The formal diagnosis of dementia generally requires ssx be present for how long? What concomitant sx are common with dementia?
depression and anxiety
- 20-30% will have depression
- 20% will have anxiety
Is dementia a normal process of aging?
1 cause of placement into nursing homes
Not at all.
Alzheimers accounts for 60-70% of dementia
What two lesions are found when investigating Alzheimer’s disease?
- neurofibrillary tangles
- beta-amyloid sheets (protein plaques outside neurons)
this vitamin, with the capability to scavenging ROS, has been studied to for Alzheimer’s disease progression, sadly, the evidence fails to support any protective theory. What is the vitamin and what was found instead that we need to be aware of?
- THROMBOSIS potential at 2000IU dose
combination therapy with estrogen and progesterone could increase risk of what?
statin’s apparently help (assoc with dec. risk of AD), but I don’t think everyone needs to be on one. Sorry allopathy.
- animals models - estrogen restores neural synapses, increases beta-amyloid sheet solubility and increases activity of choline acetyl transferase, but - RCTs in humans fail to show this and instead show increased risk of AD when combination therapy is sought
Statins are considered possibly useful in AD? IF this is the case, which enzyme is it proposed to influence and, what’s the MOA?
- stimulates alpha-secretase activity
- modulates beta-amyloid production and amyloid precursor protein metabolism
- reduces inflammatory markers
Laboratory testing for dementia include these serum studies as well as imaging to rule out what?
- CBC, ESR, electrolytes (r/o anemia, electrolyte imbalance)
- LFTs (r/o LV dysfunction)
- TSH (r/o thyroid cause)
- Serum B12 (r/o vit. def)
- Syphilis serology (anti-treponema antibody)
- HIV test (AIDS dementia)
- Imaging (r/o tumor, hematoma, abscess, stroke)
What are Lewy bodies ie what are they composed of? and does Lewy Body Dementia (DLB) overlap with any other disease?
tiny proteins INSIDE the neuron composed of
- ubiquitin protein
Lewy body Dementia (DLB) overlaps clinically w/ AD and PD
- more closely associated with PD*
In DLB, loss of what neurons account for the degradation of cognitive function? Which neurons account for the degradation of motor function? What type of drug do we need to wait to prescribe pending labs and imaging?
loss of cholinergic (acetylcholine producing) neurons - COGNITION
loss of dopaminergic (dopamine producing) neurons - MOTOR
DO NOT rx neuroleptics
which progresses more rapidly, DLB or AD?
- rapid or acute onset, esp rapid decline in the first few months
- although difficult to differentiate, need to due to DLB’s sensitivity to neuroleptics
How can we be sure someone has DLB?
when they die
biopsy on autopsy confirms dx
this is a partial NMDA receptor antagonist used to treat moderate to severe alzheimers - what is it?
- for moderate to SEVERE AD
These FDA approved AChE inhibitor drugs have been shown to
- mildly slow the rate of cognitive decline,
- improve ADLs and behavior in mild to moderate AD - what are they? (3)
- Donepezil (most selective for AChE)
- Galantamine (modifies nicotinic Rs)
- Rivastigmine (blocks butyrylcholinesterase)
This AChE inhibitor was the earliest drug used in treating AD, however - it is no longer used due to which SE?
Tacrine / Cognex
- no longer used to tx dementia
of the AChE inhibitors:
Donepezil has higher selectivity for _____
Rivastigmine also inhibits _____
Galantamine also has modifying effects on _____ receptors
G: nicotine receptors
this drug may help with movement disorder, however may aggravate psychosis in people with DLB - which medication is this?
Sinemet - may agg. DLB
DLB may be more responsive to Doepezil (than AD)
the cholinergic hypothesis - destruction of basal forebrain cholinergic neurons may be the cause of AD due to reduced cholinergic transmission - provides a rationale for the use of what in AD therapy?
Anticholinesterase inhibitors (AChE inhibitors)
- believed to enhance cholinergic transmission in the brain reducing ssx of AD
Acetylcholinesterase inhibitors are used as an antidote for what?
- organophopshate (anticholinergic) poisoning
- nerve gas exposure
So, achetylcholinesterase inhibitors are important in treating dementia, what kinds of effects do they have?
- SLUDGE + M (miosis)
What does SLUDGEM stand for?
PNS effects! chronic stimulation of muscarinic ACh receptors (cholinergic stimulation)
S - salivation L - lacrimation U - urination D - defecation G - GI upset E - emesis M - miosis (pinpoint)
this centrally acting reversible AChEI is mainly used to treat AD by increasing cortical acetylcholine. It has also been found to improve sleep apnea in AD pts - it’s oral bioavailability is 100%, it easily crosses the BBB - and with a half life of 70 hours, this baby is indicated 1x/day (even though.. it seems like it could be 1x/3 days) - what drug is it?
Donepezil / Aricept
has not been approved, but used off-label for
- vascular dementia
What is the MC experienced SE of Donepezil and other agents of this drug class?
Donepezil also may treat what additional symptom in AD?
bradycardia, N, D, anorexia, abd. pain, VIVID dreams (fun!)
can tx SLEEP APNEA in AD
Two studies have been published, suggesting Donepezil can potentially increase and improve vocabulary and expressive language for children affected with what?
This centrally acting reversible AChEI is approved for mild to moderate dementia in both AD and PD. Administered either PO or with a transdermal PATCH - in particular - this drug appears to show the MOST BENEFIT in pts showing a more AGGRESSIVE disease progression (younger age of onset, poor nutritional status, delusions/hallucinations) - which miracle drug is this?
Rivastigmine / Exelon
the presence of hallucinations seem to be a predictor of esp. STRONG responses to RIVASTIGMINE in AD and PD
What other enzyme is inhibited by Rivastigmine that may reflect the increased response seen in those experiencing hallucinations?
- has been considered for schizophrenia tx, however NO firm evidence for this
This anticholinesterase inhibitor also stimulates nicotinic ACh Rs. IT, along iwth other cholinergics has been used as a “brain enhancer” to improve memory in brain-damaged adults - which medication is this?
Galantamine / Razadyne
Huperzine A is also a brain enhancer
What are the SSX of OD in anticholinesterase inhibiting drugs and which drug is the antidote?
SSX - SEVERE N/V, salivation, sweating, bradycardia, HYPO-TN, convulsions and circulatory collapse
Antidote - ATROPINE*
Abnormal function of what type of neurotransmission is hypothesized as an additional contributor to AD etiology - leading to which receptors now being targeted for treatment of AD?
- NMDA receptors
This is a glutamatergic NMDA receptor antagonist that binds the NMDA R and inhibits prolonged calcium influx and therefore modulates neuronal excitotoxicity.
This drug also acts non-competitively as a 5HT3 antagonist with unknown AD effects - which drug is this?
Memantine / Namenda
also acts as
- agonist at dopamine D2 receptor
- antagonist nicotinic ACh R
Many individuals can develop an allergy to Rivastigmine - why?
As a patch, the adhesive material may cause the patient to break out in urticarial rash
Does Donepezil alter the course of the disease?
Does not alter course
- may slow disease progression.
When used in combination with Memantine, may improve brain functioning overall.**
Memantine is usually not a first-line agent because it increases the problem of:
What should be the main thing we first do when interviewing a patient with dementia?
- drug/med review
There are various etiologies as to why the thyroid dysfunctions (primary, secondary, tertiary) - What are they? Even though according to Chamberlain - it doesn’t matter - if hypothyroid, you replace. Period.
Primary - Autoimmune OR malnutrition and deficient iodine intake
Secondary - Pituitary dysfunction
Tertiary - Hypothalamic dysfunction
Infants that have hypothyroidism that goes unrecognized and therefore untreated will develop this condition
- severely stunted physical and mental growth
- high risk in maternal hypothyroidism
This drug is synthetic T4 that replaces normal levels of T4 and T3 - 70% is absorbed PO with slow onset of action - with a week long half-life, 1x/day dosing is preferred. It takes approx 6-8 weeks for it to achieve steady state in the body. Which drug is this mainstay of hypothyroid treatment?
Levothyroxine / Synthroid
can also be used for TSH suppression in
- thyroid nodule
- thyroid cancer
Where does T4 convert to T3?
in the periphery
Long term elevation of serum T4 may accelerate which two diseases?
What are common side effects of levothyroxine?
- hold or reduce dose if any complaints of angina*
In patients with Addison’s disease AND HYPOthyroidism, thyroid replacement without first replacing cortisol can be..?
SSX of Addison’s
- bronze pigmentation
- orthostatic HYPO-TN
- decreased Na, increased K (serum)
this thyroid hormone from desiccated animal (porcine) thyroid gland works by replacing BOTH T4 and T3. It’s taken PO and standardized to contain 0.2% iodine, 38 mcg T4 and 9mcg T3 for each 60mg dose. Which drug is this and how does it compare to synthroid?
Thyroid USP / Armour
60mg Armour = 100mcg Synthroid
when do you need to be more cautious in prescribing Armour?
in patients > 65 years
Hx of Cardiac Dz
*hold or reduce dose if any complaints of angina
This thyroid replacement is synthetic T3, ie replaces T3 - indicated in pts who have hypothyroid and have demonstrated intolerance or NO improvement with T4 replacement. It’s taken PO with 100% absorption, rapid onset and a half-life of several hours. Also indicated in MYXEDEMA coma and Wilson’s syndrome (not a recognized medical dx). Which medication is this? And what two diseases may it increase risk of?
Liothyronine / Cytomel
- similar SE to T4 replacement
MAY INCREASE RISK OF
- CAD* and
How do these thyroid medications square up to one another?
60 mg of thyroid USP/Armour is equivalent to how much Synthroid and how much Cytomel?
60 mg Thyroid USP =
100 mcg Synthroid (T4) =
25 mcg Cytomel (T3)
excess administration of thyroid hormone - either inadvertent or intentional can result in a hyperthyroid state - what is this otherwise called/
- heat intolerance
Hyperthyroidism places patients at increase risk for which two conditions?
this is a term used to describe lesions of non-pitting edema that occur in grave’s disease - they appear MC on the anterior or lateral aspects of the legs (but could appear ANYWHERE on the body) in about 5% of Grave’s patients and result from deposition of hyaluronic acid
- theory: stimulated fibroblasts produced too much glycoaminoglycan due to increased thyroid hormones
these are often used to block the adrenergic ssx of hyperthyroid - what drug class is this?
what does definitive treatment of hyperthyroid involve?
radioactive iodine ablation
- majority post-tx are rendered hypothyroid and therefore require LIFELONG thyroid hormone replacement
this thioamide inhibits transformation of inorganic iodine to organic iodine and therefore blocks production of tyroxine while inhibiting iodotyrosine coupling which prevents conversion of T3 to T4 - minimal blocking effect of T4 to T3 seen in the periphery. It’s given either PO or IV - with PO dosing it may take days to weeks to achieve therapeutic state - it is indicated for temporary (6-12mos) hyperthyroid control while more definitive therapy is decided. Which drug is this?
Methimazole / Tapazole
When administered IV, these drugs are effective in treating thyroid storm
Methimazole / Tapazole
What is a feared side effect of Methimazole / Tapazole AND Propylthiouracil (PTU)? Are they safe in pregnancy?
Agranulocytosis* feared SE
- rash, edema, arthralgias
Methimazole - NOT GIVEN DURING PREGNANCY
- can cross placenta and into mother’s milk*
Propylthiouracil (PTU) is ok’d for pregnancy
This is given to women with hyperthyroidism during pregnancy, even though it’s a Category D drug.
- crosses placenta, but less readily than Methimazole
- NOT secreted in breast milk
Methimazole is 10X more potent than Propylthiouracil, but readily crosses placenta
This thioamide inhibits transformation of inorganic iodine to organic iodine, blocking thyroxine production and inhibiting the coupling of iodotyrosine preventing T4 and T3 with a NOTABLE effect in BLOCKING PERIPHERAL conversion of T4 to T3. Commonly used prior to surgical treatment or radioactive ablation - which medication is this?
this non-selective beta blocker blocks the adrenergic symptoms of hyperthyroid (tachycardia, anxiety, etc) - it’s also emerging as a treatment for thyroid storm - what is this?
Propanolol / Inderal
- could cause impotency, depression, fatigue and sedation
This is used under the assumption that in large doses it can inhibit the release of thyroxine from the thyroid gland and therefore work in hyperthyroidism and thyroid storm - given PO or IV - it’s given short term because the beneficial effects generally don’t last longer than 2-3 weeks as the thyroid gland appears to adapt and resume thyroxine secretion - what is this hyperthyroid medication and what form is it generally given in?
Iodine / SSKI
given in the form of
supersaturated potassium iodide (SSKI)
this is utilized for the definitive treatment of hyperthyroidism and in select cases of thyroid cancer - what is this drug that appears to have minimal side effects except maybe a sore throat for a couple days and salivary gland swelling believed to resolve by sucking on hard candies?
radioactive iodine (131 Iodine)
- the thyroid gland absorbs nearly all iodine absorbed by the body, therefore SE are minimal and the actual radioactive thyroid is gone in 3-5 days, with ablative effects lasting several weeks.
Is there evidence for increased risk of malignancy in the thyroid gland or other head and neck structures with radioactive iodine?
prior to tx, pts need to be rendered euthyroid by anti-thyroid drugs and or SSKI
is radioactive iodine ok in pregnancy?
DO NOT USE IN PREGNANCY
- can IRREVERSIBLY damage the fetal thyroid tissue
- can cross into breast milk*
DELAY PREGNANCY until AT LEAST 6-12 mo post I-131 tx.
Treatment exposes ovaries to radiation
how does radioactive iodine seem to work?
radioactive emission of BETA particles destroys the tissue of the thyroid.
- generally dissolved in water and gulped down. Cheers!
for males who are intending to undergo several doses of radioactive iodine treatment for thyroid cancer - what will we need to consider?
- men who receive RAI treatment for thyroid cancer may have decreased sperm counts causing approx. 2 years of temporary infertility
This is the most severe potential manifestation of hyperthyroidism - it includes high fever, irritability, delirium, vomiting, diarrhea, dehydration, HYPO-TN and vascular collapse - in severe cases, coma and death may occur - what is this?
- hyperthyroid pts who become septic
- if euthyroid hasn’t been achieved prior to surgery
How do you treat thyroid storm?
Stabilize Patient and administer:
- IV Beta blocker (propranolol)
- IV PTU or Methimazole and
- IV iodine - stun’s gland’s ability to use iodine for thyroid hormone synthesis
Any of these 4 lab values can indicate diabetes - what are they and what are their confirmatory numbers for diabetes diagnosis?
Fasting Glucose - > 126 mg/dL
2hr oral glucose tolerance test > 200 mg/dL
Random glucose > 200 mg/dL
HbA1c > 6.5%
These two antibodies are generally present in patients with type I diabetes
anti-islet cell antibodies
glutamic acid decarboxylase antibodies
These are used in the early diagnosis of type I diabetes, and also to help differentiate type 1.5 from type 2 - what are they?
- persons with type 1.5 diabetes may test pos for insulin antibodies - type 2 rarely do.
These are often measured instead of insulin levels to differentiate type I and type II diabetes - this is because insulin concentrations in the peripheral circulation are 2-10X lower in the portal vein, whereas this other measure is more indicative of endogenous insulin production - what is this?
- made when pro-insulin splits to insulin and c-peptide (1:1)
Type I DM has low insulin, therefore low C-peptide
Type II DM, high C-peptide
what are usually absent in patients with type 2 diabetes?
anti-islet cell antibodies
- gen. due to insulin resistance and often associated with obesity.
- age of onset > 30 (exceptions, as always)
if your twin has it? You’ve got good odds - 90-100% concordance
Type 1.5 Diabetes - what will show up on lab study?
POSITIVE for anti-islet cell antibodies
similar to type 2, due to the insulin resistance picture.
BUT not as severely resistant.
Expert committee does not recognize type 1.5 to be different from type 1, autoimmune diabetes -
beta cell destruction is still happening, just at a much slower rate - lifestyle will make a difference, but only for a moment - insulin will be needed at some point.
latent onset adult diabetes (LADA) is another name for what?
type 1.5 diabetes
In a patient previously diagnosed with type 2 diabetes who is demonstrating a rapid deterioration of glucose control while taking oral medication that was previously working should have what as their working diagnosis?
type 1.5 diabetes
When someone undergoes surgery, there is something other than antibiotics that proves to be more efficacious in preventing infection - what is this? how is it controlled?
tight glycemic control
- patients on oral diabetic medications are switched to insulin prior to ANY surgery requiring no oral intake (NPO)
What is the standard of care when treating a woman with type 2 diabetes who becomes pregnant or a woman who develops gestational diabetes during her pregnancy?
- achieves tighter glucose control
- diminished risk of developing MACROSOMIA (big babies!) often associated with oral DM meds
This is increased in the last few months of pregnancy (third trimester) that can act to decrease sensitivity of the insulin receptor - what is this and how do we treat during pregnancy?
Human Placental Lactogen (HPL)
treat with insulin
this medication works by decreasing hepatic glucose production and slightly enhances insulin sensitivity in skeletal muscles - it’s the single member of the biguanide class that is currently approved in the US - with BID dosing PO daily - what is this medication?
Metformin / Glucophage
- when used alone, generally does NOT cause hypoglycemia
What pregnancy category is metformin / glucophage
unlike sulfonylureas, Metformin can cause a patient to experience what?
a modest reduction of weight (4-7 lbs)
- rather than weight gain experienced with the sulfonylureas
What are the most commonly noted complaints by patients taking Metformin? (3)
- abdominal cramping
(both of which can be reduced by using extended/slow release forms)
- metallic taste is also a common SE
Patients taking Metforming have an increased risk for what vitamin deficiency?
Vitamin B12 deficiency
- supplementation with a B-complex should be standard of care
what is the most serious side effect associated with Metformin?
- RARE but, can be fatal
This risk is markedly diminished by not using Metformin in patients with impaired renal function
discontinuing ETOH consumption
Metformin should not be started, or if started - should be stopped immediately in patients with what? What else increases the risk of this?
- procedures such as major surgery or the use of an iodinated contrast material can also increase the risk for renal insufficiency **
This class of medications stimulates intact beta cells of the pancreas to release more insulin (“like whipping a lame horse”) by partially blocking the ATP-sensitive potassium channels in the beta cell membrane, calcium release is prolonged and more insulin is released - used since the 1950s - what are these?
Cat C for Pregnancy
There are 3 (ish) generations of sulfonylureas - name them. 1st gen (2), 2nd gen (3), 3rd gen (1).
Chlorpropamide / Diabinese
Tolbutamide / Orinase
Glipizide / Glucotrol
Glyburide / Micronase
Glimepiride* / Amaryl
Glimepiride* / Amaryl
what is the most commonly noted side effect of sulfonylureas?
- increased risk of cardiovascular mortality is also associated with the sulfonylureas
which of the sulfonylureas appears to cause a greater incidence of hypoglycemia?
Gyburide / Glucotrol
All women with type 2 diabetes who become pregnant should be advised to not take a sulfonylurea drug during pregnancy nor during lactation - why?
sulfonylureas have been shown to cause this due to hyper-insulinemia which increases fetal extraction of oxygen from the fetal blood beyond which the placenta cannot replace it quick enough.
let’s drive this one home, shall we? for women who are pregnant, for someone with hepatic and/or renal failure - how would we them if they are diabetic?
As type 2 diabetes progresses, total beta cell function generally declines - therefore, as a general rule - all of the sulfonylureas become ineffective after how long? Who can’t take this medication?
5-10 years of use
ALL sulfonylureas should be AVOIDED in patients with a known SULFA allergy
- ineffective in type 1 diabetic patients and post-pancreatectomy
This is a drug class that stimulates the beta cells to release insulin by also binding the ATP sensitive potassium channels, however it’s chemically unrelated to the sulfonylureas, making them the non-sulfonylurea secretagogues. They’re great for those with sulfa-allergies, however they require a 3-4 x a day dosing regime so compliance is for sure - an issue - which class is this
- must be taken 30 minutes before any meal
Nateglinide / Starlix (less effective)
Repaglinide / Prandin
- cause weight gain and hypoglycemia
meglitinides are ok’d for combination therapy with metformin or any drug from the glitazone class, but they are STRONGLY contraindicated with this class - why?
AVOID combined use with SULFONYLUREA due to increased risk for
(they both work through same MOA)
These improve insulin sensitivity in skeletal muscle cells, fat cells and liver cells while also decreasing hepatic glucose production - they may take 6-14 weeks to achieve max effect - which drug class is this?
Thiazolidinedione’s / Glitazones
- much more expensive than sulfonylureas
Rosiglitazone / Avandia
Pioglitazone / ACTOS
which glitazone is approved for concurrent use with insulin?
Pioglitazone / ACTOS
both avandia and actos of the glitazones increase the risk of what?
Congestive Heart Failure (CHF)
- reduced bone density
- increased incidence of bone fracture
- WEIGHT GAIN 5-10 lbs
**MUST CHECK LFTs before initiating tx!
This class of medications is used to lower postprandial glucose levels when taken with every meal - by inhibiting this specific enzyme, this class interferes with - carbohydrate hydrolysis - delaying absorption of glucose and other monosaccharides what enzyme is this, effectively naming the drug class
when given with:
- sulfonylurea or
- insulin - INCREASED RISK FOR HYPOGLYCEMIA*
What side effects do we need to be aware of when prescribing alpha-glucosidase inhibitors? What pregnancy category are Acarbose and Miglitol?
- unabsorbed carbs cause fermentation and osmotic effects.
- C/I in patients with chronic intestinal diseases (IBD, ulcer, intestinal obstruction)
Categorty B - Pregnancy (but don’t forget, we use insulin in pregnancy)
In high doses, Acarbose has been associated with moderate elevations in what?
- rare reports of fatal hepatic failure
in the event of hypoglycemia - oral treatment of patients taking an alpha-glucosidase inhibitor must be with what? what?
instead of sucrose
- bc the inhibitors interfere with breakdown of sucrose
these drugs inhibit the enzyme responsible for breaking down incretins that are release after a meal - meaning in the peripheral circulation the inactivation of glucagon-like peptide 1 (GLP-1) is prevented which augments insulin secretion
Dipeptidyl peptidase-4 (DPP-4) inhibitors
*GLP-1 is a potent anti-hyperglycemic hormone
also inhibits GIP (glucose dependent insuliotropic polypeptide)
When DPP-4 inhibitors act they increase circulating levels of GLP-1 which results in what two things?
increased insulin secretion
inhibited glucagon secretion (reduces hepatic production of glucose)
Sitagliptin / Januvia is a DPP-4 inhibitor, it is approved for use in treatment of type 2 diabetes as monotherapy, or in combination with what (3)?
approved for combination therapy with
NOT APPROVED FOR USE WITH INSULIN*
both DPP-4 inhibiting drugs sitagliptin / januvia and Janumet have been linked to increased incidence of what?
increased risk of pancreatic cancer
within 10 years of treatment, approximately 75% of diabetic patients will require what?
- start with metformin, if that doesn’t work add sulfonylurea then insulin.
used alone, oral hypoglycemic drugs can lower glycosylated hemoglobin (HbA1c) by how much?
this is a synthetic injectable form of the hormone amylin - which is produced with insulin in the beta cells of the pancreas and it plays a regulatory role in slowing gastric emptying and promoting satiety which helps prevent post-prandial spikes in blood glucose. it can be used for BOTH type 1 and type 2 diabetics - which drug is this?
Pramlintide / Symlin
apart from insulin analogs, this medication is notable for being the ONLY drug to gain FDA approval for lowering blood sugar in Type 1 Diabetics since insulin was initially developed in the early 1920s. What drug is this and can it be used in combination with insulin?
Pramlintide / Symlin
because of chemical differences - symlin and insulin cannot be combined in the same vial or syringe, must be injected separately, but can be used together.
injection of this at meal time has been shown to improve A1c without causing hypoglycemia or weight gain - it may actually promote modest weight loss. But may cause nausea as initial dosing is adjusted.
Pramlintide / Symlin
- approved for Type 1 diabetics not achieving goal A1c
- approved for Type 2 diabetics who are using insulin, but still not achieving goal A1c level
This new diabetes medication is an incretin mimetic developed for Type 2 diabetes. Injected at meal time, it lowers blood glucose levels by increasing secretion of endogenous insulin - with no increased risk of hypoglycemia (unless used in combo with sulfonylurea), it’s primary side effect is nausea that gets better over time - what is this drug?
Exenatide / Byetta
- approved for type 2 diabetics not achieving goal A1c using metformin, sulfonylurea or a combo of the two.
What is the role of anabolic insulin in the body?
increased synthesis of
reduced degradation of these products as well.
- initiates DNA synthesis in some cells, initiating growth and differentiation
What is insulin derived from?
- produced in beta cells of the pancreas
The following blood markers describes what condition?
- HTN > 130/85
- Serum glucose > 110 mg/dl
- serum TGs > 150 mg/dl
- serum HDL: < 40 mg/dl (M); < 50 mg/dl (F)
- waist circumference
> 40 in males
> 35 in females
this therapy is required for survival of ALL type 1 diabetics - what is it?
- inhibits fat breakdown in adipose
- promotes TG storage
what is the half-life of insulin in the serum?
- peptide hormone, CANNOT be taken orally
- ADMIN SQ, IM, IV; new nasal delivery too
one unit of insulin is defined as - the amount required to what?
reduce blood glucose concentration in a fasting rabbit to 45 mg/dl (2.5mM)
Insulin preparations are divided into 4 categories
- long acting
Match the following to it’s proper category
- regular/humulin R
- NPH /humulin N
(onset:peak:duration - in hours)
- rapid - Lispro (.25:.5-1.5:3-5)
- short - Regular (.5-1:2-4:4-6)
- intermediate - NPH (1-3:6-10:12-18)
- long acting - Glargine (4-6:flat:24)
what is a typical, initial dose of insulin? and what is a common side effect reported after initiation of insulin therapy?
0.4-0.6 units/kg/day of regular insulin
SE: Weight Gain
What are the three potential outcomes of insulin therapy that are not intentional?
- hypokalemia (can occur post-admin due to increased K+ entry into the cell)
- fibrosis of injection sites
- muscle or fat atrophy at injection site
What the mnemonic for Hyperkalemia treatment? EVERY DOCTOR SHOULD KNOW THIS
C - check EKG, if changes use Ca gluconate IV
B - Bicarbonate / beta agonists
I - insulin
G - dextrose
K - kayexalate (if total body K is an issue)
D - hemodialysis for refractory hyperkalemia
This measure, the gold standard for diagnosis of osteoporosis, compares the patient to the population and predicts fracture risk: for every -1 SD the fracture risk doubles - what is this and what are the diagnostic numbers for osteopenia and osteoporosis
T-score (decreases by -1 for approx 10% bone loss)
T > -1 = normal
T -2.5 to -1 = osteopenia
T < -2.5 = osteoporosis
As it continues to become more negative, bone fragility/fracture risks = SEVERE osteoporosis
this is the standard devision from normal for the patient’s age group - although it is of limited benefit in terms of prognosis and clinical benefit - it’s on the DEXA - what is it?
what is the standard recommended amount of daily calcium intaking for individuals < 50 years of age? over the age of 50?
< 50 rec: 1000 mg/day
> 50 rec: 1200-1500
what is the best form of calcium?
Calcium Citrate could be better absorbed
- however, no consensus.
if from oyster shell?
- risk lead contamination
this is essential for absorbing calcium in the gut and maintaining adequate serum calcium levels as well as phosphate concentrations. It’s needed for bone growth, bone remodeling and it’s recommend daily amount has now doubled according to the American Academy of Pediatrics - what is this?
Not active until it undergoes conversion in the liver AND kidney
- 25(OH)D - calcidiol = active
for mom’s who are breastfeeding, how much vitamin D is recommended they supplement for their infant?
for breastfed and partially breastfed children
- maternal deficiency accounts for this recommendation.
this is a prescription form of vitamin D that can increase bone mass and decrease the rate of spinal fractures, however, it does increase risk of hypercalcemia, requiring frequent monitoring of patients receiving this medication - what is it?
Calcitriol / Rocaltrol
- activated Vitamin D
This supplement appears to assist in diminishing bone loss - when given with both Calcium and Vitamin D - excess intake can cause loose stool - what is this?
this element appears to improve osteoblastic activity - when combined with ranelic acid - it has been found to increase bone denisity and aid in bone growth, reducing vertebral, peripheral and hip fractures. There are two proposed mechanisms in which it works:
1 - incorporated into hydroxyapatite, where it remains for years/decades
2 - binding to the surfance of hydroxyapatite to stimulate bone formation, inhibit resorption and increase BMD.
What is this magical supplement and how much do you give for prevention vs treatment of osteoporosis?
Strontium / Strontium ranelate
- 1 gm/day to prevent osteo
- 2 gm/day to tx existing osteo
- ** ANYTHING > 2 GM/DAY MAY WEAKEN BONE ***
- could replace too much calcium in the hydroxyapatite crystal lattice
this drug class acts to inhibit osteoclast activity by encouraging apoptosis of osteoclasts OR slowing bone loss, in those who’ve experienced fracture in the past, this class reduces risk of future fracture (this is not true if the person has never had osteoporotic fracture previously). They commonly cause upset stomach and esophageal inflammation/erosion, this can be prevented by remaining upright (standing is best) for 30-60 minutes after taking medication PO - what class is this osteoporosis medication?
- 0.6-0.7% bioavailability when fasting. Ensure taken on empty stomach to avoid reducing that number even further (50% of that binds to bone, remaining excretes unchanged via kidney)
- patients who cannot follow the standing protocol should not take this medication*
this was the first FDA approved IV drug treatment for osteoporosis in post-menopausal women - a new formulation of an older drug - it’s given q3mo - what is this?
Ibandronate / Boniva
this bisphosphonate is used for both prevention and treatment of osteoporosis - it works by inhibiting osteoclast activity - taken PO, it’s 1000 times stronger than the equimolar effect of the first drug in its class, Etidronate - it works most optimally if combined with calcium and vitamin D (to promote normal bone development) - SE include erosive esophagitis, atypical femur fractures and rarely, osteonecrosis of the jaw - what drug is this?
Aldendronate / Fosamax
- recommended to be taken with 6-8 oz water, while remaining upright for 30 minutes after PO consumption
- If high risk for fracture - staying on fosamax x10yrs is of benefit
this selective estrogen receptor modulator (SERM) binds to specific E sites to promote E’s beneficial bone and lipid activity, but reduce E’s effect on endometrial and breast tissue - effectively increasing bone mass and reducing vertebral fracture risk while also reducing the incidence of breast cancer in post-menopausal women
- it’s taken PO 1x/day - what medication is this?
Raloxifene / Evista
- CI in pregnant/lactating women with PMHx of venous thromboembolic events*
hot flashes, arthralgias, myalgias, edemas, pruritis, DVT
What is a major adverse effect of Tamoxifen?
These are all greater in tamoxifen when compared to raloxifene*
On Sept. 14, 2007 the FDA approved this drug to reduce risk of invasive breast cancer in both post-menopausal women with osteoporosis OR with high risk for invasive breast cancer
Raloxifene / Evista
This is a synthetic hormone used to mimic a naturally occurring hormone produced by the parafollicular C cells of the thyroid gland that helps regulate calcium and bone metabolism by diminishing osteoclast activity - reducing the risk of spinal fractures and maybe hip fractures. This medication is used for TX of osteoporosis by inhibiting osteoclastic activity - given as a nasal spray (sometimes IV) - what is this?
calcitonin / miacalcin
- SE: nose bleed, sinusitis (with nasal spray)
this PTH analogue made from selected amino acids found in parathyroid hormone activates bone turnover by binding and stimulating osteoblasts to produce RANKL (and decrease expression of osteoprotegerin (OPG)) which indirectly stimulates osteoclasts - allowing for new bone formation in both spine and hip - significantly lowering risk of fracture and increasing bone mineral density. What is this medication that is administered SQ q24hr
Teriparatide / Forteo
- reduces risk of vertebral and nonvertebral fractures in post-meno women
- chronic exp. to PTH depletes bone stores by constantly stimulating bone turnover - causing osteoporosis, whereas intermittent exposure activates osteoblasts more than clasts - allowing for new bone formation
When taken alone, this can increase a woman’s risk for developing ENDOMETRIAL CANCER - what it is?
Estrogen / HRT / PREMARIN
vaginal bleeding, breast tenderness, clots, increase risk for GALL BLADDER DZ
A post-menopausal woman comes into your office, she still has her uterus and has osteoporosis - you give her estrogen (premarin), right?
Unopposed estrogen with a uterus increases risk of endometrial cancer. You’re an astute doctor and you would never do this to your patient.
Instead - you give estrogen in combination with progestin (PREMPRO)
- well done, doc!
the women’s health initiative, a large government-funded research study, demostrated that HRT with Prempro was associated with a modest, but definite increase in what? (3)
Prempro associated with increased risk of
- breast cancer
A large study from the National Cancer Institute indicated that long-term use of Estrogen therapy may be associated with what?
increased risk of OVARIAN CANCER
- safe to assume we only prescribe this in the shortest time frame possible
- ANY ET/HRT regimen should ONLY be considered if women is at SIGNIFICANT RISK of OSTEOPOROSIS
T/F - transdermal estrogens affect clotting in the same manner as oral
- transdermal does not affect clotting due to direct absorption into systemic circulation, avoiding first pass metabolism in the liver which is thought to cause subsequent changes to the molecule which promotes thrombolic events
- esterified estrogens or topical admin may reduce risk of blood clotting compare to oral conjugated equine estrogens (CEE)
this human monoclonal antibody approved by the FDA for treatment of osteoporosis (bone mets, RA, MM and giant cell bone tumors) by targeting RANKL - a protein produced by osteoblasts to promote maturation of pre-osteoclasts to osteoclasts - this medication inhibits this maturation countering osteoporosis - administered SQ q6mo - what is it?
Denosumab / Prolia
Known to increase susceptibility to infection
URI, UTI, cataract, constipation, rash, jt pain
many drugs prevent osteoporosis such as:
- raloxifene, premarin, eterified estratab, menet, estradiol estrace, estropipateOrtho-est, ogen, premphase (cyclic and continuous)
However, only a few TREAT (and therefore, are the ones our brains can retain) what are the three known treatment options for osteoporosis? And which one does both, prevents and treats?
Alendronate/Fosamax (TX and PX - PO)
Calcitonin/Miacalcin (TX - nasal)
Calcimar (TX - IM)
which form of endogenous estrogen is most potent in women?
- estrone is 1/10 the potency
- estriol is 1/4 potency of estradiol and estrone
(don’t ask me how this math pans out - it’s on the slides)
What is the most important therapeutic benefit of HRT? Are there side effects with this therapy?
estrogen decreases resorption of bone and therefore blunts osteoporotic process occurring with menopause
sadly - it comes with mass side effects increasing risk of - stroke - blood clots - endometrial cancer - ovarian cancer - breast cancer
this form of injected birth control can reduce fertility for as long as 10 months once taken off, it’s administered q3 mo, with efficacy lasting up to 4 months. When combined with conjugated equine estrogens (Premarin) - it’s been associated with increased risk of Breast CA, dementia and THROMBUS IN THE EYE - if combined with Estrogens in general it could increase risk for CVD (much worse if those estrogens are equine) - not recommended prior to menarche or before/during surgery (mineralcorticoid effects could effect BP) - what is this?
Medroxyprogesterone Acetate / MPA
- based on women’s health initiative, CEE (equine) and MPA are no longer given to women to prevent CVD bc increases risk for:
MI, stroke, DVT, PE, Breast CA
- younger, postmenopausal women seeking relief from hot flashes are still candidates for HRT
These bio-identical hormone options come in two separate combinations
- BiEst and
what differentiates these two and which is used more commonly?
Estradiol (20%) - MC used
this, obtained from urine of a pregnant mare - undergoes LESS first pass hepatic metabolism - it is generally given to prevent and tx osteoporosis while alleviating hot flashes, vaginal dryness and itching experienced in menopause. It works by altering GENE TRANSCRIPTION, given orally or topically - what is this medication?
Conjugated Estrogens / Premarin
a preparation of conjugated estrogens
DO NOT GIVE UNOPPOSED IN WOMEN WITH A UTERUS*
what are the two main uses of progestins?
- prevent endometrial hyperplasia due to unopposed estrogen in HRT
8 TYPES OF PROGESTIN*
Which two classes of progestins exist, which is preferred - and what are they all a chemical derivative of?
chemical derivative of testosterone (19-nortestosterone) creating ANDROGENIC EFFECTS*
ESTRANE family (first gen) - norethindrone
- Second gen - Levonorgesterel/Norgestrel
- Third gen - **PREFERRED ** Desogestrel/Norgestimate **DUE TO reduced androgenic effects
this newly developed synthetic progestin is considered 4th generation due to it’s derivation from 17a-spironolactone - used to treat secondary amenorrhea, dysfunctional UB, and endometriosis while also creating palliative care for endometrial cancer, RCC, BC and prostate cancer - what is this
- pharmacologic profile deems it closest to natural progesterone when compared to other synthetics
HIGH RISK OF THROMBOLYSIS
this synthetic derivative of progesterone can be prescribed for contraception, but also for Male to Female gender affirming hormone therapy, it can be used in menopausal females to prevent endometrial hyperplasia and cancer.. and in men? Bad men - it can be used to chemically castrate convicted sex offenders - what is this drug?
Medroxyprogesterone / Provera
- increases risk of DVT
- C/I if PMHx DVT, breast or uterine CA
- Teratogenic if taken by pregnant women
- increases LDL:HDL ratio
- High doses for CA tx - Wt gain, FACIAL EDEMA, worsening DMII
what are the most commonly prescribed type of oral contraceptive? which component, when administered in a lower dose, is associated with less risk of thombosis?
MC prescribed are combination OCPs
- estrogen (suppresses ovulation, inhibits FSH)
- progestin (prevents implantation, makes impermeable cervical mucus)
lower doses of ETHINYL ESTRADIOL are associated with reduced risk of thombosis
ethinyl estradiol/norethindrone (femcon Fe) has the same active ingredients as Ovcon 35 - so what differentiates these two OCPs?
Ovcon 35 must be swallowed
Femcon Fe - spearmint flavored chewable with iron containing placebo pill
does the pill have potential to play a role in depression?
- estrogens and progestins have been shown to decrease serotonin in the brain by increasing the enz responsible for reducing serotonin
- progestin ONLY can worsen pre-existing depression
combined oral contraceptives are contraindicated in specific populations - list them (5)
- PMHx CVD
- FMHx clot forming dz (familial factor V Leiden)
- Obese women/hypercholesterolemia
- 35+ years
multiple drugs can reduce the efficacy of the pill when they are used in conjunction with oral contraceptives - which drugs should we be paying attention to and warning patients about?
- sulfa drugs
- seizure meds
- St. John’s Wort
use of oral contraceptives for 5+ years decreases risk of what by 50%?
combined oral contraceptives appear to reduce risk of what by 40% and risk of what else by 60%?
- ovarian cancer (40%)
- endometrial cancer (60%)
As duration increases, risk reduces more dramatically
greater than 10 years of use reduces both by 80%*
this synthetic progestin, closest in profile to natural progesterone - has anti-mineralcorticoid properties that counteract the estrogen-stimulated renin-angiostensin-aldosterone system and is NOT androgenic (due to derivation from spironolactone) which reduces water retention and bloating - what is this, what are it’s two forms and how do they differ?
Yaz and Yasmin*
both contain 3mg drospirenone, but
Yaz - 20 mcg ethinyl estradiol
Yasmin - 30 mcg ethinyl estradiol
**6-7x RISK of developing THROMBOEMBOLISM compared to no contraception, 2X RISK compared to Levonorgesterel
this is the first and only hormonal contraceptive that has been shown to be effective for TX of premenstrual dysphoric disorder - what is it?
this is a branded, progestogen-only contraceptive - with long acting, reversible hormonal contraception - injected every 3 months, with immediate protection from pregnancy after receiving each injection (if given within first 5 days of menstruating) - what is this?
Medroxyprogesterone acetate / Depo-Provera IM
high dose progestogens decrease GnRH release from hypothalamus, which decreases FSH and LH release from ant. pit.
SubQ form newly available - 31% less hormone than Depo, may have fewer progestin-related SEs, still new - who knows
Depo-SubQ Provera 104
Depo-Provera has been shown to reduce the risk of what by 80%?
- there is a noted delayed in return to fertility with this injection
9-10 months after last injection, by 18 mos fertility is same as prior to depo*
A study of accidental pregnancies in Thailand found that infants exposed to Depo-Provera during pregnancy had increased risk of what? (2)
increased risk of low birth weight (80%)
increase risk of death in first year of life
Depo-provera seems great due to no estrogen adn therefore not estrogenic effects, however - due to concerns of this - the FDA added an insert that recommends stop use at 2 years (unless no other viable alternative to contraception) - why?
increased risk of Osteoporosis
due to increased bone turnover
this is an implantable progestin only form of contraception - after 3 years it must be removed - what is this?
- in office procedure done with or without local anethesia
this contraceptive can be applied q7days x 3 weeks, with one week patch free, when started within 5 days of bleeding - it’s quite effective. However, this is not an effective method if the female is > 198 LBS* - what is this form of birth control and what does it consist of?
Ortho Evra patch
- 150mcg norelgestromin
- 20mcg ethinyl estradiol
if patch-free interval exceeds 48hrs, need to R/O pregnancy before re-applying
- patches should be rotated to avoid skin irritation
- higher dose of estrogen, therefore a package insert that warms of 2x increased risk of blood clot (this is debated since it avoids first pass metab)
this hormonal contraceptive ring made of flexible plastic has both progestin and estrogen, it is efficacy is reduced if expelled or left outside the vagina x 3 hours. it can be rinsed off and re-inserted, however if > 3 hour absence, backup contraception should be used x 7days - what is this?
- WEIGHT GAIN
although MOA for this IU is unknown, copper has been shown to impair sperm mobility - while additionally promoting low-grade inflammation of the uterine lining - reducing likelihood of implantation - approved for 10 years of continuous use - name that IUD!
ParaGard / Copper Containing IUD
Canada’s is better - FlexiT - imagine, hormone AND cramping free!
what is. the long-acting synthetic progestin that is used for the non-copper IUDs?
- diminishes frequency of ovulation
- changes consistency of cervical mucus
52mg levonorgestrel releasing approx 20mcg/day
there are 3 non-copper IUDs, what are they and what mcg amt of LNg do they release/day?
Mirena (52mgLNg) - 20mcg/day (approved x5 years)
Liletta (52mgLNg) - 20mcg/day (approved x5 years)
Skyla (13.5mgLNg) - 14mcg/day (approved x3 years)
5 year pregnancy rate is 0.7%
this is a selective progesterone receptor modulator (SPRM) used for emergency contraception - in the US it’s approved for 72 hours post-intercourse, but according to the WHO - it can be effective up to 5 days post-intercourse - preventing pregnancy by delating or inhibiting ovulation and inhibiting follicle rupture - with 60% prevention of expected pregnancies - name that morning after pill!
- NOT an abortifacient
If someone is in a real bind - can take regular combination BCPs after intercourse
4 Ovral pills
2 taken q12hr x 2 doses
this is a synthetic steroid compound acting as a progestin antagonist (blockage of the progesterone Rs stops sustainment of the endometrium for implantation, reduces HCG levels and reduces progesterone production from corpus luteum) with partial agonist activity - used as an abortifacient in the first 2 months of pregnancy for chemical abortion - what is it?
Mifepristone / Mifeprex
- followed by Misoprostol
a prostaglandin E1 analog
to reduce dosage (makes 200mg efficacious)
this is helpful in medical abortions but also commonly used for inducing labor - what is this prostaglandin E1 analog?
- causes uterine contractions and ripens cervix
- can also be used in conjunction with oxytocin, which helps induce labor, but only if cervix is ripen (ie thinned)
can you use Mifepristone in the presence of an IUD?
C/I for IUD, ectopic pregnancy (SURGICAL, ALWAYS), PMHx of hemorrhagic disorders, anticoagulants (damn, WARFARIN), long term prednisone
nearly all women experience abd. pain, uterine cramping and vaginal bleeding for 9-16 days on avg
this selective estrogen receptor modulator (SERM) binds estrogen receptor sites in the BRAIN and interferes with negative feedback of E on GnRH, allowing for increased secretion of GnRH which increases FSH and LH stimulation on ovulation - given PO, this drug has the known potential risk (or therapeutic benefit) of multiple births - what is it?
Clomiphene / Clomid
if PMHx of LV disease, breast or uterine cancer - ContraIndicated*
what enzyme activates testosterone and what is this active form called?
watch out, boys
- falling in love decreases testosterone in men, increases it in women
What are the androgenic effects of testosterone?(5)
- development of male genitalia
- secondary sex characteristics
- sperm production
what are the anabolic effects of testosterone?
- protein metabolism
- dev. and preservation of muscle mass, bone mass, bone strength
- increases RBC production (which may increase blood viscosity, ischemia for the win!)
exogenous administration of. testosterone is in which condition?
- inadequate testosterone production
also used in conjuction with other hormones to tx pre-pubertal boys with
testosterone is generally administered via gel patch or IM injection - older testosterone preparations were taken orally but found to increase risk of what?
what’s the concern with testosterone administration?
increased risk of prostatic hyperplasia and or prostatic cancer is an issue that is questioned by some researchers and physicians.
what is the term for “erection lasting longer than 4 hours” - the standard disclaimer on almost all viagra commercials..
ironically, testosterone, used to help with infertility - has the adverse effect of?
lowered sperm count
- but damn, you can sure feel manly with those big muscles and atrophied testes
this androgenic hormone alters gene transcription (as all hormones do), MC given as a gel patch replaced daily and indicated for: for refractory anemia, severe osteoporosis and severe wasting conditions such as AIDS and cancer - due to it’s muscle building capability (also why it’s so commonly abused) - what is this?
when given IM
this anti-androgen, anti-estrogenic hormone is a synthetic analog of GnRH interrupting production of both T and E - it is use MC in prostate cancer, but also precocious puberty, endometriosis, uterine fibroids and some IVF protocols - what is this preparation which is given either SQ or IM?
Leuprolide / Lupron
SE decreased libido impotence N/V hot flashes, night sweats osteoporosis arthr-my-algias
this anti-androgen limits conversion of testosterone to dihydrotestosterone by inhibiting type II 5-alpha reductase - indicated for BPH, but can also be used for male pattern baldness (low dose) or prostate cancer (high dose) - taken PO - what is it?
Finasteride / Proscar
Propecia when used for hair loss (most successful in crown area for regrowth)
TERATOGENIC! WOMEN SHOULD NEITHER TAKE NOR HANDLE WHEN PREGNANT
what are commonly used as initial therapy for men with BPH?
(alpha 1 receptor antagonists)
SE - ORTHOstatic HYPO-TN, nasal congestion
these help maintain an erection by blocking the degradative action of an enzyme responsible for degrading cGMP in the corpus cavernosum therefore allowing for blood vessel relaxation and filling of the corpus cavernosum. ONLY USEFUL IN THE PRESENCE OF NO (and therefore concomitant use of nitrates while using this medication is CI) What class is this and what’s the most common medication in this class?
phosphodiesterase type 5 (PDE5) inhibitors
Sildenafil Citrate / VIAGRA
PDE5 is also present in the smooth muscle of the arterial wall making these a pristine TX for
What is cyanopsia?
seeing everything in the visual field as being tinted blue
side effect of viagra as are:
- nasal decongestant
- acute angle closure glaucoma
- MI, stroke, PRIAPISM