Endocrine Pharmacology Flashcards
Levothyroxine
Synthetic T4 that is converted to T3 by 5’ deiodinase in peripheral tissue. T3 and to a smaller degree T4 ten bind to thyroid hormone nuclear receptors in target cells to exert their effects
Indications for levothyroxine
Hypothyroidism
Myxedema coma
MOA levothyroxine
Isomer of thyroid hormone T4, which like it is converted to T3 by 5’deiodinase. T3 binds thyroid hormone nuclear receptor which results in brain maturation, bone growth, beta adrenergic effects and increased basal metabolic rate
T3 has higher potency
10x higher
Side effects levothyroxine
Hyperthyroid symptoms
What are some hyperthyroid symptoms
Tachycardia, heat intolerance, tremors, arrhythmias
PTU (propylthiouracil)/methimazole
Used in patients with hyperthyroidism
MOA PTU /M
Block action of thyroid peroxidase, thus inhibiting thyroid hormone synthesis. Additionally PTU has peripheral activity blocking conversion of T4 to the more active T3
Side effects PTU/M
Agranulocytosis and skin rash
Additional side effects of PTU
Hepatotoxicity
Additional side effects methimazole
Teratogen
Indications for PTU/M
Hyperthyroidism
Bc inhibit thyroid hormone synthesis, helping to alleviate symptoms in patients
MOA PTU/M
Inhibits thyroid peroxidase which aids in oxidation of iodide. This interrupts the organification of iodine, which leads to inhibition of thyroid hormone synthesis
PTU blocks peripheral conversion of T4 to T3-alleviates symptoms of hyperthyroidism
Pride effects PTU/M
Agranulocytosis, skin rash, hepatotoxicity(PTU), teratogen (M)
Teratogen of M
Aphasia cutis, which is a congenital focal absence of epidermis. Preg should be on PTU and not M espicially in first trimester
Insulin
Analogs of human hormone
Short duration
Intermediate duration
Long duration
Rapid activating insulin’s
For meals eaten at same time of injection
10-30 minute onset
1-3 hours peak
3-6 hour duration
Examples of rapid acting insulting
Lispro (humalog)
Aspart (novolog)
Glulisine (apidra)
Insulin lispro
Rapid acing analog of regular insulin
Before or after eating
Aspart
Analog of human insulin with a rapid onset
5-10 min before meals
Glulisine
Synthetic analog of natural human insulin
Administered close to time of eating
Short acting insulin
Within 30-60 minutes as the onset of action is 30-60
2-4 hours peak
Duration 6-10 hours
Example of short acting insulin
Regular insulting (humulin R)
Regular insulin (humulin R)
Unmodified human insulin
Before meals to control postprandial hyperglycemia or infused subQ to provide basal glycemic control.
Immediate acting insulin
Half the day or overnight often combined with rapid or short acting insulin. Onset 1-2 hours peak 4-12 hours duration 15-24 hours
Example of intermediate acting insulin
Isophane NPH (humulin N)
Isophane humulin N
Intermediate acting bc onset of action is delayed and duration is longer. Therefore this insulin type cant be administered at mealtime to control postprandial hyperglycemia, but instead is used to provide glycemic control between meals and during the night
Long acting insulin
full day
Combined when needed with rapid or short acting insulin
Onset 1 hour
No peak
Example of long lasting insulin
Detemir (levemir)
Glargine (lantus)
Detemir (levemir)
Long acting for basal control.
Canc ause weight gain or hypoglycemia more than intermediate acting NPH.
Do not mix and indicated onyl as subcutaneous injection
Glargine (lantus)
Once a day to mimic the basal rate of insulin normally in body
Indicated only as subcutaneous injection and not mixed (like detemir)
Metformin
Biguanide class of diabetic drugs. First line fo diabetes II and can also be used for PCOS
Side effects metformin
Lactic acidosis, GI distress
Who should not take metformin
Patients with renal failure
Indications for metformin
TIID
PCOS
Why metformin first line for DMII
Does not cause hypoglycemia inline othr drugs
PCOS metformin
Promote ovulation since insulin resistance may contribute to inhibition of normal ovulation. Can also assist with weight loss
MOA metformin
Unknown but decreases gluconeogenesis and increases insulin sensitivity
Side effects metformin
Lactic acidosis, GI distress (diarrhea nausea vomiting)
Contradiction to metformin
Renal failure
Creatinine greater than 1.5 mg/dL no no
Chlorpropamide and tolbutamide (or Incase 1st generation sulfonylureas)
Promote insulin release. Increasingcirculating insulin to maintain normal blood glucose levels int he body
Indications for chlorpropamide and tolbutamide
TIID who have the ability to produce insulin.
Why are first generation sulfonylureas rarely used
Lower potency and significant drug drug interactions
Side effects chlorpropamide and tolbutamide
Hypoglycemia and CV toxicity
Who should not take chlorpropamide and tolbutamide
Pregnant, breastfeeding, consuming alcohol, or taking beta blockers
MOA first generation sulfonylureas
Oral hypoglycemic rarely usedstimulate pancreatic islet cells to release insulin. Bind to ATP sensitive k channels and cause depolarization of the cell membrane. ca enters the cells while insulin is released into the blood stream
Indications 1st generation sulfonylureas
TIID
Side effects 1st generation sulfylureas
Hypoglycemia and possible cardiovascular toxicity
Hypoglycemia and sulfonylureas
Increase insulin release and may cause hypoglycemia .
Since these drugs are metabolized int he liver and excreted by the kidneys , dysfunction in either organs may cause drug toxicity and fatal hypoglycemia
Ok
1st gen sulfylurease cardiotixicity
Sudden cardiac deathmainly tolbutamide
Why no put someone on 1st gen suldyluearse on beta blocker
Reduces effects due to insulin suppression
Why avoid 1st gen sulfyurease in preg and breast feeding
Teratogen is and should be avoided during preg
Newborn severe hypoglycemia lasting 10 days.
Is in breast milk
Why avoid alcohol with 1st gen sulfyureasel drugs
Combo causes disulfiram-like reaction manifesting with flushing, palpitations, and nausea. Alcohol also potentials the hypoglycemic effects of the sulfonylurea medications
Gluburide and glipizide (2nd generation sulfonylureas)
Stimulate the release of insulin from pancreatic islet to increase the amount of circulating insulin to maintain blood glucose
Indication for 2nd generation sulfyonlureas
TIID who can produce insulin
Replace 1st gen due to their increased potency and fewer sided drug drug interactions
Side affect 2nd gen
Hypoglycemia
Who should not take 2nd gen
Alcohol
Also not breastfeeding (except glyburide
MOA 2nd gen
Replace 1st
Lower dose than 1
Clocks K channels in beta cells
Depolarizers cells..ca influx and insulin out!
Indications 2nd gen
TIID
With some pancreatic function
Side effects 2nd gen
Hypoglycemia
What patients on 2nd gen are more susceptible to hypoglycemia
Hepatitis or renal failure
2nd get are __ potent that 1st gen
More
Need lower dose
Why avoid beta blockers on 2nd gen
Can mask hypoglycemia
Also decrease the effect by suppressing the release of insulin
Why avoid alcohol with 2nd gen
Potentials hypoglycemia effects
Why avoid 2ng gen in breastfeeding
Hypoglycemia in new Borns lasting 10 days
How treat diabetic breast feeders
Insulin
Pioglitazone (thiazolidonediones)
Stimulates receptors inthe body to increase cellular responses to insulin, thus decreasing insulin resistance.
Pioglitazone is only effective int he presence of ___ and can only be used to treat ___
Insulin
TIID
Side effects pioglitazone
Upper respiratory infections, muscle pain, sinusitis, headache, and heart failure, increased risk for bladder cancer, women taking this are more prone to bone fractures
Why should liver enzymes be checked whole on pioglitazone
Liver toxicity risk
Suffix for pioglitazone
Glitazones
Also referred to as TZds
MOA thiasolidinedioners
Bind and stimulate peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear cel transcription regulator that increases cellular response to insulin, espicially in peripheral tissues. This decreases insulin resistance in TIID
Indications for thiazolidinediones
TIID
It increases uptake of glucose by skeletal muscle and fat cells, thus lowering blood sugar
IDE effects pioglitasone
Weight gain Heart failure Myalgia Hypoglycemia URI
Considerations on pioglitazone
Risk of bladder cancer if high dose
(Pain urinating sign)
Increase risk of fracture in women (do weight bearing exercises and take VD)
Monitor liver enzymes almost taken off market due to hepatic toxicity
Acarbose (precose) and miglitol (glyset) (alpha glucosidase inhibitors )
Control blood glucose by inhibiting an intestinal enzyme that converts complex carb into digestible forms so that decrease the rate of carb digestion and absorption and decrease rise of glucose after eating
Indications for alpha glucoidase inhibitors
TIID
Side effects alpha glucosidase inhibitors
Flatulence, cramps, diarrhea, and anemia..also may cause liver damage so do liver function test
MOA alpha glucosidase inhibitors
Alpha glucosidase breaks down oligosaccharides and complex carbohydrates into digestible monosaccharides. Inhibit it.
Does not rely on presence of insulin
Indication for acarbose and miglitol
TIID uncontrolled by diet and exercise
Can be given alone of with insulin and metformin
Side effects acarbose and miglitol
Flatulence, diarrhea, anemia, cramps
Anemia and acarbose and miglitol
Decrease SI ability to absorb iron
Consideration acarbose and miglitol
Monitor Liver function test (AST, ALT)
Why give oral glucose for hypoglycemia on alpha glucosidase inhibitors and not sucrose
Alpha glucosidase inhibitors interfere with sucrose hydrolysis and delta its effects
Repaglinide and nateglinide (meglitinides)
Oral hypoglycemic medications classified as gliniders
MOA glinides
Stimulate the pancreatic cells to release more insulin, decreasing blood glucose levels
Side effects meglitinides
Hypoglycemia
Why eat meglitinides within 30 min or administration
Short half life
Gemfibrozil (lopid) if taken with (meglitinides)
A cholesterol med
Decreases the metabolism rate of meglitinides and should not be administered to prevent drug accumulation leading to hypoglycemia
MOA meglitinides
Bind ATP dependent k channels on pancreatic beta cells to result in increase insulin increase by calcium influx
Indication meglitinides
TIID who have decreased circulating insulin
Alone or in combo with metformin or glitazone
Side effects meglitinides
Hypoglycemia
Considerations meglitinides
Eat within 30 minutes
Glemfibrosil increases risk of hypoglycemia(a cholesterol medication which inhibits the metabolism of meglitinides and causes drug accumulation in blood)
Horn half life
Sitagliptin (januvia and saxagliptin (onglyza) (DDP-4 inhibitors)
Antidiabetic meds that work by blocking DDP-4 enzyme, wallowing for increasedaction of incretin hormones and increased release of insulin
DPP-4 inhibitors are only effective in the presence of ___ and can only be taken by patients with ___
Insulin
TIID
Indication for DPP-4 inhibitors
Third line med for the treatment of diabetes and should only be used if first and second line medications have failed to provide adequate blood glucose control.
Side effects DPP-4 inhibitors
URI, pancreatitis, hypersensitivity reactions
Suffix DPP4 inhibitors
Gliptin
MOA DPP-4 inhibitors
DPP4 inactivated incretin hormones so when blocked, the action of incretin is increased, releasing insulin
Indications for DPP-4 inhibitors
TIID with insulin presence
Third line meds used in conjunction with diet and exercise
Side effects DPP4 inhibitors
Pancreatitis, RURI and inflammation, SJS
Consideration DPP4 inhibitors
3rd line if 1st and 2nd line fail
Pramlintide (symlin)
Injectable hypoglycemic drug indicated for type 1 and 2 diabetes. It is a synthetic amylin analog
MOA pramlintide (symlin)
Supplement mealtime insulin to maintain glucose despite insulin therapy
Side effects pramlintide
Nausea and reactions at injection site also monitor for hypoglycemia
Why avoid pramlintide with other drugs
It delay the absorption of other meds
MOA pramlintide
Synthetic amylin analog mimics amylin. Amylin decreases postprandial levels of glucose by delaying gastric emptying and suppressing glucagon secretion. Also helps decrease caloric intake by increasing the sense of satiety
Indications pramlintide
Type I and II diabetes
How should we use pramlintide
Supplement at mealtime with insulin in patients who are unable to achieve glucose control despite optimal insulin therapy
It decreases postprandial glucose levels and minimized glucose fluctuations also decreases amount of mealtime insulin needed
Side effects pramlintide
Nausea skin reactions at injection site (itching redness swelling)
Considerations pramlintide
Hypoglycemia when combined with insulin -alone it does not cause hypoglycemia so decrease insulin dose
Causes delayed absorption of other drugs since it delays gastric emptying
Give other drugs at least one hour before take it
Exenatide (byetta)
Injectable hypoglycemic drug indicated for patients with TIID
MOA exenatide (byetta)
Incretin mimetic and GLP-1 synthetic analog
Side effects exenatide (byetta)
Hypoglycemia, nausea, vomiting, diarrhea, pancreatitis, and renal failure
Since exenatide delays gastric emptying it should be administer when
At least one hour after giving other medications.
How is exenatide used
Adjunct therapy and administered with othe antidiabetic drugs
MOA exenatide
Incretin mimetic that increases release from pancreatic beta cells
GLP-1 synthetic analog mimicking action of incretin.
Describe incretin
Released from GI tract cells after meal and activate GLP1 receptors which slow gastric emptying, stimulate glucose dependent release of insulin, inhibit postprandial release of glucagon, and suppress appetite
How do stitagliptin boost incretin
Preventing breakdown of the hormone
Indications exenatide
TIID as adjunctive therapy to other antidiabetic meds such as metformin or sulfonylurea
Also used with lifestyle change
Side effects exenatide
Hypoglycemia, nausea and vomiting, diarrhea, thyroid cancer, pancreatitis, renal failure
Who should not take exenatide
History of pancreatitis
Severe renal impairment
Consideration exenatide
Give one hour after other meds and use in adjunct
Glucagon (GlucaGen)
Polypeptide hormone that causes the hepatic conversion of stored glycogen into readily available glucose.
Indications for glucagon (glucaGen)
Hypoglycemia caused by insulin overdose and not related to starvation
When is glucagon given
When IV glucose not available
Side effects glucagon (GlucaGen)
Nausea and vomiting
What do you do when patient is conscious after given glucagon
Oral carbs within an hour to avoid rebound hypoglycemia. If not improvement give 50% glucose
MOA glucagon made by the alpha cells of the pancreas, glucagon increases the amount of circulating glucose readily available for use.
Yup
What is glycogen
Form of glucose stored int he liver that converts to glucose when necessary
It promotes glycogenolysis or the hepatic conversion of stored glycogen into glucose for blood stream
What does glucagon inhibit
Glycolysis(conversion of glucose to glycogen)
Indications for glucagon
Hypoglycemic emergency
Treat immediately to prevent brain damage, coma, and death
Who is glucagon not indicated for
Hypoglycemia from starvation due to lack of glycogen stores
Side effects glucagon
Nausea and vomiting
Considerations glucagon
Reconstitute powder
Consume oral carbs after regain consciousness
50% dextrose IV if o effect
