26. 2. 2020 PharmDr. Bc. Dana Mazankova, Ph.D. Coordinator of the course Pharmaceutical Care II. Dpt. of Social Pharmacy E-mail: mazankovad@vfu.cz FAFP2 Pharmaceutical care II Seminar: Pharmaceutical care in sleep disorders - insomnia Learning outcomes Pharmaceutical care in patients with: • Sleep disorders  insomnia  snoring • Understanding of normal sleep physiology • Classification of insomnia • Description of conditions that may disturb sleep • Management of insomnia (pharmaceutical care in insomnia) Normal sleep physiology - Sleep cycle - controlled by reticular-activating system in brain - consis of two states: 1. Rapid eye movement cycle REM cycle 2. Non-rapid eye movement cycle NREM cycle - qality of sleep depends on the ration between the REM and NREM cycles Sleep cycle 1. Rapid eye movement (REM) cycle 20 – 25 % of sleep (adults) - REM sleep is associated with: - restoration of memory functions - repair of brain tissues - laying down of memories - involved neurotransmiters: catecholamines 2. Non-rapid eye movement (NREM) cycle 75 – 80 % of sleep (adults) - Non REM sleep is associated with: - repair of bodily tissues - activating neurotransmiter: serotonin Disruption of the ration between NREM and REM sleep - Sleep disorders‘ Classification 1. Insomnia 2. Breathing disorders associated with sleep 3. Hypersomnia of central origin 4. Circadian rhythm sleep disorders 5. Parasomnia 6. Movement disorders in sleep 7. Isolated symptoms, apparently normal variants and unresolved issues 8. Other sleep disorders Signs and symptoms of insomnia - taking more than 30 min to fall asleep - difficulty to maintain sleep - sleep disturbed for more than 3 nights a week - significant impairment of daytime functioning Classification of insomnia Insomnia - according to lengh: Duration Caused by Type of patients Transitional insomnia 2 – 3 days external factors – jet lag, noise, … patiets who normally do not complain of insomnia Short-term insomnia up to 3 weeks physical or emotional trauma, work stress, pregnancy sensitive patients to external trauma Chronic insomnia more than 3 weeks / month psychiatric and neurological disorders, excessive alcohol consumption, some medicines Classification of insomnia Insomnia - according to occurence Sleeping problem Early insomnia Difficulty to fall asleep Middle insomnia Waking-up during the night Late insomnia Waking-up earlier in the morning Combined insomnia Combined of above Total insomnia Total lack of sleep Health disorders associated with insomnia Psychiatric diseases Neurological diseases Somatic diseases Pregnancy Medicine-caused insomnia Drugs with negative effect to REM sleep: - amfetamine - nitrazepam - amitriptyline Drugs that can disrupt the sleep: - Antiepileptic drugs - Antidepressats - Beta-blockers - Calcium chanel blockers - NSAIDs - levothyroxine - PPI Snoring - vibrations of soft parts of the upper respiratory tract - simple snoring - affects up to 40 % of men - prevalence of snoring increases with age - risk factors: - obesity - alcohol intake - drugs (hypnotics, antidepressants, antipsychotics) - sleep apnoe Anti – snoring aids Nasal strips Nasal dilators Anti – snoring aids Mantibular devices Pharmaceutical Care in Insomnia Questions to be asked:  How long do the difficulties take?  Do you achieve sleep difficult?  Is your sleep short?  Is your sleep disturbed during night?  After waking up do you feel tired?  Ask for factors disturbing sleep  Use of drugs?  Other chronic diseases  Pregnancy Pharmaceutical Care in Insomnia Treatment possibilities: 1. Investigation of sleep disorders 2. Non-pharmacologic treatment: Sleep hygiene 3. Non-pharmacologic treatment: Cognitive behavioral therapy 4. Pharmacological treatment – hypnotics, drugs with hypnotic effect 5. Pharmacological treatment – herbal drugs 6. Pharmacological treatment of insomnia in children 1. Medical history Provide a detailed interview with patient and summarize medical history (find a risk drugs). 2. Recorders Ask the patient to complete a sleep diary to understand sleep patterns, patient’s lifestyle and symptoms. Sleep Diary Sleeping scales Investigation of sleep disorders Sleep diary Sleep council UK, https://sleepcouncil.org.uk/sleep-diary/ Sleep diary Sleep council UK, https://sleepcouncil.org.uk/sleep-diary/ Epworth sleepiness scale Provide sleep hygiene advice to patient. • Establish a routine • Lie down only when being tired • Limit sleep through the day • In the afternoon, limit caffeine, nicotine, heavy meals • Use relaxation techniques Sleep hygiene Recommend Cognitive Behavioral Therapy to patient. - type of personality - the patient's motivation - cooperation of the patient - eliminate false beliefs that are involved in the development of insomnia - e. g. the need to sleep eight hours a day Cognitive behavioral therapy Ideal hypnotic should met following criteria: • The onset of sleep in 30 minutes • Induce model of natural sleep for 6 - 8 hours • Keep the physiological sleep architecture • To ensure safe dosing • No residual effects the following morning • It should not occur tolerance and rebound insomnia • No interaction with alcohol • No effect on respiration • No interaction with CNS depressants Pharmacological treatment - hypnotics • The lowest dose • The shortest period of use • Intermittent use • Not to increase the dose without the doctor • Do not interrupt treatment without consulting the doctor • Report a change of action, adverse reactions to the doctor • Do not drink alcohol, do not take more sleeping pills together Guideline for using hypnotics It can occur at any hypnotic - addiction, tolerance, somatic dependence Withdrawal syndrome • in 1st generation after 3 months • in the 2nd generation after 12 months Addiction to hypnotic • e.g. phenobarbital • non-barbiturates: clomethiazole 1st generations of hypnotics barbiturates Short-acting: • triazolam • midazolam • cinolazepam 2nd generations of hypnotics benzodiazepines (BZD) Medium-acting: • nitrazepam • flunitrazepam • oxazepam Long-acting: • diazepam • chlordiazepoxide The main indication of BZD: - anxiolytics Hypnotic indication of BZD - disadvantages: - suppress REM sleep phase - prolong only non-REM - amnestic effects - it acts only on the benzodiazepine receptor BZD1 - selective hypnotic effect - indication: - sleep disorders, frequent nocturnal awakening, early awakening • zolpidem • zopiclon, eszopiclon • zaleplon 3rd generations of hypnotics Z - drugs Neuroleptics - chlorprothixene, chlorpromazine, clozapine, tiapride, quetiapine, olanzapine H1 antihistamines - promethazine, bisulepin, dimetinden Tricyclic antidepressants - amitriptyline, imipramine, clomipramine Antidepressants – SARI, NaSSA - trazodone - positively influences the architecture of sleep, shortens sleep, sleep deepens - mirtazapine - strong antihistaminic effect causes a hypnotic effect, but also undesirable weight gain Pharmacological treatment – other drugs with hypnotic effect - serotonine derivate - excreted by the pineal gland after reduction to light exposure of the retina - at the beginning of the night: melatonin production increases - at the end of the night: melatonin production decreases T Pharmacological treatment – hormone with hypnotic effect melatonin Effect of melatonin administered before sleep:  reduces sleep latency  reduces sleep fragmentation  extending sleep length and sleep efficiency - indication: - jet lag syndrome - elderly insomnia 2mg Circadin® - dosage: 2mg in the evening 1-2 hours before bedtime - duration of treatment: 3 weeks - indications: short-term treatment of primary insomnia in patients over 55 years and over ramelteon - syntetic agonist of melatonin MT1 a MT2 receptors Hypericum perforatum Melissa officinalis Hummulus lupulus Valeriana officinalis Passiflora Pharmacological treatment – herbal drugs - hypnotics – not recommended - sedative antihistamines - mellisa, valeriana, passiflora - homeopatics - referral to physician - solving of a primary cause of insomnia !!  inappropriate sleep habits  night mares  psychotherapeutic techniques to remove anxiety  proper sleep hygiene Pharmacological treatment of insomnia in children Thank you for your attention