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