Cushing Disease
Excess cortisol levels secondary to pituitary adenoma which results in increased secretion of ACTH (adrenocorticotropic hormone) which stimulates the adrenal glands to secrete more cortisol.
Results in metabolism, immune and tissue dysfunction
Symptoms:
- Metabolic - weight gain, fat redistribution (moon face, buffalo hump, central obesity)
- Skin - purple straie, easy bruising, thin skin
- Musculoskeletal - muscle weakness osteoporosis
- Endocrine - hyperglycemia
- Cardiovascular - HTN
Cushing Syndrome
High levels of cortisol due to any cause, including Cushing disease. Exogenous steroid use, pituitary tumor, adrenal adenoma, small cell lung cancer (produces ACTH). Presents with the same signs and symptoms as Cushing Disease.
Addison Disease
Decreased cortisol and aldosterone levels, also known as adrenal insufficiency. The most common cause is autoimmune destruction.
Signs and symptoms:
- General: fatigue, weight loss, anorexia
- Skin: hyperpigmentation (creases, gums)
- GI: Nausea, vomiting, pain
- Cardiovascular: hypotension, orthostatic
- Electrolytes: hyponatremia, hyperkalemia (low aldosterone)
Glucose-6-Phosphate-Dehydrogenase Deficiency
A hemolytic disorder that is inheirted. The G6PD helps protect RBC from oxidative damage. If certain triggers set this condition off, then these protection is removed and hemolysis occurs. Triggers - infection, drugs (sulfas, antimalarials, high dose ASA), fava beans
Secondary syphilis
Primary syphilis is seen as the asymptomatic chancre. Not really seen in the females case most time.
Secondary occurs weeks to months after the infection. Rash - diffuse, symmetric, maculopapular. Palms and soles are the classic sites. Mucous membranes.
Fasting plasma glucose level that is high
> 126
Random plasma glucose level cut off?
> 200mg/dl
Oral glucose tolerance test high cut off
> 200 mg/dl
Normal A1c level
Below <6%
Hyper VS Hypo thyroid skin characteristics
Hyper - warm, velvety
Hypo - cool, thick, coarse
Diabetes complications
KNIVES
K - kidneys (nephropathy)
N - neuropathy (peripheral)
I - infections (UTI, fungal)
V - vascular (CAD, CVA, PAD)
E - eyes (retinopathy)
S - skin changes (diabetic dermopathy)
When does screening for microvascular complications of DM begin?
Starts at age 10 or at puberty. Whichever comes first
Alpha-glucosidase inhibitors
- MOA
- Indications
- Side effects
- Commonly used examples
- Contraindications
Flush
MOA: Oral antidiabetic medications that slow carbohydrate digestion in the intestines. Inhibit alpha-glucosidase which is responsible for breaking down complex carbs in the intestines. This delayed digestion leads to a decrease in post-prandial glucose absorption.
Side effects: GI symptoms (flatulence, bloating, diarrhea) - undigested carbs are fermented leading to these effects
Hypoglycemia risk - low
Commonly used examples: Acarbose
Contraindications - IBD or significant GI disorders
Biguanides
- MOA
- Medications
- Side effects
Medications - Metformin (Glucophage)
MOA - have three main functions:
1. Inhibits glucose production by the liver
2. Increases insulin sensitivity and glucose uptake
3. Reduces intestinal glucose absorption
Does NOT stimulate insulin secretion so does not cause hypoglycemia alone.
Side effects:
- GI - nausea, diarrhea, metallic taste
- Lactic acidosis
- VB12 deficiency
- Weight neutral
FIRST line therapy for DM
Sulfonylureas
1. Prototype drug
2. Brand
3. MOA
4. Uses
5. Adverse effects
6. Interactions
7. Dose
Glyburide (diabeta) - end in “-ide”
The MOA of sulfonylureas results in stimulation of the beta-cells in the pancreas to increase insulin production. This can result in hypoglycemia if taken when glucose levels are not high enough. ATp - potassium - calcium - release of insulin
Used:
- Used for treatment and management of hyperglycemia
Adverse effects:
- Hypoglycemia - this is increased in patients that have difficulties metabolizing and excreting the drugs. Renal and hepatic insufficiency can result in worse or more often hypoglycemic episodes.
- Weight gain - insulin promotes use of calories that ingested. Prior to taking the medication, much of the sugar would just be eliminated via urine.
Interactions:
- Alcohol - alcohol intake can result in a “disulfiram reaction - flushing, nausea, palpitations. Alcohol can also increase the risk for hypoglycemia
- NSAIDS, sulfa antibiotics, and alcohol all can intensify hypoglycemia.
- Beta - blockers - suppress insulin release
Dose:
0.75 to 3mg daily - hold if NPO or hypoglycemic
What antidiabetic medication is avoided in T1DM? Why?
Sulfaonureas stimulate increased insulin production from beta cells of the pancreas. T1DM is caused by autoimmune destruction of the beta cells, so there is nothing to stimulate.
Thiazolidinediones (TZDs)
1. Prototype
2. Brand
3. MOA
4. Uses
5. Adverse effects
6. Interactions
7. Dose
8. BBW
Pioglitazone (Actos) - medications end in “-glitazone”
Actos
Reduces insulin resistance by increasing insulin utilization. Decreases glucose production by the liver. Activates PPAR gamma - a gene that helps regulate lipid and carbohydrate metabolism. Activation of this gene increases skeletal muscle and adipose tissue uptake of glucose.
Used to treat T2Dm alongside lifestyle changes and metformin. The presence of insulin is needed for the medication to work, so there is no benefit of T1DM patients taking it.
Common - URTI, headache, sinusitis, and myalgia.
Serious - Can cause ovulation in anovulatory pre-menopausal women. Contraceptive means. Possibly increases the risk for bladder cancer. Increase risk for fractures in women. Possibly hepatotoxic. Can increase LDL but also can increase HDL and lower triglycerides.
- Ovulation
- Bladder cancer
- Fractures
- Hepatotoxic
- Increase LDL and HDL, lower Triglycerides
***BBW - contraindicated in patients with HF. The medication causes a mild increase in fluid retention that is handled by patients without HF but can be detrimental in patients with the disease. Specially NYHA III or IV.
What is the BBW associated with Thiazolidinediones (TZDs) prototype? What should the patient be educated on?
The BBW is the contraindication of prescribing this medication to patients with heart failure, specially NYHA class 3 and 4. This is because the medication can cause mild fluid retention that these patients cannot tolerate.
Education should include the signs and symptoms of fluid volume overload - SOB, weight gain, edema, exertional dyspnea.
What are incretin hormones?
Gut-derived peptides that help regulate blood sugar after eating.
GLP-1 and GIP are the two hormones.
They have the following actions:
- Slow gastric emptying, preventing post-meal spikes
- Stimulate insulin secretion
- Suppress glucagon release
- Promote fullness
Meglitinides
A structurally and functionally similar medication class to sulfonylureas. They stimulate the beta cells of the pancreas to release increased insulin.
Can result in hypoglycemia. Skip doses if skipping meals.
Glucagon-like peptide-1 receptor agonist
1. Prototype medication
2. Brand
3. MOA
4. Uses
5. Adverse effects
6. Interactions
7. Dose
Liraglutide (Victoza) - medications end in “-tide”. Exenatide, Dulaglutide, Semaglutide.
Victoza
These medications are often referred to as incretin mimetics. The incretin hormones GLP-1 and GIP are gut-hormones that are released after meals and work to 1. Slow gastric emptying 2. stimulate glucose-dependent release of insulin 3. Inhibit postprandial glucagon 4. Suppress hunger.
They activate GLP-1 receptors, just like the endogenous hormones, resulting in the usual effects of these hormones.
1. Slowed gastric emptying
2. Stimulate glucose-dependent release of insulin
3. Inhibit postprandial glucagon
4. Suppress hunger
These medications can result in weight loss
Used in treatment of T2DM
Adverse effects:
- Hypoglycemia when used in combination with sulfonurea
- N/V and diarrhea are the most common adverse effects
- Pancreatitis
- Renal impairment - exacerbated by conditions or medicines that can result in dehydration
- Possibly linked to thyroid cancer
- Teratogenic
- Hypersensitivity
Dose - can be given twice daily or once weekly
Dipeptidyl peptidase-4 inhibitors
- What does the enzyme do?
- What is this medication used for?
- Names of these medications
- Effectiveness
- Side effects
DPP4 is an enzyme that breaks down incretin hormones (GLP1 and GIP). Incretin hormones work to increase insulin release after meals and suppress glucagon.
These medications are taken to increase incretin hormones to lower blood sugar levels.
DPP4 inhibitors are also known as gliptins. They are oral antidiabetic medications.
- Sitagliptin (Januvia)
- Linagliptin (Tradjenta)
etc
Gliptins on average, can lower the A1C by `0.5-1.0%
Side effects - nasopharyngitis, headache, GI upset. Pancreatitis, severe joint pain, HF. Low risk of hypoglycemia.
Dietary changes during long-term treatment with corticosteroids?
Increase potassium consumption - corticosteroids can mimic aldosterone leading to increased K secretion
Increase protein intake - long term corticosteroids can cause muscle wasting, bone loss. Increased protein can help this.
Decrease sodium intake - mimic aldosterone.
Alpha 2 activation
- Common medications of this class
Inhibitory: inhibits norepinephrine from being released. Improves sympathetic outflow.
- Sedation
- Analgesia
- Decreased blood pressure
Medications:
- Brimonidine
- Clonidine
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