hypothalamus and pituitary hormones, gonadal stuff, drugs affecting bone Flashcards
Corticotropin (ACTH)(porcine corticotropin, cosyntropin)
HT and pit. hormones -
1. Porcine corticotropin:
2. Cosyntropin (synthetic form of truncated human corticotropin)*
*fewer allergic reaction compared to animal preparation
Cosyntropin used in two diagnostic tests. **
i) Differentiate between Congenital adrenal hyperplasia &
Ovarian hyperandrogenism
ii) Used in the diagnosis of Adrenal insufficiency.
C-RH drugs (corticorelin ovine trifulate)
HT and pit. hormones - recombinant ovine CRH –> ACTH –> cortisol used to differentiate between pituitary adenoma and an adrenal tumor.
Drugs that induce increased PRL Release (dopamine antagonists)
HT and pit. hormones - • Dopamine antagonists e.g. *** By blocking Ant. Pituitary D2 Receptors
drugs that induce increased PRL release (antipsychotics)
HT and pit hormones - • 1) Antipsychotics (such Phenothiazines all non-selective DA Antagonists)
drugs that induce increased PRL release (D2 selective antagonists)
HT and pit hormones - Metoclopromide, Domperidone (Prokinetic
agents) enhance PRL secretion.
They cause drug induced (iatrogenic) hyperprolactinemia.
Drugs that Decrease PRL release (bromocriptine, cabergoline)
HT and pit hormones - • Dopamine agonists e.g. L-Dopa (a non-selective DA agonist) and D2 selective agonists like - Bromocriptine, Cabergoline – decrease PRL Release.
Helpful in overcominghyperprolactinemia by blocking Pituitary D2 Receptors.
• Mechanism of action:
Bromocriptine is a D2 selective agonist blocks Prolactin (PRL) release by binding to pituitary DA (D2) receptors.
• Indications for Bromocriptine D2 Selective Agonist:
i) Physiological - decrease Puerperal Lactation (loss of a newborn decrease milk production)
ii) decrease Abnormal Lactation – Galactorrhea amenorrhea;
iii) decrease Hyperprolactinemic amennorrhea
iii) To treat Infertile Males with Hyperprolactinemia
iv) Parkinsonism & v) Acromegaly (↑GH levels after Adulthood)
• Adverse effects:
Orthostatic hypotension, digital vasospasm, Nausea.
Another newer and effective D2 agonist – Cabergoline
therapeutic uses of oxytocin
HT and pit. hormones - ii) Breast: contracts myoepithelial cells and thus causes “Milk let down/Milk ejection”.
Note: OT does not enhance or increase milk secretion (lactation/galactopoiesis. Milk secretion – galactopoiesis is promoted by prolactin).
c) Therapeutic uses :
i) Induction and reinforcement of labour at term.
ii) Uterine inertia and incomplete abortion.
iii) Postpartum uterine atony and postpartum haemorrhage.
iv) Induction of lactation and to enhance milk let down.
vasopressin (AVP or ADH)
HT and pit hormones - Antidiuretic, vasopressor hormone (arginine vasopressin) is stored in the Post. Pit.
Functions:
• The physiological role is to reabsorb water from the renal collecting ducts in the kidney to maintain plasma volume.
• In pharmacological doses it is a vasoconstrictor/vasopressor.
• If ADH is not present, it will lead to increased water loss and this is called Diabetes Insipidus (DI).
• AVP/ADH acts on renal V2 receptor that activates adenylate cyclase and increase cAMP level. This promotes water reabsorption in the renal collecting ducts. This is the physiological role of ADH.
• In pharmacological doses, vasopressin can also promote vaso- constriction and hepatic glycogenolysis via activation of V1 receptors present on vascular smooth muscle cells (for vasoconstriction) and liver (towards causing glycogenolysis – increased release of glucose).
• Stimuli for AVP/ADH release: increase Plasma Osmolality (increased plasma sodium), decreased plasma volume leads to ADH/AVP release from the Posterior Pituitary.
desmopressin acetate (DDAVP)
hypothatlamus and pituitary hormones - • desmopressin, is a synthetic replacement for vasopressin, the hormone that reduces urine production. DDAVP [Desmopressin acetate) - a synthetic Peptide given via intranasal, s.c. or oral routes
DDAVP or AVP is INEFFECTIVE in conditions of Nephrogenic diabetes insipidus (due to defective kidney at the level of V2 Receptors). DDAVP will not work here. **
• The drug of choice for Nephrogenic Diabetes Insipidus (Nephrogenic - DI) is hydrochlorothiazide.
ii) When do we use AVP? Sealing Colonic and esophageal Varices during surgery. This is the only condition where AVP is used to arrest bleeding; it is a potent arteriolar vasoconstrictor agonist
Note: DDAVP is ineffective for this condition since it is a selective V2-Receptor agonist.
• Major Then. Uses of Desmopressin Acetate [DDAVP] are:
i) Nocturnal Enuresis in Children & Elderly Patients.
ii) For Diabetes Insipidus (DI) Neurogenic or Pituitary Deficiency.**
Note: DDAVP is Ineffective in Nephrogenic DI.
iii) Hemopilila von-Willebrand Disease- increase Factor VIII Level.
iv) Endocrine abnormality related to Increased Vasopressin/ADH Production or Syndrome of Inappropriate Antidiuretic Hormone (SIADH). In such a condition, there is Chronic Dilutional Hyponatremia (leads to increased H2O reabsorption and expansion of plasma volume; so hyponatremia occurs).
ADH Antagonists: Tolvaptan
a competitive ADH antagonist at
the V2 receptor is used to treat the SIADH (The syndrome of inappropriate antidiuretic hormone secretion or SIADH (other names: Schwartz-Bartter syndrome, SIAD—syndrome of inappropriate antidiuresis) is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source. The result is often dilutional hyponatremia in which the plasma sodium levels are lowered and total body fluid is increased. ).***
• Agents such as Demeclocycline (which opposes the ADH action) is also used to treat this condition.
Gonadotropin releasing hormone (Gn-RH) (gonadorelin)
Gonadal and others - Uses: Being a peptide, it is given through i.v. i.m. or s.c. routes. See i) and ii) below
i) Diagnostic use: A small dose of Gn-RH is given to diagnose the defect for delayed puberty.
If the failure is at the pituitary level or the ovarian level, Gn-RH will not be helpful.
If it is due to low or lack of Gn-RH from the hypothalamus, menarche will start.
ii) Stimulation with small doses of Gn-RH promotes FSH/LH release. This is used to treat infertility patients those having Hypogonadotropic Hypogonadism.
Higher pharmacological doses of Gn-RH analog, what does it do? (leuprolide acetate) (what’s abarelix) ?
gonadal and others - • Higher Pharmacological doses of Gn-RH analog – Desensitize Pituitary Receptors
• Exogenous administration of Gn-RH or its synthetic analog (Leuprolide acetate, a potent Gn-RH agonist) instead of stimulating FSH/LH release, due to prolonged and potent action, it desensitizes and down-regulates Gn-RH receptors [Gonadotrophs] on the Anterior pituitary.
Thus, Leuprolide administration in fact decreases FSH/LH after an initial flare (brief stimulation). ***
To overcome the initial flare, recently, Gn-RH competitive antagonists (eg. ABARELIX) are developed to serve as Gn-RH antagonists.
In contrast to Leuprolide, ABARELIX does not produce the initial flare.
Note: 1 eg., is given as Gn-RH analog (Leuprolide) & 1. Gn-RH Antagonist: (Abarelix).
Suppression of gonadal hormones …
gonadal and others - • Suppression of Gonadal Hormones: In contrast, Potent Gn-RH analog (Leuprolide) or Gn-RH antagonist (Abarelix) when given continuously can decrease FSH/LH and decrease sex steroid hormone levels in both males and females.
Therapeutic Uses:
• In males: decrease Prostate Cancer (decrease Androgen – testosterone level).
• In Females: decrease Endometriosis (Growth of endometrial tissues outside the Uterus in the abdominal cavity).
When FSH/LH level is decreased, prostate proliferation in males and endometriosis in females undergo regression
hormonal contraceptives
gonadal and other -
They are either, 1. Combined Hormonal Contraceptives - contain a combination of a synthetic estrogen and a synthetic progestin or 2. Progestin alone preparation – is now gaining popularity.
Estradiol undergoes first pass metabolism in the liver, so synthetic Estrogens and Synthetic Progestin combinations are used to êêFSH/LH.
Synthetic Estrogen: eg., Ethinylestradiol (EE2) or Mestranol
Synthetic Progestin: eg., Levonorgestrel, Norethynodrel, Norgestrel
Oral combined contraceptive pill (OCP or OCCP)
gonadal and others -
Oral Combined Contraceptive Pill (OCP or OCCP)
(Combination of Estrogen & Progestin through 21 days, 7 days placebo)
Gross inactivity of ovarian function: Lack of ovulation/ovum production since estrogen + progestin in the pill suppresses the release of FSH & LH from the pituitary.
• Presence of progestin from day one also ensures changes in endometrium, thick mucus in the cervix and Decreased uterine motility: Makes the mucus thick and viscous, which inhibits the penetration of sperm - Progesterone effect.
• Composition in Combined OCP:
• Estrogen Beneficial Effect:
i) Increases plasma HDL,
ii) Decreases/opposes Bone resorption caused by parathormone (PTH).
• Estrogen Undesirable Effects:
Nausea, Vomiting, Mastalgia (Breast pain), Edema,
Skin hyperpigmentation-Chloasma, Increased Withdrawal
Bleeding [if noticed decrease the dose of EE2 in the OCP]
Could Increase Coagulation Factors: Chance for increased incidence of Venous Thromboembolism (VTE),
Be cautious: if there is a previous history of VTE or Stroke, Hypertension, Myocardial Infarction - particularly in smokers & women over 30 Yrs. taking OCP. **
• Undesirable Effect of Synthetic Progestins:
i) Decreases HDL and increases LDL- cause of Dyslipidemia
ii) Weight gain, iii) Fatigue, iv) Menstrual irregularities,
v) Spotting, vii) Cholestatic Jaundice, viii) Acne, Hirsutism (beard or chest hair in women) x) Depression,
Increased hair growth [some are due to androgenic effect of synthetic progestins – if these persist, change the preparation to a less androgenic progestin].
• Overall Contraindications for Prescribing Combined OCP:
CHF, MI, VTE, Hypertension, Stroke, Peripheral Vascular Diseases, Migraine, Severe Depression, Liver Disease and Familial history of Breast Cancer or Uterine Cancer. Exercise caution.
Possible Drug Interactions when on OCP
• OCP with antibiotics (eg. Ampicillin/Amoxicillin) decrease OCP efficacy due to increased intestinal excretion by reducing the enterohepatic reabsorption of estrogen.
• Estradiol glucuronide (E2-G) presented to the gut from the liver via bile is broken down by the bacterial β-Glucuronidase to free E2 which undergoes entero-heaptic recirculation.
• In the absence of bacterial flora following a long term antibiotic regimen, more estradiol is excreted as E2-glucuronide conjugate in the feces reducing E2 reabsorption resulting in decreased E2 bioavailability.
• Carbamazepine, Phenytoin, Rifampin (CYP enzyme inducers) decrease OCP efficacy by increasing hepatic metabolism of ethinyl estradiol in OCP.
