3. Drugs acting on endocrine system

Oxytocin and Uterine Relaxants

Posterior pituitary gland secretes a number of hormones, out of which two are important:

  1. Oxytocin
  2. Vasopressin –anti diabetic

Previously it was thought that oxytocin and anti diabetic hormone resembled each other and had similar properties, but in 1953 it was discovered that oxytocin and ADH although had similar properties of uterine contractions, but differed in structure and properties.

They differ in structure at position 3 and 8, so labeled different groups of hormones.


Biosynthesis of Oxytocin

  • Oxytocin is a cyclic peptide hormone, secreted from posterior pituitary.
  • It is synthesized in the cell bodies of para ventricular nucleus.
  • It goes down the axons, and is stored within neurohypophysis.
  • The precursor is rapidly converted by proteolysis to the active hormone and secreted from nerve endings.
  • Oxytocin is also synthesized in the luteal cells of the ovary, the endometrium and the placenta.
  • Stimuli include sensory stimuli from dilation of the cervix and vagina, suckling.


It is a nine amino acid peptide composed of 9 amino acid peptide, containing a six amino acid disulfide ring and a three membrane tail.


  • Orally not highly active, degraded when given orally.
  • Administered by I/V or IM route, at times intra nasal route may be used (to stimulate milk ejection)
  • Rapidly degraded by kidney and in liver.
  • Plasma half life is 6 min.
  • Not bound to plasma proteins.
  • Destroyed by Oxytocinase (present in kidneys).


  • It is given I/V with fetal and maternal monitoring, so that fetal distress does not take place.
  • An infusion rate of 10mU/min is given and increased every 15-30 min.
  • Nasal puff in each nostril is sprayed for lactation, one puff in each nostril is used before nursing, mother is placed in sitting position, thus milk ejection is enhanced.

Mechanism of Action

  • Oxytocin acts via G protein coupled receptors which activate Ca²+ -IP³ pathway and intracellular release of Ca²+ ions.
  • Intracellular calcium release alters transmembrane ionic currents in myometrial smooth muscle cells to produce sustained uterine contractions (stimulate and enhance).
  •  Increased sensitivity of uterus to oxytocin, prostaglandins are also synthesized leading to further augmentation of effects.
  • As pregnancy advances, activity of uterus (uterine contractions) increase and so does the sensitivity to oxytocin.
  •  Weak ADH like activity.
  • Also affects myometrial smooth muscles and initiates contractions of smooth muscles leading to milk ejection.
  • Beta agonists, magnesium sulfate and inhalational anesthetics antagonize the effects.

Pharmacological actions

  1. Uterus:
  • Activity increases as reaches 3rd trimester, leading to force and frequency of uterine contractions.
  • Sensitivity is also enhanced and effects are mainly related to fundus and body of uterus.
  • Full relaxation may occur between contractions.
  1. Breast

Cause contraction of myoepithelial cells of mammary alveoli surrounding collecting ducts, leading to milk ejection from mammary alvoli, one puff is given in each nostril.

  1. CVS
  • Due to direct effect, oxytocin causes vasodilation and fall in blood pressure,
  • Increased heart rate and tachycardia,
  • Flushing might occur as well.
  1. Kidney
  • Weak ADH like activity
  • May cause retention of fluids
  • Decreased urine output, if given in high doses
  • Pulmonary edema may occur

Clinical uses of Oxytocin

1. Induction of Labor

Normal labor is allowed to progress, manipulation is not advisable, only administered in certain conditions. (Rh incompatibility, DM, preeclampsia, ecclampsia, toxemia of pregnancy, rupture of membranes)

Initially 0.5-2 units/min administered, dose may be increased within 15-30 minutes till effective uterine contractions are achieved with maternal and fetal monitoring.

2. Augmentation of Labor

If labor is not progressing.

3. Third stage of Labor and puerperium

To decrease the post partal hemorrhage, usually administered at the time of delivery of placenta to decrease the chances of post partum hemorrhage.

10-40 units oxytocin in 1 litre of 5% dextrose is infused slowly. Ergot alkaloids (ergometrine) are also utilized for this purpose (o.2-0.3 mg are given). If ergometrine is contraindicated, oxytocin may be used.

4.      Milk ejection

Enhances milk ejection.

Adverse Effects

  • Maternal and fetal deaths due to hypertensive episodes, uterine rupture, water intoxication if rapidly
  • Afibrinogenemia is also reported.


Prostaglandins are said to have similar effects, act as uterine analogs.

  • PGE2, PGF2α and 15 methyl PGF2α are potent uterine stimulants.
  • PG have been detected in maternal blood.
  • Also enhance uterine stimulant activity, may augment the contractions.

Ergometrine & Methylergometrine

  • Erogot alkaloids obtained from claviceps purpura.
  • They increase force, frequency and duration of uterine contractions.
  • Gravid uterus is more sensitive and involves the lower segment as well.
  • Partial agonist action on 5-HT2 and α adrenergic receptors.
  • Used to decrease post partum hemorrhage

Oxytocin Challenge Test

I/V oxytocin is given in a dose of  0.5 milli units/min, till three contractions are achieved in 10 minutes. Purpose of doing the test is to access fetal well being. We compare maternal blood flow with that of fetal heart rate. This is to try to access placental circulatory reserve.

Uterine Relaxants

Agents given to decrease the contractions of uterus to relax it, given in cases:

  1.  when there are chances of threatened abortion or prematurity
  2. if we want to shift mother to better health facilities unit
  3. in conditions where fetal lungs are not mature, glucocorticoids are given to allow maturation.

Labor may be slowed down for days or even weeks.


  • A β2 selective agonist.
  • It has a major uterine relaxant action.
  • Doses given as I/V infusion of 50 mcg/min, dose may be increased after every 10 minutes till tone is decreased.
  • Causes postponement of delivery in 70% cases.

Side Effects;

  1. Hypertension,
  2. hyperinsulinemia ,
  3. hypokalemia,
  4. anxiety,
  5. arrhythmias,
  6. pulmonary edema,
  7. hyperglycemia,
  8. restlessness,
  9. headache

Salbutamol and terbutaline may also be used.



Severe hypertension

Ca+ Channel blockers

  • Ca+ influx causes uterine contractions while Ca channel blockers have opposing effects.
  • Nifedipine given orally every 20-30 min till uterine contractions subside.

Magnesium Sulphate

  • Previously used, now uses are declining
  • Used to control convulsions and to reduce BP in toxemia of pregnancy.
  • Given by I/V infusion.

Side Effects;

  1. Cardiac arrhythmias,
  2. muscular paralysis,
  3. CNS and respiratory depression.
3. Drugs acting on endocrine system

Hormonal Contraceptives

Different agents are used to avoid unplanned pregnancy, for better family planning. These are agents which mainly contain hormone components within preparations and may be administered orally, in form of injectables or implant preparations.

These are the most widely used agents throughout the world, as are very affordable, convenient and easy to use.

Sex hormones

  1. Estrogen
  2. Progesterone
  3. Other sex hormones

During reproductive years, radical changes occur under the influence of these hormones in ovaries and female sexual organs. This rhythmical pattern of menstrual cycle usually consists of 28 days. On around 14th day, under influence of follicle stimulating hormones and lutenizing hormones, ovulation occurs.

Contraceptives were designed to resemble FSH and LH, causing inhibition of ovulation so that fertilization and pregnancy do not occur.

Types of Oral Contraceptives

Combination Oral Contraceptives

It contains an estrogen & progestin

Estrogens Used:

  •  Ethinyl – Estradiol
  • Mestranol

Progestins Used:

  •   Levonorgestrel
  •   Desogestrel
  •   Norgestimate
  •   Norethindrone

All preparations come as 28 day packs. Pill is taken daily for 21 days starting on the 5th day of menstruation.

Phased Regimens

a. Monophasic

b. Biphasic

c. Triphasic

Contain a fixed amount of estrogen and are very effective available as 28 day calendar packing, 1 tablet is taken daily for 21 days without interruption, whereas the next 7 tablets are placebo (pill free period). After 28 day intake, prompt bleeding occurs. Ideally started at 5th day of menstruation.

Biphasic/triphasic preparations

Preparations in which estrogens are present in fixed dose, progestins may vary with the type of preparation. 235 mcg estrogens are present in biphasic and triphasic preparations given for fixed interval during 28 day cycle. One tablet daily for 28 days, last 7 days placebo.

In biphasic preparations, one tablet is taken initially for 10 days, another type for 11 days, followed by 7 tablets.

In triphasic preparations, depending on type of preparation, one regiment tablet is taken for first 7 days, another for 8-15th day/16-21 day, followed by 7 placebo tablets.

Biphasic and triphasic preparations are ideal for females over 35 years of age, having pre-disposing factors. In 2003, FDA approved other preparations, these are:


Norgestrel-ethinyl estradiol

1 tab for 84 days without interruption followed by 7 placebo, menstrual bleeding occurs every 13th week


Medroxyprogesterone-estradiol cypioate inj. (every month)


Ethinyl estradiol-norelgestromin (patch) (weekly)


Ethinyl estradiol-etonogestrel (vaginal rings)

Progestin only Contraceptives (Minipill)

Only progestin is present, no estrogen, in order to discard side effects of estrogen to make more tolerable. A low dose progestin only pill is taken daily continuously without any gap (mostly oral)

  •    Norethindrone (350µg) or
  •    Norgestrel (75µg).

Taken without any interruption.


  •    Norgestrel subdermal implants 216mg

I/M only preparations

Medroxyprogesterone acetate  IM 150mg

Slow release contraceptive, effective for 5 years subdermally. I/M as long as 3 months.

Intrauterine Device

Contain progestin component, 2 preparations are available:





Available for yearly basis, effective as long as 5 years.

Efficacy of estrogens only preparations is very high (99%), intrauterine devices have an efficacy of 70-80%. Progestin only preparations cause inhibition of ovulation for as long as 14 weeks, long acting ones may inhibit for 18 months.

Those who plan pregnancy soon after taking off pill, may fail to get pregnant. Minipill is not advisable for early pregnancy on discontinuation, may be inhibited for weeks or months (up to 18 months)

Adverse Drug Reactions

  1. Irregular bleeding
  2. Spotting
  3. Amenorrhea
  4. Besides nausea, vomiting, headache, dizziness, restlessness, leg cramps, abdominal cramps


Long acting progestin alone

  1. Depot medroxyprogesterone acetate (DMPA) 150mg at 3 months interval.
  2. Norethindrone enanthate (NEE) 200mg at 2 month intervals.

Progestin Implant Method

  •   Progestin capsule (Etonogestrel)

Long acting progestin + long acting estrogen

  •   MPA + estradiol cypionate  IM every month.

Potential adverse effects of implants

  1. Surgical insertion/surgical removal with irregular bleeding
  2. Headache
  3. Dizziness
  4. Weight gain
  5. Decreased host tolerance
  6. Intracranial hypertension

Post coital Contraceptives

Also popularly known as morning after contraceptives, used in emergency situations like rape victims or if want to avoid pregnancy. Said to be effective 72 hours, 2 doses are ideally taken 12 hours apart.

  •  Two doses of Minipill at an interval of 12 hours (0.75mg  Levonorgestril per pill).
  •  Two pills of a high dose oral contraceptives at an interval of 12    hours( 0.25mg of Levonogestrel + 0.5mg of Ethinylestradiol per pill ).
  • Ethinyl estradiol:  2.5mg BD x 5 days
  • Diethylstilestrol:   50mg daily x 5 days
  • Mifepristone:       600mg OD+Misoprostol 400µg OD

40% of females have nausea and vomiting with these drugs, so antiemetic must be administered with them. Other side effects include leg cramps and breast tenderness.

Mechanism of action

  • Inhibition of gonadotropin release from pituitary by reinforcement of negative feedback inhibition, thus FSH, LH synthesis and release is controlled.
  • Progestin is decreased and ovulation is inhibited
  • Secretion of thick cervical mucus secretion which becomes hostile for sperm, and is inhibited
  • Failure of blastocyst to implant.
  • Uterine and tubule contraction.
  • Dislodgment of just implanted blastocyst.

Adverse Effects                  

Mild adverse effects:

1. Nausea, edema, break through bleeding –due to estrogen component, switch to less estrogen more progesterone

2. Headache

3. Migraine –stops after use for some time

4. Breast discomfort –progestin only more common

5. Changes in serum proteins –estrogen type prep, alpha 2 globulin, fibrinogen levels increase

6. Failure of withdrawal bleeding –seen in combination preparations, progestin only and some other, this effect may be inhibited

7. Confusion

Moderate Effects:

1. Break through bleeding –biphasic, triphasic decrease chances

2. Weight gain, with combination preparations and and progestin type

3. Hyper pigmentation –common, highly sensitive to UV light or dark skinned, vitamin B deficiency, reversible process

4. Acne

5. Hirsutism –those preparations having 19 nortestosterone

6. Uretral dilation –usually at time of labor

7. Vaginal infection –very difficult to treat

8. Amenorrhea –may be seen in irregular menstrual cycle, if does occur, prolactin levels are assessed.

Severe adverse effects

1. Venous thromboembolic disease –increased chances of altered clotting factors, genetic alteration of homocysteine, decreased venous blood flow, endothelial preparations

2. Myocardial infarction –incidence is increased in females above 35 years, obese, diabetic, HTN, cardiac disease or smokers having higher chances of erythrogenesis

3. Cerebrovascular disease –esp. migraine history

4. GIT

a. cholestatic jaundice

b. cholangitis

c. cholilithiasis

d. hepatocellular carcinoma

e. hepatic adenoma

Chronic adverse effects are seen due to increased levels of cholic acid with bile acids.

5. Depression -reversible

6. Cancer –decreased incidence of ovarian and endometrial cancer

In breat cancer, beneficial effects are not achieved.

7. Alopecia, skin lesions –erythema nodosa and other manifestations


  1.  Hypertension & Hyperlipedemia
  2.  Thromboembolism
  3.  Diabetes mellitus
  4.   Heart disease/ failure
  5.   Liver disease
  6.   Migraine/ headache
  7.   Cerebrovascular disease
  8.   Optic neuritis

Drug Interactions

1. Enzyme Inducers

  • Phenytoin
  • Primidone
  • Carbamezipine
  • Rifampin

2.  Suppression of intestinal microflora

  • Tetracyclins
  • Ampicillins

Noncontraceptive Uses

  1. Regular Menstration
  2. Less iron deficiency anemia & rheumatoid  arthritis
  3. Reduced menstrual blood flow
  4.  Reduced incidence of pelvic inflammatory disease & ectopic pregnancies, endometriosis
  5. Reduce incidence of Cancer (15%)
3. Drugs acting on endocrine system

Drug Treatment of Infertility (Gonadal Hormones)

Normally sequence of events start from hypothalamus with gonadotropic releasing hormones acting on gonadotropic cells of pituitary to cause release of gonadotropins, which move downwards to ovary and tetes to stimulate them, causing secretion of estrogen and progesterone. Thus hypothalamus hypophyseal axis is formed.

Any disturbance can lead to infertility, drugs act at different levels:

Drugs Affecting Gonadotropic Releasing Hormones

  • GnRH analogs/agonists
  • GnRH antagonists

GnRH & its analogs

Pulsatile release occurs which can suppress release of gonadotropins

  • Gonadorelin
  • Goserelin
  • Leuprolide
  • Nafarelin

When need for stimulation given by special pumps every 90 mins in pulses

Female Infertility

  • Stimulation of gonadotropins – LH surge, given in pulses
  • Suppression of gonadotropins
  • Suppress premature LH surge, administered in continuous manner
  • Controlled ovarian hyperstimulation – Assisted Reproductive Technique

Male Infertility

  • Hypothalamic-hypogonadotropic hypogonadism
  • Pulsatile – 3- 6 minutes

GnRH antagonists

  • Genirelix
  • Cetrorelix

Same effect as GnRH analogs given in continuous dose.

  • Suppression of gonadotropins
  • Suppress premature LH surge
  • Controlled ovarian hyperstimulation –ART

Advantage – immediate action as antagonists to receptors inhibit directly in the cells of pituitary

– short duration of treatment

Disadvantage – suppression of ovarian hormones


3 types:

a.  FSH
b. LH
c.  hCG

Different preparations are available:

  •  Menotropin (hMG) – FSH+LH
  •  FSH – Urofollitropin (uFSH)
  •   – Follitropin alfa & beta (rFSH)
  •  LH –   Lutropin alfa (rLH) (recombinant DNA technology)
  •   hCG – hCG (human urine of pregnant females)

    Choriogonadotropin alfa (rhCG)

Male Infertility

  • Used in patients of Hypogonadotropic hypogonadism
  •  Androgens –development of sexual characters
  • hCG  (steroidogenesis)
  • hMG / rFSH required for spermatogenesis    

Female Infertility

Used for Induction of ovulation


  •  hMG / rFSH (7-12 days)
  •  continuous monitoring by Serum E / USG – when follicles >18mm:
  •   GnRH agonist / antagonist to suppress premature LH surge
  • When follicles prepared, single dose of hCG leading to ovulation
  • Insemination / oocyte retrieval for ART
  • Luteal support

Adverse effects

  1.             Multiple pregnancies
  2.             OHSS
  3.             Increased vascular permeability leading to ascities
  4.             Pleural effusion, pericardial effusion
  5.             Oliguria, shock, thromboembolism


  •       Ovulation inducing agent
  •       Partial estrogen agonist (SERM)


  • Given orally 100 mg/day
  • Half life is 5-7 days
  • Extensive PPB.
  • Also undergoes enterohepatic circulation
  • Mainly excreted in urine.

Mechanism of Action and Pharmacological effects

  • As parital agonist inhibits estrogenic feedback to pituitary causing release of GnRH / Gonadotropins
  • Increased amplitude of FSH & LH pulses occurs

Therapeutic Uses

  1.  Hypothalamic-hypophyseal-ovarian system has to be intact for drug to act.
  2.  Ovulation induction – 100 mg/day for 5 days for one cycle

   – Upto 12 cycles

Adverse effects

  1. Multiple pregnancies
  2. OHSS
  3. Intensification & prolongation of afterimages
  4. Ovarian cancer
  5.  Hot flushes / headache / constipation / allergic skin reaction / reversible hair loss


–        Semisynthetic ergot alkaloid

–        D2 receptor agonist

–        Used for Hyperprolactinemia

–        Known to cause amenorrhea / Infertility


Luteal support in assisted reproductive technique.

3. Drugs acting on endocrine system

Androgens and Anabolic Steroids (Gonadal Hormones)

Source & Biosynthesis

  • Mainly by Leydig cells of testis (95% by leydig cells, 5% by adrenals)
  • In females, both ovaries and adrenals convert estradiol.
  • Same biosynthesis pathway as estrogen.


A. Natural

  • Testosterone
  • Dihydrotestosterone
  • Dehydroepiandrosterone
  • Androstenedione

B. Synthetic

Testosterone Esters

  • Testosterone cypionate
  • Testosterone enanthate

Alkylated Androgens

  • Methyltestosterone
  • Fluoxymesterone

Anabolic Androgens

  • Oxymetholone
  • Oxandrolone
  • Nandrolone decanoate

Mechanism of action

Steroidal receptors, androgenic receptors intracellularly present, binding leads to changes in pattern of synthesis of estrogen.


Routes of administration –oral, sublingual, transderma, topical

Protein binding – bind sex hormone binding globulin SHBG

5α-reductase – converts testosterone into dihydrotestosterone

Conjugation occurs and excreted in form of urates

Physiological & Pharmacological Effects

Development of primary sex characteristics

Development in utero and whole life.

Development of secondary sex characteristics

Like changes in growth of hair patterns, change in skin thickness, which becomes oilier, deepness of voice due to growth of larynx and vocal cords, muscular, skeletal growth.

Effect on growth & Ca+2 metabolism

Increased deposition, thickness of bones is increased

Epiphyseal closure is accelerated

Increase in muscular mass esp. shoulder girdle.

Metabolic effects

Androgens increase synthesis of hepatic proteins, clotting factors, triglyceride lipase, alpha 1 antitrypsin and other proteins.

Effect on water & electrolytes

Increased resorption of sodium from distal convulated tubules leading to edema in susceptible patients.

Effect on blood

Increased secretion of erythrocytes, increased RBCs

Anabolic effects

Increased activity, increased protein anabolism decreased catabolism

Increased Na, K, Ca, N

Increased tolerance in athletes.

Therapeutic Uses

  1. Replacement therapy in male
  •   Primary hypogonadism
  •   Castration
  1. Gynaecological disorders in female
  2. Male contraception
  3. Catabolic & wasting states –anabolic effects
  4. Anemia –refractory cases, now replaced by recombinant erythropoietin
  5. Osteoporosis
  6. Growth stimulators

In those young boys having delayed puberty and growth but used with caution. Also cause closure of epiphysis and can retard growth.

  1. Aging

Used to slow down aging process.

  1. Anabolic steroids in sports

Not therapeutic use but misuse, to increase performance because of anabolic effects.

Adverse Effects

In females

  1. Acne
  2. Hirsuitism

In infants

  1. Affects CNS
  2. Growth
  3. Sexual functions

In males

Hepatic dysfunction

a.      Increased bilirubin
b.      Cholestasis
c.       Jaundice
d.      Increased incidence of adenoma and carcinoma of liver
e.       Some reports of hepatic failure with use

Urogenital system

  1. Prostate hyperplasia –benign prostatic hyperplasia, urinary retention especially in older patients
  2. Also increase incidence of prostatic cancer
  3. Suppress sperm production -azospermia


  1. Aggression
  2. Psychotic behavior
  3. Psychological dependence


  1. Na retention
  2. hypertension




Other effects

  1. Acne
  2. Gynecomastia

Contraindications & Cautions

  •       Pregnant females causing masculinization of female fetus or under masculinization of male fetus.
  •       Infants
  •       Hepatic / CVS / Renal / Cancer patients (prostatic, breast)


  • Anti androgens are the inhibitors of testosterone secretion
  • They are released in non pulsatile nature,
  1. GnRH analogs – Goserelin / Nafarelin are used in Prostate Cancer
  2.  Steroid synthesis inhibitors – Ketoconazole antifungal, inhibits many enzymes of steroid synthesis
  3. 5α-reductase inhibitors – Finasteride inhibits conversion of testosterone into dihydrotestosterone.

Uses BPH / Male pattern baldness / Hirsutism

Androgen receptor inhibitors

  •             Flutamide / Bicalutamide
  •             Cyproterone 
  •             Spironolactone –inhibition of androgen and aldosterone receptor

Uses Hirsutism /   androgenic activity / Prostate Ca


  •       Drug having Progestational / Androgenic / Glucocorticoid activity
  •       Weak glucocorticoid activity, Suppression of ovarian functions
  •       Major active metabolite Ethisterone


  1.  Endometriosis
  2.  Fibrocystic disease of breast
  3.  Hematological & allergic disorders
  4.  Hemophilia
  5.  Idiopathic thrombocytopenia purpura
  6.  Angioneurotic edema

Adverse effects

  1. Weight gain
  2. edema
  3. headache
  4. hot flushes
  5. hirsutism
  6. acne
  7. breast size
  8. voice deepening
3. Drugs acting on endocrine system

Progestins and Anti Progestins (Gonadal Hormones)



21 carbon compounds to which non-phenolic ring and different groups are attached.

Source & Biosynthesis

Natural and synthetic



  •  Progestrone


1. Progestrone derivatives

  • Hydroxyprogestrone caproate
  • Medroxyprogestrone acetate

2. 17-Ethinyl testosterone derivatives

  • Dimethisterone

3. 19-Nortestosterone derivatives

  •  Norethindrone
  • Desogestrel
  •  Norgestimate


Routes of administration –oral, i/M, implants, transdermal, form of depo preparations

Hydroxylation & conjugation occurs in the body, excreted in urine

Mechanism of action

Two isoforms of progesterone receptors are present – A & B –these are intracellular receptors, mechanism is same as estrogen.

Physiological & Pharmacological Effects

Neuroendocrine effects

Because of feedback on releasing hormones regulate release of different gonadotropins and gonadal hormones

Reproductive system

Development of uterus and endometrial lining responsible for glandular growth. In secretory phase, responsible for start of menstrual bleeding.

Mammary glands

Glandular/acinar growth

Metabolic effects

  • Increased basal levels
  • Produced in response to carbohydrate diet.
  • Lipid metabolism increase in lipoprotein lipase activity, increase in LDL and cholesterol. Effect is opposite to estrogens.
  • Decreased amino acids in plasma leading to decreased nitrogen excretion.

CNS effects

  • Depressant effect hypnotic –given bedtime
  • Body temperature increased during mid cycle time increased if used as predictor of ovulation, exact mechanism is not known.

Effect on respiration

  • Increased ventilator response to carbon dioxide
  • Decreased blood carbon dioxide during luteal phase
  • Maintains pregnancy, changes responsible for placenta formation
  • Suppress uterine contractions

Adverse effects

a.      Hypertension
b.      Decreased HDL increased atherosclerosis
c.       Increased chances of breast cancer

Therapeutic Uses

  1. Contraception
  2. Hormone replacement therapy
  3. Abnormal / Dysfunctional Uterine Bleeding
  4. Dysmenorrhea / Endometriosis
  5. Diagnostic Uses

See whether estrogen, if on stoppage of progesterone withdrawal bleeding, if no estrogen no withdrawal bleeding

  1. Endometrial carcinoma –decreased chances when given with estrogen
  2. Luteal phase support –rise in temperature
  3. Premature labor
  4. Habitual abortions –controversial use



Acts on progestrone & glucocorticoid receptors 


  • Contraceptive 600 mg single dose post coital as emergency contraceptive
  • Abortifacient – PGE1

In early pregnancy during 1st two months along with PGE1 pessaries used (4-6 mg given for 4 days or 800 mg for 2 days along with 1 mg PGE1 pessary as abortifacient

  • Endometriosis
  • Cushing’s syndrome
  • Breast cancer
  • Meningiomas
3. Drugs acting on endocrine system

Estrogens and Anti Estrogens (Gonadal Hormones)



Steroids having phenol ring, many groups are attached, responsible for different pharmacokinetics and pharmacodynamics of different preparations


  • Natural/Synthetic
  • Plants (fungi)

Present in animals and humans, main source is Stallion horse urine for clinical use

Synthetic are made from plastics, pesticides and many other industrial chemicals


Androstenedione has affinity for alpha receptors, action is different in different parts of body.


A. Natural Estrogens

–        Estradiol

–        Estrone

–        Estriol

–        Equilin

B. Synthetic Estrogens

  I. Steroidal

–        Ethinyl Estradiol

–        Mestranol

–        Quinestrol

 II. Non-steroidal

–        Diethylstilbestrol

–        Chlorotrianisene

–        Methallenestril


Routes of administration –can be given by oral/I/V/transdermal/topical applications/vaginal creams, gels

In body bind hormone binding globulin

Hydroxylation & conjugation occurs in liver to inactive metabolites

Enterohepatic circulation –pass to intestine and hydrolyzed, reabsorbed and reach liver again where conjugation occurs

If given through transdermal patch or topically, less liver effects are seen.

Mechanism of action

In body two forms of estrogen receptors are present:

α & ß

When estrogen binds these isoforms, stabilizing proteins, heat shock proteins, dissociate from receptor, estrogen receptor complex is formed. These receptors then form homo & Hetro-dimers.

Bind estrogen receptor element present on promotor region of gene to modify transcription.

Enzymes, growth factors, cytokines are involved. Transcription not only involves binding with response element, but also co-regulators – co-activators are required.

It takes longer for non-genomic effects to appear, e.g. change in blood supply of uterus, increased calcium uptake by granulosa cells.

Physiological & Pharmacological Effects

Developmental Effects

Female maturation

Development of essential internal genital organs, growth, primary and secondary sexual characteristics, development of mammary glands

Male maturation

Endometrial Effects

Required for both growth and development of endometrial lining, smooth muscles, stroma and ductal region of uterus.

Metabolic & Cardiovascular Effects

Bones / Skin / Blood vessels- suppress osteoclastic activity, inhibiting resorption of bone, required for stimulation and formation of blood vessels. In vessels cause formation of nitric oxide, nitric oxide synthetase, responsible for vasodilatation.

Proteins / Lipids –increased protein synthesis, increased plasma proteins like binding proteins, globulins (corticosteroid binding, etc.), increased formation of fibrinogen, renin substrate.

Decreased LDL and cholesterol, increased HDL and triglycerides

Effects on Blood Coagulation

  1. Synthesis of clotting factors,
  2. increased hypercoagubility,
  3. decreased antithrombin III,
  4. increased plasminogen,
  5. decreased platelet adhesiveness

Effects on CNS

  1. Feeling of well being
  2. Stimulate sympathetic components esp. corticotropic release

Miscellaneous effects

Promote synthesis of progesterone receptors

Facilitate movement of intravascular fluid into extravascular space leading to edema. Decrease intravascular volume responsible for stimulation of aldosterone secretion and retention of sodium and water.

Therapeutic Uses

1. Replacement Therapy

a. Primary Hypogonadism – Turner’s syndrome

Estrogen is given to facilitate pubertal changes.

b. Castration / Oophorectomy

c. Postmenopausal Hormone Therapy

Given for different reasons:

i. Vasomotor symptoms

Hot flushes alternating with chills, very troublesome. As estrogen increases the chances of cancer, in high risk individuals, Clonidine can be given.

ii. Osteoporosis

Besides measures include:

  1. Physical activity
  2. Intake of calcium and vitamin D

Bone density at time of menopause determines.

iii. Vaginal & urogenital atrophy

Topical gels are used

iv. Cardiovascular disease

Beneficial effects on lipid profile.

v. Breast & endometrial cancers

Endometrial chances are decreased, breast cancer chances are increased if combination of estrogen and progesterone is given.

2. Colon cancer / Alzheimer’s

3. Contraception

4. Suppression of ovarian functions

5. Dysmenorrhea

Adverse Effects

1. Carcinogenic Effects

a. Breast cancer increased chances if progesterone is added

b. Endometrial cancer chances are decreased if given alone

c. Vagina –mothers treated with diethylstilbesterol if give birth to female child, increased chances of adenocarcinoma of vagina in child

2. Cardiovascular Effects

a. Thromboembolic disease increased chances

b. Edema

c. Hypertension

3. Miscellaneous Effects

Nausea / Migraine / Hyperpigmentation / Breast tenderness / Gallbladder / Cognition

Contraindications & Cautions

Care is taken in high risk individuals:

Patients having thromboembolic disease, liver disease, hypertension


Antagonize effects of estrogens

Estrogen synthesis inhibitors

GnRH analogs 

  • Buserelin & Nafarelin (suppress pulsatile release, decreased formation)
  • Aminoglutethimide (inhibit conversion of cholesterol into pregnolone)

Aromatase inhibitors

  • Anastrozole
  • Letrozole
  • Exemestane

Breast / Prostate Cancers inhibitors

Estrogen receptor antagonists

  •             Fulvestrant



Selective Estrogen Receptor Modulators

  • Tamoxifen (older used for treatment of infertility)
  • Raloxifene
  • Toremifene
  • Clomiphene

Competitive partial agonist inhibitors

Tissue-selective actions

In some areas estrogenic activity, others anti-estrogenic activity, estrogenic activity on bones, liver (protein metabolism), endometrium whereas anti-estrogenic activity on breast so used in breast cancers.


1. Breast cancer – chemoprevention 

Treatment is given for around 5 years

2. Osteoporosis – Raloxifene has more effects on bones, advantage is that has antiestrogenic activity on breast, so chances of breast cancer are not there.

3. Drugs acting on endocrine system

Thyroid Hormones and Drugs

What Are Hormones?

  • Chemicals that are released into the bloodstream
  • Regulators of specific body functions


Thyroid is the largest endocrine gland in human body, situated in front of neck. Isthmus divides it into two parts. It is mandatory for body temperature, regulation, metabolism, growth, reproductive system, etc.

In absence of thyroid, hypothyroidism occurs. If hormones are deficient at birth, congenital abnormality occurs. Cretinism appears in children. Thyroid hormones, if deficient, are replaced at birth to avoid mental and growth retardation.


Secretes three hormones:

  • Calcitonin, important in calcium homeostasis.
  • Triiodothyronine (T3) and thyroxine (T4), important in growth and metabolic function.

It is composed of large number of follicles filled with coli. Major constituent glycoprotein is thyroglobulin, secreted by the cells into coli.


  • Sources: Iodized table salt, dairy products, fish
  • Adult requirement: 150 mg, increased to 200 mg in pregnancy.
  • Iodized salt: 1 part sodium iodide added to 100,000 parts NaCl.
  •  The average dietary intake – 500 mg /day
  •  Dietary intake below 10 mg /day -synthesis of thyroid hormones inadequate
  1. After ingestion, readily absorbed from small intestine
  2. From extracellular pool, rapidly enters thyroid gland (trapping). After trapping, 30 times more iodine is present in gland than plasma.
  3. Enters through basement membrane (NaI symporter), an apical membrane another symporter pendrin is present, which controls outflow of iodide from cell.
  4. Transporter is also present in cochlea of inner ear à congenital absence leads to deafness and goiter.
  5. Different enzymes are involved in three steps:
    • Oxidation in cells by peroxidase enzyme
    • Organification –binding of iodide with tyrosine in thyroid leading to formation of monoiodotyrosine and diiodotyrosine.
    • Coupling of MIT and DIT to form T4 and T3, which are stored in gland. When required, released in blood by proteolysis.
  6. In periphery deiodination occurs (T4àT3), reused.

Thyroid Hormones

  • Cell membranes receptors: increase amino acid and glucose uptake.
  • Inner mitochondrial membrane receptors: regulate energy metabolism.


  • T4 & T3 are feed-back regulators of TSH
  • TSH is stimulated by α-adrenergic agonists
  • TSH secretion  is inhibited by:
  1. Dopamine
  2. Bromocriptine
  3. Somatostatin
  4. Corticosteroids

Conversion of T4 to T3 is decreased by:

  • Acute & chronic illnesses
  • β-adrenergic receptor blockers
  • Starvation & severe protein energy malnutrition (PEM)
  • Corticosteroids
  • Propylthiouracil
  • High iodine intake (Wolff-Chaikoff effect)

Thyroxine (T4)

Total T4 level is decreased in:

  • Premature infants
  • Hypopituitarism
  • Nephrotic syndrome
  • Liver cirrhosis
  • PEM
  • Protein losing entropathy

Total T4 is decreased when the following drugs are used:

  • Steroids
  • Phenytoin
  • Salicylates
  • Sulfonamides
  • Testosterone
  • Maternal TBI (thyroid binding immunoglobulins)

Total T4 is increased with:

  • Acute thyroiditis
  • Acute hepatitis
  • Estrogen therapy
  • Clofibrate
  • Iodides
  • Pregnancy
  • Maternal TSI



  • Soybeans
  • Millet
  • Turnip,Mustard
  • Cabbage

Thyroid Hormones

  • 99% of T3 and T4 are bound to plasma proteins (thyroid-binding globulin).
  • 0.04% T4 and 0.4% T3 occur in free form.
  • They are excreted in the bile and urine.
  • T4 has a half-life of 6-7 days; T3 has a half-life of 1-2 days.
  • Oral absorption of T4 is 80% and T3 95%
  • Readily absorbed from GIT and excreted in bile and urine.
  • Some of the circulating T4 is deiodinated to T3, the more potent and rapidly acting form.
  • 5:1 is the ratio of T4:T3 in thyroid.


Excess of thyroid hormones or over-production.

Common Signs and Symptoms of Hyperthyroidism

  1. Nervousness
  2. Irritability
  3. Difficulty Sleeping
  4. Bulging Eyes
  5. Unblinking Stare
  6. Goiter
  7. Rapid Heartbeat
  8. Increased Sweating
  9. Heat Intolerance
  10. Unexplained Weight Loss
  11. Scant Menstrual Periods
  12. Frequent Bowel Movements
  13. Warm, Moist Palms
  14. Fine Tremor of Fingers, clubbing

Emotional Symptoms of Hyperthyroidism

  1. Nervousness
  2. Restlessness
  3. Anxiety
  4. Irritability
  5. Sleeplessness or insomnia
  6. Exhaustion


It is reversible in adults. Slowing down of all body functions occurs. It is irreversible in children, as creatinism may occur.

Detected by:

  1. Low free thyroxine levels
  2. Elevated TSH

Common Signs and Symptoms of Hypothyroidism

  1. Tiredness
  2. Loss of Interest and/or Pleasure
  3. Forgetfulness
  4. Dry, Coarse Hair
  5. Loss of Lateral Eyebrow Hair
  6. Puffy Face and Eyes
  7. Goiter
  8. Slow Heartbeat
  9. Dry Skin
  10. Cold Intolerance
  11. Weight Gain
  12. Heavy Menstrual Periods
  13. Constipation
  14. Brittle Nails

How to Remember Signs and Symptoms of Hypothyroidism

Sleepiness, Fatigue, Lethargy

Loss of Memory, Trouble Concentrating

Unusually Dry, Coarse Skin

Goiter (Enlarged Thyroid)

Gradual Personality Change, Depression

Increase in Weight, Bloating or Puffiness (Edema)

Sensitivity to Cold

Hair Loss, Sparseness of Hair

Thyroid Drugs

  • Replacement therapy.
  • Treatment for hypothyroidism.
  • Suppress TSH secretion.
  • Levo isomers are more potent in increasing basal metabolic rate.

Once absorbed, their pharmacokinetic and dynamic properties are identical to endogenous thyroid hormones.

Shelf life is 2 years.


  • Synthetic levo isomer of T4.
  • Oral and I/V preparations are available.
  • Low cost & content uniformity.
  • Better standardization & stability and long duration.
  • Long half-life of T4(7 days)
  • Facilitates maintenance of a steady physiologic replacement.


  • Synthetic L-T3.
  • More difficult to monitor than T4.
  • More expensive.
  • Shorter half-life.
  • Treatment of choice for Myxedema coma.
  • Short term suppression of TSH.
  • Greater risk of cardiotoxicity.


  • Combination of levothyroxine and liothyronine.
  • Ratio of 4:1.
  • No advantage over levothyroxine so not frequently used.


  1. Cretinism –congenital hypothyroidism
  2. Adult Hypothyroidism
  3. Myxoedema coma
  4. Non-Toxic Goiter
  5. Thyroid Nodule
  6. Papillary Carcinoma of Thyroid

Adverse reactions

  1. Hyperthyroidism (or symptoms of hyperthyroidism).
  2. Cardiovascular toxicity (tachyarrhythmias, angina, and infarction)
  3. CNS stimulation
  4. Insomnia.

Classification of Antithyroid drugs

Inhibit thyroid hormone synthesis (Thioamides)

  • Propylthiouracil,
  • Methimazole,
  • Carbimazole

Inhibit iodide trapping [Ionic inhibitors]

  • Thiocyanate,
  • Perchlorates,
  • Pertechnetate

Inhibit hormone release

  • Iodides,
  • Lithium

Destroy thyroid tissue

   Radioactive Iodine

Inhibit peripheral conversion of T4 to T3

  • Amiodarone
  • β-blockers
  • Corticosteroids
  • Propylthiouracil
  • Ipodate


  • Propyithiouracil
  • methimazole,
  • carbimazole.
  1. Inhibit the peroxidase enzymes catalyzing the oxidation of iodide, iodination of thyroglbulin
  2. Inhibit coupling reaction
  3. PTU also inhibits the peripheral deiodination of T4 to T3. Do not block uptake of iodine by gland.
  4. Delay in absorption
  5. Delay in onset 3-4 weeks, because formed T4 takes time to deplete, only further formation is stopped.


Propyl thiouracil

  1. PTU is readily absorbed
  2. Bioavailability is 50-80%
  3. Volume of distribution is equal to total body water
  4. Drug accumulates in thyroid gland
  5. Secreted though kidneys, glucuronide form within 24 hours of administration.
  6. Half life in plasma is 1.5 hours (90 minutes)


  1. Completely absorbed after oral administration
  2. Accumulates in thyroid
  3. Half life is 6 hours
  4. Volume of distribution is equal to that of PTU, but excretion is slower.

Both drugs cross placenta. In pregnancy PTU is preferred, minimum dose required is given.

Methimazole causes congenital abnormality in fetus. Both drugs are excreted in breast milk in small quantity, but safe for nursing infants.


  1. Used for control of hyperthyroidism until surgery.
  2. Suppression of thyroid hormone synthesis until the effect of radioactive iodide begins.
  3. Long-term therapy of mild-to-moderate hyperthyroidism.
  4. The drugs are given orally.

Adverse effects

a.      Mild maculopapular rash,
b.      joint pain,
c.       headache,
d.      nausea,
e.       loss of hair,
f.       altered sense of taste or smell,
g.      Hepatitis,
h.      Cholestatic jaundice
i. Rare: agranulocytosis(0.1-0.5%) –most serious but not common, leading to leukopenia, sore throat, upper respiratory tract infection, immediately stop treatment.

j. Crosses the placenta and enters breast milk, which can lead to hypothyroidism in the fetus and nursing infant.


  Propylthiouracil      Carbimazole
Less potent10 times more potent
Highly PPBLess bound
Less transfer across placenta & milkCrosses the placenta
Half-life=1.5 hrs6-10 hrs
No active metabolitesActive metabolites
Multiple dosesOnce daily dose
Inhibits T3 conversion into T4Does not effect


  • Prepared in 1940s, now rarely used as sole agent.
  • Small amounts of iodine (75-100 ng/day) are required for hormone synthesis.
  • But high concentrations (+ 50 mg/day) produce autoinhibition.
  • lodides inhibit organification
  • Inhibit release of thyroid hormones.
  • Diminishes vascularity of the gland.


  1. Used only preoperatively to shrink the gland. (prior to surgical removal of the gland).
  2. Treatment of thyroid storm.
  3. Prophylaxis of endemic goiter.
  4. It is given as Lugol’s solution (iodine and potassium iodide).
  5. Effects are visible within 24 hours. It is no longer used in long-term therapy.

Adverse reactions

  1. Hypersensitivity reactions
  2. Drug fevers,
  3. Metallic taste,
  4. Bleeding disordes,
  5. Swollen salivary glands,
  6. Conjunctivitis,
  7. Rhinorrhea
  8. Gastric irritation.

Long-term use can lead to sudden disinhibition of hormone synthesis, producing acute hyperthyroidism.

Radioactive Iodine

  • Given orally or I/V.
  • Rapidly taken,absorbed,,concentrated by thyroid,incorprated into storage follicles.
  • Leads to partial or total destruction of the gland by emission of beta particles.
  • Damage to surrounding tissue is minimal.
  • Metastatic carcinoma of thyroid


  1. simple
  2. low cost,
  3. effective,
  4. easy administration,
  5. absence of pain,
  6. no surgical risk,
  7. no genetic damage.


  • Major: hypothyroidism.
  • Long latent period of response.
  • Not suitable for young patients.
  • Should be avoided during pregnancy.

Iodinated Contrast Media

  • Diatrizoate (PO), Iohexol (PO OR I/V).
  • Inhibit conversion of T4 to T3 in liver,kidney,pituitary gland & brain.
  • Useful adjunctive therapy in thyroid storm
  • Alternatives to iodides or thioamides

Beta Blockers

  • Excess thyroid hormones, upregulation of B-adrenergic receptors.
  • Tachycardia, tremors, anxiety.
  • Propranolol,metoprolol,atenolol.
  • Inhibits peripheral conversion of T4 to T3

Thyroid Storm

Acute exacerbation of symptoms of disease thyrotoxicosis, if not treated quickly, leads to death


1. Supportive

Fever controlled by antipyretics, I/V fluids, etc.

2. Drug treatment

  • Propanolol given I/V 1.2 mg after that orally 40-80 mg every 6 hours, if contraindicated, Diltiazem is used for CVS symptoms and severe tachycardia.
  • Potassium Iodide (10 drops orally daily] –retard release of thyroid hormones from gland.
  • Iodinated Contrast Media(1g orally)
  • Hydrocortisone to prevent shock
  • Antithyroid drugs to inhibit thyroid hormone synthesis.
  • Supportive therapy

When the Thyroid Doesn’t Work

3. Drugs acting on endocrine system

Adrenal hormones -Glucocorticoids Mechanism of Action, Therapeutic Uses and Adverse Effects

Adrenal hormones are released from the adrenal gland, which is divided into two parts:

  1. Adrenal cortex –hormones secreted are known as corticosteroids
  2. Adrenal medulla –hormones secreted are known as catecholamines

Anatomically adrenal cortex has three parts or layers:

  1. Zona glomerulosa –outermost concerned with secretion of aldosterone (mineralocorticoids)
  2. Zona fasciculate –secretion of glucocorticoids
  3. Zona reticularis –secretion of androgens

Regulation of Corticosteroids Secretion

Regulation is by two mechanisms:

  1. Negative feed back
  2. Positive feed back

Glucocorticoids (cortisol) production/secretion is regulated by negative feedback.


Mineralocorticoid (aldosterone) secretion regulation is by positive feedback.

Increased sympathetic activity leads to increased renin which increases aldosterone, resulting in salt and water retention


Steroids are chemically having large cyclopentanoperhydrophenanthrene nucleus.




  • Cortisol
  • Cortisone


  • Betamethasone
  • Dexamethasone
  • Prednisolone
  • Triamicinolone
  • Prednisone
  • Methylprednisolone



  • Aldosterone
  • Desoxycorticosterone acetate (DOCA)
  • Corticosterone


  • Fludrocortisone

Glucocorticoids (According to Duration of action)

1.      Short Acting (T ½   8-12 Hrs)

  • Cortisone –prodrug, converted in liver to cortisol/hydrocortisol
  • Cortisol

2.      Intermediate Acting (T ½  12-36 Hrs)

  • Prednisolone –very less mineralocorticoid activity as compared to cortisol
  • Methylprednisolone –same effects as  prednisolone except given by I/V route of administration
  • Triamcinolone –has no mineralocorticoid activity

3.      Long Acting  (T ½   36-72 Hrs)

  • Paramethasone
  • Betamethasone
  • Dexamethasone -very potent anti-inflammatory activity

Glucocorticoids Administered by Inhalation– used in bronchial asthma

  • Beclomethasone
  • Budesonide
  • Fluticasone
  • Triamcinolone
  • Mometasone

Steroids -Mechanism of Action

All steroids have the same mechanism of action, but differ in production of ultimate proteins.

  1. Crossing cell membrane

All steroids enter cell passively.

  1. Binding with cytosolic receptor

Mainly present intracellularly. Two types of receptors are involved:

  1. GR –alpha
  2. GR –beta

(GR = glucocorticoid receptor)

Receptors are distributed throughout the body. Mineralocorticoid receptors are present mainly in excretory organs like kidneys, colon and sweat glands, etc.

Receptors of glucocorticoids are present all over body.

  1. Dissociation of receptor from Hsp 90 & 70

Normally receptors are covered by regulatory proteins, which are of two types:

  1. HSP-90
  2. HSP-70

These are the heat shock proteins, the regulatory and stabilizing proteins. When steroids bind the receptors, they cause displacement of stabilizing proteins from receptor sites.

  1. Active transport of steroid-receptor complex into the nucleus
  2. Binding of activated receptor with DNA

Receptor separates and steroid binds DNA

  1. DNA transcripts the formation of specific mRNA
  2. Formation of specific protein  lipocortin (Annexin 1)

mRNA enters cytoplasm and goes to ribosomes to bind them causing formation of specific proteins by the power of translation.

  1. Lipocortin (protein) inhibits phospholipase A2

Phospholipase is responsible for generation of arachidonic acid.

  1. Inhibition of formation of arachidonic acid from phospholipid
  2. Inhibition of formation of chemical mediators, including prostaglandins and leukotrines.

This is the anti-inflammatory mechanism of glucocorticoids.

Glucocorticoids Pharmacological Actions

Effects are divided into two main categories:

1.   Metabolic Effects

a)  Carbohydrate Metabolism

  1. Steroids in carbohydrate metabolism cause and increase in blood levels of glucose.
  2. Decrease utilization of glucose
  3. Cause increase in gluconeogenesis
  4. Cause increased breakdown of glycogen

All effects lead to increased glucose levels, producing diabetogenic effect.

b) Lipid Metabolism

  1. Lipolysis occurs
  2. In high doses, redistribution of fat to other parts of the body.

c)  Protein Metabolism

  1. Have catabolic effect
  2. In high doses, cause loss of protein matrix from bones and cause thinning of skin and wasting of muscles
  3. Atrophy of skin, if applied topically
  4. Negative nitrogen balance

d) Water & Electrolyte Balance

Salt and water retention and excretion of potassium.

These effects are minor, in over dosage or prolonged use cause excretion of water

e) Excretion of urates

On prolonged administration, increase the chances of urine stone formation (urinary canaliculi)

f)  Antivitamin D activity

Some anti-vitamin activity so cause increased excretion of calcium in urine.  

g)  Augment the action of growth hormone on adipocytes

(have specific lipase enzyme).

2.  Non metabolic effects

a)  Anti Inflammatory Action

Most important effect, causing reversal of all signs/symptoms of inflammation without removing cause. Thus have non-specific effect in inflammation.

b)  Lympholytic action

Generalized decrease in lymphoid tissues in body occurs along with lymphocytopenia.

c)  Immunosuppressive action

Cause a decrease in immunity by:

  1. Causing decrease in lymphocytes (decreased antibodies formation)
  2. Stabilization of mast cell membrane
  3. Due to anti-inflammatory effect
  4. Some anti-histaminic effect

d)  Effects on Blood

  1. Cause increase in RBCs, hemoglobulin, neutrophils and platelets.
  2. Most important is that they cause decrease in eosinophils, decrease in basophils and monocytes, leading to anti-allergic effects

e)  CNS

When patient starts taking steroids (in therapeutic doses):

  1. Elation occurs
  2. Increased appetite
  3. Euphoria

If taken in high doses, lead to:

  1. Insomnia
  2. Even psychotic behaviour

f)  Decrease production of TSH & increased growth hormone production


  1. Natural steroids,
  2. After release bind specific proteins known as CBG (corticosteroid binding globulins)
  3. Metabolized in liver and excreted in urine
  4. Synthetic steroids can be given by various routes of administration:
    • Oral route
    • Topically
    • Inhalation –bronchial asthma
    • Parenteral
    • Intra-articularly –rheumatoid arthritis

Therapeutic uses of Glucocorticoids

1.  Replacement therapy in adrenal disorders

Very important logical use in

a.  Acute adrenal insufficiency

Usually occurs when steroids are given in high doses for long periods and then abruptly stopped, due to negative feedback (availability of hormones), atrophy of adrenal gland occurs.

Treatment is to give hydrocortisone or cortisol 100-200 mg 6 hourly, until condition is controlled.

When giving steroids for long periods, dose is gradually tapered off.

b.  Chronic adrenal insufficiency (Addison’s disease)

Due to tumor of adrenal cortex, infections (tuberculosis of adrenal gland) or removal, chronic insufficiency occurs.

Treatment is to give replacement therapy including glucocorticoids along with mineralocorticoids.

Cortisol in a dose of 20-30 mg, synthetic ones are given in equivalent doses.

Once patient is stabilized, two-thirds of the dose is given in the morning, while one-third in evening.

c.  Congenital adrenal hyperplasia

Very rare congenital defect in synthesis of glucocorticoids, leading to excessive formation of androgens. This may be:

  1. Congenital
  2. Defect in last step of corticosteroid because of excessive enzyme responsible for synthesis

Androgens are formed one step earlier, especially in pregnant females virulization of female fetus occurs.

Treated by administering glucocorticoids.

2.  Non-adrenal disorders (Empirical Uses)

Ist Line uses

  1.  SLE and other Collagen disorder

Autoimmune disorders, very effective and live saving.

  1.  Acute leukemias  and lymphomas

In combination with anti-neoplastic drugs

  1.  Status asthmaticus/Bronchial asthma

Hydrocortisone is given I/V 100-200 mg 6 hourly, until acute attack is controlled

  1.  Gram negative septicemia

Life threatening condition, death may occur, given in combination with anti-microbial drugs.

  1.  Cerebral edema

Medical emergency, may occur after head injury.

Dexamethasone is given for cerebral edema.

  1.  Glomerulonephritis/Nephrotic syndrome

Affect especially membranous type of glomerulonephritis.

  1.  Idiopathic thrombocytopenic purpura –sometimes repond to steroids
  2.  Aplastic anemia 
  3. Hemolytic anemia (acquired) –respond in emergency
  4. Immunosuppression

Used as immunosuppressive in:

  1. Rheumatoid arthritis
  2. Prevent transplant graft rejection
  3. Prevent graft vs. host reaction
  1.  Auto immune thyroiditis
  2.  Acute mountain sickness      

In combination with acetazolamide and carbonic anhydrase inhibitors

Advantage of combination is that acetazolamide is that these have rapid action, while acetazolamide has delayed effects.

  1.  Allergies

Especially seasonal (pollen)

  1.  Acceleration of lung maturation in  premature babies

Cortisol causes maturation of lungs and in premature infants, there is decreased release of cortisol so given to mother before delivery esp.

  1. Beclomethasone 48 hourly before delivery I/M.
  2. Again before 24 hours of delivery

15.  Dermatologic conditions

  1. Contact dermatitis
  2. Lichen planus
  3. Pemphigus
  4. Seborrhoeic dermatitis

In most skin conditions steroids are used, esp. non-infective skin conditions.

16.  Ocular conditions

  • Acute conjunctivitis
  • Choroiditis
  • Uveitis

17.  Diagnostic purpose

To access primary and secondary caused of Cushing disease (ACTH excess) give potent steroid, dexamethasone, if after administration decreased levels occur, patient has Cushing disease due to primary dysfunction of adrenal cortex.

If no effect is observed, ACTH excess is due to secondary causes (hyperpituitarism or ectopic production)

2nd/3rd Line uses

  1. Anaphylactic shock -1st line is adrenaline
  2. Ulcerative colitis
  3. Crohn’s disease
  4. Rheumatoid arthritis
  5. Osteoarthritis –non-responding
  6. Acute gout –when excessive swelling and pain occurs, along with NSAIDS and Colchicine
  7. Myasthenia gravis –along with neostigmine and physostigmine
  8. Aspiration syndrome –to avoid aspiration of gastric contents
  9. Bronchial asthma –along with other anti-asthmatics oral/inhalational

10.  Acute spinal cord injury –to avoid inflammation and edema

Untoward effects of Glucocorticoids

1. Suppression of adrenal –pituitary axis

Prolonged administration caused negative feedback leading to atrophy of adrenal cortex. Steroids are not withdrawn abruptly, otherwise Addisonians crisis occurs. Dose is gradually tapered, to allow recovery time. Once axis is depressed, it may take months or even years to recover, but when given for short period in low doses (25 mg prednisolone daily for 5-10 days) there is no need to taper off dose.

2. Iatrogenic Cushing’s syndrome –in high doses
3. Hyperglycemia

Due to increased plasma glucose, effect on carbohydrate metabolism

4. Muscle wasting/myopathy

Catabolic effect on proteins

5. CVS

May cause retention of salt and water leading to:

  1. Edema
  2. Hypertension
  3. Even cardiac failure

6. Immunological

Anti-immunity effects, leading to decreased resistance to infections and delayed healing of wounds, making more prone to infections

7. Eye

  • When used topically cause glaucoma on prolonged administration
  • Posterior subcapsular cataract
  • Corneal ulceration

8. GIT

a.      May cause peptic ulcer, due to secretion of HCl and pepsin when taken orally for prolonged periods.
b.      May aggravate ulceration,
c.       In patients of peptic ulcer, may cause painless perforation
d.      May cause increase in candidiasis of GIT
9. Bones

Due to loss of protein matrix may cause osteoporosis, leading to spontaneous fractures.

So patients taking steroids are advised to take calcium and vitamin D supplements to avoid.

10. CNS

In therapeutic doses:

  1. Euphoria
  2. Elation of mood

In excessive doses:

  1. Insomnia
  2. Psychotic behavior
  3. Aggravate psychosis esp. schizophrenia
  4. May cause increase in intracranial pressure on prolonged administration –although rare.

11. Growth suppression

Especially in children due to early closure of epiphysis

12. Hypokalemia

Due to retention of sodium and excretion of potassium. Danger is when patient is taking digoxin or diuretics.

13. Candidiasis

Usually in patients of bronchial asthma, taking steroids by inhalation, due to deposition of steroids in larynx, pharynx, leading to candidiasis.

In larynx ultimately laxity of vocal cords and hoarseness of voice.

  1. Nystatin mouth washes
  2. Azoles
  3. Amphotericin B mouth washes are used
  4. Acne & hirsutism

On prolonged administration, especially after topical use.

14. Striae and bruising –esp. when applied to skin

15. Miscellaneous

  • Delayed wound healing –decreased immunity, delayed fibrosis
  • Skin atrophy –loss of protein matrix
  • Tendon rupture
  • Menstrual disorders
  • Thromboembolism


  1. Diabetes
  2. Glaucoma
  3. CVS disorders
    • Hypertension
    • Cardiac failure


Drugs causing increased sodium and water retention along with increased elimination of potassium, acting on the late distal part and collecting tubules.

Natural are not used in therapeutics.

Aldosterone hormone cannot be given orally because:

1.      Has short duration of action
2.      In older days, when it was used, it had to be given 5-7 times a day by I/M injection


Fludrocortisone in only used nowadays.

  1. Given about 5-7 times a week
  2. Can also be given orally


  1. Treatment of adrenocortical insufficiency, replacement therapy in combination with glucocorticoids
  2. Treatment of hypotension esp. when due to excessive loss of sodium.


50-300 mcg daily. In children dose of 5 mcg/kg body weight daily by oral route of administration.

3. Drugs acting on endocrine system

Oral Anti Diabetic Drugs (Drugs Acting on Endocrine System)


Ist Generation

  • Tolbutamide
  • Acetohexamide
  • Chlorpropamide

2nd Generation

  • Glibenclamide (glyburide)
  • Glipizide
  • Glimepiride


  • Repaglinide

D-Phenyl alanine Derivative

  • Nateglinide


  • Metformin

Alpha Glucosidase Inhibitor

  • Acarbose

Thiazolidinedione Derivatives

  • Rosiglitazone
  • Pioglitazone
  • Troglitazone

Dipeptidyl Peptidase 4 Inhibitors

  • Sitagliptin
  • Pramlintide
  • Exenatide              

Sulfonyl Ureas

Chemically derivatives of sulfonamides. Divided into two main groups:

1st generation2nd generation
Older drugsNewer drugs
Less potent100 times potent

Mechanism of action

Also known as insulin secretogoug.

  1. Mainly act by causing increased secretion of insulin from beta cells of pancreas by binding receptors on surface of beta cells.
  2. Also cause increased sensitivity of tissues to insulin
  3. Also cause decrease in release of glucagon.
  4. Cause decrease in gluconeogenesis
  5. Increase in number of insulin receptors

Ineffective in type I diabetes mellitus, requiring up to 30% of beta cells to be intact for action.

Cause a decrease in conductance of ATP sensitive potassium channels à decreased conductance leads to increase in positivity inside cells à leading to depolarization resulting in à increased entry of calcium through calcium channels à increased release of insulin from beta cells.


  • Well absorbed after oral administration.
  • Extensively bound to plasma proteins, maximum is for Glibenclamide, while Chlorpropamide has the least.
  • Half life varies. 1st generation drugs have short half life (4-7 hours) and short duration of action. Chlorpropamide has long half life of 36 hours (longest in 1st generation). Acetohexamide has active metabolite having same half life (4-7 hours)
  • Second generation compounds have shorter half life of 1.5-5 hours, but have longer duration of action than 1st generation compounds, which may be due to active metabolites formed. Since more potent, usually given once daily.
  • Most drugs are metabolized in liver and excreted in urine. Chlorpropamide is 20% excreted unchanged in urine. Glipizide and Tolbutamide are mainly excreted through bile and less through urine.

Adverse Effects (4%)

  1. Hypoglycemia

More with drugs with longer half life including Chlorpropamide and Glibenclamide, in renal insufficiency, especially in elderly. Treatment is same:

  • Glucose by mouth
  • I/V
  1. Cholestatic jaundice

Since metabolized in liver, hepatotoxicity might occur.

  1. Agranulocytosis

Blood dyscrasias

  1. Anaemia (hemolytic and aplastic)

Alcohol intolerance

In presence of alcohol, there are more chances of hypoglycemia

  1. Allergic reactions

Drugs Interaction Of Sulphonylureas

1. Alcohol

  • Hypoglycemia
  • Chlorpropamide can cause disulfiram like reaction with alcohol

2. Enzyme inducers
3. Enzyme inhibitors à hypoglycemia
4. Chlorpropamide potentiates the effects of ADH on collecting tubules, also used in treatment of diabetes insipidus.

Interacting drugsType of interactionResult
ThiazidesAntagonismDiminished effect of sulphonylureas
RifampicinEnhanced metabolism of sulphonylureasDiminished effect of sulphonylureas
AspirinSulfonamidesDisplacement of sulphonylureas from plasma proteinsEnhanced effect of suophonylureas
ChloramphenicolDicoumarolDecreased metabolism of sulphonylureasEnhanced effect of suophonylureas

Preparations and dosage of Sulphonylureas


Initial dose is 500 mg while 3000 mg is max. effective dose.


250 -1500 mg

Tolazamide and Chlorpropamide:

Initially 100-250 mg while 750 to 1000 mg is maximal.


Initial daily dose 2.5 -5 mg. maximum range is 20 mg

Glipzide: Initially 5 mg. Max is 40 mg in divided doses

Gliclazide: Initially 40 – 80 mg and max is 320 mg


  • Repaglinide
  • Nateglinide

Have same mechanism of action and effects as sulfonyl ureas, but differ from others in:

  1. Rapid onset of action
  2. Short duration
  3. Are metabolized in liver, excreted in bile, thus can be given in renal insufficiency
  4. Cause less incidence of hypoglycemia as compared with sulfonyl ureas (shorter duration of action).

Nateglinide may cause severe hypoglycemia.

Sulfonyl ureas are not given in obese patients as cause increased apetite, these drugs cause less increase in weight thus can be given


Ranges between 0.5-4 mg twice or thrice daily depending upon severity.


Chemically are guanidine derivative. Most of these are withdrawn due to adverse effects including lactic acidosis. Only one drug, Metformin is used.

Mechanism of action

Although does not cause release of insulin, but for action of oral antidiabetic should be so. Mainly act by:

  1. Suppress hepatic gluconeogenesis, preventing hepatic outflow of glucose as liver is mostly responsible, especially during night time.
  2. Stimulate glycolysis leading to breakdown of glucose
  3. Inhibit absorption of glucose from intestine
  • Require some endogenous insulin secretion
  • Do not cause hypoglycemia
  • Reduce hyperlipidemia
  • Loss of appetite


  • After oral administration, less rapidly absorbed.
  • Not metabolized.
  • PPB is very insignificant.
  • Mainly excreted in urine, mostly unchanged.
  • Metformin t ½ 1.5 – 3 hrs
  • Duration of action 8-12 hrs


  1. Mainly used in treatment of type II diabetes mellitus, in combination with sulfonyl ureas and insulin. Can also be used alone.
  2. Also used in polycystic ovarian syndrome (drug causes decrease in insulin, resistance leading to ovulation in these women)

Adverse effects

  1. Mainly GIT effects:
    • GIT upset
    • Diarrhea
    • Abdominal discomfort
    • Sometimes so severe that patient may leave drug
    • Lactic acidosis –more common in patients of renal insufficiency, in alcoholics.
  1. Renal disease –as cause lactic acidosis
  2. Pregnancy
  3. Lactation
  4. Severe infections

Cause increases in HDL and decrease in LDL, beneficial for patients of cardiac diseases. Effects are over after 4-6 weeks of treatment.

Dose: start at low dose of 0.5 g, can be increased to 0.85 g tid or 1 g thrice or twice daily.

Metformin does not cause hypoglycemia, as there is no release of insulin.

Alpha Glucoside Inhibitor


Mechanism of action

  1. Inhibit alpha-glucosidase in intestinal brush border
  2. Inhibit hydrolysis of oligosaccharides to glucose
  3. Also inhibits pancreatic alpha-amylase, responsible for converting starch into oligosaccharides.

Ultimately causes decrease in conversion into glucose.


  • Not absorbed from intestine when given orally, only a small amount is absorbed, excreted unchanged in urine.
  • Most of drug is broken down by bacteria in intestines.
  • Duration of action 3-4 hrs

Dose:25-100mg bid or tid

Adverse effects

  1. Does not cause hypoglycemia when given alone
  2. GIT –as not absorbed, may cause:
    • GIT upsets
    • Flatulence
    • Diarrhea
    • Abdominal cramps


Mainly in patients suffering from GIT disease, may lead to ulceration or intestinal obstruction.

Drug interactions

Also inhibit or decrease absorption of metformine so not given in combination.

Thiazolidinediones or Glitazones

Rosiglitazone, Troglitazone withdrawn due to adverse effects. Only Pioglitazone is available.

Mechanism of action

Also known as insulin sensitizers as increase sensitivity of tissues to insulin.

  1. Mainly act by binding peroxisome proliferator activated receptor-g (PPAR-g), which is a nuclear receptor mainly concerned with regulation of glucose of lipids.
  2. bind receptors leading to increase utilization of glucose
    • Increased HDL levels, decrease in breakdown of fats
    • Expansion of S/C fat
    Thus, increased insulin sensitivity to tissues.


  • Well absorbed after oral administration.
  • Have extensive PPB.
  • Mainly metabolized in liver
  • Pioglitazone also has active metabolites, which are excreted in urine.
  • Some parent drug is also excreted in bile, so drug can be given in renal insufficiency.
  • Duration of action 12-24 hrs

Used for polycystic ovarian syndrome

Adverse effects

  1. All drugs are hepatotoxic, Troglitazone has been withdrawn due to hepatotoxic effects. Thus all patients should have regular LFTs.
  2. Rosiglitazone causes increase in LDL levels so drug is withdrawn from market (cardiovascular disease)
  3. Retention of sodium and water
  4. Increase in subcutaneous fat (increase in weight), used carefully in cardiovascular diseases.

Dose: Pioglitazone: 15-30mg o.d

Dipeptidyl Peptidase Inhibitors

Pramlintide & Exenatide

GLIP stands for glucagon like peptide. Pfzmlintide and Exenatide act through GLIIP enzyme.

Mechanism of action

Normally when patient takes glucose by mouth, increase in release of insulin occurs. Release is more when taken orally than I/V. this effect is said to be due to GLIP.

In diabetics, decrease in release of insulin in response to glucose occurs.

These drugs cause increase in activity of GLIP, so improve insulin release in response to glucose.

  • Slow gastric emptying
  • Decrease food intake
  • Increase glucose suppression of glucagon secretion
  • Promote beta cell regeneration
  • Decrease apoptosis
  • Reduce weight gain, postprandial hyperglycemia & loss of beta cells


  1. Main drawback is that since they are peptides, they cannot be given orally. They are usually given parentally.
  2. Have short duration of action

So not in practice, only long acting drugs may have some benefits.

3. Drugs acting on endocrine system

Diabetes Mellitus and Insulin (Drugs Acting on Endocrine System)

Diabetes Mellitus:

Derived from Greek word diabainain: to pass through

It is a state of high glucose levels which may lead to complications including:

  1. Atherosclerosis
  2. Renal failure
  3. Changes in eye
  4. Retinopathy
  5. Ischemic heart disease
  6. Ultimately coma and death

Patient shows an increase in blood glucose levels due to decreased utilization of glucose, leading to increase in compensatory mechanisms, resulting in increased fat metabolism, leading to formation of ketone bodies (Acetone, Acetoacetic acid, alpha ketobutyric acid). This leads to ketoacidosis and death of patient.

Symptoms of Diabetes Mellitus

Main symptoms occur when absolute or relative deficiency is seen due to various factors:

  1. polyuria
  2. polydipsia
  3. glycosuria


To give insulin. Increase in glucose levels occur due to relative deficiency of insulin. The purpose is to increase glucose metabolism and decrease fat metabolism.

Types of Diabetes Mellitus

Two types:

  1. Type-I (IDDM)

Absolute deficiency of insulin due to degeneration of pancreas, usually occurring in young age. It may be due to:

  • Viral infections
  • Autoimmunity

Insulin is required for treatment, so known as IDDM.

  1. Type-II (NIDDM)

Occurs in middle age, relative deficiency of insulin occurs. Although production may be normal but insulin antagonists may be present in blood. It is a less severe disease than type 1. Type II may lead to ketoacidosis. Insulin may not be required for treatment, it is usually due to increased activity of pancreas (overactiivty). Also has genetic basis.

Causes of insulin lack:

1. Lack of secretion –degradation of beta cells of pancreas

2. Tissues insensitivity to insulin mainly due to excessive secretion from pancreas (esp. type II occurring due to overeating)

3. Excess of insulin antagonists

a. Glucocorticoids

b. catecholamines

c. GH

d. oral contraceptives

4. Depressed release of insulin and transport

Increased blood glucose levels especially after meal is the main stimulus for the release of insulin.

It is mainly synthesized in beta cells of pancreas from pro-insulin, which comes from pre-proinsulin.

Insulin structure

It has a molecular weight of 5808. Chemically consists of 2 polypeptide chains:

  1. a chains –consisting of 21 amino acids
  2. b chains –consisting of 30 amino acids

linked together by disulfide bonds.

Mechanism of action

When insulin is released by beta cells on pancreas, it goes to target tissues present mainly in:

  1. liver,
  2. fat (adipose tissue)
  3. muscles

These contain insulin receptors. Concentration of receptors varies with the amount of insulin in blood. It is inversely proportional to the levels of insulin in blood.

If insulin is increased, downregulation of receptors occurs, leading to decrease in receptors.

After insulin release, it binds insulin receptors present on cell membrane of tissues. There are 2 parts of these receptors:

  1. alpha part –outside cell membrane
  2. beta part –transmembrane

Insulin binds alpha part. Due to binding, autophosporylation of beta part takes place.

Beta part is a kinase enzyme. When autophosphorylated, it also causes phosphorylation of other cell constituents in cell membrane, ultimately leading to translocation of glucose transporters from storage sites to cell membrane.

When these glucose transporters are transported, they cause increased utilization of glucose.


Polypeptide hormone, thus it cannot be given orally.

Routes Of Administration Of Insulin

  1. S/C, I/V, I/M but mostly given subcutaneously. In emergency I/V given.
  2. Implantable pumps
  3. Insulin pens containing catridges filled with insulin
  4. Insulin snuffs (inhalation –newer mode)(onset 30 min, peak 2-2.5 hr, duration 6 – 8 hr)
  5. Miniaturised infusion pumps
  • Half life of 5-10 minutes
  • Metabolized by insulinase enzyme in liver and kidney.
  • Most of insulin secreted by pancreas enters portal veins and goes to liver, only 15% reaches systemic circulation.
  • When given subcutaneously, entry into liver and other organs is same, thus this route is preferred.
  • Addition of certain metals to prolong duration of action e.g. zinc is added to increase duration.
  • Protamine zinc insulin is a type of long acting insulin.

Insulins Types: (According To Source)

  1. Bovine
  2. Porcine
  3. Human (recombinant DNA)

a)      Bovine differs from human insulin in 3 amino acids.

b)      Porcine differs from human insulin in 1 amino acid

c)      Human insulin is pure form –formed by recombinant DNA technique

Disadvantage of bovine and porcine form is although having same effect but increased chances of hypersensitivity reactions.

Human insulin

  1. Has rapid onset of action
  2. Has short duration of action
  3. Is less immunogenic –no or less hypersensitivity reactions

But human insulin is very expensive, so as there is no difference in action, we always use bovine and porcine forms, being cost effective. Human form is resorted to only when patient is not responding or when hypersensitivity reactions are seen.

Bovine and porcine in pure form are mono component, causing less hypersensitivity reactions as compared to older preparations. Human insulin is in pure form, so has no reactions.

Classification (According To Duration Of Action)

  1. Ultra short acting
  2. Short acting
  3. Intermediate acting
  4. Long acting
PreparationOnset of ActionPeak EffectDuration of action
Ultra – short acting
Insulin lisproInsulin aspartGlulisine20min½ hour3-4 hrs
Short acting
Soluble insulin½ – 1 hour4-6 hrs8-10 hrs
Insulin zn suspensionSemilente
Intermediate acting
NPH (isophane)
Insulin zn suspension lente2hrs6-10 hrs24 hrs
Long acting
Protamine zn insulin (pzi)4 hrs10-8 hrs36 hrs
Insulin zn suspensionUltralente
Glargine2-5 hrs5-24 hrs18-24 hrs
Insulin mixtures
Humulin 70/30 mix  (30% soluble Insulin with 70% isophane)Mixtard 30 HM (30% soluble Insulin with 70% isophane)Variable actions Depending on Predetermined Proportions of Short/intermediate or Intermediate/long acting Insulin

Doses Of Insulin

Preparations of insulin are available in the form of units. One unit of insulin is defined as:

“amount of insulin required to lower blood glucose level of a 2 kg normal rabbit from 120 – 45 mg/dl”

  • Normal amount secreted by pancreas daily is 30 -50 units/d (0.5 -0.8 units/kg) of soluble (regular) insulin
  • In IDDM, dose normally ranges between 30-50 units of insulin daily, depending on:
  1. Levels of blood glucose
  2. Physical activity of patient
  3. Diet of patient

When blood levels are more than 300mg/dl, start with 20 units of regular short acting insulin.

If blood levels are less than 200-300/dl, start with 10 units of regular insulin, with 4 units daily increments until blood levels are controlled.

  • Long acting insulins given 10-14 units/day: dose increment 4 units on alternate days
  • Ideally a combination of regular and long acting insulins is used twice daily. (regular –rapid onset, long acting –sufficient for delayed action)
  • Once dose is adjusted, two-third dose is given in morning before breakfast and one-third before evening meal.

Adverse effects of insulin

  1. Hypoglycemia

When there is change in requirement of insulin, e.g.

  • patient misses a meal,
  • increased physical activity

he may go into hypoglycemia. Due to release of catecholamines, certain symptoms appear:

  1. tachycardia
  2. sweating
  3. anxiety
  4. apprehension
  5. insomnia
  6. headache
  7. in severe cases coma ‘hypoglycemic coma’ or even death may occur


  1. give (if conscious) sugar, glucose or meal
  2. if unconscious, glucose given I/V, usually 30% glucose given by I/V drip or infusion
  3. most important is to educate the patient, as there may be damage to brain:
    • not to miss meals
    • always keep sugar, glucose to avoid
    • no increase in physical activity or excessive physical activity
    • whenever feels sympotms, take sugar to avoid hypoglycemia
  4. Lipodystrophy

Repeated injection at same site. Advised not to take injection at same site.

  1. Allergy

Animal origin –skin rash, articaria, localized or generalized

  1. Obesity (increased appetite)

May cause weight gain of patient

Treatment Of Diabetic Ketoacidosis

When treatment is not given, breakdown of fats cause diabetic ketoacidosis, which may be serious enough to cause death of patient.

1. Soluble/short acting Insulin:

Severe Ketoacidosis: 0.1 unit/kg/hr or 7 unit/hr

Less severe: 3 unit/hr

I/V drip: 40 units/l

Rapidly acting in medical emergency.

2. I/V fluids and electrolytes: Isotonic saline
5 L total fluid deficit: 500 ml Ist 20 min
2 L 90 min
1 L 90 min
1 L 120 min

3. Potassium: KCl I/V infusion 15mmol/hr by slow infusion, carefully monitored, given in hypokalemia.

4. Bicarbonate: If plasma PH< 7.0

Forms of human insulin (depending on source recombinant DNA technique)

  • emp (enzyme modified porcine)
  • prb (proinsulin recombinant in bacteria)
  • pyr (precursor insulin yeast recombinant)

Mostly used for type II diabetes –all are taken 30 minutes before meal.