Adverse Effects📝

1-Sulfonylureas (glyburide, glipizide ,glimepiride)

💜Hypoglycemia
💜hyperinsulinemia
💜wt gain

2-Glinides (repaglinide and nateglinide)

💛Hypoglycemia
💛 wt gain

3- Biguanide(Metformin)

💙git upset, including NVD
💙due to anaerobic glycolysis lead to lactic acidosis and therefore contraindicated in patients with renal dysfunction
💙vitamin B12 deficiency with long term use

4-Thiazolidinediones
(pioglitazone ,rosiglitazone)

💚liver toxicity
💚wt gain
💚fluid retention
💚associated with osteopenia and increased fracture in women
💚pioglitazone—->may cause bladder cancer
💚rosiglitazone—->increased risk of MI infarction and angina

5- a- Glucosidase inhibitors (Acarbose and miglitol)
🤎flatulence
🤎diarrhea
🤎Abdominal cramping
🤎Patients with inflammatory bowel disease, colonic ulceration, or intestinal obstruction should not use these drugs

6-DPP-4 inhibitors
(Alogliptin, linagliptin,saxagliptin,sitagliptin)
❤️well tolerated
❤️most common adverse effect being nasopharyngitis
❤️Headache
❤️Pancreatitis
❤️disabling joint pain
❤️Alogliptin and sexagliptin increase risk of Heart failure

7- Na- glucose cotransporter 2 inhibitors ( Canagliflozin,dapagliflozin,
empagliflozin,ertugliflozin)

🤍female genital mycotic infection (Vulvovaginal candidiasis)
🤍urinary tract infection
🤍urinary frequency
🤍Hypotension
🤍Ketoacidosis

8-Other agents
(bromocriptine,colesevelam)

🩵 their modest efficacy and adverse effects and pill burden limited use in clinical practice

Mechanisms

🧡Sulfonylureas +Glinides

*they have similar mechanism but Glinides hasn’t sulphonyl group

1- stimulante insulin release from B cell
2-block ATP-sensitive K channels and producing depolarization
3-Ca influx and insulin
4-reduce hepatic glucose production
5-increase peripheral insulin sensitivity
……………………………………………………….
💙Biguanides

1-reduce of hepatic gluconeogenesis
2-slow intestinal absorption of sugar
3-improve peripheral glucose uptake and utilization
……………………………………………………….
💛Thiazolidinediones

1-lower insulin resistance by acting as agonists for the PPAR-Y
2-activation of PPAR-Y regulates the transcription of several insulin responsive genes
3-resulting in increased insulin sensitivity in adipose tissue,liver and skeletal muscle
……………………………………………………….
🩷a-Glucosidase inhibitors
هذا الانزيم يحول starch الى glucose فنثبط هذا الانزيم عن طريق هذا الميكانزم
1- theses drugs reversibly inhibit
a-glucosidase enzyme
2-when taken at the start of a meal ,these drugs delay the digestion of carbohydrates
3-resulting in lower postprandial glucose levels
4-they do not stimulate insulin release or increase insulin sensitivity, therefore theses agents do not cause hypoglycemia
……………………………………………………..
💜Dipeptidyl peptidase-4 inhibitors

1- inhibit the enzyme DPP4, which is responsible for the inactivation of incretin hormones such as GLP-1
2- activation of Incretin hormones act:
-increases release of insulin
-reduce secretion of glucagon
-unlike GLP-1 receptor agonists these drugs don’t cause satiety
……………………………………………………….
💚Na-glucose cotransporter 2 inhibitors

1-inhibit SGLT2 in proximal tubules to decrease reabsorption of glucose,in tubular lumen of the kidney
2-increase urinary glucose excretion
3-lower blood glucose
4-decreases reabsorption of sodium and causes osmotic diuresis.
5-SGLT2 inhibitors may reduce systolic blood pressure
……………………………………………………….
❤️Other agents
Unknown mechanism

الامسكيو شامل لكل شيت السكري + MCQ lippincott+ Katzunge)

تلخيص فوك المواضيع الرئيسية حتى تفرقون بينها ويارب التوفيق

2-Bone metabolism

مقدمة توضيحية

💊الكالسيوم يتم تخزين منه بنسبة (99٪) في العظام والأسنان. أما الـ 1٪ المتبقية فهي موجودة في extracellular fluid and intracellular fluid

💊وايضا يلعب دور مهم في العديد من العمليات الخلوية مثل muscle contraction, enzyme activation, and neurotransmitter release

💊مكونات العظم

🤍Organic Matrix of Bone

-Collagen fibers: 90-95 % (give bone its powerful tensile strength) Ground substance: extracellular fluid + chondroitin sulfate and hyaluronic acid.

🤍Bone Salts

The crystalline salts deposited in the organic matrix of bone are composed

principally of Ca and Po4.

الكالسيوم يوفرhardness and rigidity,

بينما الفوسفات يوفر the structural support.

🔮Osteoporosis : is characterised by progressive loss of bone mass and skeletal fragility
تتميز بالفقدان التدريجي لكتلة العظام وهشاشة الهيكل العظمي

🔮Paget disease : is a disorder of bone remodeling that results in disorganized bone formation and enlarged or misshapen bones
هو اضطراب في إعادة تشكيل العظام يؤدي إلى تكوين عظام غير منتظمة وعظام متضخمة أو مشوهة

🔮Osteomalacia : is softening of the bones that is most often attributed to vit D deficiency (in children referred to as rickets)
تليين العظام الذي يعزى في أغلب الأحيان إلى نقص فيتامين د (يشار إليه عند الأطفال بالكساح)

🔮Osteoclasts : cells that break down bone, a process known as bone resorption
الخلايا التي تحطم العظام، وهي عملية تعرف باسم ارتشاف العظم*(bone resorption تعني العملية التي يقوم الجسم من خلالها بتكسير أو تحليل العظام وإمتصاصها)

🔮Osteoblasts : bone building cells synthesize new bone
تقوم خلايا بناء العظام بتكوين عظام جديدة

Prevention of Osteoporosis

💛To reduce bone loss in postmenopausal women include
حتى نحد من فقدان العظم عند النساء بعد انقطاع الطمث تتضمن التالي
1-intake of calcium and vitamin D
2-weight-bearing exercise
3-smoking cessation
3- avoidance of excessive alcohol intake

💛 Patients with inadequate dietary intake of calcium should receive calcium supplementation such as
المرضى لي يعانون من عدم كفاية تناول الكالسيوم في الجسم ننطيهم مكملات الكالسيوم مثل
1- Calcium carbonate
2-Calcium citrate

Adverse effects of calcium supplementation

💚 gas and bloating

💚Calcium may interfere with absorption of
-iron preparations
-thyroid replacement
-fluoroquinolone
-tetracycline antibiotics

and administration of these drugs should be separated by several hours.

Drugs of Osteoporosis

1-Bisphosphonates
💜alendronate
💜risedronate
💜zoledronic acid
تنتهي بمجموعة (dronate ) والاخير dronic acid
*وهاي المجموعة (تفضل)لعلاج حالة تسمى
Postmenopausal osteoporosis

💜etidronate
💜ibandronate
💜pamidronate
💜tiludronate
ايضا كلها تنتهي بمجموعة (dronate)
*وهاي المجموعة الدوائية تستخدم لعلاج
-bone disorder(osteoporosis and paget disease)
- bone metastases
-hypercalcemia of malignancy

2-Denosumab

3-Parathyroid agents
🩵Teriparatide
🩵abaloparatide
تنتهي بمجموعة (paratide) (برا تايد😁)

4-Selective estrogen receptor modulators
🩷Raloxifene

5- Calcitonin
🤍salmon calcitonin

Mechanisms

💚Bisphosphonates
1- bind to hydroxyapatite crystals in the bone and decrease osteoclastic bone resorption
2-resulting in a small increase in bone mass and a decreased risk of fractures in patients with osteoporosis
……………………………………………………….

💙Denosumab
1- monoclonal antibody that targets receptor activator of nuclear factor kappa-8 ligand
and inhibits osteoclast formation and function
……………………………………………………….

🩷Parathyroid agents (Teriparatide,abaloparatide)

1-act as agonists at the parathyroid hormone receptor
and once-daily subcutaneous administration results in stimulation of osteoblastic activity and increased bone formation and bone strength
……………………………………………………….
🩵Selective estrogen receptor
modulators(Raloxifene)

1- is a selective estrogen recentor modulator approved for the prevention and treatment of osteoporosis
……………………………………………………….
🧡Calcitonin(salmon calcitonin)
reduces bone resorption

Adverse effects

💊Bisphosphonates
1- diarrhoea
2-abdominal pain
3- musculoskeletal pain.
4-Alendronate, risedronate, and ibandronate —-> associated with esophagitis and esophageal ulcers
5- Bisphosphonates—-> osteonecrosis of the jaw and atypical femur fractures may occur and risk increase with long-term use of bisphosphonates.

💊Denosumab
1-increased risk of infections
2-dermatological reactions
3-hypocalcemia
4-rarely, osteonecrosis of the jaw
5-atypical fractures

💊Parathyroid agents
1-hypercalcemia
2-orthostatic hypotension
3-increased risk of osteosarcoma in rats

💊Selective estrogen receptor modulators

1-hot flashes
2-leg cramps
3-increased risk of venous thromboembolism

💊Calcitonin
1-rhinitis
2-nasal symptoms

MCQ + lippincott

……………………………………………………..

3-Pituitary gland and thyroid hormone

*مقدمة توضيحية

Hypothalamus—>stimulate of pituitary gland—>stimulate other glands

الجهاز الغدي endocrine system عبارة عن جهاز يفرز هرمونات والتي تفرز في الدم ثم تحمل هذه الهرمونات رسالة او إشارة إلى الخلية وهاي الإشارة ينقلها الهرمون نفسه 🫡
و response تحتاج وقت اكثر من nervous systems الذي ياخذ اجزاء من الثانية عكس الهرمون 🙄

زين شنو هو hypothalamus ؟🤔
ج/ عبارة عن جهاز عصبي مرتبط بpituitary gland الذي يتحكم بالغدد او هو

is an area of the brain that produces hormones that control: Body temperature. Heart rate. Hunger

س/ ما هي اجزاء pituitary gland ؟

1-Anterior P.G—>
*Stimulation by hypothalamus

*hormones interact with and affect several different organs, glands and tissues in your
body
*consists of hormone-secreting (epithelial cells )and is connected to hypothalamus through blood vessels

وهاي هرمونات اما تكون عبارة عن peptide or glycoprotein يكون لها تأثير مثلا على الأنسجة من خلال رسبترات معينة تستقبل هاي الهرمونات وبالتالي توصل رسالة او إشارةً إلى الخلية وبعدها يحدث تاثير الهرمون داخل الخلية



2-Posterior P.G—>

Hypothalamus is a neurological and posterior is complement of hypothalamus
يعني هو الجزء العصبي من hypo ويكون تكملة hypothalamus اي انه غشاء عصبي
على عكس interior لي يعتبر غشاء طلائي

*stimulation or released by physiologic signals such as
-high plasma osmolarity or parturition
يعني اي factors عدا hypothalamus وهذا عكس منووووو؟؟؟؟🤔 عكس Anterior لي حيكون تحفيزه والسيطرة عليه بواسطة hypothalamus

Anterior pituitary gland

💊Adrenocorticotropic hormone (corticotropic)

🤍الهرمون ( CRH ) يروح الى pituitary gland حتى تفرز (ACTH)

🤍الهرمون (CRH)يستخدم بالتشخيص للتمييز بين Cushing syndrome and ectopic ACTH-producing cells

🤍أفراز ACTH يكون اعلى مستوياته في النهار واقل مستوياته في الليل
……………………………………………………….

💊Growth hormone(somatotropin)

🤎هرمون يفرز من pituitary gland ، ويحفز نمو جميع أنسجة الجسم، بما في ذلك العظام

somatostatin المسؤول عن تثبيط هرمون النمو هو

🤎يكون اعلى مستويات لأفراز هرمون النمو هو اثناء النوم على عكس ACTH
……………………………………………………….

💊Somatostatin(growth hormone-inhibiting hormone)

❤️Inhibit GH and TSH
❤️Inhibit insulin and glucagon in pancreas
❤️Inhibit gastric in stomach also in intestine
……………………………………………………….

💊Gonadotropins
💛 FSH and LH) are produced in the anterior pituitary.
The regulation of gonadal steroid hormones depends on these agents.

💛They used in the treatment of infertility
FSH and LH:
وظيفتهم تحفيز ovaries و testis يعني زيادة الهرمونات الجنسية

……………………………………………………….

💊Prolactin

يفرز من P.G ويعمل على تحفيز إفراز milk لدى الأنثى بالإضافة إلى انه يعمل على Reducing sexual drive and reproductive function

💙Thyrotropin releasing hormone stimulates the release of prolactin and secretion is inhibited by dopamine acting at D₂ receptors
……………………………………………………….

Posterior pituitary gland
ذكرنا سابقا انه يتم تحفيز anterior عن طريق hypothalamus اما هذا النوع عن طريق عدة عوامل مثلا osmolarity او اي عامل ثاني عدا hypothalamus

تحتوي على هرمونين
🧡Oxytocin—> secreted by P.G
وظيفته يساعد على إفراز الحليب والضغط على الغدد حتى يطلع الحليب
🧡Vasopressin—> act contraction in blood vessle
-عن طريق الارتباط برسبترات الأوعية الدموية V1 ومن يرتبط بيها يحفز على تقلص الأوعية الدموية
-ويرتبط برسبتر V2 الموجود في kidney ويسحب الماء من الكلية من منطقة collecting tubules

🧡Desmopressin
هو بديل vasopressin له نشاط ضئيل على V1 Receptor لكن له تأثير اطول من vasopressin ويفضل لعلاج diabetes insipidus and nocturnal enuresis

Drugs
A- Anterior Pituitary Gland

🩷Adrenocorticotropic
hormone(corticotropic)

🩷Growth hormone (somatotropin)

🩷Somatostatin(growth hormone inhibiting hormone)
1-Octreotide
2-lanreotide
تنتهي بمجموعة reotide

🩷Gonadotropin
1- menotropins
نحصل عليه من urine ب postmenopausal women ولي هو خليط من FSH and LH

2- urofollitropin
نحصل عليه من postmenopausal women ويتكون من ( FSH) فقط

3-Follitropin
يتكون من FSH فقط ويكون مصنع يتضمن Alfa and beta
للتوضيح عند إعطاء FSH and hMG يؤدي إلى نمو البيوض ثم عند إعطاء HCG تتحرر البويضات

🩷Prolactin
used to treat high prolactin levels such as Bromocriptine and Cabergoline

B- Posterior pituitary gland
1-Oxytocin
2-Vasopressin
and Desmopressin

Mechanisms
❤️Adrenocorticotropic hormone (corticotropic)

1- ACTH binds to receptors on the surface of the adrenal cortex,

2- thereby activating G protein-coupled processes that ultimately stimulate the rate-limiting step in the adrenocorticosteroid synthetic pathway (cholesterol to pregnenolone).


3- lead to synthesis and release of adrenocorticosteroids and the adrenal androgens
……………………………………………………….
❤️Somatotropin

Somatotropin mediates its effects both
-directly by somatotropin that action on binding to target cells to stimulate a response

-indirectly by insulin-like growth factor-1 and 2 (IGF-1 and IGF-2)
……………………………………………………….
❤️Somatostatin(GH -inhibiting hormone)
1-inhibit to Growth hormone and TSH
2-inhibit to insulin and glucagon in pancreas
3-inhibit gastric in stomach also intestine
……………………………………………………….
❤️Gonadotropins

Stimulate LH and FSH from anterior pituitary gland
…………………….…………………………………
❤️Prolactin
Stimulate prolactin from anterior pituitary gland

———————————————————
💛Oxytocin

1-stimulate uterine contraction
and induce labor
2-causes milk ejection by contracting the myoepithelial cells around the mammary alveoli
……………………………………………………….
💛Vasopressin (ADH)

-act Contraction in blood vessels by binding to receptor in blood vessels V1, and upon binding, it stimulates blood vessel contraction.

-binding to the V2 receptor located in the kidney and withdraws water from the kidney from an area called collecting tubules

Theraputic Uses

💊Adrenocorticotropic hormone (Corticotropic)

1-Diagnosis for different between primary adrenal insufficiency (Addison disease associated with adrenal atrophy)and secondary adrenal insufficiency

يقصد بprimary انه المشكلة بadrenal اي بtarget
وsecondary يعني المشكلة بpituitary gland

*وACTH يستخدم بتشخيص primary and secondary وايضاً Cosyntropin يكون افضل بالتشخيص من ACTH

2- used in ttt of infantile spasms and multiple sclerosis
……………………………………………………….
💊Somatropin is used in the treatment of :
1- GH deficiency,
2- Growth failure in children,
3-treatment of HIV patients with cachexia, and
4-GH replacement in adults with confirmed deficiency.
……………………………………………………….
💊Somatostatin (GH-inhibiting hormone)

1-use in the treatment of acromegaly and in severe
diarrhea/flushing episodes associated with carcinoid tumors.
2-An intravenous
infusion of octreotide is also used for the treatment of bleeding esophageal varices
……………………………………………………….
💊Gonadotropin
-menotropins to stimulate the وهو وهو mix from FSH and LHمنovaries


-Urofollitropin used to treat infertility in women
نحصل عليه من urine للمرأة في post menopausal ولي هو خليط من FSH فقط

-Follitropin Alfa and beta is FSH

-HCG is placental hormone
ينفرز عن طريق urine للمرأة الحامل

…………………………

💊Prolactin

1-stimulate and maintain lactation.
2-it decreases sexual
drive and reproductive function
……………………………………………………….
💊Oxytocin

1-used in obstetrics to stimulate uterine contraction
and induce labor.
2-antidiuretic and pressor activities are much less than
those of vasopressin.
……………………………………………………….
💊Vasopressin

1- antidiuretic and vasopressor effects
2-major use is to treat
diabetes insipidus
3-use in septic shock
4-in controlling bleeding due
to esophageal varices

Adverse effects
💊Adrenocorticotropic hormone (corticotropic)

1-Short-term use for diagnostic purposes is usually
well tolerated.
2-With longer use, toxicities are similar to glucocorticoids and include
-hypertension,
-peripheral edema,
-hypokalemia,
-emotional disturbances,
-increased risk of infection.
……………………………………………………….
💊Growth hormone (Somatotropin)

pain at the injection site,
edema,
arthralgias,
myalgias ,
nausea,
increased risk of diabetes.

Somatropin
should not be used in pediatric patients with
-closed epiphyses,
-patients with
diabetic retinopathy,
-obese patients with Prader-Willi syndrome.
……………………………………………………….
💊Somatostatin (Growth hormone-inhibiting hormone)

octreotide include bradycardia, diarrhea, abdominal pain,
flatulence, nausea, and steatorrhea. Gallbladder emptying is delayed, and
asymptomatic cholesterol gallstones can occur with long-term treatment
……………………………………………………….
💊Gonadotropin

ovarian enlargement and possible ovarian hyperstimulation
syndrome, which may be life threatening. Multiple births can occur
……………………………………………………….
💊Prolactin
nausea, headache and, less frequently, psychosis.
……………………………………………………….
💊Oxytocin

hypertension, uterine rupture, water retention,
and fetal death may occur
……………………………………………………….
💊Vasopressin

water intoxication
hyponatremia
Abdominal pain
tremor
vertigo can also occur

💊Desmopressin
Local irritation

Thyroid Hormone

مقدمة توضيحية

١-الغدة الدرقية موقعها تحت larynx
تفرز هرمونين T3و T4

٢-لي يعمل اكثر بالجسم هو T3 لي يشتغل على الخلايا وT3 يزيد العمليات الأيضية المفيدة بتكوين الطاقة ونمو الأطفال وadult

٣- يتحول T4الى T3 لي يحفز بتكوين الإنزيمات لزيادة metabolism

٣-من ناحية activity يكون T4 تأثيره لوقت اطول وT3 وقت أقل

٤-الغدة تتألف من العديد من follicles وكل وحدة بداخلها تحتوي على colloid وتكون محاطة بcuboidal epithelial cell وبي حيكون تصنيع thyroid hormone وهناك blood vessels يصل إلى thyroid gland بعد ما تصنع الهرمونات حتى ياخذ هذه الهرمونات ويوصلها إلى باقي الجسم (كما موضح بfigure )

٥-الغدة تعتمد على iodine لي تاخذه من مصادر خارج الجسم مثلاً اخذ iodine الموجود بالملح