PSYCHOPHARMACOLOGY

Terms Psychotropic medication: Neurotransmitter: Receptor: Medications that affects psychic function, behavior or experience Neurotransmitter: A chemical that is stored in the axon terminals of the presynaptic neuron Receptor: Molecules situated on the cell membrane that are binding sites for neurotransmitters

Effects of psychotropic medications on neurotransmitters Action on NT/ Receptor Physiological effects Side effects SSRI’s Inhibit reuptake of seretonin Reduce depression Control anxiety Control obsessions Nausea, agitation, headache, sexual dysfunction Tricyclic antidepressants Inhibit reuptake of seretonoin Inhibit reuptake of norepinephrine (NE) Block NE receptor Block ACh receptor Block histamine receptor Relief of severe pain Prevent panic attacks Sexual dysfunction (NE & 5 – HT) Sedation, weight gain (H1) Dry mouth, constipation, blurred vision, urinary retention (ACh), postural hypotension and tachycardia

Cont… Medication Action on NT/ Receptor Physiological effects Side effects MAO inhibitors Increase NE & 5 – HT by inhibiting the enzyme that degrades them (MAO – A) Reduce depression Control anxiety Sedation, dizziness Sexual dysfunction Hypertensive crisis (interaction with tyramine) Trazodone & nefazadone 5 – HT2 receptor antagonism Adrenergic receptor blockade Reduce anxiety Nausea, sedation, orthostasis, priapism SSNRI’s: venlafaxine and duloxetine Potent inhibitor of seretonin & norepinephrine reuptake Weak inhibitor of dopamine reuptake Relieve pain of neuropathy (duloxetine) Relieve anxiety (venlafaxine) Nausea, increased sweating, insomnia, tremors, sexual dysfunction Bupropion Inhibits reuptake of 5-HT. NE & dopamine Reduce depression, aid in smoking cessation, reduce symptoms of ADHD Insomnia, dry mouth, tremor, seizures

Cont… Medication Action on NT/ Receptor Physiological effects Side effects Antipsychotics: phenothiazines and haloperidol Strong D, receptor blockade Weaker blockade of ACh, H1, alpha adrenergic & 5-HT2 receptors Relief of psychosis Relief of anxiety (Some) provide relief from nausea and vomitting and intractable hiccoughs Blurred vision, dry mouth, decreased sweating, constipation, urinary retention. Tachycardia EPS, increased plasma prolactin (D2), sedation, weight gain (H1), ejaculatory difficulty (5-HT2), orthostatic hypotension Antianxiety: benzodiazepines Binds to BZ receptor sites on the GABA receptor complex, increases receptor affinity for GABA Sedation Dependency (with long term use) Confusion, memory impairment, motor incoordination

Cont… Medication Action on NT/ Receptor Physiological effects Side effects Antipsychotics (novel): clozapine, olanzapine, arip[iprazole, quetiapine, risperidone, ziprasidone Receptor antagonism of 5-HT D1 – D5 (varies with drug) H1, alpha 1 adrenergic, muscarinic (ACh) Relief of psychosis (with minimal or no EPS) Relief of anxiety Relief of acute mania Potential with some of the drugs for mild EPS (D2) Sedation, weight gain (H1) Orthostasis & dizziness Blurred vision, dry mouth, decreased sweating, constipation, urinary retention, tachycardia (ACh) Antianxiety: buspirone 5-HT agonist D2 agonist D2 antagonist Nausea, headache, dizziness Restlessness

ANTIANXIETY AGENTS Indications These are also called anxiolytics and minor tranquilizers. These are used in the treatment of anxiety disorders, anxiety symptoms, acute alcohol withdrawal, skeletal muscle spasms, convulsive disorders, status epilepticus and preoperative sedation.

Cont… Side effects: Drowsiness, confusion, lethargy Tolerance; physical & psychological dependence Ability to potentiate the effects of other CNS depressants Possibility of aggravating symptoms in depressed persons Orthostatic hypotension Paradoxical excitement Dry mouth Nausea & vomiting Blood dyscrasias Delayed onset

Examples Chemical class Generic (trade) name Antihistamines Hydroxyzine (Atarax, Vistaril) Benzodiazepines Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Traxene) Diazepam (Valium) Lorazepam (Ativan) Oxazepam (Serax) Propanediols Meprobamate (Miltown) Azaspirodecanediones Buspirone (BuSpar)

ANTIDEPRESSANTS Indications: It is used in the treatment of dysthymic disorder, major depression with melancholia or psychotic symptoms, depression associated with organic disease, alcoholism, schizophrenia or mental retardation, depressive phase of bipolar disorder and depression accompanied by anxiety. These drugs elevate mood and alleviate other symptoms associated with moderate-to-severe depression

Cont… Side effects with all chemical classes: Dry mouth Sedation Nausea Discontinuation syndrome Hepatic failure Side effects with MAOI’s: Hypertensive crisis

Cont… Side effects with tricyclics: Blurred vision Constipation Urinary retention Orthostatic hypotension Reduction of seizure threshold Tachycardia; arrhythmias Photosensitivity Weight gain

Cont… Side effects with SSRI’s: Insomnia, agitation Headache Weight loss Sexual dysfunction Seretonin syndrome

Examples Chemical class Generic (trade) name Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine SSRI’s Citralopram, Fluoxetine, Fluvoxamine, Escitalopram, Paroxetine, Sertraline MAOI Isocarboxazid, Phenelzine, Tranylcypromine Others Bupropion, Maprotiline, Mirtazapine, Trazodone, Nefazodone, Venlafaxine, Duloxetine

MOOD STABILIZING AGENTS ANTIMANIC: Prevention and treatment of manic episodes of bipolar disorder, alcohol dependence, major depression ANTICONVULSANTS: All stages of seizures CALCIUM CHANNEL BLOCKERS: Angina, arrhytmias, hypertension, bipolar mania, migraine headache ANTIPSYCHOTICS: Schizophrenia, bipolar mania

Cont… Chemical class Generic (trade) name Antimanic Lithium carbonate Anticonvulsants Clonazepam, carbamazepine, valporic acid, lamotrigine, gabapentin, topiramate Calcium channel blocker Verapamil Antipsychotics Olanzapine, aripiprazole, chlorpromazine, quetiapine, risperidone, ziprasidone

Cont… Side effects of antimanic: Drowsiness, dizziness, headache Dry mouth, thirst GI upset, nausea/ vomiting Fine hand tremors Hypotension, arrhythmias, pulse irregularities Polyuria, dehydration Weight gain Side effects of calcium channel blockers: drowsiness, dizziness Hypotension, bradycardia Nausea constipation

Cont… Side effects of anticonvulsants: Side effects of antipsychotics: Nausea/ vomitting Drowsiness, dizziness Blood dyscrasias Prolonged bleeding time Risk of severe rash Decreased efficacy with oral contraceptives Side effects of antipsychotics: Dry mouth, constipation Increased appetite, weight gain ECG changes Extra Pyramidal Symptoms Hyperglycemia & diabetes

ANTIPSYCHOTIC AGENTS Indications: These are also called major tranquilizers and neuroleptics. They are used in the treatment of acute and chronic psychoses particularly when accompanied by increased psychomotor activity Selected agents are used as antiemetics in the treatment of intractable hiccoughs and for the control of tics and vocal utterances in Tourette’s disorder

Examples Chemical class Generic (trade) name Phenothiazines Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine Thioxanthene Thiothixene Benzisoxazole Risperidone Dibenzoxazepine Loxapine Dihydroindolone Molindone Dibenzodiazepine Clozapine Diphenylbutylpiperidine Pimozide Thienobenzodiazepine Olanzapine Dibenzothiazepine Quetiapine Benzothiazolylpiperazine Ziprasidone Dihydrocarbostyril Aripiprazole

Cont… Side effects of antipsychotics: Anticholinergic effects such as dry mouth, blurred vision, constipation, urinary retention Nausea, GI upset Skin rash Sedation Orthostatic hypotension Photosensitivity Hormonal effects ECG Changes Reduction of seizure threshold Agranulocytosis Hypsersalivation

Cont… Extrapyramidal symptoms (EPS) Pseudoparkinsonism Akinesia Akathisia Dystonia Oculogyric crisis Tardive dyskinesia Neuroleptic malignant syndrome Hyperglycemia and diabetes

SEDATIVE HYPNOTICS Indications: They are used in the short term management of various anxiety states and to treat insomnia. Selected agents are used as anticonvulsants and preoperative sedatives and to reduce anxiety associated with drug withdrawal

Examples Chemical class Generic (trade) name Barbiturates Amobarbital, Butabarbital, Mephobarbital, Pentobarbital, Phenobarbital, Secobarbital Benzodiazipines Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam Miscellaneous Chloral hydrate, Eszopiclone, Zaleplon, Zolpidem

Cont… Side effects: Drowsiness, confusion, lethargy Tolerance; physical & psychological dependence Ability to potentiate the effects of other CNS depressants Possibility of aggravating symptoms in depressed persons Orthostatic hypotension Paradoxical excitement Dry mouth Nausea & vomiting Blood dyscrasias Delayed onset

Newer trends – agents for ADHD Indications: These are used for ADHD in children and adults Side effects: Overstimulation, restlessness, insomnia Palpitations, tachycardia Anorexia, weight loss Tolerance, physical and psychological dependence Nausea and vomiting Constipation Potential for seizures

Examples Chemical class Generic (trade) name Amphetamines Dextroamphetamine sulfate, Methamphetamine Amphetamine mixtures Dextroamphetamine/ amphetamine Miscellaneous Methylphenidate, Dexmethylphenidate, Pemoline, Atomoxetine, Bupropion