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ANTI-ANXIETY.pdf
- 2. ANTIANXIETY DRUGS • Anxiety It is an emotional state, unpleasant in nature, associated with uneasiness, discomfort and concern or fear about some defined or undefined future threat. • Antianxiety drugs These are an ill-defined group of drugs, mostly mild CNS depressants, which are aimed to control the symptoms of anxiety, produce a restful state of mind without interfering with normal mental or physical functions.
- 3. CLASSIFICATION 1. Benzodiazepines Diazepam, Chlordiazepoxide, Oxazepam, Lorazepam, Alprazolam. 2. Azapirones Buspirone, Gepirone, Ispapirone 3. Sedative anti-histaminic Hydroxyzine 4. βblocker Propranolol
- 4. BENZODIAZEPINES Some members have a slow and prolonged action, relieve anxiety at low doses without producing significant CNS depression. BZDs act primarily by facilitating inhibitory GABAergic transmission, but other additional mechanisms of action have been suggested. Higher doses induce sleep and impair performance. Side effects that occur in their use to relieve anxiety are—sedation, light-headedness, psychomotor and cognitive impairment, confusional state (especially in the elderly), increased appetite and weight gain, alterations in sexual function. Chlordiazepoxide It was the first BZD to be used clinically. Oral absorption is slow. A smooth long lasting effect is produced. It is preferred in chronic anxiety states. Chlordiazepoxide is often combined with other drugs in psychosomatic disorders,
- 5. AZAPIRONES • Buspirone It is the first azapirone, a new class of antianxiety drugs, distinctly different from BZDs. • The mechanism of anxiolytic action is not clearly known, but may be dependent on its selective partial agonistic action on 5-HT1A receptors. • By stimulating presynaptic 5-HT1A autoreceptors, it reduces the activity of dorsal raphe serotonergic neurones. • Buspirone has weak dopamine D2 blocking action but no antipsychotic or extrapyramidal effects. • A mild mood elevating action has been noted occasionally, which may be due to facilitation of central noradrenergic system.
- 6. • Buspirone is rapidly absorbed; undergoes extensive first pass metabolism; one metabolite is active and excretion occurs both in urine and faeces. • Side effects are minor: dizziness, nausea, headache, light-headedness, rarely excitement. It may cause rise in BP in patients on MAO inhibitors, but does not potentiate CNS depressants.
- 7. βBlockers • Many symptoms of anxiety (palpitation, rise in BP, shaking, tremor, gastrointestinal hurrying, etc.) are due to sympathetic overactivity, and these symptoms reinforce anxiety. • They do not affect the psychological symptoms such as worry, tension and fear, but are valuable in acutely stressful situations.
- 8. ANTIMANIC AND MOOD STABILIZING DRUGS
- 9. LITHIUM CARBONATE Lithium is a small monovalent cation. In 1949, it was found to be sedative in animals and to exert beneficial effects in manic patients. Actions and mechanism 1. CNS Lithium has practically no acute effects in normal individuals as well as in bipolar patients. It is neither sedative nor euphorient; but on prolonged administration, it acts as a mood stabiliser in bipolar disorder. Given to patients in acute mania, it gradually suppresses the episode taking 1–2 weeks; continued treatment prevents cyclic mood changes. The markedly reduced sleep time of manic patients is normalized.
- 10. • The mechanism of antimanic and mood stabilizing action • (a) Li+ partly replaces body Na+ and is nearly equally distributed inside and outside the cells (contrast Na+ and K+ which are unequally distributed); this may affect ionic fluxes across brain cells or modify the property of cellular membranes. • (b) Lithium decreases the presynaptic release of NA and DA in the brain of treated animals without affecting 5-HT release. This may correct any imbalance in the turnover of brain monoamines.
- 11. • C) lithium in therapeutic concentration range inhibits hydrolysis of inositol-1-phosphate by inositol monophosphatase. • As a result, the supply of free inositol for regeneration of membrane phosphatidylinositides, which are the source of IP3 and DAG, is reduced. • The hyperactive neurones involved in the manic state may be preferentially affected, because supply of inositol from extracellular sources is meagre. • Thus, lithium may ignore normally operating receptors, but ‘search out’ and selectively, though indirectly, dampen signal transduction in the overactive receptors functioning through phosphatidyl inositol hydrolysis.
- 12. Other effects: Lithium inhibits the action of ADH on distal tubules in the kidney and causes a diabetes insipidus like state. An insulin-like action on glucose metabolism is exerted. Leukocyte count is increased by lithium therapy. Lithium inhibits release of thyroid hormones resulting in feedback stimulation of thyroid through pituitary
- 13. Pharmacokinetics • Lithium is slowly but well absorbed orally and is neither protein bound nor metabolized. • It first distributes in extracellular water, then gradually enters cells and penetrates into brain, ultimately attaining a rather uniform distribution in total body water. • The CSF concentration of Li+ is about half of plasma concentration.
- 14. Adverse effects Side effects are common, but are mostly tolerable. Toxicity occurs at levels only marginally higher than therapeutic levels. 1. Nausea, vomiting and mild diarrhoea occur initially, can be minimized by starting at lower doses. 2. Thirst and polyuria are experienced by most, some fluid retention may occur initially, but clears later. 3. Fine tremors are noted even at therapeutic concentrations. 4. CNS toxicity manifests as plasma concentration rises producing coarse tremors, giddiness, ataxia, motor incoordination, nystagmus, mental confusion, slurred speech, hyper-reflexia.
- 15. ALTERNATIVES TO LITHIUM • Sodium valproate A reduction in manic relapses is noted when valproate is used in bipolar disorder. It is now a first line treatment of acute mania in which high dose valproate acts faster than lithium and is an alternative to antipsychotic ± benzodiazepine. It can be useful in those not responding to lithium or not tolerating it. • Carbamazepine Soon after its introduction as antiepileptic, carbamazepine (CBZ) was found to prolong remission in bipolar disorder. Its efficacy in mania and bipolar disorder has now been confirmed. However, it is less popular than valproate as an alternative to lithium. • Lamotrigine There is now strong evidence of efficacy of this newer anticonvulsant for prophylaxis of depression in bipolar disorder. Lamotrigine is not effective for treatment as well as prevention of mania. It is now extensively used in the maintenance therapy of type II bipolar disorder, because in this condition risk of inducing mania is minimal. Lamotrigine can be combined with lithium to improve its efficacy.
- 16. HALLUCINOGENS
- 22. MOA
- 23. PHARMACOKINETICS
- 24. CANNABINOIDS
- 25. USES