Selective estrogen receptor modulators
Drugs
Tamoxifen
Raloxifene
Mechanism of action
Competitive inhibitor of estrogen binding
Mixed agonist/antagonist action
Indications
Prevention of breast cancer in high-risk patients
Tamoxifen: adjuvant treatment of breast cancer
Raloxifene: postmenopausal osteoporosis
Adverse effects
Hot flashes
Venous thromboembolism IMPORTANTT
Endometrial hyperplasia & carcinoma (tamoxifen only)
Uterine sarcoma (tamoxifen only)
Tamoxifen has a favorable effect on serum lipids, with a decrease in total and LDL cholesterol and no significant change in HDL. Serum triglycerides may increase in some patients.
ANTIHYPERLIPIDIMIC AGENTS
1.Statins
2.bile acid-binding resins reduced blood LDL levels. However, increase hepatic production of TG and can cause hypertriglyceridemia.
- Ezetimibe selectively inhibits the intestinal absorption of cholesterol and lowers LDL levels.
4.Fibrates (eg, gemfibrozil, fenofibrate) inhibit hepatic production of triglycerides and are first-line treatments for hypertriglyceridemia. IMPORTANT
5.Niacin reduces blood triglyceride levels, raises HDL levels, and decreases VLDL conversion to LDL, thereby decreasing LDL concentrations as well.
6.PCSK9 inhibitors (eg, evolocumab, alirocumab) are monoclonal antibodies that inhibit binding of PCSK9 to LDL-R, which decreases LDL-R degradation and increases the concentration of LDL-R remaining on the cell surface. This results in greater uptake of LDL in the liver and lower circulating LDL levels.
Potassium iodide
Potassium iodide (NONRADIOACTIVE )
competitively inhibits thyroid uptake of radioactive iodine isotopes and is often administered following nuclear accidents to protect the thyroid and prevent development of radiation-induced thyroid carcinoma.
DM ORAL DRUGS
1.thiazolidinedione (TZD) E.G pioglitaZONE
, a class of medications that decrease insulin resistance. BY PPAR- GAMMA
SE: HF , BONE FRACTURE
2.a sulfonylurea medication (ie, glipizIDE)
inhibit the ATP-sensitive potassium channel on the pancreatic beta cell membrane, inducing depolarization with opening of L-type calcium channels (ie, increased Ca2+ influx), stimulating insulin release. elevate the C-peptide level.
SE: HYPOGLYCEMIA ,WIGHT GAIN
3.Metformin
Mechanism of action
1.Inhibits mitochondrial glycerophosphate dehydrogenase
2.Upregulates AMP-activated protein kinase
Metabolic effects:
↓ Hepatic glucose production (gluconeogenesis)
↓ Intestinal glucose absorption
↑ Peripheral glucose uptake/utilization
↓ Lipogenesis
Pharmacokinetics:
Renal clearance IMPORTANT CHEAK CREATINIE
SE:
Diarrhea (GI UPSET)
Lactic acidosis
Vitamin B12 deficiency
Precautions/ contraindications :
Renal insufficiency (check serum creatinine)
Hepatic insufficiency
Decompensated heart failure
3.SGLT2 inhibitor (eg, canagliFLOZIN)
increased urinary glucose excretion and lower blood glucose levels
Natriuresis and osmotic diuresis due to decreased reabsorption of sodium and glucose, leading to a small decrease in extracellular fluid volume, total body sodium content, and blood pressure.
( decreased mortality in heart failure, and slowed progression of diabetic nephropathy.)
SE: UTI,VULVULITIS
DEHYDRATION,HYPRKALEMIA
- GLP-1 E.G LiragluTIDE
5.DPP-4 E.G LinagLIPTIN
helps regulate blood glucose by: IMPORTANT
1-slowing gastric emptying (LOW APPETITE)
2-suppressing glucagon secretion
3-increasing glucose-dependent insulin release.
Because the effect on insulin is glucose dependent, there is minimal risk of hypoglycemia.
SE :
RS INFECTIONS + UTI (DPP-4)
PANCRETITIS (GLP-1 )
DPP4 do not result in weight loss but are considered weight neutral.
6.Alpha- Glucosidase inhibitors E.G. Acarbose
reduced glucose absorption by small intestine
SE:
GI upset , bloating , gas
DM SQ DRUGS
1.Long-acting insulin analogues (eg, glargine) have an extended duration of action without a noticeable peak in activity and are typically given once daily to mimic basal insulin secretion.
- Rapid-acting insulins (eg, aspart, lispro) are quickly absorbed from the injection site and are given at mealtimes to replicate postprandial insulin secretion.
3.NPH, an intermediate-acting crystalline suspension of insulin with zinc/protamine, can be given twice daily when used as basal insulin. However, unlike other basal insulins, it has a noticeable peak effect and can lead to hypoglycemia
4.short acting REGULAR insulin
2.5 h peak
lasts 4-6 h
Insulin-induced weight gain
Physiologic factors
Increased peripheral glucose uptake
Increased adipose fatty acid uptake
Reduced renal glucose losses
Behavioral factors
Less rigorous dietary adherence
Eating/snacking in response to hypoglycemic symptoms
Patient counseling:
Review for changes in diet
Ask about hypoglycemic symptoms
HYPOGLYCEMIA
Symptoms of hypoglycemia fall into 2 general categories: neurogenic (autonomic) and neuroglycopenic.
1.Neurogenic symptoms are mediated via norepinephrine/epinephrine and acetylcholine release during sympathetic stimulation. Symptoms due to norepinephrine/epinephrine include tremulousness, tachycardia, and anxiety/arousal, whereas acetylcholine causes sweating, hunger, and paresthesias.
2.Neuroglycopenic symptoms are due to inadequate availability of glucose in the CNS and include behavioral changes, confusion, visual disturbances, stupor, and seizures.
This patient has reduced awareness of hypoglycemia, likely due to the use of a nonselective beta blocker (eg, propranolol) for chronic treatment of migraines and/or hypertension.
IMPORTANTTTT :Nonselective beta blockers attenuate the norepinephrine/epinephrine-mediated symptoms of hypoglycemia, but cholinergic symptoms (eg, hunger) are unaffected.
HIV TX HAART
Medication-induced body fat redistribution (sometimes called lipoatrophy or lipodystrophy) is a common adverse effect of highly-active antiretroviral therapy (HAART) and can be considered a product of 2 independent processes:
- wasting of fat from the face and extremities 2.deposition of fat in the trunk and viscera.
Metabolic effects of glucagon
Liver
↑ glycogenolysis (primary)
↑ gluconeogenesis, ↓ glycolysis (secondary)
↓ lipogenesis
Adipose
↑ lipolysis
Heart
↑ heart rate, contractility (high dose)
Useful in treating beta blocker overdose
GnRH Leuprolide
PILSUTILE VS CONTIUOUS
Leuprolide is a GnRH agonist used to treat prostate cancer.
IMPORTANT:
It initially stimulates pituitary LH secretion, which leads to a rise in androgen levels. However, the GnRH receptor is subsequently down-regulated, which dramatically drops LH release and leads to a long-term decrease in androgen production.
Benign prostatic hyperplasia is typically treated with a 5-alpha reductase inhibitor (eg, finasteride), which reduces the conversion of testosterone to DHT. This class of medications reduces DHT levels while testosterone levels remain largely unaffected.
Graves ophthalmopathy
Glucocorticoids improve Graves ophthalmopathy by decreasing the severity of inflammation and reducing the excess extraocular volume.
Graves ophthalmopathy is caused by stimulation of orbital fibroblasts by thyrotropin receptor antibodies and cytokines released by activated T-cells. Excess deposition of extracellular glycosaminoglycans and inflammatory infiltration lead to expansion of extraocular muscles and retro-orbital tissues.
GRAVES
Beta blockers are used to blunt the adrenergic manifestations of hyperthyroidism. In addition, lipid-soluble beta blockers reduce conversion of T4 to T3 by inhibiting 5’-monodeiodinase in peripheral tissues.
Hyperthyroidism causes a hyperadrenergic state characterized by hypertension, palpitations/tachycardia, sweating, heat intolerance, tremor, and hyperreflexia. Beta blockers can relieve these symptoms.
Exophthalmos in Graves disease is due to an immune-mediated increase in orbital soft tissue mass and does not improve with beta blockers.
IMPROVES BY CORTISONE
oxoanions
Certain oxoanions (eg, perchlorate, pertechnetate) inhibit the sodium-iodide symporter and reduce iodine uptake by the thyroid.
Aromatase inhibitors (eg, anastrozole)
(eg, anastrozole, letrozole, exemestane)
decrease the synthesis of estrogen from androgens, suppressing estrogen levels and slowing progression of ER-positive tumors.
BPH
reduce conversion of testosterone to dihydrotestosterone.
In men with BPH, these agents reduce prostate volume and alleviate obstruction of urinary flow. However, they are associated with androgen-deficiency effects, including decreased libido, erectile dysfunction, and decreased ejaculate volume. IMPORTANT
estrogen
An increase in estrogen activity, as seen in pregnancy or postmenopausal estrogen replacement therapy,
IMPORTANT
increases the level of thyroxine-binding globulin.
This leads to an increase in total thyroid hormone levels, but feedback control maintains normal levels of free (biologically active) thyroid hormone.
ketoconazole
androgen synthesis inhibitors
GnRH analogs (eg, goserelin)
continuous GnRH stimulation by long-acting GnRH analogs (eg, goserelin) suppresses LH and FSH release, decreasing production of estrogens in the ovarian follicle. These agents are useful for ovarian suppression in premenopausal women with ER-positive breast cancer.
Prolactinoma
Treatment
Dopamine agonist (cabergoline)
Transsphenoidal surgery
thyrotoxicosis
IMPORTANT:
##Beta blockers provide rapid relief of the adrenergic-mediated symptoms of thyrotoxicosis and can be given while awaiting diagnostic evaluation and definitive management.
Medications for weight loss
1.Sympathomimetic amines
(ie, phentermine, diethylpropion, benzphetamine)
Stimulant/CAS
High rate of weight regain
Not recommended for patients with CVD
2.Orlistat
Intestinal lipase inhibitor
Significant gastrointestinal side effects
3.Bupropion/naltrexone
CAS (antidepressant + opioid antagonist)
CAS = central appetite suppressant
Lowers seizure threshold
May also assist in smoking cessation
Sympathomimetic amines E.G. phentermine
They work by stimulating release and inhibiting reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine.
Subjective effects include an increased sensation of satiety and subsequently reduced caloric intake.
FOR BIOCHEM
IMPORTANT TO CHEAK ENOCRAINE WORD FILE
AND BIOCHEM WORD FILE
AND LYSOSOMAL STORAGE DISESE FILE
KETON
The brain, kidneys, cardiac muscle, and skeletal muscle can all utilize ketones for energy.
In the initial stages of fasting, the heart and skeletal muscle consume primarily ketone bodies to preserve glucose for the brain, but in prolonged starvation, even the brain will utilize ketone bodies for the majority of its energy needs.
IMPORTANT : erythrocytes cannot use ketone bodies for energy because they lack mitochondria.
The liver is also unable to utilize ketone bodies for energy because it lacks the enzyme succinyl CoA-acetoacetate CoA transferase (thiophorase), which is required to convert acetoacetate to acetoacetyl CoA.
