Antidepressants & antipsychotic

: Done by Hashim ghazo Mais Maloul

Antidepressants & antipsychotic ANTIDEPRESSANTS * (Drugs which can Elevate Mood (Mood Elevators : Definitions Affective disorders - mental illnesses characterized by pathological changes in mood (not thought compare with schizophrenia ( { { pathological changes in thought Unipolar disorders . 1 : Mania and depression are opposite to each other in caused .Depression pathologically depressed mood * . The cause : deficiency of monoamine in CNS

Mania excessive elation and accelerated psychomotor activity * (( aggressive) (rare The cause : over activity of monoamine in CNS Bipolar disorder (manic-depressive illness) cycling mood . 2 { both episodes mania + depression , the pt in mania in one time . and 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 of unfortunate 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 thinking . Confusion .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 monoamine .neurotransmitters (Norepinephrine (NE) &/or Serotonin (5-HT)) in the CNS Therefore, in the treatment we try to the level of these neurotransmitters

?? How we increase NT now if we think of administration of NE , it is useless cz it . it doesn't penetrate BBB . 1 produce peripheral adverse effect .2 : So we can inhibit reuptake 2 . inhibit metabolism . 1

How ever this theory fails to explain why the pharmacologic effects of any antidepressant on neurotransmission occur immediately, whereas the time course for !??the therapeutic response occurs over several weeks This suggest that decreased uptake of neurotransmitter is only the initial effects. it has been proposed that presynaptic inhibitory receptor densities in the brain decrease over 2-to-4 week period with antidepressant drug use This down regulation of the inhibitor receptors permits greater synthesis & release of neurotransmitters into synaptic cleft and enhanced signaling in the postsynaptic .neurons .Leading to therapeutic response

Proposed MOA of antidepressant

A : you can see before treatment after NT produce it's action , it's stored back to it's . presynaptic 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 PS . receptors that will increase NT release :Major classes of anti-depressants Reuptake inhibitors.1 A. Selective serotonin(5-HT) reuptake inhibitors (SSRIs) { selective inhibit reuptake { serotonin 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 of { serotonin as well as NE e.g. tri-cyclic anti-depressants { Imipramine ,Amitriptyline } , heterocyclic . antidepressant Monoamine oxidase inhibitors .2 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 the neurotransmitters

e.g. Phenelzine Atypical antidepressants .3 e.g. Mirtazapine { it block presynaptic alpha 2 receptors in CNS and by that , this will { . lead 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, -adrenergic responsible of S/Es Examples: Imipramine, Amitriptyline ----------------------------------------------Pharmacokinetics Well absorbed orally Variable first pass metabolism,TCAs have different bioavalability They have narrow-therapeutic index They have a delay in their onset of action requiring 2 weeks or longer. { all anti{ depressant , not only TCA : Therapeutic uses Major depression.1 Some panic disorder respond to TCAs.2

Imipramine has been used to control bed-wetting in children (older than 6.3 { years). { anti-muscaranic effect , it close the sphincter of the bladder Migraine and chronic pain Amitryptiline tryptizol .4

: S/Es Antimuscarinic: constipation, blurred vision, urinary retention, dry mouth , tachycardia Block serotonin,histamine receptor : Sedation Block alpha : Postural hypotension Arrhythmias Weight gain (Selective Serotonin Reuptake Inhibitors (SSRIs MOA :Blocks serotonin uptake only { Examples: 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 Primary indication is depression.1 Obsessive compulsive disorders.2 Fluoxetine is effective in treating bulimia nervosa : the person like to eat but.3 . at the same time when finish inducing vomiting : S\Es GI: nausea, vomiting, weight loss.1 Sexual dysfunction.2

(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 (HT levels-5 .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 consume (Tyramine containing food (as aged cheeses, beer, red wines

: Drug Choice Comparisons of the antidepressants showed that they are roughly equivalent in * .efficacy .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

Drugs used in Mania Mood Stabilizers : Mood stabilizing drugs

Lithium Carbonate Alternative Drugs: Carbamazepine Sodium Valproate

e.g Lithium salts

Therapeutic uses: used prophylactically for treating manic-depressive disorder & in the treatment of mania. Its safety factors & therapeutic index are very low It is Teratogenic { Able to disturb the growth and development of an embryo or fetus. } S/Es: 1.Fine hand tremor 2.Polydipsia 3.Fatigue 4.Sedation 5.Thyroid function may be decreased &should be monitored T3 & T4

DRUG TREATMENT OF PSYCHOSIS : Schizophrenia : Is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality Characterized by psychosis, hallucinations , delusions , cognitive defects, occupational and social dysfunction Gender : Affects males and females equally Males in the early 20s Females in early 30s

Schizophrenia: Positive vs Negative symptoms Symptoms= psychosis delusions, talkativeness & illusions. Respond well to traditional antipsychotic medication. Symptoms: social involvement abnormalities atypical antipsychotic medication. Positive Hallucinations and Negative Low motivation, Emotional Respond better to

Pathophysiology

Strong genetic component &some biochemical abnormality possibly dysfunction of mesolimibic or mesocortical dopaminergic neurons { dopamine over activity of the CNS }

hypothesis:

Dopamine

It claims that schizophrenia is due to over activity of dopaminergic neurons, (most drugs blocks D2 receptors) however, the dopamine hypothesis of schizophrenia is not fully satisfactory because several of atypical antipsychotics have much less effect on D2 receptors, they exert their action through the inhibition of serotonin receptors(5HT2A)

antipsychotic drugs

Classification of

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 action through inhibition of serotonin receptors

Therapeutic uses:

1.Treatment of schizophrenia 2.Treatment of intractable hiccup 3.prevention of nausea & vomiting 4.Promethazine is used to treat pruritus because of Histamine (H1) blockade ----------------------------------- 1.Endocrine effects S/Es:

Dopamine is an inhibitor of Prolactin secretion (Side effect of typical antipsychotics) Blocking D2 receptors by antipsychotics Is 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 particularly chlorpromazine, cause atropine-like effect (dry mouth, constipation, urinary retention) 4. Blocking -adrenoceptors particularly chlorpromazine & this cause postural hypotension 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 a disorder 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.

NE MAONonTyram Symp Hydro Nore NE Select A xyphe pinep atho ine ive mime hrine nylac In

Ph X

MAO

ar

Done by : Hashim Gazo Mais Maloul