pharm_psych_seiz_dem

DESIPRAMINE -- NE RI

IMIPRAMINE -- NE/5-HT RI

CLOMIPRAMINE -- NE/5-HT RI

"SOME Pts CAN FEEL FINE EVENTUALLY"

Sertraline

Paroxetine

Citalopram

Fluoxetine

Fluvoxamine

Escitalopram

mirtazapine --a2 rec antag

duloxetine -- 5ht/ne reuptake inh

venlafaxine -- low dose 5ht, high 5ht/ne ri

bupropion -- inh da uptake

NON TCA/SSRI (OTHER) DRUGS FOR DEPRESSION Tx

alpha 2 receptor antagonist = inc NE release

also blocks H1 and 5HT2 receptors = ↑weight

NON TCA/SSRI (OTHER) DRUGS FOR DEPRESSION Tx

Low dose = 5HT reuptake inhibitor

Higher dose = 5HT/NE reuptake inhibitor

NON TCA/SSRI (OTHER) DRUGS FOR DEPRESSION Tx

5HT/NE reuptake inhibitor

NON TCA/SSRI (OTHER) DRUGS FOR DEPRESSION Tx

affects DA uptake

PHENELZINE

irreversible inhibitor of MAO

must inh monoamine oxidase A!!! B/c MAO-A in brain is what breaks down NE/5-HT.

MAO-B breaks down DA.

MUSCARINIC

H1 HISTAMINE

a1 ADRENERGIC

CV

CNS

1. Dry mouth

2. Urinary retention

3. Constipation

4. Blurred vision

5. Memory impairment

6. Sexual dysfunction

7. (Tachycardia)

SEDATION

WEIGHT GAIN

ORTHOSTATIC HYPOTENSION

SEXUAL DYSFUNCTION

1. Tachycardia (anticholinergic)

2. Changes in cardiac conduction

· Normal ♥ pts: not clin signf

• · Most signf ECG changes:
• ---- Inversion or flattening of T waves

---- Incr PR interval (b/c incr intraventr conductn time)

· *Pts w/ pre-exist ♥ condtn: Incr risk of AV block

· *Overdose: severe arrhythmias

3. *Orthostatic hypotension

1. Fine, rapid tremors of extremities or ataxia (esp in elderly on high doses)

2. Manic episodes in bipolar pts

3. Lower seizure threshold: incr risk of tonic-clonic seizures

• HEPATIC TOX
• CNS
• CV
• FOOD/DRUG INTERACTIONS
• ---------------

• CNS effects (~sx of excessive stim)
• · Tremors
• · Insomnia
• · Agitation
• · Poss hypomanic or manic rxn in bipolar pts
• ----------------------

• CV effects:
• · Orthostatic hypotension b/c:
• ----Incr stim of central α2, or
• ----Accum of false transmitter “octopamine” in periph symp neurons
• ------------------------

• Food/Drug interxns: “Cheese Rxn”
• · Ingest indirectly acting sympathomim amines (e.g. in OTC decongestants) → poss hypertensive crisis

· e.g. Tyramine* not broken down by MAOA at GI → enters circ → release > nL amts of stored NE → incr BP)

1. *N/V (5-HT3)

2. *Sexual dysfunction (5-HT2): anorgasmia, ejac disturbance (b/c enhanced 5-HT transmission)

3. Late-developing weight gain* (satiation/weight loss: 5-HT2C & 5-HT1B)

4. Anxiety, insomnia, agitation (5-HT2)

5. NO risk of HTN crisis b/c no inhb MAO

6. *NO anticholinergic S/E

7. NO effects on ♥ conduction system

• 8. *NO orthostatic hypotension
• --------------------

SSRIs produce less serious S/Es than TCAs & MAOIs and are better tolerated.

Stim of 5HT3 receptors by serotonin dec appetite & causes N/V

--SSRIs --> ↑5HT in synapse --> dec weight, dec N/V

--S/Es dissipate after several weeks

"BZs help you Calm Down A LOT"

Alprazolam

Clonazepam

Diazepam

Lorazepam

Oxazepam

• Triazolam
• ---------------------

INC Cl- CONDUCTANCE BY ALLOSTERIC ACTION ON GABA-A CHANNELS --> HYPERPOL NEURONS

METABOLITE OF MOST BZs

CONJUGATED w GLUCARONIC ACID TO EXCRETE

NOT METABOLIZED BY OXIDATION

USED IN ELDERLY AS OXIDATION IS SLOWED

• 1. Sedative-hypnotic:
• -- Decr dur of stage 1, 3/4 & REM
• -- Latency to persistent sleep
• -- Incr stage 2 & total sleep time

2. Anti-anxiety (inhb of suppressive effects of punishment)

3. Anti-convulsant

• 4. Muscle relaxant effects
• (at spinal cord level)

• 5. Anterograde amnesia
• (surgery)

1. Sedation

2. Dizziness

3. Uncoordination

4. Paradoxical agitation

5. Impairment of cognitive func

6. Minimal suicide potential. BUT combo w/ ETOH (or other CNS depressant) → incr suicide potential

7. Little organ toxicity

• 8. Minimal capacity to induce hepatic enz
• --------------------------

POTENTIAL FOR ABUSE, DEPENDENCE & WITHDRAWAL

• ***Withdrawal rxn
• (esp w/ high doses of alprazolam)

o Can occur even at clinical doses

o Mostly in pts taking high doses or taking BZ for > 8 months

“Flu-like” sx:

1. Musc cramps

2. Diarrhea

3. Abdominal discomfort

4. Seizures (rare) more freq in drugs w/ shorter t1/2 (esp w/ high doses of alprazolam)

Prevent withdrawal → slowly taper dose

CLOMIPRAMINE -- REUPTAKE INH

5HT > NE

ZOLPIDEM (ambien)

ZALEPLON (sonata)

• ESZOPICLONE (lunestra)
• ----------------------

ACT THROUGH GABA-A RECEPTOR (BZ1 RECEPTOR AGONIST)

Less abuse potential (not addicting) → No Withdrawal Symptoms

• No ETOH potentiation of depression
• (DO NOT take ETOH w/ BZ).

NOT anxiolytic.

NOT anticonvulsant.

No skeletal relaxation.

Soporific (induce sleep)

Sedative - hypnotic

• Cause AMNESIA. (Get up & drive in the
• middle of the night)

• For pt w/ a hx/fam hx of barbiturate abuse who cannot sleep.
• -------------------------

ZOLPIDEM (ambien)

ZALEPLON (sonata)

ESZOPICLONE (lunestra)

HELPS WITH ONSET OF SLEEP

melatonin (MT) receptor agonist

Soporific

MT-1 & MT-2 RECEPTORS OF SUPRACHIASMATIC NUC OF HYPOTHALAMUS

• SIDE EFFECTS
• --HEADACHE
• --DROWSINESS
• --DIZZYNESS

NO ABUSE POTENTIAL

BZ RECEPTOR ANTAGONIST

• Rapidly reverses effects of BZ
• (for BZ overdose or outpatient surgery)

LIMITED USE DUE TO SHORT HALF LIFE

NON BZ ANTI-ANXIETY AGENT

SLOWER ONSET OF ACTION THAN BZ (4-8 WEEKS)

MINIMAL WITHDRAWAL POTENTIAL

• S/E
• -- DIZZINESS & NAUSEA
• -- NO ALC INTERACTION

MOA -- DIRECT ACTIVATION OF 5-HT RECEPTORS (prob 5ht-1a)

INC K+ CONDUCTION --> HYPERPOL NEURONS

• BZ
• SSRI
• VENLAFAXINE
• BUSPIRONE

• SSRI
• BZ
• TCA

• CLOMIPRAMINE
• SSRI

• NEED TO INC 5-HT
• ----------------------

• CLOMIPRAMINE
• --DERIVATIVE OF IMIPRAMINE
• --POTENT 5-HT REUPTAKE INH (UNLIKE OTHER TCAs)
• --NE REUPTAKE INH

SSRI

SSRI

ETHOSUXIMIDE

if can't tolerate -- LAMOTRIGINE

TONIC-CLONIC

• VALPROATE
• LAMOTIGINE

• CARBAMAZEPINE
• PHENYTOIN

BRIEF LOSS OF AWARENESS

EYE BLINKING

LIP SMACKING

• NO LOSS OF CONSCIOUSNESS OR
• BODY TONE

ALMOST ALWAYS SEEN IN YOUNG CHILDREN

PROLONG Na CHANNEL INACTIVATION

(same as phenytoin, ethotoin, carbamazepine)

1. Gingival hyperplasia

2. Hirsutism

3. Osteomalacia (responds to Vit D)

• 4. Megaloblastic anemia
• (responds to folate)

5 Blood dyscrasias

PROLONG Na CHANNEL INACTIVATION

WATER-SOLUBLE PRODRUG OF PHENYTOIN

PROLONGS Na CHANNEL INACTIVATION

A HYDANTOIN RELATED TO PHENYTOIN

(same as phenytoin, ethotoin, carbamazepine)

PROLONGS Na CHANNEL INACTIVATION

REDUCES LOW THRESHOLD Ca CURRENTS (T currents)

INCREASES GABA LEVELS BY STIM SYNTHETIC ENZYME GLUTAMIC ACID DECARBOXYLASE

INHIBITS DEGRADATION OF GABA

HEPATOTOXICITY

(esp when combo w/ other anti-sz meds)

PROLONGS Na CHANNEL INACTIVATION

(same as phenytoin, ethotoin, carbamazepine)

1. Bone marrow depression (leukopenia)*

2. Aplastic anemia

3. Agranuloctosis

4. Hyponatremia

• 5. H2O retention
• (serious in elderly w/ ♥ disease)

Prolong state of Na+ channel inactivation

→ ↓decr freq of repetv action potential

1. Prolong state of Na+ channel inactivation

2. Blocks excitatory (glutamate) receptors

3. Promotes realease of GABA

• Reduce low threshold Ca++ currents
• (T currents)

INC DURATION OF CHANNEL OPENING

BARBITUATE

Act at distinct allosteric binding sites on GABAA receptors

• → enhance GABA-mediated incr in Cl-
• conductance → hyperpolarization

INC FREQ OF CHANNEL OPENING

BENZODIAZEPINE

Act at distinct allosteric binding sites on GABAA receptors

• → enhance GABA-mediated incr in Cl-
• conductance → hyperpolarization

• INC FREQ OF CHANNEL OPENING
• (same as diazepam)

BENZODIAZEPINE

Act at distinct allosteric binding sites on GABAA receptors

• → enhance GABA-mediated incr in Cl-
• conductance → hyperpolarization

PROMOTE RELEASE OF GABA

MOA UNKNOWN

IV LORAZEPAM or DIAZEPAM

if not effective

IV FOSPHENYTOIN

Anticholinergic

Muscarinic antagonist (-)

• ↓Decr cholinergic dominance →
• Balances dopaminergic-cholinergic systems

Anticholinergic

Antihistamine

• Central muscarinic blockade
• (→ anti-emetic & sedative)

Dopaminergic Agents

DA precursor

Dopaminergic Agents

DA precursor

***Carbidopa is a peripheral DOPA decarboxylase inhibitor. Does NOT cross BBB.

ALLOWS MORE L-DOPA TO ENTER BRAIN

LEVODOPA + CARBIDOPA

Combo benefits:

1. Can decr dose of levodopa

2. Effective dose of l-dopa can be reached more quickly in the initial therapy

• 3. Avoids antagonism of therapeutic efficacy of l-dopa by pyridoxine (Vit B6).
• --Pyridoxine (Vit B6) enhances decarboxylase.

4. Elim n/v (a S/E of levodopa)

5. Decr ♥ S/E (of levodopa. Cardiac arrhythmias & transient tachycardia).

Dopaminergic Agents

DA agonist (+)

Directly stim DA receptors

Dopaminergic Agents

DA agonist (+)

Directly stim DA receptors

Dopaminergic Agents

MAOB inhibitor (-)

Elevates DA levels

Also poss neuroprotective

Dopaminergic Agents

• Catechol-O-methyltransferase inhibitor (-)
• (comt)

Elevates DA levels

Also poss neuroprotective

• HALOPERIDOL -- USMLE DOC
• --DA RECEPTOR ANTAGONIST
• --S/E SEVERE TERDIVE DYSKINESIA

• FOR PEDS:
• --CLONIDINE OR GUANFACINE, a-ADREN RECEPTOR AGONIST
• --RISPERIDONE, ATYP ANTIPSYCHOTIC

• AMPHETAMINE
• DEXTROAMPHETAMINE
• PHENTERMINE
• METHYLPHENIDATE
• ATOMOXETINE
• MODAFINIL
• THEOPHYLLINE
• CAFFEINE

MODAFANIL

RELEASES DA, NE, AND 5-HT

NOT USED FOR ADD/ADHD

CAFFEINE AND THEOPHYLLINE

INDIRECT ACTING SYMPATHOMIMETICS

RELEASE CATECHOLES FROM INTRANEURONAL STORES

BLOCK CATECHOL REUPTAKE

Esp with i.v. use

1. Marked CNS stim

2. Paranoid psychosis

3. ♥ Hypertensive crisis

4. ♥ Tachycardia

5. ♥ Arrhythmias

6. Hyperthermia

7. Convulsions

• 8. Coma
• ---------------------------------

CHRONIC

Continued use → marked tolerance

• → psych & physio dependence
• (→ withdrawal syndrome)

• Amphetamine psychosis
• o Hallucination
• o Delusions of persecution
• o Feelings of omnipotence

Continued use → marked tolerance

→ psych & physio dependence

(→ withdrawal syndrome)

• Amphetamine psychosis
• o Hallucination
• o Delusions of persecution
• o Feelings of omnipotence
• ---------------------------------

ACUTE

• Esp with i.v. use
• 1. Marked CNS stim
• 2. Paranoid psychosis
• 3. ♥ Hypertensive crisis
• 4. ♥ Tachycardia
• 5. ♥ Arrhythmias
• 6. Hyperthermia
• 7. Convulsions
• 8. Coma

• AMPHETAMINE DERIVATIVE
• (cns stim)

ANOREXIANT

LOWER ABUSE POTENTIAL

SCHEDULE 4

SAME MOA AS AMPHs

FDA --> SHORT-TERM Tx OBESITY

ADHD Tx (cns stim, methylphenidate)

RELEASE NE AND DA FROM NEURONS AND BLOCK REUPTAKE

SCHEDULE II -- HIGH ABUSE POTENTIAL

ADHD Tx (cns stim, dextroamphetamine)

RELEASE NE AND DA FROM NEURONS AND BLOCK REUPTAKE

RITALIN

SCHEDULE II -- HIGH ABUSE POTENTIAL

ADHD Tx (cns stim)

SELECTIVE NE REUPTAKE INH

DON'T GIVE WITH MOAI

• ADVERSE
• --HEADACHE, AGGRESSION & IRRIT IN KIDS
• --PALPITATIONS, INSOMNIA, URINARY RET IN ADULTS

• BLACK BOX WARNING
• --INC RISK SUICIDAL THOUGHTS IN KIDS/ADOLESCENTS

90% COMPLETELY OXIDIZED TO CO2 AND H2O BY GASTRIC AND HEPATIC ENZYMES

• GASTRIC ADH METs 20%
• --ADH PRODUCES ALDEHYDE WHICH IS THEN CONVERTED BY AlDH TO CO2/H2O

HEPATIC ADH AND AlDH

AVAILABILITY NAD+ RATE-LIMITING STEP

• MICROSOMAL ENZYME OXIDIZING SYSTEM (MEOS)
• --DOESN'T NEED NAD+
• --INDUCED BY CHRONIC HIGH ETHANOL

ZERO-ORDER KINETICS

EFFECTS OF ETHANOL ON MEMBRANES

• ENZYMES (nonspecific)
• --NA/K ATPase, ADENYL CYCLASE, PROT KINASE C
• --VOLTAGE-GATED ION CHANNELS: Ca & Na

• NEUROTRANSMITTER EFFECTS (specific)
• --INC STIM EFFECTS AT LOW DOSES. DEC GABA AND INC DA IN NEC ACCUMBENS
• --DEC STIM AT HIGHER DOSES. INC GABA AND INH GLUT AT NMDA RECs

ACUTE

• PRODUCT OF ADH ENZ IS EXCESS H+
• --TRANSIENT HYPERGLYCEMIA IF GLYC STORES, HYPOGLYCEMIA w DEC GLUCONEOGEN
• --HYPERLACTIC ACIDEMIA
• --HYPERURICEMIA
• --HYPERLIPIDEMIA AND KETOACIDOSIS

INC NADH/NAD+ RATIO

CHRONIC

--NADH INDUCED INH OF GLYCEROPHOS DEHYD LEADS TO INC GLYCEROPHOS AND ESTER OF FATTY ACIDS (triglycerides)

--DEC OXIDATION OF FATTY ACIDS

--HEPATIC ACCUM OF NEUTRAL FAT (fatty liver)

DOWNREG OF GABA RECs

UPREG OF GLUT NMDA RECs

INC CENTRAL NOREPINEPHRINE ACTIVITY

DISULFIRAM

INH AlDH CAUSING BUILDUP OF ALDEHYDE IN BODY -->

• ALDEHYDE SYND
• --CUTANEOUS VASODILATION
• --THROB HEADACHE
• --RESP DIFFICULTIES
• --NAUSEA
• --COPIOUS VOM
• --SWEATING
• --CHEST PAIN
• --BLURRED VISION
• --HYPOTENSION
• --ORTHOSTATIC SYNCOPE
• --CONFUSION

WOOD ALCOHOL

ADH --> FORMALDEHYDE + AlDH --> FORMIC ADIC

HEADACHE, VERTIGO, VOM, DYSPNEA, BLURRED VISION

METABOLIC ACIDOSIS

FORMIC ACID --> DESTRUCTIVE INFLAM OF RETINAL GANGLION

• Tx
• --SUPPORTIVE
• --CORRECT ACIDOSIS
• --ETHANOL TIES UP ADH

ANTIFREEZE

ADH --> GLYCOALDEHYDE + AlDH --> GLYCOLIC ACID --> --> OXALIC ACID

CNS DEPRESSION FOLLOWED BY METABOLIC ACIDOSIS

NEPHROTOX DUE TO OXALIC ACID CRYSTAL DEPOT IN RENAL TUBULES (crystals of ca+ oxalate found in urine)

• Tx
• --SUPPORTIVE
• --CORRECT ACIDOSIS
• --ETHANOL TIES UP ADH

• BOTULINUM TOX
• CISATRACURIUM
• VECURONIUM
• SUCCINYLCHOLINE

NMJ -- PRESYNAPTIC

BLOCKS VESICULAR ACh RELEASE (snap prots)

-facilitate endotracheal intubation

-adjunct to anesthesia to dec reflex movement & relax sk muscle to get to operative site

-facilitate mechanical ventilation

MUSCLE RELAXANT

ACTS ON NMJ *postsynaptic

COMPETITIVE NON-DEPOL BLOCKADE

NON-HEPATIC METABOLISM

*onset 4-6 min & duration 45-60 min

• *contain at least 1 pos charged quaternary
• ammonium group permitting electrostatic attraction & binding to neg charged
• alpha subunit of ACh receptor

• large bulky molecules bind receptor & competitively block access of ACh to
• postjunctional receptor

affinity for receptor but no intrinsic activity

muscle will still respond to direct electrical stim

may also block prejunc Na channels

blockade can be overcome by inc ACh in synapse thru acetylcholinesterase inhibitors

MUSCLE RELAXANT

NMJ -- POSTSYNAPTIC

NON-COMPETITIVE DEPOL BLOCKADE

*onset 1-1.5 min & duration 6-10 min

binds to alpha subunit of ACh receptor --> transient disorganized muscle contraction

also enters motor end plate Na channels --> flickering of ion conductance, fasiculations

Not degraded by esterases as quickly as ACh so rec stays depol

Phase 1 = initial blockade w/ depol. ACh inc blockade

desensitization & membrane repol BUT as long as S occupies receptor, membrane can’t be depol again

• Phase 2 = now competitive block that can be
• reversed by acetylcholinesterase
• inhibitors

Used for brief surgical procedures

• rapidly hydrolyzed by plasma cholinesterases
• --> only small amt reaches NMJ

*diffusion away from motor end plate accounts for its brief duration of action

• *pts w/ atypical cholinesterases or low
• cholinesterase exhibit a prolonged
• blockade

• *adverse reactions:
• -bradycardia
• -cardiac dysrhythmias
• -inc intraocular, intragastric & intracranial
• pressure
• -myalgia & myoglobinuria

• *should be used w/ caution in pts w/ ocular
• disorders

*pts w/ myasthenia gravis are resistant to effects

*pts w/ burn injuries or trauma (esp CNS) respond w/ marked hyperkalemia (due to inc in receptors over injured site)

*depolarizing agents drug/drug interactions:

-any agent that lowers serum K should be used w/ caution since dosage requirements may increase

ACTION IN CNS

*interneuron (polysynaptic reflexes)

*inc GABA mediated inh synaptic transmission to dec spinal interneuronal signaling (BZ)

• *dec motor reflexes (spasticity)- sprains,
• arthritis, myositis, fibrositis

*dec muscle hypertonicity & rigidity

• *palliative & do not alter course of
• primary lesion

ADVERSE

• *sedation
• *w/ continued use- tolerance & dependence

MUSCLE RELAXANT w ACTION IN CNS

· Interacts w/ GABA-B receptors linked to K channels → hyperpol cells of presynaptic membrane of Glut neurons in Spinal Cord → prevent release of glut onto alpha motor neurons

→ dec efferent excitation of spastic skeletal muscle

used for flexor spasms & sk muscle rigidity assoc w/ MS & spinal cord injury

• ADVERSE
• *sedation
• *mental confusion
• *weakness
• *sudden withdrawal --> auditory & visual hallucinations

MUSCLE RELAXANT: ACTS ON SKEL MUSC (not nmj)

INH RYANODINE REC Ca+ CHANNEL FUNCTION IN SARCO RET --> INH RELEASE OF Ca DURING EXCITATION

• Therapeutic Uses:
• * strokes, ms,
• * postencephalitic athetosis, dystonia
• · Spasticity from SC injury
• · Malignant Hyperthermia
• · Neuroleptic Malignant Syndrome

• ADVERSE
• --MUSCLE WEAKNESS & FATIGUE

"Atypical Compounds Quickly Restore One's Zest"

• Aripiprazole
• Clozapine
• Quetiapine
• Risperidone
• Olanzepine
• Ziprasidone

nigrostriatal = no effect = no EPS

mesolimbic = block of D2-receptors = no positive symptoms

mesocortical = enhanced D2-receptor stim = improved negative symps

tubuloinfundibular = no effect = no hyperprolactinemia

nigrostriatal tract = BLOCK DA = EPS = BAD, schlimm, malo

mesolimbic tract = BLOCK DA to prevent positive symptoms = GOOD, gut, bueno

mesocortical = does not help neg sympts and may even make them worse because neg sympts appear to result from a lack of D2-receptor stim = BAD

TI = BLOCK D2 = hyperprolactinemia = gynecomastia, amenorrhea = BAD

• CHLORPROMAZINE
• (equal d2/5-ht block)

• HALOPERIDOL
• (mostly d2)
• D2 ANTAGONISTS

ATYP ANTI-PSY

partial agonist at D2-receptors. agonist when little DA is being released, but antagonist when excessive DA is released

SAME S/E FOR BOTH

• 1. Anti-adrenergic (mostly α1 & α2):
• o Sedation
• o Orthostatic hypotension

• 2. Anti-cholinergic:
• o Dry mouth
• o Blurred vision
• o Urinary retention
• o Sinus tachycardia
• o Constipation

• 3. Anti-histamine (H1):
• o Sedation
• o Weight gain

• Exceptions:
• -- Risperidone & Quetiapine are NOT
• anticholinergic
• -- Olanzopine VERY antihistaminic

• 1.
• Skin rxns
• (photosensitivity)

• 2.
• Jaundice

• 3.
• Ventricular arrhythmias

• 4.
• Agranulocytosis (<0.01%)

• TYPICALS:
• 1. Pseudoparkinsonism: rigidity, tremor, shuffling gait

2. Acute dystonia: muscle spasms

3. Akathisia: motor restlessness

4. Tardive dyskinesias (TD): oral-facial dyskinesias. Late onset. Poss IRREV.

• ATYPICALS:
• (less incidence of eps)

• 1. NO dystonia
• 2. Some akathesia
• 3. Risperidone: dose-related EPS
• 4. NO tardive dyskinesia

• Clozapine:
• --DECR TD in pts on typical neuroleptics
• --Granulocytopenia (Agranulocytosis)

RISPERIDONE

ESP CLOZAPINE AND OLANZAPINE

INH 5-HT2 AND H1 --> WEIGHT GAIN

CAN LEAD TO TYPE II DIABETES AND HYPERLIPIDEMIA

CLOZAPINE

TYPICAL

ATYPICAL

ATYPICAL

• (+) Symptoms:
• Excessive ↑↑↑ dopaminergic actvy in limbic system

• 1. Hallucinations
• 2. Delusions
• 3. Conceptual disorg in speech & beh
• 4. Agitation

• (-) Symptoms:
• Reduced ↓↓↓ dopaminergic actvy in prefrontal cortex

• 1. Social & emotional withdrawal
• 2. Blunted affect
• 3. Poverty of speech
• 4. Anhedonia (lack of pleasure)
• 5. Avolition (lack of initiating goal directed behavior)

• -diabetes insipidus
• -hypothyroidism
• -dysrhythmias
• CNS:
• FINE HAND TREMOR

• GI:
• N/V

• KIDNEY:
• TUBULAR FUNC IMPAIRMENT
• --POLYURIA IN 50%
• --DEC CONC ABILITY

• DERM:
• --PSORIASIS
• --MACULOPAP AND ACNE

• WEIGHT GAIN --> NONCOMPLIANCE

Prophylactic "sandwich" therapy is designed to eliminate both highs (mania) and lows (depression)

valproate (for mania) + lamotrigine (for depression)

atypical antipsychotic drug (for mania) + lamotrigine (for depression)

aripiperazole (for mania and depression)

LOCAL ANESTHETIC

Ester- hydrolyzed by plasma cholinesterase to water soluble metabolites which are elim by kidney

short duration of action

LOCAL ANESTHETIC

Amide- metabolized largely by liver to metabolites that are excreted by kidney

Intrinsic vasodilator properties

• Effective topically & also orally as an
• antiarrhythmic agent

• Hepatic dz or dec hepatic blood flow dec
• metabolism

LOCAL ANESTHETIC

• Ester w/ sig greater potency (16X greater)
• compared to procaine

Prolonged duration of action due to slow ester hydrolysis

• NOT used in peripheral nerve blocks due to
• prolonged duration of action & potential for toxicity

Blocking voltage-gated Na channels

Selectively bind to channels in inactivated –closed state to prevent their change to activated-open

Effect is greater in rapidly firing axons

Inc in threshold for elec excitability

Dec rate of rise of depol phase of AP

Lengthened refractory period

Resting membrane potential not sig affected

Elec changes are progressive w/ an inc number of Na channels blocked due to absorption of local anesthetic

Nerve fibers differ in susceptibility based on size & myelination --> A delta, B & C fibers are smallest & least myelinated so are blocked first --> PN sensation reduced before motor is blocked

*preferentially block small fibers b/c distance over which fibers can passively propagate an impulse is shorter