Pharmacology Flashcards
CRH stimulates ___ release that leads to eventually release of ___?
ACTH/cortisol
Cortisol has negative feedback mechanism to lower ___ and ___ production?
CRH and ACTH
What are the 2 function of cortisol?
Carb metabolism (stress response)/immune function
Cortisol increase serum ___ level to maintain adequate ___ supply to the brain
Glucose/glucose
Cortisol increase or decrease BP?
Increase by upregulate alpha-1 receptors
Cortisol has pro or anti-inflammatory effects?
Anti-inflammatory
Naturally occurring mineralocorticoids are ___ and ___
Aldosterone and DOC
___ has weak mineralocorticoids effect?
Cortisol
Glucocorticoid is ___?
Cortisol
Cortisol has high/low/similar binding affinity to aldosterone receptor than aldosterone?
Similar
What prevents cortisol from binding AR?
11beta-HSD2 converts cortisol to cortisone (don’t bind to AR)
When do we use supraphysiological dosage of glucocorticoid?
For general anti-inflammatory usage
Pituitary adenoma is also called?
Cushing’s disease
Wide purple looking abdominal striae appears in what?
Cushing’s syndrome
2 of these positive tests are needed to diagnose Cushing’s syndrome?
24-hr urine free cortisol excretion/low dose overnight dexamethasone suppression test/midnight salivary cortisol level
How does dexamethasone suppression test work?
Give dexa at night—->act as cortisol—>suppress the release of ACTH and CRH—>decrease cortisol level—>check cortisol level in the morning (normally should be low)
Why dont we use ketoconazole for Cushing’s anymore?
Hepatotoxicity
What function does Metyrapone tested for? and how?
AP: if AP is normal—>metyrapone blocks cortisol production—>ACTH and 11-deoxycortisol increase (precursor)
Which drug creates glucocorticoid resistance?
Mifepristone
Which drug is used to treat cortisol induced psychosis?
Mifepristone
What is the side effect of Mifepristone?
Adrenal insufficiency
How does Mifepristone causes hypokalemia?
High cortisol level overwhelm 11beta-HSD2—>cortisol binds to AR—>hypokalemia
Which drug is for Cushing’s disease?
Pasireotide
What are primary and secondary adrenal insufficiency? and what is secondary adrenal insufficiency affect?
Primary—>something wrong with the adrenal glands
Secondary—>something wrong with the AP—>low ACTH—>low cortisol, not affect aldosterone
2 main causes of secondary adrenal insufficiency?
Iatrogenic/hypopituitarism
What causes the hyperpigmentation in primary adrenal insufficiency?
High ACTH level
Signs of acute adrenal insufficiency?
HoTN/nausea/vomitting/hyperkalemia (no aldosterone)/hyponatremia (increased ADH)
What drug is used to test for adrenal insufficiency?
Cosyntropin—>ACTH analog—>look for cortisol level
How do you treat chronic primary adrenal insufficiency?
Cortisol/aldosterone replacement maintenance
How to treat acute adrenal crisis?
IV fluid/high dose glucocorticoid (dexa or hydro)
What to do when pt with adrenal insufficiency is ill?
Increase dose of glucocorticoid
Treatment resistance HTN with hypokalemia, think?
Primary aldosteronism
How to diagnose 21-hydroxylase deficiency?
Cosyntropin—>increase 17-OH pregnenolone
Treatment for 21-hydroxylase deficiency?
Steroids (also suppress ACTH—>suppress androgen production)
What are the 2 toxicity of steroids?
Cushing’s syndrome/adrenal insufficiency with sudden withdraw
Thyroid produces which 3 hormones and where are they produced?
T3, T4 and calcitonin/colloid
How does iodide transported inside of colloid and what maintains the gradient?
I-Na symporter/Na K pump maintains the gradient
What do enzymes D1 and D2 do and where are they found?
Convert T4 to T3
D1: liver and kidney
D2: anywhere else
What does the enzyme D3 do?
Inactivate T3
What is the key enzyme in thyroid hormone production?
Thyroid peroxidase
How is thyroid hormone transported from colloid to blood?
endocytosis—>endosome—>fuse with lysosome—>release free thyroid
How does goiter occur in hypothyroidism?
TSH level increase—>thyroid size increases
Which population of pts need more dose of levothyroxine?
Infants and children
When do you need to readjust dosage for thyroid hormone replacement therapy?
4-6 weeks
What underlying disease should you be aware when given thyroid hormone replacement?
CAD/pregos—>need enough for fetal brain development
Both hyper and hypothyroidism causes birth defect
What is the mechanism of Grave’s disease?
Autoantibodies bind to TSH receptor on thyroid glands and produce thyroid hormone
What does nodular goiter produce?
Excessive amounts of thyroid hormones
Young pt with hyperthyroidism, what is the first treatment?
Anti thyroid drugs
What is the process of thyroxine production?
Tyrosine—(thyroid peroxidase)—>diiodotyrosine—(thyroid peroxidase)—>thyroxine
Which drug has lower risk for developing agranulocytosis, methimazole or propylthiouracil?
Methimazole
Which drug is used to treat hyperthyroidism in prego?
Propylthiouracil
How long does radioactive iodine need to start working?
Over 4 weeks
Why is radioactive iodine therapy contraindicated in prego and breast feeding pt?
Prego—>expose fetus to radiation
Breast feeding—>iodine pass into milk
What are cortical and trabecular bones?
Shafts of long bone/spine, ribs, pelves and etc.
40% of Ca is bound to?
Albumin
Hypercalcemia and PTH increases or decrease phosphorus excretion from the kidney?
Increase
The release of PTH needs which ion?
Mg2+
How does Vitamin D becomes active?
Become 25, OH Vit D in liver—>then become 125 (OH)2 Vit D in the kidney
What is the most common cause of primary hyperPTH?
Adenoma
What is the Ca/PTH/urine Ca level for familial hypocalciuric hypercalcemia?
Elevated Ca/normal PTH/low urine Ca
What is the normal serum Ca level?
8-10
Why do we use fluid to treat hypercalcemia?
To increase Ca excretion
What is the most common cause of secondary hyperPTH?
Renal disease—>phosphorus retention and low production of 125 (OH)2 D—>increase PTH
What causes tertiary hyperPTH?
Long standing secondary hyperPTH—>parathyroid gland become autonomous
What should you check first when see a low Ca level?
Albumin
What is the Ca and phosphorus level with Vit D deficiency?
Low Ca and phosphorus
Low phosphorus put pt in risk of ___ and ___?
Osteomalacia/rickets
What is the T score of bone density scan for osteoporosis?
Smaller than -2.5
How should biphosphonate being taken?
Take it first thing in the morning with empty stomach and full glass of water—>remain upright for 30mins
What catalyzes the formation of 1,25 (OH)2 D in the kidney?
1-alpha-hydroxylase
If PTH increase, 1-alpha hydroxylase increase or decrease?
Increase
1-alpha hydroxylase is also called?
1,25 (OH)2 D
Testosterone is converted to DHT by what enzyme in the peripheral?
5 alpha reductase
What is the diagnostic value of HBa1c for DM?
over 6.5
What is the legacy effect regarding DM?
Treat younger pt aggressively, even if they don’t control their blood sugar well later on, they still have fewer complications
What is incretin and what is the most important incretin in human?
Incretin is secreted in the ileum and colon—>it stimulates insulin secretion
Glucagon like people 1 (GLP-1)
What does GLP-1 do? and what is it metabolized by?
Stimulate insulin
promote fullness
suppress glucagon secretion
DPP-4
GLP-1 is increased or decreased in type 2 DM?
Decreased
Pt with risk of severe hypoglycemia should be prescribed ___? and what do you give in the hospital with this situation?
Glucagon injection/IV dextrose
Reasons for oral DM therapy inadequacy?
Stress/diet/steroid usage
How is detemir dosage dependent?
Low dose—>intermediate
High dose—>long lasting
What is U-100 mean in terms of insulin con.?
100 units of insulin per mL
Why is insulin secreted during fasting?
To counter glucagon and prevent ketone acidosis
What’s the advantage of premixed insulin?
Longer shelf life/easier to use (mix long acting with intermediate or low)
What’s the disadvantage of premixed insulin?
Unable to match carb intake or physical activity/
When do we give insulin IV?
Give regular insulin for DKA
Why injecting insulin in the ab region?
Most stable absorption
What should the pt be taking caution when injecting regular insulin?
Regular insulin does not act right away—>might experience hypoglycemia after the meal
Which kind of insulin is the least expensive?
NPH (intermediate)
What would be a cheap program to manage DM? what is its disadvantage?
Regular insulin for breakfast/NPH for lunch/regular for dinner/NPH before bedtime
hypoglycemia at night
What would be a more physiological approach to manage DM?
Use basal insulin (Glargine) daily and then fast acting for each meals
How should the dosage insulin for each meal be determined?
Depends on how much carb is the pt eating
What happens when a pt injects insulin at the same place?
Lipohypertrophy
What kind of insulin is in the Continuous Subcutaneous Insulin Infusion (insulin pump)? and what is its advantage?
Fast acting/you can set basal rate and bolus
The more the pt monitor their glucose level, the better or worse they manage their glucose level
Better
Where do continuous glucose monitoring and finger pricking take the glucose level from?
Continuous: interstitial space (can be a lag)
Finger pricking: capillary
which type of DM do the pt uses continuous glucose monitoring more often?
Type I
What is the first line treatment for type I DM?
Basal bolus insulin therapy—>insulin pump/meal time insulin
What tests should you run for pt with DM?
Lipid panel/kidney and liver function
What else should you screen with type I DM?
Celiac
Difference between primary and secondary adrenal insufficiency?
No hyperkalemia/hyperpigmentation for secondary
Hypoglycemia is more common in secondary
What is the normal value of cortisol?
18-20 ug/ml
What is ACTH stimulation test and what is it for?
Cosyntrophin (ACTH analog)—>cortisol level should increase normally—>exclude primary adrenal insufficiency/but can’t exclude secondary
In what situation can ACTH stimulation test be given after steroid therapy?
If the steroid hasnt been given for a couple of days prior
If cortisol or cortisone were not given
How to avoid HPA axis suppression with chronic therapy?
Use it less than 3 weeks/use alternate day therapy
What is the effect of steroid on bones?
It can induce osteoporosis (Glucocorticoid induced osteoporosis)
What kind of bone does steroid effect?
Trabecula bones
How does glucocorticoid affects Ca absorption?
It inhibits intestinal Ca absorption and causes hypercalciuria
What is glucocorticoid’s effect on leukocyte?
They inhibit leukocyte migration
What is the mechanism of glucocorticoid on immunosuppressing?
Inhibit prostagland and leukotriene production/also inhibit COX 2
Ketoconazole decreases the production of ___ and ___?
Androgen/cortisol
What does thyroid peroxidase do?
It converts iodide into iodine
Why PTU is recommended over methimazole during the 1st trimester of pregnancy?
PTU is more protein bound—>safer
Insulin is increased by what 4 factors?
Glucose/sulfonylurea/M-agonist/beta 2 agonist
Which receptor agonist would decrease insulin?
Alpha 2 agonist
What kind of pt are more likely to develop lactic acidosis when taking metformin?
Pt with renal dysfunction or CHF
What else Metformin can be used for besides DM?
PCOS to offset insulin resistance
What does DPP-4 do?
Degrade GLP-1
What does incretin do?
Secreted by small intestine—>increase insulin and decrease glucagon to lower glucose
What does SGLT-2 do?
Located in proximal tubule to reabsorb glucose
What drugs to give for diabetic neuropathy?
Gabapentin and TCAs
Insulin promote or inhibit fatty acid synthesis in the liver?
Promotes
What population is more prone to “Flatbush diabetes”?
Black/hispanic—>type II DM with DKA
What is the triad for hyperosmolarity hyperglycemia state?
Hyperglycemia/hyperosmolarity/dehydration
Which one has a higher level of serum glucose. DKA or HHS?
HHS (>600)
How much glucose reduction per hour is the goal to correct DKA/HHS?
50-75 mg/dL/hr
When do you give dextrose when managing DKA/HHS
when glucose comes down to 200-300
Which one corrects faster, ketoacidosis or hyperglycemia?
Hyperglycemia corrects faster than ketoacidosis
Why do we need to overlap IV and subQ insulin when the pt is coming out of DKA/HHS?
It takes subQ insulin 1-2 hours to start working
What happens to intracellular K+ during acidosis?
K moves from intra to extracellular to try to buffer the blood—>K seems high—>but actually losing it through excretion—>hypokalemia (ventricular arrhythmia)
What does insulin do to K?
It drives K back into the cell
What ion value should you check before you start insulin for DKA/HHS pt?
K—>if low—>replenish K first and then start insulin
When do we give bicarb to acidosis pt?
When pH is smaller than 6.5 (severe hyperkalemia)
What would happen to K level when giving bicarb?
Hypokalemia
What happens to the Na and phosphate level during DKA?
low
Which ketone is the prominent one in DKA?
beta-hydroxy-butyric acid
What happens to the level of beta-hydroxy-butyric acid/acetoacetic acid/acetone?
Beta-hydroxy-butyric acid is transformed to acetoacetic acid and then to acetone for excretion
What value do we use to determine if the pt is out of DKA?
Closed anion gap/glucose7.3
How do we know that the pt is out of HHS?
Normal osmolality/normal mental status
What is the major complication upon correcting DKA?
Cerebral edema
Which one has higher mortality, DKA or HHS?
HHS (elderly)
What’s the formula for anion gap?
Na - (Cl + HCO3)
What is normal anion gap?
12
What is Winter’s formula? what does it measure?
PaCO2 = 1.5xHCO3 + 8+-2/evaluate respiratory compensation
What does it indicate if the measured PCO2 is higher or lower than the calculated PCO2?
If measured is higher than the calculated—>additional respiratory acidosis
If measured is lower than the calculated—>additional respiratory alkalosis
What is the rule of thumb for PaCO2?
Should be last 2 digits of pH
What is the concept of delta delta?
When anion gap goes up by 1, bicarb drops by 1
In other words—>change in anion gap = change in bicarb
What does it indicate if delta bicarb is greater or less than delta anion gap?
Greater—>anion gap acidosis + non anion gap acidosis (drive bicarb down)
Less—>anion gap acidosis + metabolic alkalosis (drive bicarb up)
What is the triad of DKA?
Hyperglycemia/metabolic acidosis/high ketone
What is the treatment approach for DKA?
Fluid and then insulin or K (check K level—>might have to give K before insulin)
What is the formula for osmolality?
2xNa + urea/2.8 + glucose/18
What would cause decompensation?
Infection/infarct/insulin
What are essentials for dialysis?
Semipermeable membrane/anticoagulant
What is the process of peritoneal dialysis?
Infusion of balanced salt solution with dextrose—>let it sit—>toxin diffuses across the peritoneal membrane—>drain it out
How does AV fistula work?
Dilate vein for insertion of dialysis
Drug dosing formulas are only useful for ___ renal function
Stable
Pt with end stage renal disease (dialysis) need to restrict what intake?
Fluid (kidney can’t put out urine)/sodium/potassium/phosphate
What are the hormone imbalance seen in end stage renal disease pt?
Low EPO/high PTH/low Vitamin D (decrease 1 alpha hydroxylase)
What are the symptoms of uremia?
Loss of appetite/nausea/metallic taste/serositis (pericarditis)
What are the factors that contribute to whether a drug should be replaced after dialysis?
Size (if small)/volume of distribution (if in blood)/no protein bound/duration of dialysis
Besides phosphate restricting, what else should be given with dialysis pt?
Phosphate binders
Should dialysis pt restrict protein intake?
No, encourage protein intake prevent malnurishment
What formula is used for dose adjustment for end stage renal disease pt?
Cockcroft gault formula
When do you start giving maintenance drugs for kidney transplantation?
Days after kidney starts to work
How is the dose for cyclosporin and tacrolimus?
High level in the first month and then taper over the next 2 months
How should mTOR inhibitors be dosed?
High dose early and lower dose later
What are 2 drugs that might increase tacrolimus level?
Diltiazem/fluconazole
Azathioprine interacts with what drug?
Allopurinol
TZD is contraindicated in pt with what condition?
CHF
All oral diabetic medications are contraindicated in what population? What to use instead?
Pregos/insulin injection
If a pt is on glargine daily and lispro for dinner, what is determining her glucose level when she wakes up the next morning, glargine or lispro?
Glargine
What 2 kinds of oral diabetic medications should not be used together?
Sulfonylurea and meglitinide
High Ca and low phosphorus indicates? How?
Excess PTH/High PTH—>high Ca—>bind to more phosphorus—>low phosphorus
What’s the difference between PTU and methimazole?
PTU additionally block the peripheral conversion of T4 to T3
Which drug has higher chance of causing agranulocytosis, PTU or methimazole?
PTU
