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Lecture 9: Endocrine Hormones

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I. Pituitary & Thyroid Hormones:

A. Pituitary Hormones:

i) Anterior Pituitary Hormones:

corticotropic Hormone (ACTH):-1) Adreno precursor for ACTH.responsible for synthesis & release of the →*CRH

*Release from pituitary gland in pulses according to diurnal rhythm

in evening) 6 am & (Release

& differentiate between Cushing's syndromediagnosis to *CRH is used in

.producing cells -Ectopic ACTH

Adrenocorticosteroids synthesis. →Adrenal Cortex →:* ACTH*M.O.A

(Cholesterol & Pregnenolone).

Cosyntropin. →*Synthetic form

*Therapeutic Uses:

Addison's :adrenal insufficiencyry 1entiate between differ1) Diagnosis to

adrenal ry2Secondary ACTH due to Adrenal atrophy) or syndrome (

ACTH from pituitary gland). (due to insufficiency

). West Syndromein the ttt of multiple sclerosis & infantile spasm (→2) ACTH

: Toxicities similar to glucocorticoids.*Adverse effects

:Somatotropin)(2) Growth Hormone

*GHRH→GH from pituitary gland → during sleep.

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By increasing age.

in humans. ineffective*GH from animal sources is

Directly →:M.O.A*

Through somatomedins (Insulin like growth factor IGE-II & IGF-II)→

Acromegaly.

.GH insufficiency →1) Children Therapeutic Uses:*

N.B: Normal Thyroid status should be preserved.

2) GH→ Anti-aging hormone

*Synthetic form→ Somatrem.

*Somatrem & Somatotropin shouldn't be used in closed epilepsy & Intracranial

mass enlarged.

Somatostatin):(Inhibiting hormone -3) Growth Hormone

).5& SSTR 2rs (SSTR*Acts on specific recepto

*It inhibits the action of Somatotropin & TSH.

*It inhibits Insulin, Glucagon & Gastrin.

.Used in the ttt of Acromegaly →Octreotide (Synthetic form)*

Secretory diarrhea caused by tumor producing vasoactive intestinal peptide

(VIPomas).

Flatulence, Nausea, gall bladder stones & delayed gall bladder *Adverse effects:

emptying.

N.B: Analog of human GH (Pegvisomant)→ antagonist of GH receptors.

Used for ttt of Acromegaly.

:Gonadorelein)(Releasing Hormone -4) Gonadotropin

*GnRH→ Release FSH & LH.

.Histrelin& elinNafar, Goserelin, Leuprolide :Synthetic analog*

antagonize action of Gonadotropins.

∴ used in prostatic cancer & precocious puberty.

libido. : hot flushes, sweating & Woman1) Adverse effects:*

testosterone, bone pain, hot flushes, : initially Men2)

gynecomastia & libido.

,(human menopausal gonadotropin) HMG :5) Gonadotropins(Human chorionic HCG& )(Follicle stimulating hormone FSH

):gonadotropin

*Used for ttt of infertility.

*HMG→ Found in urine of menopausal women (FSH & LH).

*HCG→LH agonist.

*Urofollitropin & Follitropin beta→ (FSH analog).

:Important*

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*Injection FSH or HMG (5-12days)→ Ovarian growth & Maturation, Then

).(in womenOvulation occurs →injection HCG

Sexual maturation. →: HCGIn Men*

HMG→ Spermatogenesis.

enlargement. ovarianbirth & multiple: gynecomastia, Adverse Effects*

6) Prolactin: Similar in structure to GH*

receptors). -2*Its secretion is inhibited by Dopamine (D

*Prolactin→ lactation & sexual drive

used in → Cabergoline) & Bromocriptine( agonists -2D*

Hyperprolactinemia (galactorrhea & hypogonadism).

-Also used in microadenoma & macroprolactinoma.

*Adverse effects: Nausea, Headache & Psychiatric problems.

Posterior Lobe Hormones: )ii

A. Oxytocin:

*Used in Obstetrics (I.V) & Milk ejection (Intranasal spray).

*C.I. in abnormal fetal presentation, premature births & fetal distress.

.structurally resembles oxytocin B. Vasopressin:

water permeability & reabsorption. →receptors -2V→*In kidney

∴ used for ttt of Diabetes Insipidus. V.C. →Vascular smooth muscles →1V*

*S.E: hyponatremia, Bronchoconstriction & tremors.

∴ Caution with Asthma, Epilepsy & CAD.

C. Desmopressin:

receptors. -1*As Vasopressin but with minimal activity on V ∴ No V.C (& Longer duration). *Used in Nocturnal enuresis & Diabetes Insipidus.

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Thyroid Hormones:B.

: responsible for growth, development & )4Thyroxin (T) & 3Triidothyronine (T1. metabolic activity.

metabolism. 4& PO2+Ca :Calcitonin2.

*Disturbances in Thyroid hormones:

Bradycardia, coldness, mental & physical slowing & dwarfism. a. Hypothyroidism: Tachycardia, Nervousness, Tremors & heat production. b. Hyperthyroidism:

*Synthesis:

2 peroxidase I -1) Iodide uptake I 2) Amino acid uptake Thyroglobulin. 3) Iodination→

4) Condensation.

.4& T 3T →5) Proteolytic release

*Regulation of Synthesis: .2uptake peroxidase I -Stimulation of I →TSH →TRH

* Antibodies for peroxidase are diagnostic for Hashimoto's thyroiditis. iodotyrosine.-Monoiodotyrosine + di →3*T

iodotyrosine X 2.-Di →4*T

*M.O.A:

formation of RNA & protein synthesis →specific receptors 3deiodination T 4T

*Pharmacokinetics:

-Food, Calcium & Aluminium → absorption. -Metabolized by Cyp 450.

*ttt of Thyroid gland disorders:

Hypothyroidism: ttt of 1. Elevates TSH. →)4Levothyroxine (T

).4N.B. Levothyroxine sodium (synthetic form of natural thyroid hormone T

.4T sodium Levothyroxine of g 100 = )3(T sodium Liothyronine of g25

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2. ttt of Hyperthyroidism: thyroid:a. Removal of part or all of the

) Isotope 131( Iby using radiation - -Younger →doesn't need pretreatment with Methimazole. - Older → most patients become hypothyroid due to pretreatment with Methimazole.

b. Inhibition of Thyroid synthesis: .Methimazole& Propyl thiouracil (pTu)By using

-M.O.A: Inhibit→ Iodination. Coupling.

3T →4inhibit conversion of T →pTu - - pTu (several doses) while Methimazole (once daily).

c. Thyroid storm: - BB→ Propranolol. - Diltiazem → Alternative for asthma & H.F -pTu, Iodides & glucocorticoids (Shock).

d. Blockade of hormone release: -Iodide. -Employed in fatal thyrotoxic crisis or prior to surgery.

Severe mouth & metallic taste. Adverse Effects:*

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:II. Insulin & Other Glucose Lowering Drugs *Insulin secretion:

1. High blood glucose level 2. Sulfonyl urea. 3. GIT Hormones 4. Autonomic mediators

Insulin →influx 2+Ca →channels +block K →ATP →cells - →High B.G.L-

secretion.

*Aspart, Lispro & Glulisine > Regular insulin > Glargine & Detemir.

*Types of Insulin:

LARG →preparations:1. Rapid & Short acting

insulin-Regular, Glulisine, Aspart, Lispro

- Regular insulin is soluble, short acting & Zinc crystalline.

-Lispro differs from regular in lysine & proline in position 28 & 29 are reversed.

∴ Rapid absorption & rapid action. -Taken to mimic the post prandial insulin secretion & used along with long- acting insulin.

(NPH) (Insulin isophane) 2. Intermediate acting

= edrona. Neutral Protamine Hag

Regular insulin crystalline zinc + Protamine polypeptide in Neutral PH.

- Not used in emergency.

-Usually used with short or rapid acting.

(Used with Lispro in combination).Neutral Protamine Lispro →b. NPL

3. Long acting Insulin:

isoelectric point of glargine is lower than the human insulin →Insulin glargine -

∴ ppt at injection site ∴ long acting. →slow dissociation →bind to Albumin →Fatty acid side chain →Insulin Detemir-

long acting.

:in market *Insulin Combinations

1) 70/30 NPH / Regular.

2) 50/ 50 NPH/ Regular. 3) 75/25 NPL/ Lispro.

2 doses. →Standard ttt 3 or 4 doses. →Intensive ttt

Pramlintide. →*Synthetic Amylin Analogs:

*Pramlintide→ adjunct to meal time insulin therapy. - It delays gastric, emptying, post prand. glucagon secretion & improves satiety. -S.C injection.

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*Oral Glucose lowering drugs:

A. Insulin secretagogues: influx. 2+Channels & Ca +Insulin secretion by blocking K 1) →:*M.O.A

2) Hepatic glucose production. 3) Insulin sensitivity.

hypoglycemia (highest hypoglycemic weight gain, Adverse effects: *) & Cholestatic Jaundice.effects among all agents

Safe in pregnancy. →Glyburide -

Sulphonylurea:1. , Tolbutamide

,Glyburide Glimepride& Glipizide

Stimulates release of insulin from Pancreas. M.O.A:* As Sulfonyl urea, however Rapid onset & Short duration (post prandial). -Used in combination with Metformin or glitazones. - Shouldn't be used with Sulfonyl urea due to overlapping M.O.A.

1) Hypoglycemia < Sulfonyl urea. *Adverse effects: Severe hypoglycemia with Gemfibrozil** 2)

(antihyperlipidemic). 3) Caution with Hepatic Impairment.

2. Meglitinides: & Repaglinide

Nateglinide.

B. Insulin sensitizers: gluconeogenesis. Hepatic glucose output by 1) *M.O.A:

2) Slow glucose absorption from intestine & uptake. HDL. - LDL & VLDL -: V.IMP

- Loss of weight due to loss of appetite. السكر لمرضي يستخدم انه الصح ولكن تخس علشان غلط بتستعمله الناس ساعات كدة علشان

.الوزن لتقليل و للسكر كمنظم

: due to abnormal conversion of) Lactic acidosis1 * Adverse Effects: pyruvate to Lactic acid. 2) C.I in pts with Renal/ Hepatic failure. 3) C.I. in M.I, H.F, Severe infection & Ketoacidosis.

Other Uses:* Ovulation. →Insulin resistance →ttt of Polycystic ovary disease

جلوكوفاج بيدى الدكتور دايما المبايض علي تكيسات لوجود نتيجة الحمل تآخر حالة في

1. Biguanides:

Metformin(Glucophage®)

Activated Receptor -Targets Peroxisome Proliferator M.O.A:* (PPAR) in fat, muscle & liver to insulin resistance.

retention (worsen H.F): 1) weight gain due to fluid Adverse effects* 2) Osteopenia & fracture.

Polycystic ovary disease. →: As MetforminOther Uses*

2. Thiazolidindiones: (Glitazones)

(Actos)Pioglitazone )(AvandiaRosiglitazone

(-)

Glucose Glucosidase- Oligosaccharides

∴ delays intestinal glucose absorption (post-prandial).

Flatulence, intestinal obstruction & Inflammatory bowel diseaseS.E: *

Glucosidase Inh.: -3. Acarbose

.Miglitol

(---) Glucagon like peptide 1 (GLP-1) DPP-4 Inactive. (Incretin hormone)

∴ prolong activity of Incretin hormones→ Insulin release in response to meals.

4. Dipeptydpeptidase 4:-inhibitors DPP

Sitagliptine (Januvia®)

Exenatide 5. Incretin mimetics:

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from past exams:**Important Extra Notes 36 hours (1 1/2 day).-: duration 24Zinc Insulin –1. Protamine

the →Zinc insulin + Regular insulin (1:1)-2. Upon mixing Protamine

duration of action will be as Protamine-Zinc insulin alone→ Why? Because excess Protamine in Protamine zinc insulin will bind essentially all of regular insulin converting it to Protamine zinc insulin.

3. Patients with Diabetes II should: 1) schedule yearly eye examination. 2) Include Lutin in their vitamin supplement because pts with long term diabetes develop Retinopathy.

العين عدسة على عتامة حصله مجدى خالو زى

24 hrs-18 4. Insulin Zinc suspension:

Ultralente are 5. Q) Long acting insulin such as Protamine zinc insulin & why? →used in relatively few pts

Because they provide insulin conc. too low to handle acute glucose challenges related to meals, they also produce relatively high insulin conc. at night.

administering Sympathomimetic decongestant in patients taking when6.

why? →patient insulin requirement insulin, e.g. Phenyl propanolamine→ Conversion of Glycogen to Glucose.

7. Causes of death in diabetic patients:

(DKA).Diabetic Ketoacidosis →If type I diabetes- M.I because of glycosylated products associated with →If type II diabetes -

diabetes accelerate the atherosclerotic process.

8. Insulin Lente= 70 % ultralente+ 30% semilente. (24 h) (Crystalline) (Amorphous)

9. Glucogenesis involves formation of glucose from: Non carbohydrate sources (amino acids, lactate & glycerol).

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III. Estrogens & Androgens:

-Anti

Androgens

Androgens Progestins Selective

-Estrogen

Modulators =

Anti oestrogens.

Estrogens:

*Finasteride *Dutasteride *Flutamide *Nilutamide *Bicalutamide

*Danazol *Fluoxymesterone *Nandrolone *Oxandrolone * Testosterone cypionate *Testosterone

enanthate

*Norgestrel *Desogestrel *Levonorgestrel *Norethindrone *Norethindrone-acetate *Medroxy-progesterone -Drospirenone

Clomiphen Raloxifen Tamoxifen Toremifene

*Diethyl Stilbesterol *Estradiol *Ethinyl estradiol *Estriol *Estrone. *Mestranol oxidized by liver Ethinyl estradiol.

pristone.Mife →progestrone-Anti

A. Estrogens:

premenopausal& it is the principle in ovarySecreted by women.

a. Estradiol:

).placenta(secreted by pregnancyDuring b. Estriol: women MenopausalThe principle in c. Estrone:

Synthetic d. Ethinyl estradiol: Selective-Estrogen Modulators (Tamoxifen,………) e. Non steroidal:

*Therapeutic Uses:

for menopausal symptoms as, :Menopausal hormone therapy-1) Post a. Vasomotor instability (hot flushes). b. Vaginal Atrophy. c. Osteoporosis.

Hypogonadism: ry2) 1

انوثة مظاهر وجود عدم sex characters in young women ryTo stimulate development of 2

(11-13 years).

*Pharmacokinetics: rapid metabolism. →: Estradioloccurring1. Naturally

∴ Micronized form is available. : Ethinyl Estradiol & Mestranol.2. Synthetic

Prolonged action.

*Adverse Effects: 1) Breast Cancer. 2) M.I 3) Thromboembolism 4) Nausea

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Receptor Modulators (SERMS)= -2. Selective Estrogen

VV.IMP oestrogen: -Anti

اخرى اماكن فى antagonistك و اماكن فى agonistك بيشتغلوا دول

cancer. breastin antagonist1) *Acts as as it may cause Uterusin the ) Partial agonist 2

endometrial hyperplasia.

hot flushes, menstrual disturbances & *Adverse Effects: endometrial hyperplasia.

1. Tamoxifen:

*Act as: 1) Oestrogen agonistic effects on bone mass and lipid 2) Antagonistic effects at other oestrogen-receptive tissues, eg breast and endometrium (EXAM 2014).

vertebral bone density & bone resorption, Used to*

menopausal women.ttt of osteoporosis in post ∴ fractures. .for prevention of breast cancer*Has been approved

& Thromboembolism. leg cramps: Hot flushes, *Adverse effects

absorption by 60 %. Cholestyramineadministration with -: CoC.I*

∴ shouldn't be taken together.

Raloxifen:2.

(Evista®)

menopausal breast cancer.-Post*Use: As Tamoxifen but without endometrial hyperplasia. *Adverse Effects:

3. Toremifene:

*Partial agonist (Estrogen) interferes with –ve feedback of estrogen on hypothalamus→ GnRH→ Gn→ stimulates ovulation.

Used in infertility associated with anovulatory cycles.∴

Nausea, flushes & headache. *Adverse Effects:

4. Clomiphen

(Clomid®)

اللي للناس دواء اشهر

توائم بيجيب بتخلف مش

,Norethindrone, Levonorgestrol, Desogestrol, Norgestrol 3. Progestogens:

Drospirenone& Medroxyprogesterone Norethindrone acetate,

1) Hormonal deficiency.Uses: * 2) Contraception in combination with oestrogen 3) Control bleeding of dysfunctional uterine & dysmenorrheal.

Provera) 3 months contraception.-injectable (Depo →Medroxy progesterone*

Headache, weight gain, depression & change in libido. -*Adverse effects:

- may have androgenic activity→ acne & hirsutism.

∴ Norgestimate & Drospirenone→ has least androgenic activity & used with women with acne & hirsutism.

-Medroxyprogesterone→ Osteoporosis (short duration).

: Used with Misoprostol to terminate Mifepristone progestin:-4. Anti

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gestation.

5. Contraceptives:

a. Combined Oral Contraceptives COCs:

Constant dose of Oestrogen + Progesterone. →Monophasic combination- ofConstant dose of Oestrogen + Increasing dose →Triphasic combination-

Progesterone over 3 successive 7- day periods. Ethinyl estradiol, Mestranol.Estrogens used: * Norgestrol, Levonorgestrol, Norethindrone (acetate), *Progestins used:

Drospirenone & Norgestimate.

b. Transdermal patch: Norelgestromine. Progestin used:–: Ethinyl estradiol. Oestrogen used-

*3 weeks & 1 week patch free. *Withdrawal bleeding may occur. : Less frequent dosing.*Advantages over oral

c. Vaginal ring: *3 weeks & 1 week free.

Etonorgestrel. →usedProgestin -nyl estradiol. Ethi → Estrogen used-

NorgestrolNorethindrone & only pills: -d. Progestin *Less effective than combination therapy. *S.E: Anxiety due to possibility of pregnancy & Menstrual disturbances. *Used with breast feeding females as it doesn't affect milk production.

Etonorgestrel. →e. Progestin implants الزراع فى تتزرع كبسولة

S.C. *Capsule of 4- cm is implanted S.C & offer contraception for 3 years.

Levonorgestrel →)uterine device (IUD-f. Progestin Intra *Up to 5 years contraception. *Not used with women having a history of ectopic pregnancy

or Pelvic inflammatory disease.الرحم خارج حمل

g. Post Coital Contraception "Emergency pill/ Plan B": * Doses of progestin or estrogen given within 72 hrs of unprotected intercourse

dose. stdose after 12 hours of 1 nd& a 2 Ethinyl estradiol. →Estrogen-Levonorgestrel. →Progestin-

release of LH & FSH from ve feedback inhibition & - →Estrogen1) *M.O.A: pituitary gland.

thickening of uterus. release of LH & →Progestin2) ∴ Transport of sperm.

headache, N, V & Fluid retention. :Major1) Adverse Effects:* : Thromboembolism, M.I & HTN.CVS2)

endometrial & ovarian cancer. →Carcinogenicity3) Abnormal glucose tolerance & weight gain. →Metabolic4)

HDL. VLDL & LDL, :Estrogen →Serum lipids5) HDL. VLDL & LDL, : Progestin

women over 35 years.Oral with * *C.I:

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*Pregnancy *Thromboembolic disease.

,Dihydrotestosterone (DHT)−5 , teroneTestos 6. Androgens:

.Androstenedione& Dehydroepiandosterone (DHEA)

reductase DHT−Testosterone 5 M.O.A:* Testosterone Aromatase Estrogen (in brain & liver).

due to testicular dysfunction. ry1 →hypogonadism →Androgenic: 1) Uses*

due to hypothalamus & pituitary gl. ry2 & chronic wasting associated withSenile osteoporosis →Anabolic2)

human immunodeficient virus or cancer. -Speed recovery after surgery & burns.

vv.imp)( Danazol3) Endometriosis:

ttt of endometriosis & fibrocystic breast disease. libido. breast size, voice deepening & Weight gain,S.E:

*Also Nafarelin acetate (intranasal is used).

Athlete's & body builders. →4) Unapproved use

Anabolic ratio (Orally active). 2Androgenic: 1has FluoxymesteroneN.B 15 more Anabolic action than testosterone.-(oral) has 3 Oxandrolone-

*Adverse Effects:

Acne, growth of hair, voice deepening, male pattern baldness & menstrual irregularities.

1. Women:

Priapism (painful & persistent errection of penis), spermatogenesis & gynecomastia.

2. Men:

Abnormal sex maturation & premature closure of epiphyseal plates. الطول عن مسئول العظام فى جزء

3. Children:

Premature closure of epiphyseal plates. 4. Athletes:

imp Androgens: -7. Anti

(---)

Testosterone 5- reductase DHT

*Used in Benign prostatic hyperplasia (BPH) → Finasteride & Dutasteride

*Flutamide (Androcure®) is used in prostatic cancer in males.

*Nilutamide & Bicalutamide.

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steroid Hormones:IV. Adrenocortico

Mineralocorticoids& Glucocorticoids

I. Adrenal Cortex: * Glucocorticoids→ feedback inhibition of Glucocorticoid, TSH & GH synthesis (Take care in ttt of children).

*Stress→ Glucocorticoids→ resistance to stress→ HOW?

By raising plasma glucose→provide body with energy required to combat stress.

*M.O.A of Glucocorticoids:

Lipid soluble steroid diffuse across cell membrane & binds to a cytoplasmic receptor→

receptor forms a dimmer→ translocation to the nucleus→ binding to glucocorticoid

response element which acts as a factor that turns gene on or off.

(This mechanism requires time to produce effect).

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*Immediate effects include interaction with catecholamine to mediate dilation of

vascular & bronchial musculature or Lipolysis.

A. Glucocorticoids:

:*Therapeutic Uses

adrenocortical insufficiency ry1. Replacement therapy for 1

: Adrenal Cortex dysfunction.Cause* (Addison's disease):

identical to natural Cortisol :Hydrocortisone a): ttt by*

-Dose: 2/3 dose given in morning & 1/3 in afternoon→ why?

Because normally the production of Cortisol is diurnal with peak early

in the morning→ decline→ then small peak in late afternoon.

synthetic mineralocorticoid with some glucocorticoid :Fludrocortisone b)

activity to raise mineralocorticoid activity to normal level.

] [CRH ry] or 3[ACTH ry2. Replacement therapy for 2

.Hydrocortisone ttt by: adrenocortical insufficiency:

*The synthesis of Mineralocorticoids in adrenal cortex is less impaired than that

of glucocorticoids.

3. Diagnosis of Cushing Syndrome:

glucocorticoids either from excess : Hypersecretion of *Cushing Syndrome

release of Corticotropin by Pituitary or an Adrenal tumor.

How? →test suppression Dexamethasone By*

-If Glucocorticoid release→ Pituitary dependent Cushing syndrome

- If doesn't suppress release→ adrenal tumor.

N.B. Chronic ttt with high doses of glucocorticoid cause Cushing syndrome.

4. Replacement for Congenital Adrenal hyperplasia (CAH): : a group of diseases resulting from enzyme defect in the synthesis of one or Def*

more adrenal steroid hormones.

Virilization. →Overproduction of androgens in females. e.g

Androgen production. →CRH & ACTH ve feedback –: Corticosteroids ttt

: (bronchial asthma, allergic rhinitis & drug allergies).5. ttt of Allergies

:6. Acceleration of Lung maturation

syndrome in premature infants.respiratory distress *To avoid

: Beclomethasone is given 48 & 24 hrs before delivery (given I.M).ttt

7. Relief of Inflammatory Symptoms:

Eosinophils, Basophiles, Monocytes & Lymphocytes by 1. :M.O.A*

redistributing them from circulation to lymphoid tissue but Neutrophils.

2. Inhibition of the ability of Lymphocytes, Leukocytes & macrophages to

respond to antigen.

.2nhibition of phospholipase Aproduction of PG & LT due to i 3.

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4. Histamine release from mast cells.

1) Rheumatoid arthritis 2) Osteoarthritis *Uses:

3) Inflammatory conditions of the skin.

*Another use due to above actions: ttt of Leukemia & Lymphoma.

g term Corticosteroid ttt""Lon*Adverse Effects:

absorption. 2+because they suppress intestinal Ca :Osteoporosis1.

How?→may cause Diabetes Mellitus 2. Hyperglycemia:

-They stimulate protein catabolism & Lipolysis→ provide building blocks

needed for glucose synthesis.

- Gluconeogenesis from amino acids→ blood glucose.

3. Cushing Syndrome:

(redistribution of fat-puffy face- body hair growth & acne, appetite).

due to stimulation of gastric acid secretion. 4. Peptic Ulcer:

by enhancing vasoconstrictor action of adrenergic stimuli on 5. Hypertension:

small vessels & due to oedema.

catabolism. : due to 6. Reduce wound healing

viral & fungal".immunity "bacterial, due to Risk of infection: 7.

C.I. with Digoxin. ∴ 9. Hypokalemia Cataract. &8. Glaucoma

Pharmacokinetics:*

*Drugs oxidized in liver metabolites→conjugated to glucouronic à or sulfates→

appear in urine.

: Betamethasone > Dexamethasone > Triamcinolone, prednisolone, Potency*

prednisone & Methyl prednisolone > Cortisone, Hydrocortisone.

activity. Mineralocorticoid 1: Gluco1 have Hydrocortisone & Cortisone. N.B 1

: prodrug of Prednisolone.Prednisone2.

* Appetite so used in Cancer chemotherapy.

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*The only Glucocorticoid that have no effect in fetus→ why?

a. Isn't converted to the active cpd prednisolone by fetal liver.

b. Any prednisolone formed by mother is converted to prednisone by Fetus.

umatic disorders.& RheCrohn's disease c. Used in ttt of

:Withdrawal*

-Large doses of glucocorticoid more than 2 weeks→ suppression of

Hypothalamic- Pituitary- Adrenal (HPA) axis occur→ abrupt withdrawal→

How to overcome? →acute renal insufficiency syndrome that can be lethal

a) Alternate-day administration.

b) Gradual withdrawal.

*Important Extra Notes from past exams:

ttt of seasonal & perennial allergic rhinitis →Fluticasone& Budesonide1.

(intranasal steroids).

must be administered several minutes Beclomethasone dipropionate (Aerosol):2.

after bronchodilator→ why?

To enhance penetration of Beclomethasone into bronchial tree.

is 4 times more potent than Hydrocortisone. Prednisone3.

ids with a lesser degree of mineralocorticoid activityGlucocortico4.

i.e. Can be used in pts with CHF.

Dexamethasone, Betamethasone, Methyl prednisolone, Triamcinolone.

to a patient 11 years old with Prednisolone isn't given e.g. . Oral Corticosteroids 5

: 1) Inhaled prednisolone.asthma but can be givenchronic

2) Long acting Theophylline.

because it differs in Prednisolone >>> active than hydrocortisone6.

conformation at ring A.

why? →we use occlusive dressing or plaster eroids:For Topical Corticost7.

To enhance absorption of Corticosteroid.

8. Put (T) or (F):

-Hydrocortisone is best ttt for Rosacea (F).

Hydrocortisone isn't suitable for ttt of Rosacea.

t for I.V injection of Hydrocortisone.is used as a solven Propylene glycol9.

differs from most glucocorticoids because it doesn't increase Triamcinolone10.

appetite.

Deoxycorticosterone& Fludrocortisone :B. Mineralocorticoids

.-3O, HCO2, H+reabsorption of Na →*Aldosterone

.+, H+ Reabsorption of K

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*Elevated Aldosterone level→ Hypokalemia & Alkalosis

O retention.2, H+B.P. due to Na

ttt by Spironolactone.

KAMES/ TM. →Adrenocorticoid Synthesis:C. Inhibitors of

S.E & Notes: Uses: M.O.A: Drug: 1. Hirsutism

O 2, H+2. Na

retention.

1. Used to test adrenal

function (old method).

2. ttt of pregnant

women with Cushing

syndrome.

in final step *Blocks

Glucocorticoid synthesis

(11- hydroxylation)→ so

11-deoxycortisol,

adrenal androgens,

potent mineralocorticoid

11-deoxycorticosterone.

1. Metyrapone:

1. It is used together

with Dexamethasone.

2. Tamoxifen

replaced it in ttt of

breast cancer.

1. ttt of breast cancer→

how? By reducing or

eliminating androgen &

estrogen production.

2. ttt of malignancies of

adrenal cortex.

*Inhibit conversion of

Cholesterol to

Pregnenolone →

synthesis of all hormonally

active Steroids.

-2. Aminoglutethimide:

Aromatase

Inhibitor.

ttt of patients with

Cushing syndrome.

*Inhibit all gonadal &

adrenal steroid hormone

synthesis.

3. Ketoconazole

(Antifungal)

GIT S.E Reversibly inhibit 3-B-

hydroxysteroid

dehydrogenase→

aldosterone, Cortisol &

gonadal hormone

synthesis.

4. Trilostane:

ttt of inoperable pts

with ectopic ACTH

syndrome.

Potent progesterone

receptor antagonist.

5. Mifepristone:

1) Hyperkalemia

2) Gynecomastia

3) Menstrual

disturbances.

1) Hyperaldosteronism

2) Hirsutism in women

→ How?

by interference with

androgen receptor in

hair follicle.

Aldosterone &

Testosterone antagonist

6. Spironolactone:

ttt of HTN. Aldosterone antagonist

that binds specifically to

mineralocorticoid receptor

so it avoids S.E of

Spironolactone.

7. Eplerenone:

Epinephrine 80% →Catecholamines →B. Adrenal medulla

Norepinephrine 20%.

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