Exam III Flashcards
The formal diagnosis of dementia generally requires ssx be present for how long? What concomitant sx are common with dementia?
6 mos
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?
Vitamin E
- THROMBOSIS potential at 2000IU dose
combination therapy with estrogen and progesterone could increase risk of what?
Alzheimer’s disease
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
- alpha-synuclein
- 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?
DLB
- 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?
Memantine
- 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
HEPATOTOXIC
- 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
D: AChE
R: Butyrylcholinesterase
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?
parasympathetic effects
- 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
- DLB
- 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?
Autism
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?
butyrylcholinesterase inhibition
- 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?
glutamatergic neurotransmission
- 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:
confusion
What should be the main thing we first do when interviewing a patient with dementia?
polypharmacy
- 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
Cretinism
- 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?
cardiac disease
osteoporosis
What are common side effects of levothyroxine?
Palpitations
Tachycardia
Heat intolerance
Anxiety
- 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..?
FATAL
SSX of Addison’s
- hypoglycemia
- bronze pigmentation
- FATIGUE
- 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
- Osteoporosis
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/
thyroiditis facticia
- heat intolerance
- exophthalmos
- anxiety
Hyperthyroidism places patients at increase risk for which two conditions?
Osteoporosis
Cardiac disease
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
Pretibial myxedema
more appropriately
“thyroid dermopathy”
- 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?
beta blockers
what does definitive treatment of hyperthyroid involve?
surgical removal
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
Propylthiouracil (PTU)
What is a feared side effect of Methimazole / Tapazole AND Propylthiouracil (PTU)? Are they safe in pregnancy?
Agranulocytosis* feared SE
other SE’s:
- hypothyroid
- 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.
Propylthiouracil (PTU)
- 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?
Propylthiouracil (PTU)
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?
Nope.
prior to tx, pts need to be rendered euthyroid by anti-thyroid drugs and or SSKI
is radioactive iodine ok in pregnancy?
Nope.
Category X
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?
sperm banking
- 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?
THYROID STORM
AT RISK:
- 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?
insulin antibodies
- 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?
c-peptide (connecting)
- 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?
INSULIN*
- 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
