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Dr. Shane Bradley
Psychopharmacology Outline Winter/Spring 2013
Drugs Used to Treat Anxiety
Benzodiazepines
Bind to type A aminobutyric acid (GABAA) receptor complex on the alpha subunit, which is known as the benzodiazepine (BZ) or
omega receptor. The GABAA complex is associated with neuronal chloride channels, and when benzodiazepines bind to their
receptors, increasing the affinity of GABA for its receptor site enhances the channel opening effect. This increases the frequency
of chloride-channel opening, creating a hyperpolarized cell membrane that prevents further excitation. From
https://secure.pharmacytimes.com/lessons/200306-01.asp
Indications/uses include anxiety d/o, panic d/o, mania, seizure d/o, phobias, insomnia, alcohol withdrawal, muscle spasm,
agitation, catatonia, akathisia, night terrors
Side effects
sedation, cognitive impairment, anterograde amnesia
respiratory depression at high doses or with alcohol
may worsen obstructive sleep apnea symptoms
disinhibition in susceptible individuals
Effect on sleep
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decrease in sleep latency, increase in sleep time, an increase in Stage 2 sleep, and a small decrease in delta and REM sleep
Diazepam- very long half life; excellent muscle relaxant
Chlordiazepoxide- very long half life; excellent for alcohol withdrawal
Clonazepam- long half life; also used in many forms of seizures
Estazolam- short to medium
Temazepam- short to medium
Oxazepam- short to medium
Alprazolam- short to medium
Lorazepam- medium
Midazolam- very short, operation pre-sedate, amnestic
Triazolam- very short
Antihistamine: Hydroxazine, very safe; side effects = anticholinergic at high doses
Diphenhydramine, very safe, side effects = anticholinergic at high doses
Unique mechanism of action: Buspirone
5-HT 1A (presynaptic) agonist. This effect decreased serotonergic tone in the dorsal raphe, which is COMPLETELY counterintuitive to what you
would expect from an anxiolytic. It also binds to dopamine type 2 (DA 2) receptors (presynaptic) as an antagonist, thereby increasing
dopaminergic tone. It also increase noradrenergic tone in the locus ceruleus.
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Considered less effective than benzodiazepines, but some studies show similar result. Considered particularly safe.
Alpha (2) adrenergic agonists
prazosin
prazosin found helpful in reducing PTSD related nightmares- evidence-based
Beta Blockers
propranolol (Inderal) is primary BB of choice in mental health.used for akathisia, lithium-induced tremor, performance
anxiety & aggressive behavior (hyperarousal) (other lipid soluble = pindolol, labetolol, metoprolol)
avoid in asthma, diabetes if patient is prone to hypoglycemia (especially if prone to hypoglycemia unawareness), bradycardia,
second or third degree heart blocks
Drugs Used to Promote Sleep
perspective: http://www.medscape.com/viewarticle/759336
Melatonin agonist:
Ramelteon Side effect note: generally safe, rare hyperprolactinemia, half life 2-5 hours/fx last 8
Specific Gaba 1A agonists
http://www.medscape.com/viewarticle/759336http://www.medscape.com/viewarticle/759336http://www.medscape.com/viewarticle/7593368/13/2019 Drug List Psychopharm
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Drugs Used to Improve Mood and/or Decrease Anxiety
SSRIS
Half-life
Short:paroxetine & fluvoxamine (
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Serum Hypotonic (< 275 mOsm/L)
Serum Sodium Falling (100 mOsm/L)
Urinary Sodium >30 mEq/L
Treatment
Fluid restriction
If Na < 120 mEq/L consider hypertonic saline to correct sodium (but no faster than 1
mEq/L/h) Intravenous urea Demeclocycline Lithium (rarely used)
Table from: http://openanesthesia.org/index.php?title=SIADH:_lab_findings
Serotonin syndrome (hi risks: SSRI +MAOI, SSRI + lithium, SSRI + TCA)
>> diarrhea, tremor, sweating, restlessness, hyperreflexia
progression of symptoms if untreated disorientation, rigidity, fever >> coma, seizures >> >> death (approximately 10%
mortality rate)
.Many medications/substances have serotonin activity:
dextromethorphan, fentanyl, meperidine, sumatriptan,
St Johns Wort, MDMA (ecstasy), LSD, many others
Consider total serotonergic load- Supplements (tryptophan, 5-HT), Herbs (St. Johns Wort),other antidepressants (venlafaxine, bupropion,
trazodone), other drugs with serotonergic effects (meperidine, dextromethorphan,and the triptans )
-------- In reality, usually only a problem with the pharmaceuticals.
NOTE on Drug-Drug Interaction and antidepressants
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000583/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000695/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000695/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000583/8/13/2019 Drug List Psychopharm
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SSRI levels tend not to be altered by other drugs but can potentially increase levels (inhibit metabolism) of certain drugs . The drugs
that are most likely to do this include: fluoxetine, fluvoxamine, paroxetine. Specific drug-drug interactions are less important than
knowing SSRIS may inhibit P450 pathways of drugs sensitive to/dependent on P450 metabolism
Paroxetine- especially strong level of evidence for PTSD, short half life can set stage for withdrawal
Sertraline
Fluoxetine- Numerous drug-drug interactions, very long half life prevents withdrawal
Citalopram
Escitalopram- understand this is the S-isomer, the more biologically active molecule
Fluvoxamine
Nefazodone- irreversible liver toxicity
SNRIS (mild elevations in blood pressure, hyperhidrosis, tachycardia, decreased appetite, headache, insomnia, delayed ejaculation)
Atomoxetine- used primarily for attention/ADHD
Duloxetine- extensive data in pain, FDA approved for fibromyalgia
Venlafaxine- most effective antidepressant; severe withdrawal syndrome (anxiety, nausea, restlessness, irritability, electric shock paresthesias,
fatigue, headache, dizziness)
Dexvenlafaxine- metabolite of venlafaxine, idea was to create better steady state concentrations at lower doses therefore more potency with
fewer side effects- hasnt really held up to scrutiny
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Tricyclics (SNDRI)
Pharmacologically promiscuous:
Muscarinic M1 receptor antagonism - anticholinergic effects including altered mental status/confusion, resting tachycardia, dry mucous
membraines, dilated pupils, dizziness, emesis, constipation, urinary retention, flushed/hot skin, emesis, fever
Histamine H1 receptor antagonism - sedation and weight gain
Adrenergic receptor antagonism(NE) - postural hypotension
Direct membrane effects - reduced seizure threshold, arrhythmia
Serotonin 5-HT2 receptor antagonism - weight gain (and reduced anxiety)
NE 5HT Ach Sed (hist) Comments
amitriptyline (Elavil) low high high high pain, migraine, anxiety
clomipramine (Anafranil) low high high high tx OCD; SSRI-like FDA approval OCD
desipramine (Norpramin) high low low low activating
doxepin (Sinequan). low low mod high used for insomnia; very antihistaminic- used for hives, FDA approval insomnia
imipramine (Tofranil). low low mod mod pain; enuresis FDA approval enuresis
nortriptyline (Pamelor).. mod low mod mod chronic pain
protriptyline (Vivactil) high low mod low least sedating
MAOI Inhibitors
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Inhibit degradation of monaomines (norepinephrine, serotonin, melatonin, dopamine).
Phenelzine, Isocarboxazid, Tranylcypromine: non selective (MAO-A and B) and irreversible (enzyme is permanently inhibited and its activity will
not be replaced until body makes more). These non-selective irreversible drugs create dangerous situations if dietary intake of certain amines is
high. Tyramine= hypertensive crisis; foods rich in tyramine include Foods containing considerable amounts of tyramine include meats that areaged, smoked, pickled, mostpork (exceptcuredham),chocolate;alcoholic beverages;and fermented foods, such as
mostcheeses (exceptricotta,cottage,cream),sour cream,yogurt,shrimp paste,soy sauce,soybean condiments, tofu,tempeh,miso
soup,sauerkraut,broad (fava) beans,green bean pods,snowpeas,avocados,bananas,pineapple,eggplants,figs,peanuts,Brazil nuts,yeast.
Levodopa= psychosis, agitation, nausea; from fava beans
Selegiline- selective for MAOI-B; no dietary concerns at lower doses; become less selective at higher doses
Unique mechanism:
L-methylfolate; probably completely safe; especially useful in folks with MTHFR insufficiencies secondary to mutation
L-methylfolate is the precursor to serotonin, norepinephrine, dopamine, that is able to cross BBB. MTHFR in the brain then begins process that
ultimately leads to production of these psychoactive amines.
Seehttp://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1938for nice article
Unique mechanism:
Bupropion
MOA: inhibition of presynaptic dopamine and norepinephrine reuptake transporters; Increased activity of vesicular monoamine transporter-2,
the transporter pumping dopamine and norepinephrine from the cytosol into presynaptic vesiclesFDA approved: smoking cessation (Zyban), Major Depression, Seasonal Affective Disorder
High Yield Facts:
Less sexual side effects (may actually help)
Less weight gain, may help with weight loss
Less likely to trigger mania than SSRIs
Doses over 300 mg associated with seizures
Unique mechanism:
http://en.wikipedia.org/wiki/Porkhttp://en.wikipedia.org/wiki/Curing_(food_preservation)http://en.wikipedia.org/wiki/Hamhttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Cheesehttp://en.wikipedia.org/wiki/Ricottahttp://en.wikipedia.org/wiki/Cottage_cheesehttp://en.wikipedia.org/wiki/Cream_cheesehttp://en.wikipedia.org/wiki/Sour_creamhttp://en.wikipedia.org/wiki/Yogurthttp://en.wikipedia.org/wiki/Shrimp_pastehttp://en.wikipedia.org/wiki/Soy_saucehttp://en.wikipedia.org/wiki/Soybeanhttp://en.wikipedia.org/wiki/Tofuhttp://en.wikipedia.org/wiki/Tempehhttp://en.wikipedia.org/wiki/Miso_souphttp://en.wikipedia.org/wiki/Miso_souphttp://en.wikipedia.org/wiki/Sauerkrauthttp://en.wikipedia.org/wiki/Vicia_fabahttp://en.wikipedia.org/wiki/Green_beanhttp://en.wikipedia.org/wiki/Snow_peahttp://en.wikipedia.org/wiki/Avocadohttp://en.wikipedia.org/wiki/Bananahttp://en.wikipedia.org/wiki/Pineapplehttp://en.wikipedia.org/wiki/Eggplanthttp://en.wikipedia.org/wiki/Ficushttp://en.wikipedia.org/wiki/Peanuthttp://en.wikipedia.org/wiki/Brazil_nuthttp://en.wikipedia.org/wiki/Yeasthttp://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1938http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1938http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1938http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1938http://en.wikipedia.org/wiki/Yeasthttp://en.wikipedia.org/wiki/Brazil_nuthttp://en.wikipedia.org/wiki/Peanuthttp://en.wikipedia.org/wiki/Ficushttp://en.wikipedia.org/wiki/Eggplanthttp://en.wikipedia.org/wiki/Pineapplehttp://en.wikipedia.org/wiki/Bananahttp://en.wikipedia.org/wiki/Avocadohttp://en.wikipedia.org/wiki/Snow_peahttp://en.wikipedia.org/wiki/Green_beanhttp://en.wikipedia.org/wiki/Vicia_fabahttp://en.wikipedia.org/wiki/Sauerkrauthttp://en.wikipedia.org/wiki/Miso_souphttp://en.wikipedia.org/wiki/Miso_souphttp://en.wikipedia.org/wiki/Tempehhttp://en.wikipedia.org/wiki/Tofuhttp://en.wikipedia.org/wiki/Soybeanhttp://en.wikipedia.org/wiki/Soy_saucehttp://en.wikipedia.org/wiki/Shrimp_pastehttp://en.wikipedia.org/wiki/Yogurthttp://en.wikipedia.org/wiki/Sour_creamhttp://en.wikipedia.org/wiki/Cream_cheesehttp://en.wikipedia.org/wiki/Cottage_cheesehttp://en.wikipedia.org/wiki/Ricottahttp://en.wikipedia.org/wiki/Cheesehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Hamhttp://en.wikipedia.org/wiki/Curing_(food_preservation)http://en.wikipedia.org/wiki/Pork8/13/2019 Drug List Psychopharm
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Trazodone (priapism, low blood pressure)
binds at 5-HT2 receptor---
--acts as a serotonin agonist at high doses and a serotonin antagonist at low doses
--inhibits serotonin reuptake, as SSRIs
--It weakly blocks presynaptic alpha2-adrenergic receptors and strongly inhibits postsynaptic alpha1 receptors
DOES NOT affect the reuptake of norepinephrine or dopamine within the CNS.
Unique mechanism:
Mirtazepine (somnolence, increased appetite)
MOA: 1. antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in
NE release. 2. Agonist/antagonist at multiple sites:
------Blocks alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT which increased activity at at 5-HT and 5-HT1
which decreases anxiety
-----weak antagonist at 5-HT1receptors and as a potent antagonist at 5-HT2(particularly subtypes 2A and 2C) and 5-HT3receptors.
What you need to know: increases activity at some 5-HT, decreases at others, resulting in decreased anxiety---very effective anxiolytic
Drugs Used to Treat Psychosis and Agitation
Mechanism: All block dopamine with various affinities
Typical Antipsychotics:1.Phenothiazines:
a. Aliphatic side chain: Chlorpromazine
b. Piperidine side chain: Thioridazine
c. Piperazine side chain: Trifluoperazine, Fluphenazine
2.Butyrophenones: Haloperidol
3.Thioxanthenes: Thiothixene
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4. Other heterocyclics: Pimozide, Loxapine
High potency: fluphenazine, trifluoperizine, thiothixene, haloperidol, pimozide
medium-low sedation, high EPS, low AC
FTTHP: five truly terrible harsh pills
Low potency: chlorpromazine, mesoridazine, thioridazine
medium-high sedation, low-medium EPS, high AC
MCT: medications creating tiredness
Medium potency:perphenazine, loxapine, molindone
low-medium sedation, high EPS, low-medium AC
MLP: moderately lethal pills
EPS: extrapyramidal symptomsAC: anticholinergic effects
ALL OF THESE ARE EXTRAPYRAMIDAL SYMPTOMS
Acute dystonia
sustained muscular contraction of neck, eyes, throat
generally occurs soon after starting medication
Akathisia
uncomfortable continuous motor restlessness can occur any time in treatment but generally in first week(s)
easily misdiagnosed as the underlying psychiatric disorder
Treat with Beta Blocker primarily propranolol (must be lipid soluble)
Parkinsonism
tremor, muscle stiffness, slowed movement, drooling, masked face
generally occurs beyond 1 week after starting medication
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Tardive dyskinesia (TD)
spastic facial distortions and tongue movements, rhythmic small movements
may extend to neck, trunk, and extremities
delayed effect, usually beyond 6 months from starting medication
risk increases with duration of exposure to antipsychotic, lithium, age, other neurological diagnosis
known to occur without antipsychotic therapy
may be permanent, occur on discontinuation or resolve on own
Neuroleptic malignant syndrome (NMS)
pipe-like rigidity, fever, tremor, altered level of consciousness
hypotension, tachycardia
laboratory abnormalities- elevated WBC & CK
mortality 10-20%
can occur any time in course of treatment
SPECTRUM
Also, Anticholinergic effects (NOT EPS)
dry mouth, blurred vision, constipation, urinary retention, mydriasis (dilated pupils)
AND
Hyperlipidemia, weight gain, impaired glucose tolerance/diabetes
Haloperidol- treatment of choice for delirium, agitation
Chlorpromazineheavily sedating; approved for use in children
ThioridazineBlack Box QTc prolongation
Loxapine
Molindone
PerphenazineCATIE trial supported equivalent to atypicals
http://en.wikipedia.org/wiki/Chlorpromazinehttp://en.wikipedia.org/wiki/Thioridazinehttp://en.wikipedia.org/wiki/Loxapinehttp://en.wikipedia.org/wiki/Molindonehttp://en.wikipedia.org/wiki/Perphenazinehttp://en.wikipedia.org/wiki/Perphenazinehttp://en.wikipedia.org/wiki/Molindonehttp://en.wikipedia.org/wiki/Loxapinehttp://en.wikipedia.org/wiki/Thioridazinehttp://en.wikipedia.org/wiki/Chlorpromazine8/13/2019 Drug List Psychopharm
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Thiothixene
Trifluoperazine
Fluphenazine
Prochlorperazine
Pimozide- approved for Tourettes
Atypical neuroleptics/antipsychotics: Dopamine blockade AND Serotonin blockade. Serotonin is like a brake to dopamine.
When you block dopamine, there are side effects from that blockade. BUT, when you also block receptor activity that is itself
braking dopamine, you ameliorate those effects.
Also used for:
schizophrenia and other psychotic disorders
acute bipolar mania & maintenance
augmentation of antidepressants & mood stabilizers
aggression & impulsivity
Risperidone- approved for aggression in autism, like typicals at high doses
Olanzapine- high likely diabetes/elevated lipids
Clozapine- agranulocytosis, seizure risks, diabetes/elevated lipids
Quetiapine- very low EPS risk
Asenapine
Ziprasidone- QTC prolongation
http://en.wikipedia.org/wiki/Thiothixenehttp://en.wikipedia.org/wiki/Trifluoperazinehttp://en.wikipedia.org/wiki/Fluphenazinehttp://en.wikipedia.org/wiki/Prochlorperazinehttp://en.wikipedia.org/wiki/Prochlorperazinehttp://en.wikipedia.org/wiki/Fluphenazinehttp://en.wikipedia.org/wiki/Trifluoperazinehttp://en.wikipedia.org/wiki/Thiothixene8/13/2019 Drug List Psychopharm
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Iloperidone
Lurasidone- may have less propensity for negative effects on cognition
Aripiprazole- nausea, akithisia common side effects; other EPS very rare; DIFFERENT mechanism, sort of- works as partial agonist/antagonist,
potentially titrating its own dopamine blockade
Drugs Used to treat extrapyramidal symptoms
Anticholinergics All these treat extrapyramidal symptoms (EPS):
tremor, stiffness, drooling, dystonias
akathisia may not respond to ACs
tardive dyskinesia usually little response to ACs
Side effects all anticholinergic: fever, hot/flushed skin, constipation, blurred vision, urinary retention, dry mucous membranes
benztropine (Cogentin) M1 muscarinic acetylcholine receptor antagonist
least sedating, most commonly used
trihexyphenidyl (Artane): M1 muscarinic acetylcholine receptor antagonist
diphenhydramine (Benadryl) (antihistamine)
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Drugs Used to Improve Attention
Stimulants-
Side effects for stimulants are all the same = agitation/aggression, tics, tremors, seizures, increased adrenergic tone: tachycardia/blood pressure,sweating, mood swings, hyperthermia, psychosis
Amphetamines- block reuptake of norepinephrine and dopamine- when binding to presynaptic receptors, actually turn reuptake channels into
releasing channels
Dextroamphetamine
Levoamphetamine/Dextroamphetamine- mixed salts; contains both isomers
Lisdexamphetamine- prodrug; turns into dextroamphetamine upon cleavage of lysine; very long acting/smoother pharmacokinetic/dynamiccurves = less abuse potential
Methylphenidate- blocks reuptake of norepinephrine and dopamine
Dexmethylphenidate-dextrorotatory enantiomer ofmethylphenidate
Drugs Used to Promote Wakefulness
Unique mechanism of action: Modafinil
http://en.wikipedia.org/wiki/Dextrorotatoryhttp://en.wikipedia.org/wiki/Methylphenidatehttp://en.wikipedia.org/wiki/Methylphenidatehttp://en.wikipedia.org/wiki/Dextrorotatory8/13/2019 Drug List Psychopharm
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Valproic Acid--- blocks high-frequency, repetitive neuronal firing by blocking voltage-dependent sodium channels, augment the action
of GAD (glutamic acid decarboxylase), a GABA-synthesizing enzyme, restricts GABA-T (GABA transaminase), an enzyme that speeds the
degradation of GABA.
can be dosed rapidly to treat acute mania
more effective than lithium in rapid cycling & mixed states
approved for migraine prophylaxis
serum levels can be helpful in guiding dosing, 70-100
nausea, weight gain, unsteadiness (ataxia), hair loss, tremor
liver dysfunction, decreased platelets (thrombocytopenia)
pancreatitis (rare but potentially serious)
polycystic ovary disease per reports
ammonia levels can be increased particularly in those rare individuals with genetic metabolic deficits
Carbamazepine.stabilizes the inactivated state ofVoltage-gated sodium channels,making fewer of these channels available to subsequently
openthe affected cells are less excitable untilthe drug dissociates.
GI: nausea, constipation, diarrhea, appetite loss
CNS: sedation, dizziness, unsteadiness, confusion
benign rashes common, catastrophic rashes rareStevens Johnson Syndrome- severe exfoliative erythematous rash with
systemic inflammation
many possible serious abnormalities in CBC- DECREASES..agranulocytosis
http://en.wikipedia.org/wiki/Voltage-gated_sodium_channelhttp://en.wikipedia.org/wiki/Voltage-gated_sodium_channelhttp://en.wikipedia.org/wiki/Voltage-gated_sodium_channel8/13/2019 Drug List Psychopharm
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may reduce sodium levels (hyponatremia)
liver function abnormalities rare but possible
used in acute mania and bipolar maintenance..effectiveness within two weeks
more effective than lithium in rapid cycling & mixed states, less effective in bipolar related depression
serum levels to guide dosing, 4-12 mcg/ml
multiple significant drug-drug interactions (DDI) affecting both other medications (reducing their levels) & other medications
affecting it (increasing carbamazepine levels)
induces its own metabolism so may need to adjust dose over several weeks, half life decreases to 12-17 hours
DECREASES levels of OCPs, tricyclics, prednisone, Coumadin; fluoxetine, diltiazem, verapamil, erythromycin all INCREASE levels
of carbamazepine\
Oxcarbazepine
Does not have the enzyme-inducing effects of carbamazepine
tolerated better
Less drug-drug interactions
Hyponatremia, dizziness, ataxias, less blood dyscrasias
Lithium
Lithium has been found to decrease the activity and function of the Na+/K+/-ATPase pump in the CNS and especially in the
hippocampus.
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Lithium induced ADP ribosylation of the Gi G protein (therefore inactive).. increases basal levels of CAMP.at the same time, lithium
attenuates receptor-mediated activation of Adenylate Cyclase (AC) through a reduction in Gs subunit coupling. This results in a decrease
in the peak levels of stimulus induced CAMP. ?BALANCING EFFECT
rats....reduced levels of arachidonic acid and its products, which can contribute to inflammation AND increased levels of a metabolite
called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is
the precursor to a wide range of anti-inflammatory compounds known as docosanoids.
Lithium- features
Only mood stabilizer without significant anticonvulsant properties
up to 70% response rate
demonstrated effectiveness in reducing suicidality
less effective in rapid cycling and mixed bipolar states
serum levels guide dosing; above 1.3 toxic .7-1.2 therapeutic; above 3.5 dialyze
lab draw 8-12 hrs after last dose
excreted through the kidneys
minimal liver mediated drug-drug interactions (but see next slide for other medication issues)
Lithium- side effects
fine tremor, weight gain, nausea
increased thirst and urination
more severe toxicities include coarse tremor, gait instability, vomiting, diarrhea, confusion
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increased risk of toxicity with fluid or salt restriction, hot weather/sweating, use of anti-inflammatory drugs, ace inhibitors &
angiotensin receptor blockers, diuretics
may cause kidney and thyroid dysfunction so regular monitoring of creatinine, BUN and TSH are necessary
females /kids are at much greater risk of lithium related thyroid dysfunction
Lamotrigine----Inhibits voltage-dependent sodium channels, resulting in decreased release of theexcitatoryneurotransmitters glutamate and
aspartate.these act on NMDA receptors
Minimally sedating unlike most other mood stabilizers
Appears to be especially effective in bipolar depression.
Early use as an anticonvulsant in children raised concerns about potentially life-threatening rash (Stevens-Johnson syndrome
=toxic epidermal necrolysis).
Levetiracetam----binds to SV2A (synaptic vesicle protein 2A)..which is thought to.block conduction propagation (may also be from influences
on presynaptic calcium channels)
Topiramate--blockage of voltage-dependent sodium channels, augmentation of gamma-aminobutyrate acid activity at receptor, antagonism of
AMPA/kainate subtype at glutamate binding sites
Side effects: weight loss, cognitive dulling, kidney stones, metabolic acidosis, at moderate to high doses makes oral contraceptives ineffective
FDA Approved for MANIA
Aripiprazole
Carbamazepine
Chlorpromazine
Divalproex
Lithium
Olanzapine
Quetiapine
Risperidone
Ziprasidone
FDA Approved for Bipolar Maintenance
http://professionals.epilepsy.com/page/table_9steps_mechanism.htmlhttp://professionals.epilepsy.com/page/table_9steps_mechanism.htmlhttp://professionals.epilepsy.com/page/table_9steps_mechanism.htmlhttp://professionals.epilepsy.com/page/table_9steps_mechanism.html8/13/2019 Drug List Psychopharm
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Lithium, Ziprasidone, Quetiapine, Risperidone, Aripiprazole, Olanzapine, Lamotrigine
Drugs Used to Treat DementiaUnique mechanism of action: Memantine (Namenda) ; moderate to severe
Blocks the toxic effects associated with excess glutamate and regulates glutamate activation- thought to block flow of current
through channels of N-methyl-d-aspartate (NMDA) receptors; may have more broad psychiatric application
Well done study supported some help in severe dementia
May be of more benefit in vascular dementia
Actylcholinesterase inhibitors
GI side effects are very common. Also insomnia. Rare but serious side effects include GI bleed. Benefits are modest. Thorough examination of
data suggests slowing of loss versus significant improvement.
donepezil (Aricept); approved for mild, moderate, and severe; minimal side effects
galantamine (Reminyl); mild to moderate; also stimulates nicotinic receptors
rivastigmine (Exelon); mild to moderate
tacrine (Cognex) not used due to liver toxicity
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Drugs Used to Treat Substance Abuse
buprenorphine/naloxone (Suboxone)
treatment for opioid dependence
diminishes cravings, evidence-based for maintenance of sobriety from opioids
contains both an agonist & antagonist----Buprenorphine: partial agonist activity at mu-opioid receptors, binds tightly and
prevents agonism of opioids Naloxone: antagonist; Naloxone was added to Suboxone in an effort to dissuade patients from
injecting the tablets---can trigger withdrawal, short half-life , attenuate any euphoria and abuse potential
naltrexone (ReVia)
opioid antagonist, longer half life and active metabolite makes it useful for treatment
Can trigger withdrawal if opioid dependent and using in last 7-10 days
Evidence for ETOH abstinence maintenancein combination with psychotherapy
Rationale for opioid abstinence but no data to support
potential liver toxicity
disulfiram (Antabuse) for ETOH abuse
deterrentmakes you sick
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