psychopharmacology (other psychoactive drugs)

3 main types of psychoactive drugs

sedatives: benzodiazepines

hypnotics: barbiturates

anxiolytics: azapirones

examples benzodiazepines (list the main 3)

diazepam (Valium)

alprazolam (Xanax)

lorazepam (Ativan)

how do benzodiazepines work

increase GABA activity by acting as agonists at GABA receptors

what are benzodiazepines used to treat

anxiety, insomnia, seizures, and alcohol withdrawal

benzodiazepines vs SSRI/SNRI for anxiety

benzo = fast acting, immediate short-term relief from acute anxiety BUT they don’t help cognitive symptoms of anxiety and long-term use can lead to tolerance and dependence

SSRI/SNRI = better for chronic anxiety and cognitive symptoms BUT less impact on physiological symptoms and more unpleasant side effects

side effects of benzodiazepines

drowsiness and sedation

weakness and unsteadiness

impaired memory and concentration

anticholinergic effects

sexual dysfunction

disorientation and confusion (in older adults)

paradoxical effects (especially in children and older adults) [e.g., excitability and anxiety]

tolerance, dependence, and withdrawal (which can cause rebound anxiety and depression, anorexia, delirium, and seizures)

how to taper benzodiazpines

depends on dose, half-life, and how long they’ve been taking it

a longer taper is required for benzos with a shorter half-life (e.g., alprazolam, lorazepam)

what happens if you combine benzodiazepines with alcohol or blood pressure meds

combining benzos with alcohol can cause synergistic depressant effects which can be lethal

combining benzos with certain meds for high blood pressure (e.g., central agonists, alpha blockers) can cause a dangerous drop in blood pressure

examples of barbiturates (list the main 3)

thiopental (Pentothal)

amobarbital (Amytal)

secobarbital (Seconal)

how do barbiturates work

increase GABA activity

what are barbiturates used to treat

anxiety, insomnia, seizures

side effects of barbiturates

drowsiness, dizziness, confusion, ataxia, cognitive impairment, paradoxical excitement

chronic use can lead to tolerance, dependence, and withdrawal

dangers of barbiturates

chronic use can lead to tolerance, dependence, and withdrawal

sudden withdrawal can cause seizures, delirium, and death

can be lethal if combined with alcohol

example of an azapirone (and its advantage)

buspirone (BuSpar)

does not cause sedation, dependence, or tolerance

what are azapirones used to treat

GAD and other anxiety disorders

side effects of azapirones

dizziness, dry mouth, sweating, nausea, headache

how do narcotic-analgesics (Opioids) work

mimic effects of the body’s natural analgesics (endorphins and enkephalins)

example of natural opioids (4) and synthetic/semi-synthetic opioids (4)

natural = opium, morphine, heroin, codeine

synthetic/semi-synthetic = methadone, oxycodone, hydrocodone, fentanyl

what are narcotic-analgesics (Opioids) used for

pre-surgery anethetic

pain

heroin detox (methadone specifically)

what is methadone used for and how does it work

heroin detox

doesn’t produce pleasurable effects but does reduce the craving for heroin and reduces withdrawal symptoms

side effects of narcotic-analgesics (Opioids)

dry mouth

nausea

pupil constriction

postural hypotension

drowsiness

dizziness

constipation

respiratory depression

overdose: convulsions, coma, death

dangers of narcotic-analgesics (Opioids)

chronic use leads to dependence, tolerance, withdrawal

overdose can cause convulsions, coma, and death

drug overdose is the leading cause of accidental deaths in the US, and opioids are the most frequent

withdrawal symptoms of narcotic-analgesics (Opioids)

initial withdrawal symptoms are similar to the flu: runny nose, watery eyes, nausea, muscle aches, fever, yawning

followed by: insomnia, abdominal cramps, vomiting, diarrhea, rapid heartbeat, elevated blood pressure

how do beta-blockers work

inhibit activity of the sympathetic nervous system

what are beta-blockers used for

hypertension, cardiac arrhythmias, migraines, essential tremor

propranolol (Inderal)

beta-blocker used to treat anxiety but its more effective for somatic symptoms than psychological symptoms (e.g., apprehension, worry, dread)

side effects of propanolol

hypotension, decreased sex drive, insomnia, nausea, vomiting, dry eyes

abrupt discontinuation can cause rebound hypertension, tremors, headaches, confusion, and cardiac arrhythmia

what are mood stabilizers used for

bipolar disorder

examples of mood stabilizers

lithium (Eskalith, Lithobid)

anticonvulsant drugs

what is Lithium used for

the first-line drug for acute mania and classic bipolar disorder (euphoric mania without rapid cycling)

side effects of lithium

nausea, vomiting, diarrhea, metallic taste, increased thirst, weight gain, hand tremor, fatigue, impaired memory and concentration

danger of lithium

lithium levels must be checked regularly to avoid lithium toxicity, which can cause seizures, coma, and death

what are anticonvulsant drugs used for

acute mania and bipolar disorder with mixed features

examples anticonvulsant drugs (list the main 2)

carbamazepine (Tegretol)

valproic acid (Depakene)

side effects of anticonvulsant drugs

nausea, dizziness, sleepiness, lethargy, ataxia, tremor, visual disturbances, impaired concentration

danger of too much valproic acid

liver failure

danger of too much carbamazepine

liver failure

agranulocytosis (low white blood cell count)

aplastic anemia

drugs for treating Alzheimer’s Disease

cholinesterase inhibitors

NMDA receptor antagonist

what do cholinesterase inhibitors do

slow the progression of Alzheimer’s by delaying the breakdown of acetylcholine

examples of cholinesterase inhibitors

tacrine (Cognex) - no longer prescribed due to risk of liver failure and other serious side effects

donepezil (Aricept) - approved for severe Alzheimer’s

rivastigmine (Exelon) - approved for mild to moderate Alzheimer’s

galantamine (Razadyne) - approved for mild to moderate Alzheimer’s

example NMDA receptor antagonist (1) and how it works

memantine (Namenda) - approved for moderate to severe Alzheimer’s

slows progression of Alzheimer’s by regulating the activity of glutamate

what 2 neurotransmitters do Alzheimer’s drugs target

acetylcholine and glutamate

psychostimulants

the first-line pharmacological treatment for ADHD

example psychostimulants

methylphenidate (Ritalin, Concerta)

pemoline (Cylert)

amphetamine-dextroamphetamine (Adderall)

what do psychostimulants do and how do they work

increase attention and concentration, decrease hyperactivity and impulsivity

effects on academic achievement are unclear

work by increasing dopamine and norepinephrine activity in the prefrontal cortexs

side effects of psychostimulants

insomnia, nervousness, decreased appetite, weight loss, abdominal pain

can suppress growth in children but this can be reversed with “drug holidays” during school vacations

impact of psychostimulants on cognitive functioning in college students & adults

positive effect: attention, mood

no effect: reading comprehension/fluency

negative effect: working memory, academic performance

second- and third-line drugs for ADHD (list the main 3 and how they each work)

atomoxetine (Straterra) - norepinephrine reuptake inhibitor, most commonly prescribed non-stimulant drug for ADHD, useful at treating core ADHD symptoms in patients with tics, sleep disorder, anxiety, or depression

guanfacine (Intuniv) - alpha-2-adrenergic agonist, originally used to treat high blood pressure, also used when patients have Tourette’s or tics

clonidine (Kapvoy) - alpha-2-adrenergic agonist, originally used to treat high blood pressure, also used when patients have Tourette’s or tics

third-line drugs for ADHD (what are they [2] and how do they work)

certain antidepressants including the tricyclic desipramine (Norpramin) and the NDRI buproprion (Wellbutrin)

reduce symptoms of ADHD by increasing dopamine and norepinephrine

drugs for alcohol use disorder (list the 4 and how they each work)

disulfiram (Antabuse) - causes nausea and vomiting, shortness of breath, tachycardia, throbbing headache, dizziness, and other unpleasant symptoms when taken with alcohol

naltrexone (ReVia) - reduces pleasurable effects of and cravings for alcohol

acamprosate (Campral) - reduces craving

topiramate (Topamax) - anti-seizure medication not yet approved by FDA for alcohol use disorder but is used off-label. like naltrexone, reduces pleasurable effects of and cravings for alcohol.

drugs used to treat tobacco use disorder and how they work

nicotine replacement therapy (NRT) - assumes a stable low level of nicotine prevents the withdrawal symptoms that often trigger relapse when they stop smoking

buproprion - originally used for MDD but also found to prevent relapse following smoking cessation by reducing craving and withdrawal symptoms

varenicline - reduces nicotine craving and the rewarding effects of smoking

medications for cocaine use disorder

none approved by FDA

some evidence that buproprion, topiramate, and several psychostimulants (e.g., modafinil, dextroamphetamine, and mixed amphetamine salts) may be effective for increasing abstinence

tetrahydrocannabinol (THC) (what is it, how does it work, what is it used for)

main ingredient of cannabis

exerts its psychoactive effects by stimulating release of dopamine in the ventral striatum (nucleus accumbens) which is an essential component of the brain’s mesolimbic dopaminergic reward pathway

used to treat: anorexia, weight loss caused by AIDS, chemotherapy-induced nausea and vomiting

psychedelic drugs (and how do they work)

LSD - GAD, increases effects of serotonin and dopamine 

psilocybin - MDD, treatment resistant depression, increases effects of serotonin and glutamate

both are serotonin agonists (i.e., they increase the effects of serotonin)

granted FDA breakthrough therapy designation 

drug half-life

the time needed for the blood level of the drug to decrease to 50% of its peak level

used to determine time interval between doses

• shorter half-life = shorter time between doses

• longer half-life = longer time between doses

many drugs have longer half-lives for older adults due to age-related changes in the metabolism and elimination of these drugs (rule of thumb is to “start low and go slow”)

drug tolerance

when repeated use results in a gradual reduction in the drug’s effects, resulting in need to increase dose to produce the get the same effectsc

drug cross-tolerance

when tolerance to one drug produces tolerance to other drugs in the same class

example: tolerance to alcohol causes tolerance to benzodiazepines and barbiturates because they are all central nervous system depressants 

what does therapeutic index (TI) measure

a drug’s safety (lethal dose 50, toxic dose 50, effective dose 50)

how is the therapeutic index (TI) calculated according in animal vs human studies

animals: LD50/ED50

humans: TD50/ED50

lethal dose 50, toxic dose 50, effective dose 50

lethal dose 50: the minimum dose that had a lethal effect in 50% of test sample (low LD50 = more lethal than high LD50)

toxic dose 50: the minimum dose that had a toxic (harmful) effect in 50% of test sample (low TD50 = more harmful than high TD50)

effective dose 50: the minimum dose that had a therapeutic (desired) effect in 50% of test sample (low LD50 = more lethal than high LD50)

narrow vs wide therapeutic windows

narrow = when ED50 is the same or higher than LD50 or TD50 the therapeutic index (TI) is 1.0 or less. not very safe and require close monitoring because the dose that produces the desired effect therapeutic effect is equal to or higher than the dose that produces a lethal or toxic effect

wide - when ED50 is lower than LD50 or TD50 the therapeutic index (TI) is larger than 1.0. safer because the dose that produces the desired effect therapeutic effect is lower than the dose that produces a lethal or toxic effect