Endocrine Flashcards
With regards to glucocorticoids, which of the following statements is correct?
A Fludrocortisone is used both orally and as a topical agent
B Methylprednisolone has no mineralocorticoid effects
C Prednisone is 4 times more potent than hydrocortisone
D Dexamethasone has a short half life
C
Explanation
Fludrocortisone is only given orally. It has potent salt retaining activity and are used in the treatment of adrenocortical insufficiency associated with mineral orticoid deficiency
Methylprednisolone has salt retaining properties (only slight) and dexamethasone has a long half life of 36-54hrs. Dexamethasone has the highest anti-inflammatory properties of the group. Prednisone is 4 times the potency of hydrocortisone and prednisolone is 5 times the potency of hydrocortisone.
Anti-inflammatory strengths:
Cortisone-0.8;
Hydrocortisone-1;
Prednisone-4;
Prednisolone-5; Methylprednisolone-5; Fludrocortisone-10
Note: this answer reflects the anti-inflammatory strengths of the glucocorticoids and not their mineral corticoid strengths seen in other questions
With regard to oral hypoglycaemics which of the following statements is correct?
A Lactic acidosis is more common with metformin than phenformin
B Chlorpropramide has a half life of 4-6 hours
C Tolbutamide and glipizide are sulphonylureas
D Metformin is more effective once weight is controlled
C
Explanation
Lactic acidosis is more common with phenformin and, as a result, has been taken off the market. It had a mortality of 50% once lactic acid developed.
Metformin is not more effective once weight is controlled.
Chlorpropramide has a half life of 32hrs.
Sulphonylureas (SU) can cause hypoglycaemia where as the buguanides (B) don’t. Metformin does not require functioning pancreatic beta cells for its action
SU= tolbutamide, tolazamide, acetohexamide, chlorpropamide, glyburide, glipizide, glimepiride.
B= metformin, phenformin, buformin
Which of the following has the most potent mineralcorticoid activity?
A Corticosterone
B Cortisone
C Cortisol
D Aldosterone
D
Explanation
Mineralocorticoid Potency- potenct relative to hydrocortisone (cortisol) of 1
Aldosterone 200-1000
Fludrocortisone 250
Cortisone 0.8
Prednisolone 0.3 (prednisone 0.3)
Dexamethasone 0
Which of the following is NOT an action of glucagon?
A Smooth muscle contraction
B Positive chronotrope
C Stimulates gluconeogenesis
D Positive inotrope
A
Explanation
Glucagon has a potent inotropic and chronotropic effect on the heart, mediated by binding to G protein-coupled receptors leading to increased cAMP similar to the process in the liver. Thus, it produces an effect very similar to that of β-adrenoceptor agonists without requiring functioning β receptors
Glucagon raises blood sugar at the expense of stored hepatic glycogen. It does not have any effect on stored skeletal glycogen, because of a lack of receptors on the skeletal muscle. Pharmacological amounts of glucagon cause release of insulin from normal pancreatic b cells, catecholamines from pheochromocytoma and calcitonin from medullary carcinoma cells
Glucagon relaxes smooth muscle of the GIT system. However, this mechanism has not been fully identified. Some studies failed to produce any demonstrable changes in the longitudinal contraction and tonicity of the lower oesophagus. The recent experimental evidences have suggested that the inhibitory effect of glucagon on the motility of the smooth muscle of the alimentary tract may not be due to its direct action on the receptor, but to its interference with intramural cholinergic neuronal transmission.ED usage: for FOOD BOLUS as an example of its (theoretical) ability to relax smooth muscle
Source: Effect of glucagon on the motility of oesophageal smooth muscle: Lin SZ et al
Insulin causes all of the following EXCEPT?
A Inhibition of gluconeogenesis
B Increase in glycogen synthesis in the liver
C Decrease in glycogenolysis in the liver
D Increase in lipolysis in the liver
D
Explanation
Insulin is a polypeptide containing two chains of 51 amino acids linked by disulphide bridges. It is synthesized in the rough endoplasmic reticulum of the beta cells of the pancreas. Insulin is a small protein with a molecular weight in humans of 5808.Lipogenesis occurs as does muscle development, glycogen synthesis and storage in liver and muscle, triglyceride synthesis and storage in adipose tissue. In the liver there is a decreased glucose output due to decreased gluconeogenesis, increased glycogen synthesis and increased glycolysis. (This is an intermediate effect of insulin)
Regarding metformin, which of the following statements is correct?
A It does not require functioning pancreatic B cells for its action
B It causes a mild lactic acidosis
C It is a sulphonylurea
D It is similar to chlorpropamide
A
Explanation
Metformin is a biguanide and can cause a significant lactic acidosis (and is contraindicated in the presence of renal or liver disease or condition which result in tissue anoxia). Chlorpropamide is a sulfonylurea and a different class of hypoglcaemics. Metformin is an insulin-sparing agent and does not increase weight gain or cause hypoglycaemia in such patients. Their blood glucose lowering action does not depend on the presence functioning pancreatic B cells.
Insulin causes which of the following effects?
A Lipoprotein lipase is inhibited by insulin to hydrolyze triglycerides from lipoproteins
B Decreases triglyceride synthesis and very-low density lipoprotein formation
C Inhibits glycogenolysis in the liver
D Decreases ribosomal protein synthesis in muscle
C
Explanation
Endocrine effects of insulin
Effects on the liver:
Reversal of catabolic features of insulin deficiency
- Inhibits glycogenolysis
- Inhibits conversion of fatty acids and amino acids to keto acids
- Inhibits conversion of amino acids to glucose
Anabolic action
- Promotes glucose storage as glycogen
- Increases triglyceride synthesis and very-low density lipoprotein formation
Effects on muscle:
- Increased protein synthesis
- Increases amino acid transport
- Increases ribosomal protein synthesis
- Increased glycogen synthesis
- Increases glucose transport
- Induces glycogen synthase and inhibits phosphorylase
Effects on adipose tissue:
- Increased triglyceride storage
- Lipoprotein lipase is induced and activated by insulin to hydrolyze triglycerides from lipoproteins
Glucose transport into cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport
Intracellular lipase is inhibited by insulin
After treatment for hyperthyroidism a patient has fever and neutropenia, which is the likely drug?
A Amiodarone
B Propranolol
C Propylthiouracil
D Radioactive iodine
C
Explanation
The most dangerous complication of the thiamides (which includes propylthiouracil and methimazole) is agranulocytosis. It is infrequent but potentially fatal. It occurs in 0.3-0.6% of patients but may be increased in the elderly and those taking higher concentrations of the drug. The reaction is usually reversible once the drug is discontinued but antibiotics may be needed for complicating infections. The cross sensitivity between the two thiamides is 50% so switching between the two drugs in patients with severe reactions is not recommended. Other more common side effects include a maculopapular rash and fever which occurs in 3-12% of patients.
A patient requires treatment for benign prostatic hyperplasia. Which of the following antiandrogens is a 5 alpha reductase inhibitor?
A Spironolactone
B Flutamide
C Finansteride
D Cyproterone acetate
C
Explanation
Testosterone acts intracellular in target cells. In skin, prostate, seminal vesicles and epididymis, it is converted to 5 alpha dihydrotestosterone by 5 alpha reductase. In these tissues dihydrotestosterone is the dominant androgen. The distribution of this enzyme in the foetus is different and important in the developmental implications
Finansteride is a 5 alpha reductase inhibitor. It reduces the size of the prostate in men with benign prostatic hyperplasia
Cyproterone acetate are effective antiandrogens that inhibit the action of the androgens at the target organ
Spironolactone, a competitive inhibitor of aldosterone also competes with dihydrotestosterone for the androgen receptors in target tissues.
Flutamide is a potent antiandrogen. It is not a steroid but is a competitive antagonist at the androgen receptor
A patient with Grave’s disease is treated with hydrocortisone. What is the mechanism of action of hydrocortisone?
A Accelerates breakdown of T4
B Blocks release of T4
C Blocks conversion of T4 to T3
D Blocks synthesis of T4
C
Explanation
PREVENTING PERIPHERAL CONVERSION OF THYROXINE TO TRIIODOTHYRONINE (T4-T3)
The peripheral conversion of thyroxine to triiodothyronine, which is responsible for 85% of triiodothyronine present in the circulation, is blocked by propylthiouracil, propranolol, and glucocorticoid. Nevertheless, for propylthiouracil and propranolol, this effect is not quantitatively significant. Therefore, glucocorticoids such as hydrocortisone or dexamethasone are essential in treatment. Glucocorticoid use in thyroid storm also improves survival rates. In patients who have severe thyrotoxicosis, especially in conjunction with hypotension, treatment with glucocorticoids is a standard practice because of the possibility of relative adrenal insufficiency.
Source: Tintinalli’s Emergency medicine
On which organ does progesterone have a stimulatory effect?
A Gut
B Lungs
C Heart
D Bladder
B
Explanation
Progesterone alters the function of the respiratory centres
The ventilator response to CO2 is increased by progesterone but synthetic progestins with an ethinyl group do not have respiratory effects. This leads to a measurable reduction in arterial and alveolar PCO2 during pregnancy and in the luteal phase of the menstrual cycle
Progesterone also has effects on
Brain: depressant and hypnotic effects on the brain.
Breast: alveolar development
Endometrium: maturation following ovulation
Body temp: increases
Kidneys: competes with aldosterone for the mineral corticoid receptor in the renal tubule causing a decrease in sodium reabsorption.
Liver: promotes glycogen storage
Which of the following insulin formulations has a time to onset of 5-15 minutes?
A Insulin detemir
B Regular insulin
C Insulin lispro
D Insulin glargine
C
Explanation
Insulin lispro, aspart and glulisine are rapid and short-acting insulin. Onset of their actions is around 5-15m. The onset of action of regular insulin is 30-60 minutes. The textbook still categorises regular insulin as a short acting insulin preparation. Insulins: detemir, degludec, glargine and NPH are all long-acting insulin that mimics basal daily insulin secretion.
Extra:
Formulations
IV or SC administration
Rapid and short acting:
Clear solution, neutral pH
Rapid onset, short duration
Short-acting regular soluble insulin is used for IV infusion, as it immediately dissociates on dilution and thus is able to be more precisely delivered
Long-acting:
Clear solution
Slow onset, prolonged action
Daily administration mimics basal insulin secretion
Extra:
The current textbook lists lispro and aspart as rapid-acting insulins
Rapid = lispro, aspart, glulisine = onset 5 - 15 minutes, peak 1hr - insulin of choice for use in continuous devices
Short-acting = Regular insulin = onset 30 minutes, peak 2-3 hours - only insulin that should be given IV
Intermediate = NPH, isophane = onset 2-5 hours, duration 4 - 12hours - often mixed with short or rapid-acting insulins
Long-acting = glargine (onset 1-1.5hr, max 4-6hr, duration 11-24hrs, acidic formulation), determir (onset 1-2hr, duration >12hr)
A 50-year-old man has develops increasing size of his joints, deepening of his voice and a change in shoe size over the past six months. Which medication is most likely to be effective in treating his condition?
A Cortisol
B Insulin
C Octreotide
D Glucagon
C
Explanation
Octreotide is a long-acting somatostatin analogue that inhibits endocrine and paracrine factor secretion, including insulin, glucagon, gastrin, GH and TSH. It is 45 times more potent than somatostatin at inhibiting GH, but only twice as potent in reducing insulin secretion – hyperglycaemia therefore rarely occurs.
What is the equivalent dose of dexamethasone and prednisolone compared to 200mg hydrocortisone?
A 8mg, 50mg
B 2mg, 20mg
C 1mg, 10mg
D 2mg, 25mg
A
Explanation
Pharmocolgy TB: Dexamethasone = 30x relative potency for anti-inflammatory effect. Prednisolone = 4x relative potency for anti-inflammatory effect. Therefore, equivalent doses 6.66mg Dexamethasoneand 50mg Prednisolone – closest answer is 8mg & 50mg
Note: Physiology TB reports Dexamethasone is 25x potency – so would give the correct answer of 8mg
Which drug has both a greater anti-inflammatory and salt-retaining effecting than hydrocortisone?
A Betamethasone
B Prednisolone
C Fludrocortisone
D Dexmaethasone
C
Explanation
Fludrocortisone has 10x relative potency for anti-inflammatory compared to hydrocortisone (cortisol), and 250x salt-retaining
Which anti-thyroid treatment should be used for a pregnant woman in her 1st trimester?
A Propanolol
B Carbimazole
C Propylthiouracil
D Potassium iodide
C
Explanation
Propylthiouracil reserved for 1st trimester pregnancy, thyroid storm, or those intolerant of methimazole treatment. Also inhibits peripheral deiodination of T4 to T3, and increased risk of severe hepatitis.
Extra:
What is the best choice of treatment in pregnant patients with hyperthyroidism?
Antithyroid drugs are the treatment of choice for hyperthyroidism during pregnancy. They inhibit thyroid hormone synthesis by reducing iodine organification and coupling of MIT and DIT. Methimazole (MMI), propylthiouracil (PTU), and carbimazole have been used for the treatment of hyperthyroidism during pregnancy. The pharmacokinetics of MMI is not altered in pregnancy; it has been reported that serum PTU concentrations may be lower in the third than in the first and second trimesters of gestation. Use of PTU should be restricted to first trimester of pregnancy, after which change to MMI is recommended. Although adrenergic b-blocking agents may be used for the management of hyper-metabolic symptoms, their use should be limited to a few weeks because of possible intrauterine growth retardation and, if used in late pregnancy, they may be associated with transient neonatal hypoglycaemia, apnoea, and bradycardia.
Source: Management of hyperthyroidism during pregnancy and lactation Fereidoun Azizi and Atieh Amouzegar Research Institute for Endocrine Sciences, Endocrine Research Center, Shahid Beheshti University (MC), PO Box 19395-4763, Tehran 198517413, Islamic Republic of Iran (Correspondence should be addressed to F Azizi; Email: azizi@endocrine.ac.ir)
Which oral anti-diabetic drug can cause B-12 deficiency
A Gliclazide
B Pioglitazone
C Glipizide
D Metformin
D
Explanation
Metformin interferes with the calcium-dependent absorption of vitamin B12-intrinsic factor complex in the terminal ileum, and vitamin B12 deficiency can occur after many years of metformin use. Periodic screening for vitamin B12 deficiency should be considered, especially in patients with peripheral neuropathy or macrocytic anaemia. Increased intake of calcium may prevent the metformin-induced B12 malabsorption.
Source: Katzung Pharmacology 15ed
Which oral diabetic medication can cause B12 deficiency?
A Tolbutamide
B Glipizide
C Metformin
D Rosiglitazone
C
Explanation
The main anti-diabetic drug linked to vitamin B12 deficiency is metformin. While other medications used to treat diabetes might contribute to B12 issues indirectly through various mechanisms (e.g., affecting gut health), metformin is the one consistently identified as having a direct impact on B12 absorption
Metformin interferes with the calcium-dependent absorption of vitamin B12-intrinsic factor complex in the terminal ileum, and vitamin B12 deficiency can occur after many years of metformin use.
