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What class of drugs is first line for depression and anxiety in dementia patients?
Use this antipsychotic in treatment refractory patients
This med has the most prolactin elevation of any antipsychotic
Which antipsychotic causes potentially fatal agranulocytosis?
What is the overall cause of Parkinson's Disease?
Destruction of dopamine neurons in the substantia nigra
Which pathway is more active in Parkinson's?
The indirect pathway. It inhibits movement.
What effect does decreased dopamine have on gutamate and movement?
Decr dopamine = decr direct pathway = decr glutamate = decr stimulation of cortex = decr facilitation of movement = incr indirect pathway = decr glutamate = incr inhibition of movement
What are the 4 cardinal symptoms of Parkinson's?
probable diagnosis if 2 of the 4
- resting tremor
- postural imbalance
AEs of selegiline
worsens existing psychosis and dyskinesias
Can COMT inhibitors be used as monotherapy in PD?
- mad as a hatter
- blind as a bat
- hot as a hare
- dry as a bone
- red as a beet
What is the major advantage of amantadine?
suppresses levodopa induced dyskinesias
Initial treatment of Parkinson's should be with these agents (top 3)
- DA agonist
Adjunctive treatment for wearing off of L-dopa in PD
- COMT inhibitors
- MAOB inhibitors
- DA agonists
Which type of seizures are bilaterally symmetrical and without local onset?
- Includes: Grand mal, Absence, etc
Which type of seizures begin locally?
- Partial, or focal.
- Can be simple (no loss of consciousness) or complex (impaired consciousness).
Which med is best for absence seizures?
Ethosuximide because it is the narrowest-spectrum
Narrow-spectrum antiepileptic meds should be limited to use in what type of epilepsy?
Focal epilepsy with partial and secondarily generalized seizures
Which AED can cause dose-related thrombocytopenia?
Which AEDs cause decreased bone density?
Phenobarb and phenytoin
What are some main SEs of CBZ?
- bone marrow suppression (decreased WBC count)
Which AEDs cause hyponatremia?
CBZ and oxcarbazepine
What meds can be used for chronic (maintenance) treatment of opioid addiction?
- buprenorphine with naloxone (suboxone)
What endogenous CNS substances does alcohol affect?
- endogenous opiates
Initial management of cocaine-induced chest pain - acute coronary syndrome ACS
- ASA, BZD
- IV nitro, nitroprusside or phentolamine (for persistant HTN)
- Avoid B-blockers (b/c alpha would still be stimulated and could lead to worse coronary vasospasm)
Mgmt of acute cocaine intoxication
- Treat hyperthermia, seizures, agitation (e.g. BZD)
- Manage cardiovascular complications
Which med used for relapse prevention in alcohol abuse disorder is nephrotoxic?
Acamprosate - CrC must be over 30 to use this
What is the metabolite of cocaine that is looked for in urine testing?
Which alcohol abuse disorder drugs used for relapse prevention are hepatotoxic
How does clonidine work in treating opioid addiction?
- It's an alpha-agonist
- helps with anxiety
- shortens time of WD sx
- normalizes neurochemistry to make pt less addicted
Which cholinesterase inhibitor has the most GI SEs?
What SE does Rivastigmine have that the other CIs do not?
dose-dependent weight loss
How long must you be on 10 mg donepezil before titrating up to 23 mg?
at least 3 months
SEs of all cholinesterase inhibitors
- urinary incontinence
- bradycardia, syncope
- salivation, sweating
Which 2 meds should not be used in Parkinson's disease (one is for dementia, one is an AP)?
- Memantine - may worsen psychiatric sx or cognition
- Olanzapine may exacerbate PD
Which CI comes in a patch formulation?
What are environmental risk factors for AD?
- age, vascular disease risk factors, head injury, decreased brain reserve capacity
- diabetes increases risk 3-fold
What medications may have a protective effect against dementia?
- HMG-CoA reductase inhibitors
What is the effect of estrogen on dementia?
- Possible protective effect
- In studies
Which drugs show improvement in neuropsychiatric symptoms of dementia (in studies)?
What are precautions/relative contraindications for ALL cholinesterase inhibitors?
- sick sinus syndrome
- supraventricular cardiac conduction abnormalities
- peptic ulcer disease
- bladder obstruction
What are precautions when giving Memantine?
- severe renal or hepatic impairment
- meds or dietary changes that alkalinize the urine - could decrease renal excretion of the medication
What added SEs does donepezil have that other CIs don't?
- musculoskeletal issues
What would be an appropriate med to use for insomnia in AD patients that will not contribute to cognitive impairment?
Nonpharmacologic interventions for treatment of pts with AD
- minimize environmental triggers
- redirect patient attention (minimize noise, background distraction, personal discomfort)
What meds should be used in delirium and when are they warranted?
- neuroleptics (haloperidol is DOC, I think ?)
- used when sx compromise safety or interfere with medical care
Which anticonvulsant medications may cause cognitive effects? Which 2 cause fewer?
Which anticonvulsants have the least significant drug interaction potential?
Which anticonvulsants inhibit hepatic metabolism and which induce it?
- Valproate is an inhibitor
- Phenytoin, Phenobarb, Primidone, CBZ are inducers
What is the first line drug for primary generalized seizures (absence, myoclonic, tonic-clonic)?
VPA (but really ethosuximide is best for absence)
Which antiepileptic requires adjustment when contraceptive pills are started or d/c'd? Why?
- OCs enhance its clearance
- (pregnancy also increases its clearance)
Which antiepileptic is the worst choice for a pregnant woman?
What is the initial treatment for status epilepticus and what is the DOC?
- lorazepam is DOC
What antiepileptic is a concern because of PEG?
- Sodium: 136-145
- Potassium: 3.5-5
- Chloride: 96-106
- pCO2: 35-45
- HCO3: 22-27
- RR: 18
- Magnesium: 1.7-2.1
- Calcium: 8.5-10.5
- Phosphorus: 2.7-4.5
- Osmolality: 275-290
- BUN: 5-20
- Glucose: 70-110
- Prealbumin: 20-40
2 possible causes of metabolic alkalosis
- loss of acid (vomiting, diuretics)
- Gain of bicarb
Cause of respiratory alkalosis
causes of respiratory acidosis
- (depression of resp center, decreased diffusion, loss of bellows action of chest)
causes of metabolic acidosis
- gain of a strong acid
- loss of bicarb
What is the normal anion gap and how is this useful?
12 +/- 4
- it helps us determine the cause of metabolic acidosis
- - if it is because of gain of HCl or loss of bicarb, the anion gap is normal
- - if it is d/t gain of exogenous acid, the anion gap is increased = anion gap acidosis
name causes of anion gap acidosis and non-anion gap acidosis
- Ethylene glycol
- Renal tubular acidosis
- diarrhea (loss of bicarb)
What order of metabolism does phenobarbital have?
What is the equation to calculate serum osmolality?
2[Na] + Gluc/18 + BUN/2.8
Which hormone controls Na reabsorption? What stimulates its release?
aldosterone; perfusion pressure in the kidney
What hormone controls reabsorption of water? When is it secreted?
ADH; when osmolality is high
What is the overall cause of non-anion gap acidosis?
loss of bicarb or gain of HCl (TPN, renal tubular acidosis, diarrhea)
What is the overall cause of anion gap acidosis?
Gain of exogenous acid
What does a BUN/Scr > 20 tell us?
pt is probably dehydrated and could be having kidney problems d/t poor perfusion
What are Dr. Jameson's 2 sodium rules?
- #1. Salt rules volume. (if you have too much volume, this means you have too much salt) - talking about TOTAL BODY sodium here
- #2. Water rules tonicity. - talking about SERUM sodium and FREE water
If a pt is on diuretics and you give free water, what happens to sodium? What if you replace the fluid with normal saline?
- If replace with free water - hyponatremia
- If replace with NS - hypernatremia
What does a high Na level tell you in terms of free water?
you have lost free water and must replace it
How do you get free water? How do you get more volume?
- give D5W
- secrete ADH
- drink it
- pull it in with glucose
- add sodium
- secrete aldosterone
What is happening with sodium and water in hypotonic hypovolemic hyponatremia? How do we treat it?
- Total body sodium is down
- Free water is low overall (relatively high, though)
- restore circulating volume (use NS)
- minimize sodium loss
- stop diuretics
What is happening with sodium and water in hypotonic isovolemic hyponatremia? How do we treat it?
- Serum sodium is low
- Total body sodium is normal
- Free water is high
Treat with NS + loop diuretic + ADH inhibitor (because of SIADH)
What is SIADH? What drugs can cause it? What is the long term treatment for it?
- syndrome of inappropriate antidiuretic hormone
- too much ADH
- ADH should be "off" because the osmolality is low, but it isn't
- CBZ and oxcarbazepine
- antidiuretic hormones
long term tx: demeclocycline
What is happening with sodium and water in hypotonic hypervolemic hyponatremia? What can cause it? How do we treat it?
- Total body sodium is high
- Total body H2O is high
- Serum sodium is low
Causes: (things that turn on aldosterone leading to hypervolemia) Heart failure, cirrhosis, nephrotic syndrome, renal failure
Treatment: restrict sodium and water intake (< 1 - 1.5 L/d), give diuretics (lasix)
How much should Na be increased by per day when treating hyponatremia? How quickly should it be decreased when treating hypernatremia?
- increase by NMT 12 mEq/L/day
- decrease by 0.5 - 1 mEq/L/day
What must you first correct before you are able to correct low potassium?
A deficit of what electrolyte causes increased potential for digoxin toxicity?
What level of potassium requires treatment for hypokalemia? What would that treatment be? Rates if given IV?
- < 3
- KCl is the only appropriate treatment
- can give 20 mEq/h if using central line - must monitor ECG
- can give only 10 mEq/h if using peripheral line
- NEVER give IV push
What potassium imbalance can acidosis temporarily cause?
hyperkalemia - goes away when acidosis is corrected, so be careful
What are the steps in treating hyperkalemia, and the treatments used in each step?
- 1. stabilize the heart - use Calcium Chloride
- 2. Drive K+ intracellularly - use insulin + glucose
- 3. Remove from the body - use Kayexelate or Lasix
- 4. Decrease intake
What is the preferred treatment of hypomagnesemia?
What are the effects of magnesium on the CV system?
relaxant/sedative type actions: dilates veins and arteries, decreases BP, relaxes muscles
How do we rid the body of Magnesium naturally?
What effects do PTH, Vitamin D, and Calcitonin have on serum calcium?
- PTH increases it
- Vitamin D increases it
- Calcitonin decreases it
What is the equation for corrected Calcium?
[(4 - albumen) x 0.8] + serum Ca
What ECG abnormality can hypocalcemia cause?
prolonged QT interval
Why must we always check magnesium level in treatment of hypocalcemia?
Have to treat low Mg before IV Calcium can increase serum calcium levels
Which hypophosphatemia treatment does not contain sodium? Which contains potassium? Which does not contain potassium?
- K-phos original does not have sodium
- both K-phos products contain potassium - the original has more than the neutral formulation
- Fleet phospho-soda and sodium phosphate both do not contain potassium
Treatments for hyperphosphatemia
What are usually the first choice antipsychotics (3)?
Which SGAs have the most risk of metabolic problems such as unmasking of diabetes, hyperlipidemias, and weight gain? The least?
- Clozapine and olanzapine are the worst
- Ziprasidone and aripiprazole are the best - they are weight neutral
Which SGA has been FDA approved to reduce the risk of recurrent suicidal behavior in schizophrenia?
What are the 2 major AEs associated with clozapine and how are they treated?
- Agranulocytosis - stop drug
- Seizures - if continued tx is indicated, add VPA and keep doses of clozapine to < 900 mg/d
What is the significance of the DI between clozapine and CBZ?
- both cause agranulocytosis
- worsening of psychosis
What is the interaction between clozapine and fluoxetine?
increased clozapine concentrations and increased risk of its SEs
Which SGA is approved to treat schizophrenia in children and adolescents?
Risperidone is a substrate of what CYP enzyme? What drugs does this lead to DIs with?
- CYP 2D6 (it is a substrate)
- it has DIs with 2D6 inhibitors and inducers, especially SSRIs
What is the metabolite of risperidone that is available as an injectible?
paliperidone - may have even more prolactin elevation than risperidone
Which first line SGA is the most expensive and has less risk of EPSEs than risperidone?
- (the EPSEs are dose dependent)
What DIs does olanzapine have?
which SGA is tied with clozapine for the highest risk of metabolic problems?
Which SGA is indicated for schizophrenia, acute bipolar mania, and acute bipolar depression?
What CYP enzyme is quetiapine a substrate of?
What is a major SE of quetiapine?
Main advantages of ziprasidone
- little to no weight gain
- minimal metabolic effects
- (note: must give with food to increase bioavailability)
Which SGA has the most risk of QT prolongation? What drugs does this lead to DIs with?
- Antiarrhythics, Antihistamines, Erythromycin, possibly TCAs
Which SGA is the first drug simultaneously approved for both acute schizophrenia and manic or mixed bipolar disorder in adults? What dosage form does it come in?
Asenapine - only comes in SL tablets
What receptors does aripiprazole work on?
- D2 partial agonist
- 5-HT1A partial agonist
- 5-HT2A partial antagonist
- (acts like antagonist in mesolimbic and agonist in mesocortical)
Which SGA may decrease prolactin concentrations?
which SGA is less sedating than other SGAs
Which SGA is approved for adolescents with schizophrenia?
aripiprazole (and risperidone too)
which SGA is approved as adjunctive treatment of treatment-resistant depression?
What effects are of greatest concern with clozapine?
What effects are of greatest concern with risperidone?
- dose-dependent EPSEs
- prolactin increase
What effects are of greatest concern with olanzapine?
- weight gain
- dose-dependent EPSEs
What effects are of greatest concern with quetiapine?
lack of effect on negative symptoms of schizophrenia
What effects are of greatest concern with ziprasidone?
- lack of effect on negative symptoms of schiz
- dose-dependent EPSEs
- QTc prolongation
- (note: little weight gain)
What effects are of greatest concern with aripiprazole?
Name some Anticholinergic SEs
- memory dysfxn
- dry eyes
- exacerbation of angle closure glaucoma
- blurred vision
- urinary retention
CIs for clozapine
- agranulocytosis or granulocytopenia (or hx of it)
- uncontrolled epilepsy
- severe renal disease
CIs for ziprasidone
- recent MI
- Hx of arrhythmias
- QT prolongation
- drugs that can prolong QT interval
all SGAs need to be titrated up to effective dose except which one?
Which SGA is the best to use in a pt with diabetes?
What dextrose content and osmolarity is allowed when giving through a peripheral line?
- dextrose content NMT 10%
- osmolarity must be less than 900 mOsm/L
Equation for TPN osmolarity
[grams of dextrose/L x 5] + [grams of amino acid/L x 10] + [mEq cations/L]
What must sodium in a TPN be limited to?
What 2 electrolytes should be avoided together in TPNs? Why?
Calcium and Phosphorus - can form precipitates
Which calcium salt is preferred in TPN?
Most drugs are incompatible with TPN. Which are commonly added (are compatible)?
insulin and H2 blockers (ex. ranitidine)
How long is a TPN good for? How often do the tubes need to be changed?
- good for 24 hours
- change tubes q24h if fluids have lipids; q72h if only a dextrose and AA sol'n
What rate must dextrose infusion be limited to?
How should we correct the TPN in hypercapnia?
reduce calories and dextrose in TPN
What effect does propofol use have on TPN?
It is a lipid based emulsion that provides 1.1 kcal/ml of the infusion. Need to reduce lipid in the TPN.
What adjustments should be made to TPN if the BUN is > 50 mg/dL? Which patients would this be a concern in?
- Reduce the amino acid goal
- Concern in renal patients
If a TPN patient is acidotic what adjustments should be made? In an alkalotic patient?
- If acidotic: reduce chloride and increase acetate
- If alkalotic: reduce acetate and increase chloride
When should a patient receive glutamine and arginine supplementation in TPN?
In patients with chronic renal insufficiency receiving chronic TPN what vitamin should be reduced?
What is refeeding syndrome?
- characterized by simultaneous hypophosphatemia, hypokalemia, hypomagnesemia and sometimes deficiency in thiamine and sodium
- Occurs from fat metabolism becoming the main source of energy in starvation, then feeding being begun again and a shift to carbohydrate metabolism occurs. Pt needs ATP and there is a sudden cellular uptake of phosphate leading to severe hypophosphatemia which can lead to neurologic, cardiac, respiratory, and hematologic abnormalities, even death.
If a TPN patient's prealbumin is low, what do we do?
This means the protein synthesis is low and we must increase carbs and AAs
Where is albumin made, what is its half-life? What are the levels for depletion being considered mild, moderate, severe?
- It is made in the liver
- Half life of 20 days
- Mild depletion = 2.8 - 3.5 g/dl
- Moderate depl = 2.1-2.7 g/dl
- Severe depl = < 2.1 g/dl
What is transferrin?
A blood plasma protein for iron delivery
What are the K+ and Na+ goals for TPN?
- K+ is 40-100
- Na+ is 80-150
How do you figure out the calorie goal when formulating TPN?
BEE x Stress Factor
How do you figure out the fluid goal when formulating TPN?
1500 ml for the first 20 kg of weight and 20 ml/kg for each add'l kg
How do you figure out the protein goal when formulating TPN?
- Ranges from 0.6-2.0g/kg/d
- Common is 1.2-2
- Renal failure is 0.6-0.8
How do you figure out the lipid goal when formulating TPN?
- it is approx 1/3 of the non-protein calorie goal
- usually around 0.7 - 1.1 g/kg
How do you figure out the dextrose goal when formulating TPN?
it's the difference betw the calorie goal and the AA + lipids (or about 2/3 of the non-protein calorie goal)
What is black cohosh used for?
PMS, hot flashes
What is cranberry used for?
Prevention of recurrent UTIs
What is echinacea used for?
boosts the immune system
What is feverfew used for?
What is fish oil used for?
HTN, hyperlipidemia, mental health, anticoagulant, CHD, stroke
What is flaxseed used for?
constipation, diarrhea, diabetes, menopause, HTN, CAD, hyperlipidemia
What is garlic used for?
What is horse chestnut seed used for?
venous conditions, eczema, leg pains, hemorrhoids, phlebitis, menstruation
What is ginkgo used for?
- cerebral circulatory disturbances
- peripheral arterial circulatory disturbances
What is Asian Ginseng used for?
- "adaptogen" for increasing resistance to environmental stress
What is milk thistle used for?
What is saw palmetto used for?
What is St. John's Wort used for?
What is valerian used for?
- nervous disturbance of sleep
What is glucosamine/chondroitin used for?
osteoarthritis, inhibition of breakdown of cartilage
What is Coenzyme Q-10 used for?
CHF, HTN, stable angina, ventricular arrhythmias, cancer, heart surgery, periodontal disease
What is melatonin used for?
- circadian rhythm sleep disorders in the blind
- jet lag
What type of formula should trauma, burn, head/neck CA, and critically ill/mechanical ventilation patients have for EN?
- immune-modulating formulation:
- nucleic acids
What type of EN formulation is best for ARDS and severe respiratory failure patients?
- one that has anti-inflammatory lipids and antioxidants
- "pulmonary" formulas not recommended
When should a pt with severe acute pancreatitis receive EN?
What EN formula should pts with severe liver disease receive?
standard polymeric formulations
What product added to EN gives 3 g/L of protein?
What supplement can be added to EN to give 6 g/L of carbohydrate?
What product can be added to EN to give 10 g/L of fat?
What do fructooligosaccharides or FOS do?
they help stimulate growth of beneficial GI bacteria
Which 2 alpha-agonists are used clinically? When are they typically used?
- Clonidine- drug addiction
- Methyldopa- pregnancy/breastfeeding
Which other HTN med may be used in pregnancy (besides methyldopa)?
labetalol - it has the most data in pregnancy
Best HTN meds to use in Diabetes are
ACEIs and ARBs
Recommended HTN treatment in migraine
Beta blockers (especially non-selective such as verapamil)
Which HTN meds should be avoided in asthma/COPD?
Recommended HTN treatment in tachycardia/Afib
beta-blockers and non-DHP CCBs
HTN meds to avoid in depression
- alpha-2 agonists
HTN meds to avoid in bradycardia/AV block
- non-DHP CCBs
HTN meds to avoid in pregnancy
ACEs and ARBs
Best HTN med to use in osteoporosis
Which HTN meds should be used in renal insufficiency patients? Which should be avoided?
- use: ACEs, ARBs, loops
- avoid: K+ sparing, thiazides
Stages of HTN
- normal <120/<80
- prehypertension 120-139/80-89
- stage 1 HTN 140-159/90-99
- stage 2 HTN >160/>100
Order of potency of statins
Which hyperlipidemia med is the DOC for high LDL?
Which hyperlipidemia med is the DOC for high LDL and high TG?
Which hyperlipidemia med is the DOC for high LDL, high TG, and low HDL?
Which is the DOC for treating high TG, low HDL, or both?
What is the DOC for treatment and prevention of DVT and PE in pregnancy?
When is APTT measured?
When a pt is on treatment doses of unfractionated heparin
What is the dose of UH for prevention?
5000 units SQ q8-12h
What is the treatment dose for UH?
- loading dose is 80 units/kg IV
- maintenance is 18 units/kg IV
What is the length of treatment with UH?
d/c when INR has been therapeutic for 24 hours for a minimum of 5 days
What is the prophylactic dose of enoxaparin?
30 mg SQ bid (or 40 mg SQ qd)
What is the treatment dose of enoxaparin?
1 mg/kg SQ bid
What is the antidote for bleeding caused by heparin?
What drugs can be used to treat clots in a pt with HIT, Heparin-induced thrombocytopenia?
- Direct thrombin inhibitors (lepirudin, argatroban)
MOA of warfarin
inhibits vitamin K-epoxide reductase which decreases levels of vitamin K in the body
What is the duration of therapy with warfarin in a pt who is being treated for their first VTE?
What is the goal INR for most patients?
How long is warfarin treatment in a patient with recurrent DVT/PE?
For a pt with thrombosis who has had a mechanical valve replacement what is the duration of warfarin therapy and what is the goal INR?
When is warfarin therapy started in a DVT/PE patient?
as soon as APTT is therapeutic from heparin
How long should heparin and warfarin therapy be overlapped?
at least 5 days
What is the starting dose of warfarin in treatment of DVT/PE? In prophylaxis?
- 5-10 mg PO QD for treatment
- 2.5 - 5 mg PO QD for prophylaxis
For reversal of bleeding and/or high INR what actions do we take and at what INR levels?
- INR of 3-5 and pt not bleeding, hold 1-2 doses and resume tx at lower dose
- INR of 6-9 and pt not bleeding, stop therapy, give 2.5 mg PO Vitamin K, recheck in 24 h
- INR of 10-20 and pt not bleeding, stop therapy, give Vitamin K 5 mg PO, recheck INR in 24 h
- INR >20 or seriously bleeding, stop therapy, give Vitamin K 10 mg IV infusion, recheck INR q 6-12 h, may repeat Vitamin K IV q 12 h, may supplement with fresh frozen plasma or prothrombin complex concentrates, resume heparin therapy until patient responsive to warfarin
Are warfarin and heparin compatible with pregnancy and breastfeeding?
- Warfarin not with pregnancy - Category X - ok to use heparin
- Warfarin ok in breastfeeding - heparin no
The 10A drugs that interfere with warfarin
- azole antifungals
- anti-inflammatory agents
- alternative remedies
Why do we tell patients on coumadin to take their medication in the evening?
Because if they come into the clinic and their INR is high, we can still adjust that day's dose
Which class of antihypertensives should be avoided in patients with severe PAD?
Which receptor on the platelet adheres to the subendothelium?
What factors/parts of the coagulation cascade does Thrombin (Factor IIa) activate?
- Protein C
- Factor VIII
- Factor V
At what point in the coagulation cascade do both pathways merge into one?
At factor X
What receptor on the platelet allows platelets to adhere to each other?