Exam II: RAAS, Diabetes drugs Flashcards
Dipines like amlodipine are ?
Calcium channel blockers
Two types of calcium channel blockers based on chemical structure? (Give an example of each)
- Dihydropyridines (DHPs) - amlodipine etc.
2. Non-Dihydropyridines (non-DHPs) - diltiazem, verapamil
Name three differences between DHPs and non-DHPs as far as their effects on the body.
- Dihydropyridine (DHP) CCBs tend to be more potent vasodilators
- Non-dihydropyridine (non-DHP) agents have more marked negative inotropic effects (lower heart rate)
- Non-DHPs more advantageous for patients with chronic kidney disease and diabetic nephropathy.
How do Calcium Channel Blockers (CCBs) control blood pressure?
CCBs regulate Ca2+ influx into cells. This hinders heart contractility, relaxes smooth muscle in the arterial wall and lowers blood pressure.
In addition to vasodilation, what effects do non-DHPs have on the heart?
Decrease the heart rate by depressing atrioventricular (AV) node conduction
What is Raynaud’s Prevention? What medication drug class can treat this disorder?
Raynaud’s Prevention - an idiopathic condition affecting the hands and fingertips, causing them to become cold, spastic, numb and ulcerated.
Dipines can treat this disorder.
This drug class can treat angina (chest pain), afib, tachycardia can migraines.
CCBs
Dipines
Adverse Drug Reactions: Peripheral edema, Orthostasis, Heart block. Name the drug class. (Hint: Treats hypertension)
Non-DHP CCBs
Diltiazem and verapamil
What type of drugs should be used with caution when a patient a taking a CCB? (2)
- Drugs metabolized by Cytochrome P450 3A4
2. Non-DHPs taken with beta blockers
Cautions to take when giving CCBs with these two type of patient populations. (Hint: think age and heart failure)
- Do not use non-DHPs for patients with a a left ventricular ejection fraction of <40%
- Initiate at lower doses in older patients
“RAAS” drugs stands for?
Renin Angiotensin Aldosterone System Antihypertensives
Types of RAAS inhibitors (3)? Give brief description for each.
- ACE inhibitors - Prevents Angiotensin I from being converted to angiotensin II which prevents vasoconstriction and activation of aldosterone
- Angiotensin II receptor blockers (ARBs) - Angiotensin II cannot bind to its receptor
- Direct Renin Inhibitors – Target renin coming directly from the kidneys (prevents the RAAS pathway from occurring to increase BP)
Briefly describe the RAAS pathway.
Lower blood pressure sensed in the kidneys
- Renin released from the kidneys to the blood
- Renin cleaves angiotensin in to angiotensin I (inactive) in the liver
- Angiotensin converting enzyme (ACE) converts Ang I to Ang II (active)
4a. Ang II acts on adrenal cortex - stimulates aldosterone release - Water and sodium retention
5a. Ang II acts on various AT receptors throughout the body to cause cause vasoconstriction, decrease urine output and fluid retention.
Blood pressure increased
Difference between “pril” and “prilat”? ie. Enalapril vs Enalaprilat
Enalaprilat - active metabolite, poorly absorbed, must be admin IV
Enalapril - prodrug (inactive), can be given PO
What type of RAAS drug are “pril” drugs like Benazepril? Also describe mechanism of action.
ACE inhibitors
Prevents conversion of angiotensin I to angiotensin II (potent) by competitive inhibition of ACE
ACE inhibitors AND ARBs are first line therapies for hypertension in what cases? (Name the common factors between the two) –> 6
- Non-African American patients
- Patients with albuminuria
- HF or LVEF less than or equal to 40%
- Coronary Artery Disease
- Post Myocardial Infarction
- Recurrent stroke prevention
Contraindications for ACE inhibitors AND ARBs.
- Bilateral renal artery stenosis (narrowing of renal arteries)
- Pregnancy
- Angioedema (swelling between skin and mucosa typically in the lips) –> most common in African American patients
Adverse reactions for ACE inhibitors AND ARBs. (4)
- Increases in serum creatinine (limited increase as much as 30% okay)
- Hyperkalemia
- Angioedema (occurs 2-4x more in African Americans)
- Dry cough
Angioedema and cough is much less common in ACE inhibitors or ARBs?
Less common in ARBs
What must be monitored when a patient is taking an ACE I or ARB?
Reassess SCr (serum creatine) and potassium K in 1-2 weeks after initiation or dose titration
Much more frequently in patients with renal impairment
Potassium Supplements and other medications that can increase potassium
Cause drug interactions with what type of RAAS drugs?
All three types
ACE I (pril)
ARB (sartan)
DRI (kiren)
Four drug-drug interactions present for ACE inhibitors. (Besides potassium increasing meds)
- Lithium carbonate (ACE I drugs increase lithium levels)
- K+ sparing diuretics like Triamterene + HCTZ - increased risk of hyperkalemia
- NSAID - both drugs affect the kidneys
- Food
What type of RAAS drug are “sartan” drugs like Olmesartan? Also describe mechanism of action.
Angiotensin II Receptor Blockers (ARB)
Inhibits the binding of Angiotensin II to receptors, making the Angiotensin II ineffective as a vasoconstrictor
Also no Na+ retention effect.
What type of RAAS drug are “kiren” drugs like Aliskiren Hemifumarate (Tekturna®)? Also describe mechanism of action.
Direct Renin Inhibitor
Directly inhibits the RAAS at its point of activation; reduces the production of Angiotensin I and Angiotensin II
Therapeutic indication (1) for Aliskiren Hemifumarate (Tekturna®) –> Direct Renin Inhibitor.
Hypertension
Contraindications for Aliskiren Hemifumarate (Tekturna®) –> Direct Renin Inhibitor. (4)
- Pregnancy
- Concomitant use of ACE I and ARBs in diabetic patients - risk of hypotension, renal impairment and hyperkalemia.
- Concomitant use of ACEI or ARBS in patients with a Creatinine Clearance (CrCl) of <60 mL/min/1.73m2 - tests kidney function
- Concomitant use of cyclosporine or itraconazole
High fat meals increase absorption of Aliskiren Hemifumarate (Tekturna®) –> Direct Renin Inhibitor.
True/False
False
High-fat meals decrease absorption substantially
Patients with renal insufficiency should avoid this RAAS drug?
Aliskiren Hemifumarate (Tekturna®) –> Direct Renin Inhibitor.
All hypoglycemic drugs do what? Other names to describe these drugs (2)
Reduce blood glucose
Antidiabetic drugs = antihyperglycemic drugs = hypoglycemic drugs
Where is insulin produced and secreted? What stimulates its release?
Islets of Langerhans β cells in pancreas
Stimulated by increased blood glucose
Two goals of therapy in diabetes mellitus?
- Regulate levels of blood glucose/maintain normal glucose levels
- Avoid ketoacidosis and hypoglycemia
Percentage of patients with DM in the US. Are most diagnosed? More males or females?
14.3% with DM in US
Most undiagnosed in this percentage
Slightly higher percentage of males
Symptoms/signs of DM?
- Polydipsia (Great thirst)
- Polyuria (Frequent dilute urination)
- Polyphagia (Great hunger)
- Weight Loss (Typically Type I)
What sign gives a definitive diagnosis of DM?
HbA1c above 6.5%
Five comorbidities associated with DM.
- Cardiovascular
- Diabetic peripheral neuropathy
- Amputation of Limbs
- Renal [nephropathies]
- Ocular damage [retinopathy]
What is diabetes insipidus?
Caused by a deficiency of the pituitary hormone vasopressin
Failure of renal absorption that leads to larger amounts of dilute urine
What are the levels of blood glucose for pre-diabetic patients (fasting mg/dL and HbA1c)?
Fasting blood glucose 100-125 mg/dL
HbA1c 5.7-6.4%
IDDM (insulin dependent diabetes mellitus)
JODM (juvenile onset diabetes mellitus - insulin deficiency)
Type I or Type II DM?
Type I DM
Insulin desensitization or insulin resistance
Type I or Type II DM?
Type II DM
List risk factors for Type II DM. (7)
- Genetic predisposition
- Age
- Obesity
- Hypertension
- Hypercholesterolemia
- History of gestational diabetes
- Lack of anaerobic exercise
What is gestational diabetes and how common is it?
Pregnant patients with hyperglycemia who were not previously diagnosed (14% of pregnancies usually between the 5-6 month)
Exogenously administered insulin is mandatory in what type of diabetes? Optional in what type?
Mandatory - Type I
Optional - Type II
Diet and exercise is recommended in which type of DM?
Type I and Type II no matter how controlled blood glucose levels are.
Diet and exercise is crucial for all patients.
Routes of administration for exogenous insulin.
SubQ, IM, IV
Normal levels for blood glucose (mg/dL) - fasting, random and oral glucose tolerance test.
Fasting - less than 100 mg/dL
Random - less than 200 mg/dL
Oral glucose tolerance - less than 140 mg/dL
When is an oral glucose tolerance test taken?
2 hours post ingestion of glucose drink
blood glucose vs. HbA1c?
HbA1c reflects your average blood glucose level over the last 10-12 weeks
Each % reduction in HbA1c is equivalent to BG level of how many mg/dL?
% point reduction in HbA1c = 40 mg/dL
At that HbA1c level must exogenous insulin be added to a Type 2 diabetic therapy?
HbA1c > 9%
Nomenclature for sulfonylureas (diabetes) - 5
AMIDE, RIDE, ZIDE, GLI, GLY
First line therapy for Type 2 diabetes
Metformin
How do sulfonylurea lower blood sugar?
Interact with ATP sensitive K channels in the beta cells, thus increase the secretion of insulin
Indications for sulfonylureas. (include off label)
Type II diabetes - not as first line
Off label - diabetes insipidus
Advantages and disadvantages of sulfonylurea therapy.
Advantages – low cost
Disadvantages – weight gain, risk for hypoglycemia
Sulfonylurea drugs cannot be discontinued even if goal HbA1c levels are reached.
True/False
False
These drugs are not intended for continuous use.
A holiday can be attempted if HbA1c goal is reached.
Allergic skin reactions, somnolence, GI upset, pharyngitis.
Adverse reactions seen with this type of hypoglycemic drug?
Sulfonylureas
AMIDE, RIDE, ZIDE, GLI, GLY
Hypoglycemia is a risk of taking hypoglycemic drugs. What are the symptoms?
Usually seen with blood glucose < 70 mg/dL
- Weakness, dizziness, tremors, sweating
- Confusion
- Tachycardia
Pregnancy category for sulfonylureas except for Glyburide.
Category C, except GLYBURIDE (category B)
Glipizide, glyburide and glimepiride are what generation of sulfonylureas?
2nd generation
Chlorpropamide. drug class? generation?
First generation Sulfonylurea
Formin drug class and pharmacological effect on the body?
Biguanides
- Decrease hepatic glucose production
- Increase secretion of GLP-1
- Decrease GI absorption of glucose
How much are Formin drugs supposed to lower HbA1c?
Expected to lower HbA1c 1-1.5%
What is the box warning for Formin drugs?
Lactic acidosis
Symptoms of lactic acidosis? (5)
- Bradycardia, arrhythmias
- Malaise
- Somnolence
- Respiratory dysfunction
- Abdominal pain
Cautions (2) and adverse drug effects (1) when taking Formin drugs?
- May cause GI issues (diarrhea, nausea)
- Renal impairment - not recommended
- Acute liver injury - not recommended
Advantages and disadvantages of taking Formin drugs?
Advantages
- HbA1c reduction by 1-1.5%
- Weight neutral
- Low (no) risk for hypoglycemia
Disadvantages
- GI side effects
- Risk of lactic acidosis
Hypoglycemic drugs with low/no risk hypoglycemia?
- Formin - ie. Metformin
- Glitazone - ie. Pioglitazone
- Gliptin - ie. Sitagliptin (Januvia®)
- Tide/Glutide - ie. Dulaglutide (Trulicity®)
- Gliflozin - ie. Empagliflozin (Jardiance®)
Glinide drugs like Repaglinide are in what chemical drug class? What pharmacological effects do these drugs have?
Meglitinide non-sulfonylureas
- Stimulate insulin release
- Faster onset but shorter duration (rapid release of insulin)
- Reduce hepatic glucose production
Why should a Glinide drug like Repaglinide be taken 15 minutes before a meal?
Lessens risk of hypoglycemia
Advantages of Glinide drugs (meglitinide non-sulfonylureas) over Formin drugs (sulfonylureas). (3)
- More dosing flexibility
- Better glucose control after meals - Rapid onset, shorter duration
- Shown to have better outcome
Disadvantages of Glinide drugs (meglitinide non-sulfonylureas) over Formin drugs (sulfonylureas). (2)
- Marginal HbA1c reduction (0.5-1%)
2. Risk of hypoglycemia
What is the chemical class of Glitazone drugs like Pioglitazone? What pharmacologic effects does it have on the body?
Thiazolidinediones
“Insulin Sensitizers”
1. Reduce insulin resistance
- Increase insulin sensitivity in adipose tissue, skeletal muscle and liver
- Reduce hepatic glucose production
Rosiglitazone maleate (Avandia®) has been formally approved to be taken with insulin.
True/False
False
Pioglitazone is the only Thiazolidinedione drug formally approved to be taken with insulin.
Weight gain, heart failure, anemia, increased fracture risk.
Side effects of what hypoglycemic medication class?
Thiazolidinediones
Rosiglitazone maleate (Avandia®)
Pioglitazone
Rosiglitazone - increased risk of MI
Pioglitazone - increased risk of bladder cancer
True/False
True
How long does it take Glitazone (Thiazolidinediones) drugs to affect blood glucose?
about 2 weeks
A patient fasting for a long period of time can discontinue a Glitazone (Thiazolidinediones) drug.
True/False
True
Warning and precautions for patients taking Glitazone (Thiazolidinediones) drugs?
- Liver impairment (use with caution) - test liver function
- Weight gain
- Peripheral edema (usually in ankles and feet)
Symptoms of abnormal liver function. Especially for patients taking a Glitazone (Thiazolidinediones) drug.
- Jaundice
- Fatigue
- Abdominal pain
Advantages and disadvantages of taking Glitazone (Thiazolidinedione) drugs.
Advantages
- HbA1c reduction 1-1.5%
- Low risk of hypoglycemia
Disadvantages
- Weight gain
- Edema
Gliptin drugs like Saxagliptin (Onglyza®) pharmacological effects on the body? (2)
Dipeptidyl peptidase-4 inhibitors (DPP-4 Inhibitors)
- Suppress glucagon secretion
- Incretin-Mimetic agents - potentiate insulin release and decrease glucagon release
Gliptin drugs like Saxagliptin (Onglyza®) can be used with insulin.
True/False
False
Not to be used in combination with insulin
What hypoglycemic drugs are weight neutral? (2)
- Gliptin - ie. Sitagliptin (Januvia®)
2. Formin - ie. Metformin
Advantages and disadvantages of Gliptin (DPP-4 inhibitors) drugs.
-Advantages
- Weight neutral
- Well tolerated
- Low/no risk of hypoglycemia
Disadvantages
- Marginal reduction of HbA1c (0.5-1%)
- Hypersensitivity reactions (rare) –> Steven-Johnson Syndrome, Anaphylaxis
What are Glucagen® Hypokit, Gvoke HypoPen® used for?
rDNA origin - SubQ injection for hypoglycemic crisis –> treats low blood sugar
What is the chemical class of Tide/Glutide hypoglycemic drugs? What pharmacological effects do they have on the body?
Synthetic peptide
Glucagon-like peptide-1 receptor agonists [GLP-1 Receptor Agonists]
Incretin-mimetic agents
- Suppress glucagon secretion
- Increase glucose dependent insulin secretion
- Slow gastric emptying
- Promote satiety
Tide/Glutide drugs like Dulaglutide (Trulicity®) are weight neutral.
True/False
False
Tide/Glutide drugs have been associated with weight loss
Tide/Glutide drugs like Dulaglutide (Trulicity®) is injected insulin.
True/False
False
These drugs are administered SubQ. However, it is not insulin.
Therapeutic indications for Tide/Glutide drugs like Dulaglutide (Trulicity®)?
Mono or combo therapy for Type 2 diabetes in conjunction with diet and exercise.
What combination therapies exist with Tide/Glutide drugs like Dulaglutide (Trulicity®)?
Can be given in combination with metformin or glimepiride or thiazolidinediones.
Most GLP-1-RA products can also be administered with insulin
Advantages and disadvantages of GLP-1 RA
drugs (Tide/Glutide)?
Advantages
- HbA1c reduction 1-1.5%
- Weight loss
- Low/no hypoglycemia risks
- Reduction in the risk of cardiovascular morbidity/mortality
Disadvantages
- No oral option
- Pancreatitis
- GI side effects
What pharmacological effect do Gliflozin (ie. Empagliflozin (Jardiance®)) drugs have on the body?
Sodium-glucose co-transporter 2 inhibitor (SGLT-2 inhibitor)
- Reduce the reabsorption of glucose
- Increase urinary glucose excretion
- Reduce both fasting and post-prandial blood glucose and HbA1c
Advantages and disadvantages of SGLT-2 Inhibitors (Gliflozin)?
Advantages
- No risk of hypoglycemia
- Weight loss
- Reduction in blood pressure
Disadvantages
- Marginal effect on HbA1c (0.5-1% reduction)
- Pancreatitis
- Hepatic failure
- Urinary tract infection
Name the two Alpha-glucosidase Inhibitors.
Acarbose (Precose®)
Miglitol (Glyset®)
Alpha-glucosidase Inhibitors pharmacological effect on the body?
Inhibit the alpha-glucosidase intestinal enzyme that hydrolyze carbohydrates to monosaccharides in the small intestine
- Delays the absorption of carbs (including glucose) from the GI tract
Alpha-glucosidase Inhibitors can be taken on an empty stomach.
True/False
False
Must be taken with each meal (usually TID)
GI side effects: Flatulence, diarrhea, abdominal pain
