7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 1/51

1

CORTICOSTEROIDSProf. Dr. Shah Murad

shahmurad74@yahoo.com

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 2/51

2

►Corticosteroids are a class of steroidhormones that are produced in the adrenalcortex.

►Corticosteroids are involved in a wide range of physiologic systems such as

►stress response,

►immune response and regulation of inflammation,

►

carbohydrate metabolism,►protein catabolism,

►blood electrolyte levels, and

►behavior.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 3/51

3

►Glucocorticoids such as cortisol controlcarbohydrate, fat and protein metabolism and

are anti-inflammatory by preventingphospholipid release, decreasing eosinophil action and a number of other mechanisms.

►Mineralocorticoids such as aldosterone 

control electrolyte and water levels, mainly bypromoting sodium retention in the kidney.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 4/51

4

common natural hormones

►corticosterone (C21H30O4),

►cortisone (C21H28O5, 17-hydroxy-11-dehydrocorticosterone)

►aldosterone  

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 5/51

5

Biosynthesis

►The corticosteroids are synthesized from cholesterol within the adrenal cortex.

►Most steroidogenic reactions are catalysed byenzymes of the cytochrome P450 family. They are

located within the mitochondria and requireadrenodoxin as a cofactor

► Aldosterone and corticosterone share the first part of their biosynthetic pathway.

►The last part is either mediated by the aldosteronesynthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearlyidentical (they share 11β-hydroxylation and 18-hydroxylation functions).

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 6/51

6

►Moreover, aldosterone synthase is foundwithin the zona glomerulosa at the outeredge of the adrenal cortex; 11β-hydroxylase

is found in the zona fasciculata andreticularis.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 7/51

7

Classes of corticosteroids

►Corticosteroids are generally grouped into fourclasses, based on chemical structure.

► Allergic reactions to one member of a classtypically indicate an intolerance of all membersof the class.

"Coopman classification"

The highlighted steroids are often used in thescreening of allergies to topical steroids

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 8/51

8

►Group A

►(short to medium acting glucocorticoids)Hydrocortisone, Hydrocortisone acetate,

Cortisone acetate, Tixocortol pivalate,Prednisolone, Methylprednisolone, andPrednisone. 

►Group B►Triamcinolone acetonide, , Mometasone, Amcinonide, Budesonide, Desonide,Fluocinonide, Fluocinolone acetonide, and

Halcinonide. 

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 9/51

9

►Group C

►Betamethasone, Betamethasone sodiumphosphate, Dexamethasone, Dexamethasonesodium phosphate, and Fluocortolone. 

►Group D

►

Hydrocortisone-17-butyrate,Betamethasone valerate,Betamethasone dipropionate, Prednicarbate, , ,, , and Fluprednidene acetate 

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 10/51

10

Routes of adm: of Corticosteroids

► 1. Topical steroid for use topically on the skin, eye,and mucous membranes.

► 2. Inhaled steroids for use to treat the nasal mucosa,sinuses, bronchii, and lungs.

► 3. Oral forms - such as prednisone and prednisolone.

► 4. Systemic forms - available in injectibles for useintravenously and parenteral routes

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 11/51

11

Uses

►Synthetic drugs with corticosteroid-likeeffect are used in a variety of conditions,ranging from brain tumors to skin diseases.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 12/51

12

►Dexamethasone and its derivatives arealmost pure glucocorticoids, whileprednisone and its derivatives have some

mineralocorticoid action in addition to theglucocorticoid effect.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 13/51

13

►Fludrocortisone (Florinef) is a syntheticmineralocorticoid.

►Hydrocortisone (cortisol) is available forreplacement therapy, e.g. in adrenalinsufficiency and congenital adrenalhyperplasia.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 14/51

14

►Synthetic glucocorticoids are used in thetreatment of joint pain or inflammation(arthritis), temporal arteritis, dermatitis,

allergic reactions, asthma, hepatitis, systemiclupus erythematosus, inflammatory boweldisease (ulcerative colitis and Crohn's disease),

sarcoidosis and for glucocorticoid replacementin Addison's disease or other forms of adrenalinsufficiency.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 15/51

15

►Topical formulations are also available forthe skin, eyes, lungs, nose, and bowels.

►Corticosteroids are also used supportively toprevent nausea, often in combination with5-HT3 antagonists (e.g. ondansetron).

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 16/51

16

►Typical undesired effects of glucocorticoidspresent quite uniformly as drug-inducedCushing's syndrome.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 17/51

17

►Typical mineralocorticoid side effects arehypertension (abnormally high bloodpressure), hypokalemia (low potassium

levels in the blood), hypernatremia (highsodium levels in the blood) without causingperipheral edema, metabolic alkalosis and

connective tissue weakness

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 18/51

18

►Corticosteroids can cause permanent eyedamage by inducing central serous retinopathy (CSR, also known as central serouschorioretinopathy, CSC).

► A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to

topical skin creams, to eye drops (Tobradex),to Prednisone have been implicated in thedevelopment of CSR.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 19/51

19

►Cortisone, often mispelled cortizone, brandname Cortone, is a corticosteroid used totreat arthritis pain and inflammation.

►Cortisone acetate may also be given in anintramuscular injection (cortisone shot).

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 20/51

20

►Prednisone is a potent medication which isused to treat many inflammatory conditionsincluding rheumatoid arthritis.

►It is important to know the proper use of the drug and be aware of the potentialserious side effects.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 21/51

21

►Steroid withdrawal symptoms can occur if corticosteroid drugs are not discontinuedgradually.

►

Tapering the dose of steroids minimizescorticosteroid withdrawal symptoms.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 22/51

22

►Glucocorticoid-induced osteoporosis is bothpreventable and treatable.

►Glucocorticoids (steroids) are the mostcommon cause of drug-inducedosteoporosis.

Th t t id i ft i d t d

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 23/51

23

►The term steroids is often misunderstood.

►

Corticosteroids (a class of drugs used to treatarthritis and many other conditions) are often just called "steroids".

►So what's in a name? Confusion results whenthey are mistaken for anabolic steroids (drugsused by athletes to boost strength and enhancephysical performance).

►What is the difference between anabolicsteroids and corticosteroids? 

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 24/51

24

► According to the National Institute of GeneralMedical Sciences, the term "steroid" is a chemicalname for any substance that has a characteristicchemical structure consisting of multiple chemicalrings of connected atoms. Some commonexamples of steroids are:

► Vitamin D

►

cholestrol► estrogen

► cortisone

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 25/51

25

►Steroids are critical for keeping the bodyrunning smoothly.

► Various steroids have important roles in thebody's reproductive system and both thestructure and function of membranes

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 26/51

26

anabolic steroids

► According to the National Institute on Drug Abuse, anabolic steroids are syntheticsubstances related to the male sex hormones

(androgens).

►They promote growth of skeletal muscle

(anabolic effect) and the development of malesexual characteristics (androgenic effects).

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 27/51

27

►The proper term for these compounds actuallyis "anabolic / androgenic" steroids:

► “anabolic”  refers to muscle-building

► “androgenic”  refers to increased masculinecharacteristics

► “steroids”  refers to the class of drugs 

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 28/51

28

► Anabolic steroids are available legally onlyby prescription, to treat conditions thatoccur when the body produces abnormally

low amounts of testosterone, such asdelayed puberty and some types of impotence. 

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 29/51

29

 Anabolic steroids

►They are also prescribed to treat bodywasting in patients with AIDS and otherdiseases that result in loss of lean muscle

mass.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 30/51

30

 Abuse

► Anabolic steroids are being abused by some athletesand others to enhance performance or improvephysical appearance. Abuse of anabolic steroids canlead to serious health problems, some of which are

irreversible. Major side effects can include:► liver tumors► cancer► jaundice

►high blood pressure► kidney tumors► severe acne► trembling

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 31/51

31

►In males, side effects may include shrinking of the testicles and breast development.

►In females, side effects may include growth of facial hair, menstrual changes, and deepenedvoice. In teenagers, growth may be halted

prematurely and permanently.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 32/51

32

►Corticosteroids or glucocorticoids, often justcalled "steroids", are drugs closely related tocortisol, a hormone which is naturally

produced in the adrenal cortex (the outerlayer of the adrenal gland).

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 33/51

33

►Corticosteroids act on the immune systemby blocking the production of substancesthat trigger allergic and inflammatory

actions, such as prostaglandins.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 34/51

34

Corticosteroids

►Betamethasone (Celestone)

►Budesonide (Entocort EC)

►Cortisone (Cortone)

►Dexamethasone (Decadron)►Hydrocortisone (Cortef)

►Methylprednisolone (Medrol)

► Prednisolone (Prelone)

► Prednisone (Deltasone)

►Triamcinolone (Kenacort, Kenalog)

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 35/51

35

Corticosteroids (Steroids): Benefitsvs. Risks

►Corticosteroids are powerful drugs which canquickly reduce swelling and inflammation,greatly improve symptoms and provoke

incredible results.

►However, there are potential consequences and

side effects.

►The power of corticosteroids should not befeared, but must be respected.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 36/51

36

►To maximize benefits, but minimize potentialside effects, steroids are usually prescribed inlow doses or for short durations.

►The potent effect of corticosteroids can resultin serious side effects which mimic Cushing'sdisease, a malfunction of the adrenal glandsresulting in an overproduction of cortisol

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 37/51

37

The list of potential side effects islong and can include:

► increased appetite and weight gain► deposits of fat in chest, face, upper back , and stomach► water and salt retention leading to swelling and edema► high blood pressure

► diabetes► osteoporosis ► cataracts► acne► muscle weakness► thinning of the skin► increased susceptibility to infection► stomach ulcers► psychological problems such as depression

► adrenal suppression and crisis

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 38/51

38

Tappering off the dose of steroids

►

Side effects are minimized by taking thelowest doses possible (that still yields positiveresults) and following doctor's orders.

►It is important to avoid self regulation of thedosage, either by adding more or stopping thedrug without a schedule.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 39/51

39

►Steroids must be gradually reduced to permitthe adrenal glands to resume natural cortisolproduction.

►Eliminating doses too quickly can result inadrenal crisis (a life-threatening state causedby insufficient levels of cortisol).

► Another possible complication to coming off steroids is withdrawal syndrome, or reboundeffect, which is the body's exaggerated

response to removal of the drug.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 40/51

40

Prednisone 

►Prednisone is a synthetic drug closely related tocortisol, a hormone which is naturally producedin the adrenal cortex.

►Prednisone is used to treat rheumatoid arthritis,systemic lupus erythematosus, polymyositis,polymyalgia rheumatica, giant cell arteritis,vasculitis, and other inflammatory conditions

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 41/51

41

►The use of oral corticosteroids is associatedwith an increased risk of fracture, but thereis limited information on the relationship

between corticosteroid dose, bone mineraldensity (BMD), and fracture

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 42/51

42

►Oral corticosteroid treatment is associatedwith osteoporosis and an increased risk of fracture

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 43/51

43

►fracture risk doubles with each standarddeviation reduction in bone mineral density(BMD)

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 44/51

44

►It is not known whether the same is true forcorticosteroid-induced osteoporosis.

►There is some evidence that fracturesassociated with the use of corticosteroid occurat a higher BMD (bone mineral density ) than

those caused by involutional osteoporosis,although this has been disputed

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 45/51

45

PERMISSIVE EFFECTS

►Besides therapeutic effects, glucocorticoids alsopossess some effects which are called

 “permissive” effects.

►It means that in the absence of glucocorticoids,many normal functions become deficient.

►For example, in the absence of glucocorticoids,the lipolytic responses of fat cells tocatecholamines, ACTH and growth hormone are

diminished.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 46/51

46

EFFECTS ON METABOLISM 

►Glucocorticoids promote glycogen depositionin liver by inducing glycogen synthetase andpromoting Gluconeogenesis.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 47/51

47

►They inhibit glucose utilization by peripheraltissues.

►They cause increased release of glucosefrom liver.

►They cause hyperglycemia and thusstimulate insulin release.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 48/51

48

►They stimulate lipase and cause lipolysis.

►

They also promote lipolysis due to glucagon,growth hormone, adrenaline and thyroxine.

►

The cAMP induced breakdown of triglycerides isenhanced and fatty acids and glycerol arereleased into the circulation.

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 49/51

49

►The increased insulin release stimulateslipogenesis and to a lesser degree inhibitlipolysis, leading to a net increase in fat

deposition

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 50/51

50

►Glucocorticoids cause breakdown of proteinsand mobilization of aminoacids fromperipheral tissues.

►This protein breakdown is manifested as ---muscle wasting, lipolysis, loss of osteiod

from bone and thinning of skin

7/30/2019 Corticosteroids 091011154448 Phpapp01

http://slidepdf.com/reader/full/corticosteroids-091011154448-phpapp01 51/51

51

►Thus glucocorticoids are catabolic.►They try to maintain glucose supply to brain,

during starvation, by exerting following effects.

►Gluconeogenesis.

►Inhibition of peripheral glucose uptake.

►Release of aminoacids from muscle catabolism.

►Stimulation of lipolysis.