Psycho-pharmacology

Psychopharmacology is the branch of

pharmacology that deals with the study of the actions, effects, and development of psychoactive  drugs.

In its broadest sense it means the study of all pharmacological agents that affect mental and emotional functions.

Specifically to the study and synthesis of drugs used in the control of psychiatric illnesses,

CONCEPT

The mentally ill in early communities were generally cared for by family members, however, in severe cases they sometimes ended up in almshouses or jails. Because mental illness was generally thought to be caused by a moral or spiritual failing, punishment and shame were often handed down to the mentally ill and sometimes their families as well.

The Treatment of Psychiatry disorders in the past has often constituted of merely institutionalisation (i.e administration in ansylym or mental hospital)

with the advent of psychopharmacology in the 6th decade has brought treatment of Psychiatric disorder within the realm of scientific medicine

HISTORY OF TREATMENT IN PSYCHIATRY

AntipsychoticsAntidepressantsMood stabilizing drugsAnti anxiety and hypno-sedativesAnti epilepticsAlcohol and drug dependenceAntiparkinsoniansMiscellaneous drugs-(e.g Stimulants , drug used in

treatment of eating disorder, alcohol dependence, anaesthetic,dementia,drugs used for child psychiatry, vitamines calcium channel blocker and other drugs)

CLASSIFICATION OF PSYCHOTROPIC DRUGS

CLASSIFICATION,PROPERTIES And common side effects OF ANTIPSYCHOTIC DRUGS

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE

Wt.gain

Increase prolactin

I.Phenothiazines

A. Aliphatic

Chlorpromazine

300-1000

50-100 +++ +++ + ++ ++

Triflupromazine

100-400

30-60 ++ ++ ++ ++ ++

B. Piperidines

Mesoridazine

100-400

______ ++ + + ++ +

Thioridazine

300-600

______ +++ ++ + ++ +

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE Wt.gain

Increase prolactin

C.Piperazine

Fluphenazine

2-20 _____ + + +++ + +++

Prochlorperazine

45-150 40-80 IM

+ + +++ + +++

Trifluoperazine

15-50 1-5 IM

+ + +++ + +++

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE Wt.gain

Increase prolactin

Thioxanthines

A.Aliphatics

1.Chlorpromazine

75-600 25-75 +++ ++ ++ ++ ++

B. Piperazines

1.Flupentixol 3-18 _____ + + ++ ++ ++

2.Thiothixene 6-60 2-6 IM + ++ ++ ++ ++

3.Zuclopenthixol

25-150 50-600 IM

++ ++ ++ ++ ++

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE

Wt.gain

Increase prolactin

III.Butyrophenone

1.Haloperidol 5-30 5-10 IM + + +++ + +++

2.Trifluperidol 0.5-8 2.5-5 IM +/- +/- +++ + ++

IV.Diphenylbut-ylpiperidines

1.Penfluridol 20-60 mg/w

____ + + ++ + ++

2.Pimozides 4-20 ____ + + ++ + +++

V. Indolic Derivatives

1.Molindone 50-225 ______ ++ 0 + +/- +/-

VI.Dibenzopine

1.Lorxapine 25-250 _____ ++ ++ ++ + +++

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE Wt.gain

Increase prolactin

C.Benzisoxales

1.Iloperidone 4-24 _____ 0 + + ++ 0

2.Paliperidone 3-12 _____ + ++ + ++ +++

3.Resperidone 2-8 _____ + ++ + ++ +++

D.Benzisothazolyl

1.Ziprasidone 40-160 _____ +/- + 0 +/- +/-

E.Thienobenzodiazepine

1.Olanzapine 5-20 2.5-10 IM

++ + +/- +++ +

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE

Wt.gain

Increase prolactin

A.Dibenzodiazepines

1.Clonazipine

50-900 ____ +++ +++ 0 +++ 0

B.Substituted Benzamides

1.Amisupride 400-1200

____ +/- + + + +++

2.Sulpiride(not called atypical usually)

400-2400

____ +/- + + + +++

ATYPICAL /2ND GENERATION ANTIPSYCHOTICS

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE Wt.gain

Increase prolactin

E.Dibezodiazepine

Quetiapine 150-750

____ ++ +/- 0 ++ 0

F. Partial Agonist

1.Aripiprazole

5-30 _____ 0 0 0 +/- 0

2. Bifeprunox

20 _____ 0 0 0 +/- 0

G.Dibenzothiepin

1.Zotepine 75-300 ______ ++ +/- + ++ ++

Drug OD(mg/dl)

PD (mg)

Sedation

Hypoten-sion

EPSE Wt.gain

Increase prolactin

H.Dibenzooxepinopyrrole

1. Asenapine 5-10 ____ 0 +/- 0 +/- 0

The estimates of the common side effect in the table mention are roughly given and is an empirical guideline to the clinical use. The dosage can be change as per the requirement of the patient, clinical symptoms and severity.

EPSE=Extra Pyramidal Side Effect** 0=Absent, +/- = Probable/Very little + = Mild, ++ =Moderate, +++ = Severe

The exact mechanism of action of antipsychotic is unknown however one of the major mechanism appears to be anti-dopaminergic activity

of these drugs

Block D2-receptor which are mainly present in mesolimbic-mesocortical system (concern with emotion) nigo-striatal system & tubero-infundibulum systemExtra Pyramidal side effect (EPSE) are cause due to blockade

in mesolimbic system, & hyperprolactinemia cause by blockade in tubero-infundibular system.

Sedation is caused by histaminergic blockade which are usually highest for drugs such as Chlorpromazine and thioridazine.

Antipsychotic Drugs: Mechanism of action

Atypical or 2nd generation Antipsychotic has action only on mesolimbic system but has no eefect on nigro-striatal or tubero-infundibular system.

The SGAs and clude Risperidone,Quetiapine,Olanzapine, Amisulpride,Papiperidone,Zointepine,Ziprasidone and Aripiprazole.

so it reduce s/e such as Extapyrimidal s/e (EPSE)and hyperprolatinemia s/e

It mainly act on D4 & 5-HT2 receptor and has weak D2 antagonism

less incidence of tardive dyskinesia & Neuroleptic Malignant syndrome.

Second Generation Antipsychotics

Anti Psychotic Drug:IndicationOrganic Psychotic disorder

Non organic Psychotic disorder

Delirium Schizophrenia

Dementia Schizo-Effective disorder

Drug induce psychosis

Acute psychoses

Other: Organic hallucination

1.Mania 2.Bipolar

Organic delusion disorder

Major Depression

Secondary mania Delusional disorder

Neurotic & other psychiatric Disorder

Medical Disorder

Severe, intractable & disabling anxiety

Hungtington Chorea

Rx refractory OCD

Intractable hiccup

Anorexia Nervousa

Nausea & Vomiting

Tic disorder e.g Gilles de la tourette syndrom

Autonomic Side effects Dry Mouth, Constipation, Cycloplegia,Mydriasis, Urinary Retention Central Anti Cholinergic Syndrome (Delirium) Impotence, Impaired Ejaculation.Extra Pyrimidal Side Effects Parkinsonian Syndrome (esp tremor), Akanthisia (Motor restlessness), Acute Dystonia, Rabbit Syndrome (Peri oral tremor), Tardive Dyskinesia (late onset oro-facial dyskinesia), Neuroleptic Malignant Syndrome(Fever,EPS,High CPK

catotonic symptom and autonomic dysfunction)

AntiPsychotic Medication: Side Effect

Other Central Nervous System Side Effects Seizure, Sedation Depression or Pseudo

depressionMetabolic And Endocrine side effects Weight Agin,Diabetes, Galactorrhea with/without

AmenorrheaAllergic Side effect: Cholestatic Jaundice, Agranulocytosis

Cardiac Side effect EKG Changes (e.g QTc Prolongation)

Ocular Side EffectGranular side effect not know in cornea and

lens,Pigmentatary retinopathy resembling retinitis pigmentosa.

Dermatological side effect:Contact dermatitis, Photosensitivities reaction,Bleu-ray metallic Discoloration

ANTIDEPRESSANT DRUG

Drug use to treat depressive disorder

Also know as Mood elevator and thymoleptic

Drugs Oral dose Sedation Orthostatic hypotension

Anticholinergic

Tricyclic Tertiary amines

1.Amitriptylline

75-300 +++ +++ +++

2.Clomipramine

75-250 ++ ++ ++

3.Dosulepin 75-300 +++ +++ ++

4. Doxepine 75-300 +++ +++ +

5.Imipramine 75-300 ++ ++ ++

6.lofepramine

70-210 + + +

7.Tri-Imipramine

75-300 +++ ++ ++

CLASSIFICATION AND PROPERTIES OF ANTIDEPRESSANT

Drugs Oral dose Sedation Orthostatic hypotension

Anticholinergic

B Ticyclic 2nd Amine1.Desipramine

75-300 +/- + ++

2.Nortriptyline

75-200 + ++ +

3.Protriptyline

15-60 0 ++ ++

C. Tricyclic Antidepressant

1.Amoxapine 150-400 + + ++

2.Maprotiline 75-225 ++ ++ ++

3..Mianserin 30-120 +++ +/- +/-

D.Bicyclic Antidepressant

1.Viloxazine 100-300 +/- +/- +/-

Drugs Oral dose Sedation Orthostatic hypotension

Anticholinergic

II. SSRI

1.Citalopram 20-40 +/- +/- 0

2.Estitalolopram

10-20 +/- +/- 0

3.Fluoxamine 20-60 +/- 0 0

4.Fluvoxamine

50-300 +/- +/- +/-

5.Paroxetine 20-40 +/- 0 +/-

6.Setraline 50-200 +/- 0

IV SNRIs

1.Duloxetine 60 +/- +/- +/-

2.Venlafaxine 50-200 +/- +/- +/-

Drugs Oral dose Sedation Orthostatic hypotension

Anticholinergic

IV.NSREs

Tianeptin 37.5 + 0 +/-

V.NaSSAs

Mirtazapine

15-45 +++ + +/-

VI.NDRI

Bupropion 150-450 Activating 0 0

VII.SARIs

Nefazodone

200-600 ++ + +/-

Trazodone 150-400 +++ +/- +/- NSREs= Norepinephrine Serotonine Reuptake Enhancer NaSSAs=Noeadrenergic and Specific Serotonergic Antagonists NDRI=Norepinephrine Dopamine Reuptake Inhibitor SARIs=Serotonine Antagonist and Reuptake Inhibitor

Drugs Oral dose Sedation Orthostatic hypotension

AntiCh

VIII.NARI

1.Reboxetine +/- +/- +/-

IX.MAOIs

A.Reversible Selective MAO-B Inhibitor

1.Selegiline 5-10 Use in Parkinsonism

B.Reversible Selective MAO-A inhibitor(RIMAs)

1.Meclobemide 300-600 Activating 0 0

X.Melatonin Receptor agonist & 5-HT2c antagonist

1.Alomelatin 20-50 + 0 0

It increase catecholamine levels in brainTCA:1. Blocking the reuptake of

norepinephrine,serotonine and/or Dopamine at the nerve terminal thus increase NE,5-HT and/or DA level at the reactor site

2. Down regulation of Beta adenergic receptor

MOA OF ANTIDEPRESSANT

Depression:Depressive Episode (also called Major

depression,endogenous depression)Depressive episode with melancholia (with or

without ECTs)Depressive Episode with Psychotic feature

(with antipsychotic or ECTs)Dysthymia (with Psychotherapy)

INDICATION OF ANTIDEPRESSANT

Reactive depression (with Psychotherapy)Depressive equivalent and masked depressionAtypical DepressionSecondary Depression (e.g in Hypothyroidism,

cushing Syndrome)Abnormal Grief Reaction

EnuresisAttention Deficit disorder with HyperactivitySchool PhobiaSeparation anxiety disorderSomnambulismNight tremor

Child Psychiatric Disorder

Panic AttackAgoraphobiaObsessive compulsive

disorder with or without depression

Cataplexy (associated with narcolepsy)

Aggression in ElderlyEating Disorder

Borderline Personality Disorder

TrichotillomaniaDepersonalisation

syndromePost traumatic stress

syndromeGeneralise Anxiety

DisorderNarcotic dependenceAlcohol Dependence

Other Psychiatric Disorder

Chronic PainMigraine

Medical Disorder

MOOD STABILISING DRUG

These drug are usually effective in treatment of mania Therefore the words Antimania is often use to describe them.

Effective in preventing Mood swing in Bipolar Disorder

These Drug include Lithium , Valproate , Carabamazepine and

Lamotrigine

LITHIUM

INDICATION: Rx of Acute ManiaProphylais of Bipolar mood Disorder Rx of Schizo -effective disorderProphylaxis of Unipolar mood disorderRx of cyclothymia Rx Of Acute DepressionRx Acute AlcoholismRx of Impulsive Aggression

LITHIUMAtomic no. 3 and Atomic Wt. 7 It’s the smallest alkali ion

It effect the Na+ K+ ATPase and accumulates intracellularly as substitute of Na+

It inhibit the adenyle Cyclase and thus decrease cAMP (II Messenger) intracellularly

It accelarate the presynaptic reuptake and destruction of catecholamine,like norepinephrine

It inhibit the release of the catecholamine in synapseIt decrease the post synaptic serotonin 5-HT2 receptor

sensitivityIt stabilizes the membrane, along with Ca++ and Mg++It decreases the Ca++ mobilisation from the

intracellular pools by ITP(inositol-triphophate)- dependent Ca++ channels (II Messenger system)

MECHANISM OF ACTION

Lithium Carbonate (300mg tablets;400mg sustained release tablet)

Lithium citrate (300MG/5ML liqiud)Before starting treatment,it is essential to

ensure normal functioning of kidney, thyroid, heart and CNS

Clinical Use: Lithium

Routine and general systemic physical examination

Routine blood count(Hb,TC,DC)Urine:R/E and MicroscopicECGRFT (blood urea,serum creatinine)24hours

urine volume, urine specific gravity).TFT (T3,T4,TSH)

After starting Lithium it is necessary to investigate.

Doses:Initial starting dose for lithium is 900-1200mg/dl

given in 1-3 doses.During Rx it is essential to estimate blood level of

lithiumTherapeutic levels=0.6-1.2 mEq/L (for Rx of Acute

Mania)Prophylactic levels=0.6-1.0 mEq/L (for relapse

prevention in Bipolar)Toxic lithium levels >2.0mEq/LWhen stopping lithium Rx it is essential to taper the

dose over several days / weeks in order to minimise the risk of relapse on discontinuation

Lithium

Side effects:LithiumI. Neurologic: Tremor, Muscular weakness,Cogwheel

rigidity,Seizure,Neurotoxicity(Delirium,cerebellar sign,abnormal involuntary movement seizure & later coma)

II.Renal: Polyuria, polydipsia, Tubular changes,Nephrogenic diabetes

insipidus, Nephrotic syndromeIII. Cardiovascular: similar to those of Hypokalemia (T-wave depression)IV. Endocrine Goitre,Hypothyroidism,Wt.Gain,Abnormal TFTV.Gastrointestinal: Nausea,Vomiting,Diarrhoea,metallic taste, and abdominal painVI.Dermatological: Acneiform eruption, Papular eruption and exacerbation of PsoriasisVII. S/E during pregnancy: Teratogenic,Ebstein anomaly,secretion in milk 30-100 % of maternal

Lithium level therefore cause toxicity in Infant

VALPROATE

Valproate Dosage- 1000-3000mg/day oral dose in divided dose

Therapautic blood level is 50-125mg/ml

Valproate

Bipolar DisorderNeurological Disorder- Migraine and pain

Syndrome,Trigeminal Neuralgia, and Neuropathic pain,Seizure(Absence seizure,complex partial seizure,myoclonic seizures and generalise tonic clonic seizure)

Other: Behavoural agitation in dementia,severe symptom in mental retardation,ADHD and conduction disorder,Schizoaffective disorder (bipolar type),alcohol withdrawal,tadive dyskinesia,impulse control disorder,panic disorder and borderline personality disorder.

INDICATION-Valproate

Side effect: ValproateAdverse effect is more common with valproate

concentration above 100mg/dlCommon side effect are nausea , sedation ,

tremor, flushing, weight gain thrombocytopenia , menstrual disturbance, n hair loss

Other most serious, though relatively uncommon include Hepatic toxicity , Acute hemorrhagic pancreatitis and Steven-Johnson Syndrome.

CARBAMAZEPINE

Carbamazepine Dosage- 600-1600mg/day orally in divided doseRx is best monitored with repeated blood levels

Therapautic blood level are 4-12

SEIZURES Complex partial seizure (CPS) Generalised tonic clonic seizures Alcohol withdrawal seizures (rum fits) PSYCHIATRIC DISORDERS: Bipolar mood disorder Impulse control disorder and aggression Psychosis with epilepsy Borderline personality disorder Cocaine withdrawal syndrome PAROXYSMAL PAIN SYNDROME Trigeminal neuralgia Phantom limb pain

INDICATIONS:carbamazepine

Diplopia,drowsiness,dizziness,nausea,vomiting ataxia,

Skin rash, Steven-johnson syndrome(erythema multiforme major),photophobia,

cholestatic jaudice ,acute oliguria with hypertension,leucopenia and thrombocytopenia purpura.

The most dangerous side effect include bone marrow depression (causing aplastic anemia) agranulocytosis and cardiovascular collapse.

Side effect: carbamazapine

ANTI ANXIETY & HYPNOSEDATIVES

WHAT IS ANXIETY??It is an emotional state, unpleasant in nature, associated with uneasiness, discomfort and concern or fear about some re -defined or undefined future threat.

Anxiety is being in a state of stress, which is brought upon by many stressors.

It is the normal human response.

Anxiety is regarded as a disorder only when it occurs in the absence of appreciable degree, or kind, of threat or danger.

CLINICAL PRESENTATIONS

Palpitations.Chest pain.Breathlessness.Sweating, chills, nausea.Trembling, fear of dying or losing control.

Numbness, feeling of detachment.

ANTI-ANXIETY DRUGSBenzodiazepines.Azapirones.Sedative anti-histaminic.β-blocker.Newer drugs

BENZODIAZEPINES

Mode of actionModulates the gamma-amino butyric acid(GABA),the main inhibitory neuro- transmitter of CNS,by influencing the GABAa receptor complex.

The GABAa receptor complex includes binding sites for BZD,barbiturates and steroids. the chlorine ion channel is controlled by the GABA binding site.When the neuro transmitter GABA binds with the receptor it triggers a conformational change in the pore, allowing more chlorine to enter the cell.

Resulting in hyperpolarisation of cell membrane, increasing the firing threshold and producing an inhibition of action potential firing.

Upon binding,BZDs lock the GABAa receptor into a conformation that increases the binding of GABA.

Increased GABA binding increases the frequency of opening the chlorine channel and amplifying the inhibitory effect.

Class of drug

Elimination T1/2 (hr)

Oral DosageMg/day

Parenteral dose(mg)

Active metabolites

Comments

Very short acting1.Triazolam

2.Midazolam

2-5

2-5

0.125-0.25

α-hydroxy triazolam.

Rapid oral absorption, marked as hypnotic, used as anesthesia

Short acting1.Oxazepam

2.Lorazepam

3.Temazepam4.Alprazolam5.Estazolam

5-15

10-20

10-20

6-20

8-24

15-120

2-6

15-30

0.5-6

1-2

1-2 iv or im

Oxazepam

α-hyroxy alprazolam

Slow oral absorption,high dependence potential

Class of drug

Eliminati

on T1/2 (hr)

Oral DosageMg/day

Parenteral dose(mg)

Active metabolites

Comments

Long acting1.Chlordiazepoxide2.Diazepam

3.Flurazepam4.Chlorazepate5.Nitrazepam6.Prazepam

7.Halazepam8.Clonazepam9.Quazepam

25-48

14-90

30-100

30-100

20-60

30-60

30-60

20-40

40-160

15 -100

2 – 60

15-60

7.5-60

5-20

20-60

40-160

0.5-20

7.5-15

50-100 iv slowly2-20 iv or im

2-5 im

Desmethyl-demoxypamNordiazepam

Desmethy-hydroxy-ethyl-flurazepamNordiazeapamNordiazepam

Nordiazepam,diazepam

Nordiazepam

Erratically absorbed after IM injection,Marked as hypotic,Hydrolyzed to active form in stomachMarked as hypnoticSlow oral absorptionAlso used in mania .probably selective for BZD receptor l and may cause less cognitive and motor disturbances

INDICATIONS OF ANTI-ANXIETY DRUGS Triazolam and midazolam:- For Generalized

anxiety, panic attacks. Oxazepam,Lorazepam,Temazepam,Alprazola

m, Estazolam—For Insomnia,nightmares,muscle relaxation, drug withdrawal, acute mania attacks

Chlordiazepoxide,Diazepam,Flurazepam,Chlorazepate,Nitrazepam,Prazepam,Halazepam,Clonazepam,Quazepam—For Minor surgery, acute psychosis,narcoanalysis,anti convulsant,somnambulism,agitation depression attacks.

AZAPIRONESClass of drug

Elimination T½

Dose Mode of action

Adverse effects

Buspirone

Gepirone

Ispapirone

2-3.5 hrs 15-30mg/day

5-HT1a partial agonist and a selective DA autoreceptor antagonist

Dizziness.headache,lightheadedness and diarrhoea.

SEDATIVE ANTI-HISTAMINES

Mode of actionSelective anxiolytic action with sedation.

Seldom used nowadays.Diphenhydramine, Hydroxyzine and Promithazine.

ΒETA-BLOCKERSExample is propranolol effective in peripheral manifestations of anxiety.

C/I in asthmatics and cardiac conditions.

Dose is 40-240mg/day.

NEWER DRUGSBuspirone-non BZD anti-anxiety drug.

its is a 5-HT1a partial agonist and a selective DA auto-receptor antagonist. also inhibits the auto-firing of neurons.

It does not seem to act on BZD receptor. It is anxio-selective with no sedative action, and no anti-anticonvulsant or muscle relaxant properties.

Dose is 15-30mg/day, in a thrice daily schedule due to short half-life.not useful in t/t of panic disorders.

Zopiclone—belongs to a new class of group, the cyclopyrrolone.They act on GABA receptors but at a site different from that of BZDs.Has a short duration of action as well as shorter onset.Elemination t½ is 4-6hrs.

Usual dose is 3.75-7.5 mg at bed time. Side effects include bitter taste, dry

mouth,drowsiness,nausea and headache

Clinically superior to BZDs in subjective awakening quality, well being and attention span in morning.

Zolpidem—it is an imidazopyridine derivative which is marketed as a hypnotic.

It is administered in a dose of 5-10 mg for hypnotic use. It has a half life of 2-3 hrs; therefore it is useful in treatment of difficulty in initiation of sleep(initial insomnia).

Side effects include drowsiness,dizziness,headache,depression,nausea,dry mouth and myalgia.

It should not be used for more than two weeks at one time.

Safety in children, in pregnancy and lactation is not proven.

Zolpelon-it is a pyrazolo-pyrimidine derivative, marked as a hypnotic. It acts on omega-1 benzodiazepine receptor located on the alpha sub-unit of the GABA-A receptor complex, with a very little effect on omega-2 and omega-3 receptors.

Given in a dose of 5-10 mg for hypnotic use.T½ being of 1 hr with a rapid onset of effect.

Side effects include headache,drowsiness,dizziness,nausea and myalgia.It should not be used for more than 2 weeks at one time.

Other drugs—these include suriclone(a cyclopyrrolone derivative; a hypnotic), bretazenil and imidazenil(partial benzodiazepine agonists; anxiolytic without sedation; rapid onset of action),abecarnil(β-carboline partial agonist at benzodiazepine receptor; anxiolytic and anti-convulsant),tiagabine,riluzole,and alpidem(anxiolytic).

Pregabalin is licensed for treatment of anxiety in some countries. Cognitive behavior therapy with or without medication is helpful in treatment of several anxiety disorders.

ANTI-EPILEPTICS

WHAT IS EPILEPSYIt is a brief recurrent disorder of cerebral function that is usually associated with disturbance of consciousness and accompanied by a sudden, excessive electrical discharge of cerebral neurons.

ANTI-EPILEPTICSBarbituratesDeoxybarbituratesHydantoinIminostilbeneSuccinimideAliphatic carboxylic acidbenzodiazepines

PhenyltriazineCyclic GABA analogueNewer drugs

Class of drug

Elimination T½

Dose Indications

Mode of action

Adverse effects

Phenobarbitone

Primidone

80- 120 hrs

6-14 hrs

60- 180 mg/day

250-500mg BD

Primary generalized tonic clonic,partial seizures.

GABAa receptor mediated synaptic inhibition

HangoverIdiosyncrasyHypersensitivityDependence.

Phenytoin 12-24 hrs

200-400 mg/day as single dose.

Generalized T-C,simple and complex partial, status epilepticus,trigeminal neuralgia

Prolongation of sodium channel inactivation.

Gum hypertrophyHirsutismHypersensitivityMegaloblastic anemiaOsteomalaciaHyperglycemia

Class of drug

Elimination T½

Dose Indications

Mode of action

Adverse effects

Carbamazepine

20-40hrs 600-1800mg/day in 2-3 divided doses

Primary generalized tonic clonic,partial seizures.

Prolongation of sodium channel inactivation.

Sedation,dizziness,vertigo,diplopia,ataxia.

Ethosuximide

48 hrs 750-1250mg/day as single dose

Absence seizures

Inhibition of T type calcium current

G-I intolerance,Mood changes,headache,drowsiness.

Class of drug

Elimination T½

Dose Indications Mode of action

Adverse effects

Valproic acid

10-15 hrs

400-3000mg/day in 2-3 divided doses

Absence seizures,GTCS,SPS and CPS

Prolongation of Na channel inactivation.Attenuation of Ca mediated T current.

Rise in serum transaminase,alopecia,curling of hair,inc. blood ammonia,fulminant hepatitis

Clonazepam

Clobazam

Diazepam

24 hrs

35 hrs

30-60 hrs

1-12 mg/day10-60mg/day0.2-0.5mg/kg

Myoclonic szrs

GTCS,SPS,CPS

Insomnia,anxiety,night b4 surgery

Facilitation of GABA mediated Cl channel opening.

Sedation,dullnessThrombophlebitis,respiratory depression, fall in BP.

Class of drug

Elimination T½

Dose Indications

Mode of action

Adverse effects

Lamotrigine

24hrs 50mgday-300mg/day

Add on therapy in refractory partial and GTCS

Modifies maximal electroshock and decreases electrically evoked after-discharge duration.

Sleeplessness,dizziness,diplopia,ataxia and vomiting

Gabapentin

6-8 hrs

300mg/day

Absence seizures,GTCS,SPS and CPS

Enhances GABA release and inhibits PTZ induced clonic seizures.

Mild sedation,tirdeness,dizziness and unsteadiness

ALCOHOL AND DRUG DEPENDENCE

WHAT IS DEPENDENCE??According to ICD-10 the dependence syndrome is a cluster of physiological , behavioral and cognitive phenomena in which the use of a substance or a class takes much higher priority for a given individual than other behaviors that once had great value.

PSYCHOACTIVE SUBSTANCE ABUSEDrug Route of

administration

Physical dependence

Psychic dependence

Tolerance

Alcohol Oral ++ ++ +

Opioids Oral,IV,smoking +++ +++ +++

Cannabis(Marihuana)

Smoking,oral +,-- ++ +

Cocaine Inhalation,oral,smoking parental

+,-- ++

Amphetamines

Oral,parentral ++ ++ +++

Drug Route of administration

Physical dependence

Psychic dependence

Tolerance

Lysergic acid diethyl amide(LSD)

Oral + +

Barbiturates Oral,parentral

++ ++ +++

Benzodiazepines

Oral,parentral

+ + +

Volatile solvents

Inhalation +,- ++ +

Phencyclidine (PCP)

Smoking,inhalation,parentral,oral

+,- + +

Caffeine Oral + ++ +

Nicotine Oral,smoking

+ ++ +

TREATMENTAddiction is a complex but treatable

disease that affects brain function and behavior.

No single treatment is appropriate for everyone.

Treatment needs to be readily available.

Remaining in treatment for an adequate period of time is critical.

Effective treatment approaches include—

Detoxification

Treatment Relapse

prevention

DETOXIFICATIONSymptoms produced by the

removal of the toxin(alcohol).The aim of detoxification is

symptomatic management of emergent withdrawal symptoms.

Drug of choice are usually benzodiazepines.

Chlordiazepoxide(80-200mg/day)Diazepam (40-80mg/day)

TREATMENT Behavior therapy-aversion therapy,

using either a sub-threshold electric shock or an emetic such as apomorphine.

Other methods like(covert sensatisation,relaxation techniques, assertiveness training, self control training and positive reinforcement) has been used along with aversion therapy.

Considered unethical in treatment of alcohol dependence.

Psycho-therapy—both group and individual. patient is educated about the risks of continuing alcohol use.

Motivational enhancement therapy with or without cognitive behaviour therapy and life style modification.

The deterrent agents—disulfiram(tetraethyl thiuram disulfide)

When alcoholics ingested by a person who is on disulfiram,alcohol-derived acetaldehyde cannot be oxidised to acetate and this leads to accumulation of acetaldehyde in blood.

This causes the disulfiram ethanol reaction(DER) characterized by

flushing,tachycardia,hypotension,tachypnoea,palpitation,headache,sweating,nausea,vomiting,giddiness and a sense of impending doom.

Onset of reaction occurs within 30minutes becomes full blown within 1 hr and subsides within 2 hrs of ingestion of alcohol.

The usual dose is 250-500mg/day.

Parkinsonism

WHAT IS PARKINSONISM??Extrapyramidal motor disorder characterized by rigidity, tremor and hypokynesia with secondary manifestations like defective posture and gait, mask like face sialorrhoea,dementia may accompany.

ANTI-PARKINSONISM'S

Drugs affecting brain dopaminergic system

Dopamine precursor-Levodopa(L-dopa).

Peripheral decarboxylase inhibitor-carbidopa,benserazide.

Dopaminergic agonist-bromocriptine,pergolide,piribedil,ropinirole,pramipexole

MAO-B inhibitors-SelegilineCOMT inhibitors-entacapone,tolcapone

Dopamine facilitator-Amantadine.

DRUGS AFFECTING BRAIN CHOLINERGIC SYSTEM

Central anticholinergics-trihexyphenidyl(benhexol),procyclidine,biperidine.

Anti-histaminics-orphanadrine,promithazine.

LEVODOPA (L-DOPA)Mode of action-Orally administered L-dopa after

absorption crosses blood brain barrier and gets metabolized to dopamine.

Dopamine cannot cross BBB so,a peripheral decarboxylase inhibitor is given such as carbidopa or benserazide.

DOSAGE AND T1/2Started with a low dose of

50mg/dose. Full therapeutic effect may take 4-8 weeks. Maximum dose is 800-1000mg/day.

Plasma t1/2 of levodopa is 1-2 hrs.

ADVERSE EFFECTSAt initiation of therapy-

nausea,vomiting,postural hypotension, cardiac arrhythmias, exacerbation of angina, alteration of taste sensation.

After prolonged therapy-abnormal movements, fluctuation in motor performance.

PERIPHERAL DECARBOXYLASE INHIBITORSCarbidopa and benserazide are

given along with levodopa to increase the t1/2 in periphery and make more of it available to cross BBB and to reach its site of action.

Maintenance dose is 0.4-0.8g of levodopa with 75-100mg carbidopa or 100-200mg of benserazide given in 3-4 divided doses.

DEMENTIA

WHAT IS DEMENTIA??Refers to acquired global impairment of intellect, memory and personality(cognitive function) in the absence of gross clouding of consciousness or motor involvement.

COGNITION ENHANCERS Nootropic (cognition enhancer)-

piracetam Metabolic enhancer-

dihydroergotoxine(codergocrine),nicergoline,piribedil

Cholinergic activators-tacrine,rivastigmine,donepezil,galantamine

Vasoactive cerebral protector-pyritinol(pyri-thyoxine) ,ginkgo biloba

INDICATIONS Senile dementia and confusional states

of old age. Mental retardation and learning

problems in children. Cerebrovasular accidents-to hasten

recovery of neuronal function. To reduce impairment of consciousness

following brain surgery, memory impairment after ECT,and central vertigo.

Class of drug Dose Mode of action

Adverse effects

Piracetam

Dihydroergotoxine(Codergocrine)

Nicergoline

Piribedil

0.8-1 g TDS

1-1.5mg TDS

30mg OD

50mg OD

Enhances learning and memory. Facilitates inter hemisphere information transfer. Increased tonic cortical control on subcortical areas.

Gastric discomfort,excitement,insomnia,dizziness and skin rash.

What we have learned so far…

The drug groups can be chosen according to the pattern and severity of the disorders. Accordingly the dosage of the drugs can be managed.

Pyscho-pharmacology is one of the important measures in the management of the mental disorders.

Thank you…