Psychiatry Pharmac😍

ANTI-PSYCHOTIC DRUGS

• Cause of psychosis: 
• Excessive dopamine in brain.

• Classification of Anti-psychotics:



1. Typical Anti Psychotics
• [D2 Blockers]
2. Atypical Anti Psychotics
• any other mechanism;
• mainly 5HT2 Blockers > D2 block
• Eg:
• Aripiprazole (exception)
• 5 HT2 blocker >> Partial D2 agonist
• less extrapyramidal symptoms
• less weight gain
• Low intrinsic activity,
• high affinity for D2 receptor,

Typical Antipsychotics/ First generation Antipsychotics

• 1. Strong D2 #:
• Haloperidol [Highest risk of EPS]

• 2. Weak D2 #:
• Chlorpromazine

• Side Effects:

Receptor Blocked	Side Effects	Associated Drug Type
D2 Blockade	Extrapyramidal symptoms (EPS), Endocrinal side effects	High potency (e.g., Haloperidol)
M1 Blockade	Anticholinergic side effects: blurring of vision, dry mouth, urinary/fecal retention	Low potency drugs
Alpha-1 Blockade	Orthostatic hypotension	—
H1 Blockade	Sedation, weight gain	—

• Chlorpromazine:
• Corneal and lenticular deposits.
• Color: Photosensitivity (Blue-grey skin on exposure to sunlight).
• Cholestatic jaundice.
• Mnemonic: CCCC
• MOA
• Blocks M1, Alpha 1, H1 receptors
• moderate weight gain risk

• Haloperidol:
• High D2 potency, high EPS.

• Thioridazine:
• Retinal pigmentation (Irreversible).
• Brown vision
• Salt and pepper retinopathy
• Cardiac arrhythmias (increased QTC interval).
• Retrograde ejaculation.
• Least EPS among typicals.
• Thio Ridazine :
• Thio Ridazine → rid of
• Brown (Brown vision) Cuteee (QT prolongation) with colorful eyes (RP),
• like Salt and Pepper () movie
• but ejaculated retrograde ()

• Penfluridol:
• Longest acting antipsychotic.

Side Effects with Antipsychotics

1. Extra pyramidal symptoms (EPS):

• Cause: Blockade of D2 receptors in Nigrostriatal Pathway

• More common in Typical > Atypical Antipsychotics.

• Mnemonic: ADAPT
• AD - Acute Dystonia
• A - Akathisia
• P - Drug-induced Parkinsonism
• T - Tardive Dyskinesia
• Night - Neuroleptic Malignant Syndrome

EPS	Symptom	Cause	DOC / Treatment
Akathisia (most common)	• Inner Restlessness • Rocking, pacing. Akathisia → Akath	Unknown	Beta-blockers (DOC), Benzodiazepines
Acute dystonia (earliest)	• Abnormal posturing, • Facial grimacing • Eyes rolling upwards: Oculogyric crisis. • Neck: Torticollis. • Jaw: Trismus. • Laryngospasm. Stonia → stone like abnormal posturing	• ↓ Dopamine, • Metoclopramide inj.	Anticholinergics (DOC): • Benzhexol [Trihexyphenidyl] • Benztropine, Biperiden • Diphenhydramine Antihistaminic: • Promethazine
Drug induced Parkinsonism/ Tremor predominant	• Tremor, Bradykinesia • Rabbit syndrome (perioral tremors)	• ↓ Dopamine, • Metoclopramide inj.	• Benztropine, • Diphenhydramine, • Trihexyphenidyl (benzhexol)
Tardive dyskinesia (most late)	Facial dyskinesia • tongue protrusion • lip smacking • choreiform hand movements, • pelvic thrusting Limb dyskinesia • piano finger movement • foot tapping	D2 hypersensitive → (due to prolonged downregulation) → upregulation Anticholinergics are contraindicated in TD	VMAT-2 inhibitors: • Valbenazine, • Deutetrabenazine Thaadi (Tardive) varumbo → Piano vayikkum() , tap dance () kalikum → but thaadi varan time edukkum (Late) Thaadiyum Vaalum (Valbenazine)
Neuroleptic malignant syndrome (most lethal)	Muscle rigidity, Hyperthermia, ANS instability	D2 Block	Dantrolene (DOC), (⛔ Ryr) Bromocriptine, Amantidine (Activate D2)

• VMAT ⛔ →Also used in chorea

 

 

2. Endocrinal Side Effects

• Cause: Blockade of D2 Receptors in Tuberoinfundibular Pathway.

• Dopamine (DA) is inversely proportional to Prolactin (PRL).

• Leads to Hyperprolactinemia.

• Causes:
• Decreased libido (males/females),
• Galactorrhea,
• Amenorrhea (females).

NOTE

• Other EPS causing drugs
• Metoclopramide >>> Domperidone

Atypical Anti-Psychotics

• D2 and 5HT2A Antagonism.

• Less EPS, Hyperprolactinemia.

• More Metabolic S/E (Weight gain, Diabetes, etc.).

Clozapine

• DOC: For resistant Schizophrenia.

• MOA:
• Antagonist D4>D2
• 5HT 2A/2C

Advantages:

• Lesser risk of EPS and hyperprolactinemia.

• Effective against both Positive as well as negative symptoms.

• Only antipsychotic with anti-suicidal property.

• Used for treatment-resistant schizophrenia.
• No response to atleast 2 class of antipsychotics

Adverse effects are: Mnemonic: SAM

• Sedation (Most common adverse effect)

• Sialorrhea (MC side effect)
• Wet Pillow

• Seizures
• [Dose dependent]

• Agranulocytosis
• [Dose independent]
• Mnemonic: Close Car (Clozapine, Carbimazole)
• Weekly CBC → 1st 6 months,
• then bi-weekly → 6 months,
• then monthly → 1 year.
• Stop if WBC <3000/mm³ or ANC <1500/mm³.

• Myocarditis → [Dose independent]

• Agranulocytosis and myocarditis are idiosyncratic → [Dose independent]

• Cause lipodystrophy syndrome characterized by:
• ↑ Glucose
• ↑ Lipids
• Weight gain
• Insulin Resistance
• Risk is highest with clozapine.

• Mnemonic: Close in Lodge (LDS) → Full thadicha (LDS) → epozhum thuppal olipich (sialorrhea) kidan (sedation) urangunna → Eneekkumbo seizure (dose dependent) varunna → Epozhum infection varunna (Agranulocytosis)

Contraindications:

• WBC <3500/mm³,

• bone marrow disorder h/o,

• h/o clozapine-induced agranulocytosis,

• With use of another bone marrow suppressants
• (e.g., carbamazepine).

Long Acting Injectable (LAI) Antipsychotics (Depot)

• Intramuscular injection (monthly/bi-weekly).

• For patients with poor compliance.

• Z track technique used to prevent leaking.

Other Atypical Antipsychotics

• Quitapine
• Cataract

• Risperidone:
• Increased EPS, Hyperprolactinemia.
• Off label use in OPD
• OCD
• PTSD
• Dementia

• Amisulpride:
• Increased EPS, Hyperprolactinemia.

• Ziprasidone:
• Increased QTC interval.
• Low risk for weight gain.
• Zebra → run behind zebra → ↓ weight

• Aripiprazole:
• Partial D2 agonist;
• D2, 5HT2A antagonist.
• M/c → Akathisia.
• Low risk of weight gain and Least prolactin elevation.
• Arippa → used for tea and milk → ↓↓ milk and weight gain

• Brexpiprazole:
• Partial D2,
• 5HT1A agonist;
• 5HT2A antagonist.

• Cariprazine:
• Most effective against negative symptoms > Risperidone
• Partial D2, D3, 5HT1A agonist (D3>D2);
• 5HT2A antagonist.

• Pimavanserin:
• 5HT2A inverse agonist.
• Used for delusion/hallucination in
• Parkinson's disease → No EPS S/E
• DOC for levodopa induced psychosis.
• Causes increased QT interval.
• Mnemonic: Cute (QT ↑↑ ) Pima () Says there is Van () in Park ()

Atypical Antipsychotics: Side Effects

ACUTE MANIA

• Patient is usually aggressive and violent.

• Rx of Acute Episode: 
• Sedatives [Antipsychotics/ BZD] +
• Lithium.

• Prophylaxis: Lithium is DOC.

• Bipolar disorder: DOC is lithium.

Lithium

• Mood stabilizer.

• John FJ Cade conducted studies proving it a mood stabilizer.

• Monovalent ion.

• Completely absorbed after oral administration.

• Does not bind to plasma protein.

• Not metabolized.

• Excreted through kidneys.

Pharmacokinetics:

• Half-life is 24 hours.

• Narrow Therapeutic Index.

• Given thrice a day.

TDM Drugs

Digoxin

Aminoglycosides

Theophylline

Lithium

Anti arrhythmics

Antiepileptic (Phenytoin )

Antidepressants (TCA)

Methotrexate

Calcineurin Inhibitor

Therapeutic drug monitoring:

• For measuring plasma concentration:
• Sample taken at 12 hours after last dose.

Treatment range: 0.5-1.5mEq/L

• Acute mania: 1-1.5mEq/L ( 0.8-1.2 mEq/L)

• Maintenance: 0.6- 1.2 mEq/L (0.5-0.8 mEq/L)

• Toxicity: >1.5mEq/L.

• If >4 → Dialysis needed

Anti-suicidal property.

• Clozapine

• Lithium

Adverse effects

• S/E of Lithium:
• L - Leucocytes ↑↑, Loss of hair, appetite.
• I - Increase
• T - Tremors [MC] -fine (DOC-propranolol)
• H - Hypothyroidism > hyperthyroidism
• I U - ↑↑ Urine
• Lithium induced diabetes insipidus
• DOC: Thiazides, K sparing diuretics (Amiloride)
• Drug interaction:
• Thiazides decrease lithium clearance,
• may cause lithium toxicity.
• M - Avoided in Mothers
• [Lithium in pregnancy]
• Ebstein anomaly (Box shaped heart)



• thyroid disease,
• Floppy baby syndrome.

Lithium toxicity

• Body treats lithium like sodium.

• Low sodium diet or dehydration
• body absorbs sodium and also lithium,
• leading to toxicity.

• Drugs increasing toxicity are:
• Lisinopril
• Indomethacin
• Thiazides
• ↑ renal reabsorption of lithium → causing toxicity

• Mnemonic: Lithium

• Fasting causes toxicity
• ↑↑ Fasting → Body conserve Na → Li also reabsorbed → ↑ Toxicity

• Decreased Seizure threshold → ↑ Risk of seizure during ECT

Symptoms of Lithium Toxicity

• Toxicity (DAT):
• D - Diarrhea
• A - Agitation & Ataxia
• T - Tinnitus
• Mnemonic: Come back if DAAT symptoms come

• Mild to moderate (1.5-2 mEq/L)
• GI: Vomiting & abdominal pain.
• CNS: Ataxia, nystagmus, muscle weakness.

• Moderate to severe (2-2.5 mEq/L)
• GI: Anorexia, Nausea, vomiting.
• CNS:
• Hyperactive deep tendon reflex
• convulsion
• stupor
• Coma.

• Severe (> 2.5 mEq/L)
• Generalized convulsion,
• oliguria,
• renal failure,
• death.

Tremor Notes:

• Lithium:
• Therapeutic dose → fine tremors,
• Overdose → drowsiness & coarse tremors.

• Sodium Valproate:
• Therapeutic dose → fine tremors,
• Overdose → drowsiness (no tremors).

Treatment

• Stop lithium, correct hydration.

• Removal of unabsorbed lithium from GI tract:
• Polyethylene glycol.
• Sodium polystyrene sulphonate.

• Mnemonic: Lithium Polyanu → Polyethylene, Polstyrene

• In severe cases: Haemodialysis.

DEPRESSION

ANTI DEPRESSANTS

• Chosen according to side effect profile.

• Takes 3-4 weeks for action.

• Typical Anti-Depressants: 
• Act by ↑ 5HT.
1. Selective
• SSRI
2. Non Selective
• TCA
• SNRI

• Atypical Anti-Depressants: 
• Act by other mechanisms

Typical Antidepressants

These may be:

• 1. MAO - A Inhibitors:



• Moclebemide
• Reversible inhibitors of MAO-A.

Reuptake Inhibitors:

1. Monoamine Oxidase Inhibitors (MAOIs)

• 1st class of approved antidepressants.

• ⛔ metabolism of monoamines (5HT, NE, DA).

Cheese reaction/tyramine-induced hypertensive crisis:

• Tyramine in cheese, beer, fish, red wine.

• MAOIs ⛔ tyramine metabolism,
• causing hypertensive crisis.

Cheese Reaction

• Patient eats together
1. Tyramine containing food
• (Cheese, wine, etc.)
• Displacement of NE
2. MAO Inhibitors
• (Anti-depressants)
• NE not metabolised

• Accumulation of NE
• Hypertensive crisis

• DOC: Phentolamine

• Mnemonic: A depressed patient taking MAO I → celebrates New year (cheese and wine) → comes to EM with ↑ BP

2. Non-Selective Reuptake Inhibitors

• Inhibit the reuptake of both 5HT and NA.

• Two classes: TCA and SNRI.

TCAs: Tricyclic and Tetracyclic Antidepressants

• Mechanism: Blocks serotonin and norepinephrine transporters.

Secondary effects:

• Antagonist at muscarinic, H1, alpha-1, alpha-2 receptors.

• Blocks voltage-sensitive sodium channels.

• Avoid in Narrow angle glaucoma.

• Mnemonic: Don't give TC to blind

• Most Suicidal risk → Avoid in suicide

Tricyclic drugs:

• Clomipramine, Amitriptyline, Imipramine, Nortriptyline.

TCA (Toxicity):

• Mnemonic:
• TC kodukkumbo ulla effects

Treatment:

• I.V. sodium bicarbonate (Serum alkalization).

• Activated charcoal.

• No role for hemodialysis (high volume of distribution).

• Mnemonic: TC & Acid (Met Acidosis) → TC thannu pettannu → Eye blurred (blurred vision → glaucoma) ayi, dry mouth () ayi → nenjidippu kuudi (Arrythmia) → thalakarangi (Postural hypotension) → Bodam poi (Sedation) → kidann seizure adich

Serotonin Norepinephrine Reuptake Inhibitors (SNRI)

• Also known as dual reuptake inhibitors.

• Action: ↑ 5 HT and ↑ NA.

• Drugs:
• Venlafaxine, Desvenlafaxine.
• Levomilnacipran, Duloxetine, Milnacipran.

• Side effects similar to SSRIs.

• Lesser adverse effects than TCAs.

• DOC for severe depression.

• S/E: Hypertension:
• especially with higher dose of Venlafaxine.

• Mnemonic: NRi de veedu → Dulex paint adich Venillavu polakki

Discontinuation Syndrome

• Due to abrupt stop of drug.

• Usually appears within 1–7 days after stopping the drug

• Seen with short-acting drugs:
• venlafaxine, fluvoxamine, paroxetine.

• NRI has Flu → We give advice → Don't stop tablet → When (Venlafaxine) Flu (Fluvoxamine) Pass (Paroxetine) → Flu like symptoms

• Not seen with long-acting drugs like fluoxetine.

• Symptoms:
• Flu-like symptoms (lethargy, weakness, headache).
• Insomnia, Nausea, Irritability.
• Imbalance (dizziness, lightheadedness)
• Sensory disturbances (e.g., "electric shock" sensations, paresthesias)
• Hyperarousal (e.g., anxiety, agitation)

3. Selective Serotonin Reuptake Inhibitors

• Drug of choice for Depression.

• Discontinuation syndrome (Least with Fluoxetine).

• Indication of SSRI:
• DOC for mild-moderate depression.
• DOC for all neurotic disorders like:
• Anxiety related disorder
• GAD
• OCD
• Bulimia
• Phobia
• PTSD
• Impulse control disorders

• Drugs:
• Sertraline, Fluoxetine, Paroxetine.
• Citalopram, Escitalopram.
• Vilazodone, Fluvoxamine.

• Escitalopram:
• Most serotonin selective
• Mnemonic: Yes S (serotonin)

• Vilazodone:
• SPARI (serotonin partial agonist & reuptake inhibitor).
• Mnemonic: Vilasini → Saree (SPARI) for my PYARI

• Fluvoxamine:
• Used for OCD.

Side Effects (SSRIs)

• GI:
• Nausea (most common), diarrhea, anorexia, dry mouth.
• Weight gain, constipation (esp. paroxetine).

• CNS:
• Anxiety (Due to up-regulation of 5HT2 receptors).
• insomnia, sedation, vivid dreams.

• dry mouth, sweating

• Sexual dysfunction:
• Due to 5HT2 receptor stimulation.
• Most common with long-term treatment.
• Decreased libido, inhibited orgasm (Anorgasmia).
• Delayed ejaculation
• Fluxetine
• (Dapoxetine used for Premature ejaculation)
• Least → Mirtazepine

• Miscellaneous:
• Hyponatremia, especially in the elderly.

Pregnancy (SSRIs)

• Not major teratogens.

• Avoid Paroxetine:
• can cause cardiovascular defects.

• SSRIs/SNRIs late in pregnancy
• cause persistent pulmonary hypertension in newborn.
• low APGAR score,
• ADHD
• delayed developmental milestones.

Paroxetine

• Discontinuation syndrome

• Avoid in Pregnancy

• Constipation

Atypical Anti-Depressants

• Less sexual side effects.

NDRI (Norepinephrine dopamine reuptake inhibitors)

• Bupropion
• Low risk of sexual dysfunction, sedation, weight gain.
• Used for smoking cessation.
• Side effect: seizure (at higher dosage).
• Contraindicated in bulimia nervosa and anorexia nervosa.

NaSSA (Noradrenergic & specific serotonin antidepressants)

• Mirtazapine
• Sexual side effects not seen.
• Atypical antidepressants
• Least sexual side effects
• from Mizapur → to NASSA

• Side effects:
• Sedation (m/c)
• Weight Gain

Serotonin modulator & stimulator

• Vortioxetine
• Agonist at 5 HT1A.
• Partial Agonist at 5 HT1B.
• Antagonist at 5HT3
• 5 HT reuptake Inhibitor property.
• Sexual side effects can occur, comparatively less

Other Novel agents

• Brexanolone

• Vilazidone

• Esketamine (S-Enantiomer of Ketamine)
• Mechanism: NMDA Antagonist.
• Nasal Spray (FDA approved 2019).
• For Treatment-resistant Depression.
• Used with an oral Antidepressant.

• Gepirone
• Agonist/partial agonist at 5HT1A.
• Approved by FDA in 2023 for MDD.
• Contraindicated in:
• Prolonged QTc interval >450msec.
• Congenital long QT syndrome.
• Guppy → Cute → QT prolongation

• Other Drugs:
• Amineptin - ↑ Reuptake of 5-HT
• Tianeptin - ↑ Reuptake of 5-HT

Novel antidepressant

• Vilasini (Vilazidone) depression karanam Novel (Novel antidepressant) ezhuthi

• Amina (Amineptin) Vilasiniyodu (Vilazodone) yes keettikko (Esketamine) en paranj → Apo smoke eduthu kalanju (bupropion)

Condition / Context	SSRI Preference / Exception
First-line medical management	SSRIs for GAD, OCD, Panic disorders, Depression
GAD (Generalized Anxiety Disorder)	Sertraline
Panic Attacks	All SSRIs except Fluoxetine
OCD (Obsessive Compulsive Disorder)	All SSRIs except Citalopram
Safe in breastfeeding	Sertraline
Safe in MI	Sertraline
Post-partum depression	Brexanolone/Allopregnanolone Mnemonic: Breast feeding (Brexanolone), Pregnancy (Allopreg)
Treatment resistant depression	Esketamine (nasal spray) → blocking NMDA receptors of Glutamate.
Smoking	Buprepion
↓ Libido in females	Flibanserin Mnemonic: Fling Bang → to ↑ libido in females