Antidote: Flumazenil (Anexate)- GABA receptor

antagonist
DRUGS FOR PSYCHIATRIC &
NEUROLOGIC DISORDERS B. Barbiturates
MOA: Barbiturates increase the duration of
Excitatory neurotransmitters GABA-mediated chloride ion channel opening
- opens Na or Ca channels/ influx 1. Ultra-short (20 min): Thiopental (Pentothal)
depolarization (more positive) nerve 2. Short-acting (3-8 h):
impulse Pentobarbital (Nembutal)
- e.g. Norepinephrine, Dopamine, Amobarbital (Amytal)
Acetylcholine, Glutamate, Aspartate 3. Long-acting (1-2 d): phenobarbital (Luminal)
Inhibitory neurotransmitters Uses:
- opens Cl channels hyperpolarization 1. induction of anesthesia- Thiopental
(more negative) no nerve impulse 2. seizures in children- Phenobarbital
- e.g. glycine, gamma-aminobutyric acid 3. anxiety- Pentobarbital, Amobarbital
(GABA)
S/E:
Sedative-Hypnotics (Minor Tranquilizers) Drowsiness, dependence, respiratory
depression, paradoxical excitation
Anxiety Cytochrome P450 induction
Types: inc. metabolism dec. drug levels
1. Panic disorder- recurrent unexpected panic (warfarin, theophylline, phenytoin,
attacks that can occur with agoraphobia in which valproate,carbamazepines, oral
patients fear places in which escape might be contraceptives)
difficult.
2. Specific phobia- intense fear of particular Others sedative-hypnotics:
objects or situations (e.g. snakes, heights); most 1. Zolpidem (Ambien, Stilnox)
common psychiatric disorder - not a Bz but acts on Bz receptor
3. Social phobia-intense fear of being 2. Chloral hydrate
scrutinized in social or public situations (e.g., - ‘knockout drops’
giving a speech, speaking in class). - converted to trichloroethanol (active)
4. Generalized anxiety disorder- intense - for preoperative sedation
pervasive worry over virtually every aspect of life 3. Antihistamines
5. Post-traumatic stress disorder- persistent - diphenhydramine (Benadryl),
reexperience of a trauma, efforts to avoid doxylamine
recollecting the trauma, and hyperarousal - (Unisom), hydroxyzine (Atarax, Iterax)
6. Obsessive-compulsive disorder- recurrent
obsessions and compulsions that cause
significant distress and occupy a significant
portion of one’s life Antipsychotics
- aka neuroleptics, major tranquilizers
- “Neuroleptics” because of their
TREATMENT:
tendency to cause movement disorders
A. Benzodiazepines
- Increase the frequency of GABA-mediated - “Major tranquilizers” vs minor
chloride ion channel opening tranquilizers (eg. benzodiazepines)
1. Short-acting (2-8 hrs) Psychosis
- Oxazepam (Serax) - symptoms of delusions, hallucinations,
- Triazolam (Halcion) and disorders of thought
- Clonazepam (Klonopin, Rivotril) - due to inc. dopamine levels (as in
- Midazolam (Versed, Dormicum) amphetamines)
2. Intermediate-acting (10-20 hrs)
- Lorazepam (Ativan) Schizophrenia
- Alprazolam (Xanax, Xanor) - characterized by positive and negative
- Temazepam (Restoril) symptoms, a pattern of social and
3. Long-acting (1-3 days) occupational deterioration, and
- due to active metabolites persistence of the illness for at least 6
- Diazepam (Valium, Anxionil) months
- Flurazepam (Dalmane) - - 1% of population, inheritable
- Chlordiazepoxide (Librium) Positive symptoms:
Uses: 1. Hallucinations- auditory, visual, tactile,
1. Anxiety- alprazolam, diazepam and/or olfactory hallucinations; voices
2. Seizures- diazepam, clonazepam, that are commenting
lorazepam 2. Delusions- persecutory, grandiose,
3. Insomnia- flurazepam, midazolam paranoid, religious; thought
Pre-operative sedation- midazolam broadcasting, thought insertion
3. Bizarre behavior- aggressive/agitated,
S/E: odd clothing or appearance, odd social
• drowsiness, dependence
behavior, repetitive-stereotyped behavior
• respiratory depression (+ ethanol, other CNS
depressants)
 Movement Disorders:
1. Extrapyramidal symptoms (EPS)
Negative symptoms- affective flattening, alogia,
- aka neuroleptic-induced parkinsonism
asociality
- most common (15%)
Positive symptoms respond more consistently - coarse tremors, rigidity, bradykinesia
with medications. Negative symptoms are less - Risk: high potency
responsive. - Tx: lower dose, anticholinergics
2. Acute Dystonia
- Muscular spasm, involuntary movement
- Spasmodic torticollis, trismus, tongue
protrusion, opisthotonos, upward mov’t of
eyes (oculogyric crisis)
- Risk: high-potency antipsychotics

- Onset: early in tx (days)

- Tx: IM/IV anticholinergics (benztropine,
diphenhydramine, biperiden)

3. Akathisia
- Subjective feeling of muscular discomfort
- Agitated, pace relentlessly, alternately sit
and stand
- Risk: recent increase/onset of meds
- Onset: 1st month of therapy
- Tx: beta-blockers (propranolol), BZDs
(lorazepam), clonidine
4.Neuroleptic malignant syndrome (NMS)
- idiosyncratic, life-threatening
- Motor: Muscular rigidity, dystonia, agitation
Typical Atypical
Thioridazine (Mellaril, Clozapine (Clozaril, - Autonomic: hyperpyrexia, hypertension
Melleril) Leponex) - Tx: discontinue meds, supportive,
Chlorpromazine (Thorazine, Quetiapine dantrolene, bromocriptine
Laractyl, Psynor) (Seroquel)
Perphenazine (Trilafon) Ziprasidone
Thiothixene (Navane) (Geodon, Zeldox) 5. Tardive dyskinesia
Fluphenazine (Prolixin, Aripiprazole (Abilify) - choreoathethoid movements
Modezine, Phlufdek, Olanzapine - Tongue protrusion/twisting,lip puckering
Sydepres) (Zyprexa)
Haloperidol (Haldol, Quetiapine - Risk: elderly, long-term tx, female,
Serenace) (Seroquel) - Onset: years after tx
Risperidone - Tx: lower dose, change meds
(Risperdal)
OTHER ADVERSE EFFECTS:
- Agranulocytosis- clozapine, chlorpromazine
- Pigmentary retinopathy- thioridazine
- ECG changes- prolonged QT interval-
ziprasidone

Other uses of antipsychotics:

1. Antiemetic (blocks dopamine receptors)-
prochlorperazine
2. Intractable hiccups- chlorpromazine
3. Pruritus (antihistamine)- promethazine
(Zinmet, Thaprozine

Chemical Classification
Antidepressants
- Phenothiazines
o Aliphatic- chlorpromazine
Depression
o Piperazine- fluphenazine,
- lack of NE, serotonin, dopamine
perphenazine
o Piperidine- thioridazine
1. Tricyclics Antidepressants (TCAs)
- Butyrophenones- haloperidol
- three-ring nucleus
- Thioxanthenes- thiothixene
- prototypes: amitriptyline, imipramine
- Dihydroindolines- molindone
(Tofranil)
- Diphenylbutylpiperidines- pimozide
- Dibenzoxapine- clozapine, quetiapine
- Benzisoxazole- Risperidone
Others:
Clomipramine (Anafranil) Desipramine
(Norpramin), trimipramine
(Surmontil)Maprotiline, nortriptyline (Pamelor),
protriptylineDoxepine, amoxapine,
Dosulepine/Dothiepin (Prothiaden

MOA: inhibits neuronal reuptake of NE, serotonin,

dopamine

S/E:
orthostatic hypotension (alpha blocker)
Dry mouth, constipation, blurred vision,
urinary retention- (anticholinergic ) Lithium carbonate (Eskalith, Quilonium)
Cardiac toxicity - DOC
Sexual dysfunction - unknown mechanism
2. Serotonin-specific reuptake inhibitors (SSRIs) - Narrow therapeutic index
MOA: inhibits serotonin reuptake - Therapeutic range: 0.6-1.2 mEq/L
- fluoxetine (Prozac)- prototype Adverse Effects
sertraline (Zoloft), paroxetine (Paxil,
Minor: tremor, polyuria, gastrointestinal
Seroxat),
distress, memory problems, acne exacerbation,
fluvoxamine (Luvox, Faverin),
weight gain
Citalopram (Celexa, Lupram),
Long term: hypothyroidism
Escitalopram (Lexapro)
Toxicity: ataxia, coarse tremor, confusion, coma,
S/E: impotence/dec. libido,
sinus arrest, and death
+ MAO inhibitor serotonin syndrome-
Interactions:
hyperthermia, muscle rigidity, myoclonus
diuretics- dec. Na inc. Li;
excessive Na intake dec.Li
3. Monoamine oxidase inhibitors (MAOIs)
MAO A- serotonin, norepinephrine
MAO B- dopamine
Anticonvulsants
Seizures
- phenelzine (Nardil), isocarboxacid,
- Excessive abnormal electrical discharge
tranylcypromine (Parnate)- inhibits both
from cortical neurons
MAO A and MAO B
- Causes: idiopathic, CNS infection, fever,
- moclobemide (Aurorix)- inhibits MAO A
metabolic disturbance , cerebral trauma
only;
Epilepsy
for depression - recurrent unprovoked seizures
- selegeline- inhibits MAO B only; for
Parkinsonism Types
1. Partial Seizure
S/E: hypertension (+ tyramine-rich foods- - Focal area in the brain is involved
cheese, chicken liver, beer, red wine) - Types:
a. Simple partial
Other antidepressants: o No impairment of consciousness
1. Venlafaxine (Effexor) o motor or sensory symptoms
- Serotonin and NE reuptake inhibitor
(SNRI) b. complex
2. Mirtazapine (Remeron) - with impairment of consciousness
- noradrenergic and specific - with automatisms
2. Generalized
serotonergic antidepressant (NaSSA)
- Entire brain is involved
3. Trazodone (Desyrel), Nefazodone (Serzone) a. Tonic-clonic/ Grand mal
- Inhibits reuptake of serotonin, - Tonic phase- loss of consciousness,
antagonist at 5-HT2 rigidity
S/E: priapism (prolonged, painful - Clonic phase- jerking movements of
erection) entire body
4. Tianeptine (Stablon) b. Absence/ Petit mal
- selective serotonin reuptake enhancer - In children
(SSRE) - brief loss of consciousness (10s) blank
stare, blinking, facial twitching
Antimanic Agents/Mood Stabilizers c. Myoclonic
- brief jerks
Bipolar disorder
- depression with manic episodes MOAs:
1. Sodium channel blockers
- Phenytoin, carbamazepine, valproic
acid
2. Calcium channel blockers
- Ethosuximide
 S/E:
GI
disturbance, headache, dizziness, rare: blood
dyscrasia, SJS, SLE
3. GABA-mediated
- Benzodiazepines, phenobarbital, 7. Benzodiazepines
gabapentin, tiagabine - diazepam, lorazepam for status epilepticus,
frank seizures
Indications - clonazepam for myoclonic seizures
S/E: CNS depression
1. GTC and partial seizures
- valproic acid, carbamazepine, phenytoin
2. Absence
- ethosuximide, valproic acid
3. Myoclonic 8. Gabapentin (Neurontin)
- clonazepam, valproic acid - GABA analog/ for partial seizures
4. Status epilepticus S/E: CNS depression: drowsiness, dizziness,
ataxia
- diazepam, lorazepam, phenytoin
Febrile seizures- phenobarbital 9. Lamotrigine (Lamictal)
- for partial seizures/ blocks Na channels
1. Phenytoin (Dilantin, Epilantin) S/E: headache, dizziness, ataxia, rashes, SJS
- MOA: closes Na channels
CNS: ataxia, nystagmus, diplopia 10. Topiramate (Topamax)
Connective: hirsutism, gingival hyperplasia - derivative of fructose
“Fetal hydantoin syndrome”- cleft palate, - Na-channel blocker, potentiates GABA
congenital heart disease, microcephaly, growth S/E: drowsiness, ataxia, headache
and mental retardation
CyP450 inducer (carbamazepine, valproate, 11. Tiagabine (Gabitril)
warfarin, OCPs) - prevents uptake of GABA
Displaced from protein binding by aspirin, S/E: confusion, dizziness
sulfonamides
12. Magnesium Sulfate
Fosphenytoin- aqueous (phenytoin: ethylene - for eclampsia (HTN + proteinuria + seizures)
glycol), given IM/IV S/E: CNS, cardiovascular and respiratory
depression
2. Carbamazepine (Tegretol) Antidote: Calcium chloride/gluconate
- also used for trigeminal neuralgia
MOA: closes Na channels ANTI-PARKINSON DRUGS
S/E: Parkinson’s disease
CNS effects: dizziness, ataxia, diplopia - cardinal signs: tremors (resting), rigidity,
GI: nausea, vomiting akinesia, postural difficulties
Metabolic: hyponatremia - pill-rolling tremor, mask-like facies, bent
Hematopoietic: leukopenia posture, shuffling gait, depression, dementia
Derma: rashes, SJS - due to loss of dopamine-producing neurons in
CyP450 inducer (warfarin, phenytoin, valproate, the substantia nigra
OCPs), autoinducer (induces its own metabolism) - imbalance between acetylcholine and dopamine
3. Valproic Acid + Na valproate (Depakene) Drugs for Parkinson’s Disease
Divalproex Na (Depakote)
- closes Na channels - Dopamine precursor- levodopa/carbidopa
- 90% protein bound- displaced by phenytoin - Dopamine agonist- bromocriptine, pergolide
and aspirin - MAO inhibitors- selegeline
S/E: - COMT inhibitors- entacapone
GI disturbance, rare pancreatitis and - Amantadine
hepatotoxicity, sedation and ataxia at high - Muscarinic antagonists- benztropine,
doses,
trihexyphenidyl
fetal malformation (spina bifida)
CyP450 inhibitor (phenytoin, carbamazepine,
Phenobarbital) Levodopa-Carbidopa (Sinemet)
- most effective drug, however prolonged use
decreases its efficacy
4. Phenobarbital / Phenobarbitone (Luminal)
- dopamine does not cross the blood-brain barrier
- MOA: GABA-mediated
- levodopa can penetrate the brain and
- for seizures in children
decarboxylated to dopamine
S/E: sedation, paradoxic hyperactivity in children
- levodopa is decarboxylated in the GIT- nausea,
and elderly, CyP450 inducer (warfarin, phenytoin,
vomiting, arrhythmia, hypotension
valproate, OCPs)
- carbidopa- inh. peripheral decarboxylase
5. Primidone (Mysoline)
- related to Phenobarbital, acts on GABA receptor Interactions:
+ MAOIs HTN
S/E: CNS depression
+ pyridoxine inc. decarboxylase activity
6. Ethosuximide (Zarontin)
+antipsychotics block dopamine receptors
- for absence seizures
- closes Ca channels
A. Ergot-derived Dopamine Agonists:
1. Bromocriptine (Parlodel, Provasyn)
o ergotamine derivative (from ergot
Claviceps purpurea)

o also used in treatment of

hyperprolactinemia- galactorrhea,
amenorrhea, impotence
S/E: same as levodopa, arrythmia

2.Pergolide (Permax)

o Ergosine derivative
o S/E: same as levodopa, arrythmia

B. Non-ergot dopamine agonists

1. Pramipexole (Sifrol)
S/E: hypotension, drowsiness,
hallucinations, constipation

2. Ropinirole (Requip)
S/E: syncope, hypotensions, hallucinations,
drowsiness

C. MAO (Monoamine oxidase) Inhibitor

1. Selegiline / Deprenyl (Eldepryl)
- selective MAOB inhibitor
S/E: HTN (high doses also inhibits
MAOA)

D. COMT (Catechol O-methyl transferase)

Inhibitors
1. Tolcapone (Comtan, Tasmar)
S/E: hepatotoxicity

E. Dopamine releaser
1. Amantadine (Symmetrel)
- also used as antiviral for influenza
S/E: livedo reticularis (skin discoloration),
seizures in overdose

F. Anticholinergics/ Antimuscarinics
benztropine (Cogentin), biperiden (Akineton),
trihexyphenidyl (Artane)
- For mild symptoms especially tremors
S/E: dry mouth, constipation, urinary
retention, blurring of vision