Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
328 Cards in this Set
- Front
- Back
|
What are the precursors of acetylcholine?
|
choline & acetyl CoA
|
|
|
What enzyme performs the rate-limiting step of acetylcholine synthesis?
|
choline acetyltransferase
|
|
|
How is acetylcholine cleared from the synaptic cleft?
|
broken down by acetylcholinesterase into acetate & choline
|
|
|
What is the major excitatory neurotransmitter in the brain?
|
glutamate
|
|
|
What is the major inhibitory neurotransmitter in the brain?
|
GABA
|
|
|
What is the major inhibitory transmitter in the spinal cord?
|
glycine
|
|
|
From what molecule is glutamate synthesized, and what enzyme performs the rate-limiting step?
|
glutamine, glutaminase
|
|
|
What are the two types of acetylcholine receptors, and what is the major difference between them?
|
nicotinic AChR (ion channel) and muscarinic AChR (GPCR)
|
|
|
From what molecule is GABA synthesized?
|
glutamate (GABA=gamma-aminobutyric acid)
|
|
|
Which of the three GABA receptors (GABA-A, GABA-B, GABA-C) is a GPCR?
|
GABA-B. GABA-A and GABA-C are ion channels.
|
|
|
From which amino acid is glycine synthesized?
|
serine
|
|
|
What enzyme catalyzes the rate-limiting step of GABA synthesis?
|
glutamate decarboxylase (GAD)
|
|
|
How are catecholamines removed from the synaptic cleft?
|
a combination of transporters, MAO, and COMT
|
|
|
What amino acid is the precursor for all the catecholamines?
|
tyrosine
|
|
|
Are the catecholamines excitatory or inhibitory?
|
excitatory
|
|
|
Which areas of the brain are the primary producers of dopamine?
|
substantia nigra & ventral tegmental area
|
|
|
Which area of the brain is the primary producer of norepinephrine?
|
locus ceruleus
|
|
|
Describe the synthesis of the catecholamines, from tyrosine to epinephrine.
|
TYROSINE is converted by tyrosine hydroxylase (rate-limiting) to DOPAMINE, which is converted to NOREPI, which is converted to EPI
|
|
|
What is the precursor of histamine, and what enzyme catalyzes its conversion?
|
histidine, histidine decarboxylase
|
|
|
What area of the brain is the primary producer of serotonin (5-HT)?
|
Raphe nucleus
|
|
|
What amino acid is the precursor of serotonin, and what enzyme catalyzes its conversion?
|
tryptophan, tryptophan hydroxylase (5-HT=5-hydroxy tryptophan)
|
|
|
What are some examples of neuropeptides?
|
substance P, endorphins, enkephalins
|
|
|
Do endocannabanoids facilitate or inhibit inhibition?
|
Inhibit inhibition
|
|
|
Are endocannabinoids synthesized from amino acids, lipids, or nucleotides?
|
lipids
|
|
|
How are endocannabinoids degraded?
|
hydrolyzed by FAAH (fatty acid amide hydrolase)
|
|
|
Which TCA is used for the treatment of OCD?
|
clomipramine
|
|
|
Name 5 TCAs.
|
nortriptyline, amitriptyline, clomipramine, imipramine, desipramine (best mnemonic I could come up with = N-ACID...)
|
|
|
Which two TCAs have the fewest anti-muscarinic side-effects?
|
desipramine & nortriptyline
|
|
|
Name the 3 major pharmacologic actions of TCAs.
|
1) inhibit the reuptake of biogenic amines (norepi & serotonin). 2) block muscarinic cholinergic receptors. 3) block alpha-1 adrenergic receptors.
|
|
|
Name the major side-effect of TCAs that is due to the alpha-1 adrenergic blockade.
|
orthostatic hypotension
|
|
|
Name the cardiac side-effects of TCAs that are due to the inhibition of reuptake of biogenic amines.
|
tachycardia, arrhythmias (from increased norepi; also caused by muscarinic blockade)
|
|
|
What are some side-effects of TCAs that are due to the muscarinic blockade?
|
From head to toe: confusion, sedation, blurred vision, dry mouth, tachycardia, cardiac arrhythmias, urinary retention, constipation (note: this list may not be exhaustive)
|
|
|
Which TCA is most commonly used for enuresis?
|
imipramine
|
|
|
Which TCA is most commonly used for chronic pain?
|
amitriptyline
|
|
|
Are the side-effects of TCAs generally worse in the young or the elderly?
|
elderly (slower metabolism of drug)
|
|
|
Why are TCAs fatal in overdose?
|
In high doses, TCAs can cause cardiac arrhythmias and seizures.
|
|
|
How do you treat cardiac arrhythmias caused by TCAs?
|
lidocaine and propanolol
|
|
|
How do you treat seizures caused by TCAs?
|
diazepam or lorazepam
|
|
|
What are the symptoms of TCA withdrawal?
|
nausea, dizziness, headache, diaphoresis, increased salivation
|
|
|
What is the mechanism of action of mirtazapine?
|
blocks 5-HT2 receptors
|
|
|
What are two problematic side-effects of mirtazapine?
|
sedation, weight gain
|
|
|
What anti-depressant can also be used for smoking cessation?
|
buproprion (depression=Wellbutrin, smoking cessation=Zyban)
|
|
|
Which anti-depressant is most commonly used for insomnia?
|
trazodone
|
|
|
Which anti-depressant can produce priapism?
|
trazodone
|
|
|
What is the mechanism of action of trazodone?
|
inhibition of serotonin reuptake AND blockade of 5-HT2 receptors
|
|
|
What is the major advantage of SSRIs over TCAs?
|
Most important is probably that they are not sedating. Also little effect on norepinephrine reuptake (fewer cardiac SEs); less activity at muscarinic receptors (the #2 cause of discontinuation of TCAs); less activity at alpha-1 receptors (less orthostatic hypotension)
|
|
|
Do SSRIs cause hypersomnia or insomnia?
|
insomnia
|
|
|
Name 6 SSRIs.
|
Mnemonic:
Effective-Escitalopram For-Fluvoxamine, Fluoxetine Sadness-Sertraline Panic-Paroxetine & Compulsions-Citalopram |
|
|
What are 3 psychiatric symptoms of serotonin syndrome?
|
confusion, hypomania, akathisia
|
|
|
What are 4 neuromuscular symptoms of serotonin syndrome?
|
muscle twitching, myoclonus, tremor, hyperreflexia
|
|
|
Besides psychiatric and neuromuscular side effects, name 3 additional symptoms of serotonin syndrome.
|
headache, diaphoresis, priapism
|
|
|
Which SSRI is most commonly used to treat premature ejaculation?
|
paroxetine (for some people, SSRIs can cause delay to orgasm instead of anorgasmia)
|
|
|
Name 3 SNRIs.
|
duloxetine, venlafaxine, desvenlafaxine (mnemonic=DVD)
|
|
|
Name the distinguishing side-effect of SNRIs.
|
hypertension
|
|
|
What side-effect of SSRIs affects at least 50% of patients?
|
sexual dysfunction (decreased libido and/or anorgasmia)
|
|
|
Do SSRIs cause hypersomnia or insomnia?
|
insomnia
|
|
|
What are 3 psychiatric symptoms of serotonin syndrome?
|
confusion, hypomania, akathisia
|
|
|
What are 4 neuromuscular symptoms of serotonin syndrome?
|
muscle twitching, myoclonus, tremor, hyperreflexia
|
|
|
Besides psychiatric and neuromuscular side effects, name 3 additional symptoms of serotonin syndrome.
|
headache, diaphoresis, priapism
|
|
|
Which MAOI is a selective MAO-B inhibitor?
|
selegiline
|
|
|
Name the 3 nonselective MAOIs.
|
phenelzine, isocarboxazid, tranylcypromine
|
|
|
Why must you stop MAOIs 10-14 days before taking contraindicated drugs or tyramine?
|
because they irreversibly inhibit MAO, meaning that new enzymes must be synthesized, and this takes time
|
|
|
What do MAOs normally degrade?
|
All of the catecholamines (dopamine, norepi, epi) and serotonin.
|
|
|
How long do all anti-depressants take to work?
|
Usually a minimum of 2-3 weeks (can cause mania sooner) and a maximum of 6-8 weeks
|
|
|
Why might MAOIs be used in depressed hypertensives?
|
Lower blood pressure (and can cause orthostatic hypotension)
|
|
|
Which class of anti-depressants has the highest frequency of hepatotoxicity?
|
MAOIs
|
|
|
What class of drugs are contraindicated with MAOIs? What might happen if they are combined?
|
sympathomimetics (epi, phentermine, etc.) & tyramine (cheese, fermented foods, red wine). Hypertensive crisis may occur
|
|
|
How does lithium work?
|
unknown
|
|
|
Is lithium more effective for mania or depression?
|
mania
|
|
|
How is lithium metabolized?
|
It's not. It's only excreted by the kidneys. (Remember, it's just an ion!)
|
|
|
What are the neurologic side effects of lithium?
|
fatigue, weakness, confusion, slurred speech, tremor, ataxia, seizures
|
|
|
What is a prominent endocrine side-effect of lithium?
|
can cause hypothyroidism
|
|
|
What are the GI side-effects of lithium?
|
nausea, vomiting, diarrhea
|
|
|
Name 3 antiepileptics commonly used for the treatment of bipolar disorder.
|
valproic acid, lamotrigine, carbamazepine
|
|
|
Aside from lithium and antiepileptics, what class of drugs can be used to treat mania?
|
anti-psychotics
|
|
|
How is lithium metabolized?
|
It's not. It's only excreted by the kidneys. (Remember, it's just an ion!)
|
|
|
What is one advantage of antiepileptics over lithium for the treatment of bipolar disorder?
|
Lithium has an even lower therapeutic index, and blood levels must be measured frequently so that the dose can be properly titrated.
|
|
|
How does lithium cause polyuria and polydipsia?
|
Inhibits the action of ADH
|
|
|
Does lithium cause weight loss or weight gain?
|
weight gain
|
|
|
Name 3 antiepileptics commonly used for the treatment of bipolar disorder.
|
valproic acid, lamotrigine, carbamazepine
|
|
|
Why can't you give bupropion to someone with an eating disorder?
|
Bupropion lowers the seizure threshold, and when combined with an electrolyte imbalance, has a high risk of seizures.
|
|
|
Can CNS depressants ever cause excitation?
|
Yes, at the dose between their calming, relaxing effects and their sleep-promoting effects.
|
|
|
What do you call CNS depressants that cause calm and relaxation?
|
anxiolytics (used to be called tranquilizers or sedatives)
|
|
|
What do you call CNS depressants that promote sleep?
|
hypnotics
|
|
|
What do you call CNS depressants used to cause loss of consciousness?
|
anesthetics!
|
|
|
What is the mechanism of the paradoxical excitation caused by CNS depressants?
|
CNS depressants generally promote neuronal inhibition. At certain levels, they paradoxically inhibit inhibitors, thus causing excitation.
|
|
|
What chemical quality determines the pharmacokinetics of barbiturates?
|
how lipophilic they are (more lipophilic = rapid, short action)
|
|
|
Which barbiturate can be used prophylactically to treat seizures?
|
phenobarbitol (it's long-acting)
|
|
|
What are the ultrashort-acting barbiturates (2)?
|
thiopental and thiamylal
|
|
|
Which barbiturate can be used to carry out the death penalty?
|
thiopental
|
|
|
What are the short- to intermediate-acting barbiturates?
|
secobarbital, pentobarbital
|
|
|
Are barbiturates CYP450 inducers or inhibitors?
|
inducers
|
|
|
What receptors to barbiturates bind to?
|
GABA-A. They facilitate the binding of GABA, thus increasing the length of channel opening. At high doses, they can open the channel themselves. At ultrahigh doses, they can affect other ion channels.
|
|
|
Do benzodiazepines or barbiturates have a lower therapeutic index?
|
barbiturates
|
|
|
Name the symptoms that occur when one withdraws from barbiturates.
|
restlessness, anxiety, insomnia, weakness, orthostatic hypotension. Rarely, life-threatening convulsions
|
|
|
Why might one use barbiturates in head trauma?
|
Because they are CNS depressants, barbiturates reduce overall brain activity (by inducing a coma, in this case). By decreasing the brain's need for oxygen, they help prevent neuronal damage and death during the episode of hypoxia.
|
|
|
In what rare genetic condition are barbiturates contraindicated?
|
Contraindicated in acute intermittent porphyria (increase porphyrin levels)
|
|
|
What drug is involved in 50% of homicides?
|
alcohol
|
|
|
What drug is involved in up to 70% of suicides?
|
alcohol
|
|
|
What percentage of Americans abuse alcohol? Are dependent?
|
Abuse=4%, dependence=5% for a total of 9%
|
|
|
Can alcohol pass into the breastmilk?
|
yes
|
|
|
Describe the major pathway of ethanol metabolism.
|
ethanol --> acetaldehyde via alcohol dehydrogenase; acetaldehyde --> acetate via aldehyde dehydrogenase
|
|
|
What is the minor pathway of ethanol metabolism?
|
CYP450, only when alcohol dehydrogenase is saturated
|
|
|
How are neurons affected by ethanol?
|
stimulates GABA receptors, inhibits NMDA receptors (glutamate), and disrupts neuronal membranes. THERE IS NO ETHANOL RECEPTOR!
|
|
|
Name the 3 types of glutamate receptors.
|
AMPA, NMDA, kainate
|
|
|
You feel warm after ingesting ethanol. Are you more prone to hyperthermia or hypothermia?
|
Hypothermia. You are vasodilated, meaning you lose heat and are at risk for hypothermia.
|
|
|
What are 2 ways in which alcoholism may cause malnutrition?
|
1) Drinking lots of "empty" calories deficient in important nutrients instead of eating 2) Alcohol inhibits intestinal enzymes, impairing nutrient absorption
|
|
|
How does alcohol cause diuresis?
|
inhibition of ADH
|
|
|
What are the symptoms of acute alcohol withdrawal?
|
a hangover - early awakening, anxiety, tremor, headache, etc.
|
|
|
What are the symptoms of withdrawal in someone with alcohol dependence?
|
tremors, agitation, anxiety, hyperexcitability, autonomic hyperactivity, hyperthermia, toxic psychosis (w/ hallucinations), seizures, death
|
|
|
What is delirium tremens?
|
The severe form of withdrawal in someone with alcohol dependence. TRIAD: seizures, autonomic instability, hallucinations. 20% mortality rate.
|
|
|
What demographic is most likely to die from acute alcohol intoxication?
|
college students
|
|
|
In the US, how many deaths per year are related to alcohol?
|
300,000-400,000
|
|
|
What are the symptoms of Wernicke-Korsakoff syndrome?
|
confusion, oculomotor abnormalities, ataxia, polyneuropathy, learning & memory problems, confabulation, hallucinations
|
|
|
What vitamin deficiency is thought to cause Wernicke-Korsakoff syndrome in alcoholics?
|
thiamine (vitamin B1)
|
|
|
What are the hematologic effects of chronic alcohol use?
|
anemia (folic acid deficiency, iron deficiency, bleeds); bone marrow suppression
|
|
|
What percentage of alcoholics develop cirrhosis?
|
15%
|
|
|
What 4 criteria are required for the diagnosis of fetal alcohol syndrome?
|
1) pre- or postnatal growth deficiency (<10%ile)
2) 3 FAS facial features (smooth philtrum, thin upper lip, small palpebral fissures) 3) CNS damage (significant structural, neurological, or functional impairment) 4) Known exposure to alcohol during in utero |
|
|
What is the best treatment for alcohol withdrawal?
|
benzodiazepines
|
|
|
Should alcoholics drink in healthy moderation after recovery?
|
no, complete abstinence is necessary to prevent relapse
|
|
|
What antibiotic can cause a disulfiram-like reaction?
|
metronidazole
|
|
|
Describe the metabolism of methanol.
|
methanol --> [alcohol dehydrogenase] --> formaldehyde --> [aldehyde dehydrogenase] --> formic acid
|
|
|
What are the symptoms of methanol poisoning?
|
severe acidosis, optic nerve damage --> blindness, and/or death
|
|
|
What is the treatment for acidosis caused by methanol poisoning?
|
sodium bicarbonate
|
|
|
How does the administration of ethanol help treat methanol poisoning?
|
Because the two are metabolized by the same enzymes, ethanol competes with methanol for metabolism. This slows the metabolism of methanol, resulting in fewer toxic effects.
|
|
|
Where are the dopaminergic neurons involved in addiction located?
|
ventral tegmental area
|
|
|
Where do the dopaminergic neurons involved in addiction project?
|
to the nucleus accumbens
|
|
|
What is the function of the nucleus accumbens?
|
"reward center"
|
|
|
How many people die of tobacco-related causes annually in the US?
|
>425,000 (there is actually a billboard keeping the yearly tally on Santa Monica & Veteran)
|
|
|
What is the leading preventable cause of death in the US?
|
tobacco use
|
|
|
In a given year, what percentage of smokers can quit on their own?
|
2-7% (Dr. Pechnick: 2-3%, Dr. Fong: 7%)
|
|
|
What receptor does nicotine bind? Where are these receptors located (3 places)?
|
nicotinic ACh receptors at the neuromuscular junction, autonomic ganglia, and CNS. The beta2 subunit appears to be particularly important in addiction.
|
|
|
What organ metabolizes most of the nicotine in cigarette smoke?
|
the lungs
|
|
|
Does nicotine cross into the breastmilk?
|
yes
|
|
|
What happens if you somehow overdose on nicotine?
|
seizures
|
|
|
What are the methylxanthines?
|
caffeine (coffee), theophylline (tea), and theobromine (cocoa)
|
|
|
What percentage of the US population regularly consumes caffeine?
|
80-90%
|
|
|
What liver enzyme metabolizes caffeine?
|
CYP1A2
|
|
|
Does nicotine enhance or decrease the effects of caffeine?
|
Enhance, by slowing metabolism
|
|
|
Is caffeine an agonist or an antagonist? At which receptor?
|
Antagonist of the adenosine receptor. Since adenosine is an inhibitory neurotransmitter, you are inhibiting inhibition, leading to CNS stimulation.
|
|
|
What are the symptoms of caffeine withdrawal?
|
headache, fatigue, impaired psychomotor performance, depression
|
|
|
Why might you see caffeine used in a NICU?
|
apnea of prematurity
|
|
|
What psychiatric disorders might be exacerbated by caffeine use?
|
anxiety, insomnia, panic disorder
|
|
|
Does caffeine induce or inhibit the metabolism of clozapine, olanzapine, and fluvoxamine?
|
inhibits their metabolism, increasing their effectiveness
|
|
|
Name 3 amphetamines.
|
amphetamine, dextroamphetamine, methamphetamine
|
|
|
Do amphetamines cross the placenta and into breastmilk?
|
yes
|
|
|
What are the 3 pharmacologic actions of amphetamines?
|
1) Increases dopamine and norepi release. DA causes the high, norepi causes the side-effects
2) inhibits catecholamine reuptake 3) inhibits MAO Summary: all 3 actions increase dopamine and norepi |
|
|
What is one sign that someone may have taken a high dose rather than a low dose of amphetamines?
|
stereotypy
|
|
|
According to Dr. Pechnick, what are the 3 ways most methamphetamine addicts stop using?
|
1) become so tolerant that use is pointless 2) get arrested 3) run out of money (and #4 i'm adding--death)
|
|
|
What are the symptoms of amphetamine withdrawal?
|
intense hunger, sleeping, fatigue, lassitude, depression (can be to the point of suicide)
|
|
|
What is one non-psychiatric indication for amphetamines and methylphenidate?
|
fatigue secondary to cancer
|
|
|
What is one drug you really, really, really don't want to take if you have a psychotic illness?
|
amphetamines; they exacerbate psychosis and can even cause paranoid psychosis in otherwise healthy users
|
|
|
What are 3 ways you can take amphetamines?
|
injection, orally, snorting
|
|
|
What are the adverse effects of amphetamines?
|
irritability, tremor, dizziness, insomnia, depression, hyperthermia, paranoid psychosis, seizures, coma, death
|
|
|
How might you die of amphetamine overdose?
|
cardiac arrhythmia, stroke (due to hypertension), seizures
|
|
|
How does methylphenidate work?
|
it inhibits the reuptake of dopamine
|
|
|
What 2 psychiatric conditions are treated with methylphenidate?
|
ADHD and narcolepsy
|
|
|
How is pemocline different from methylphenidate?
|
Pemoline is longer-acting, otherwise very similar
|
|
|
Do people abuse modafinil?
|
no
|
|
|
What is one benefit of using modafinil in people who need to stay awake, such as narcolepsy, sleep apnea, and work shift disorder?
|
you can still fall asleep when you want to
|
|
|
According to Dr. Pechnick, what is THE most addictive drug?
|
cocaine
|
|
|
Why does crack cocaine have a more rapid onset than other forms?
|
Because you bypass hepatic first-pass metabolism. Onset in only 8-10 seconds
|
|
|
What is the only legitimate use of cocaine?
|
as a local anaesthetic, especially in ophthalmology
|
|
|
What might be added to cocaine to increase its potency?
|
lidocaine, which can cause cardiac arrest
|
|
|
What physiological mechanism causes most of the dangerous effects of cocaine use?
|
Vasoconstriction --> MI, stroke, bowel ischemia, placental ischemia. Other dangerous sequelae are cardiac arrhythmias (due to norepi also) and psychosis (dopamine).
|
|
|
What is the difference between substance abuse and substance dependence?
|
Substance abuse: maladaptive use that causes harm. Substance dependence: physiological dependence, including tolerance and withdrawal, that causes harm. You can have abuse without dependence (e.g., college student binge drinking once a month).
|
|
|
Are men or women more vulnerable to addictive disorders?
|
men
|
|
|
Excluding caffeine and nicotine, what percentage of the adult population meets the criteria for substance abuse or dependence?
|
13%
|
|
|
What percentage of individuals with addiction seek treatment?
|
only 10%
|
|
|
What are the mesolimbic and mesocortical pathways?
|
They connect the ventral tegmental area (of the midbrain, hence meso) to the nucleus accumbens (mesolimbic) and prefrontal cortex (mesocortical)
|
|
|
What areas of the cortex are most involved in addiction?
|
orbitofrontal cortex
|
|
|
What percentage of the population abstains from alcohol (>1 yr without a drink)?
|
40%
|
|
|
What is the national rate of smoking?
|
20%
|
|
|
What percentage of people who use heroin become dependent on it?
|
23%
|
|
|
Is there a marijuana withdrawal syndrome?
|
YES. Like nicotine withdrawal, it consists of craving, anxiety, irritability, and insomnia.
|
|
|
Marijuana use may precipitate or unmask what serious psychiatric disorder?
|
psychosis
|
|
|
What are the physical signs of cocaine intoxication?
|
dilated pupils, elevated heart rate and blood pressure, emotionality, hyperactivity, euphoria
|
|
|
What has a longer half-life: cocaine or methamphetamine?
|
Methamphetamine (24-30 hrs.) has a longer half-life than cocaine (20-30 mins.)
|
|
|
What percentage of the population has compulsive (pathological) gambling?
|
1-2%
|
|
|
What are some sequelae of long-term methamphetamine use?
|
weight loss, severe dental problems, mood disturbance, anxiety, confusion, insomnia, violence
|
|
|
If someone has failed treatment for substance abuse multiple times, is there still hope?
|
YES! Try again!
|
|
|
How does disulfiram work, both medically and pharmacologically?
|
Medically: creates adverse response to drinking by making you feel sick
Pharmacologically: blocks acetaldehyde dehydrogenase, leading to a build-up of acetaldehyde |
|
|
What happens if you drink alcohol while taking disulfiram?
|
Build-up of acetaldehyde --> flushing, tachycardia, nausea, vomiting, anxiety, dizziness
|
|
|
Why is it difficult for patients to comply with acamprosate therapy?
|
must be taken 6 times a day
|
|
|
What is the pharmacologic action of acamprosate?
|
NMDA and glutamate blockade
|
|
|
What is acamprosate used for?
|
the treatment of alcoholism
|
|
|
Can you drink safely while taking acamprosate?
|
yes, and you won't have any bad side-effects (unlike disulfiram). Instead, acamprosate works by reducing the desire to drink.
|
|
|
What is the pharmacologic action of naltrexone, which is used to treat alcohol dependence?
|
opioid antagonist
|
|
|
What is the disadvantage of injectable naltrexone compared to oral?
|
Because injectable naltrexone is given monthly, and thus lasts for a whole month, you can't withdraw it if the patient develops serious side-effects such as hepatitis or dysphoria/suicidality.
|
|
|
What is the mechanism of action of methadone?
|
long-acting opioid agonist
|
|
|
If a patient receiving methadone is admitted to the hospital, can you continue the methadone regimen?
|
No, you must confirm that the patient is actually registered with a methadone clinic.
|
|
|
What class of drugs should not be mixed with methadone?
|
benzodiazepines
|
|
|
What is one advantage of buprenorphine over methadone?
|
Buprenorphine can be given as a regular prescription, rather than requiring the patient to go to clinic every day. However, to prescribe buprenorphine, the physician must complete a training course.
|
|
|
The natural quit rate for cigarette smoking is only 2-7% over one year. If you briefly counsel the patient about quitting at an office visit, will it make a difference?
|
YES, it will double the likelihood that they will successfully quit (4-14%).
|
|
|
How do you chew nicotine gum correctly?
|
Chew normally until you feel a "peppery tingle", then hold the gum between the cheek and gums to allow the nicotine to be absorbed in the mouth rather than the GI tract.
|
|
|
What happens if you chew nicotine gum like regular gum (continuous chewing)?
|
The nicotine will be absorbed either not at all or in the upper GI tract, which can cause nausea and diarrhea.
|
|
|
Besides depression, what is an indication for bupropion?
|
smoking cessation (20% success)
|
|
|
What are 2 rare but important side-effects of bupropion?
|
Increased risk of seizures and worsening of depression/suicidality.
|
|
|
How does varenicline work?
|
It is a partial nicotine agonist (40% success)
|
|
|
What is the pharmacologic treatment for stimulant (cocaine/amphetamine) addiction?
|
There is none. :( However, you can use psychosocial treatment.
|
|
|
What is the pharmacologic treatment for marijuana addiction?
|
There is none. :( However, you can use psychosocial treatment.
|
|
|
What class of drugs used to be called "minor tranquilizers"?
|
benzodiazepines
|
|
|
What class of drugs used to be called "major tranquilizers"?
|
anti-psychotics
|
|
|
Which benzodiazepine has good intramuscular absorption and should be used in emergencies (e.g., status epilepticus)?
|
lorazepam
|
|
|
Do benzodiazepines cross into the breastmilk?
|
yes
|
|
|
Describe the metabolism of diazepam.
|
Diazepam --> nordiazepam --> oxazepam --> inactive. Has a long half-life because the metabolites are active.
|
|
|
What is the approximate half-life of diazepam?
|
100 hours
|
|
|
Why should you be cautious when giving long-acting benzodiazepines to the elderly?
|
Because they have such long half-lives, they can accumulate easily. Also a concern with hepatic dysfunction.
|
|
|
Name three long-acting benzodiazepines.
|
diazepam, chlordiazepoxide, clonazepam
|
|
|
Which three benzodiazepines have intermediate half-lives?
|
lorazepam, oxazepam, temazepam
|
|
|
Which two benzodiazepines have short half-lives?
|
triazolam, midazolam
|
|
|
Why do triazolam and midazolam have such short half-lives?
|
They are converted immediately to inactive metabolites.
|
|
|
Which benzodiazepine is most commonly used for the induction of anesthesia?
|
midazolam
|
|
|
Why are benzodiazepines now used instead of barbiturates?
|
Greater therapeutic index. Why? Because benzodiazepines enhance the activity of GABA only, whereas barbiturates also open the channel themselves and affect other receptors.
|
|
|
How do benzodiazepines work?
|
They bind to the GABA-A receptor and potentiate the effects of GABA. Unlike barbiturates, they cannot open the channel themselves or affect other receptors.
|
|
|
Aside from a greater therapeutic index, what is another advantage of benzodiazepines over barbiturates?
|
Benzodiazepines do not induce CYP450
|
|
|
Can you overdose on benzodiazepines?
|
Only rarely, unless you combine them with other CNS depressants such as alcohol. This is because we now have ventilators that can keep people on depressants alive until the drug is out of their system. (And we have flumazinil).
|
|
|
Put these effects of benzodiazepines in order from first to last as you increase the dose: promote sleep, reduce anxiety, anticonvulsant, produce sedation
|
LOW DOSE --> reduce anxiety, produce sedation, promote sleep, anticonvulsant --> HIGH DOSE
|
|
|
What is the major advantage of using benzodiazepines instead of SSRIs for the treatment of anxiety?
|
Benzodiazepines work immediately (within an hour). SSRIs take weeks. One strategy is to start a patient on both, and then taper the benzo after a few weeks.
|
|
|
What is the antidote to benzodiazepine + alcohol overdose?
|
flumazinil
|
|
|
Does benzodiazepine tolerance develop to its anxiolytic effects, its sedative effects, or both?
|
Tolerance develops only to the sedative effects.
|
|
|
Do you have to worry about benzodiazepine dependence in every patient?
|
Generally not. Only 1-2% of benzo users develop physical dependence. These tend to be people with pre-existing addictions, especially to alcohol.
|
|
|
What happens when you have benzodiazepine withdrawal?
|
anxiety, jitteriness, insomnia, loss of appetite, seizures
|
|
|
Are benzodiazepines ever used alone for anesthesia?
|
Yes, when used alone they can safely induce very short losses of consciousness or conscious sedation.
|
|
|
What is the most common cause of reversible confusion in the elderly?
|
benzodiazepine use
|
|
|
What is the major side-effect of benzodiazepines?
|
excessive sedation (e.g., when used for insomnia, they can cause a "hangover")
|
|
|
Benzodiazepines can cause anterograde amnesia. Why might this be beneficial?
|
When used as conscious sedation, benzodiazepines are useful in that the patient often does not remember the procedure.
|
|
|
What is flumazinil?
|
a competitive benzodiazepine antagonist used in cases of overdose
|
|
|
Are benzodiazepines ever used alone for anesthesia?
|
Yes, when used alone they can safely induce very short losses of consciousness or conscious sedation.
|
|
|
What is the most common cause of reversible confusion in the elderly?
|
benzodiazepine use
|
|
|
What is the major side-effect of benzodiazepines?
|
excessive sedation (e.g., when used for insomnia, they can cause a "hangover")
|
|
|
Benzodiazepines can cause anterograde amnesia. Why might this be beneficial?
|
When used as conscious sedation, benzodiazepines are useful in that the patient often does not remember the procedure.
|
|
|
What is flumazinil?
|
a competitive benzodiazepine antagonist used in cases of overdose
|
|
|
Which is better for panic attacks: lorazepam or buspirone?
|
Lorazepam. Buspirone does not work for panic attacks.
|
|
|
Which can be combined with alcohol: buspirone or benzodiazepines?
|
buspirone can be safely combined with alcohol
|
|
|
What is the major advantage of buspirone over benzodiazepines?
|
Buspirone produces little or no sedation and only slight impairment of cognition. (Additionally, it can be safely combined with alcohol, and thus is preferable in alcoholics.)
|
|
|
Is buspirone better at treating the psychological or physical symptoms of anxiety?
|
Buspirone is better for treating the psychological symptoms.
|
|
|
How do you dose MAOIs when used for panic attacks?
|
Must be taken chronically; cannot just take at the time of the attack (unlike benzodiazepines).
|
|
|
What anti-histamine is used in the treatment of anxiety?
|
hydroxyzine
|
|
|
What class of anxiolytics is best for performance anxiety and stage fright?
|
B-blockers like propanolol and atenolol
|
|
|
What is the major indication for temazepam, and how long does it take to work?
|
insomnia, takes up to 1 hour to work
|
|
|
What is the advantage of triazolam over temazepam for insomnia? What is the disadvantage?
|
Advantage: triazolam acts faster than temazepam and has less "hangover." Disadvantage: triazolam has such a short half-life that patients may still suffer late insomnia (i.e., waking too early)
|
|
|
What is the mechanism of action of the hypnotics zolpidem, zaleplon, and eszopiclone?
|
While structurally unrelated to benzodiazepines, they bind a subtype of the same 'receptor' on the GABA-A receptor and enhance the actions of GABA
|
|
|
Can you mix zolpidem with alcohol?
|
No!
|
|
|
Name the three non-benzodiazepine benzodiazepine receptor agonists.
|
zolpidem, zaleplon, eszopiclone ("zzz drugs")
|
|
|
What is ramelteon?
|
a melatonin receptor agonist
|
|
|
Which three anti-histamines have been used as hypnotics?
|
doxylamine, diphenhydramine, hydroxyzine
|
|
|
What are the 2 main treatment options for opioid dependence?
|
methadone and buprenorphine
|
|
|
When were antipsychotics first introduced into Western medicine?
|
the mid-1950's
|
|
|
Of the typical anti-psychotics, which is most frequently used today?
|
haloperidol, both acutely and chronically
|
|
|
What are the two chemical classes of typical anti-psychotics?
|
phenothiazines and butyrophenones
|
|
|
What was the first (Western) anti-psychotic?
|
chlorpromazine
|
|
|
Which anti-psychotic was first available in depot (long-acting injectable) form?
|
fluphenazine
|
|
|
Name two phenothiazines.
|
chlorpromazine and fluphenazine
|
|
|
Name the butyrophenone that is used in emergency situations to sedate highly agitated patients?
|
haloperidol
|
|
|
Name the FOUR pharmacologic activities of typical anti-psychotics.
|
1) block dopamine receptors 2) block muscarinic cholinergic receptors 3) block a1 adrenergic receptors 4) block H1 histamine receptors
|
|
|
Why do we think that dopamine blockade is the efficacious pharmacologic activity of typical anti-psychotics?
|
Clinical efficacy increases as D2 affinity (antagonism) increases.
|
|
|
Name the FOUR dopamine pathways affected by typical anti-psychotics.
|
mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular
|
|
|
What side effects of anti-psychotics result from the dopamine blockade of the tuberoinfundibular pathway?
|
Dopamine blockade leads to an increase in prolactin release, which can cause gynecomastia, galactorrhea, and amenorrhea.
|
|
|
What side effect of anti-psychotics results from the dopamine blockade of the nigrostriatal pathway?
|
Extrapyramidal side effects (EPS)
|
|
|
What is the 2 side effects of anti-psychotics attributable to the histamine blockade?
|
sedation, weight gain
|
|
|
Which dopaminergic pathway is thought to lead to positive symptoms of psychosis? Negative symptoms?
|
Overactivity of the mesolimbic pathway is thought to lead to positive symptoms. Underactivity of the mesocortical pathway is thought to lead to negative symptoms.
|
|
|
Why are anti-psychotics less effective at treating negative symptoms?
|
Negative symptoms likely result from underactivity of the mesocortical dopamine pathway, so dopamine blockers are of little utility and may even make some negative symptoms worse.
|
|
|
What is the mesolimbic pathway?
|
Dopamine projections from the midbrain (ventral tegmental area) to the limbic system (hippocampus, amygdala, nucleus accumbens, etc.)
|
|
|
What is the mesocortical pathway?
|
Dopamine projections from the midbrain (ventral tegmental area) to the prefrontal cortex.
|
|
|
What is neuroleptic syndrome?
|
A side effect of anti-psychotics (especially typicals) that causes psychomotor slowing, sedation, drowsiness, restlessness, and ataraxy (emotional indifference).
|
|
|
Does tolerance develop to the anti-psychotic effects of dopamine blockers? What about to neuroleptic syndrome?
|
Tolerance does not develop to the anti-psychotic effects but usually develops to the neuroleptic syndrome after a few weeks.
|
|
|
How long does it take for typical anti-psychotics to have an anti-psychotic effect?
|
Days to weeks. However, sedation can occur immediately, which is why they are given as sedatives in the ER. Neuroleptic malignant syndrome can happen immediately as well.
|
|
|
How do anti-psychotics decrease the seizure threshold?
|
By increasing the synchronization of neuron firing.
|
|
|
Which two typical anti-psychotics are used as anti-emetics?
|
prochlorperazine, promethazine
|
|
|
How do anti-psychotics cause weight gain?
|
They increase appetite and decrease satiety. Atypicals may also alter metabolism, leading to weight gain (as part of the metabolic syndrome).
|
|
|
Which causes the most weight gain: typical anti-psychotics, atypical anti-psychotics, or anti-depressants.
|
Atypical anti-psychotics, followed by typical anti-psychotics. Anti-depressants cause the least weight gain, and some cause none (e.g., bupropion)
|
|
|
Blockade of what receptor causes the following side effects of typical anti-psychotics: orthostatic hypotension, blurred vision, dry mouth, constipation, urinary retention.
|
anti-muscarinic effect
|
|
|
Do anti-psychotics have sexual side effects?
|
Yes, they can cause inability to ejaculate and/or decreased libido.
|
|
|
What is the pharmacologic treatment of choice for psychotic depression?
|
antidepressant + anti-psychotic
|
|
|
What is the non-pharmacologic treatment of choice for psychotic depression?
|
electroconvulsive therapy
|
|
|
What is the treatment of choice for schizoaffective disorder, depressive type?
|
anti-psychotic + anti-depressant
|
|
|
What is the treatment of choice for schizoaffective disorder, bipolar type?
|
anti-psychotic + mood stabilizer
|
|
|
What is the treatment of choice for psychotic bipolar disorder?
|
mood stabilizer + anti-psychotic
|
|
|
Are anti-psychotics effective for prophylaxis of mania?
|
No, but they can be useful in acute mania and in preventing the psychotic features of mania (and depression) in patients with bipolar. Note: some atypicals, such as quetiapine, are thought to have mood stabilizing effects, but these are minor.
|
|
|
What is the current first-line therapy for schizophrenia?
|
atypical anti-psychotic, except don't start with clozapine (agranulocytosis!)
|
|
|
What is one problem with using anti-psychotics for the treatment of agitation in people with dementia?
|
Anti-psychotic use in the elderly with dementia actually increases death rates. You have to balance quality vs. quantity of life.
|
|
|
Are anti-psychotic drugs useful in the treatment of drug-induced psychosis (from, say, corticosteroids or stimulants)?
|
Yes.
|
|
|
How long should someone with schizophrenia or schizoaffective disorder take an anti-psychotic?
|
For life.
|
|
|
How long should someone with psychotic depression take an anti-psychotic?
|
For at least 4 months after psychotic symptoms subside; after that, most patients are able to taper off the anti-psychotic but must remain on the anti-depressant, sometimes for life.
|
|
|
What is the pharmacologic treatment of choice for Tourette's syndrome?
|
haloperidol
|
|
|
Which typical anti-psychotic is used as an anti-pruritic?
|
trimeprazine
|
|
|
What can be used to treat intractable hiccups? (Hint: think of intractable hiccups as similar to Tourette's)
|
anti-psychotics
|
|
|
There are 3 main categories of extrapyramidal side effects of anti-psychotics. Name 2 that are early-onset and 1 that is late-onset.
|
Early-onset: Parkinsonian syndrome and acute dystonic reaction. Late-onset: tardive dyskinesia.
|
|
|
What three drugs can be used to treat the early-onset extrapyramidal side effects of anti-psychotics?
|
benztropine, trihexyphenidyl (muscarinic blockers) and diphenhydramine (histamine and muscarinic blocker)
|
|
|
What is an acute dystonic reaction?
|
Acute simultaneous contraction of agonist and antagonist muscles, resulting in frightening and painful symptoms such as torticollis, oculogyric crisis, or grimace.
|
|
|
How can tardive dyskinesia be life-threatening?
|
Patients can have trouble eating and choke or aspirate on food.
|
|
|
Is tardive dyskinesia permanent?
|
Often it is. If caught and treated early, it can sometimes be reversed.
|
|
|
How do you treat tardive dyskinesia?
|
Switch anti-psychotics or slowly taper the current anti-psychotic.
|
|
|
What are the risk factors for tardive dyskinesia?
|
Being on typical anti-psychotics for a long time, at high doses, and being female.
|
|
|
What is the mortality rate of neuroleptic malignant syndrome?
|
38% :(
|
|
|
What are the symptoms of neuroleptic malignant syndrome?
|
Hyperthermia, Akinesia, Rigidity, Mutism (HARM); sometimes mistaken for catatonia, but take the patient's temperature - if elevated, it's likely NMS!
|
|
|
What are the pharmacologic treatments for neuroleptic malignant syndrome?
|
dopamine agonists like bromocriptine, muscle relaxants like dantroline
|
|
|
Why are atypical anti-psychotics currently front-line therapy for psychosis, rather than the typicals?
|
They are generally better tolerated because they a) cause less sedation and b) cause less extrapyramidal side effects.
|
|
|
What is the most efficacious anti-psychotic?
|
clozapine
|
|
|
Are atypical or typical anti-psychotics more efficacious?
|
Similar efficacy, except that clozapine (an atypical) is slightly better
|
|
|
Name the first 6 atypical anti-psychotics.
|
Mnemonic (from FirstAid): it's ATYPICAL for OLd CLOSets to QUIETly RISPER from A to Z - olanzapine, clozapine, quetiapine, risperidone, aripiprazole, ziprasidone
|
|
|
Which atypical anti-psychotic is notorious for causing the most weight gain?
|
Olanzapine. Aripiprazole and ziprasidone (the newest 2) cause the least weight gain.
|
|
|
Which atypical anti-psychotic is notorious for being the most sedating?
|
quetiapine (trade name = Seroquel, which can help you remember). Some doctors use quetiapine for insomnia, even in non-psychotic patients, which is controversial.
|
|
|
What 2 receptors do atypical anti-psychotics bind that best explain their efficacy?
|
D1/D2 and 5-HT2A antagonists
|
|
|
Which atypical anti-psychotic has a different mechanism from the others? What is the mechanism?
|
Aripiprazole is a partial agonist at D2, rather than an antagonist. One way to remember this is that aripiprazole (Abilify) is FDA-approved for augmentation in depression, and depressed people have LOW dopamine--hence partial agonism.
|
|
|
Why might antagonizing 5-HT2A receptors cause anti-psychotic activity?
|
The 5-HT2A system modulates the dopamine system, and so antagonism here may also modulate dopaminergic activity.
|
|
|
What is the major drawback of atypical anti-psychotics compared to typicals?
|
Often cause metabolic syndrome
|
|
|
Are typical or atypical anti-psychotics more likely to cause problems with prolactin?
|
typicals
|
|
|
Are typical or atypical anti-psychotics more likely to cause type II diabetes?
|
atypicals
|
|
|
Overall, are typical or atypical anti-psychotics safer?
|
Hard to say. Typicals cause more extrapyramidal side effects, but atypicals cause more metabolic syndrome and its sequelae (type II diabetes, dyslipidemia, etc.)
|
|
|
What is the most dangerous side effect of clozapine and is the reason it is not used as first-line treatment for psychosis?
|
agranulocytosis
|
|
|
Do atypical anti-psychotics bind muscarinic and a1 receptors, like typicals do?
|
Yes, but generally to a lesser extent.
|
|
|
What drug is most commonly used to treat the agitation and psychosis of delirium?
|
haloperidol
|
|
|
Does delirium require high or low doses of anti-psychotics, compared to primary psychotic disorders?
|
delirium requires LOW doses of anti-psychotics
|
|
|
Should you use benzodiazepines for a typical case of delirium?
|
NO. They have no benefit and might actually worsen symptoms.
|
|
|
What are some situations in which you might use benzodiazepines for delirium?
|
Delirium due to alcohol or benzo withdrawal; to raise seizure threshold; severe akathisia
|
|
|
How might endogenous or exogenous corticosteroids impair memory?
|
By damaging the hippocampus.
|
|
|
What is the mechanism of long-term potentiation?
|
After glutamate signaling at the NMDA receptor, Mg2+ is displaced, leading to Ca2+ influx. The final result of this Ca2+ influx is that more AMPA receptors are inserted into the synaptic membrane. After LTP, the same amount of glutamate has more effect because there are more AMPA receptors.
|
|
|
What is the mechanism of long-term depression (the neural phenomenon, not chronic MDD)?
|
Opposite of LTP. Results in internalization of AMPA receptors. After LTD, the same amount of glutamate has less effect because there are fewer AMPA receptors.
|
|
|
What are ampakines?
|
A developing class of drugs that bind to AMPA receptors and enhance LTP. They are being studied as cognitive enhancers.
|
|
|
What is the pharmacologic mechanism of action of memantine?
|
uncompetitive partial antagonist at NMDA receptors
|
|
|
How might memantine work for Alzheimer's disease by blocking NMDA receptors?
|
As a partial antagonist at EXTRAsynaptic NMDA receptors, memantine is thought to protect against excitotoxic neurodegeneration and to "balance" activity at glutamate synapses.
|
|
|
Are the effects of activating intra- and extrasynaptic NMDA receptors additive or opposing?
|
usually opposing
|
|
|
What is the pharamcologic action of donezepil?
|
acetocholinesterase inhibitor
|
|
|
How does donezepil work for Alzheimer's disease?
|
Donezepil is an AChE inhibitor. It works by increasing ACh levels at cholinergic synapses, which are known to degenerate in AD.
|
|
|
How does nicotine enhance cognition?
|
Much of the brain receives cholinergic projections from the basal nucleus of Meynert. These projections promote memory and attention. Nicotine agonizes nicotinic ACh receptors. (Note: this might explain why about 80% of people with schizophrenia smoke, usually heavily - it helps with cognitive deficits!)
|
|
|
What is the effect of estrogen on the hippocampus?
|
Enhances LTP. This might be why many people complain of memory problems around menopause.
|
