It is due to the loss of dopamine (DA) neurons in the substantia nigra, which leads to symptoms of: Tremor at rest,

Cogwheel rigidity, Akinesia, Loss of postural reflex.

Strategy: Either to increase DA effects or block ACh in the basal ganglia
Drugs MOA T. USE AE Contraindication NOTE
LEVODO Levodopa + A precursor and DA Effective in early years. 1. NV, Anorexia, tachycardia, 1. Vit B6

stages.
and anti-Ach) during early stages and reserve L-dopa and DA agonists for later
A common approach is to use the low-efficacy drugs (Selegiline, amantadine,
L-dopa ˃ Bromocriptine ˃ amantadine ˃ anticholinergic.
PA Carbidopa carboxylase inhibitor mydriasis, urine & saliva 2. MOAIS
discoloration 3. Antipsychotics (…..)
2. Hallucination, Dyskinesia,
Mood changes
3. Wearing-off effect
MOA-B Selegiline, Selective MOA-B inhibitor ↑ levodopa action Has ↓ hypertensive crisis
inhibitor Rasa… & Rasagiline is irreversible Metabolize to amphetamine (but not Rasa)
Safinamide selective & 5x potent
COMT Entacapone Selective reversible ↓ Wearing off effect in pts Similar to Levodopa.
inhibitors and COMT inhibitors Tolcapone has longer DOA, but + Fulminating liver necrosis
Tolcapone (But Entacapone frequent dosing, No Necrosis)
DA Bromocriptine Longer DOA Ergot:
AGONIST Pergolide Ergot: Similar to levodopa (except dyskinesia)
Apomorphine - In pts with motor fluctuation & dyskinesia. Non-Ergots:
Pramipexole - Ineffective in no response to levodopa. Caution:
Ropinirole Non-Ergots - n psychiatric pts
- Ropin for restless leg Syndrome - MI or vascular Dz
- Apo for Acute off phase of advance Dz. - Fibrosis (spaces)
Non-ergots
Not fibrosis or vascular Dz
NMDA Amantadine - ↑ Dopamine release _ Restless, agitation, toxic psychosis.
inhibitor (Antiviral) - Block Ach _ Due to Ach, DA, Glut blockade
- Inhibit NMDA glutamate _ Tolerance within 6 month
receptor.
Anti Ach Benztropine Due to Ach blockade - BPH
trihexyphenidy - Glaucoma
- Pyloric stenosis
 Anxiolytic and Hypnotic Drugs
BENZODIAZEPINE Binds to 1. ANXIETY - Drowsiness Flumazenil is IV GABA receptor
GABA-A o GAD, PANIC (alprazolam) - confusion antagonist with rapid onset and
A. Short-acting (3-8hrs) receptors o PHOBIA, Performance anxiety - Ataxia short duration of action.
 Mida zolam 2. Sleep Disorder - Cognitive impairment AE:
 Oxa zepam o Triazolam for pts not falling asleep Seizure (if benzo-controled seizure
 Alpra o Tema for frequent awakening  Are lipophilic or TCA or antipsychotic usage)
B. Intermediate (10-20) o used for limited time 1-3w  Actual DOA differs
 Tema zepam 3. Amnesia  Cross placenta
 Esta zolam o Short acting for procedures  Dependence
 Lora zepam o Midazolam prior to anesthesia
C. Long-acting (1-3 D) 4. Seizure
 Dia zepam o Clonazepam
 Flura zepam o Lora & Diazepam for status E.
 chlordiazepoxide o Lora, Dia, oxa for alcohol withdraw
5. Muscle spasm in MS & CP
Other Anxiolytics Mediated by For chronic (not short-term or as-need) Not anticonvulsant & muscle Benz are used in first few week
(BUSPIRONE) 5-HTA1, & D2 Rx of GAD relaxant. NV, Dizziness & Headache. with SSRI, SNRI.
receptors
BARBITURATE Binds to & - Anesthesia (not now) Hypnotic dose leads hangover. Contra in porphyria
A. Ultra-short (sec-30mi) potentiate - Anti-epilepsy (Pheno) only if other Induce CYP450
 Thiopental GABA-A. failed. Withdrawal Sx: tremor, NV,
B. Short acting Block Glut - Anxiety, tension, insomnia (suppress anxiety, seizure, Cardiac Arrest.
 Pento, Seco, Amo receptor REM) Butalbital in combo with other Overdose: shock-like
 Butalbital cold drugs.
C. Long acting - Cross placenta.
 Pheno-Barbital
Zolpidem GABA (BZ1 o Mid-night awakening Oxidation by CYP 3A4 Zaleplon: fewer cognitive problem.
Zaleplon receptor) o Not anti-epileptic, muscle relaxant Headache, anterograde Amnesia, H1/2 = 1 hr. 3A4.
Eszopiclone o Little withdrawal, rebound insomnia next-morning. Eszopiclone: effective for 6
o No effect on sleep stages Sleep-walking, driving, months. & 6hr. AE: dry mouth,
edema, unpleasant taste.
Ramelteon, MT1 & MT2 No other effects. ↑ prolactin level
Tasamelteon agonist ↓ Latency of sleep. Dizziness, fatigue, somnolence
Anti-histamine (doxylamine, OTC) Anti-depressant (Doxepin, approved) Su
Mild type insomnia mirtazapine & trazodone off-label
SSRI Inhibit 5-HT Depression (childhood = flu & Fluoxetine → active Serotonin syndrome:
fluoxetine reuptake. escital, OCD = flu & sertraline) metabolite. Hyperthermia, rigidity, sweating, myoclonus, vital
sertraline Take 2 weeks to Social Anxiety, panic Sleep: sign & mental changes.
fluvoxamine act OCD, GAD, posttraumatic Paroxetine, fluvoxa. (sedating) Discontinuation syndrome:
citalopram stress. Bulimia Nervosa Fluoxetine sertral. (activating) Flu-like, agitation, nervousness, sleep changes.
escitalopram Premenstrual dysphoric Sexual dysfunction:
paroxetine disorder.

SNRI Inhibit both 5- Depression +pain (SSRI can’t) Insomnia, Sexual dysfunction,
Duloxetine HT & NE Pain syndromes Constipation, Dizziness, sweating, dry mouth.
(Cymbalta) Dulo = both ↑ BP & HR
Venlafaxine (Effexor) Venla = 5-HT, GI Sx common with Dulo.
both. Dulo is 2D6 inhibitor.
Tricyclic Anti- Inhibit 5-HT & - MDD, panic Anti-cholinergic: Aggravate
Depressant NE reuptake. - Chronic Pain syndromes a-blockade:  Bipolar disorder
A. Tertiary amine - Migraine (amitriptyline) H1 blockade → sedation  BPH
 Clo, I, tri Also Block - Bet-wetting (I) Weight gain  Close-angle glaucoma.
 Doxepin - a-adrenergic - Insomnia (↓ dose doxepin)  Epilepsy
 Amitriptyline - cholinergic ↓ Sexual dysfunction.  Arrhythmia
B. Secondary - histaminic  NI → lethal
 Desipramine Amoxapine block
 Nortriptyline D2 & 5-HT2
C. Tetracyclic Maprotiline &
 Amoxapine Desi just block
 Maprotiline NE.
MAO inhibitor Irreversibly For unresponsive Depression. Amphetamine-like stimulant. Should not be:
tranylcypromine inhibit MOA-A, B The Last resort. Drug-food interaction - Co-administered SSRI??
phenelzine Only (tyramine): ↑ catecholamine
Selegiline Selegiline??? Stroke, Seizure, occipital
Isocarboxazid headache. Stiff neck.
 -
Explanation A. 1st generation (conventional)
- Competitive inhibitors and is associated with movement disorder (EPS)
a. Phenothiazine include:
i. Chlorpromazine (Thorazine) and Thioradazine (Mellaril), which are low-
potency phenothiazine.
ii. Fluphenazine (Prolixin) which is a high-potency phenothiazine.
b. Thiothixene (Navane), pimozide (Orap), and haloperidol are also high-potency
antipsychotics.
B. 2 generation (atypical)
nd

Have Less EPS, but More metabolic problems (DM, hypercholesterolemia, weight gain)
I. Risperidone (Risperdal) have 5-HT2 receptor-blocking activity and fewer EPS than the
typical
II. Clozapine (Clozaril) also blocks 5HT2-receptors as well as D-receptors.
i. It induces the fewest extrapyramidal symptoms, effective in pts that are
refractory to other antipsychotics
ii. Can cause agranulocytosis; white blood cell counts must be monitored
III. Olanzapine (Zyprexa) is similar to clozapine but does not cause agranulocytosis. it leads
to metabolic syndrome
MOA

Action Anti-psychotic: (+) symptom by D2 receptor blockade. (-) symptom by 2nd generation
(clozapine), [not responding to 1st.]
EPS: due to Ach prominence and DA blockade in nigrostreatal pathway. Rx by anti-cholinergic
(Benztropine). Thioradazine can be used Bcz of its anti-Ach activity.
Antiemetic: blockade of D2 in CTZ area.
Anti-cholinergic: Thioradazine, chlorpromazine, clozapine & olanzapine have anti-Ach activity
can be used in EPS.
Others:
- a-adrenergic blockade
- alter Tem-regulating mechanism
- in pituitary, ↑ prolactin
- H1 blocking causes Sedation (olanzapine)
- Sexual dysfunction & weight gain
Therapeutic Schizophrenia: for (+) symptom: 1st generation, For (-) symptom and resistant Dz: 2nd
Use generation with H2A-blocking activity.
NV: prochlorperazine
Other:
- Disruptive behavior 2° to autism: Risperidone & Aripiprazole
- Intractable hiccups: chlorpromazine
- Tourette Dz (phonic tic): pimozide
- Bipolar Disorder: Lurasidone
- Rx-refractory Depression: Aripiprazole, Brexpiprazole Quetiapine
Adverse EPS: time- and dose dependent: dystonia ˃ Akathesia ˃ Parkinson-like Sx ˃ tardive dyskinesia.
effect Tardive dyskinesia: fly-catching movement of tongue. Rx = Deutetra- & Valbenazine. WHY???
Neuroleptic malignant syndrome: muscle rigidity, fever, altered Mental status, unstable BP &
myoglobinemia.
Contra / Lower seizure threshold
caution In older pts with dementia-related behavior & psychosis
Monitor mood changes
Name MOA USE AE
Benzodiazepines Bind to GABA Emergency acute seizure
Carbamazepine Block Na channel
Headache, dizziness, diplopia. Rash, psychiatric Ds,
Eslicarbazepine Block Na channel Focal (in adult)
Hyponatremia
Oxcarbazepine (MHD) Block Na channel (+ Ca) Focal (Partial) seizure (adult & child) Hyponatremia (in elders ↓ its use)
Ethosuximide Block T-type Ca channel Absence seizure
Lacosamide Block Na channel, bind to CRMP2 Focal seizure Headache, fatigue
Rufinamide Unknown, Act on Na channel Seizure with lennox-Gastuat syndrome Shorten QT
Zonisamide Multiple, Na, Ca, C
Unknown, enhance or convert to Focal seizure & post-herpetic neuralgia.
Gabapentin
GABA. Binds to a2-subunit of Ca. DOC in OLDERs
Binds to a2-subunit of Ca Focal seizures, peripheral neuropathy,
Peregabalin
channel. post herpetic neuralgia & fibromyalgia
Vigabatrin Irreversible inhibitor of GABA-T
Tiagabine Block GABA reuptake. Focal seizure. (Normal shouldn’t use)
Focal, generalized, absence. Lennox-
Lamotrigine Block Na & Ca channels. Slow titration (due to serious Rash)
Gastuat syndrome. Bipolar Ds
Brivaracetam Unknown, binds to SVP2 Focal (in adult)
focal, myoclonic, 1° generalized TC
levetiracetam Binds to SVP2 Mood changes (change it)
seizures in adults and children
Inhibit 2C19, co-administer with phenytoin → ↓conc.
Multiple, Na, NMDA, Ca, GABA Focal, 1° generalized TC seizures.
Topiramate Weight loss, paresthesia, Renal stone, glaucoma,
(potentiate) Migraine.
oligohidrosis & hyperthermia.
Multiple, Na, NMDA, Ca, GABA
Felbamate Refractory seizure (lennox-Gastuat Syn) Induce 3A4, inhibit 2C19. Anemia, hepatic failure
(potentiate)
a-A3H5M4PA antagonist → Psychiatric: aggression, hostility, homicidal ideation,
Perampanel Focal & Generalized TC (˃12 years)
↓excitation anger.
Phenobarbital & primidone Potentiate GABA Status epileptics when other fail.
Phenytoin & Fosphenytoin
Block Na channel in inactive Focal, generalized TC, status epileptics CNS depression: nystagmus, ataxia, Gingival
(IM)
state. hyperplasia, Peripheral neuropathy & osteoporosis
Phenytoin Na: not IV or IM.
Valproic acid & Divalproex Block Na, GABA-T & act on Ca Focal & 1° generalized seizure. ˃ 2 years & woman avoided. Inhibit 2C19 & UGT.