Pharmacology-2 Dietitian Program 2024-2025 PDF

Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader 1- Hypothalamic Hormones 1- Corticotrophin releasing hormone (CRH): It stimulates the secretion of both ACTH and β-endorphin from the anterior pituitary. 2- Thyrotrophin releasing hormone (TR...

Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader 1- Hypothalamic Hormones 1- Corticotrophin releasing hormone (CRH): It stimulates the secretion of both ACTH and β-endorphin from the anterior pituitary. 2- Thyrotrophin releasing hormone (TRH): It stimulates the release of thyrotrophin from the anterior pituitary which stimulates the thyroid to produce thyroxin. 3- Gonadotrophin releasing hormone (GnRH): It stimulates the release of luteinizing hormone and follicle stimulating hormones. 4- Growth hormone releasing hormone (GHRH): It produces rapid elevation in plasma growth hormone levels. 27 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader 5- Growth hormone inhibiting hormone (GHIH,somatostatin): It has inhibitory effect on the release of growth hormone. In addition it also inhibits the release of glucagon, gastrin and thyrotrophin. Octreotide; a synthetic analog of somatostatin. Its half-life is longer than that of the natural compound. Used for acromegaly. 6- Prolactin inhibiting hormone (PIH): It is dopamine and it acts as the physiological inhibitor of prolactin release. 2- Pituitary Hormones ◼ The pituitary gland is a small, rounded body attached to the base of the brain. It is composed of the 28 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader ◼ Anterior lobe: The secretion hormones is regulated by hypothalamus ◼ Intermediate lobe ◼ Posterior lobe Anterior Pituitary Hormones 1- Growth Hormone (Somatotropin, GH) Secretion: ◼ Increases by hypoglycemia, fasting stress and GHRH. ◼ Decreases by glucose, corticosteroids and administration of GHIH Control: A- Hypothalamus: (GHRH & SS) B- Ghrelin is a peptide hormone secreted from the stomach. Ghrelin stimulates secretion of growth hormone. C- Blood level of IGF-1 Growth Hormone (GH; somatotropin) Physiological effect of growth hormone A- Direct effects 1. Stimulates secretions of insulin-like growth factor-1 (IGF-1) 2. Stimulates lipolysis 29 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader 3. Increase blood glucose level B- Indirect effects are mediated primarily by IGF-1 1. promote growth of long bones, 2. Stimulates protein synthesis in muscle and other tissues 3. increased protein synthesis and decreased oxidation of proteins 4. by stimulating triglyceride breakdown and oxidation in adipocytes 5. have anti-insulin activity on carbohydrates Growth hormone abnormalities A- GH deficiency ⚫ Pituitary dwarfism: a deficiency of growth hormone secretion before puberty results in growth retardation ⚫ Main symptoms: Short stature, Absent or delayed sexual development B- Growth hormone excess 1- Gigantism (giantism; excess GH before puberty): The affected person will continue to grow upwards, as well as outwards; have disproportionately long limbs 2- Acromegaly (excess GH in adults). Enlargement of bones of the extremities (hands, feet, jaw, and nose) as well as the viscera enlarge. 3- 30 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader Drugs acting on growth hormone  Agonist treatment of Dwarfism Stimulation of growth in children In Turner’s syndrome (genetic disorder that affects females. The main characteristics include short stature and infertility) To counteract the wasting that occur in AIDS Body building by athletes Human GH is now produced by recombinant DNA technology, either somatrem (Protropin) or somatropin (Humatrope and others)  Antagonist Treatment of excess GH 1-Octreotide & Lanreotide (long-acting preparation) Inhibits GH secretion. 2- Dopamine agonists:( bromocriptine and cabergoline, inhibit growth hormone release in up to 50% of acromegalics. 3-GH receptor antagonist ex. Pegvisomant 2-Thyroid-Stimulating Hormone (Thyrotropin, TSH) 1. stimulates growth of thyroid gland 2. increases blood flow to thyroid gland 3. stimulates synthesis and release of T3& T4 from the thyroid. 4. stimulates iodide uptake TSH is available for diagnostic purposes to differentiate between pituitary and thyroid gland failure. Increase plasma thyroid hormone indicates abnormal function of pituitary while no rise in thyroid hormone indicates thyroid insufficiency. 3. Adrenocorticotrophic hormone (ACTH, or corticotropin) 31 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader ACTH acts on adrenal cortex 1. Stimulating the synthesis of Glucocorticoids, Mineralocorticoids & Androgens 2. Stimulates the secretion of cortisol from the adrenal gland 3. In the fetus, ACTH stimulates the synthesis of dehydroepiandrosterone sulfate (DHEA-S) which prepare the mother for giving birth. 4. Responsible for the maintenance of adrenal weight ACTH agents and uses 1- ACTH (corticotropin) 2- Cosyntropin (Cortrosyn) synthetic form closely resembles ACTH with longer duration can be taken monthly Used to diagnose adrenal disorders, treat deficiencies (rarely, since it is easier and less expensive to treat with glucocorticoid) 4. Prolactin ✓ Prolactin is responsible for normal development and maturation of mammary glands (Mammotropic effect). ✓ Stimulation of milk production (lactogenic effect). 32 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader ✓ During pregnancy prolactin level is high but high level of estrogen caused decrease in the effect of prolactin on milk ✓ After delivery estrogen level is decreased leading to lactation by prolactin action. Abnormality ⚫ Hyperprolactinemia. Elevated prolactin levels (>100 ng/mL) in the absence of stimulatory factors ⚫ Causes of hyperprolactinemia: 1- Prolactinoma (pituitary prolactin secreting tumors), 2- Drugs such as phenothiazines, Cimetidine, fluoxetine, Reserpine 3- Hypothalamic dysfunction, tumors, tuberculosis, sarcoidosis, 4- Renal failure, liver diseases and, primary hypothyroidism ⚫ Common manifestations of hyperprolactinemia In women: amenorrhea, infertility and galactorrhea. In men: hypogonadism, decreased sex drive, decreased sperm production, impotence, breast enlargement (gynecomastia). Drug treatment Dopamine agonists Suppress the release of prolactin as well as GH 1- Bromocriptine and pergolide the doses, usually 5 mg/day, the main side effects, nausea and postural hypotension. 2- Cabergoline (Dostinex),: Long-lasting dopaminergic agonist have been found to be at least as effective and has a lower incidence of side effects and can be taken once or twice/week 3- Quinagolide: non ergot drug bitter tolerated Uses: Hyperprolactinemia, Infertility, Parkinsonism& Acromegaly, stop lactation 33 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader B- Posterior Pituitary Hormones ◼ The posterior lobe does not produce or secrete any hormone. ◼ The polypeptide hormone oxytocin and vasopressin are synthesized in the hypothalamic neurons and are then transported down the axon of the nerve fibers to the posterior pituitary where they are stored until required. Hormones of the posterior pituitary gland (Vasopressin, ADH) Anti-diuretic Hormone Physiologic effects 1. The renal effects (Conserve body water); is mediated through V2 receptors and occurs at very low concentration resulting in increased water retention through its effect on distal and collecting tubules 2. Vasopressor effect through activation of V1 receptors. It requires much concentration of vasopressin and involves intracellular calcium mobilization resulting in vasoconstriction of all blood vessels leading to rise in blood pressure 3. Increase in circulating levels of two proteins involved in blood coagulation: factor VIII and von Willebrand’s factor Diabetes insipidus: ◼ Disease state results from deficiency of ADH (Hypothalamic "central" diabetes insipidus) or abnormality in its receptor (Nephrogenic diabetes insipidus) Desmopressin: Vasopressin has been modified to desmopressin ◼ Characters It has minimal activity at the V1 receptor, making it largely free of pressor effects. It is longer-acting than vasopressin. ◼ Clinical uses Central diabetes insipidus. Nocturnal enuresis, or bedwetting, in children. 34 | P a g e  Pharmacology-2 Dietitian Program 2024-2025 Prof Dr Manar A Nader In people with mild hemophilia A Desmopressin is administered intranasally. Oxytocin Pharmacological actions Oxytocic effect: ✓ oxytocin stimulates the uterine smooth muscles resulting in contraction of the uterus. ✓ The pregnant uterus is more sensitive to the effect of oxytocin than the non pregnant uterus. ✓ It probably aids in the expulsion of the fetus from the uterus. On the mammary gland:  Oxytocin is very important for the ejection of milk from lactating breast in response to suckling stimulation On cardiovascular system:  Oxytocin in large doses appears to have a transient relaxant effect on vascular smooth muscles resulting in decrease in blood pressure, flushing and reflex tachycardia. Clinical Indications Induction and maintenance of labor. Control of postpartum bleeding and uterine hypotonia in the third stage of labor. Side effects: ✓ Excess oxytocin may cause violent uterine contractions leading to uterine rupture ✓ Fetal bradycardia and perhaps fetal or maternal death. ✓ Anaphylactic and other allergic reactions, nausea, vomiting and pelvic haematoma may also occur. 35 | P a g e