WOMEN GYNACOLOGY-PART-I

FEMALE OVARY SYSTEM

INTRODUCTORY

Basically the female sexual system differs from male sexual system by the separation of the genital pathways from the urinary path ways where as in males both are united at the outlet level to form a combined urino-genital system.Here we will see the entire pharmaco-gynaecology of women comprehensively in parts by parts.

 Ovaries are major female reproductive parts situated at either side of the trunk embedded in the pelvic cavities of the female as tiny glands.These glands composed of tiny follicles known as Graafian Follicles.They are the main secreters of the female sex hormones known as estrogens.
The estrogens are mainly responsible for all changes at the age of puberty of the females and account for the secondary sexual characters of the females.
The direct action of estrogens causes the healthy development of the ovaries,fallopian tubes,uterus vajina and breast.
Also estrogens causes the shiny and soft female skin and structrure by evenly distributing the fat of the body.
Neuroendocrine Regulations of Mensuration
The hypothalamus which is situated at just below the thalamus in the brain secretes a hormone known as Gonadotropin Releasing Hormone (GnRH) in a pulsative manner.Then the GnRH act pulsatively on the anterior pituitary and stimulate it to release pulsatively the Gonadotropic Hormones or Gonadotropins which are the two hormones similar to male,the LH(the leutinizing hormone) and the FSH (the follicle stimulaing hormone).These two hormones act in a pulsative manner on the ovaries and causes the maturation of the follicle into ovum,and the secretions of the ovarian hormones estrogens and progesterone.
Progesterone exert a feed back mechanism on hypothalamus and pituitary whereas estrogen is having a feed back mechanism on pituitary only.
The full development of the follicle into ovum takes a theorital period of 11 to 14 days which is the mid cycle of the menses.At this this point the matured ovum detach itself from the ovary and enter into the fallopian tube and wait their for fertilization by a single spermatozoa.The ovum's life time is only 24 hrs whereas the sperm's life time is 72 hrs.The empty space occuppied by the detached ovum develops into a yellow gland known as Corpus Luteum which begins to secrete more progesterone and estrogen by the action of LH which  by feed back mechanism stop the stimulation of the overy further by the hypothalamus pituitary axeses until the cycle ends with fertilization or empty completion.If the ovum get successfully fertilized the progesterone and the corpus luteum will function throughout the entire period of pregnancy to protect the fetus.If not during the next half the cycle the corpus luteum begins to caese.The progesterone prepare the endometrium of the uterus like a cushion convenient for the reception of the fertilized ovum into it for stay.If no fertilization at the end of the period the entire things whould be shed off as menses.Then the next cycle would be resut.In the entire process the secretions of the steroids from the hypothalamus and pituitary axes must be pulsative with a regular intervals otherwice a continue secretion may cause continue stimulation of the ovaries which will result in painfull amenorrhea.

MALE HYPER GONADISM-TREATMENTS

ANTI ANDROGENIC TREATMENTS

Anti androgenic treatments are options prescribed for the treatments when androgens are over dosed and the male sex organs are over powered to precipitate so many unwanted serious and non serious side effects.

If androgens are administered carelessly without a doctor's supervision the following side effects are observed.

1.Over musculinization

2.Over virilization

3.Hirutism in women

4.Depression of menses,acne and clitoral enlargement

5.Rarely hepatic adenomas and carcinomas

6.Cholestatic jaundice

7.Prostatic hyperplasia. 

Anti Androgens

1.Gonadotropin Releasing alalogues:- Leuprolide or Gonadorelin

This drug is available as subcutaneous daily dose injection and should be prescribed by a doctor and given by him in his office.This drug resembles structurally similar to the hypothalamus gonadotropin releasing hormone and imitating it and thereby suppressing the release of gonadotropic hormone and thereby inhibiting the gonads.At the inistial state it may incease the levels of LH and FSH the two gonadotropins,but on continuation of the treatment it will suppress their levels 

Mostly used in Prostate enlargement

2.Receptor Inhibitors:- Cyproterone  Bicalutamide and Fluamide

It is a non steroidal synthetic androgen receptor blocker mostly used for treating Prostate Cancer.

Also can be used to treat hyper androgenic actiivity and hirutism in women.

 Bicalutamide is a newer medicine and because of its more convenience and lesser side effects it mostly replaces Flutamide.

3.Steroid synthesis Inhibitors:- Ketaconazle,and Spinolactone(Aldactone)

4.5-a-Reductase Inhibitors:-Dutostride and Finastride

These drugs can be taken orally according to doctor's advise.They inhibit the conversion of the less active testosterone into the more active dihydrosterone by inhibiting the enzyme 5-a-Reductase. 

MALE INFERTILITY-TREATMENTS -PART -II

MALE HYPOGONADISM-TREATMENT OPTIONS

We have already seen in the last post a normal healthy male has  well developed male sex organs as he receives proper androgenic expression from the second month of his fetal life in his mother's womb.The developing testes in the fetal life also produce another poly peptide hormone known as Mullerian Inhibiting Hormone that

inhibit the development of the Mullerian Duct in the fetus.In this stage Testosterone act subsequently,on the Wolffian ducts and differentiate it into the epididymis,vas deferens and semen vesicles.

On the other side dihydrotestosterone causes fusion and elongation of the labioscrotal fold to form male urithra,penis,and scortum and virilize the urogenital sinus to form the prostate.

After doing these works the plasma concentrations of androgens begins to decline and at birth it is essencially undetectable in the baby's blood.

At the age of puberty the androgens will magically reappear in the blood and act directly on the testes to produce male puberty signs.

Lack of sufficient androgen secretions at the fetal life will result in male sexual insufficiency or Male Hypogonadism in later life.

Symptoms of Male Hypogonadism

1.Underdevelopments of the male sex organs

2.Feminism-Female characters because of the estrogenic effects like soft voice,soft and shining skin with evenly distributed fat throughout the body etc.

3.Absence of virilzation

4.Absence of puberty

5.Declined spermatogenesis results in male infertility

6.Impotence

7.Weight Loss

8.Anemia

Unfortunately all the above defects can be corrected by the androgen replacement therapies except the declined sperm production for which upto date there are no known guaranteed therapies.

Androgens have two effects such as Andrgenic and Anabolic accordingly they can be divided into two as per their purposes of use as follows

1.Androgenic Androgens

 These androgens are used to produce purely androgenic effects in those individuals who suffers hypogonadal functions.Eventhough they have considerable anabolic effects that can be undermined are can be used for added benefits.

(e.g)1.Testosterone injections

        2.Esters of testosterone for oral use such as testosterone-17-enanthate (Delatestryl) is a long acting one

        3.Methyl testosterone or fluoxymesterone a potent orally acting testosterone ester.

2.Anabolic Androgens

These compounds are mostly synthetic or structurally modified testosterones in order to abolish the unwanted androgenic effects.

(e.g) 1.Oxandrolone (Oxandrin)

         2.Stanozolol (Winstrol)

         3.Fluoxymesterone

         4.Nandrolone phenylpropionate (Durabolin)

Causes of Male Hypogonadism

Testosterone by itself not active in all tissue receptors to produce the male functions unless it is converted into the more potent dihydrotestosterone.There are two enzymes present in our body for the conversion of tesosterone as follows

1)5-a-reductace-1 This enzyme is present in all the non genital skin and liver.Any damages in these areas may result in the lack of this enzyme and cause hypogonadism in spite of the testosterone production is normal

2)5-a-reductase-2 This enzyme is present in the skin of the genitals and the urogenital pathways.Any disease or damages may result in suppression of this enzyme and causes male hypogonadism  
Treatments for both hypogonadism and anabolic therapies are all subjected to be under Doctor's supervision.Since all the above mentioned androgens as either androgenic or anabolic

 are all hormones with serious side effects.
Side effects of Androgens
1.Over musculinization
2.Extra virilization in male
3.Hirutism in women (mustache and beard formed)
4.Depression of menses,acne and clitoral enlargement.
5.Rarely liver carcinomas and adenomas
6.Cholestatic jaundice
7.Prostate enlargement.

MALE SEXUAL DEFICIENCY AND INFERTILITY-TREATMENTS

MALE SEXUAL DISORDERS-MALE INFERTILITY

Sexual disorders and infertility are not uncommon in both male and female in modern days.These defects are frequently correlate with our diet,lifestyle,and emotional atmosphere.Stress and diet are playing important roles for hypogonadism the sexual dysfunctions of the male and female gonads followed by diseases and other organal disorders.In this post we concentrate about male sexual problems such as infertility,impotence and over activity of the sex organs.

The Hormones Of Sex in Men

There are variety of sex hormones are produced in men by various organs such as testes,the male sex organs prostate adipose tissues and adrenal glands.The predominant and the active forms are testosterone and dihydrotestosterone secreted by testes.These two hormones are accounting 99% male sexual characters.Out of these two hormones the dihydrotesosterone is more powerful and produce variety of androgenic reactions in our body.The most unwaned effect of his hormone is the enlargement of prostate gland and we will not deal with this here.

Testis also produce Androsterone,Androstenedione a testosterone metabolite.Androsterone is a weak horemone and its role of male sexual nature is negligible and it is formed by metabolizing dihydrotestosterone..The precursor hormone androstenedione will be converted into testosterone by peripheral tissues as per the need.

Adrenal glands also secretes in small amount of a male sex hormone known as Dehydroepiandrosterone which is also not very active.

There are metabolites of dihydrotestosterone  known as 5-a-androstane-3-a,17-beta-diol,and androsterone which are also weak in action.
In out side the testes some tissues especially brain tissues metabolise testosterone into female sex hormone the estradiol in men which is accounting and giving calmness and closure of the penis in resting periods most probably after a coitus or ejaculation.Esradiol is produced by testes also.Approximately 50 mic grams of estradiol is produced in normal man.Overproduction may result in feminism in men.
For treatments of hypogonadism it is found to be moral to administer Testosterone either by mouth or by other routes according to above studies.But the problem is the liver which readily metabolize testosterone 100% on administration by any route and inactivate it.To prevent this there are oral and pareneral preparations testosterone which is esterified to protect it from inactivation.These esters when they pass liver they get metabolized by liver and release testosterone into the circulation without inactivation.Oral testoserone and dihydrotestosterone are not effective than injections.
Recent findings have given an advantage oral preparation of modified testosterones such as methaneolone acetate and testosterone undecanoate.and these orally successful.
In oral preparations fluoxymesterone is a good androgen but a poor precursor of estrogen
But 19-nortestosterone is as strong as dihyrotestosterone in androgenic effects. 

SYNTHESIS AND SECRETIONS OF MALE SEX HORMONES

Testosterone in plasma usually occurs at high concentrations usually in three phases of life.

1.At the embryonic phase in this stage the plasma testosterone beginst to appear when a ovum is fertilized as a male embriyo and rises day by day reaches its peak high level at the eighth week and declines to bottom at the time of delivery.

2.At the neo natal period. After the birth it sarts again to reach its peak level at neonatal period of about one year and decline to bottom at the age pre-puberty.At puberty the pituitary hrough the hypothalamus secretes two hormones known as Luteinizing Hormone(LH) and Follicle Stimulating Hormone (FSH).

Gonadoropins begins to secrete in a pulsative manner as puberty progresses during both sleep and wake positions.During puberty the hypothalamus and pituitary both respond to the feed back mechanism of gonadotropin secretions very weakly.

Prior to puberty when the organs not well matured the plasma concentration of testosterone in a male 20 ng/dl.(0.7 nM)

as the puberty progresses the secretions also correlate with it and the male reaches the adult age the plasma concentrations of the testosterone is 300 to1000 ng/dl(10 to 35 nM) and the rate of production is 2.5 to 11 mg per day.In plasma 40% of the testosterone are bound to androgen binding globulin,58% are bound to other plasma proteins.2% is free in plasma which contributes to the androgenic activity.
Albumin bound testosterone is dissociating in the capillary bed for ready entry into the cells for actions.
LH and FSH from pituitary are regulating the development of testicles,and the production of sperm.Growth hormone also synergize the activities of LH and FSH.Estrogens suppress the LH action and reduce the secretion of testosterone.
Testoserone is a steroid and it is synthesized from cholesterol by the testes by the stimulating effect of pituitary LH on the Ledig cells of the testes.FSH on the other hand stimulate the seminiferous tubules to produce sperm.FSH also has an augumenting effect on LH.The spermatogenetic effects of both LH and FSH are all through the production of testosterone.
The injection of Human Chorionic Gonadotropin represents only the effects of LH. 
Administration of testosterone to men with hypogonadism and men who have been castrated(Eunuchism) is affecting the functions of LH and FSH.
In normal man estradiol is produced by testes and as well as brain.Brain and other tissues are converting a fraction of male sex hormone o female sexhormone the estradiol in a similar manner to testes.15% of he estradiol secreted by testes in a normal man.
In normal man the adrenal cortex is producing a minor quantity of testosterone through its precursor androsenedione but is not sufficient to represent the male nature.But in case of adrenocortex hyperplasia or cancer the production will be large.
Physiological effects of Male Sex Hormones
Androgens at the embroyanic age minutely secreted by testes and adrenal cortex withou any pituitary stimulation is virilizing regulating and maintaining the male urogenital parts of the male embryo.
In neo natal age they help the sexual developments within the central nervous system
At puberty they help the boy to become a well developed adult man.At this age the testes begins to enlarge.The penis and scortum start to grow,and pubic body hair beard and mustache begins to appear.Early in puberty,penial erections,nocturnal ejaculation and masturbations are frequent in most boys.
At the same time the growth promoting nature of the androgens contribute to increase in height,well established bone structure and musculin protein anabolic developments will leads into increase in height and weight.Physical vigor is increased.Testes developed into its full size.The skin become thick and oily.More proliferated sweat glands which are prone to plugging ang infections which results in pimples and acne formations.
Subcutaneous fat is lost and the veins under the skin appear prominently.Voice becomes deep. 
Secondary sexual characters begins to appear.
Heriditary appearance like baldness may begins to start like recession of the hairline at the temples and thinning of the hair at the crown.
At the end of this stage the bone growth attains to end.After this a further 1 or 2 cm growth is possible.
On behavior also androgens have major role.Men's aggressive rough and rude behavior are all due to androgens.Administration of male sex hormones may definitely influence the mood of a normal individual.These are the bases for treatments of male insufficiency with androgens.
When androgens are given to an prepuberty boy or a eunucoid young man the events of normal puberty are duplicated but there may be a time of laps (1 to 2 or more years) may take to establish the full virilization.
Shortly after starting the treatment inapropriate  erections with embarrassing frequencies may begins to surface with discomforts.Tolerance will develop as the treatment continues and these discomfort will be eased and subsided.Increased physical vigor and a general feelings of wellbeing ensued after a few weeks of the treatments.
The penis begins to grow followed by a distinct change in the voice.
Auxillary and pubic hair become more luxuriant.
The rapidity of the skeletal and muscular growth is very impressive in boys treated at or before the time of normal puberty.
The height growth increase 10 cm or more during the first year of treatments followed by diminishing for next 2,3 years.
With continued treatment development with the growth of a beard and body hair as a late expression of therapy.

Actions of Androgens On Normal Male

Normally,at the second month of the fetal life androgens start to be secreted by the baby's testicles and establish their important role of differentiation and development of the male reproductive system.

 

 

INFLAMMATORY DISEASES-I -ASTHMA

ASTHMA

ASTHMA a tracheobronchial  inflammatory disease in which air flow restrictions happen due to bronchospasm results in wheezing,breathing difficulty,cough and cold.Of the two types of asthma namely allergic and non allergic the allergic type is more common which 95% of the people suffer.

In many cases of asthma increased numbers of inflammatory cells such as eosinophils,lymphocytes and macrophages are found to be present in the alveolar fluids.These are not found much in the alveolar lavage of the normal individual.These inflammatory cells are even found in the asthmatic person's broncho alveolar lavage who's lung function is at normal baseline and no recent asthma exacerbations.These inflammatory cells are found in both allegic and non allergic asthmatic patients.

Hence asthma is purely an inflammatory disease. 
Causes of Asthma  
1.Inflammation of the bronchial wal
2.Constriction of the bronchial smooth muscle
3.Increased mucus secretions
Clinical symptoms
Shortness of breath
coughing
Wheezing
Use of accessary muscles of respiration such as mouth breathing
Chest tightness
Precipitators of Asthma
Allergens  
These agents stimulate mast cells to release various inflammatory agents like histamins,leucotriens,and chemotactic factors that promote bronchiolar spasm and thickening of the
 mucus.
Infections  
Like viral upper respiratory infections exclusively in children in whom commonly these infections precipitate asthma.
Psychological factors 
These factors like stress and other confused states may cause asthma but not readily recognizable 

Treatments

The treatment options are as follows and fortunately all the available asthma treatment options described below are safely and aggressively can be used for pregnant ladies without any harm.

1.Sympathomimetic agents 

Mostly beta-2 adrenergic agonists are more suitable in this class of drugs as they are powerfully dilating the bronchial trunk by increasing cyclic Adinosine Monophosphate (cAMP)

(e.g)Pirbuterol;

        Terbutalin

        Albuterol and

        Salmeterol

These medicines can be safely administered by inhalation and because heir absorption in the systemic circulation is poor and hence side effects are minimal

These are the drugs of choice to get immediate releif from an acute attack as the onset of their action is quick.

Side effects Tremor and tachycardia.

2.Corticosteroids

Steroids reduce inflammations by reversing mucosal edema,by decreasing the capillary permiability and they inhibit the release of inflammatory agents such as leucotrienes,and cytokines.

Corticosteroids can be used both acute and chronic asthma.Since corticosteroids are not broncho dilators and hence a bronchodilator also must be included in the treatment regimens.

For acute exacerbations systemic steroids should be given via oral or i.v. routes followed by a maintenance therapy by inhalation.

(e.g.) 1.Beclomethasone

          2.Flunisolide

          3.Triamcinolone

          4.Fluticasone.

Side effects

Inhaled steroids may sometimes produce cough,oral thrush and dysphonia

Systemic steroids like prednisone can cause glucose metabolism defects,increased hungry;weight gain;hypertension,adrenal deficiency

3.Anticholinergics

Anticholinergics can cause bronchodilation and decreased mucosal secretions by blocking cholinergic nervous system. 

(e.g.) Ipratropium (Atrovent) is the best example in this class of anti asthmatics.

Uses 1.Asthma

         2.Chronic Obstructive Pulmonary Disease (COPD)

Side effects

1.Dry mouth

2.Sedation

3.Blurred vision

4.Urinary retension

5.Constipation. 

Because of inhalation many of the above side effects may not be seen as the drug is poorly go into the circulation.

4.Leucotriene Inhibitors

They inhibit the formation of leucotrienes from ecosatetranoic acid (Arachidonic acid)

e.g. 1.Zileuton (Zyflo)

        2.Zafirlucast (Accolate)

They can be taken orally

These medicines are used for chronic maitenance therapy and should not be used for acute attacks.

Side Effects

1.Zileuton is causing liver damage

2.Zafirlukast-Allergy

5.Theophyllin

Similar to sympathomimetic agents this also causes bronchodilation by increasing cAMP level.It is also having anti inflammatory effect.

Drug interactions Serious drug interactions are observed if theophyllin is used concomitantly with cimetidine end erythromycin as the later medicines will increase the theophyllin plasma concentration by competitively inhibiting its metabolism by liver cytochrom 450 enzyme.

Side effects and symptoms of overdose

1.Tremor;2.Insomnia;3.G.I.distress.

6.Mast cell stabilizers

e.g.Cromolin and Nidocromil

Can be used for prevention

Side effects Cromolyn causes pulmonary edema,cough and wheezing

Nedocromil causes mouth bitterness 
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ANEMIA-TREATMENTS

ANEMIA-AN OVERVIEW

Anemia is defined as a condition at which there are below normal levels of Red Blood Cells (RBC),Hemoglobin,and Hematocrits concentrations.

Hematocrit refers to the RBC count in total percentage.It is otherwise meaning that RBC in Packed Cell Volume(PCV) or Erythrocyte Volume Fraction(EVF).

Increasing the blood plasma volume disrespect to its hematocrit may also produce a temporary anemic condition as during pregnancy.

Comprehensively the growth factor known as erythropoietin a hormone secreted mainly from the kidneys and a little from liver acts on the bone marrows to produce and release RBCs in the blood.In emergency situations like accidents,starving and other incidents that causes heavy blood loss while RBC counts go down below normal the cells present at the cortex of the kidneys works hard and produce and release 100% erythropoietin in the blood.In this case the participation of liver is negligible.

Lack of erythropoietin will produce several forms of anemias and most importantly during Chronic Renal Failure.

Erythropeitin is not the sole responsible factor for erythropoiesis because it need several cofactors such as more importantly the sufficient supply of iron.In the absence or deficiency of iron the bone marrow will not properly respond to erythropoietin..

Uses of Erythropoietin

This medicines are used to correct anemias associated with Chronic Kidney Failure and Bone Marrow Failure 

Side effecs 

Can cause thrombosis and hypertension because of excessive over production of erythrocytes. 

Types of Anemias

1.Microcytic anemia is defined as the presence of very small discoloured or pale coloured (microcytic hypochromic) red blood cells which are unable to carry sufficient oxygen because of its hemoglobin deficiency.Mostly this anemia is caused by insufficient dietry supply of iron and blood loss through internal bleeding such as ulcer bleeding in the stomach and menstural bleeding.

Children at the ages of rapid growth need more iron.If they do not get sufficient iron supply in that ages (the teen ages) they would possibly develop this kind of anemia.

Iron :-Most of the iron in our body is present as hemoglobin and the remaining portion is present as transporter protein known as transferrin,ferritin and hemosiderin

Iron supplements should be given only to iron deficiency anemias.

Iron in the form of ferrous compound is more advantageous to be taken to produce the required benefits.Oral ferrous supplements are more convenient to take as parenteral preparations such as deep intra muscular injections may often cause muscular necrosis and pain.These are reserved only for emergency situations.

Toxicities 

1.Iron if taken carelessly on an empty stomach may produce damages and necrosis at the stomach and intestinal walls 

2.On high dosages iron can produce shock,metabolic acidosis,and even death

Treating Iron intoxications

Produce deep emesis and remove the unabsorbed drug from the stomach by vomiting( Excess ingetion of coconut milk may be help full)

Give Deferoxamine a chelating agent to inactivate the iron already mixed with the digestive juice.

Regular phlebotomy (A regular periodical blood testing) should be performed.

2.Pernicious Anemia and Vitamin B-12 Deficiency

Pernicious anemia  is well defined as a condition in which there is very insufficient quantity of RBC,and it is differing from Iron Deficiency Anemia (IDA) in which there is sufficient quantity of RBC is present but all of them are micro sized under developed and inefficient to carry oxygent because of their hemoglobin and iron deficiency.

Symptoms

1.Tiredness

2.Weakness

3.Shortness of Breath

4.Pale skin

5.Chest Pain

6.Hand and Foot Numbness

7.Difficult to balance on standing and walking.

Causes

Our stomach cells are producing a substance known as the intrinsic factor.Vitamin B-12 with the help of this factor keep and maitain the red blood cells healthy.

Either a deficiency in the supply of vitamin B-12 or the secretion of the intrinsic factor or both may cause pernicious anemia

Stomach cell damage by ulceration ,surgery,and tapeworm infection may cause the intrinsic factor secretion.

Vitamin B-12 can be given orally and as an intramuscular injection.

Side effects of vitamin B-12

Fortunately there are no known side effects to this vitamin have been established.

Folic Acid and Megalo Blastic Anemia (MBA)

Megloblastic Anemia is a condition in which there are unusually very large red blood cells (Megaloblastic or Macrocytic) without nucleous inside.

This is mainly due to the deficiency of folic acd which is needed by the cell to synthesize DNA.Lack of Vitamin B-12 may also can be a cause for this type of anemia but with sufficient supply of folic acid alone can cure this provided that there is no vitamin B-12 deficiency as because folic acid alone cannot cure the neurological defects.In such cases Folic acid with vitamin B-12 supplements should be prescribed.

Remember that body can store vitamin B-12 for longer time for years and years but folic acid stores will run out in months.Hence in most cases for treating MBA only folic acid supplements are enough but the deficiency of vitamin B-12 should first be ruled out. 

Folic acid is a well known needed vitamin during pregnancy as its deficiency will leads to neural tube defects.

Causes for folate deficiency 1.Inadequate dietary sources

2.Pregnancy

3.Drugs such as Phenytoin

4.Drugs such as oral contraceptives.
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CALCIUM HOMEOSTASIS-III-HYPERCALCEMIA

HIGHER BLOOD CALCIUM LEVELS-TREATMENTS

When the blood calcium levels rises above the normal range the condition is known by medical terms as Hypercalcemia.If left untreated it may result into serious unwanted consequences.

Symptoms

Although the patient is asymptomatic but he may demonstrate the following consequences:-

1.Weariness

2.Renal stones

3.Constipation

4.Stomach pain

5.Weakness

6.Confusion

7Delirium 

Causative Diseases

These causes can easily be remembered by the ananym CHIMPANZEES

Calcium suplementations used in excess

Hyperparathyroidsm

Iatrogenic (Urinary retension of calcium by overuse of thiazide diuretics)

Malignancy/Milk alkali syndrom caused by excessive intake of calcium and alkali through milk.

Paget's disease(Abnormal bone destruction and reformation) 

Addison's Disease

Neoplasm

Zollinger-Ellison's syndrom

Excess vitamin-D

Excess vitami-A

Sarcoid a disease in which there are abnormal collections of inflammatory cells to form granuloma 
TREATMENT OPTIONS
1.Rehydration with saline and diuresis with loop diuretics like furosamide
2.Bisphosphonates
3.Calcitonin
4.Gallium nitrae
5.Plicamycin
6.Glucocorticoids
1.Bisphosphonates
a)Etidronate
b)Pamidronate
Mechanism Bisphosphonates are working by inhibiting osteoclastic activity that means they reduce both bone resorption and bone formation of hydroxyapatite crystals.  
Routes of admn:- Etidronate by oral and i.v.
                              Pamidronate by i.v. only
Uses 1.Malignancy associated hypercalcemia
         2.Paget's disease
         3.Bone osteoporosis.
2.Calcitonin
A 32 member aminoacid peptide synthesized and secreted by the parafollicular C cells of the thyroid gland
Mechanism 
It decreases osteoclastic bone resorption as well as kidney calcium and phosphorus reabsorption.
Uses
1.Paget's disease
2.Hypercalcemia
3.Osteoporosis
Salmon fish calcitonin is more potent than humen calcitonin and have longer half life.
Side effects
1.Allergic reactions
2.Gastri Intestinal distress
3.Flushing,redness and tingling of the face.
3.Gallium nitrate
Gallium nitrate is working by bone resorption and thereby it decreases blood calcium levels.
Use Malignant hypercalcemia
Toxicity Nephrotoxic
4.Plicamycin
This is a cell destructing antibiotic reduces blood calcium levels
Mechanism
It inhibit the action of PTH on osteoclasts and also inhibiting the action of vit.D
Use Malignant hypercalcemia and Paget's disease
Toxicity 1.Thrombocytopenia and hemorrhage
               2.Liver and Kidney toxicity
               3.Nausea and vomiting and loss of appetite.
5.Glucocorticoids
(e,g) Prednisone
Mechanism These medicines work by decreasing calcium absorption by the intestines and increasing the calcium excretion by kidneys.
Uses Hypercalcemia due to lymphoma and sarcoid.