What is sleep? o Sleep is a state when our senses and motor actvity are relatively suspended; there is a total or partial unconsciousness and all voluntary muscles are inactive. o Sleep is a body s rest cycle. o Sleep is anabolic state- a period when our bodies are producing new bone, muscular and nervous tissue and repairing them.
Why is sleep important? o Sufficient sleep is essential for maintaining optimal physical health, mental and emotional functioning, and cognitive performance. o Inadequate sleep time and poor quality sleep interfere with quality of life and can be hazardous to health
Age How much sleep is needed? New Born Babies requirement of sleep in hours Up to 18 Hrs 1 to 12 months 12 to 15 hrs 3 to 5 years 11 to 13 hrs 5 to 18 years 9 to 11 hrs Adults 7 to 8 hrs
Normal Sleep Pattern
Insomnia Insomnia is a sleep disorder that is characterized by difficulty falling and/or staying asleep. Types of Insomnia Primary Insomnia:- Sleep problem directly not associated with any other health condition. Secondary Insomnia:- Sleep problem because of something else (Health problem)
Causes of Insomnia Causes of acute insomnia can include: Significant life stress (job loss or change, death of a loved one, divorce, moving)illness. Emotional or physical discomfort Environmental factors like noise, light, or extreme temperatures (hot or cold) that interfere with sleep Some medications (for example those used to treat colds, allergies,depression, high blood pressure, and asthma) may interfere with sleep Interferences in normal sleep schedule (jet lag or switching from a day to nig shift, for example) Causes of chronic insomnia include: Depression and/or anxiety Chronic stress
Diagnosis Complaint that the sleep is: Brief or inadequate Light or easily disrupted Non-refreshing or non-restorative
Transient insomnia Types of insomnia < 4 weeks triggered by excitement or stress, occurs when away from home Short-term 4 wks to 6 mons, ongoing stress at home or work, medical problems, psychiatric illness Chronic Poor sleep every night or most nights for > 6 months, psychological factors (prevalence 9%)
Management of Insomnia Treat underlying Medical Condition Treat underlying Psychiatric Condition Improve sleep hygiene Change environment CBT Cognitive behavior Therapy : primary insomnias, transient insomnia Pharmacological Light, melatonin,
Medications of Insomnia Benzodiazepines Lorazepam Clonezepam Temazepam Flurazepam Quazepam Alprazolam Triazolam Estazolam Non Benzodiazepines (Imidazopiridine) Zolpidem Zolpidem CR Zeleplon Eszopiclone Both these classes act on the GABA A receptors (BzRA) in PCN
Other classes of medications Antidepressants Trazadone Mirtazapine Doxepin Amitryptyline Antipsychotics Olanzapine Quitiepine Melatonin Receptor Agonists Melatonin Ramelteon Miscellaneous Valerian Diphenhydramine Cyclobenzaprine Hydroxyzine
Zolpidem tartrate It is a short-acting nonbenzodiazepine hypnotic. It potentiates GABA, an inhibitory neurotransmitter, by selectively binding to GABA A receptors. It works quickly, usually within 15 minutes, and has a shortest half-life Zolpidem generally preserves all of the stages of sleep, and has minor effect on REM sleep
Zolpidem acts by selectively binding the α1 subunit of GABA A receptor, thereby facilitates the GABA mediated neuronal inhibition. There are two members of the GABA family of receptors, the GABA A and the GABA B. While the GABA B receptors are metabotropic or G-coupled protein complexes, the GABA A receptors are ionotropic or ligand gated ion channels. The GABA A receptors have five subunits: two alphas, two betas, and one gamma as seen in Figure. When bound by an agonist the GABA A receptors open to increase the influx of chloride ions causing hyperpolarization of the cell. Mechanism of Action
Zolpidem Tartrate Binds to GABA A receptor at alpha-1 subunit Facilitates GABA mediated Neuronal inhibition Increases the frequency of opening of Cl - Channel Membrane Hyperpolarization CNS Depression Initiating Sleep
Zolpidem Pharmacokinetics Bioavailability: 70% (oral) 92% bound in plasma Metabolism: Metabolized in the liver by CYP3A4 Excretion: 56% renal 34% fecal Half-life: 2-3 hours
Zolpidem vs BZDs Zolpidem act selectively on alpha-1 subunit of GABA receptors; Doesn t cause any type of memory impairment. Zolpidem has a very short half life (2-3 hrs); Provides freedom from next day drowsiness Zolpidem offers quick onset of sleep; Within 15 minutes. On prolong use of Zolpidem; Possibly less tolerance occur. Zolpidem has lower abuse liability & dependence than BZDs Zolpidem shows no withdrawal effects; Minimal rebound insomnia
Salient Features of Zolpidem in Insomnia
Melatonin A hormone secreted by the pineal gland contains light-sensitive cells or has nervous connection from the eyes converts serotonin into melatonin The Melatonin/Serotonin cycle melatonin serotonin neurotransmitter of the sleeping producing centres tryptophan high in milk
Functions of melatonin Melatonin regulates the body s internal clock. It also increases sleep propensity as well as duration of stage-2 sleep. free radical scavenging in all cells a potent antioxidant with anti-aging and anti-cancer properties helps to protect embryonic fetuses assists in maintaining immune system health and virus protection
The 24-Hour Cycle of Melatonin Production
Melatonin Production as per Age
Mechanism of Action Melatonin promote sleep by regulating the sleep/wake rhythm through their actions on melatonin receptors (MT1 & MT2) present in the SCN, a unique mechanism of action not shared by any other hypnotics. Pharmacokinetic data Bioavailability: 30 50% Metabolism: Hepatic via CYP1A2 mediated 6-hydroxylation Half-life: 35 50 minutes Excretion: Renal
Brand Name :- Composition:- Each Tablet Contains Zolpidem tartrate Melatonin 10 mg 3 mg Indication:- Transient Insomnia Acute & Chronic Insomnia
Brand Name :- Composition:- Each Tablet Contains Zolpidem tartrate Melatonin 5 mg 3 mg Indication:- Transient Insomnia Acute & Chronic Insomnia
Target Doctors- Presentation :- 1. Neurologists 2. Psychiatrists 3. Cons. Physicians 4. General Physicians Lexa Tablets:- 10 x 10 Tablets Lexa-H Tablets 10 X 10 Tablets MRP 59.00/ 10 Tablets MRP 47.00/ 10 Tablets
Competitors for Lexa & Lexa-H tablets Brand Name Composition Company name MRP Zolsoma- FC (10 s) Stressnil (10 s) Nitrest (10 s) Zolfresh (10 s) Zolpidem 10mg + Melatonin 3 mg Alprazolam 0.25/0.5mg + melatonin 3mg Zolpidem 10mg Sun Pharma Zolpidem 10/5mg Pulse Pharma 49 INR per strip Aristo Pharma 17.45/24.9 INR per strip Abbott India 94 INR/strip 108.5/61 INR per strip Meloset Melatonin 3mg Aristo Pharma 30.47/strip
Inputs for Lexa 1. Pair of compressed Pillows Qty 5 per 2. Samples of Lexa and Lexa-H tablets Qty.