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STEP1 > ENDOCRINE PHARM > Flashcards

ENDOCRINE PHARM Flashcards

1
Q

Tesamorelin

A

GHRH analog

Mechanism:

Stimulate GH receptors

Clinical Use:

  1. Growth hormone deficiency
  2. Turner syndrome
  3. HIV-associated lipodystrophy

Side Effects:

  1. Short stature (e.g., in children with CKD)
  2. Idiopathic intracranial hypertension
  3. Increased insulin resistance
  4. Prepubertal gynecomastia
  5. Slipped capital femoral epiphysis
  6. Progression of scoliosis
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2
Q

Pegvisomant

A

GH receptor antagonist

Mechanism:

Block GH receptor

Clinical Use:

Acromegaly

Adverse Effects:

Hepatotoxicity

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3
Q

Bromocriptine

A

Mechanism:

Dopamine agonists

Clinical Use:

  1. Prolactinoma
  2. Parkinson disease
  3. Neuroleptic malignant syndrome
  4. Malignant hyperthermia

Adverse Effects:

  1. Nausea, vomiting
  2. Orthostatic hypotension
  3. Confusion, hallucination
  4. Dyskinesia
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4
Q

Cabergoline

A

Mechanism:

Dopamine agonists

Clinical Use:

  1. Prolactinoma
  2. Parkinson disease
  3. Neuroleptic malignant syndrome
  4. Malignant hyperthermia

Adverse Effects:

  1. Nausea, vomiting
  2. Orthostatic hypotension
  3. Confusion, hallucination
  4. Dyskinesia
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5
Q

Conivaptan

A

ADH antagonists

Mechanism:

  • Block vasopressin receptors and decrease water reabsorption in the renal collecting duct
  • Dual V1A and V2 receptor antagonism

Clinical Use:

  1. Euvolemic hyponatremia (e.g., SIADH)
  2. Hypervolemic hyponatremia (e.g., congestive heart failure)
  3. ADPKD
  4. Liver cirrhosis (short-term vaptan treatment in patients with hyponatremia and ascites due to liver cirrhosis improves free-water excretion and serum sodium levels)

Adverse Effects:

  1. Hypernatremia
  2. Hypotension
  3. Dry mouth
  4. Nausea, vomiting, stomach pain
  5. Increase in thirst, hunger, urination
  6. Weight loss

Contraindications:

  1. Dehydration
  2. Hypernatremia
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6
Q

Desmopressin

A

ADH analog

Mechanism:

  • Act on the V1 and V2 receptors
  • Release vWF stored in the endothelium

Clinical Use:

  1. Central DI
  2. Von Willebrand disease
  3. Hemophilia A
  4. Nocturnal enuresis

Adverse Effects:

  • Hyponatremia
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7
Q

Demeclocycline

A

ADH antagonist

Tetracycline

Mechanism:

  • Block V2 receptors and decrease water reabsorption in the renal collecting duct
  • Inhibits adenylyl cyclase activation and decreases cAMP levels after binding to the V2 receptors.

Clinical Use:

  1. Euvolemic hyponatremia (e.g., SIADH), using one of its side effects
  2. Hypervolemic hyponatremia (e.g., congestive heart failure)
  3. Bacterial infections (primarily an antibiotic)

Adverse Effects:

  1. Hypernatremia
  2. Nephrogenic DI (specific to demeclocycline)
  3. Hypotension
  4. Dry mouth
  5. Skin reactions
  6. Nausea, vomiting, diarrhea

Interactions:

  1. Birth control (↓ effectiveness)
  2. ↓ Absorption of cations such as calcium, iron, magnesium

Contraindications:

  1. Pregnancy (teratogenic)
  2. Breastfeeding
  3. Children under the age of 8
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8
Q

Tolvaptan

A

ADH antagonist

Mechanism:

  • Block vasopressin receptors and decrease water reabsorption in the renal collecting duct
  • Selective V2-receptor antagonism

Clinical Use:

  1. Euvolemic hyponatremia (e.g., SIADH)
  2. Hypervolemic hyponatremia (e.g., congestive heart failure) ADPKD
  3. Liver cirrhosis (short-term vaptan treatment in patients with hyponatremia and ascites due to liver cirrhosis improves free-water excretion and serum sodium levels)

Adverse Effects:

  1. Hypernatremia
  2. Hypotension
  3. Dry mouth
  4. Nausea, vomiting, stomach pain
  5. Increase in thirst, hunger, urination
  6. Weight loss

Contraindications:

  1. Dehydration
  2. Hypernatremia
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9
Q

Terlipressin

A

ADH analog

Mechanism:

  • Act on the V1 and V2 receptors
  • Release vWF stored in the endothelium

Clinical Use:

  1. Central DI
  2. Von Willebrand disease
  3. Hemophilia A
  4. Nocturnal enuresis

Adverse Effects:

  • Hyponatremia
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10
Q

Dronabinol

A

Mechanism:

  • Cannabinoid receptor agonist
  • Activation of CB1 and CB2 receptors

Clinical Use:

  1. Appetite stimulation (e.g., in HIV patients)
  2. Chemotherapy-induced emesis

Adverse Effects:

  1. Sedation
  2. Euphoria/dysphoria
  3. Hallucinations
  4. Dry mouth
  5. Autonomic effects (tachycardia, orthostatic hypotension)
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11
Q

Megestrol Acetate

A

Mechanism:

  • Synthetic progestin
  • Unclear mechanism (possible anti-inflammatory action can reduce cytokine levels, which primarily contribute to cachexia that is associated with cancer and HIV)

Clinical Use:

  1. Appetite stimulation (cancer cachexia, AIDS)

Adverse Effects:

  1. Thromboembolism risk
  2. Edema
  3. Adrenal suppression and Cushing syndrome (glucocorticoid-like activity of megestrol is responsible for these side effects)
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12
Q

Liraglutide

A

GLP-1 agonist

Mechanism:

  • Activation of GLP-1 receptor

Clinical Use:

  1. Weight loss (↑ satiety)
  2. Diabetes

Adverse Effects:

  1. Nausea and vomiting
  2. Pancreatitis
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13
Q

L-thyroxine (levothyroxine, liothyronine) Interactions

A

Increased dosage necessary

  1. Estrogen
  2. SERM (increase thyroxin-binding globulin (TBG) in the serum)
  3. Bile acid-binding resins
  4. Omeprazole
  5. Calcium carbonate (reduces gastrointestinal absorption of thyroid hormone)
  6. Phenytoin
  7. Carbamazepine (increases metabolism of thyroid hormones)
  8. Propranolol (reduces conversion of T4 to T3)

Reduced dosage necessary

  1. Glucocorticoids (decrease TBG in the serum)
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14
Q

Mitotane

A

Mechanism:

Directly inhibits the synthetic function of the adrenal cortex.

Clinical Use:

Treat adrenal tumors in patients who cannot undergo resection.

Contraindicated in pregnancy due to its teratogenic effects.

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15
Q

Insulin Pharmacokinetics

A
  • The absorption time determines the onset, peak, and duration of effect (the degree of blood circulation in subcutaneous tissue significantly influences absorption time)
  • Prolonged insulin absorption time
  1. Cold injection site (cold temperatures trigger vasoconstriction, significantly reducing blood flow at the injection site)
  2. Obesity (associated with relatively poor blood circulation in subcutaneous fatty tissue)
  3. Peripheral injection site (e.g., absorption is much slower after injections into the thigh compared to injections into the abdominal skin)
  4. Superficial subcutaneous injection (deeper layers of the skin have more capillaries, which increases the rate of absorption)
  • Shorter insulin absorption time
  1. Manipulative therapy (e.g., massages) (massage increases blood flow to tissue, which, in turn, improves insulin absorption)
  2. Deep subcutaneous injection
  3. Injection into the abdominal skin around the navel
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16
Q

Insulin Adverse Effects

A
  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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17
Q

Insulin Drug Interactions

A

Certain drugs can either increase or decrease insulin demand.

  • Increased insulin demand
  1. Thiazide diuretics and loop diuretics (increase insulin demand indirectly by depleting potassium and magnesium ions, which in turn reduces the efficacy of pancreatic β cells. Adequate potassium substitution should be considered, if necessary)
  2. Heparin
  3. Glucocorticoids
  4. Immunosuppressive drugs (e.g., calcineurin inhibitors) (insulin resistance may increase in transplant patients who are treated with ciclosporin or tacrolimus in combination with glucocorticoids)
  5. Tricyclic antidepressants (most of the classic tricyclic antidepressants cause weight gain, which leads to increased insulin resistance. Therefore, selective serotonin reuptake inhibitors (SSRIs) should be preferred over tricyclic antidepressants in patients with diabetes, although there is anecdotal evidence that SSRIs may induce hypoglycemia)
  6. Antipsychotic drugs (especially haloperidol, clozapine, olanzapine, risperidone, and quetiapine cause weight gain and trigger increased insulin resistance)
  7. Lithium
  8. HIV-protease inhibitors (abdominal obesity is one side effect of protease inhibitors that increases insulin resistance)
  9. Thyroid hormones (have a catabolic effect, enhance the mobilization of glucose, and increase the risk of hyperglycemia)
  10. Estrogen (contraceptives) (promote the secretion of growth hormones and increase insulin resistance due to their anabolic effects)
  11. Sympathomimetic drugs that interact with the β1-adrenergic receptor (e.g., dobutamine) (temporary tendency to hyperglycemia is typical at the beginning of dobutamine therapy. Insulin pumps should be adjusted accordingly)
  12. Derivatives of nicotinic acid
  • Decreased insulin demand
  1. Analgesics (e.g., NSAIDs, tramadol)
  2. Antibiotics (e.g., cotrimoxazole and other sulfonamides , fluoroquinolones)
  3. Antimalarial drugs (e.g., mefloquine, quinine)
  4. MAO inhibitors
  5. Fibrates
  6. Haloperidol
  • Either increased or decreased insulin demand
  1. Ethanol
  2. Beta blockers (slow down glycogenolysis and glycolysis, which may lead to a decrease in insulin demand. They can also mask symptoms of hypoglycemia. However, long-term treatment with beta blockers usually increases insulin demand by blocking the release of insulin from the pancreas)
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18
Q

Lispro

A

Rapid Acting Insulin

  • Onset → 5–15 minutes
  • Peak → ∼ 1 hour
  • Duration → 3–4 hours
  • Rapid absorption due to immediate dissociation into individual insulin molecules
  • No time interval between injection and meal necessary
  • Usually combined with long-acting insulin
  • For poor glucose tolerance

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type1 DM, type 2 DM, GDM (posprandial glucose control.

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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19
Q

Aspart

A

Rapid Acting Insulin

  • Onset → 5–15 minutes
  • Peak → ∼ 1 hour
  • Duration → 3–4 hours
  • Rapid absorption due to immediate dissociation into individual insulin molecules
  • No time interval between injection and meal necessary
  • Usually combined with long-acting insulin
  • For poor glucose tolerance

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type1 DM, type 2 DM, GDM (posprandial glucose control.

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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20
Q

Glulisine

A

Rapid Acting Insulin

  • Onset → 5–15 minutes
  • Peak → ∼ 1 hour
  • Duration → 3–4 hours
  • Rapid absorption due to immediate dissociation into individual insulin molecules
  • No time interval between injection and meal necessary
  • Usually combined with long-acting insulin
  • For poor glucose tolerance

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type1 DM, type 2 DM, GDM (posprandial glucose control.

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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21
Q

Mention Rapid Acting Insulins Preparations

A
  1. Lispro
  2. Aspart
  3. Glulisine

1-hr peak

(no LAG)

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22
Q

Regular Insulin

A

Short Acting Insulin

  • Onset → ∼ 30 minutes
  • Peak → 2–3 hours
  • Duration → 4–6 hours
  • Recommended interval between injections and meals → 15–30 minutes
  • Often used in combination with long-acting insulin
  • The only insulin available for intravenous use

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type 1 DM, type 2 DM, GDM, DKA (IV), HHS, hyperkalemia (+ glucose), stress hyperglycemia
  • Standard insulin option for lowering blood glucose levels in an acute setting

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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23
Q

Mention Short Acting Insulin Preparations

A

Regular Insulin

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24
Q

NPH Insulin

A

Intermediate Acting Insulin

  • Onset → 1–2 hours
  • Peak → ∼ 6–10 hours
  • Duration → 10–16 hours
  • Crystalline suspension consisting of regular insulin (with a high level of solubility) and protamine (with a low level of solubility)
  • Recommended interval between injections and meal, if it is the only antidiabetic drug used → 30–60 minutes
  • Often used in combination with rapid-acting or short-acting insulin
  • Usually administered twice daily
  • Made by mixing insulin with extract fish semen
  • Composed of a crystalline suspension of insulin with protamine and zinc
  • Poor glycemic control during meals and during night (not short nor long acting)

Mechanism:

  1. Bind insulin receptor (tyrosine kinase activity).
  2. Liver → increase glucose stored as glycogen.
  3. Muscle → increase glycogen, protein synthesis.
  4. Fat → TG storage.
  5. Cell membrane → K+ uptake.

Clinical Use:

Type 1 DM, type 2 DM, glucocorticoid-induced hyperglycemia

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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25
Q

Mention Intermediate Acting Insulin Preparations

A

NPH

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26
Q

Glargine

A

Long Acting Insulin

  • Onset → 1–4 hours
  • Peak → flat; not defined
  • Duration → ∼ 24-36 hours
  • More consistent effect and longer duration of action compared to NPH insulin
  • Often used in combination with rapid or short-actinginsulin
  • Administered once or twice daily
  • Subcutaneous injection
  • Sustain a plateau efficacy to maintain more stable insulin levels
  • Has a pH of 4 and forms a microprecipitate at the injection site, resulting in delayed absorption.

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type 1 DM, type 2 DM, GDM (basal glucose control)

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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27
Q

Detemir

A

Long Acting Insulin

  • Onset → 1–4 hours
  • Peak → flat; not defined
  • Duration → ∼ 24-36 hours
  • More consistent effect and longer duration of action compared to NPH insulin
  • Often used in combination with rapid or short-actinginsulin
  • Administered once or twice daily
  • Subcutaneous injection
  • Sustain a plateau efficacy to maintain more stable insulin levels
  • Has a pH of 4 and forms a microprecipitate at the injection site, resulting in delayed absorption.

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake.

Clinical Use:

  • Type 1 DM, type 2 DM, GDM (basal glucose control)

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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28
Q

Degludec

A

Long Acting Insulin

  • Onset → 1–4 hours
  • Peak → flat; not defined
  • Duration → ∼ 24-36 hours
  • More consistent effect and longer duration of action compared to NPH insulin
  • Often used in combination with rapid or short-actinginsulin
  • Administered once or twice daily
  • Subcutaneous injection
  • Sustain a plateau efficacy to maintain more stable insulin levels
  • Has a pH of 4 and forms a microprecipitate at the injection site, resulting in delayed absorption.

Mechanism:

  • Bind insulin receptor (tyrosine kinase activity).
  • Liver → increase glucose stored as glycogen.
  • Muscle → increase glycogen, protein synthesis.
  • Fat → TG storage.
  • Cell membrane → K+ uptake

Clinical Use:

  • Type 1 DM, type 2 DM, GDM (basal glucose control)

Side Effects:

  1. Hypoglycemia (the required dose of insulin depends on individual levels of physical activity, alcohol consumption, and stress (stress increases the dose of insulin required))
  2. Weight gain (due to the anabolic effect of insulin)
  3. Lipodystrophy at the injection site (patients should regularly change injection sites to avoid lipodystrophies)
  4. Hypokalemia (due to activation of the Na+/K+ ATPase)
  5. Allergic or hypersensitivity reactions
  6. Edema (extremely rare side effect and mainly occurs after starting intensive insulin therapy in patients with longstanding hyperglycemia and/or newly diagnosed diabetes mellitus)
  7. Pain and erythema at the injection site
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29
Q

Mention Long Acting Insulin Preparations

A
  1. Detemir
  2. Glargine
  3. Degludec
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30
Q

Metformin Mechanism

A

Biguanides

  • Glycemic efficacy → lowers HbA1c by 1.2–2% over 3 months
  • Weight loss (often desired) or weight stabilization
  • No risk of hypoglycemia
  • Beneficial effect on dyslipidemia
  • Reduces the risk of macroangiopathic complications in patients with diabetes
  • Must be paused prior to surgery
  • Cost-effective
  • Inhibit hepatic gluconeogenesis and the action of glucagon via inhibition of the mitochondrial isoform of glycerophosphate dehydrogenase in the liver
  • Increase glycolysis, peripheral glucose uptake (increase insulin sensitivity).
  • Enhances the effect of insulin
  • Reduction in insulin resistance via modification of glucose metabolic pathways
  • Inhibits mitochondrial glycerophosphate dehydrogenase (mGPD) → ↓ hepatic gluconeogenesis and intestinal glucose absorption and the action of the glucagon
  • Increases peripheral insulin sensitivity → ↑ peripheral glucose uptake and glycolysis
  • Lowers postprandial and fasting blood glucose levels
  • Reduces LDL, increases HDL
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31
Q

Metformin Adverse Effects

A

Biguanides

  • Do not cause hypoglycemia
  • GI upset
  • Promote weight loss (often desired)
  • Vitamin B12 deficiency (impairs the enteral absorption of vitamin B12)
  • Metallic taste in the mouth (dysgeusia)
  • Metformin-associated lactic acidosis
    • High-risk groups
      1. Elderly individuals (existing dehydration may be sufficient to trigger metabolic decompensation with subsequent lactic acidosis)
      2. Patients with renal insufficiency or CHF
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32
Q

Metfortmin Contraindications

A

Biguanides

  • Renal failure (if creatinine clearance < 30 mL/min)
  • Intravenous iodinated contrast medium (the elimination of metformin is reduced by the administration of iodinated contrast medium, even if overt renal failure does not develop (contrast-induced nephropathy))
  • Heart failure, respiratory failure, shock, sepsis (processes associated with hypoperfusion and hypoxemia)
  • Alcoholism
  • Severe liver failure (impaired clearance of lactate increases the risk of lactic acidosis)
  • Chronic pancreatitis, starvation ketosis, ketoacidosis, sepsis (conditions involving the production of acidic metabolites)
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33
Q

Metformin Interactions

A

Biguanides

  • Sulfonylureas (the simultaneous administration of metformin and sulfonylurea may be associated with an increase in cardiovascular mortality)
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34
Q

Pioglitazone Mechanism

A

Glitazones/Thiazolidinediones

  • Safe to use in renal impairment
  • Glycemic efficacy → lowers HbA1c by 1% in 3 months
  • Favorable effect on lipid metabolism → ↓ triglyceride, ↓ LDL, ↑ HDL
  • No risk of hypoglycemia
  • Onset of action is delayed by several weeks (this delay results from the slow upregulation of proteins involved in increasing insulin sensitivity (e.g., adipokine, GLUT4))
  • Activation of the transcription factor PPARγ (peroxisome proliferator-activated receptor of gamma type in the nucleus) → ↑ transcription of genes involved in glucose and lipid metabolism → ↑ levels of adipokines such as adiponectin and insulin sensitivity → ↑ storage of fatty acids in adipocytes, ↓ products of lipid metabolism (e.g.,free fatty acids) → ↓ free fatty acids in circulation → ↑ glucose utilization and ↓ hepatic glucose production
  • Decrease insulin resistance
  • Increase GLUT 4 expression
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35
Q

Rosiglitazone Mechanism

A

Glitazones/Thiazolidinediones

  • Safe to use in renal impairment
  • Glycemic efficacy → lowers HbA1c by 1% in 3 months
  • Favorable effect on lipid metabolism → ↓ triglyceride, ↓ LDL, ↑ HDL
  • No risk of hypoglycemia
  • Onset of action is delayed by several weeks (this delay results from the slow upregulation of proteins involved in increasing insulin sensitivity (e.g., adipokine, GLUT4))
  • Activation of the transcription factor PPARγ (peroxisome proliferator-activated receptor of gamma type in the nucleus) → ↑ transcription of genes involved in glucose and lipid metabolism → ↑ levels of adipokines such as adiponectin and insulin sensitivity → ↑ storage of fatty acids in adipocytes, ↓ products of lipid metabolism (e.g.,free fatty acids) → ↓ free fatty acids in circulation → ↑ glucose utilization and ↓ hepatic glucose production
  • Decrease insulin resistance
  • Increase GLUT 4 expression
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36
Q

Mention Glitazones/Thiazolidinediones

A
  1. Pioglitazone
  2. Rosiglitazone
37
Q

Rosiglitazone Clinical Use

A

Glitazones/Thiazolidinediones

May be considered as monotherapy in patients with severe renal failure and/or contraindications for insulin therapy

38
Q

Rosiglitazone Adverse Effects

A

Glitazones/ thiazolidinediones

  • ↑ Risk of heart failure
  • ↑ Risk of bone fractures (osteoporosis) (take vitamin D)
  • Fluid retention and edema
  • Weight gain
  • Hepatotoxicity
  • Myalgia
  • Rosiglitazone → ↑ risk of cardiovascular complications like cardiac infarction or death
39
Q

Rosiglitazone Contraindicatios

A

Glitazones/ thiazolidinediones

  1. Congestive heart failure (NYHA III or IV)
  2. Liver failure
40
Q

Pioglitazone Adverse Effects

A

Glitazones/ thiazolidinediones

  • ↑ Risk of heart failure
  • ↑ Risk of bone fractures (osteoporosis) (take vitamin D)
  • Fluid retention and edema
  • Weight gain
  • Hepatotoxicity
  • Myalgia
41
Q

Pioglitazone Clinical Use

A

Glitazones/Thiazolidinediones

May be considered as monotherapy in patients with severe renal failure and/or contraindications for insulin therapy

42
Q

Pioglitazone Contraindications

A

Glitazones/ thiazolidinediones

  1. Congestive heart failure (NYHA III or IV)
  2. Liver failure
  3. Pioglitazone → history of bladder cancer or active bladder cancer; macrohematuria of unknown origin
43
Q

Mention First Generation Sulfonylureas

A
  1. Chlorpropamide
  2. Tolbutamide
44
Q

Chlorpropamide

A

First Generation Sulfonylurea

Mechanism:

  • Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion (the use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment)
  • Extrapancreatic effect → ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

Clinical Use:

  • Patients who are not overweight, do not consume alcohol, and adhere to a consistent dietary routine
  • Generally not frequently used

Adverse Effects:

  1. Life-threatening hypoglycemia; increased risk under the following circumstances:
    • Simultaneous intake of CYP2C9 inhibitors (e.g., amiodarone, trimethoprim, fluconazole)
    • Patients with renal failure (because sulfonylureas are excreted via the kidneys, renal failure can result in accumulation. Hypoglycemia due to accumulation of long-acting glyburide may persist for several days, requiring extensive glucose substitution. Short-acting agents have a lower risk of accumulation and hypoglycemia)
    • Decreased carbohydrate intake (diets or periods of fasting)
    • Elevated glucose utilization (e.g., unaccustomed physical activity)
    • Sulfonylurea overdose
  2. Alcohol intolerance (first-generation agents): disulfiram-like reaction
  3. Weight gain
  4. Hematological changes → granulocytopenia, hemolytic anemia
  5. Allergic skin reactions
  6. Sulfonylureas are associated with more cardiovascular (macrovascular) complications than metformin.
  7. β-cell apoptosis → studies suggest that sulfonylureas induce β-cell apoptosis in human islet cells.

Contraindications

  1. Severe cardiovascular comorbidity (there is evidence that cardiovascular diseases may be exacerbated by sulfonylurea exposure during the course of disease)
  2. Obesity
  3. Sulfonamide allergy (particularly long-acting substances)
  4. Severe liver and kidney failure
  5. Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
45
Q

Glimepiride

A

Second Generation Sulfonylurea

Mechanism:

  • Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion (the use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment)
  • Extrapancreatic effect → ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

Clinical Use:

  • Patients who are not overweight, do not consume alcohol, and adhere to a consistent dietary routine
  • Generally not frequently used

Adverse Effects:

  1. Life-threatening hypoglycemia; increased risk under the following circumstances:
    • Simultaneous intake of CYP2C9 inhibitors (e.g., amiodarone, trimethoprim, fluconazole)
    • Patients with renal failure (because sulfonylureas are excreted via the kidneys, renal failure can result in accumulation. Hypoglycemia due to accumulation of long-acting glyburide may persist for several days, requiring extensive glucose substitution. Short-acting agents have a lower risk of accumulation and hypoglycemia)
    • Decreased carbohydrate intake (diets or periods of fasting)
    • Elevated glucose utilization (e.g., unaccustomed physical activity)
    • Sulfonylurea overdose
  2. Alcohol intolerance (first-generation agents): disulfiram-like reaction
  3. Weight gain
  4. Hematological changes → granulocytopenia, hemolytic anemia
  5. Allergic skin reactions
  6. Sulfonylureas are associated with more cardiovascular (macrovascular) complications than metformin.
  7. β-cell apoptosis → studies suggest that sulfonylureas induce β-cell apoptosis in human islet cells.

Contraindications

  1. Severe cardiovascular comorbidity (there is evidence that cardiovascular diseases may be exacerbated by sulfonylurea exposure during the course of disease)
  2. Obesity
  3. Sulfonamide allergy (particularly long-acting substances)
  4. Severe liver and kidney failure
  5. Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
46
Q

Glipizide

A

Short-acting second Generation Sulfonylurea

Mechanism:

  • Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion (the use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment)
  • Extrapancreatic effect → ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

Clinical Use:

  • Patients who are not overweight, do not consume alcohol, and adhere to a consistent dietary routine
  • Generally not frequently used

Adverse Effects:

  1. Life-threatening hypoglycemia; increased risk under the following circumstances:
    • Simultaneous intake of CYP2C9 inhibitors (e.g., amiodarone, trimethoprim, fluconazole)
    • Patients with renal failure (because sulfonylureas are excreted via the kidneys, renal failure can result in accumulation. Hypoglycemia due to accumulation of long-acting glyburide may persist for several days, requiring extensive glucose substitution. Short-acting agents have a lower risk of accumulation and hypoglycemia)
    • Decreased carbohydrate intake (diets or periods of fasting)
    • Elevated glucose utilization (e.g., unaccustomed physical activity)
    • Sulfonylurea overdose
  2. Alcohol intolerance (first-generation agents): disulfiram-like reaction
  3. Weight gain
  4. Hematological changes → granulocytopenia, hemolytic anemia
  5. Allergic skin reactions
  6. Sulfonylureas are associated with more cardiovascular (macrovascular) complications than metformin.
  7. β-cell apoptosis → studies suggest that sulfonylureas induce β-cell apoptosis in human islet cells.

Contraindications

  1. Severe cardiovascular comorbidity (there is evidence that cardiovascular diseases may be exacerbated by sulfonylurea exposure during the course of disease)
  2. Obesity
  3. Sulfonamide allergy (particularly long-acting substances)
  4. Severe liver and kidney failure
  5. Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
47
Q

Glyburide

A

Long-acting second Generation Sulfonylurea

Mechanism:

  • Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion (the use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment)
  • Extrapancreatic effect → ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

Clinical Use:

  • Patients who are not overweight, do not consume alcohol, and adhere to a consistent dietary routine
  • Generally not frequently used

Adverse Effects:

  1. Life-threatening hypoglycemia; increased risk under the following circumstances:
    • Simultaneous intake of CYP2C9 inhibitors (e.g., amiodarone, trimethoprim, fluconazole)
    • Patients with renal failure (because sulfonylureas are excreted via the kidneys, renal failure can result in accumulation. Hypoglycemia due to accumulation of long-acting glyburide may persist for several days, requiring extensive glucose substitution. Short-acting agents have a lower risk of accumulation and hypoglycemia)
    • Decreased carbohydrate intake (diets or periods of fasting)
    • Elevated glucose utilization (e.g., unaccustomed physical activity)
    • Sulfonylurea overdose
  2. Alcohol intolerance (first-generation agents): disulfiram-like reaction
  3. Weight gain
  4. Hematological changes → granulocytopenia, hemolytic anemia
  5. Allergic skin reactions
  6. Sulfonylureas are associated with more cardiovascular (macrovascular) complications than metformin.
  7. β-cell apoptosis → studies suggest that sulfonylureas induce β-cell apoptosis in human islet cells.

Contraindications

  1. Severe cardiovascular comorbidity (there is evidence that cardiovascular diseases may be exacerbated by sulfonylurea exposure during the course of disease)
  2. Obesity
  3. Sulfonamide allergy (particularly long-acting substances)
  4. Severe liver and kidney failure
  5. Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
48
Q

Tolbutamide

A

First Generation Sulfonylurea

Mechanism:

  • Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion (the use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment)
  • Extrapancreatic effect → ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

Clinical Use:

  • Patients who are not overweight, do not consume alcohol, and adhere to a consistent dietary routine
  • Generally not frequently used

Adverse Effects:

  1. Life-threatening hypoglycemia; increased risk under the following circumstances:
    • Simultaneous intake of CYP2C9 inhibitors (e.g., amiodarone, trimethoprim, fluconazole)
    • Patients with renal failure (because sulfonylureas are excreted via the kidneys, renal failure can result in accumulation. Hypoglycemia due to accumulation of long-acting glyburide may persist for several days, requiring extensive glucose substitution. Short-acting agents have a lower risk of accumulation and hypoglycemia)
    • Decreased carbohydrate intake (diets or periods of fasting)
    • Elevated glucose utilization (e.g., unaccustomed physical activity)
    • Sulfonylurea overdose
  2. Alcohol intolerance (first-generation agents): disulfiram-like reaction
  3. Weight gain
  4. Hematological changes → granulocytopenia, hemolytic anemia
  5. Allergic skin reactions
  6. Sulfonylureas are associated with more cardiovascular (macrovascular) complications than metformin.
  7. β-cell apoptosis → studies suggest that sulfonylureas induce β-cell apoptosis in human islet cells.

Contraindications

  1. Severe cardiovascular comorbidity (there is evidence that cardiovascular diseases may be exacerbated by sulfonylurea exposure during the course of disease)
  2. Obesity
  3. Sulfonamide allergy (particularly long-acting substances)
  4. Severe liver and kidney failure
  5. Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
49
Q

Mention Second Generation Sulfonylureas

A
  1. Glyburide (long-acting agent)
  2. Glipizide (short-acting agent)
  3. Glimepiride
50
Q

​Nateglinide

A

Meglitinide (sulfonylurea analogue)

Tolerated well by patients with chronic kidney disease (especially repaglinide)

More expensive than sulfonylureas

Mechanism

  • Similar mechanism of action to that of sulfonylureas)
  • Blockage of ATP-sensitive potassium channels of the pancreatic beta cells → depolarization of the cell membrane → calcium influx → insulin secretion
  • Meglitinides should be taken shortly before meals (in contrast to (long-acting) sulfonylureas, meglitinides are short-acting agents (half-life of ∼ 30–60 min) that primarily affect blood glucose levels shortly after intake)

Clinical Use:

  • Particularly suitable for patients with postprandial peaks in blood glucose levels, but overall rarely prescribed

Adverse Effects:

  1. Life-threatening hypoglycemia, especially in patients with renal failure (less of a risk than with sulfonylureas)
  2. Weight gain
  3. Hepatotoxicity (rare)

Contraindications → severe liver failure

Interactions → sulfonylureas

51
Q

Repaglinide

A

Meglitinide (sulfonylurea analogue)

Tolerated well by patients with chronic kidney disease (especially repaglinide)

More expensive than sulfonylureas

Mechanism

  • Similar mechanism of action to that of sulfonylureas)
  • Blockage of ATP-sensitive potassium channels of the pancreatic beta cells → depolarization of the cell membrane → calcium influx → insulin secretion
  • Meglitinides should be taken shortly before meals (in contrast to (long-acting) sulfonylureas, meglitinides are short-acting agents (half-life of ∼ 30–60 min) that primarily affect blood glucose levels shortly after intake)

Clinical Use:

  • Particularly suitable for patients with postprandial peaks in blood glucose levels, but overall rarely prescribed

Adverse Effects:

  1. Life-threatening hypoglycemia, especially in patients with renal failure (less of a risk than with sulfonylureas)
  2. Weight gain
  3. Hepatotoxicity (rare)

Contraindications → severe liver failure

Interactions → sulfonylureas

52
Q

Exenatide

A

Glucagon-like Peptide Receptor-1 Agonists (incretin mimetics)

Subcutaneous injection

Mechanism:

  • GLP-1 agonists directly enhance the effect of incretin via exogenous “incretin” intake. As with all agonist drugs that enhance the effect of an endogenous substance, the effects and side effects are particularly pronounced when increasing the dose.
  • Incretin effect → food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect
  • Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)

Side effects

  1. Weight loss (may be wanted)
  2. No risk of hypoglycemia
  3. Gastrointestinal symptoms
    • Nausea, vomiting
    • Strong feeling of satiety (often desired)
    • Pancreatitis and potentially pancreatic cancer
  4. Potential risk of medullary thyroid cancer (MTC) (further investigation required)

Contraindications

  1. Preexisting symptomatic gastrointestinal motility disorders
  2. Chronic pancreatitis or a family history of pancreatic tumors
  3. Personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2)
53
Q

Liraglutide

A

Glucagon-like Peptide Receptor-1 Agonists (incretin mimetics)

Subcutaneous injection

A rapid-release formula that is administered daily, liraglutide is also approved for the treatment of severe obesity with secondary complications.

Mechanism:

  • GLP-1 agonists directly enhance the effect of incretin via exogenous “incretin” intake. As with all agonist drugs that enhance the effect of an endogenous substance, the effects and side effects are particularly pronounced when increasing the dose.
  • Incretin effect → food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect
  • Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)

Side effects

  1. Weight loss (may be wanted)
  2. No risk of hypoglycemia
  3. Gastrointestinal symptoms
    • Nausea, vomiting
    • Strong feeling of satiety (often desired)
    • Pancreatitis and potentially pancreatic cancer
  4. Potential risk of medullary thyroid cancer (MTC) (further investigation required)

Contraindications

  1. Preexisting symptomatic gastrointestinal motility disorders
  2. Chronic pancreatitis or a family history of pancreatic tumors
  3. Personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2)
54
Q

Albiglutide

A

Glucagon-like Peptide Receptor-1 Agonists (incretin mimetics)

Subcutaneous injection

An extended-release formula that is administered once a week

Mechanism:

  • GLP-1 agonists directly enhance the effect of incretin via exogenous “incretin” intake. As with all agonist drugs that enhance the effect of an endogenous substance, the effects and side effects are particularly pronounced when increasing the dose.
  • Incretin effect → food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect
  • Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)

Side effects

  1. Weight loss (may be wanted)
  2. No risk of hypoglycemia
  3. Gastrointestinal symptoms
    • Nausea, vomiting
    • Strong feeling of satiety (often desired)
    • Pancreatitis and potentially pancreatic cancer
  4. Potential risk of medullary thyroid cancer (MTC) (further investigation required)

Contraindications

  1. Preexisting symptomatic gastrointestinal motility disorders
  2. Chronic pancreatitis or a family history of pancreatic tumors
  3. Personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2)
55
Q

Dulaglutide

A

Glucagon-like Peptide Receptor-1 Agonists (incretin mimetics)

Subcutaneous injection

Mechanism:

  • GLP-1 agonists directly enhance the effect of incretin via exogenous “incretin” intake. As with all agonist drugs that enhance the effect of an endogenous substance, the effects and side effects are particularly pronounced when increasing the dose.
  • Incretin effect → food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect
  • Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)

Side effects

  1. Weight loss (may be wanted)
  2. No risk of hypoglycemia
  3. Gastrointestinal symptoms
    • Nausea, vomiting
    • Strong feeling of satiety (often desired)
    • Pancreatitis and potentially pancreatic cancer
  4. Potential risk of medullary thyroid cancer (MTC) (further investigation required)

Contraindications

  1. Preexisting symptomatic gastrointestinal motility disorders
  2. Chronic pancreatitis or a family history of pancreatic tumors
  3. Personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2)
56
Q

Mention Glucagon-like Peptide Receptor-1 Agonists (incretin mimetics)

A
  1. Exenatide
  2. Liraglutide
  3. Albiglutide
  4. Dulaglutide
57
Q

Sitagliptin

A

Dipeptidyl peptidase-4 inhibitors (gliptins)

Mechanism:

  • Indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 → ↑ insulin secretion, ↓ glucagon secretion, delayed gastric emptying

Adverse Effects:

  1. No risk of hypoglycemia unless insulin and/or insulinotropic drugs are used simultaneously because insulin release is glucose-dependent
  2. Usually no weight changes
  3. Gastrointestinal symptoms → diarrhea, constipation (milder than in GLP-1 agonist exposure)
  4. Arthralgia
  5. ↑ Feeling of satiety (often favorable) due to delayed gastric emptying
  6. Nasopharyngitis and upper respiratory tract infection
  7. Urinary infections (mild)
  8. ↑ Risk of pancreatitis
  9. Worsening renal function, acute renal failure
  10. Headaches, dizziness

Contraindications

  1. Liver failure
  2. Renal failure
  3. Hypersensitivity
58
Q

Saxagliptin

A

Dipeptidyl peptidase-4 inhibitors (gliptins)

Mechanism:

  • Indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 → ↑ insulin secretion, ↓ glucagon secretion, delayed gastric emptying

Adverse Effects:

  1. No risk of hypoglycemia unless insulin and/or insulinotropic drugs are used simultaneously because insulin release is glucose-dependent
  2. Usually no weight changes
  3. Gastrointestinal symptoms → diarrhea, constipation (milder than in GLP-1 agonist exposure)
  4. Arthralgia
  5. ↑ Feeling of satiety (often favorable) due to delayed gastric emptying
  6. Nasopharyngitis and upper respiratory tract infection
  7. Urinary infections (mild)
  8. ↑ Risk of pancreatitis
  9. Worsening renal function, acute renal failure
  10. Headaches, dizziness

Contraindications

  1. Liver failure
  2. Renal failure
  3. Hypersensitivity
59
Q

Linagliptin

A

Dipeptidyl peptidase-4 inhibitors (gliptins)

Mechanism:

  • Indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 → ↑ insulin secretion, ↓ glucagon secretion, delayed gastric emptying

Adverse Effects:

  1. No risk of hypoglycemia unless insulin and/or insulinotropic drugs are used simultaneously because insulin release is glucose-dependent
  2. Usually no weight changes
  3. Gastrointestinal symptoms → diarrhea, constipation (milder than in GLP-1 agonist exposure)
  4. Arthralgia
  5. ↑ Feeling of satiety (often favorable) due to delayed gastric emptying
  6. Nasopharyngitis and upper respiratory tract infection
  7. Urinary infections (mild)
  8. ↑ Risk of pancreatitis
  9. Worsening renal function, acute renal failure
  10. Headaches, dizziness

Contraindications

  1. Liver failure
  2. Renal failure
  3. Hypersensitivity
60
Q

Mention Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

A
  1. Sitagliptin
  2. Saxagliptin
  3. Linagliptin
61
Q

Acarbose

A

α-glucosidase inhibitors

Mechanism:

  • Inhibit alpha-glucosidase (a brush border enzyme expressed by intestinal epithelial cells) → delayed and ↓ intestinalglucose absorption and ↓ carbohydrate breakdown, resulting in ↓ hyperglycemia after food ingestion
  • Particularly effective in controlling postprandial blood glucose levels
  • The undigested carbohydrates reach the colon, where they are degraded by intestinal bacteria, resulting in the production of intestinal gas.

Adverse Effects:

  1. No risk of hypoglycemia
  2. Gastrointestinal symptoms (flatulence, bloating, abdominal discomfort, diarrhea) (because of reduced digestion of complex carbohydrates in the gastrointestinal tract, carbohydrates are digested by intestinal bacteria in the colon. This results in gastrointestinal side effects. Gradually titrating the dose normally minimizes these side effects)

Contraindications

  1. Severe renal failure
  2. Inflammatory bowel disease
  3. Conditions associated with malabsorption
62
Q

Miglitol

A

α-glucosidase inhibitors

Mechanism:

  • Inhibit alpha-glucosidase (a brush border enzyme expressed by intestinal epithelial cells) → delayed and ↓ intestinalglucose absorption and ↓ carbohydrate breakdown, resulting in ↓ hyperglycemia after food ingestion
  • Particularly effective in controlling postprandial blood glucose levels
  • The undigested carbohydrates reach the colon, where they are degraded by intestinal bacteria, resulting in the production of intestinal gas.

Adverse Effects:

  1. No risk of hypoglycemia
  2. Gastrointestinal symptoms (flatulence, bloating, abdominal discomfort, diarrhea) (because of reduced digestion of complex carbohydrates in the gastrointestinal tract, carbohydrates are digested by intestinal bacteria in the colon. This results in gastrointestinal side effects. Gradually titrating the dose normally minimizes these side effects)

Contraindications

  1. Severe renal failure
  2. Inflammatory bowel disease
  3. Conditions associated with malabsorption
63
Q

Mention α-Glucosidase Inhibitors

A
  1. Acarbose
  2. Miglitol
64
Q

Mention Amylin Analog

A
  1. Pramlintide
65
Q

Pramlintide

A

Amylin analog

Should be administered at least 1 hour after others medication because decrease the gastric emptying

Never after a meal

Mechanism:

  • Work on pancreas
  • Decrease postprandial glucose
  • Slow blood glucose uptake
  • Decrease glucagon release
    Decrease gastric emptying
  • Increase satiety

Side Effects:

  1. Hypoglycemia (in setting of misstimed prandial insulin)
  2. Nausea
  3. Diarrhea

Contraindications:

  1. Gastroparesis
66
Q

Medications That Can Be Used for Weight Loss In Diabetic Patients

A
  1. Metformin
  2. GLP-1 agonist
  3. SGLT-2 inhibitors
  4. Orlistat
  5. Pramlintide
67
Q

Drugs for Diabetes Mellitus Management that Causes Weight Loss

A
  1. GLP-1 analogs (exenatide, liraglutide)
  2. Biguanides (metformin)
  3. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (canagliflozin, dapagliflozin, empagliflozin)
  4. Amylin analog (pramlintide)
68
Q

Drugs for Diabetes Mellitus Management that Causes Weight Gain

A
  1. Sulfonylureas
    • 1st generation → chlorpropamide, tolbutamide
    • 2nd generation → glimepiride, glipizide, glyburide
  2. Meglitinides (ateglinide, repaglinide)
  3. Glitazones/thiazolidinediones (pioglitazone, rosiglitazone)
69
Q

Carbimazole

A

Thionamide

Slow onset of action (3–4 weeks) (onset after T4 stores are depleted)

Mechanism:

  • Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis.

Clinical Use:

  • Hyperthyroidism
  • PTU used in first trimester of pregnancy (due to methimazole teratogenicity)
  • Methimazole used in second and third trimesters of pregnancy (due to risk of PTU-induced hepatotoxicity).
  • Not used to treat Graves ophthalmopathy (treated with corticosteroids).
  • After radioactive iodine treatment
  • Before radioactive iodine treatment or thyroidectomy (normal/near-normal thyroid function needs to be achieved before either radioactive iodine treatment or surgery in order to minimize the risk of thyroid storm)
  • Thyroid storm

Adverse Effect:

  1. Allergy/hypersensitivity
    • The most common side effect is a pruritic rash (particularly with methimazole)
    • Rarely, severe effects such as exfoliative dermatitis, polyserositis, and acute arthralgia occur
    • If mild, switch to propylthiouracil; if severe, avoid thioamides because of the risk of cross-sensitivities
  2. Hematologic side effects
    • Agranulocytosis
      • Rare but dangerous (affects ∼ 0.5% of patients; more common in elderly and those taking high doses)
      • Rapidly reversible with discontinuation of treatment
      • Recurrent URI and chronic cough after starting methimazole suspect agranulocytosis (leukopenia)
    • Aplastic anemia
    • Thrombocytopenia
  3. Hepatotoxicity (seen with propylthiouracil use)
    • Hepatitis
    • Cholestatic jaundice
    • Liver failure
  4. Teratogenicity → increased risk of congenital malformations with carbimazole and methimazole (e.g., aplasia cutis)
  5. Other
    • Diffuse goiter
    • Impaired sense of taste (dysgeusia)
70
Q

Methimazole

A

Thionamide

Onset after T4 stores are depleted

Methimazole has a faster onset of action and fewer side effects than propylthiouracil

Mechanism:

  • Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis.

Clinical Use:

  • Hyperthyroidism
  • PTU used in first trimester of pregnancy (due to methimazole teratogenicity)
  • Methimazole used in second and third trimesters of pregnancy (due to risk of PTU-induced hepatotoxicity).
  • Not used to treat Graves ophthalmopathy (treated with corticosteroids).
  • After radioactive iodine treatment
  • Before radioactive iodine treatment or thyroidectomy (normal/near-normal thyroid function needs to be achieved before either radioactive iodine treatment or surgery in order to minimize the risk of thyroid storm)
  • Thyroid storm

Adverse Effect:

  1. Allergy/hypersensitivity
    • The most common side effect is a pruritic rash (particularly with methimazole)
    • Rarely, severe effects such as exfoliative dermatitis, polyserositis, and acute arthralgia occur
    • If mild, switch to propylthiouracil; if severe, avoid thioamides because of the risk of cross-sensitivities
  2. Hematologic side effects
    • Agranulocytosis
      • Rare but dangerous (affects ∼ 0.5% of patients; more common in elderly and those taking high doses)
      • Rapidly reversible with discontinuation of treatment
      • Recurrent URI and chronic cough after starting methimazole suspect agranulocytosis (leukopenia)
    • Aplastic anemia
    • Thrombocytopenia
  3. Hepatotoxicity (seen with propylthiouracil use)
    • Hepatitis
    • Cholestatic jaundice
    • Liver failure
  4. Teratogenicity → increased risk of congenital malformations with carbimazole and methimazole (e.g., aplasia cutis)
  5. Other
    • Diffuse goiter
    • Impaired sense of taste (dysgeusia)
71
Q

Propylthiouracil

A

Thionamide

Slow onset of action (3–4 weeks) (onset after T4 stores are depleted)

Mechanism:

  • Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis.
  • Blocks 5′-deiodinase → decrease peripheral conversion of T4 to T3.
  • Blocks Peripheral conversion.

Clinical Use:

  • Hyperthyroidism
  • PTU used in first trimester of pregnancy (due to methimazole teratogenicity)
  • Methimazole used in second and third trimesters of pregnancy (due to risk of PTU-induced hepatotoxicity).
  • Not used to treat Graves ophthalmopathy (treated with corticosteroids).
  • After radioactive iodine treatment
  • Before radioactive iodine treatment or thyroidectomy (normal/near-normal thyroid function needs to be achieved before either radioactive iodine treatment or surgery in order to minimize the risk of thyroid storm)
  • Thyroid storm

Adverse Effect:

  1. Allergy/hypersensitivity
    • The most common side effect is a pruritic rash (particularly with methimazole)
    • Rarely, severe effects such as exfoliative dermatitis, ANCA-associated vasculitis (propylthiouracil), polyserositis, and acute arthralgia occur
    • If mild, switch to propylthiouracil; if severe, avoid thioamides because of the risk of cross-sensitivities
  2. Hematologic side effects
    • Agranulocytosis
      • Rare but dangerous (affects ∼ 0.5% of patients; more common in elderly and those taking high doses)
      • Rapidly reversible with discontinuation of treatment
      • Recurrent URI and chronic cough after starting methimazole suspect agranulocytosis (leukopenia)
    • Aplastic anemia
    • Thrombocytopenia
  3. Hepatotoxicity (seen with propylthiouracil use)
    • Hepatitis
    • Cholestatic jaundice
    • Liver failure
  4. Teratogenicity → increased risk of congenital malformations with carbimazole and methimazole (e.g., aplasia cutis)
  5. Other
    • Diffuse goiter
    • Impaired sense of taste (dysgeusia)
72
Q

Potassium iodides

A

Lugol’s iodine (oral potassium iodide)

Saturated solution of potassium iodide (SSKI)

Rapid onset of action (within a week)

Mechanism:

  • Inhibit proteolytic cleavage of T3 and T4 from thyroglobulin → inhibits thyroid hormone release
  • Also decrease thyroid vascularity and decrease the size of the gland

Clinical Use:

  1. Pretreatment before thyroid surgery (decreases vascularity → less operative blood loss; decreases thyroid hormone release → reduced risk of thyroid storm)
  2. Adjunctive therapy in thyroid storm (iodides must be given at least an hour after antithyroid drug administration to prevent the iodide from being used as a substrate for new hormone synthesis and possible worsening of the thyroid storm)
  3. Adjunctive therapy in hyperthyroidism (rarely used as a sole therapy in hyperthyroidismsince the thyroid overcomes the iodide block within a few weeks)
  4. Used as prophylaxis to decrease radioactive iodine uptake in the thyroid gland (e.g., after a nuclear accident or I131 overdose in patients undergoing radioactive iodine ablation)

Adverse Effects:

  • Side-effects are rare and often mild.
  • Oral/gastric mucosal irritation (e.g., aphthous ulcers, metallic taste) → to avoid mucosal irritation, iodides should be consumed with food or diluted with fluids.
  • Allergy/hypersensitivity → rash, angioedema; rarely, severe anaphylactic reactions can occur
  • Teratogenicity → contraindicated in pregnancy because they can cross the placental barrier and cause fetal goiter
  • Iodides delay and decrease the effects of radioactive iodine. They must be stopped at least a week before radioactive iodine ablation.

Contraindication

  1. Pregnancy
73
Q

Octreotide

A

Long Acting Somatostatin Analog

Mechanism:

  • ↓ Insulin and glucagon secretion
  • ↓ Growth hormonesecretion
  • ↓ Gastric acid and pepsinogen secretion
  • ↓ Pancreatic and small bowel fluid secretion
  • ↓ Gallbladdercontraction → ↓ biliary drainage
  • Splanchnic vasoconstriction (inhibits secretion of various splanchnic vasodilatory hormones)

Clinical Use:

  1. Acute esophageal varices bleeding (not in prevention)
  2. Acromegaly
  3. Carcinoid syndrome
  4. VIPoma
  5. Acromegaly
  6. Gastrinoma
  7. Glucagonoma

Adverse Effects:

  • Nausea
  • Cramps
  • Steatorrhea
  • Increase risk of cholelithiasis due to CCK inhibition.
74
Q

Mention Somatostatin Analogs

A
  1. Octreotide
  2. Lanreotide
75
Q

Lanreotide

A

Long Acting Somatostatin Analog

Mechanism:

  • ↓ Insulin and glucagon secretion
  • ↓ Growth hormonesecretion
  • ↓ Gastric acid and pepsinogen secretion
  • ↓ Pancreatic and small bowel fluid secretion
  • ↓ Gallbladdercontraction → ↓ biliary drainage
  • Splanchnic vasoconstriction (inhibits secretion of various splanchnic vasodilatory hormones)

Clinical Use:

  1. Acute esophageal varices bleeding (not in prevention)
  2. Acromegaly
  3. Carcinoid syndrome
  4. VIPoma
  5. Acromegaly
  6. Gastrinoma
  7. Glucagonoma

Adverse Effects:

  • Nausea
  • Cramps
  • Steatorrhea
  • Increase risk of cholelithiasis due to CCK inhibition.
76
Q

Synthetic analog of aldosterone with little glucocorticoid effects

A

Fludrocortisone

77
Q

Fludrocortisone

A

Mechanism:

  • Synthetic analog of aldosterone (predominantly mineralocorticoid activity) with little glucocorticoid effects.
  • Mineralocorticoid and glucocorticoid activity

Clinical Use:

  • Mineralocorticoid replacement in 1° adrenal insufficiency.

Adverse Effects:

  • Similar to glucocorticoids
  • Also edema, exacerbation of heart failure, hyperpigmentation.
78
Q

Cinacalcet

A

Calcimimetic

Mechanism:

  • Modulation of calcium-sensitive receptor (CaSR) in parathyroid glands → ↑ sensibility of the receptor to circulating Ca2+ → inhibition of PTH release
  • Increase the calcium sensitivity of parathyroid chief cells and therefore modulate unregulated and excessive PTH secretion in response to the moderate serum calcium changes observed in pHTP

Clinical Use:

  1. Primary hyperparathyroidism after failed parathyroidectomy
  2. Hypercalcemia in hemodialysis patients with secondary hypoparathyroidism due to CKD
  3. Parathyroid carcinoma with hypercalcemia

Adverse Effects:

  1. Gastrointestinal → nausea, vomiting, diarrhea
  2. Hypocalcemia

Contraindications

  1. Hypocalcemia
  2. In patients with osteoporosis → bisphosphonates
  3. Avoid lithium and thiazide diuretics.

Interactions: strong inhibition of CYP2A6

79
Q

Mention Phosphate Binders

A
  1. Sevelamer
  2. Calcium acetate
  3. Calcium carbonate
  4. Lanthanum
80
Q

Sevelamer

A

Phosphate binder

Mechanism:

  • Binds phosphate in the gut (sevelamer is nonabsorbable) → ↓ phosphate absorption → ↓ serum phosphate → ↓ PTH

Clinical Use:

  • Hyperphosphatemia caused by chronic kidney disease

Adverse Effects

  1. Gastrointestinal → nausea, vomiting, diarrhea, constipation, pain
  2. Hypophosphatemia
  3. Fatigue
  4. Joint pain
81
Q

Calcium Acetate

A

Phosphate binder

Mechanism:

  • Binds phosphate in the gut (nonabsorbable) → ↓ phosphate absorption → ↓ serum phosphate → ↓ PTH

Clinical Use:

  • Hyperphosphatemia caused by chronic kidney disease

Adverse Effects

  1. Gastrointestinal → nausea, vomiting, diarrhea, constipation, pain
  2. Hypophosphatemia
  3. Fatigue
  4. Joint pain
82
Q

Calcium Carbonate

A

Phosphate binder

Mechanism:

  • Binds phosphate in the gut (nonabsorbable) → ↓ phosphate absorption → ↓ serum phosphate → ↓ PTH

Clinical Use:

  • Hyperphosphatemia caused by chronic kidney disease

Adverse Effects

  1. Gastrointestinal → nausea, vomiting, diarrhea, constipation, pain
  2. Hypophosphatemia
  3. Fatigue
  4. Joint pain
83
Q

Lanthanum

A

Phosphate binder

Mechanism:

  • Binds phosphate in the gut (nonabsorbable) → ↓ phosphate absorption → ↓ serum phosphate → ↓ PTH

Clinical Use:

  • Hyperphosphatemia caused by chronic kidney disease

Adverse Effects

  1. Gastrointestinal → nausea, vomiting, diarrhea, constipation, pain
  2. Hypophosphatemia
  3. Fatigue
  4. Joint pain
84
Q

Mention Cation Exchange Resins

A
  1. Sodium polystyrene sulfonate (falling out of favor due to adverse effects)
  2. Sodium zirconium cyclosilicate
  3. Patiromer (cation-exchange polymer)
85
Q

Sodium Polystyrene Sulfonate

A

Cation-exchange resins

Falling out of favor due to adverse effects

Mechanism:

  • These drugs release Na+ or Ca2+ ions in the gut, which are exchanged for K+, thereby enhancing enteral K+ elimination.

Clinical Use:

  • Nonurgent lowering of K+
  • Often used for treatment of chronic hyperkalemia.
  • Onset of action takes several hours, so it is not recommended as monotherapy in acute hyperkalemia

Adverse Effects:

  1. Gastrointestinal upset (eg, diarrhea)
  2. Hypokalemia
  3. Hypercalcemia (due to luminal exchange of calcium)
  4. Hypomagnesemia (due to off-target binding of other positive ions)
  5. Sodium polystyrene sulfonate carries a risk of intestinal necrosis (especially if combined with the laxativesorbitol) and should be avoided in patients with abnormal bowel function.

Interactions:

  • Bind to certain medications (eg, ciprofloxacin, levothyroxine)
86
Q

Sodium Zirconium Cyclosilicate

A

Cation-exchange resins

Mechanism:

  • These drugs release Na+ or Ca2+ ions in the gut, which are exchanged for K+, thereby enhancing enteral K+ elimination.

Clinical Use:

  • Nonurgent lowering of K+
  • Often used for treatment of chronic hyperkalemia.
  • Onset of action takes several hours, so it is not recommended as monotherapy in acute hyperkalemia

Adverse Effects:

  1. Gastrointestinal upset (eg, diarrhea)
  2. Hypokalemia
  3. Hypercalcemia (due to luminal exchange of calcium)
  4. Hypomagnesemia (due to off-target binding of other positive ions)

Interactions:

  • Bind to certain medications (eg, ciprofloxacin, levothyroxine)
87
Q

Patiromer

A

Cation-exchange polymer

Mechanism:

  • These drugs release Na+ or Ca2+ ions in the gut, which are exchanged for K+, thereby enhancing enteral K+ elimination.

Clinical Use:

  • Nonurgent lowering of K+
  • Often used for treatment of chronic hyperkalemia.
  • Onset of action takes several hours, so it is not recommended as monotherapy in acute hyperkalemia

Adverse Effects:

  1. Gastrointestinal upset (eg, diarrhea)
  2. Hypokalemia
  3. Hypercalcemia (due to luminal exchange of calcium)
  4. Hypomagnesemia (due to off-target binding of other positive ions)

Interactions:

  • Bind to certain medications (eg, ciprofloxacin, levothyroxine)
88
Q

Telotristat

A

Mechanism:

  • Inhibit tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis.

Clinical Use:

  • Reduce peripheral serotonin production in patients with carcinoid syndrome to treat diarrhea.
89
Q

Calcipotriene

A

Vitamin D analog

  • Mechanism:
    • Activates the vitamin D receptor, a nuclear transcription factor
    • Acts by inhibiting T cell and keratinocyte proliferation and stimulating keratinocyte differentiation
  • Clinical Use:
    • Plaque psoriasis

STEP1 (38 decks)

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