Antidepressant and Antimanic drugs Flashcards
what is the mechanisms of antidepressants
NE and 5-HT signalling
Most effective antidepressants maintain NE and or 5-HT signlat (Block metabolism (MAOI), or block reuptake (TCA, SSRI
what is the mechanism of antimanics
reduce neuronal activity
What are the types of Anti-depressants
MAOIs
TCAs
SSRIs
SSNRIs
NDRIs
Alpha-2 receptor anatagonists
What are MAOIs
monoamine oxidase inhibitors
phenylzine and Selegiline
what are TCAs
tricyclic antidepressants
Amitriptyline
imipramine
what are SSRIS
selective serotonin reuptake inhibitors
fluoxetine
citalopram
sertraline
paroxetine
esctalopram
what are SSNRIs
Serotonin-NE reuptake inhibitors
venlafaxine
duloxetine
desvenlafaxine
levomilnacipran
what are NDRIs
NE-DA reuptake
Bupropoin(wellbutrin)
whare are alpha-2 receptor antagonists
mirtazapine
What are MAOI MOA
associated with mitochondria in neurons and glial cells
MAO A is more common than MAO B
antidepressant MAOIs are irreversible and nonselective MAO inhibitors affecting NE, 5-HT and DA
what are the adverse effects of MAOIs
interactions with foods and other drugs - tyramine and sympathomimetic drugs
weight gain
orthostatic hypotension
insomnia
hepatotoxicity (phenelzine)
sexual dysfunction
Narrow therapeutic index
What are Tyramine containing foods
aged cheese
draft beer
dried/aged foods
smoked foods
tofu
what drug interactions do MAOIs have
sympathomimetics: ephedrine, amphetamine (hypertensive crisis)
Antidepressants: re-uptake inhibitors (hypertensive crisis and Serotonin syndrome)
What is TCAs MOA
SERT (5-HT re-uptake transporter) blocker
NET (NE transporter) blocker
results in enhanced NE and 5-HT signaling - alpha 1 and 5-HT1
what are TCA adverse effects
H1R blocker: drowsiness, sedation, weight gain
MAchR blocker: blurred vision, dry mouth, constipation, urinary retention, tachycardia, cognitive dysfunction
alpha 1 and 2 AR partial blocks: postural hypotension, dizziness, relfex tachycardia
Na+ channel block: cardiac conduction delays -HIGHLY DANGEROUS IN OVERDOSE
narrow TI
What are the tertiary amines
Amitriptyline and Imipramine
metabolized by CYP450 demethylation
What are TCA drug interactions
other antidepressants
Cardiovascular drugs (Na+ channel blockers)
antimuscarinic drugs
CYP450 interactions
What are the MOA for SSRIs
What are the adverse effects of SSRI medicatiosn
GI disturbances
long-term weight gain
anxierty, agitation, insomnia, suicidal throughts
headache
sweating
sexual dysfunction
“black box” warning for use in children/adolescents for increased suicidal thoughts
Serotonin syndrome
what type of SSRI has the lowest risk in children
fluoxetine (prozac)
what medication are people switched to who are affected by SSRI sexual dysfunction
Bupropoin (wellbutrin) for decreased libido
what is serotonin syndrome symptoms
hyperreflexia
CNS excitation
mental state: anxiety/agitation
autonomic excitation: hypertension, hyperthermia
what is the treatment of Serotonin syndrome
Benzodiazepine - sedation
cyproheptadine (first get anti-histamine with serotonin antagonistic properties)
when is serotonin syndrome most often seen
over dose or drug combination of SSRI with MAOI
What the the most common side effects of SNRIs
nausea
what is high doses of SNRIs associated wtih
treatment emergent hypertension - do not give to CAD
what is venlafaxine used for
Major depression,
GAD,
panic disorders,
social phobias
what is duloxetine used for
major depression
GAD
pain relieving drug for
diabetic peripheral neuropathy
fibormyalgia
MSK pain
OA
what is the only antidepressant medication available without direct serotonergic effects
Bupropion (wellbutrin)
what is Bupropoin used to treat
depression and nicotine dependence
what is a side effects of Bupropion
anxiety
why is Trazodone not commonly used in full antidepressant doses
too sedating for most patients to tolerate in full antidepressant doses
what is trazodone used for in lower doses
hypnotic
what is Nafazodone
generally very well tolerated among patients with depression, anxiety and insomnia BUT “black bock” warning for hepatotoxicity
what is mirtazapine
unique (pre-synpatic) MOA
increase release of EN and 5-HT
less Nausea and sexual dysfunction
also has anti-histamine effect causing sedation
weight gain is often a significant problem
what types are medications used to treat anxiety disorders
SSRI, SNRI, TCAs, MAOI, SSRIs
what drugs are used for insomnia + depression
trazodone, mirtazapine
what are drugs used for pain syndromes
TCAs, SNRIs
what drugs are used for ADD
Bupropion
what drugs are used for eating disorders
SSRIs, Mirtazapine
what medication is used for nicotine dependence
Bupropion (wellbutrin)
what are important antimanic drugs
lithium
anticonvulsants
atypical antipsychotics
what are anticonvulsants used for antimanic management
carbamazepine
lamotrigine
valproic acid
what are atypical antipsychotics used for antimanic management
quetiapine
risperidone
what are mood stabilizers used for
bipolar disorder
acute mania
acute dpression
mixed bipolar sates
prophylaxis against manic recurrence
prophylaxis against depressive recurrence
what are the classes of mood stabilizers
Class A: stabilize from ABOVE baseline - anti-manic without causing depression
Class B: stabilize from BELOW baseline - antidepressant without precipitating/accelerating mania
what is lithium used for
efficacy in bipolar disorder
best for prophylaxis against manic recurrence
can be used in acute manic states
poorest for acute depression, mixed states
what is the MOA of Lithium
blocks recyling of inositol phosphates
thus, signaling Gq coupled receptors is desensitized
what are the AE of Lithium
pass through BBB and can pass to unborn fetus and milk of nursing mothers
renal effects
tremor
weight gain
hypothyroidism - TSH needs to be checked
V/D, ataxia, come - intoxication
Drug interactions with antidepressants and diuretics
what are anticonvulsants to treat
mania and seizures
What are antiolytic medications used
GABA modulators
Non-Benzodiapepine - GABA - agonist Hypnotics
Non-GABA anxiolytics
what are GABA modulators used for anxiety
Benzodiazepines
(diazepam, clonazepam, lorazepam, temazepam)
what is a benzodiazepine antagonists
flumazenil
what are non-benzodiazepine GABA-agonist hypnotic
Zolpeidem
what are NON-GABA anxiolytics
antidepressants (TCA, MAOI, SSRI)
Trazadone
Mirtazapine
Buspirone
Propranolol
what is GAD
generalized anxiety disorder
general symptoms of motor tension, autonomic hyperactivity for atleast one month
what type of medications may induce anxiety
stimulants
nasal decongestants/asthma treatments
dopaminergic
or drug withdrawal
when are benzodiazepines used
acute anxiety
short term treatment
while waiting for longer-term preventatives to become fully active
or as an adjunct to preventative treatment when needed
what are barbitates used for
historical treatment of anxiety, insomnia and is still used in epilepsy and anesthesia induction
what is the best option for fast relief of panic attack
Benzodiazepine
why do we use caution in long-term use of Benzodiazepines?
concerns for tolerance, dependence and abuse
what are important Benzodiazepines
diazepam
clonazepam
alprazolam
lorazepam
temazepam
what are the therapeutic uses of Benzodiazepine
anxiety attacks
insomnia
agitation
alcohol withdrawal
sedation for variety of procedures and anesthetic induction
status epilepticus and some epilepsy
post-injury muscle tension
what are the adverse effects of Benzodiazepine
sedation (unless desired)
ataxia/falls (elderly concern)
impaired motor performance (driving)
impaired cognition/confusion (not good for test anxiety)
anterograde amnesia (short half-life)
disinhibition of impulses
relatively safe in overdose
how do we treat benzodiazepine overdoses
flumazenil - benzodiazepine receptor antagonists
what medications are flumazenil not effective against
barbiturate overdose
what are controversies with benzodiazepines
tolerance
withdrawal
abuse and dependence
what are the fast onset benzodiazepines
diazepam and temazepam
what are slow onset benzodiazepine
clonazepam
what are intermediate onset benzodiazepines
alprazolam and lorazepam
what is Buspirone
NON-GABA anxioloytic
non-sedating anxiolytic
effective only with chronic use
partial agonist at pre- and post-synaptic 5-HT1A receptors - some antagonist activity at D2 receptors
show some antidepressant and antipsychotic activities
what are the pharmacokinetics of buspirone
rapidly absorbed orally
extensively hepatic metabolism to form several active metabolytes
well tolerated by elderly but may have low clearance
what are the adverse effects of buspirone
Dizziness, headache, GI upset
combo with MAOIs can cause tachycardia and hypertension
what is propranolol
Beta adrenoreceptor antagonist
decreases sympathetic overactivity
decreased HR and BP
used for performance anxiety
what medications treat GAD
SSRI, SNRI, Buspirone, Benzodiazepine
what medicatiosn treat phobic anxiety
benzodiazepines
TCA and MAOI
what medications treat panic disorders
benzodiazepines
TCA and MAOI
what medications treat OCD
SSRI
what medications treat PTSD
SSRI, buspirone
what medication treats performance anxiety
propranolol
what medication treats sedation
benzodiazepines
what medications reduce REM sleep and NREM sleep
Benzodiazepines and Barbiturates
how quickly does hypnotic medication tolerance occur
tolerance occurs within 1-2 weeks
what is a short acting benzodiazepine used for sleep
Temazepam
what is temazepam used for
fast acting but used to decrease sleep latency
short term use - not a treatment for chronic insomnia
what non-benzodiazepine hypnotics are used for sleep
zolpidem, eszoplicone, zaleplon
they are agnoists that bind similar to benzodiazepines, but to only a subset of GABAa receptors that are associated with sleep
produce pure sedation
what are the adverse effects of Zolpidem/eszoplicone
safety: high therapeutic index unless combined with other CNS depressants
can cause daytime drowsiness
concerns for complex sleep behaviors (sleep walking/driving)
can exaggerate the deleterious hypoxic effects of obstructive sleep apnes
abuse potential
what are the pharmacokinetics of zolpidem/eszoplicone
readily absorbed orally
short elimination half-life
metabolized by CYP450 oxidation - may have interaction with drugs that use/affect these enzymes
what are other drugs with hypnotic activity
antihistamine: diphenhydramine
hypnotic antidepressants: doxepin (TCA), trazodone(5-HT2 antagonist), Mirtazepine (SNRI with antihistamine effects)
what is the only antidepressant FDA approve for insomnia
Doxepin (TCA)
what are first generation antipsychotic drugs
classical D2 antagnoists
what are second generation antipsychotic drugs
atypical antipsychotics
what is the treatment for neuroleptic malignant syndrome
bromocriptine
what are the classical D2 antipsychotic antagonists
haloperidol
what are the atypical antipsychotics
risperidone
olanzapine
clozapine
quetiapine
aripiprazole
what are characteristics of schizophrenia
Positive symptoms: disordered thinking, delusions, paranoia, hallucinations(esp. auditory)
Negative symptoms: emotional withdrawal, depression
what are adverse effects of D2 antagonists
acute dystonic reactions
parkinsonian symptoms (tremor or rigidity)
akathisia (restlessness)
hyperprolactinemia
what are side effects of Haloperidol
sedation: early onset, tolerance
hypotension
extrapyramidal effects: tremor, akinesia, akithesia, tardive dyskinesia, neuroleptic malignant syndrome
what is Tardive dyskinesia
looks like someone is always chewing something
what is neuroleptic malignant syndrome
hyperpyrexia (101-107 degrees)
autonomic instability
confusion, altered sensorium
elevated creatinine kinase levels from muscle breakdown
renal failure due to myoglobinuria
what increases the risk of neuroleptic malignant syndrome
higher likelihood with 2 or more concomitant antipsychotics
what is the treatment of neuroleptic malignant syndrome
often in ICU
aggressive IV hydration and diuresis
discontinuation of the offending medications
IV BROMOCRIPTINE
dantrolene sodium for intractable hyperpyrexia
what is Risperidone
blocks D2=5-HT2 (better for negative symtpoms)
high potency
few side effects: still have risk for extrapyramidal side effects but lower than haloperidol
what is Clozapine
blocks D4=5-HT2
low potency
effective against both positive and negative symptoms
very low risk of extrapyramidal effects
what does clozapine increase risk of
agranulocytosis, so often reserved for patients with extrapyramidal effects of haloperidol
what is Quetiapine
antagonist to D1, D2, 5-HT1A and 5-HT2
similar effectiveness as Risperidone with less chance of motor side effects
Side effects: very sedating, other D2-related side effects
choice in psychotic patients suffering from sleep disorders
at is Olanzapine
properties similar to Quetiapine, with slightly more effectivness, but also more intense side effects
what are difficulties in treating schizophrenia
family/community support and psychotherapy are essential
compliance is a problem: side effects and paranoid delusions of poisoning is common
what is an opiate
drugs derived from opium
ex. morphine, heroin, codeine
what is an opioid
substances that have morphine-like activity and act on opioid receptors
what are the kinds of opioids
natural, endogenous opioid peptides and synthetic
what is the MOA of opioids
opens K+ channel, blocks Ca2+ channels, receptor coupled to Gi = decrease in cAMP, leads to hyper-polarization and inactivation of neuron
what are the CNS effects of opioids
analgesia, drowsiness, change in pain reaction, euphoria, cough suppression
what are the side effects of opioids
N/V constipation, itching, respiratory suppression
what is codeine
pro-drug
converted to morphine in the liver by CYP450
need for metabolism causes “ceiling effect”
patients who do not express much CYP2D will not have effectiveness
CYP2D blocked by antidepressant SSRIs, so codeine is not effective
less potent than morphine
oral
analgesic, antitussive, antidiarrheal
what is the choice of opioids for inpatient chronic pain patients
morphine (2 Hour t1/2)
what is the choice of opioids for outpatient chronic pain
long acting opioid
methadone or time-release oxycodone (15-40h T1/2)
what is the opioid for acute short-term pain
rapid onset, short-acting
codeine or oxycodone (2-6 hours t1/2)
what is the opioid for general anesthesia
potent
short acting
Fentanyl (2-4 h t1/2)
what opioids are metabolized by CYP3A
methadone, oxycodone and fentanyl
what opioids are metabolized by CYP2D
codeine (low in some patients)
how is morphine metabolized
by glucouronidation
FIRST PASS EFFECT leads to low oral availability
advantage: low drug interactions
what are opioid drug interactiosn
other opioids
other CNS depressants (anxiolytics and hypnotics)
Antidepressants (TCA and MAOI)
antipsychotics
CYP inhibitors for orally active opioids
what opioids are common in avuse
heroin
fentanyl
oxycontin
what is methadone
synthetic derivative of morphine
orally active, long acting
less euphoria
used in the treatment of addiction
what is buprenophine
partial agonist/antagonist
slow onset of action, slow departure from receptors
reduces craving and blocks effects of heroin
what are the symptoms of opioid overdose
stupor, coma
pinpoint pupils (miosis)
depressed respiration
needle marks
what is dextromethorphan
centrally acting cough suppressant
d isomer of morphine derivative
no analgesia or addictive properties unless severaly abused
what is loperimide
Imodium
methadone skeleton
phenylpiperidine moiety
achieves antidiarrheal activity
cannot cross BBB
