men is more than ——— drinks per day or more than ——— drinks per week. For women, it is more than ——— drinks per day or more than ——— drinks per week
4
14
3
7
Wernicke’s encephalopathy caused by
thiamine (vitamin B1) deficiency resulting from poor nutrition; Acute and can be reversed with thiamine therapy
Features of Wernicke’s encephalopathy
Ataxia (broad-based)
confusion
ocular abnormalities
(nystagmus, gaze palsies)
What is the treatment for Wer- nicke’s encephalopathy?
High dose parenteral (IV or IM) thiamine should be given for 2–7 days, followed by daily oral thiamine
Give all patients with altered mental status ——— before glucose, to avoid ———
thiamine
precipitating Wernicke–Korsakoff syndrome (Thiamine is
a coenzyme used in carbohydrate metabolism)
If left untreated, Wernicke’s encephalopathy may progress to Korsakoff syndrome, which is
Chronic amnestic syndrome (Reversible in only about 20% of patients)
Features: Impaired recent memory, anterograde amnesia, compensatory confabulation (unconsciously making up answers when memory has failed)
First line tx alcohol use disorder:
Naltrexone (Opioid receptor antagonist; reduces cravings and the “high” associated with alcohol intoxication)
Acamprosate (Likely modulates glutamate transmission.)
Second line tx alcohol use disorder:
Disulfiram (Blocks aldehyde dehydrogenase, causing buildup of acetaldehyde and aversive symptoms (flushing, headache, nausea/vomiting, palpitations, shortness of breath))
Topiramate (Anticonvulsant; potentiates GABA and inhibits glutamate receptors)
Naltrexone for alcohol use disorder: pros vs cons
Pros: First-line treatment. Available as an oral tablet (can be taken daily, or as-needed on drinking days), or monthly injection. Can allow some patients to engage in moderate alcohol use without escalating to binge drinking.
Cons: Will precipitate withdrawal in patients with physical opioid dependence. Can interfere with anesthesia (e.g., for acute injury or planned surgeries). Risk of LFT elevation.
Acamprosate for alcohol use disorder: pros vs cons
Pros: First-line treatment. Can be used for patients with liver disease. Typically used for relapse prevention in patients who have already stopped drinking.
Cons: Contraindicated in severe renal disease
Alcoholism may be associated with the development of what syndrome:
reversible confusion, ophthalmoplegia, and ataxia (Wernicke’s, give thiamine)
OR
Making stuff up (confabulations)/amnesia + Wernicke sxs which are largely not reversible (Korsakoff’s psychosis)
In alcohol withdrawal, differentiate the ——— sxs associated with Delirium Tremens from the ——— sxs associated with alcoholic hallucinosis
seizures and autonomic instability
visual hallucinations and relative autonomic stability
A 50 y/o known alcoholic presents to the ER with tonic clonic seizures. BP 180/110, HR 118, T 100.1. How long since his last drink?
~12-24hrs. (bimodal peak at 8 and 48hrs)
A 50 y/o known alcoholic presents to the ER with tonic clonic seizures. BP 180/110, HR 118, T 100.1. How long till he develops confusion, fluctuations in consciousness and feeling of ants crawling on him (formication)?
~48-72 hrs (2-3 days) since last drink is the when delirium tremens usually
start
(When admit someone for alcohol detox at least got to watch them for 72 hrs; preferably a day longer than that at 96 hrs (4 days))
A 50 y/o known alcoholic presents to the ER with tonic clonic seizures. BP 180/110, HR 118, T 100.1. His blood alcohol level is 225mg/mL. How long till its out of his system?
~9hrs, Alcohol is metabolized by zero order kinetics (same amt/unit time = 25mg/hr)
(Alcohol metabolized by zero order kinetics so if you have a “buttload” of alcohol in your system, it will take longer than if you have less; zero order kinetics is a certain amount of drug metabolized per unit time, not a certain percentage)
What is the average rate of alcohol metabolism?
Between 15 and 35 mg/dL per hour
Zero-order elimination of drug: definition and example drugs
Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp decreases linearly with time. (Capacity-limited elimination)
Examples of drugs—Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations) (PEA (a pea is round, shaped like the “0” in zero-order))
Zero-order elimination of drug: impact on half-life over time
Time of t1/2 decreases as concentration decreases
First-order elimination of drug: definition and example drugs
Rate of first-order elimination is directly proportional to the drug concentration (ie, constant fraction of drug eliminated per unit time). Cp decreases exponentially with time. (First-order=Fraction=Flow-dependent elimination)
Applies to most drugs
First-order elimination of drug: impact on half-life over time
Time of t1/2 is constant as concentration decreases
A 50 y/o known alcoholic presents to the ER with tonic clonic seizures. BP 180/110, HR 118, T 100.1. If his medications included propranolol, lactulose, and allopurinol, what would be the best sign to monitor for his withdrawals?
Beta-blockers mask the signs of autonomic hyperactivity, but you can follow hyperreflexia to dose the benzos during w/drawal
(Propranolol will blunt tachycardia; one of signs autonomic instability is hyperactive reflexes- this will still be there with beta blocker)
A 50 y/o known alcoholic presents to the ER with tonic clonic seizures. BP 180/110, HR 118, T 100.1. Best initial treatment of our patient?
Many patients become physically dependent on benzodiazepines and require
increasing amounts for the same clinical effect (i.e., tolerance)
(potential for abuse)
How is benzodiazepine overdose treated?
Flumazenil; however, be careful not to induce withdrawal too quickly—this can be life threatening.
Which substances of abuse have potentially fatal withdrawal syndromes?
Alcohol, benzodiazepines, and barbiturates
Flumazenil’s MOA is ——— used for treating ———
very short-acting BZD antagonist
BZD overdose (Use with caution when treating overdose, as it may precipitate seizures)
Flumazenil is used for ——— BUT its use can cause ———
benzodiazepine overdose reversal
seizures especially in those patients with a low seizure threshold (Use with caution, and have an airway cart ready in case airway control becomes necessary)
(Remember that benzodiazepine withdrawal can be life threatening)
What is a potential consequence of using benzodiazepines with alcohol?
BDZs can be lethal when mixed with alcohol. Respiratory depres- sion may cause death.
Half life and examples of long acting vs intermediate acting vs short acting benzos:
Long acting (half-life: >20 hours)
• Diazepam (Valium)
• Clonazepam (Klonopin)
Intermediate acting (half-life: 6–20 hours)
• Alprazolam (Xanax)
• Lorazepam (Ativan)
• Oxazepam (Serax)
• Temazepam (Restoril)
Short acting (half-life: <6 hours)
• Midazolam (Versed)
In chronic alcoholics or those with liver disease, use benzodiazepines that are
not metabolized by the liver
There are a LOT of them: Lorazepam
Oxazepam
Temazepam
Benzos should not be given for long periods of time to prevent
“dependence” (if ever see answer of recurrent prescription for benzo- almost always wrong- because addictive)
Our next patient comes in w/ confusion, ataxia, and you find pic below on physical exam: Dx? Best first step?
Wernicke Encephalopathy. Caused by thiamine deficiency Give thiamine 1st, then glucose containing fluids.
(Pic is showing ophthalmoplegia) (so w/ wernicke expect confusion, ataxia, and either jiggly or paralyzed eyes)
(Remember give thiamine first before glucose b/c can’t utilize glucose unless have thiamine as co-factor; glucose before thiamine worsens encephalopathy)
Our next patient comes in w/ confusion, ataxia, and you find pic below on physical exam: Could progress to?
Can progress to Korsakoff’s syndrome (irreversible damage to mamillary bodies, etc)- apathy, anter/retrograde amnesia and confabulation. Can see MB atrophy on MRI
(Wernicke reversible with administration of thiamine)
Chronic amphetamine use leads to accelerated
tooth decay (“meth mouth”)
