Ch.16 Psychotherapeutic Drugs

Anxiolytic Drugs- Indications

Benzodiazepines are the largest & most commonly prescribed anxiolytic drug class because they offer several advantages over the other drugs used to treat anxiety. Used sometimes for ethanol withdrawal, insomnia, muscle spasm, seizure disorders and as a adjuncts in anesthesia. Used as adjunct therapy for depression because depressive & Anxious symptoms often occur 2gether.

Antidepressant Drugs- Part 1

Choice for major depressive disorders useful in treating other disorders such as dysthymia( chronic low-grade depression) , schizophrenia( as an adjunctive drug), eating disorders and personality disorders. Some are also used in the treatment of HA, chronic pain syndrome, Sleep Disorders, premenstrual syndrome, and hot flashes A/W menopause. Drugs used to treat affective disorders increased levels of neurotransmitter concentration in the CNS these transmitters include serotonin(AKA 5-hydroxytryptamine) , dopamine and norepinephrine. Alterations in the levels of these neurotransmitters are responsible for causing depression.

Monoamine Oxidase Inhibitors- Toxicity

Clinical symptoms of Overdose does not appear until about 12 hours after ingestion. Primary signs & symptoms are cardiovascular and neurological. Most serious cardiovascular effects are tachycardia and circulatory collapse and the neurological symptoms of major concern are seizures & coma. Hyperthermia and miosis are usually present in overdose. Treatment is to eliminate the ingested Toxin and protect the organs at greater risk for damage the brain and the Heart. Treatment includes urinary acidification to a pH of 5 and hemodialysis. IV hypotensive drugs to treat hypertensive crisis.

2nd- Generation Antidepressants- Trazodone (Desyrel, Oleptro)

In the triazolopyridine drug class. First to selectively inhibit serotonin reuptake but minimal effect norepinephrine reuptake. Minimal adverse effects on the cardiovascular system. Indicated for treatment of depression and used as a non-addictive drug treatment for insomnia. Adverse effects include strong sedative qualities especially in the elderly. Sedative quality helpful with patients who have comorbid anxiety/ insomnia. Has been associated in rare cases of transient nonsexual priapism (dangerously sustained penile erection result of alpha- adrenergic blockade.) Interacts with azole antifungals, phenothiazines & protease inhibitor, All increase the risk of Trazodone toxicity. Carbamazepine levels increase & decrease trazodone levels. Don't use if recently used MAOIs.

Tricyclic Antidepressants- Interactions

Increased anticholinergic effects are seen when taken with anticholinergic and phenothiazine. When taken with MAOIs increase therapeutic and toxic effects such as hyperpyretic crisis (excessive fever).

Antipsychotic Drugs- Haloperidol (Haldol)

Indicated for long term treatment of psychosis. Contraindicated in patients in a comatose state those taking large amounts of CNS depressants and those with Parkinson disease due to its antidopaminergic effects. Can cause Extrapyramidal symptoms & tardive dyskinesias. Long duration of action which is useful in treating patients with schizophrenia. Given IV in acute situations.

Benzodiazepines- Dizepam (Valium)

Indication: Relief of anxiety, management of alcohol withdrawal, reversal of status epilepticus, preoperative sedation & less frequently as an adjunct for relief of skeletal muscle spasms. Active metabolites can accumulate in patients with hepatic dysfunction, because it is metabolized primarily in the liver. This results in additive, cumulative effects that may be manifested as prolonged sedation, respiratory depression or coma. Avoided if patient has major hepatic compromise. Adverse Effects: HA, Confusion & slurred speech Interactions: Alcohol & oral contraceptives. Longest acting

Benzodiazepine-Lorazepm (Ativan)

Intermediate-acting Good absorption & bioavailbility when given IM. can be irritating to muscle & must be diluted. Can be given IV push is useful in treating acutely agitated patients who are undergoing mechanical ventilation. Indications, Contraindications &AE similar to alprazolam

Tricyclic Antidepressants-Toxicity

Lethal especially when taken with alcohol. Primary organ system affected are the CNS & Cardiovascular system. Death usually due to seizures or dysrhythmias. No antidote only thing to do is reduce drug absorption by giving multi doses of activated charcoal. Giving Na bicarbonate speeds up elimination by alkalizing the urine. CNS damage avoided by giving diazepam. Cardio events decrease by giving antidysrhythmics. Basic life support to maintain vital organs are needed until enough has been eliminated out the body.

Lithium Part 2

Levels above 1.5-2.5 mEq/L begin to produce toxicity levels: GI discomfort, tremors, confusion, somnolence (drowsiness), seizures & possible death. Most serious adverse effect: Cardiac dysrhythmia. Others: Drowsiness, slurred speech, epilepsy-type seizures, Choreoathetotic movements (involuntary wavelike movements of the extremities), ataxia (generalized disturbance of muscular coordination) & hypotension. Long term treatment may lead to hypothyroidism. Drug interaction: thiazide diuretics, ACE inhibitors, NSAIDs (All can cause toxicity)

2nd- Generation Antidepressants- Fluoxetine (Prozac)

1st SSRI marketed for the treatment of depression. Initially indicated for the treatment of depression can also be used for bulimia, OCD, panic disorder & premenstrual dysphoric disorder. Contraindications include known drug allergies and concurrent MAOI therapy. Adverse effects include anxiety, dizziness, drowsiness, insomnia. Interactions: benzodiazepines (reduce benzodiazepine clearance). Buspirone (reduce effect). Antipsychotic (elevated levels) & propanfenone.

2nd- Generation Antidepressants- Interactions

2nd generation antidepressants are highly albumin period when given with other drugs that are highly protein-bound (Warfarin & Phenytoin) they compete for binding sites of the surface of albumin this results in more free unbound drugs and therefore more pronounced drug effect. Some inhibit cytochrome p450 enzyme. Inhibition of this enzyme results in higher levels of these drugs with the potential of toxicity. Use a washout period of 2-5 weeks between these drugs & MAOIs.

Atypical Antipsychotics- Risperidone (Risperdal)

More active at the serotonin receptors. Has a high affinity for Alpha 1 and Alpha 2 adrenergic receptors and histamine 1 receptors. Indicated for schizophrenia including negative symptoms and causes of minimal extrapyramidal. Adverse effects include elevated prolactin levels, abnormal dreams, insomnia, dizziness, headache. Drug interactions include CNS depressant, antihypertensives. The long-acting injectable form is called Risperdal Consta and 1 IM injection last approximately two weeks. Must continue to take PO for 3 weeks at the first injection to ensure adequate blood levels from injection. Paliperidone also comes as a long-acting injection(invega sustenna) which lasts 1 month

Antipsychotic Drugs- Indications

Most commonly schizophrenia. The more is learned their indications have been expanded to include anxiety and mood disorders. They block serotonin receptors and dopamine receptors in the chemoreceptor trigger Zone in the brain and inhibit neurotransmission in the vagus nerve in the GI tract. Additional blocking of dopamine receptors in the brain stem reticular system also allows atypical drugs to have anxiolytic or antianxiety effects.

Anxiolytic Drugs-Contraindications

Narrow angle glaucoma, due to their ability to cause mydriasis. Pregnancy due to their sedative properties & risk for teratogenic effects

Tricyclic Antidepressants- Indications

Neuropathic pain syndrome and insomnia. Imipramine is used for childhood enuresis(bedwetting) & clomipramine is useful in the treatment of OCD. Can be used to increase weight due to increase appetite.

Anxiolytic Drugs- Adverse Effects

Overexpression of their therapeutic effects, in particular CNS depression. Hypotension. Hyperactivity and aggressive behavior (More likely to occur in children, adolescents & elderly with dementia.) Rebound disinhibition can occur in elderly patients upon tapering of doses or discontinuation, an elderly patients experiences marked sedation for 1-2 hrs followed by marked agitation & confusion for several hrs afterward.

Tricyclic Antidepressants- Adverse Effects Part 1

Undesirable effects of tca's are a result of their effects on various receptors, especially the muscarinic receptors (a cholinergic receptor), & to a lesser degree adrenergic, histaminergic, dopaminergic & serotonergic receptors. Blockage of cholinergic receptors results in the undesirable anticholinergic adverse effect the most common man constipation and urinary retention. Nortriptyline & desipramine have less have less anticholinergic activity & are preferred in the elderly. Adrenergic & dopaminergic receptors can lead the disturbance in cardiac conduction in hypotension. Histaminergic blockade can cause sedation and serotonergic blockage can't alter the seizure threshold and cause sexual dysfunction.

2nd- Generation Antidepressants - Contraindications

Use of MAOIs with the past 14 days & therapy with certain antipsychotic drugs such as thioridazine/ mesoridazine. Significant history of cardiac disease or seizures this is a relatively uncommon but reported cardiac effects and alterations in seizure threshold. Bupropion is also contraindicated in cases of eating disorders and seizure disorders because it can lower the seizure threshold.

Tricyclic Antidepressants-Contraindications

Use of MAOIs within the previous 14 days, and pregnancy. Not recommended impatience with any acute or chronic cardiac problems or a history of seizures, because both contraindications are associated with a greater likelihood of death upon TCA overdose

Anxiolytic Drugs- Benzodiazepines Alprazolam (Xanax)

Used for panic disorders. Adverse effects: confusion, ataxia, HA Interactions: Alcohol, antacids, oral contraceptives Oral dissolving tablet is used for treatment of anxiety disorder, short term relief of anxiety symptoms, treatment of anxiety A/W depression & treatment of panic disorders. Short acting

Mood-Stabilizing Drugs

Used to treat bipolar illness (cycles of mania, hypomania, & depression).

Antipsychotic Drugs

Used to treat serious mental illnesses such as drug-induced psychoses, schizophrenia and autism. Also used to treat extreme Mania, bipolar disorder, depression, certain movements disorders such as Tourette syndrome and nausea. Producers state of Tranquility and act on abnormal functioning nerves. Phenothiazine are the largest chemical class of antipsychotic drugs.

Tricyclic Antidepressants- Amitriptyline (Elavil)

. Now commonly used to treat insomnia and neuropathic pain. Contraindications: drug allery, pregnancy & recent MI. Very potent anticholinergic properties which leads to adverse effects such as dry mouth, constipation, blurred vision, urinary retention, dysrhythmias. Only available for oral use.

Antipsychotic Drugs- Adverse Effects

Agranulocytosis( lack of granulocytes in blood)& hemolytic anemia. CNS effects include drowsiness, neuroleptic malignant syndrome(fever,cardiac instability & myoglobinemia-presence in the blood of muscle breakdown proteins, unstable BP). Extrapyramidal symptoms(pathological changes to the pyramidal portion of the brain. Motion disorders such as Parkinson's disease. drug induced state is psuedoparkinsonism characterized by akathisia-motor restlessness & acute dystonia-painful muscle spasms) tardive dyskinesias ( contractions of oral and facial muscles & choreoathetosis- wave-like movements of extremities) Cardiovascular effects caused by Alpha receptor blockade include postural hypotension prolong QT intervals. Endocrine system- insulin resistance, weight gain and changes in serum lipid levels. Development of metabolic syndrome( increased glucose levels, blood pressure, abnormal cholesterol levels, excessive body fat around the waist all these occurring together increases the risk of heart disease, stroke and diabetes

Tricylic Antidepressants- Adverse Effects Part 2

Anorexia, dry mouth, blurred vision, constipation, gynecomastia, sexual dysfunction ,altered blood glucose levels, urinary retention, agitation , anxiety, ataxia, cognitive impairment, sedation, headache, insomnia, skin rash, photosensitivity, weight changes, orthostatic hypertension, blood dyscrasias (disorder of the cellular elements of the blood) MAOIs: dizziness, nausea, syncope, hypertension & dyskinesias (abnormality or impairment of voluntary movement)

2nd- Generation Antidepressants

Associated with fewer and less severe systemic adverse effects. Selective serotonin reuptake inhibitors. Serotonin norepinephrine reuptake inhibitors.

Mood- Stabilizing Drugs- Lithium part 1

Available in 2 forms: Lithium carbonate and Lithium Citrate. Pontentiate (increase power) serotonergic neurotransmission. Lithium ions alter Na ion transport in nerve cells, which results in a shift in catecholamine metabolism. Lithium levels to produce therapeutic effect is close to the toxic levels. Management acute mania: serum 1-1.5 mEq/L Long term maintenance levels: 0.6 & 1.2 mEq/L . Measure blood levels every 8-12hrs Na & Lithium ions are both monovalent + ions & can effect one another. Na needs to be monitored & kept in range to maintain therapeutic lithium levels. Contraindications: dehydration, known Na imbalance, major renal/ cardiovascular disease ( all these increase the risk for lithium toxicity.)

Hypothesis of Depression

Biogenic amine hypothesis: hypothesis used to explain depression. It postulates that depression results from a deficiency of neronal in synaptic catecholamines primarily norepinephrine in Mania from excess amines at the a generic receptor sites in the brain. Premissive hypothesis: led to the creation of the selective serotonin reuptake inhibitors. Postulate that reduce concentration of Serotonin or the predisposing factors in patients with affective disorders. Depression results from the crease and both the serotonin and catecholamines levels where is Mania results from increased dopamine and non epinephrine levels but decreased serotonin levels. Dysregulation Hypothesis: essentially a reformulation of the Biogenic amine hypothesis. Vuse depression and other affective disorders not simply in terms of decrease and increase catecholamines activity but as a failure of the regulation of these systems.

Antipsychotic Drugs- MOA

Block dopamine receptors in the brain which decreases the dopamine concentration in the CNS. Conventional phenothiazine block the dopamine receptors postsynaptically in certain areas of the CNS such as the limbic system and the basal ganglia. These areas are associated with emotions, cognitive function and motor function. These receptors blocking produce a tranquilizing effect in psychotic patients. Both the therapeutic and toxic effects of these drugs are the direct result of the dopamine blockage in these area. The atypical antipsychotic drugs block specific dopamine receptors called dopamine 2 receptors as well as specific serotonin receptors in the brain known as serotonin(5-HT2). Sufficiency in improving the positive symptoms of schizophrenia in these beneficial effects may even increase over time. So call positive symptoms include hallucinations, delusions and conceptual disorganization. Conventional drugs are less effective in the manager of negative symptoms such as apathy, social withdrawal, blunt effect , Poverty of speech & catatonia.

Atypical Antipsychotics- Clozapine (Clozaril)

Compared to a conventional drugs it more selectively block The dopaminergic receptors in the mesolimbic region of the brain. Conventional drugs block dopamine receptors in the area of the brain called the neostriatum but blockage in this area is believed to given rise to extrapyramidal adverse effects. Because Clozapine has very weak dopamine blocking abilities in these areas of the brain it is associated with minor or no extrapyramidal symptoms period makes us the drug of choice for patients who have Parkinson's disease. Extremely useful and treatment of patients for whom therapy with antipsychotic drugs has failed especially those with schizophrenia.Indicated for schizophrenic patient to have shown high risk for suicidal behavior. Adverse effects include the potential for agranulocytosis, a dangerous disorder of white blood cells under production that is drug-induced. For this reason patients beginning therapy require weekly monitoring of white blood cell accounts for the first six months of therapy. Drug needs to be discontinued if the count Falls below 3000/mm3 and withheld until it rises above this value. Recommended that WBC counts be evaluated weekly for 4 weeks after discontinuation of the drug. Contraindicated in patients with myeloproliferative disorders, severe granulocytopenia, CNS depression or angle closure glaucoma and in comatose patients. Interaction include alcohol and other CNS depressants levodopa(diminished therapeutic effects) , antihypertensives(risk of hypotension)

Tricyclic Antidepressants- MOA

Correcting and balance in the neurotransmitter concentration of Serotonin and norepinephrine at the nerve endings in the CNS(Biogenic amine hypothesis). This is accomplished by blocking the presynaptic reuptake of neurotransmitters which makes them available for transmission of nerve impulses to adjacent neurons in the brain. Some also believe that these drugs may help regulate malfunctioning neurons (Dysregulation Hypothesis).

Anxiolytic Drugs-MOA

Decrease anxiety by reducing overactivity in the CNS. Benzodiazepines exert their effects by depressing activity in the areas of the brain called the brainstem and the limbic system. Benzodiazepines are believed to increase the action of GABA, which is an inhibitory neurotransmitter in the brain that blocks nerve transmission in the CNS.

2nd- Generation Antidepressants - Indications

Depression is there primary indication they also show benefit in treating of variety of other mental and physical disorders. These include bipolar disorder, obesity, eating disorders, OCD, panic attack, social anxiety disorder, PTSD, premenstrual dysphoric disorder, neurologic disorder myoclonus & alcoholism.

Antipsychotic Drugs- Contraindications

Drug allergy, comatose state and possibly significant CNS depressant, brain damage, liver or kidney disease, blood dyscrasias or uncontrolled epilepsy

Antidepressant Drugs- Part 2

Early aggressive antidepressant treatment increases the chances for full remission period the first six to eight weeks of therapy constitutes the acute phase. Primary goal during this time obtain a response to the drug therapy and to improve the patient's symptoms. Should be maintained and effective dose for additional 8 to 14 months after remission of depression symptoms. Choosing an antidepressant the patience previous psychotropic drug response history needs to be considered. A non-response is defined as failure to respond to at least 6 weeks of therapy with adequate dosage. Dosage optimization which involves careful upward titration of doses for several weeks. Most severe cases of refractory depression May warrant an attempt at treatment with Electroconvulsive therapy.

Antipsychotic Drugs- Interaction

Grapefruit juice

Miscellaneous Drug- Buspirone (BuSpar)

Has a agonist activity at both serotonin & dopamine receptors. Indicated for treatment of anxiety & is always administered on a schedule basis, as opposed to the benzodiazepine they are administered PRN or schedule. Lacks the sedative properties & dependency potential of benzodiazepine. Adverse Effects: Paradoxical anxiety, dizziness, blurred vision, HA & nausea. MAOIs shouldn't be used due to the risk of hypertension. A washout period of at least 14 days. Drugs that inhibit cytochrome p-450 enzyme system.

2nd- Generation Antidepressants- Mirtazapine (Remeron)

Promotes the presynaptic release of both serotonin and norepinephrine in the brain. This is due to its antagonist activity in the presynaptic Alpha 2 adrenergic receptors. It does not inhibit the reuptake of either of these neurotransmitters. Associated with sedation due to histamine 1 receptors is usually dosed once-daily at bed time. Indicated for treatment of depression including that associated with bipolar disorder. Sometimes helpful in reducing the sexual adverse effects in male patients receiving SSRI therapy. Known to be an appetite stimulant and this can be a helpful and underweight depressed patients are harmful and those who are already overweight. Contraindicated recent use the MAOIs. Adverse effects include drowsiness, abnormal dreams, dry mouth, constipation, increase appetite & asthenia(weakness/ lack of energy). Drug interactions include addictive CNS depressant effects with alcohol and cyp inhibitors. Available only for oral use

Serotonin Syndrome

Rare collection of symptoms resulting from elevated levels of the neurotransmitter serotonin. Enhance his brain serotonin activity. Common symptoms include delirium agitation, tachycardia , sweating , myoclonus(muscle spasm), hyperflexia, shivering, coarse tremors, extensor plantar muscle.

Monoamine Oxidase Inhibitors

Rarely used as a antidepressant used to treat Parkinson's disease. Disadvantage is potential to cause hypertensive crisis when taken with stimulant medications or with substance containing tyramine (found in many common foods and beverages.) They inhibit the MAO enzyme in the CNS. Amines such as dopamine, serotonin & norepinephrine are not broken down. This alleviates symptoms of depression. Sympathomimetic drugs can also interact with MAOIs & cause a hypertensive crisis. Washout period of 2-5 weeks between MAOIs & SSRIs are needed to decrease chance of serotonin syndrome.

Atypical Antipsychotics

Reduce effect on prolactin levels compared with conventional drugs and improve in the negative symptoms associated with schizophrenia. Show a lower risk for neuromuscular malignant syndrome extrapyramidal adverse effects & tardive dyskinesias. Antagonist activity at the D2 receptor is believed to be the mechanism of their antimanic activity. Serotonin Agonist activity at various 5h2 receptor subtypes and Alpha 2 adrenergic Agonist activities are A/W anti-depressive activity. Alpha one adrenergic receptors activity is associated with orthostatic hypertension and H1 receptor antagonist activity is associated with both sedative and appetite stimulating effects. Clozapine & olanzapine are a/w with the most weight gain, risperdone & quetiapine less a/w & ziprasidone is neutral. Sedating effects May diminish over time and can be helpful for patients with insomnia.

2nd- Generation Antidepressants- Bupropion

Relatively weak, but measurable effects on the brain serotonin activity, little to no effect of monoamine oxidase. Strongest therapeutic activity appears to be primarily dopaminergic and noradrenergic. Treatment of depression also indicated as an aid in smoking cessation(sustained-release form MOA: modulate dopamine & norepinephrine levels in brain these neurotransmitters are believed to play an important role in maintaining nicotine addiction) . Adjunct antidepressant for patients experiencing sexual adverse effects secondary to SSRI therapy. Contraindicated in patients who have known drug allergies, seizure disorders(drug lowers seizures threshold) currently have anorexia nervosa and bulimia. Adverse effects include dizziness, confusion, tachycardia, agitation, trimmers & dry mouth. Available only for oral use

Monoamine Oxidase Inhibitors- Selegiline Transdermal Patch (Emsam)

Selective MAO-B Inhibitor. Indicated for major depression. Adverse effects and drug interactions are the same as for the oral dosage form. Patients need to avoid exposing the patch to external sources of heat such as heating pad electric blankets on them or even prolonged direct sunlight does heat sources speed up absorption.

2nd- Generation Antidepressants- Duloxetine (Cymbalta)

Serotonin norepinephrine reuptake inhibitor. Indicated for depression and generalized anxiety disorder. Also indicated for pain resulting from diabetic peripheral neuropathy or fibromyalgia. Contraindications known drug allergies and concurrent MAOI use and it worsen an uncontrolled angle closure glaucoma. Adverse effects include dizziness, drowsiness, headache, GI upset, anorexia & hepatotoxicity. drug interactions SSRI & triptans (increased risk of Serotonin syndrome) & alcohol. Only available for oral use.

2nd- Generation Antidepressants- MOA

The inhibition of Serotonin reuptake is primarily mechanism of action of the SSRIs although SSRIs may also have weak effects on norepinephrine and dopamine reuptake. Serotonin norepinephrine reuptake inhibitors. SNRIs inhibits the reuptake of both serotonin and norepinephrine.

2nd- Generation Antidepressants- Adverse Effects

The most common are insomnia, weight gain and sexual dysfunction. Sexual dysfunction caused by the ssris is primarily related to inability to achieve orgasm. One potential hazardous adverse effects of any drug or combination of drugs that have serotonergic activity is known as serotonin syndrome.