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226 Cards in this Set
- Front
- Back
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Equation for volume of distribution, dose, and plasma concentration
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Dose (mg) = Vd (L) x Cp (mg/L)
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Treatment for cyanide ingestion
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amyl nitrate
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Carbon monoxide treatment
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oxygen
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narcotic overdose tx
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narcan aka naloxone 2 mg IV q 2-3 min up to 10 times
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treatment of ethylene glycol or methanol ingestion
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ethanol bolus 0.6 g/ kg
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treatment of organophosphate poisioning (cholinesterase inhibitors)- symptoms lacrimation, salivation, defecation, bradycardia.
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treat with atropine 1 mg -> 2mg increasing doses, as well as pralidoxime which regenerates cholinesterase.
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treatment of salicylate OD
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alkaline diuresis, goal ph of urine 8.0 and volume 1 L/hr.
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Dig toxicity- heart block, PVCs (increased ventricular irritability, can lead to v fib) tX?
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dig antibody (dig i bind)
treat low K. pacemaker if needed. avoid cardioversion as it can cause v fib |
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iron od
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gastric lavage and chelator deferoxamine
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stepwise approach to seizures
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lorazepam 2-4mg iv
phenytoin 20mg/kg pentobarbitol 20 mg/kg + intubate |
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Dose, advantages and disadvantages of haloperidol for agitation
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Haloperidol 5-10mg IV
advantage no respiratory supression disadvantage - sedation, QT prolongation, hypotension |
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Dose, advantages and disadvantages of Lorezepam for agitation
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Lorazepam 2-4 mg IV
advantage- prevents seizures, good for non specific drug intoxication, long duration 4-8hrs disadvantage- respiratory depression |
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Dose, advantages and disadvantages of Midazolam for agitation
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Midazolam 4-8 mg IV
Shorter duration then Lorazepam 1-2 hrs which is good for ETOH intoxiction. Risk of respiratory depression. |
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Dose, advantages and disadvantages of Olanzapine for agitation
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Olanzapine 10 mg
less respiratory depression Disadvantage cost, anticholinergic |
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Dose, advantages and disadvantages of Ziprasidone for agitation (aka Geodon)
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Ziprasidone 40 mg
Less respiratory depression Disadvantage is cost, QT prolongation |
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3 drugs that are over90% protein bound which will have decreased efficacy in conditions with low albumen ie pregnancy, renall failure, liver failure,burns.
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warfarin, valproic acid, phenytoin
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CYP 3A4 inhibitors (decrease drug metabolism, increase drug levels)
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clarithromycin, erythromycin
diltiazem, verapamil fluoxamine ketoconazole amiodarone grapefruit juice |
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CYP 3A4 Inducers (increase drug metabolism, reducing drug levels)
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Carbamazepine, phenytoin
rifampin, rifabutin st johns wort |
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CYP2D6 Inhibitors (absent in 7% of caucasians) - increase drug levels
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amiodarone, quinidine
amitryptyline, nortriptyline, citalopram, sertraline, venlafaxine haloperidol |
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CYP 2C19 inhibitors (increase drug levels
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(omeprazole, fluoxamine, cimetidine)
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goals of phase 1 drug studies
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determining dose, schedule and toxicity, interactions, goal to gather data with teh expectation of <5% of patients to respond. Patients are very closely followed.
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goals of phase II drug studies
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larger numbers of patients, goal to find specific population and show that the drug is efficacous, less concerned with side effects.
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goals of phase III drug studies
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larger number of patients up to 100's, very restricted by line of therapy, goal is to prove that the drug works better then other established drugs or with less side effects . Higher chance of being randomized and receiving alternative treatment vs phase 1 studies.
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Top 3 type of cancer deaths for males/females
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males: lung, prostate, colon
females: lung, breast, colon |
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what is targeted cancer therapy?
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there is a specific target that the drug is designed to interfere with ie EGFR in NSCLC. There is a wider therapeutic margin but not necessarially fewer side effects when outside the therapeutic range.
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what is the goal of adjuvant therapy
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to reduce the risk of recurrance
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what is neoadjuvant therapy
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goal is tumor reduction preoperatively
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treatment approaches in rectal cancer by stage
stage 1 stage 2 stage 3 stage 4 |
stage 1- surgery
stage 2-surgery with pre (neoadjuvant) or post op (adjuvant chemo/radiation stage 3 surgery with pre or post op chemo/radiation stage 4 chemotherapy, palliative radiation or surgery |
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treatment approaches in colon cancer by stage
stage 1 stage 2 stage 3 stage 4 |
stage 1 surgery
stage 2 surgery stage 3 surgery and adjuvant chemo stage 4 chemo |
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MOA of 5FU fluorouracil
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blocks DNA binding, side effects include fatigue and diarrhea
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MOA of bevacuzimab
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monoclonal antibody that inhibits new blood vessel formation
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most commonly diagnosed cancers
women men |
women breast , lung, colon
men prostate, lung colon |
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most common sites of lung cancer mets
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bone, liver, adrenals, brain
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treatment of lung cancer by state
stage 1 stage 2 stage 3 stage 4 |
stage 1 surgery
stage 2 surgery + adjuvant chemo stage 3 chemo, radiation, surgery - multimodal therapy stage 4 systemic therapy (chemo or biologics) |
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4 main types of lung cancer
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mesothelioma 3%
carcinoid 1% SCLC 15% NSCLC 81% -adenocarcinoma 40% -large cell carcinoma 10% -SCC 30% -bronchoalveolar carcinoma 5% |
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Lung cancer therapy with Gefitnib targets TKI. What patient base is most appropriate?
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chemonaive, never smoker, asian, adenocarcinoma,>18, must have expression of the EGFR mutation
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Substance Dependence classification:
5 physiologic and 2 symptoms regarding loss of control |
tolerance, withdrawal, use more then intended, has tried to cut down, spends a great deal of time using the substance, reduction in time doing other enjoyable activities
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Substance abuse
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interferes with role obligations, use in hazardous situations, legal/social/ interpersonal problems results because of use + substance dependence.
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MOA of antibuse/disulfiram
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blocks alcohol dehydrogenase causing headache, nausea, dizziness, tachycardia. Side effects include hepatitis, neuropathy, optic neuritis, metalic taste, fatigue, headache. Make sure patient has 0 etoh level then load 500mg qd for 5 days and then 250 mg qd
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vivitrol or revia (naltrexone) moa
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blocks opoid receptors reducing dopamine release preventing euphoria from drinking/narcotics Vivitrol is a depot injection q month
risks include opioid withdrawal, hepatic failure, acute hepatitis. |
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how do you make a diagnosis of diabetes?
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2 fasting blood sugars >126 or one random >200. Also now you can check hA1c and if > 6.5
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Metformin:
MOA, side effects, contraindications, dosing? |
First line drug. Works by increasing hepatic sensitivity to decrease gluconeogenesis, increases insulin production, lowers fasting blood sugar. Contraindicated in renal failure. Side effects of diarrhea and bloating resolve in a few days. Start 500mg in the evening, increase to 1000 BID goal dose in 2 weeks if minimal side effects.
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Class of diabetic drug that increases insulin sensitivity
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Thiazolidinediones TZDs
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This class of drug binds K channel on beta cells causing calcium influx and increased insulin release. Risks include hypoglycemia.
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Sulfonylureas
such as glyburide glipizide glimepiride |
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Meglitinides
MOA, side effects |
Also a direct secretagogues which increase insulin secretion by binding K channels but faster. Can cause hypoglycemia.
Examples include Repaglidine and Nateglinide. |
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class?
glyburide |
sulfonylureas
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class?
glipizide |
sulfonylureas
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class?
flimepiride |
sulfonylureas
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class?
repaglinide |
meglitinide
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class?
Nateglinide |
meglitinide
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what is the MOA of Byetta?
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Byetta is a GLP 1 analogue, GLP1 is secreted by the intestine and stimulates insulin roduction from the pancreas. Byetta must be given as an injection. GLP 1 also reduces postpradndial glucagon secretion, increases satiety and slows gastric emptying resulting in a slower glycemic load.
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What is the MOA of Januvia (Sitagliptin)?
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Januvia inhibits the enzyme DPP 4 which breaks down GLP 1 so that it remains in the body longer. However it is not as effective as Byetta which increases the levels of GLP 1 more drasticly.
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How do you start insulin in a T2Diabetic? What is the rule for increasing the dose?
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Continue oral agents and begin a 10 unit insulin dose at bedtime. Consider Glargine as it is long acting or NPH as it is intermediate acting. If the FBS in the morning is >140 increase the dose by 4 units. If the blood sugar is 12-140 increse the dose 2 units until at target glucose of 80-120.
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MOA for Thiazolidinediones? Risks?
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Rosiglitazone (Avandia) or Pioglitazone (Actos) are agonists to the nuclear receptors PPARs. Avandia may be associated with a slight increased risk of heart disease.
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MOA of Acarbose? Side effects?
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Acarbose inhibits carbohydrate uptake in the intestine (inhibits alpha glucosidase) Main disde effect is flatulence and diarrhea.
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This drug for Parkinson's Disease and restless leg is also used for diabetes although the MOA is unknown.
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Bromocriptine
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3 Types of fast acting insulin
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Lispro
Aspart Glulisine |
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Short acting insulin (1)
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Regular
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Intermediate acting insulin
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NPH
Lente |
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Long acting insulin
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Glargine
Detemir |
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What is the basal insulin dose for
1) insulin sensitive? 2) insulin resistant |
1) 0.2 u/kg
2) 0.4 u/kg Give half long acting at night. Give half divided among meals |
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How do you calculate correction factor for preprandial blood sugar?
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Calculate how much above 100 goal the blood sugar is.
ie) if blood sugar is 200 you need to correct the blood sugar by 100. Divide 1600/total daily dose of insulin. If a 100 kg person then the insulin dose is 20 if insulin sensitive, so for each dose of insulin the blood sugar is reduced by 1600/20 =80. So the dose would be 100/80 = 1.25 |
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Definition of osteoperosis
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low T score -2.5 the standard deviation or if T score not available and low trauma fracture.
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When should patients be treated for osteoperosis?
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Women or men 50 + with low trauma fracture
50+ years with T scre -2.5 Patients on chronic steroids >3 months Women with osteopenia with additional risk factors where the 10 year risk is 20% or more |
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What is the dose for Vit D supplementation?
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1000 international units
Target levels of 25 OH D3 should be >30, levels of >50 associated with reduction in all cause mortality |
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What is the dose for Calcium supplementation?
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1000 mg / day
Adolescents 1200 / day Pregnant/ Lactating women 2000mg/ day |
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MOA of Forteo?
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PTH hormone analogue. At a low daily dose it is anabolic and builds bone by directly stimulating osteoblasts. Best for patients on steroids which directly inhibits osteoblasts. Small risk of osteosarcoma shown only in rats. May only use Forteo for 2 year duration
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Name 3 bisphosphonates- antiresorptive agents
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Alendronate
Risedronate Ibandronate |
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What is the MOA of Denosumab?
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It is a anti RANK ligand antibody which inhibits osteoclast activity. unlike bisphosphonates it is not recycled and must be given continuously.
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Do you ovulate while on OCP? Why yes or no?
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No. High levels of progesterone inhibit FSH and LH. Because progesterone supresses the LH surge there is no ovulation.
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What hormone is responsible for endometrial proliferation?
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Estrogen
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How soon after birth should a mother begin the OCP?
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3 weeks otherwise risk of ovulation.
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What are 2 common side effects due to the estrogen in the OCP and how do you address?
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1) nausea- take the pill in the evening an hour after dinner or at bed with a snack.
2) breast tenderness- resolves within 3 months. |
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Why do some women get breakthrough bleeding on the OCP after taking the pill for a long duration without any prior problems?
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The endometrium in these women is atropic and fragle and these women may need a higher dose of estrogen to allow m,ore buildup of the endometrium.
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In anovulatory bleeding what hormone is deficent and why do these women have heavier periods when on the pill initially?
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High estrogen and low progesterone. There is no progesterone for the LH surge to occur. When they start the pill they have a very thick endometrium and when menses occurs it may take up to 4 cycles for the endometrium to fully shed back to the normal level.
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Name 3 absolute contraindications to OCP use?
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Contraindicated in women wiht a past PE, MI , CVA or thrombophlebitis, liver dysfunction, breast cancer, smokers >35 or pregnant. Relative contraindication in migranes with neurological symptoms due to vasospasm and in uncontrolled HTN and sickle cell disease.
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Name 2 common drugs that increase the clearance of the pill? Name 1 drug that the pill increases drug clearance so that it requires a higher dosage?
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1) Griseofulvin and Rifampin both require that you increase OCP dose to 50.
2) If women is on the pill and starts Lamictal she will likely need to increase her Lamictal dose by 50% due to OCP increased clearance. |
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Why should Depoprovera not be used for longer then 2 years?
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Risk of reversable osteoporosis. This method of contraception may be better for women with difficult to control seizures and sickle cell. However there is some risk of depression and weight gain in 5%.
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If women have early spotting in their periods what do they need and why.
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Give additional progesterone to stabilize the uterine lining. If there is bleeding late in the cycle it is usually due to atrophy of the lining and responsive to estrogen.
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Waht is the best non hormonal treatments for vasomotor symptoms of menopause?
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SSRIs: Effexor 25mg BID, Paxil 20 mg QD, Prozac 20mg QD
Alternatives include clonidine and soy. Hormonal treatment of menopause includes OCPs, oral or injectable progesterones and patche ie Estraderm, Combipatch, Vivelle |
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Name 3 risk factors for osteoporosis
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past fracture,postmenopausal female sex, dementia, caucasian/asian, tobacco or ethanol use, low BMD, low physical activity, poor health, family history.
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Minimal HRT for Bone preservation?
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premarin 0.625 mg or Estrace 1mg. HRT decreases vertebral fx risk by up to 80% and hip and wrist fracture by 25%. Estrogen stabilizes bone by increasing osteoblast activity, increasing Ca absorption and increasing vit D activity.
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Minimal dose of progestin exposure require d for protection against endometrial hyperplasia and endometrial cancer in HRT?
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12 days q month.
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Risks of HRT
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Risk is increased with non hormonal replacment ?10 yrs and age >65
Slight increased risk of thrombosis, possibly protective for stroke and MI Incresed risk of breast cancer if used for >10 years (increased 30%) but back to baseline after 2 years of discontinuation possible benefit in altzheimers if started early reduction in colon cancer by 60% Estrogen helps protect bone from osteoporosis |
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A patient presents with chest pain, what pharmacologic management do you offer?
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1. sublingual nitro for ischemic pain
2. morphine sulfate 20mg for continued pain/ air hunger 3. BB (metoprolol 5 mg IV q 5 min) or CCB (non dihydropyridine like verapamil or diltiazem) to reduce cardiac demand 4. chewed 325 mg Aspirin or 300mg clopidogrel if allergic 5. PPI if hx of GIB 6. If cardiac cath is planned patient will likely have tripple antiplatelet therapy with ASA, heparin and a 2B3A inhibitor like abicimab or eptifibatide |
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Contrast the MOA of bivalirudin vs heparin.
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bivalirudin is a irreversable direct thrombin blocker
heparin indirectly inhibits thrombin |
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Platelets can be activated (and thus blocked) in 4 ways. What are the targets?
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1. clopidogrel blocks ADP activation
2. Aspirin blocks COX1 activation 3. GP IIb/IIIa inhibitors (abxicimab or eptifibate) 4. Collagen/thrombin,TXA2 (indirectly blocked by heparin |
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Contrast the two IIb/IIIa inhibitors and when to use which one?
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monoclonal antibody inhibits platelet aggregation
1. Abxicimab: irreversably binds to the receptor, to reverse infuse platelets. Used in STEMI. Better to use in renal disease 2. Eptifibate- Reversable binding so when you infuse more platelets those too become inactivated. Used in NSTEMI. Requires renal clearance. |
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MOA of heparin and reversal agent?
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Heparin indirectly inhibits thrombin.
Reverse with protamine. Don't over dose protamine as it too can cause anticoagulation. |
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What direct thrombin inhibitor would you use in a patient with HIT?
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Give bivalirudin. It is an alternative to heparin. Irreversalbe action. Requires renal dosing.
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ICU Drugs: main effects
Norepinephrine |
most potent vasoconstricter, primarially alpha effect
mild beta positive ionotrope effect fast onset |
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ICU Drugs: main effects
Epinephrine |
not as effective as norepinephrine
both alpha and beta effects so it vasoconstricts and is positive ionotrope. |
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ICU Drugs: main effects
Dobutamine |
positive ionotrope
primarily beta effect some hypotension increases stroke volume |
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ICU Drugs: main effects
phenylephrine |
primarily alpha agonist
potent vasoconstrictor |
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ICU Drugs: main effects
Dopamine |
potent vasoconstrictor
dopa, beta and alpha agonist protects kidneys by causing renal vasodilation |
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Contrast the vasodilators nitroglycerin and nitroprusside.
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Nitroglycerin- dilates coronary and peripheral Arteries and Veins. Helps treat vascular spasm in unstable angina.
Nitroprusside- potent Vasodilator only. Can lower BP. Good for hypertensive emergiencies. Can cause cyanide toxicity (metabolic acidosis) |
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Which opioid is longer acting fentanyl or morphine or meperidine (demerol)
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fentanyl is the fastest acting onset <90 sec and shortest duration 30-60 min
demerol (meperidine) has onset in 10 min and intermediate duration of 2-3 hours Morphine has onset in 3 minutes and duration of 3-4 horus (longest) Reversal of any of these is with naloxone. |
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Name a class III antiarrythmic often used for A fib
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Amiodarone
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This drug treats paroxysmal supraventricular tachycardia but if there is AVNRT (nodal reentry) it will break and normal rhythm will resume otherwise the rate will only slow.
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Adenosine
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Name major risk factors for CHD
(six) |
family history of early CHD <55 male, <65 if female
age: male >45, female >55. HTN (BP >140/90) Smoker Diabetes Low HDL <35 |
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What are the LDL goals for
1) CHD 2) two or more risk factors 3) less then two risk factors |
1) 100 (optional 70)
2) <130 3) <160 |
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How do statins protect against heart disease?
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improved vasodilation of endothelium
stabilizes atherosclerotic lesions reduces inflammatory stimuli regression or slowed progression of atherosclerotic lesions (HMG co A reductase inhibitors) |
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Is UFH renally cleared? How about LMWH or Fondaparinux?
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Unfractionated heparin is not renally cleared and has the shortet duration of 8-12 h. LMWH and Fondaparinux are both renally cleared and they both last up to 24 hours.
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Test question:
Are anticoagulation factors still present on anticoagulation with Warfarin? |
Yes. Warfarin just decreases the production of factors that can get activated in the future. That is why you start with heparin. It takes 5 days to reduce the pool!
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How do you follow Warfarin vs Heparin?
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PT or INR for Warfarin (first dose will decrease factor 7 but factor 2 takes 5 days to be inactivated, so the INR is not really that reflective of clotting ability). Goal INR is 2-3. Monitor INR every 2 days until stable.
aPTT for Heparin. |
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What are the two components in the antiplatelet agent Aggrenox.
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Aggrenox contains aspirin and dipyridamole it is a cox inhibitor plus a TXA2 inhibitor as well as a weak vasodilator to prevent stroke.
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MOA of Plavix (Clopidogrel)
Dosing? |
Plavix is a ADP inhibitor of platlet aggregation
75 mg po daily, takes 4-7 days to take effect which is much slower then aspirin which inhibits platelts within 2 hours. |
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What is the CHADS2 score and what is it used for?
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The CHADS2 score is a system to determine the agressiveness for A fib therapy. 1 point given for CHF, HTN, Age >75, Diabetes and 2 pointsfor stroke.
2 or more risk factors anticoagulate 2-3 with Warfarin, otherwise give ASA or if 1 risk factor can do either. |
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Name a new direct thrombin (IIa) inhibitor
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Dabigatran is a direct thrombin inhibitor.
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Describe the Frank Starling Curve
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CO vs EDFV. The heart after an MI has its curve lowered requiring higher end diastolic volumes to produce adequate cardiac output. This is why people with CHF retain fluid.
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What three factors can you influence to increase stroke volume
review: CO = HR x SV |
SV can be improved by increasing contractility and preload and by reducing afterload.
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Name 3 causes of systolic heart failure
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-due to inability to pump blood adequately out
direct destruction of the heart from MI, cardiomyopathy (dilated), myocarditis. tachycardia,drugs (cocaine), hyperthyroidism, volume overload or mitral regurgitation. |
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Name 3 causes of diastolic heart failure
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diastolic heart failure is failure to fill
caused from too high an afterload - aortic stensois, HTN, fibrosis (retrictive of hypertrophic cardiomyopathy), external compression (pericardial fiborsis or effusion) |
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Name the 4 main drug interventions for chornic CHF
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1. diuretics first and foremost (loop, thiazide)
2. Antihypertensives (ACEI or ARB) 3. Spironolactone or Eplerenone (less gynecomastia) 4. BB- can cause bronchospasm, beware of possible neg ionotrope effect although will prevent future remodeling. |
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Name the main 3 interventions in acute decompensated CHF
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1. IV diuretics
2. IV vasodilators (nitrates are preferable if BP allows)- reduce afterload 3. positive pressure ventilation, intubation if necessary 4. IV positive ionotropes if in shock - may need to discontinue pt home BB |
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Name 2 loop diuretics. What is one that is not a sulfa?
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Loops: furosamide, torsamide, bumex
non sulfa include ethacrinic acid |
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How much do you change diuretic dose going from po to IV.
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Half the dose when going to IV.
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Why are ACEI great in protecting teh kidneys in hypertension but must be used with caution with renal failure + CHF
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ACEI causes afferent vasoconstriction which protects the kidneys from HTN assault but can leave the kidneys lacking blood supply when pressures are low.
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Name 2 positive inotropes and their MOA
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Digoxin (K/Na exchanger)
Dobutamine (Beta agonist) Milrinone (PDE inhibitor) |
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What is the main treatment for heart failure with normal ejection fraction?
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diuretics and treatment of the underlying disorder ie the HTN
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In the setting of a hypertensive emergency what is the DBP cut off?
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>130 DBP although the end organ damage is due to the rapid rate of rise not the absolute value.
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What is the main drug for the treatment of HTN emergency?
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Nitroprusside- most potent vasodilator.
Alternatives include Nitroglycerine Diazoxide Labetalol Nicardipene (dihydropyramidines recall work primarily on the smooth muscle of the vasculature) |
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Initial goals of management in HTN emergency?
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Reduction in BP of 20%
if tolerated continue dropping the BP by 10% every 2-3 hrs until DBP 90mm BP. Risk of reduced Cerebral blood flow and coma if you drop them too quickly. |
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Best oral antihypertensive drug in the emergent circumstance, and often the first drug combined with a BB when weaning a patient off of nitroprusside.
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Minoxidil
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Define and describe the treatment for the following BP
120-139/ 80-89 |
Prehypertension
Treat with lifestyle changes |
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Define and describe the treatment for the following BP
140-159/ 90-99 |
Stage 1 Hypertension
Start thiazide plus another agent if BP is twenty points above goal |
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Define and describe the treatment for the following BP
>160/>100 |
Stage 2 Hypertension
Start thiazide plus another agent if BP is twenty points above goal |
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whats the difference between innoculation, vaccination and immunization?
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innoculation= purposeful infection
vaccination= you give an antigen but you don't know if the patient is going to mount an adequate response. immunization= immunity has been provided |
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What are the two live vaccines given today?
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Rotavirus
Influenza given intranasally |
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Beta 1 selective BB (heart specific some negative ionotropes and slow HR)
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"A -BEAM "
acebutalol betaxolol esmolo atenolol metoprolol |
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Drugs that cause gynecomastia
Some Drugs Create Awesome Knockers |
Spironolactone, Digitalis, Cimetidine, Alcohol Ketoconazole
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CYP 450 Inhibitors (lower drug levels)
I C(see) KEGS (go down) |
I- Isoniazid
C- Cimetidine K- Ketoconazole E- Erythromycin G- Grapefruit S- Sulfonamides |
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CYP 450 Inducers
Boston Redsox Gotta Play Quality Competitions "to go up" |
B- Barbituates
R- Rifampin G- Griseofulvin P- Phenytoin Q- Quinidine C- Carbamazepine |
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Name 3 causes of atypical pneumoniae.
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Mycoplasma, Legionella, Chlamydia, viruses
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What are the top 3 organisms you worry about with PNA in a patient with COPD?
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S. pneumo
H influenza Moraxella Catarrhalis |
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What are the top 3 organisms you worry about with PNA after a recent viral URI?
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S. pneumo
S. aureus H influenzae |
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What organisms are you concerned when considering aspiration pneumonia?
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GPC and anerobes
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Main causes of CAP in patient < 60 yo with no comorbidities?Name 4
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S. pneumoniae
Mycoplasma Chlamydia H influenzae |
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In addition to S. pneumonia and H flu what other 3 organisms are you concerned with in patient > 60 years with comorbidities?
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S. aureus, Gram Neg Bacteria (Klebsiella) Legionella
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ABCs of treating anaphylactoid reactions
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Adrenaline (epi) 0.3-0.5 mg IM
Benadryl 25-50 mg po Corticosteroids 60 mg methylpregnisolone IV q 6hr + O2 and IV Consider Cimetidine and Albuterol |
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Name 4 cross substances that cross react with lasix.
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ABC-K
Avacados Bannas Chestnuts Kiwis |
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When is there peak GC levels? Trough?
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GC peak is 8am, trough is midnight.
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what is the function of cortisol?
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Cortisol supresses the immune system and inflammation. It also increases glucose by gluconeogenesis and aids in fat protein and carb metabolism.
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How does cortisol exhert its anti inflammatory effects?
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1) genomic effects by passifively diffusing across cell emmbranes and interacting with DNA to reduce proinflammatory mediators (this takes time approx 5 days)
2)More immediate effect is that the glucocorticoid binds to lymphocytes and monocytes and lessens their activity via receptor mGCR. 3) Suppresses COX2, causes neutrophilia, vasconstriction and many other moderate effectors of immunity. |
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What happens to the following cell types on a patient on steroids?
monocytes neutrophils lymphocytes dendrites |
monocytes- monocytopenia
neutrophils- increased due to increased release from bone marrow and decreased release to periphery. lymphocytes- lymphopenia- T cells are redistributed to tissues and apoptosis is increased (dendrites also have increased apoptosis) |
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Give an example of the 3 main classes of hormones:
GC MC sex hormones |
GC- cortisol
MC- aldosterone sex hormones - DHT |
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What is the equivilant dose between
cortisone vs prednisone vs dexamethasone? |
25mg cortisone = 5 mg of prednisone = 0.75mg of dexamethasone.
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Why do dexamethasone and betamethasone (36-54h) have such a longer half life then prednisone (12-36h) or cortisone (8h)?
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Due to the flourine group in place of the methyl.
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Most common drug and dosing for acute steroid regimen?
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1-2 mg/kg/day of prednisone divided in BID dosing
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What is the dose for crisis pulse steroid therapy and drug of choice?
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IV methylprednisolone 1 geam QD for 3-5 days, often given as 250 mg IV q6hrs or 500 mg IV BID
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What two steroids cross the placenta?
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betamethasone and dexamethasone cross the placenta.
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How do you test if a person is adrenally supressed during an acute stressor?
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Cosyntropin (Cotrosyn) stim test
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What is an adequate stress dose of steroids?
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200-300 mg Solucortef (Hydrocortisone) over the first 24 hours then taper by half each day.
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Names: Cortisol
oral IV |
oral hydrocortisone
IV solucortef |
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Names: Methylprednisolone
oral IV |
oral is medrol
IV is solumedrol |
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Names: Triamcinolone
IM/IA |
Kenalog
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What systemic side effects can you get from iris dilators?
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The iris can be dilated by relaxing the sphinctor by antimuscarinic agents like atropine and so the side effects are similar to atropine like tachycardia, hallucinations, fushing, disorientation.
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Common iris dilator (anti muscarinic) that has a short duration of action (1hr)
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Mydriacil is a fast acting iris dilator. Unlike atropine a similar antimuscarinic but can last up to 3 weeks, or an intermediate dilator Scopolamine which can last 3-5 days
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What is a counterindication to dilating the iris?
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History of narrow angle glaucoma.
-beware of pseudoephedrine in a narrow angle patient as it can have some dilating effects as well as scopolamine (both common OTC drugs). |
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Name 2 opthalmic anesthetic agents? Why can they not be prescribed or used chronically.
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Huge potential for abuse. Can cause loss of eye and loss of vision.
Tetracaine Proparacaine. |
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MOA of Fluoroquinolones?
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Inhibit DNA Gyrase so the DNA tangles.
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MOA of Aminoglycosides like neomycin, gentamycin, tobramycin?
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Ribosone- inhibits protein synthesis.
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Name two 3rd gen FQ
Name 1 4th generation FQ |
Ciprofloxacin, Levofloxacin, Ofloxacin are 3rd generation
Moxifloxacin and Gatifloxacin are 4th Gen MOA- DNA Gyrase inhibition |
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Treatment of bacterial conjunctivitis:
red eye with discharge, minimal pain some loss of vision |
Treat with broad specturm abx ie Trimethoprim (sulfa based anti folic acid abx) 7-10 day duration.
Avoid Neomycin as 10% have contact derm reaction which clouds the picture. |
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Treatment of bacterial keratitis:
pain, white spot on cornea, decrease in vision, contact lens wearer. treat with? |
FQ ie Moxifloxacin aka Vigamox 0.5% and Ancef or
Ciprofloxacin (for pseudomonas) and vancomycin for MRSA |
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Treatment for HSV Keratitis- you note ulceration of teh cornea. Association with the oral erruption.
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Antiviral. Viroptic topical preparation or systemic treatment with Acyclovir/ Famvir
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Treatment of ocular allergy -redness, itching, irritation
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Panatol (mast stabilizer and ocular antihistamine) 2 drops BID
Avoid topical steroids . |
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Name 3 causes of reversible dementias (20% of dementias)
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drugs and toxins (this includes alcohol)
mass lesions (tumors, hematomas) NPH Systemic disease (B12 defi hypotyroidism) infectious/inflammatory diseses (MS and syphilis) TBI Depression |
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Name 3 causes of irreversible Dementias (80% of dementias)
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Alzheimers disease
Frontotemporal lobar degeneration Vascular dmentia Lewy Body Dementia/ PD Huntington's Disease HIV associated dementia Creutzfeldt Jakob Disease TBI |
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Most common cause of dementia in the elderly
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Alzheimers
- more common in women. -prevalence is 5-10% after age 65 and up to 40% after age 85. |
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Name 2 cholinergic drugs which improve Altzheimers disesae by inhibiting the enzyme cholinesterase wich degrades ACh.
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Donepezil (Aricept)
Rivastigmine (Exelon) Reminyl and Razadyne |
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An alternative drug choice for alzheimers other then cholinesterase inhibitors is NMDA receptor antagonist and is considered neuroprotective, name this drug?
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Memantine (Namenda) is a NMDA antagonist used for altzheimers.
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How do you define hyperuricemia? in males vs females?
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Males >7
females >6 usually women present after menopause and only 15% of patients with hyperuricemia develop gout, this only increases to 30-50% if serum uricemic acid level is >10. Don't treat asymptomatic hyperuricemia. |
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What nucleotide is degraded into uric acid? What foods is this base contianed in?
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Purine
In meats and seafood |
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Name 2 X linked genetic traits that cause gout in younger populations.
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There is an upregularion in PRPP synthetase or a decrease in HGPRT.
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MOA of allopurinol?
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Xanthine oxidase inhibitor.
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What does the synovial fluid in gout show?
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inflammatory with >20000 cells mostly neutrophils and neg birefringent crystals.
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What Drugs cause decreased excretion of Uric Acid?
CANT LEAP |
Cyclosporine
Alcohol Nicotinic acid Thiazide diuretics Loop Diuretics Ethambutol Aspirin Pyrazinamide (TB) Losartin can actually protect against Uric acid levels increasing from thiazides. |
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What is the treatment of acute gouty arthritis?
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Treat comorbid illnesses
NSAIDs Colchicine Corticosteroids Analgesics |
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What NSAID is first choice in Gout?
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Indomethacin starting at 50mg QID x 1 day
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Chrons vs UC ? diarrhea +/- blood, stricture/obstruction, fistulae, perforation/abscess, malabosrption, perianal disease, can involve entire GI tract but most commonly ileocecal 41%. Cobblestoning, focal ulceration, skip lesions, discontinuous. Histology shows transmural ulceration and granulomas. +ASCA (–)P-ANCA 80% have a resection.
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Chrons
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Chrons vs UC? bloody diarrhea, colonic (rectum) most don’t extend past the sigmoid colon. Rectum involves diffuse ulceration, continuous, pseudopolyps. Histology shows superficial ulceration often with crypt abscesses (not specific). +P-ANCA, -ASCA. 30% have a colectomy after 15-25 yrs. Severity is ranked based on the number of stools a day, ie >4 stools a day considered mod/severe.
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Ulcerative Colitis
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MOA of % ASA Compounds for IBD ie Sulfasalazine and Mesalamine. Indications?
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Inhibits prostaglandin synthesis, scaves free radicals. Indicated for moderate Colitis. Side effects include n/v/ha
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Name 2 antibiotics indiated in parianal disease, fistulizing disease and maintenance post ileal recection in IBD?
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Metronidazole 10-20mg//kg/d
Ciprofloxacin 500 mg BID |
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Name a foam corticosteroid used in Chron's Colitis (not indicated if there are fisutlas)
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Budesonide (Entocort) used in moderate ileaitis and right sided chron's colitis. Induces remission, not for maintenance.
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Name a purine synthesis inhibitor used in IBD which induces T cell apoptosis. Pancreatitis is the major side effect, as well as myelotoxicity and hepatotoxicity. As well as increased risk of B cell lymphoma,up to 4x.
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Thiopurines including Azathioprine and 6 mercaptopurine are immunomodulators which require 8 weeks to work for maintenance therapy in IBD
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MOA of methotrexate? Main side effects. Use in Chrons.
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Methotrexate is a folate analogue which inhibits T cell s. Aovid alcohol as there is a risk ofr hepatitis and hepatitic fibrosis, myelotoxicity and mouth sores.
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Name 2 calcineurin inhibitors and their side effects.
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Cyclosporine and Tacrolimus. Side effects include nephrotoxicity, parethesias and tremors. Only used for IBD when in hospital and failed steroids. Careful monitoring of trough levels.
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3 Biologics used in IBD: MOA?
Remicade Humira Certolizumab |
TNF alpha inhibitors. Biologics are used in severe CD and UC and when there is fistulizing disease.
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Major side effect of the new biologic agent used in IBD called Tysabri, an alpha 4 integrin inhibitor.
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Since Tysabri can cross the BBB the risk for the JCvirus causing multifocal leukoencephalopathy is increased.
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What conditions conditions do you get baseline LFTs before treating for TB
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HIV infection, hx of liver dz, alcoholism, pregnancy
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Describe the standard treatment regimen of TB
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2 month initial phase with 4 drugs: Isoniazid, rifampin, pyrazinamide, ethambutol. Continuation phase additional 4 months with isoniazid and rifampin.
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What are the two best drug choices for treating TB in a patient with liver disease?
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Streptomycin and Ethambutol.
Alternative treatment regimens include FQ and aminoglycosides. |
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When are Mesalamine and Sulfasalazine indicated for IBS?
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These 5 ASA compounds are indicated for moderate colitis and are free radical scavengers. Side effects include n/v/ha
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Is isoniazid a cyp450 inducer or inhibitor
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Isoniazid a TB med is an inhibitor of CYP450 increasing other drug levels. Rifampin commonly given with Iosniazid is an CYP 450 inducer and has a predominant effect
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Most and least hepatotoxic TB drugs?
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Most toxic TB drug is PZA (pyrazinamide). Least toxic is ethambutol.
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For mild liver disease do you hav eto change the TB regimen?
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No just monitor LFTs carefully. Avoid PZA in moderate liver toxicity. Change to rifampin, ethambutol or FQ if severe.
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Name anti rank ligand
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Denosumab
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Most cost effective therapy for prostate cancer
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Diethylstilbestrol (DES)
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Cause of migranes?
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Inflamation of the dura/vessels causes pain and associated autonomic dysfunction. Spreading cortical depression causes aura.
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Name 2 migrane aborting drug classes?
Name 2 migrane preventing drugs? |
1) ergots (dihydroergotamine) and tryptans (Imitrex, Zomig) to abort migranes
2) Tricyclics, BB, antieleptics, anxiolytics are all helpful in avoiding migranes. |
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What is the least anticholinergic TCA?
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Desimprime is the least anticholinergic. Giving a bedtime dose helps with side effects, good for migrane prevention.
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OTC migrane cocktail?
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NSAID, Meclizine, Draminine, Antiacids, Benadryl, Alcohol
Abort- caffeine, stimulants, cold shower, avoid food triggers. |
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Patient tells you that their head hurts all the f-ing time. Long duration >10 yrs. Adjunt of muscle pain, depression ,sleep problems, Dx?
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Chronic Daily Headache.
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Patient with Horners syndrome, sharp retroocular pain. Patient is a male smoker. Site is teh ciliary ganglion.Frequent grouped headaches. Dx?
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Cluster headache. Tx is oxygen and tryptans
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Contrast acut and chronic rejection, cell types, timing?
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Acute (cellular) 1w-3mo. Mixed inflammatory cells
Chronic (Fibrotic) rejection >6 months. A cellular fibrosis. |
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Treatment for organ transplant rejection?
For steroid refractor rejection? |
High dose Solumedrol for 3 days or prednisone
Steroid refractory try OKT3 T cell antibody or antibody to IL2 |
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Pros and cons of tacrolimus and cyclosporine in acute rejection?
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Tacrolimus has lower mortality, morbidity and steroid resistant rejection then cyclosporine (but its side effects are worse, it can cause diabetes!)
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Name 2 calcineurin blockers in transplant meds
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Cyclosporine and Tacrolimus.
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Your transplant patient is obese and has metabolic syndrome. What drugs do you want to try to avoid in his treatment regimen to prevent diabetes and CV events?
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Cuyclosporine is associated with hypertensionv
Tacrolimus and prednisone are associated with diabetes Sirolimus is associated with hyperlipidemia. |
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Which two transplant meds have the most renal toxicity?
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Tacrolimus and cyclosporoin (calcineurin inhibitors) have most renal problems. 30% of liver tx patients have CRF in 10 years
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What class of transplant drug has neutropenia as a main side effect?
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Purine inhibitors lead to decreased cell counts, these include MMP and azathioprine. Follow WBC counts.
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Can NSAIDs cause elevated LFTs?
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YES YES YES
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What side effects do non specific nsaids have in addition to blocking COX 1 ?
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COX 2 inhibition results in teh blocking of prostacyclins hwich help with vasodilaton and inhibition of platelet aggregation.
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Common culprit for aseptic meningitis?
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NSAIDs specifically ASA.
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Name a weakly basic drug with increased absorption in the less acidic gastric environment of the elderly?
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TCAs amitryptaline.
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Lipid soluble drugs such as benzos (especially Librium (chloriazepoxide)and Valium (diazepam) are particularly dangerous in what population?
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The relatively high fat content in the elderly makes lipid soluble drugs mor edangerous.
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What are the best benzo choices for the elderly?
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Oxazepam, tamazipam, lorazepam are best for the elderly because they have shorte rhalf lives, fewer toxic metabolites, less fat solublel.
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What is the yearly decrease in hepatic blood flow by year after age 40?
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You lose 1% every year after age 40, ie 50 year old is at 90% of their previous hepatic flow.
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Name 3 drugs that need to be renally dosed.
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Digoxin, Aminoglycosides, Ranitidine (H2 blockers), PCN, Allopurinol, Cephalosporins (Except ceftriaxone), Amantadine, Lithium, Reglan, Gabapentin, LMWH (Doltaparin).
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Give an example of a drug with a small Vd (very water soluble) which will require increased dosing in infants.
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Aminoglycosides will be higher doses in kids vs adults.
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Name a drug with a high Vd which will require larger dosing in obese patients.
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Lorazepam and propofol are lipid soluble with high Vd.
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Symptoms and treatment of Mustard Gas Exposure?
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pancytopenia, rash and blistering, delayed duration of response (2-4 hours later), conjunctivitis, burning skin, upper airway injury rarely BOOP. Increases risk for lung and skin CA. Decontaminate and symptom control
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Symptoms and treatment of nerve "gas" exposure?
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SLUDGE- salivation, lacrimation, urination, diarrhea, gastroenteritis. These individuals also twitch and can seeze due to ACh excess at the neuromuscular junction. Nerve gas works by blocking acetylcholinesterase. Treatment is with Atropine and anticholinergic which blocks the muscarinic receptors helping decrease secretions while Pralidoxime helps regenerate cholinesterase and block teh nicotinic sites. Additional skeletal muscle supression is needed with benzos to prevent seizures.
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What combo drug has both atropine and pralidoxime?
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Duodote.
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What drug do people take in preparation for a nerve gas strike which has a shorter term blocking of cholinesteras?
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paridostigmine
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