Pharm Section 5 Flashcards
psychiatric disorders or mental illness may involve either a ______ or ______ in one or more chemical mediators
excess or deficiency
schizophrenia is associated with an excessive amount of….?
dopamine
depression is associated with a deficient amount of….?
serotonin
psychiatric symptoms can be caused by what?
drug effects underlying illness psychopathology psychosocial factors withdrawal from drugs
when diagnosing mental illness, what should you be sure to rule out?
drug-induced psychiatric symptoms
DSM
Diagnostic and Statistical Manual of Mental Disorders. Standard criteria for diagnosing mental disorders.
DSM IV vs V?
Critics say that DSM V includes too much diagnostic inflation.
normal grief > major depressive disorder
forgetfulness > neuro-cognitive disorder
temper tantrum > disruptive mood dys-regulation disorder
overeating > binge eating
PMDD > mental illness
Psychiatric illness in A Beautiful Mind (and treatments)
Schizophrenia
Treatments: clorpromazine (Thorazine), then risperidone (Risperdal)
schizophrenia
characterized by delusions, hallucinations, disorganized speech/behaviors, social/occupational dysfunction, grossly abnormal psychomotor behaviors, negative symptoms. Must have at least two symptoms for 6 mo with 1 mo. active symptoms.
schizophrenia epidemiology
affects ~1% population in all cultures. affects men and women equally. Onset later in women. 10% lifetime suicide risk with schizophrenia.
antipsychotic drug group
aka neuroleptics or psychotropics
used to treat schizophrenia
first antipsychotics
phenothiazines, 1950s in Paris
dopamine
neurotransmitter associated with feelings of pleasure and well-being. Associated with “addicting” agents.
MOA for typical antipsychotics
block postsynaptic dopamine receptors and increase dopamine turnover by blocking the D2 somato-dendritic auto-receptor. Decreases dopamine neurotransmission.
Typical antipsychotics and side effects
D2 blockade responsible for extrapyramidal symptoms (EPS) of typical antipsychotics, plus antiemetic and hiccup relief. EPS include: akasthesia, parkinsonian symptoms, dystonia, and tardive dyskinesia. Other side effects include: sexual dysfunction, orthostatic hypotension, anticholinergic effects, poikilothermia, hyperprolactinemia, tranquilization, cardiac toxicity, and neuroleptic malignant syndrome.
MOA for atypical antipsychotics
mixed neuro-receptor agonists with low-affinity dopamine D2 blockade and high-affinity serotonin 5HT blockade
Side effects of atypical antipsychotics
Much less likely to cause EPS, but cause serious metabolic side effects (weight gain, T2 diabetes, hypercholesterolemia, and metabolic syndrome)
blocking dopamine D2 receptor causes what effects?
EPS, increased prolactin levels, antiemetic effects, and decreases intractable hiccups
blocking the serotonin 5HT2 receptor causes what effects?
mitigates some EPS
anxiety
insomnia
blocking the H1 receptor causes what effects?
drowsiness
increased appetite
weight gain
blocking the alpha-1 adrenergic receptors causes what effects?
orthostatic hypotension
dizziness
reflex tachycardia
blocking the muscarinic/cholinergic receptors causes what effects?
dry mouth, constipations, blurred vision, urinary retention
akasthesia
EPS characterized by motor restlessness, agitation, and aggression
Parkinsonism symptoms
EPS characterized by slow movement, apathy, masked face, social withdrawal, flattened affect, “pill-rolling” movement
Dystonia
EPS characterized by acute muscle spasms like oculo-genic crisis (eyes roll back in head), etc.
what can sometimes treat coulee-genic crises?
Artane, Cogentin, or Benadryl
Tardive Dyskinesia (TD)
EPS characterized by persistent and involuntary hyperkinetic abnormal movements, such as spasms of tongue, face, lips, neck, trunk, and limbs. Dopamine probably plays role. Associated with long-term antipsychotic use. More likely with typical antipsychotics than atypical antipsychotics.
poikilothermia
temperature regulation abnormalities
hyperprolactinemia
overproduction of prolactin that leads to amenorrhea, gynecomastia, and galactorrhea.
neuroleptic malignant syndrome (NMS)
rare, rapidly developing, occasionally lethal reaction caused by acute reduction in dopamine activity resulting from drug-induced dopamine blockade. S/s include: rigidity, hyperthermia, tachycardia, hypertension, diaphoresis, incontinence, and confusion.
treatment for NMS?
skeletal muscle blocker dantrolene (Dantrium)
dopamine agonist bromocriptine (Parlodel)
black box warning for antipsychotics
cause increased risk of death with off-label use for behavioral problems in older people with dementia
atypical antipsychotics are generally approved for schizophrenia and…?
bipolar disorder/disease
chlorpromazine (Thorazine)
typical antipsychotic (phenothiazine) than also has many other uses (nausea, hiccups)
thioridazine (Mellaril)
typical antipsychotic (phenothiazine) rarely used due to black box warning for OTc prolongation resulting in torsades de points arrhythmias and sudden death.
trifluperazine (Stelazine)
typical antipsychotic (phenothiazine) with high potency and the most EPS.
fluphenazine decanoate (Prolixin)
typical antipsychotic (phenothiazine) that’s a long-acting form for injections. Lasts 3-4 weeks and helps assure compliance.
thiothizene (Navane)
typical antipsychotic (non-phenothiazine)
loxapine (Loxitane)
typical antipsychotic (non-phenothiazine)
halperidol (Haldol)
typical antipsychotic (butyrophenone). has a long acting form (halloo dacanoate) to ensure compliance. Still used a lot in jails, but has a lot of EPS.
Clozapine (Clozaril, Fazaclo)
the first atypical antipsychotic. Most effective antipsychotic agent, but only used for refractory patients because of risk of neutropenia, agranulocytosis, seizures, and myocarditis. Causes little to no EPS. Distributed through monitored program. REMS registry.
Olanzapine (Zyprexa)
atypical antipsychotic. oral tablet or long-acting injection. chemically similar to clozapine but without agranulocytosis. Major weight gain (30% gained more than 20lbs in 3 mo). Carries FDA DRESS warning and requires continuous monitoring for reaction for at least 3 hours after injection.
Risperidone (Risperdal)
atypical antipsychotic comes in oral tablets or long acting injections. Causes more EPS than other atypicals. Approved for kids and adolescents with autism. Drug in A Beautiful Mind.
Quetiapine (Seroquel)
atypical antipsychotic with dibenzothiazepine ring (clozapine and olanzapine). Abused for sedative and anti-anxiety effects (esp. among inmates/substance abusers). Called “quell” or “baby heroin.” Not controlled substance.
Ziprasidone (Geodon)
atypical antipsychotic that prolongs QTc at higher doses. FDA DRESS warning…reaction may start with rash all over.
Aripiprazole (Abilify)
atypical antipsychotic with slightly different MOA: dopamine system stabilizer (partial D2 agonist–adjusts dopamine instead of totally blocking it). FDA warning for impulse control (gambling, shopping, eating, sex). Fewer side effects compared to other atypicals
Paliperidone (Invega)
atypical antipsychotic that is the active metabolite of risperidone (Risperdal). 24-hour extended release form.
Iloperidone (Fanapt)
atypical antipsychotic that is reportedly better tolerated than some others but may prolong QTc interval like Geodon.
Asenapine (Saphris)
atypical antipsychotic that comes as sublingual tablet. Is inactive if swallowed (important for “cheekers”) and carries FDA warning for severe allergic reactions, including anaphylaxis and angio-edema.
Lurasidone (Latuda)
atypical antipsychotic marketed with less metabolic effect and 1x/day dosing. 10th atypical.
Brexipiprazole (Rexulti)
atypical antipsychotic approved for tx of adult schizophrenia and as an add on for adult major depressive disorder. Med Letter says no reason to use this over aripiprazole (Abilify) which has longer history and proven efficacy/safety and costs less.
Cariprazine (Vraylar)
atypical antipsychotic approved for schizophrenia and bipolar disorder. Carries boxed warning for inc. risk of death in tx elderly with dementia-related psychosis. Adverse effects: tremor, slurred speech, involuntary muscle movements.
FDA class labeling change for atypical antipsychotics?
patients should be monitored at least every 6 mo for diabetes, obesity, and hypercholesterolemia.
What should be included when initiating long-term antipsychotic therapy for the first time?
Make sure to include an Rx for daily orals because the long-acting injectables take a while to generate a therapeutic effect. E.g.: Kingsport woman who killed mom after switching.
Atypical antipsychotics in children?
Risperidone/ Risperdal is good first choice, Olanzapine/Zyprexa is worst. Concern about metabolic effects: monitor weight, BP, BGC, and lipids every 6 mo. Some may gain 10-20lbs in 3 mo. and they inc. risk for T2 diabetes by 3-fold even for short therapy.
Psychotropic drugs are most commonly prescribed for children to treat what condition?
ADHD
atypical antipsychotics and depression?
some are approved for resistant depression. especially useful if have depression and psychotic symptoms, but can be used for patients with just depression and no psychotic symptoms.
what are some CMS recommendations for reducing the # of elderly in nursing homes on antipsychotics?
evaluate all PRN antipsychotics
evaluate any antipsychotics used for 3+ mo
evaluate all antipsychotic Rxs for new pts
evaluate all rxs initiated on nights/weekends
evaluate “off-label” use
discontinue when possible.
What were the results of the CMS initiatives to reduce antipsychotic use in nursing homes?
use of these meds fell by 9.1% TN went from 4th in Rxs to 48th…huge reduction in antipsychotic use in nursing homes. Improves quality of life and health care costs. TN lowered #s through training sessions for providers.
what percentage of patients with depression respond to 1st line pharmacotherapy?
Fewer than 50%
2009 SAMHSA report on TN and MDD?
Tennessee had highest rate of people with a major depressive disorder in the last year
what percentage of women ages 50-64 are on antidepressants?
25%
DSM-V criteria for diagnosing depression?
must experience 5 out of following 9 symptoms: depressed mood, loss of interest, weight change, sleep disturbance, psychomotor agitation or retardation, fatigue, feelings of worthlessness/guilt, loss of concentration, suicidal ideation
chronic depression diagnosis in DSM IV vs V?
DSM IV: dysthymia
DSM V: persistent depressive disorder
Onset of action for antidepressants?
May see side effects in a number of hours, but don’t actually start to get the therapeutic effect for around 2 weeks. May take 6+ weeks to achieve maximum benefit from antidepressants.
neurotransmitters involved in the pharmacology of depression include?
Norepinephrine
Dopamine
Serotonin primary
First line recommendations for treating major depression in adults?
SSRI
SNRI
bupropion (Wellbutrin)
mirtazapine (Remeron)
First line recommendations for treating depression in adults?
sertraline (Zoloft)
escitalopram (Lexapro)
First line recommendations for treating depression in kids/adolescents/young adults?
fluoxetine (Prozac)
Most clinicians start with what when treating depression? What if that doesn’t work?
SSRI. If doesn’t work, switch to another SSRI or try antidepressant from another class. Then start trying combinations like SSRI and bupropion (Wellbutrin) or adding augments like an antipsychotic.
TCAs
tricyclic anti-depressants that probably interfere with repute of norepinephrine at the neuronal membrane. Not used much anymore because to anticholinergic effects, cardio-toxicity, and suicide.
side effects of TCAs
anticholinergic (dry mouth, constipation, etc)
cardio-toxic (dysrhythmias)
weight gain
dosing considerations for TCAs?
dose at bedtime to decrease awareness of side effects and because get sedation
amitriptyline (Elavil)
first TCA
imipramine (Tofranil)
TCA. also used for enuresis (urinary incontinence)
nortriptyline (Pamelor)
TCA
desipramine (Norpramin)
TCA
clomipramine (Anafranil)
TCA. also used for OCD.
doxepin (Sinequan, Adapin)
TCA. more sedative effects than others, so used to tx anxiety or insomnia.
SSRIs
Selective serotonin re-uptake inhibitors that block the reabsorption of serotonin, increasing available levels in the brain.
Why do SSRIs have less sedative and cardiovascular effects than TCA drugs?
they bind significantly less to histamine, acetylcholine, and norepinephrine receptors.
Why are SSRIs first-line agents for treating depression?
proven efficacy favorable side effect profile long-term tolerance 1x/day dosing wide therapeutic index
What are some side effects of SSRIs?
nausea, headache, nervousness, insomnia, fatigue, weight change (usually loss), sexual dysfunction, GI and cranial bleeds (dec. platelet aggregation), hypo-natremia, withdrawal (discontinuation syndrome), Serotonin syndrome, osteoporosis, increased fracture risk, pregnancy issues/birth effects, “bizarre” behavior and murder, and cardiac issues (prolonged QT interval)
Boxed warning for all antidepressants?
should not be used in anyone under the age of 25, even though many are approved for kids.
What is the dangerous period during initiation of SSRI treatment?
first week or two considered the “dangerous period” when people may have violent tendencies towards others or self
SSRIs and safety in pregnancy?
some concern for autism, absolute risk very small. some concern for birth defects, absolute risk very small.
SSRIs and osteoporosis?
SSRIs inhibit serotonin transport protein…also found in bone. Inc risk for fractures.
What is serotonin syndrome? how is it treated?
a life-threatening condition caused by excessive levels of serotonin in the brain. S/s: altered mental status, fever, tachycardia, HTN, agitation, tremor, myoclonus, hyper-reflexia, ataxia, incoordination, diaphoresis, shivering, and GI symptoms. Usually occurs because of drug interactions. Treat with benzodiazepines or anti-serotonergic agent cyproheptadine (Periactin).
What should SSRIs and SNRIs not be used with?
MAOIs or drugs with MAOI activity (like St. John’s Wart). Can cause serotonin syndrome
How do SSRIs impact sexual function? What drugs can help with this side effect?
serotonin is involved in inhibitory sexual activity and dopamine/norepinephrine are involved in excitatory activity. when increase serotonin, more sexual inhibition than excitement. Decreases libido/sex drive/ ability to perform sexually. Type 5PDE inhibitors (Viagra, Cialis) and Bupropion (Wellbutrin) may help with this side effect.
fluoxetine (Prozac)
SSRI with long half life. Requires longer wash out period before switching to MAOI. Approved in children >8 years for major depression and >7 years for OCD.
fluoxetine and olanzapine (Symbyax)
combination of SSRI antidepressant and antipsychotic used to treat bi-polar disease and treatment-resistant depression (TRD)
Sarafem
fluoxetine approved for PMDD
Prozac Weekly
once-weekly administration for stable patients
sertraline (Zoloft)
SSRI
paroxetine (Paxil)
SSRI that’s worst choice for pregnancy (category D)–causes heart defects.
paroxetine mesylate (Brisdelle)
SSRI? contains lesser amount of paroxetine than antidepressant formulation. First non-hormonal drug approved to treat hot flashes
citalopram (Celexa)
SSRI with warning to limit dose to avoid changes in electrical activity @ heart and serotonin syndrome. Don’t exceed 40mg/day in general and don’t exceed 20mg/day in women on estrogen BC or over 60 years.
Escitalopram (Lexapro)
SSRI L-enantiomer of citalopram (Celexa). Approved for depression in pediatric patients >12 years. Reasonable 1st-line choice for general depression in adults.
All SSRIs are averrable as…?
generics
SNRIs
serotonin/norepinephrine re-uptake inhibitors that block the re-uptake of serotonin and norepinephrine, so called “dual action” antidepressants. More likely to increase BP than SSRIs because they act on norepinephrine.
SNRI and withdrawal?
Patients can experience intense withdrawal symptoms after missing only one dose of an SNRI.
Venlafaxine (Effexor)
SNRI that may be more effective than SSRI, not enough evidence to tell.
Desvenlafaxine (Pristiq)
SNRI. Metabolite of venlafaxine. Hoped it would be longer acting than 1x/day formulation but no evidence of such. May be less effective for depression. Warn patients about ghost tablet in stool.
Duloxetine (Cymbalta)
SNRI approved for MDD, diabetic peripheral neuropathy pain, chronic pain, and fibromyalgia management. Not actually approved for general depression, but still used for it.
Levomilnacipran (Fetzima)
SNRI approved for MDD. Active isomer of Milnacipran (Savella).
Milnacipran (Savella)
SNRI approved for fibromyalgia management, but not for psychiatric use.
Vortioxetine (Brintellix, now Trintellix)
aytpical antidepressant often listed as an SSRI. A serotonin modulator and stimulator (inhibits re-uptake and is a partial serotonin agonist). May cause more nausea than some other antidepressants.
Hetero-cyclic antidepressants
Aka multiple-receptor agents. Antidepressant agents that affect one or more of serotonin, norepinephrine, acetylcholine, and dopamine neurotransmitters
trazodone (Desyrel, Oleptro)
heterocyclic antidepressant that works like an SSRI with alpha-adrenergic and histamine blocking action. Used in the treatment of MDD, generalized anxiety, and insomnia. Anxiolytic effect. Widely used off-label as a hypnotic (many call it their “sleeping pill”). Most likely drug to cause priapism in males.
bupropion (Wellbutrin)
heterocyclic antidepressant that inhibits the re-uptake of dopamine and epinephrine. Greater potential for seizures than other antidepressants. Less adverse sexual side effects > may improve sexual function. May cause weight loss. May be abused or diverted for cocaine-like high.
bupropion (Zyban)
bupropion formulation used for smoking cessation
Mirtazapine (Remeron)
heterocyclic antidepressant, not chemically related to any other class of antidepressants. MOA: increases central nor-adrenergic and seroton-ergic activity. Useful for patients with coexisting depression and anxiety. Faster one, less sexual dysfunction than SSRIs.
Vilazodone (Viibryd)
heterocyclic antidepressant that not many people use. First approved SSRI and serotonin 5HT receptor partial agonist. Prescribers Letter says doesn’t work any better than fluoxetine or citalopram and has more GI side effects.
MAOIs
monoamine oxidase inhibitors. there are two types (A and B).
MAOI interactions
interacts with tyramine in foods (beer, wine, cheese) to cause HTN crisis.
interacts with all other antidepressants
interacts with many drugs like sympathomimetics
Phenelzine (Nardil)
MAOI Type A agent (only used 4-5th line or in psych hospitals). Cause HTN.
Tranylcypromine (Parnate)
MAOI Type A agent (only used 4-5th line or in psych hospitals). Cause HTN.
Isocarboxazid (Marplan)
MAOI Type A agent (only used 4-5th line or in psych hospitals). Cause HTN.
Selegiline (EMSAM)
MAOI Type B agent. Prevents catabolism of dopamine in the brain. Used orally for Parkinson’s disease or trans-dermally for depression. Don’t cause HTN in <10mg/day doses.
perphenazine and amitriptyline (Triavil, Etrafon)
combination product (phenothiazine and TCA) marketed for “nerves” and “sleep”
ketamine and depression
used off-label for fast-acting treatment of severe depression. More for acute depression than chronic. Conflicting reports on efficacy, but APA expects to support it’s use for severe depression.
esketamine
ketamine-like drug seeking 2018 FDA approval for rapid treatment of severe depression
rapastinel
ketamine-like drug on the horizon for treatment of severe depression
St. john’s Wart and depression
has MAOI-like effects and is used widely around the world for antidepressant effects. Side effects: photosensitivity, drug interactions (induces CYP450 system), and inc risk of cataracts. Conflicting results for efficacy.
omega-3 fatty acids and depression
confusing data on efficacy, but meta-analysis found moderate to strong effects of omega 3’s as adjunct to antidepressant therapy.
bipolar disease
formerly known as manic-depressive disorder. affects ~1% adults. Most commonly diagnosed between 18 and 24 years. Chronic condition with cycles of mania, depression, and normal mood. Without treatment, patients often engage in harmful behaviors (substance abuse, suicide attempts).
lithium carbonate
mood stabilizer used most often for treatment of bipolar disease. Historically drug of choice for mania, but does have some toxic effects. Narrow therapeutic index, so requires monitoring.
only medication proven in literature to prevent suicide
lithium carbonate. 87% reduction of suicide risk.
side effects of lithium
tremors, nausea/vomiting, fatigue, anorexia, late-stage seizures, dec, renal function, hypothyroidism, and hypercalcemia.
drug therapy for bipolar disease?
mood stabilizers (lithium carbonate and citrate)
anticonvulsants (carbamazepine, valproate, and lamotrigine)
antipsychotics/ antidepressants/ benzodiazepines (augment tx for mania)
omega 3 fatty acids (less depression, fewer relapses)
anticonvulsants proven effective for bipolar disease
carbamazepine (Tegretol)
valproate (Depakote)
lamotrigine (Lamicatal)
mainstay of treatment for bipolar disease/ 1st line treatment
mood stabilizers, specifically lithium or valproate (Depakote).
1st line for bipolar patients that are also depressed
Lamotigine (Lamictal)
What is added to mood stabilizers for severe mania in bipolar patients?
antipsychotics such as olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal).
What is added to mood stabilizers for depression in bipolar patients?
antidepressants (Don’t use them alone though…can trigger mania)
What drug works best for mixed episodes in patients with bipolar disease?
Valproate (Depakote)
PTSD
post-traumatic stress disorder characterized by hyper arousal and flashbacks. 4th most common psychiatric disorder.
first line therapy for PTSD?
psychotherapy and SSRI or SNRI
If two trials of SSRI or SNRIs fail, what should be tried for PTSD?
heterocyclic antidepressant mirtazapine (Remeron), then a TCA.
What can be added to antidepressants to help decrease hyperarousal and re-experiencing symptoms?
atypical antipsychotics, but don’t use them alone (don’t help)
what can help reduce nightmares associated with PTSD?
Prazosin (Minipress)–sympatholytic
what are used for insomnia and anxiety with PTSD, but should be discouraged because may worsen fear response?
benzodiazepines
what should be used to aid sleep in patients with PTSD?
trazodone (Desyrel) or non-bezo/”Z” hypnotics
what should be used to treat acute pain related to traumatic injuries and why?
use analgesics aggressively. Adequate pain management lowers risk of developing PTSD.
what are recommendations re: opioid use and PTSD/traumatic pain?
usual precautions: try to limit opioid use, especially chronic use.
what are recommendations for propranolol and PTSD patients?
originally thought it might lessen memory or traumatic events, but no evidence so don’t recommend using it
sedative-hypnotics
drug class used to treat insomnia, sleep disturbances, or to put people to sleep for medical procedures
insomnia
condition characterized by difficulty initiating or maintaining sleep that affects 30% of general population (10% chronic).
side effects of insomnia
nighttime sleep disturbances, daytime fatigue, lack of energy, poor concentration and memory, irritability, moodiness, problems accomplishing tasks
non-pharmacologic treatments for insomnia
changing sleep patterns/habits, relaxation, cognitive therapy
many clients that suffer from insomnia also suffer from what conditions?
anxiety, depression, or both
FDA labeling requirement for sedative-hypnotic drug class?
must include stronger language about the potential for severe allergic reactions and complex sleep-related behaviors (sleep walking and driving, for example). Most also mention risk for somnambulism.
most common type of drugs used as sedative/hypnotics and anxiolytics?
benzodiazepines (BZDs) and non-benzo receptor agonists (NBRAs)
mechanism of action for BZDs
stimulate neurotransmitter GABA that has sedative effects and increase chloride ion influx and inhibit the release of serotonin
overdose and BZDs
rare unless taken with alcohol or other CNS depressant (synergistic effects with these(
BZDs and abuse potential?
all of them have potential for abuse and are CS IV.
BZDs and impairment
increase the risk of motor vehicle crash similar to blood alcohol levels between .06 and .11
flurazepam (Dalmane)
BZD used as a hypnotic
temazepam (Restoril)
BZD used as a hypnotic
triazolam (Halicon)
BZD used as a hypnotic
quazepam (Doral)
BZD used as a hypnotic
estazolam (ProSom)
BZD used as a hypnotic
BZDs and sleep stages
BZDs prolong sleep stages 1,2 (light sleep) and suppress sleep stages 3,4 (deep sleep)
how to reverse BZDs?
flumazenil (Romazicon)
hypnotic agents of choice and why?
NBRAs because they don’t affect sleep stages
zolpidem (Ambien)
CS IV NBRA with onset ~30 min and 6-8 hour duration. Available in several dosage forms. Recommended lower dose to avoid next-day impairment, especially in women.
Ambien CR
controlled-release form of ambient to help maintain sleep. Next day hangover.
Zolpimist
ambient oral spray
Edular/ Intermezzo (means intermission)
sublingual form of ambien
zaleplon (Sonata)
CS IV NBRA with onset 7-27 minutes and duration <5 hours. Can dose multiple times a night as long as have 4 hours until wake time. Little hangover next day.
Exzopiclone (Lunesta)
CS IV NBRA with longest 1/2 life. For long-term use. Dysguesia (bitter metallic) complaints. Dose reduced to 1mg to avoid next-day impairment/drowsiness.
Ramelteon (Rozerem)
melatonin receptor agonists that increases the production of melatonin @ brain. not a CS, no evidence of abuse. helps people fall asleep, not stay asleep. 8 mg 1/2 hour before bedtime. Taking more doesn’t work better. Recommended for shift workers, jet lag.
Tasimelteon (Hetlioz)
melatonin receptor agonist approved for “non-24” wake disorder in totally blind people. specialty drug, expensive ($148k/year).
chloral hydrate (Noctec)
CS IV sedative-hypnotic not used much today, but works for transient insomnia. Withdrawal = disrupted sleep and intense nightmares. Was drug used in Mickey Finns.
OTC antihistamines as sedatives
diphenhydramine and doxylamine used as sleep aids, but not recommended because of next-day sedation and anticholinergic effects
antidepressants as sedatives
useful when depression is the source on insomnia. Don’t use if not depressed. Trazodone (Desyrel) used most often.
barbiturates as sedatives
sometimes used in hospital but not much outpatient because of abuse potential, low therapeutic index, respiratory depression, lethality in overdose, and rapid tolerance development. Secobarbital (Seconal) and pentobarbital (Nembutal) used some.
Marilyn Monroe overdose
Secobarbital (Seconal)
lethal injection barbiturate
Pentobarbital (Nembutal)
Elvis overdose
21 drugs in system including barbiturates
doxepin (Silenor) as sedative
old antihistamine now approved for insomnia
Kava
supplement used as a sedative, but don’t recommend because it’s hepatoxic
Valerian
supplement used as sedative, but no info on dosage, concerns of purity. Mentioned in Diary of Anne Frank for anxiety.
Melatonin
produced in pineal gland @ brain. Serotonin when light, converted to melatonin when dark. supplemented for shift workers and jet lag.
Suvorexant (Belsomra)
CS IV orexin receptor antagonist used as sedative. “Turns off wakefulness.” Side effects: sleep driving, eating, cataplexy, next-day impairment.
alcohol as sedative
widely used, but not recommended because it causes initial CNS depression followed by rebound excitation, which disrupts sleep.
anesthesia and conscious sedation drugs
used for pre-op sedation and some medical procedures.
midazolam (Versed)
CS IV water soluble BZD used for pre-op sedation. Patients can respond, but provides total amnesia.
Lorazepam (Ativan)
CS IV BZD used for delirium tremens and ICU sedation
propofol (Diprivan)
not CS anesthetic used for induction and maintenance of general anesthesia. Abused mostly by medical professionals, Michael Jackson. Not reversible–no antidote. Induces and end anesthesia quickly. Associated with minimal post-op confusion. Also used for refractory status epilepticus.
fospropofol (Lusedra)
Anesthetic. Water-soluble prodrug to propofol. Fewer problems than lipid-formulated propofol (pain at catheter site, etc). Loss of consciousness takes 4 minutes (vs. 1 circulatory time with propofol).
etomidate (Amidate)
Anesthetic that’s shorter-acting than midazolam (Versed) with less “hangover”
Dexmedetomidine (Precedex)
Sedative/Analgesic. alpha-2 agonist. ICU sedation. 8x more selective than clonidine. May reduce duration of mechanical ventilation, enhance patient comfort, and lower prevalence of delirium. Onset 15-30 minutes (longer than midazolam or propofol). No respiratory depression. Decreases blood pressure and other cardiovascular effects.
general anesthetics
sedatives that cause respiratory depression. Hearing (8th cranial nerve) lost last.
redheads and anesthesia
require 20% more anesthesia and analgesia because are more sensitive to pain.
nitrous oxide (laughing gas)
general anesthetic. inhalation/volatile agent. Not completely anesthetic, an adjunct.
isoflurane (Florane)
general anesthetic. inhalation/volatile agent.
enflurane (Ethrane)
general anesthetic. inhalation/volatile agent. nephrotoxic.
desflurane (Suprane)
general anesthetic. inhalation/volatile agent. administered via vaporizer. quick acting.
sevoflurane (Ultane)
general anesthetic. inhalation/volatile agent.
thiopental sodium (Pentothal)
general anesthetic. IV agent. used to be part of lethal injection.
etomidate (Amidate)
general anesthetic. IV agent.
methohexital (Brevital)
general anesthetic. IV agent.
fentanyl (Sublimaze)
general anesthetic. IV agent. Used frequently
droperidol/ fentanyl (Innovar)
general anesthetic. IV agent. Used for neuroleptanesia.
propofol (Diprivan)
general anesthetic. IV agent. Used frequently
ketamine (Ketalar)
general anesthetic. IV agent. produces dissociative anesthesia. highly abused.
remifentanil (Ultiva)
general anesthetic. IV agent. used as analgesic during general anesthesia.
flumazenil (Romazicon)
BZD reversing agent (BZD antagonist). used to treat BZD overdose and reverse BZD sedation during anesthesia. Only administered via rapid IV injection (highly irritating). Doesn’t treat hypoventilation produced by BZDs. Shorter duration than BZDs, watch for re-sedation.
anxiolytics
drugs used to treat or manage anxiety disorders such as acute anxiety, generalized anxiety disorder, panic disorders, social phobias, PTSD, and OCD.
what are the most often used classes of drugs to treat anxiety disorders?
BZDs
SSRIs (antidepressants)
SNRIs (antidepressants)
others: neuroleptics, anticonvulsants, anti-HTN, antidepressant (when present with anxiety)
anxiolytic BZDs
equally effective for most forms of anxiety. all show tolerance and are CS IV. physical dependence may develop with chronic use and cause rebound anxiety or withdrawal symptoms (esp. with shorter acting drugs).
BZDs and elderly patients
BEERS list! Don’t use BZDs with elderly patients because increased risk of delirium, memory impairment, falls, and hip fractures.
FDA “reminder” warning for BZDs
FDA warns not to use them in patients with primary depressive disorder or psychosis because they can exacerbate preexisting depression. For patients with depression, use concurrent antidepressants with BZDs.
BZDs and CNS depressants
don’t use with other CNS depressants because this combo can lead to potentially fatal respiratory depression
chlordiazepoxide (Librium)
BZD used as anxiolytic. 1st BZD discovered.
diazepam (Valium)
BZD used as anxiolytic. IV push, IM, or rectal gel. Also used for seizures.
lorazepam (Ativan)
BZD used as anxiolytic.
oxazepam (Serax)
BZD used as anxiolytic.
clorazepate (Tranxene)
BZD used as anxiolytic.
clonazepam (Klonopin)
BZD used as anxiolytic. Primarily used for seizure disorders.
alprazolam (Xanax)
BZD used as anxiolytic. Most commonly used BZD. Approved in larger doses for panic attack. Highly abused “bars”, “totem poles”, “tombstones”
clobazam (Onfi)
BZD used as anti epileptic for Lennox-Gastaut syndrome (LGS). Other countries used as anxiolytic too.
Buspirone (BuSpar)
anxiolytic with similar efficacy to BZDs. Works best in BZD virgin. No additive effect with alcohol, driving not impaired. Not CS.
Meprobamate (Equanil)
CS IV anxiolytic. Muscle relaxant Soma is metabolized to meprobamate, so Soma has abuse potential. Not used much today.
Hydroxyzine (Vistaril)
antihistamine used as anxiolytic. Not CS. used for relaxation. Often combined with analgesics. Very irritation–only give deep IM.
Phenobarbitol
CS IV drug used primarily for seizure disorders but sometimes as anxiolytic. Very long acting.
Pragabalin (Lyrica)
CS V GABA agonist approved for neuropathy and epilepsy, but used off-label as anxiolytic.
Beta-blockers as axiolytics
used mainly for performance anxiety or acute anxiety reaction (“stage fright”)
club drugs
MDMA/Ecstacy (CS I)
ketamine
flunitrazepam (Rohypnol)
Sodium oxybate/GHB “date rape drug”
“minimal brain dysfunction”
ADD/ADHD used to be called this. Accurate because thought that areas of brain lack sufficient levels of dopamine, norepinephrine, and serotonin leading to disorders. Deficiencies in areas that control impulse behaviors, cannot filter distractions or focus well.
Three subtypes of ADHD
predominantly hyperactive-impulse
predominantly inattentive
combined
ADHD diagnosis
6 or more inattention and hyperactivity symptoms present for at least 6 months.
ADHD is manifested by…?
inattentiveness, impulsiveness, and sometimes hyperactivity
adults vs kids medicated for ADHD
now more adults are prescribed meds for ADHD than children. Rates of children affected by ADHD are skyrocketing though (mostly in boys)
APA recommendations now suggest that children as young as _____ be treated with methylphenidate if behavioral therapy not successful
4 or 5 years old
AHA recommendations for kids starting ADHD drugs
recommend that all kids be given EKG prior to imitating ADHD therapy. conflicting recommendations from different entities, but FDA still recommends ADHD drugs not be used in patients with serious heart problems.
ADHD treatment should begin with what?
oral stimulant. Stimulants are effective in about 70% of patients with ADHD.
Amphetamines
CS II drugs that stimulate the entire CNS and cause excessive dopamine release. Frequently abused.
Adderall
CS II amphetamine approved for treatment of adult ADHD. High potential for abuse.
lisdexamphetamine (Vyvanse)
CS II prodrug to dextroamphetamine. Reduces abuse potential. Longer acting. also approved for binge eating.
methamphetamine (Desoxyn)
not used for ADHD. Manufactured illegally in meth labs. 1 dose lasts 6-8 hours. “Mother of all dopamine agonists”–releases more than sex or cocaine.
synthetic cathinone
“bath salts”. synthetic stimulants that mimic effects of cocaine, but more addictive than meth. Mice pressed button 600 times for bath salts vs. 60 times for meth.
gravel/flakka
synthetic cathinone drug that stimulated cardiovascular and CNS. Results in paranoia, euphoria, hallucinations, kidney failure. No rage, but worst paranoia ever seen.
methlyphenidate (Ritalin)
CS II drug used to treat ADHD. Side effects include CNS stimulation, insomnia, nervousness, inc. BP, priapism, tachy-arrhythmias, anorexia, and possible stunted growth.
Concerta
CS II once-a-day formulation of methylphenidate
dexmethylphenidate (Focalin)
CS IImore potent isomer of methylphenidate. For patients that need flexibility of rapid-onset methylphenidate.
Metadate CD
CS IImethylphenidate for “sprinkling” administration (on food)
Daytrana
CS II 1st transdermal for of methylphenidate. 2 hour delay in onset of action. Skin sensitivity, reactions significant problem.
Quillivant XR
CS II 1x/day, extended-release, liquid form of methylphenidate
Non-stimulant treatments for ADHD
Atomoxetine (Strattera)
alpha-2 adrenergic agonists
Guanfacine (Intuniv)
Clonidine (Klonopin)
Atomoxetine (Strattera)
non-stimulant SSRI treatment for ADHD. not controlled substance. enhances norepinephrine. Black box warning: don’t use in under 25s because of suicidal ideation
alpha-2 adrenergic agonists for ADHD tx
mechanism unknown, but probably involves the prefrontal cortex, regulates attention, and plays role in impulse control and working memory.
Guanfacine (Intuniv) for ADHD tx
approved for hypertension under other brand name. Now approved for ADHD in children and adolescents.
Clonidine (Klonopin) for ADHD tx
approved under other name for hypertension. Now approved as non-stimulant tx for ADHD in children and adolescents. 1st and only FDA approved ADHD tx indicated as add-on therapy for stimulant medication. can also be used as mono therapy for ADHD.
antidepressants/mood stabilizers for ADHD treatment
kids do best on despiramine (Norpromin) or imipramine (Tofranil) (SSRIs have less side effects). Bupropion (Wellbutrin) also effective.
anticonvulsants for ADHD treatment
may be effective (Valproate/Depakote and carbamazepine/Tegretol)
anxiolytics for ADHD treatment
busiprone (BuSpar) seems best for patients that are hyperactive and aggressive
antipsychotics for ADHD treatment
Haldol, Risperdal, and Zyprexa are used to treat ADHD patients that are angry, aggressive, and/or out-of-control. None are actually approved to treat kids with ADHD, though many are prescribed off-label for this.
Iron for ADHD treatment
iron plays role in dopamine function, so may play role in ADHD. Check iron levels in kids with ADHD symptoms. Iron is appropriate when levels are deficient.
ADHD treatment and learning?
mixed reports on whether or not ADHD treatment is beneficial for long-term benefits in learning, academic achievement, grades. Overall seems that there isn’t much effect.
most used drug for treatment of narcolepsy or excessive daytime sleepiness?
CS IV non-amphetamine stimulant modafinil (Provigil)
modafinil (Provigil)
most used drug for treatment of narcolepsy
traditional treatments for narcolepsy?
CNS stimulants like amphetamines or methylphenidate (Ritalin)
armodafinil (Nuvigil)
CS IV active isomer of modafinil (Provigil). Marketed to “keep you awake”. has longer 1/2 life than modafinil.
sodium oxybate (Xyrem)
CS III orphan drug used to treat cataplexy (loss of muscle tone associated with narcolepsy). CNS depressant. related to GHB, potential for abuse.
obesity
chronic disease process with many adverse health effects. TN 4th most obese state in 2015.
cornerstone of weight loss programs
lifestyle and behavior modification
goal for weight reduction
5-10% of patient’s baseline weight within 6-9 months.
% of student overweight in Knox county?
40%
international obesity trend?
rising at extraordinary rate for three decades
most popular measure for obesity?
BMI
better predictor of CV risk than BMI?
waist girth
non-drig management of obesity?
diet modification
exercise
behavior modification
surgery
drug treatment of obesity?
six drugs approved to treat obesity, some short and some long term.
obesity drugs not approved in TN
benzphetamine (Didrex)
diethylpropion (Tenuate)
Phendimetrazine (Bontril)
phentermine (Adipex-P, Suprenza)
CS IV drug approved for the tx of obesity in TN
orlistat (Xenical, Alli) MOA
block pancreatic lipase, prevents GI absorption of fat by up to 1/3.
supplement recommended with orlistat (Xenical, Alli)?
supplement fat-soluble vitamins–drug reduces their absorption.
indications for obesity drugs?
BMI > 30 or BMI > 27 with at least on comorbidity.
orlistat(Xenical, Alli) also approved for what?
to delay the onset of T2 diabetes in obese patients, including kids 12-18.
adverse effects of orlistat (Xenical, Alli)?
no CNS effects
adverse GI effects: oily spotting, flatus with discharge, fecal urgency and incontinence **subside after a few months
other adverse effects: liver and kidney injury
Lorcaserin (Belviq)
CS IV drug approved to treat obesity.
MOA of lorcaserin (Belviq)
It’s a serotonin 5HT agonist, so has potential for abuse b/c of euphoria and is CS IV
side effects of lorcaserin (Belviq)?
best tolerated of obesity drugs
most common: URI, headache, nausea
caution: don’t combine with SSRIs, tramadol, or dextromethorphan
phentermine/topiramate (Qsymia)
CS IV drug approved to treat obesity. some concerns over inc BP and birth defects, but approved anyway. weight loss of 9-13% in 56 weeks. most weight loss of obesity drugs
bupropion/naltrexone (Contrave)
first rejected in 2011, then approved to treat obesity in 2014. Do not use with opioids…will block effects.
Liraglutide (Saxenda)
injectivle GLP-1 analog for tx of T2 diabetes and for chronic weight management. Initial doses lower, but titrated max dose higher than other drugs
dietary supplement and fiber for weight loss
increase in soluble and insoluble fiber associated with weight loss
conjugated linoleic acid (CLA) for weight loss
no proof that it affect weight loss
hydroxycitrine for weight loss
supposedly inhibits lipid production, not proven for weight loss. Similar to ephedra (banned)
bitter orange/ country mallow for weight loss
called heartleaf, different source of ephedra (banned)
chromium for weight loss
promises to burn fat, side effects include headache, insomnia, altered cognition and perception
cortisol blockers for weight loss
ads claim they help by lowering “stress” hormone, but proof that they actually lower cortisol levels or cause weight loss
