WEIGHT CONTROL AND SLEEP AIDS-PART-V

SLEEP LOSS- TREATMENTS

In the previous post, we have seen a comprehensive encyclopedia of sleep and insomnia and their maps. In this emotional modern lifestyle insomnia with its various forms becomes a common problem. Even after lying in the bed getting a night of good sleep is a difficult procedure for many individuals.

Hence this post is dedicated to being guidance and treatment to tackle the problems of insomnia.

Guidances

The following general procedures are helpful to have a good hygienic sleep. The followings are the nonmedical approaches:-

1.Establishing a regular bedtime

2.Going to bed when tired and ready to sleep

3. If anxiety interferes get out of the bed and have a relaxed short walk, read some relaxing books, have a warm bath, or do some relaxing exercises.

4. Avoid hard exercises at bedtime.

5. Avoid alcohol because it will break sleep into fragments.

6. Avoid stimulants such as coffee, PPA, nicotine, and pseudoephedrine

7. Make sure that bedroom and bed are comfortable

8. Avoid small afternoon naps.

Treatments

Drug Treatments of Transient and Short term Insomnia:-

In general wakefulness and sleep, are antagonizing each other to control brain activities. Several nerve transmitters are involving in these antagonizing activities.serotonin and gamma-aminobutyric acid is the two known central neurotransmitters that slowly promote sleep.

Acetylcholine a central transmitter is maintaining REM sleep.

Catecholamines such as noradrenaline, adrenaline, and dopamine are the central neurotransmitters that cause wakefulness and antagonizing sleep.

Individuals may vary greatly in their natural levels of neurotransmitters and their sensitivity to these chemicals.

These theories are helpful to describe the actions of some medications on sleep patterns.

Hypnotics have their effects by modifying the secretions and receptor responses of serotonin, GABA, acetylcholine histamine and catecholamines

The goals of the hypnotic treatments of short term and transient insomnia are to restore day time work capacity and to eliminate the self-induction of anxiety-provoking thoughts.

The general norms of the hypnotic treatments are advising the patients not to take hypnotic drugs to more than three consecutive nights followed by one-night medicine free. This is to minimize tolerance and habit formation and to have a self-practice to control the stress that night. 

Prescription hypnotic agents

Benzodiazepines are the drugs of choice for treating transient and short term insomnia.

The mechanism of action is by acting on its receptors situated adjacent to the GABA receptors, they facilitate and enhance the actions of GABA the sleep-promoting hormone on its own receptor.

Benzodiazepines are available as follows

Short-Acting (2 to 8 hours)

1.Oxazepam

2.Clonazepam

3.Midazolam

4.Triazolam 

Intermediates (10 to 20 hours)

1.Temazepam

3.Lorazepam

4.Alprazolam

Long Actings(1 to 3 days)

1.Chlordiazepoxide

2.Diazepam

3.Flurazepam

The route of administration of benzodiazepines are both oral and by I.V or i.m. injections

Since benzodiazepines are metabolized in the liver and excreted through urine caution should be taken while using these medications during renal and liver insufficiencies. 

Many of the metabolites of benzodiazepines are very active.

Drug dependence 

Prolonged use can produce dependence.

Sudden withdrawal may cause confusion, anxiety, and agitation.

Side Effects

1.Drowsiness and confusion (the most common side effects)

2.Ataxia (dysfunctions and noncooperative nerve movements)

3.Dizziness

4.If taken with other CNS depressants benzodiazepines will cause respiratory depression and death.

Flumazenil is the antidote for benzodiazepine poisoning its effects lasts for 1 hour only and hence repeated dose is necessary for heavy poisoning.

Zolpidem

It is a newer drug and has an advantage over benzodiazepines by having minimum side effects and withdrawal symptoms.

Even though it is not a benzodiazepine it acts on the benzodiazepine receptor to produce the effects.

Side effects

1.Nightmares

2.Agitations

3.Headaches

4.GI distress

5.Dizziness

6.Daytime drowsiness

Barbiturates are less commonly prescribed to treat insomnia because of its serious and excessive respiratory depressing effects.

OTC DRUGS

The FDA has approved two antihistamines such as Diphenhydramine and Doxylamine

These antihistamines are commonly used in cough syrups and because of their serious anticholinergic effects caution should be taken by those who have extrapyramidal effects such as tardive dyskinesia, Akathesia, and Parkinson disease. Also, it should be taken with caution by those who have Prostatic enlargement.

 

   

WEIGHT CONTROL AND SLEEP AIDS- PART IV

SLEEP AIDS

Sleep is the healthy process of the body to keep it healthier. So many healthier procedures are performed during the process of sleep, such as growth, preparation of waste products like creatinine, urea, and lactic acid to be excreted in the urine. sleep maintains our body's metabolism and growth in a normal way. The digestive system is regulated. During sleeping the workloads of all our involuntary smooth muscles like heart, lungs, and visceral organs are minimized in order to boost them with fresh energy. Sleep refreshes our nervous system. Our blood is cleaned from waste and toxic products by healthy sleep.

Sleep time and quality vary among individuals. The usual range of sleep time per night is 5 to 10 hours.

Sleep requirements are changing according to the person's age. Newborns may sleep up to 18 hours. Preteens usually fall asleep within 5 to 10 minutes with deep sleep. By adulthood, 7 to 8 hours of sleep gives good rest. In the old age, six hours may suffice. In general, according to the modern theory, it is not the length of the sleep but it is the deepness of the sleep is more important.

Polysomnography includes Electro Encephalo Gram (EEG), the Electro Oculo Gram (EOG) and the Electro Myo Gram (EMG) recordings to note the changs during sleep 

Stages

By using polysomnography the scientists discovered five stages of sleep

1.One rapid eye movement (REM) stage

2.Four nonrapid eye movement (NREM) stages.

In normal sleep, REM occupies 25% by leaving the remaining 75% in the NREM stages.

In the NREM stages, the last third and fourth stages are considered as deep sleep stages or collectively known as delta sleep stages.

Most dreams occur during the REM stage and the degree of the restfulness of sleep depending on the amount of REM stage.

Most medications used to treat sleeplessness including the OTC medicines interfere with some parts of the sleep stages especially with the REM stage.
INSOMNIA
Insomnia is the interrupted sleep cycle or insufficient sleep that results in impaired daytime performances. Insomnia must be defined more with the depth of the sleep than with the length of the sleep.
Insomnia should be diagnosed with the deficiencies in the day time performances and not the number of hours  slept as the primary determinant of the diagnosis
Occasional one or two sleepless nights or with insufficient sleep is not important to be considered as insomnia. The pathologically concerning the situation with long time sleeplessness if it contains frequent microsleeps or extreme tiredness otherwise no need to worry.
Patients after a restful night sleep if they wake up in the morning with full freshness and satisfactory and feel no need to have an afternoon nap can reassure themselves that they have no insomnia. It is not necessary to have a sleep of 8 hours. Oftentimes a simple reassurance can be a cure for insomnia.
Insomnia is of three types as follows:-
1.Transient 
In this case, if a person cannot have a night sleep in less than 7 days then it is known as transient insomnia. Causes include shift work or acute anxiety
2.Short -term
This type lasts for 1-3 weeks. Causes of short term insomnia can be usually identifiable and self-limiting such as grief, pain, noise, or a tension provoking situation.
3.Long- term  
This type of insomnia lasts for more than 3 weeks. Chronic insomnia is caused by some underlying diseases most probably such as Hyperthyroidism or Arthritis and requires a thorough diagnoses of patients' physical and mental health.

General causes of insomnia

1.Intrinsic causes 

A. Psychophysiologic insomnia is a condition in which the patient associated with increased wakefulness with the bedroom and the sleep time routine.

B. Restless legs syndrome is characterized by extremely uncomfortable sensations in the leg muscle at rest which are relieved by moving the legs up and around.

C. Sleep Apnea can be obstructive or centrally mediated. The hallmark is breathing that stops for short periods during sleep. Patients with sleep apnea should not use hypnotics or OTC medicines.

2.Extrinsic causes 

A. Adjustment sleep disorders are prompted by a stressful situation.

B. Inadequate sleep hygiene  is caused by a lifestyle that reduces the amount of quality sleep

C. Hypnotic, stimulant, or alcohol dependency is caused by dependence, tolerance, or over-reliance on a particular drug of abuse.

3.Circadian sleep disorders

A. Delayed sleep phase syndrome occurs in people whose natural sleep times are altered due to work.

e.g.If a person should be at work at 8 a.m but gets tired after 2 a.m. and wakes at 10 a.m.would be affected by this disorder.

B. The jet lag syndrome is a problem primarily for people who frequently travel across several time zones.

4. Psychiatric disorders

such as major depressive disorders result in poor sleep that usually improves on proper antidepressant treatments

 

 

WEIGH CONTROL AND SLEEP AID PART-III

OTC WEIGHT LOSS DRUGS

A local anesthetic like benzocaine is available on OTC as a category-1 medicine. This acts on the nerve endings in the oral cavity to produce numbness and thereby decreases the feeling of taste at the taste buds to some people.

Available for oral use as lozenge, gum, and candy

3.5mg is the dosage form available in order to keep in the mouth for some period before food.e.g.Slim Mint; Diet Aid.

Phenylpropanolamine or PPA is another OTC medicine chemically and action-wise related to amphetamine as an adrenergic agonist. e.g.Dexatrim;Acutrim;Prolamine

It is available as 37.5 mg in an immediate releasing dosage form which should be taken about. 30 min before food 

75 mg which is the maximum dose is the approved dose in sustained release dosage forms.

Since PPA is sympathomimetic drug care should be taken by the patients who have heart diseases, hypertension, diabetes, and hyperthyroidism.

When used in controlled dosage PPA is milder than amphetamines in producing side effects

Other PPA side effects are CNS stimulation such as insomnia, nervousness, and headache

PPA Drugs Interactions

1.Cold and allergic rhinitis medicines

2.Antihypertensive drugs(Antagonizing)

3.Other sympathomimetics(Synergizing)

Other OTC weight-loss medicines are Bulk Laxatives Which by producing a feeling of stomach fullness suppress the hungry. 

WEIGHT CONTROL AND SLEEP AID-PART-II

PRESCRIPTION WEIGHT CONTROL DRUGS

In the previous post, we have seen some diet formulas available in the pharmacies as OTC weight control preparations.

When you buy these slimming formulas please be careful about their contents. Because high protein is very important to protect our vital body organs and functions.

The formula branded as "Last Chance Diet" marketed in the mid 70s in U.S.caused several deaths from cardiovascular complaints and the casualties is observed due to the lack of nitrogen balance because of the product's contents of poor quality protein formula.

By keeping these important points in later years high-quality protein formulas with some proportions of carbohydrates and fat like Optifast, Medifast, and Health Management Resources(HMR) are appearing in the market. Although these products are safe and free from fatalities as they supply daily 400 to 800 calories sufficient for our body, yet maintenance of weight loss over a long term use is still in question.

Slimfast and Ultraslimfast are high-quality protein food replacement formulas that appeared in the market in later years. These proved some successes as they replace one or two main meals of the day.

Prescription Medications

1.Amphetamine

2.Methamphetamine

3.Phenmetrazine.

All the above drugs are acting as slimming drugs by suppressing the hungry. Amphetamines are indirect adrenergic agonists by releasing norepinephrine from its stores at presynaptic nerve terminals

These medicines are no more in use because of their high potency of toxicities and drug abuse.

Drugs that are marketed later are:-

1.Phendimetrazine

2.Diethylpropion

3.Phentermine

4.Fenfluramine

These drugs too show little drug abuse but are allowed to use for short term purposes such as for not more than a few (8 to 12) weeks on medical prescription only. 

Similar to amphetamines these drugs also act by indirectly agonizing the adrenergic nervous system in a lesser degree, but has other routes of action too such as through CNS by suppressing safe center in the hypothalamic ventromedial nucleus  

Fenfluramine is acting through the serotonin pathway.

Side effects

1.Restlessness

2.Insomnia

3.Tremors

4.Tachycardia

5.Diarrhea

6.Nausea

7.Dry mouth 

8.Mydriasis

9.Drug abuse

In general, all the side effects are very similar to adrenergic stimulations and hence patients with cardiac arrhythmias and other cardiovascular problems should seek medical advice

For Long Term Uses

At last, a modified fenfluramine known as Dexfenfluramine is allowed by the FDA for chronic treatment of obesity on prescription. The drug suppresses the appetite and carbohydrate cravings by increasing the availability of serotonin in the brain which is safer than norepinephrine  

WEIGHT CONTROL AND SLEEP AIDS-PART-1

OBESITY TREATMENTS (OTC)-PART-1

Obesity is best defined as the surplus body fat that causes an increase in body weight by 20% of an individual's normal weight to be according to his height and BMI

People with overweight with a large abdomen are more likely in worse health than people who have fat distributed around their hips and limbs.

Waist measurement ratios of greater than0.95% in men and 0.80% women are with a greater chance of death rates.

Causes 

There is a medical belief that obesity is caused by ingesting more calories to the body than that the body can able to use it. The excess calories would be deposited as fat on the abdomen, hip, and limb.

Elevated Body Weight SetPoint

Some people who have this set point when they try to lose weight by fasting or low-calorie intake a compensatory adjustment in metabolism results in regaining their weight back. Hence even if these people are taking less food or fasting they cannot lose their instead it may increase.

Heredity

Another point is heredity which is an important factor as a cause of obesity. Anyone member of the family was obese the gene will be carried out to his or her descendants.

Food cues

Obese people are more responsive to food cues such as taste, smell, and sight of food.

Pathology

Many studies show that obesity can cause hypertension, diabetes mellitus, and osteoarthritis.

Women who gained 30 to 50 kg weight by her age at 18 may have a minimum 25% chance of getting a heart attack.

People who are 20% or more above their ideal body weight are having more chances to suffer the following disorders;-

1.Amenorrhea

2.CHF

3.Cancers of cervix,endometrium,colon,gallbladder,prostate and uterus.

4.Coronary Heart diseases such as Angina and MI

5.Diabetes Mellitus

6.Fatty liver

7.Gallbladder disease

8.Hirsutism

9.Hypertension

10.Hypertriglyceridemia

11.Respiratory tract infections

12.Varicose veins

The risks of obesity can be better determined by the ideal weight and the Body Mass Index(BMI)

The BMI can be easily calculated by the following formulas

1. Weight in kgs is divided by the squared height in meters

2. Weight in pounds multiplied by 700 is divided by squared height in inches

Researches show that the overall risk of developing heart disease is related to BMI as follows:-

1.BMI of 25 or less--Low risk

2.BMI of 25 -30  - Low to Moderate

3.BMI above 30-- High

Programs

1. A weight loss goal of 1-2 lbs per week is appropriate

2. To lose 1lb per week can be achieved by expending 3500 by work or decrease calorie intake by 3500 during that week.

3. For example, a patient who normally intakes 4000 calories per day must decrease his daily intake by 500 calories per day so that in one week he can decrease his calorie intake by 7x500=3500.

Balanced diets with calories derived from carbohydrates, protein, and fat are optimal. The fat calorie intake should be minimized by 30 % from less than 10% saturated fat.

Fat contains 9 calories per gram

Carbohydrates and proteins contain 6 calories per gram.

Fewer calorie diets (300-800) can help but with proper intake of proteins in order to maintain the Lean Body Mass.

During this procedure, patients should watch for electrolyte imbalance, postural hypotension, and ECG abnormalities

Formula Diets are available at OTC of the pharmacies such as Slimfast  which contains high proteins.

These preparations are instructed to take full mealtime by replacing it. When you replace the full meals once or twice per day by these formula diets your body gets the least calories per day. Most of these preparations contain high-quality proteins with no carbohydrates and fats.

Exercises are also can help to shed some weight.

 

DIABETIC NEPHROPATHY

END STAGE KIDNEY DAMAGE-DM-ESKD

Our body's metabolic and other wastes are excreted out by various means. But a major chunk especially the protein metabolic wastes such as Blood Urea Nitrogens and Creatinin which should be cleaned out 100% from our blood are excreted by kidneys. If kidneys are not functioning properly these deadly poisonous wastes will remain in our blood to produce a fatality.

Kidney damages are of two types such as Acute or reversible and Chronic or irreversible. Chronic Kidney Damages (CKD) and End-Stage Kidney Damages (ESKD) are the major causes of Diabetic mortality.

Chronic and improperly managed hyperglycemia is one of the major causes of nephropathy. Diabetic nephropathy is a leading cause of ESKD.

A nephron is one of the million basic units by which our two kidneys are composed and made of.

In brief, a nephron is composed of a capsule-like structure known as the Bowman's Capsule which forms the head as in the figure above. Inside the capsule, there is a meshwork of tiny blood vessels known as the Glamerulus through which the blood is filtered off.

The Bowman's Capsule descends downwards to a tubule known as the proximal convoluted tubule (PCT) through which the filtrate passes and subjected to various proportions of reabsorptions and secretions.

The proximal tubule further descends down to a small loop like a narrow U tube known as Loop of Henley which has no activities on the filtrate. The loop again ascends to form the distal convoluted tubule (DCT) in which again there are certain proportions of reabsorptions and secretions on the filtrate.

Finally, the filtrate after subjected to various reabsorptions and secretions to form the final shape to form the urine and will be guided to pass through the collecting duct followed by the ureter which leads to the urinary bladder.

These units are by God's Grace present in each kidney many and many and approximately one million nephrons are present in each kidney. More than a certain proportion of these units if they get damaged irreversibly by some diseases such as DM and Hypertension the result is the ESKD.

Diabetic nephropathy is a slowly progressing disease with no symptoms in the beginning but if unattended properly with longstanding mismanagement of DM the disease progresses to the final stage of ESKD. Fortunately, the progression is slow and may take hardly 10 to 15 years.

The nephropathy is caused by the damages in the glomerular filter barrier (GFB) a fine meshwork of small tiny blood vessels to carry blood. Diabetes mainly damages these tiny blood vessels by improper glucose metabolism and by forming toxic active oxidative products. It is classified as small blood vessel complications of diabetes.

Signs and Symptoms

During its early course, the nephropathy is mostly asymptomatic. As the disease progress slowly and the symptoms appear after 10 to 15 years when the progression attains ESKD.These ESKD symptoms are as follows:-

1.Tiredness

2.Headaches

3.General feelings of illness

4.Nausea and Vomiting

5.Frequent urine

6.Lack of hungry

7.Itchy skin

8.Leg swelling.

If anyone of the above symptoms are present please check for albuminuria, BUN, and creatinine.

Major Causes

1.Long-standing Diabetes Mellitus (especially type-1.)

2.Long-standing Hypertension

3.Heavy smoking

4.Family history of kidney problems

Mechanism

Diabetes causes an imbalance of glucose metabolism and damage blood vessels by producing toxic oxidative chemicals.

As we already knew the head of the nephrons is composed of a fine blood filtering meshwork made out of tiny blood vessels known as Glomerular Filter Barrier (GFB) which will allow only water and small molecules through the meshwork to be filtered off by leaving large protein molecules like albumin, and microalbumin, and lipids to stay in the blood itself.

As nephropathy progresses this glomeruli meshwork also progressively undergo damages and the filter processes become improper by tearing off the meshwork so that albumin and other large molecules also will be filtered off.

Diagnosis

1. Albumin and microalbumin tests in the urine may show their presence  (Normal value for albumin is <30mg/24 hrs;

The normal range for microalbumin is 30 -299 mg/24 hrs)

If clinically the total albumin presence exceeds 300mg/24 hrs then it is concluded that there is nephropathy.

People with DM are recommended to undergo the albumin test in the urine annually with an immediate beginning of test if diagnosed positively for type-2 diabetes because the onset of the disease is not well established in the beginning, and begin after five years in case of type-1 diabetes.

To test the kidney function the established glomerular filter rate (eGFR) should be measured by the 24-hour collection of urine.

The normal range is 90 - 120ml/min/1.73square meter 

Treatments

The aim of the treatment is to slow down the disease progression and to reduce the related complications

The drugs of choice are the hypertensive group of medicines the Angiotensin Converter Enzyme Inhibitors such as enalapril, captopril, and benazepril.

Angiotensin-II is a polypeptide that playing an important role in regulating total peripheral resistance(TPR) and altering kidney functions. 

Renin an enzyme secreted by the kidneys acts on a kind of plasma protein the angiotensinogen when blood enters into the glomeruli to form angiotensin-I. Another enzyme is known as angiotensin-converting enzyme acts on it and converting it into angiotensin-II. This is the active form of regulating kidney functions. It causes in distal tubule to increase the reabsorption of sodium with the exchange of potassium through a hormone known as vasopressin so that more concentrated urine formed.

ACE inhibitors prevent the formation of this substrate and alter the process by eliminating more sodium out and ease the blood pressure and protect the kidney to function normally.

To see the video of top delicious fruits can be taken safely by diabetics, please click 

To download the thorough illustrative article regarding diabetes please click 

   

 

DIABETIC NEUROPATHY

DIABETIC NERVE DAMAGES

We have already seen in our first post that what is diabetes mellitus (DM) and how it is developing and all other basics of its pathology and therapeutics.

Here we will see one of the DM's major complications the Diabetic Neuropathy which affects almost all parts of our body that are innervated.

Our entire body system needs energy for its daily activities. Our body gets its energy 100% from the burning of glucose a carbohydrate within each cell of all tissues including neuronal tissues of our body.

Glucose metabolism is basically regulated and maintained by a hormone known as insulin from the pancreatic beta islets of our body.

Lack of insulin impairs glucose metabolism and the cells would become depleted of energy, tired, and die. The tissues would be damaged and become ischemic.

These complications mostly happened in nerve tissues during DM and the result is Diabetic Neuropathy, the nerve damages of diabetes.

Normally the peripheral nerves are blood supplied by very small arteries known as vasa-nervorum. Diabetes damages and narrowing these arteries and thereby block the blood supply to the nerves.

Types of Conditions Associated With DN

1.Third nerve palsy

The third cranial nerve and its branches are supplied to our oculomotor system (Eye system)

Any damage to these third cranial nerves will affect the eye movements. The affected individual will feel difficult to move his eyes.

2.Mononeuropathy

In this condition, anyone nerve supply to the peripheral organ or part of our body is affected and that will result in loss of movement, sensation, and other functions of that nerve. The nerve is mostly supplied to outside the brain and spinal cord and hence it is known as peripheral neuropathy.

Mononeuropathy may affect any part of the peripheral organs or parts of the body leads to loss of sensations, weakness, paralysis, tingling, burning pain, and abnormal sensations.

3.Mononeuropathy multiplex 

In this condition as in mononeuropathy there instead of one nerve, there are two or three nerves are damaged.

4.Diabetic Amyotrophy

 Also known as lumbosacral-radiculoplexes-neuropathy, or femoral neuropathy. It is a polyneuropathy involved by many nerves supplied to the peripheral parts. This is the most common type among the other diabetic neuropathies which affects thighs, hips, buttocks, and legs. The symptoms are painful muscles, muscle wasting, and muscle weakness. It commonly occurs in type-2 DM patients.

The common symptoms start all of the sudden onsets with mild pain in the buttocks, hip, and thighs first on one side of the body followed by increased severity and then affect both sides. These symptoms develop and finally affect the lower limbs so that the patient cannot sit to stand or stand to sit without assistance.

5.Autonomic Neuropathy

In this, the nerve damages are extended to the Autonomic Nervous System (ANS) which controls our body's vital organs such as heart, lungs, liver, kidneys, and various other involuntary organs.

The symptoms are similar to autonomic deficiencies such as orthostatic hypotension or postural hypotension in which you feel the lower tension during when you change the position from sitting to standing.

Other symptoms are Dry mouth, Tachycardia, Tunnel vision, Difficulty swallowing, Bowel incontinence, Blurred vision, Urinary incontinence, Constipation, Anhydrosis, Sexual problems. In simple, there is adrenergic hyperactivity.

General Symptoms of DN

1.The trouble with balance while standing or walking

2.Numbness and tingling of extremities

3.Desensthesia, abnormal sensation to a body part.

4.Diarrhea

5.Erectile problems

6.Urinary incontinence

7.Facial and eye movement difficulties

8.Vision changes

9.Dizziness

10.Muscle weakness

11.Difficulty in swallowing

12.Speech difficulties

13.Retrograde ejaculation(ejaculation into the bladder instead of the urethra)

14. Face muscle twitching.

Treatments

Treatments are primarily the treatment for the DM-Type-2 followed by other symptoms control by 

1.Tricyclic antidepressants to releive pain,e.g.Amitryptylin;imipramin 

2.Selective Serotonin-Norepinephrin Reuptake Inhibitors(SSNRI) for pain releiving,e.g.venlafaxine,duloxetine

3.Selective Serotonin Reuptake Inhibitors SSRI),e.g.fluoxetin,paroxetin

4.Anti epileptic drugs,e.g.Pregabalin,and Gabapentin