12-2.Antidepressants.doc

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Antidepressants

& antipsychoticDone by:

Hashim ghazo

Mais Maloul

Antidepressants & antipsychotic*ANTIDEPRESSANTS

Drugs which can Elevate Mood (Mood Elevators(Definitions:

Affective disorders- mental illnesses characterized by pathologicalchanges in mood (not thought compare with schizophrenia

{ pathological changes in thought{(

1.Unipolar disordersMania and depression are opposite to each other in caused:

*Depression pathologically depressed mood.The cause : deficiency of monoamine in CNS.


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*Mania excessive elation and accelerated psychomotor activity( aggressive) (rare(

The cause : over activity of monoamine in CNS2.Bipolar disorder (manic-depressive illness) cycling mood

{ both episodes mania + depression , the pt in mania in one timeand in depression in other time.

*severe highs (mania) and lows (depressive episodes(

It is common & normal emotion in which people becoming depressed as a result ofunfortunate domestic and social conditions, sometimes the depression is

disproportionate to precipitating factors or there may be no obvious cause at all.

In females more than males.

Clinical presentation:

*Emotional symptoms:Sadness.

Hopelessness.

Loss of interest in usual activities.

Feeling of guilt.

*Physical symptoms

Fatigue

Sleep disturbance

Pain (especially headache(

Appetite disturbance or

Intellectual or cognitive symptoms*

Decreased ability to concentrate or slow thinkingConfusion.Poor memory for recent events.

*Reduced self-esteem & self-confidence.

*Ideas or acts of self harm or suicide.

What is the cause of depression?Monoamine theory

Suggests that depression results from functionally deficient monoamineneurotransmitters (Norepinephrine (NE) &/or Serotonin (5-HT)) in the CNS.

Therefore, in the treatment we try to the level of these neurotransmitters


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A : you can see before treatment after NT produce it's action , it's stored back to it'spresynaptic by reuptake process.B : if NT bind to presynaptic receptor , it will inhibit NT release.Acute effect : the anti-depressant inhibit reuptake process.

C : chronic effect : not only inhibit the reuptake but also down regulation of PSreceptors that will increase NT release.

Major classes of anti-depressants:

1.Reuptake inhibitors

A. Selective serotonin(5-HT) reuptake inhibitors (SSRIs) { selective inhibit reuptakeserotonin{

e.g. Fluoxitine

B. Selective norepinephrine(NE) reuptake inhibitors { selective inhibit reuptake nor-

epinephrine{e.g. Reboxitine

C. None Selective NE/5-HT reuptake inhibitors(TCAs) { can inhibit reuptake ofserotonin as well as NE{

e.g. tri-cyclic anti-depressants { Imipramine ,Amitriptyline } , heterocyclicantidepressant.

2.Monoamine oxidase inhibitors

Mono amine oxidase is responsible for metabolism of monoamines like epinephrine

NE dopamine so if I block the enzyme , I inhibit the metabolism and increase theneurotransmitters


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e.g. Phenelzine

3.Atypical antidepressants

e.g. Mirtazapine { it block presynaptic alpha 2 receptors in CNS and by that , this willlead to release NE{ .

Tricyclic antidepressants (TCAs(

MOA:

non-selective , Inhibit reuptake mechanism which is responsible for termination of

the synaptic action of NE & 5-HT in the brain

Blocking of receptors :TCAs also block muscarinic,serotonin, histamine, -adrenergicresponsible of S/Es

Examples: Imipramine, Amitriptyline

-----------------------------------------------

Pharmacokinetics

Well absorbed orallyVariable first pass metabolism,TCAs have different bioavalabilityThey have narrow-therapeutic indexThey have a delay in their onset of action requiring 2 weeks or longer. { all anti-

depressant , not only TCA{

Therapeutic uses:

1.Major depression2.Some panic disorder respond to TCAs


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3.Imipramine has been used to control bed-wetting in children (older than 6years). { anti-muscaranic effect , it close the sphincter of the bladder{

4.Migraine and chronic pain Amitryptiline tryptizol

S/Es:

Antimuscarinic: constipation, blurred vision, urinary retention, dry mouth ,tachycardiaBlock serotonin,histamine receptor : SedationBlock alpha : Postural hypotensionArrhythmiasWeight gain

Selective Serotonin Reuptake Inhibitors (SSRIs(

MOA :Blocks serotonin uptake onlyExamples: Fluoxetine {prozac{

Its more better than non-selective because:SSRIs have little activity to block muscarinic , histamine H1, -adrenergic receptors& relatively safe in over dose.

------------------------------------------

Therapeutic uses:1.Primary indication is depression

2.Obsessive compulsive disorders3.Fluoxetine is effective in treating bulimia nervosa : the person like to eat but

at the same time when finish inducing vomiting.

S\Es:

1.GI: nausea, vomiting, weight loss

2.Sexual dysfunction


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Monoamine Oxidase Inhibitors (MAOIs(

Monoamine Oxidase enzyme found in mitochondria , gut and liver.MOA: Inactivate monoamine oxidase A & B enzymes permitting neurotransmitter

molecules to escape degradation ( NE&5-HT levels(

MAO A : metobolize NE , serotonin and.

MAO B : metabolize dopamine

Example: phenelzine

-----------------------------------------------

MOA of monoamine oxidase inhibitors

Indicated for depressed patients who are unresponsiveness or allergic to TCAs*

*Because of their risk for drug & drug food interaction, MAOIs are considered

to be the last line agents.

*S/Es

Hypertensive reaction may occur in patients taking MAO inhibitors and consumeTyramine containing food (as aged cheeses, beer, red wines(


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Drug Choice:

*Comparisons of the antidepressants showed that they are roughly equivalent inefficacy.

*Individual patients may respond better to one drug than to another.*SSRIs are not sedative, safe in overdose and have mild adverse effects so they are

widely prescribed.*Finding the right drug and the right dose must be accomplished empirically.

Bipolar Disorder:


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Drugs used in Mania Mood Stabilizers :

Lithium Carbonate

Alternative Drugs:

Carbamazepine

Sodium Valproate

Mood stabilizing drugs

e.g Lithium salts

Therapeutic uses:used prophylactically for treating manic-depressive disorder & in thetreatment of mania.

Its safety factors &

therapeutic index are very low It is Teratogenic{ Able to disturb the growth and development of an embryo orfetus. }

S/Es:

1.Fine hand tremor2.Polydipsia3.Fatigue4.Sedation5.Thyroid function may be decreased &should be monitored T3 & T4

DRUG TREATMENT OF PSYCHOSIS :

Schizophrenia :

Is a psychiatricdiagnosis that describes a mental disorder characterized by abnormalities inthe perception or expression of reality Characterized by

psychosis, hallucinations , delusions , cognitive defects,occupational and social dysfunction

Gender : Affectsmales and females equally

Males in the early20s Females in early 30s
http://www.medterms.com/script/main/art.asp?ArticleKey=3225http://www.medterms.com/script/main/art.asp?ArticleKey=3424http://www.medterms.com/script/main/art.asp?ArticleKey=3225http://www.medterms.com/script/main/art.asp?ArticleKey=3424


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Schizophrenia:Positive vs Negative symptoms

PositiveSymptoms= psychosis

Hallucinations and

delusions, talkativeness & illusions.Respond well to traditional antipsychotic medication. NegativeSymptoms:

Low motivation,social involvement Emotionalabnormalities

Respond better toatypical antipsychotic medication.

Pathophysiology

Strong genetic component &some biochemical abnormality possibly dysfunction ofmesolimibic or mesocortical dopaminergic neurons { dopamine over activity of theCNS }

Dopaminehypothesis:

It claims that schizophrenia is due to over activity of dopaminergic neurons, (mostdrugs blocks D2 receptors) however, the dopamine hypothesis of schizophrenia is notfully satisfactory because several of atypical antipsychotics have much less effect onD2 receptors, they exert their action through the inhibition of serotonin receptors(5-HT2A)

Classification of

antipsychotic drugs


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The antipsychotic drugs or (Neuroleptics) are classified:

1.Typical "Classical antipsychotics"E.g.: Chlorpromazine, Haloperidol

MOA: they are antagonists at dopamine D2 receptors

2. Atypical antipsychotics

E.g.: Clozapine

MOA: They block dopamine receptors & they appear to exert part of their actionthrough inhibition of serotonin receptors

Therapeutic uses:

1.Treatment of schizophrenia2.Treatment of intractable hiccup3.prevention of nausea & vomiting4.Promethazine is used to treat pruritus because of Histamine (H1) blockade

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S/Es:

1.Endocrine effects


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Dopamine is an inhibitor of Prolactin secretion(Side effect of typical antipsychotics)

Blocking D2 receptors by antipsychoticsIs thus Prolactin level & this resulting in lactation, amenorrhea , galactorrhea &infertility in women. Impotence in men.

2. Sedation due to H1 blocking effect.(Side effect of typical antipsychotics)

3.Blocking muscarinic receptors particularlychlorpromazine, cause atropine-like effect (dry mouth, constipation, urinary retention)

4. Blocking -adrenoceptors particularly chlorpromazine & this cause posturalhypotension

5. Antipsychotic-induced motor disturbances(Side effect of typical antipsychotics)

a. Acute, reversible extrapyramidal effects:

1. Parkinsonian symptoms,Blocking dopamine receptors in the nigrostriatal pathway.

2. Akathisia : motor restlessness.

3. Acute dystonia : involuntary twisting of the muscles in the head and neck .

b. Chronic extrapyramidal effects(Side effect of typical antipsychotics)

Slowly developing tardive dyskinesia {Tardive dyskinesia comprises mainly adisorder resulting in involuntary, repetitive body movements of muscles of the face &the limbs; & may be irreversible } , develops after months or years in patients treated

with classical antipsychotic drugs

Atypical drugs exhibits a lower potential for extrapyramidal symptoms.

Done by :Hashim GazoMais Maloul

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