Pharm 39 Objectives Flashcards
What is the type of insulin deficiency in type-1 DM?
- Lack proper B-cell function and insulin deficient
- Insulin is life-saving drug for pts with type 1
What is the type of insulin deficiency in type-2 DM?
- Insulin resistant - suboptimal response to insulin
- Insulin can be administered to overcome resistance and promote increased cellular glucose uptake
What is Amylin and where is it produced and released by?
- “satiety” (fullness) hormone
- Produced in and released by pancreatic B-cell and co-secreted w/insulin
What are the physiologic actions of Amylin (pharm name Pramlintide)?
- Reduced appetite
- Decreased gastric motility/slows gastric emptying
- Lowers post-prandial glucose peak
- Decrease glucagon release
What is Glucagon secreted by?
Secreted by pancreatic a-cells
What are the physiologic actions of Glucagon?
- SubQ injection to increase glucose during hypoglycemic emergencies
- Relaxation of smooth muscle in GI tract
- Positive inotropic and chronotropic effect of the heart.
What is Glucagon-like peptide (GLP) secreted by?
Secreted by the intestinal L-cells, not the pancreas.
What are the physiologic actions of GLP 1?
- Inhibits glucagon secretion
- Potent stimulator of insulin syntheses and release
- Slows gastric emptying and has anorectic effect
What are the physiologic actions of GLP 2?
Primary GI effects
Somatostatin causes widespread inhabitation of what?
Inhibition of endocrine and exocrine fxn of pancreas, gall bladder, and gut
Somatostatin inhibits secretion of what hormones?
- Growth hormone
- Glucagon
- TSH
- Insulin
- LH
- Vasoactive intestinal peptide (VIP)
- PTH
- Calcitonin
What are the similarities of the various insulin preparations?
- All “human insulin”
- Equipotent (ie: equal serum concentration reduce serum glucose similarly)
- All given by injection (most are subQ injection, except insulin-R is given IV)
What are the differences of the various insulin preparations?
Pharmacokinetic properties differ based on onset rapidity and duration of action.
What is rapid acting insulin good for?
Good for post-prandial glucose spikes (ie: meal time coverage)
What is the onset, peak, and duration of rapid acting insulin?
- Onset: 5-15 min
- Peak: 1-2 hrs
- Duration: 3-4 hrs
What is the onset, peak, and duration of short acting SubQ insulin?
- Onset: 15-60 min
- Peak: 2-4 hrs
- Duration: 4-8 hrs
What is the onset, peak, and duration of short acting IV insulin?
- Onset: <15 min
- Peak: 15-30 min
- Duration: 5-15min
What is the onset, peak, and duration of intermediate acting insulin?
- Onset: 2-4 hrs
- Peak: 4-12 hrs
- Duration: 10-20 hrs
What is the onset, peak, and duration of long acting insulin?
- Onset: 1-3 hrs
- Peak: no peak?
- Duration: 18-24+ hrs
What are the generic rapid acting insulin names?
- Lispro
- Aspart
- Glulisine
What is the generic short acting insulin names?
- Regular insulin (SubQ)
- Regular insulin (IV)
What is the generic intermediate acting insulin name?
- Neutral Protamine Hagedorn (NPH)
What is the generic long acting insulin names?
- Detemir
- Glargine
- Degludec
In general terms what modifications are made to make a rapid-acting insulin faster acting than regular insulin?
- Longer acting is d/t slow release from the injection site
- Rapid-acting inhibits hexamer formation allowing it to produce a rapid-acting effect from the injection site.
What 2 diabetes medication classes are most likely to incite hypoglycemia?
- Insulin
- Sulfonylureas (2nd gen agents higher potency compared to 1st)
How do you manage a hypoglycemic episode in a conscious pt?
- Oral glucose dose of 15 gram
- Monitor BD and repeat dose after 15 min if necessary
- Glucagon may be given to a conscious patient, but oral glucose is preferred.
How do you manage a hypoglycemic episode in an unconscious pt?
- Subcutaneously-injected glucagon
- Once the patient is conscious, the patient should receive some glucose supplementation to replenish hepatic glycogen stores.
- Intravenous glucose (a.k.a., “dextrose”) is an acceptable alternative to glucagon when practical.
What step of insulin release is the mechanism of action of the sulfonylurea (and other secretagogue) drugs?
Closing the ATP sensitive potassium channel
What is the MOA of Metformin (Biguanides)?
- “insulin sensitizer”
- Decreases hepatic glucose production
- Decreases intestinal absorption of glucose
- Improves insulin sensitivity (increases peripheral glucose uptake and utilization)
What is the effectiveness of Metformin?
- 1st line
- Lowers A1c by 1.0%, potentially 1.5%
- Mono-therapy or used w/ any anti-diabetic drugs
What are the CI of metformin?
- Concern for lactic acidosis
- Kidney disease
- Acute/unstable HF
- Drug interactions: Furosemide, anti-HIV, phenytoin, EtOH
What level of GFR do you NOT want to start Metformin? Also, what level of GFR do you need to d/c Metformin in a pt that has been taking it.
- Don’t start: <45 mL/min
- Discontinue: <30 mL/min
What are the ASEs of Metformin?
- Nausea
- Diarrhea
- Abdominal cramping
- Reduce vitamin B12 - megaloblastic anemia is rare
- Tablets can be malodorous (ER tabs usually less so)
What should you have a pt do to improve GI tolerance to Metformin?
- Take at the end of meal
- ER formulation
- Start with 500mg daily or BID then increase
What is the MOA of Thiazolidinediones?
- Agonism of PPAR-y receptor located on adipose tissue
- Promotes uptake of circulating fatty acid in fat cells and increases cellular glucose uptake.
What is the effectiveness of Thiazolidinediones?
- Highly efficacious
- However, improvement of A1c occurs overtime, weeks to months, 1.0 to 1.5%
What is the CI of Thiazolidinediones?
Hepatocellular disease in pts with ALT levels >2.5x the normal level
- Monitor liver enzyme
What is the ASEs of Thiazolidinediones?
- Water retention and weight gain or increase adiposity
- Bone density loss
- Increased fracture risk in women and maybe men
Water retention caused by Thiazolidinediones may worsen or cause what?
- May worsen or be confused w/ HF S/Sxs
- Macular edema
- Anemia
What is a BBW of Thiazolidinediones?
May cause of exacerbate CHF
What is the MOA of Sulfonylureas?
- Binds to and inhibits sulfonylurea receptor-1 (SUR1)
- Closes K-channel
- Leads to B-cell depolarization and insulin exocytosis.
What is the effectiveness of Sulfonylureas?
- Variable effectiveness in lowering A1c
- 2nd Gen: 0.5-1.5%
What is the CIs of Sulfonylureas?
- Avoid in pts w/sulfa allergies
What is the ASE of Sulfonylureas?
Hypoglycemia
What is the MOA of Glinides (short-acting secretagogues)?
- Closes ATP- senstive K+ channel of pancreatic B cell to stimulate insulin release
What is the effectiveness of Glinides (short-acting secretagogues)?
- Shorter acting, give prior to eat meal
- A1c lowering only 0.5-1.0%
- No sulfa group
- Multiple doses 3-4x per day
- $$$
What are the CIs of Glinides (short-acting secretagogues)?
- Do not use w/ insulin of other secretagogues
- If a meal is missed hold dose.
What is the MOA of Glucagon-like-peptide (GLP)-1 agonists?
- Stimulates inulin secretion
- Suppresses post-prandial glucagon secretion
- Slows gastric emptying
- Produce an anorectic effect
What is the effectiveness of Glucagon-like-peptide (GLP)-1 agonists?
- Works well on reducing serum glucose levels including post-prandial glucose
- Victoza: 1.0% or more reduction in A1c
- Decreased risk for MI
What is the CI of Glucagon-like-peptide (GLP)-1 agonists?
Pts with person or family hx of medullary thyroid carcinoma or in pts with multiple endocrine neoplasia syndrome type 2 (MEN 2)
What is the minor ASEs of Glucagon-like-peptide (GLP)-1 agonists?
- Nausea
- Some weight loss
- Slows absorption of other orally administered drugs
- Risk for hypoglycemia when used in combinations w/ insulin or an insulin secretagogues
- HA
- Infections
What is the serious ASEs of Glucagon-like-peptide (GLP)-1 agonists?
- Pancreatitis
- Immunological rxns
- Acute kidney injury
- Angioedema
What is the BBW for Glucagon-like-peptide (GLP)-1 agonists?
Thyroid c-cell tumors
What is the MOA of Dipeptidyl peptidase (DPP-4) inhibitors?
- Inhibition of dipeptidyl peptidase-4
- Increases endogenous GLP-1 concentration
- DPP-4 is a ubiquitous enzyme that metabolize the incretins (ie GLP-1)
What is the effectiveness of Dipeptidyl peptidase (DPP)-4 inhibitors?
- Not as effective, 0.5% to 0.8% reduction of A1c.
- But advantage is that it is oral administration and weight neutral
- Preferred over GLP-1 by most pts
- Can be used as monotherapy or w/ metformin to decrease A1c up to 1.5 to 2.0%
What is the CI of Dipeptidyl peptidase (DPP)-4 inhibitors?
Do not used w/ GLP-1 d/t MOA
What is the ASE of Dipeptidyl peptidase (DPP)-4 inhibitors?
Risk for Hypoglycemia when used with SU
What is the MOA of SGLT-2 inhibitors?
- Low blood glucose by increase urinary excretion of filtered glucose
- Allows for reabsorption via the sodium glucose co-transporter SGLT
(This transporter can become saturated and that’s what causes glycosuria.)
What is the effectiveness of SGLT-2 inhibitors?
- A1c reduction of 1.0%
- Low risk for hypoglycemia
- Can reduce systolic BP 3-5 pts
- Weight loss
- Reduce CHF and renal events w/ DM2
(eGFR >30 and estimated urine albumin excretion >300 mg/day)
What is the CIs of SGLT-2 inhibitors?
- Severe renal impairments and reduce glucose lowering effect in pts with impaired kidney fxn
- In women with increased risk for GU infxn
What is the ASEs of SGLT-2 inhibitors?
- GU infections: vaginal candidas
- Diabetic ketoacidosis w/o elevated glucose “Euglycemic DKA”
- Associated w/ amputation
- Fournier gangrene
- Fracture risks
What is 1st line tx for DM?
Metformin and/or Insulin tx
What is 2nd line tx for DM?
- GLP-1 agonist
- SU
- DPP-4 inhibitors
- SGLT-2 inhibitors
What is 3rd line tx for DM?
- a-Glucoside inhibitors
- Bile sequestrants (colesevelam)
- Thiazolidinediones
- Bromocriptine
What should you start with and when should you consider switching to insulin?
Start with oral and switch to insulin if do not meet goal with combination of three or more oral agents
What is the ABCDE for tx of DM?
- Abstinence from tobacco
- B/P (<140/90)
- Cholesterol (moderate/high-intense statins)
- Diabetes meds (A1c <7%) and Diet
- Ecotrin=Aspirin and Exercise
What were the issues with Phenformin?
- Higher rates of mortality and lactic acidosis
- Monitor in any pt but CI in pt with kidney disease or acute/unstable heart failure
What were the issues with Troglitazone?
Rare but severe liver toxicity
What were the issues with Rosiglitazone?
Myocardial infarction
What were the issues with Pioglitazone?
Poss. lower liver and MI risks but increased risk of bladder cancer
What is the ACC/AHA guidelines that identify how pts w/ DM should be treated with statins?
Ages 40-75 should receive moderate intensity statin therapy w/ an option of using high intensity stating therapy for those with > or equal to 7.5% 10 yr ASCVD risk.
What is high intensity statin therapy?
- LDL lowering from baseline by 50% or more.
- Only two statins are capable of this, Rosuvastatin and Atorvastatin (at the very highest dose of 80 mg, but many patients may only be able to tolerate 40 mg
What is moderate intensity statin therapy?
- LDL lowering of 30-50%.
- All of the statins (some at the highest doses for the less potent statins) are capable of this degree of LDL lowering.
What are pt at risk for when they have both HTN and DM?
- MI
- CVA
- Microvascular endpoints
- Amputation or death from PVD
- Heart failure
What are the best tx options for type 1 and 2 in pts with both HTN and DM?
- Type 1: ACE-inhibitors
- Type 2: ARBs (most evidence) ACE-inhibitors can be used as well)
What is the target BP for type 2 pts with both HTN and DM?
<140/90 but <130/80 if tolerated and possible
What are the two most commonly used antiplatelet drugs used in patients with diabetes?
- Aspirin (usually 81 mg)
- Clopidogrel to reduce risk for CV events in pts with DM
What are the names of the 2nd gen Sulfonylureas (“SFUs” or “SUs”)?
- Glipizide
- Glyburide
- Glimepiride
What are the names of the Non-sulfonylureas/short-acting secretagogues?
- Repaglinide
- Nateglinide.
What are the names of the Thiazolidinediones?
- Pioglitazone
- Rosiglitazone.
What are the names of the Glucagon-like-peptide-1 agonists (GLP-1)?
- Exenatide
- Exenatide ER
- Liragultide (Victorza and Saxenda)
- Dulaglutide
What are the names of the Dipeptidyl-peptidase-4 inhibitors (DPP-4)?
- Sitagliptin
- Saxagliptin
- Linagliptin
- Alogliptin
What are the names of the Sodium-glucose transport inhibitors (SGLT-2)?
- Empagliflozin
- Canagliflozin
- Dapagliflozin
- Ertugliflozin
When would you use Liragultide (Saxenda)?
- Use as an adjunct to reduce calorie diet and increased physical activity for chronic weight management in adult pts w/ obesity or overweight + weight related comorbidity
