Exam 3 Flashcards
Basic functional unit of the kidney
Nephron
Four functionally distinct regions of the nephron
Glomerulus
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Where does filtration occur in the kidney?
Glomerulus
What is reabsorbed in the kidney?
99% of water, electrolytes, and nutrients
Where does reabsorption occur in the kidney?
Specific sites along the nephron:
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting duct (distal nephron)
Through filtration and reabsorption, what is also regulated in the kidneys?
Sodium-potassium exchange
Regulation of urine concentration
Three basic functions of diuretics:
- Cleansing of extra cellular fluid and maintenance of ECF volume and composition
- Maintenance of acid-base balance
- Excretion of metabolic wastes and foreign substances
Three main classifications of diuretics:
Loop diuretics
Thiazides
Potassium-sparing
Two types of potassium-sparing diuretics:
Aldosterone antagonists
Nonaldosterone antagonists
Definition of diuretics
Drugs that increase urinary output
Two major applications of diuretics
Treatment of hypertension
Mobilization of edematous fluid to prevent renal failure
Mechanism of action of diuretics
Blockade of sodium and chloride reabsorption
Best site of action of diuretics
Proximal tubule produces greatest diuresis
Adverse effects of diuretics
Hypovolemia
Acid-base imbalance
Electrolyte imbalances
Prototype drug for loop diuretics
Furosemide (Lasix)
Mechanism of action of Furosemide (Lasix)
Acts on ascending loop of Henle to block reabsorption
Pharmacokinetics of Furosemide (Lasix)
Rapid onset (PO 60 min; IV 5 min)
Therapeutic uses of Furosemide (Lasix)
Pulmonary edema
Edematous states
Hypertension
Adverse effects of Furosemide (Lasix)
Hyponatremia, Hypochloremia, dehydration
Hypotension (volume loss, relaxation of venous smooth
muscle)
Hypokalemia
Ototoxicity
Hyperglycemia
Hyperuicemia
Can Furosemide (Lasix) be used during pregnancy? Why or why not?
No, because too risky when balancing fluid/electrolytes of both mom and baby
Normal range of potassium levels
3.5-5.0
Drug interactions of Furosemide (Lasix)
Digoxin
Ototoxic drugs
Potassium-sparing diuretics
Lithium
Antihypertensive agents
Nonsteroidal anti-inflammatory drugs
Administration routes for Furosemide (Lasix)
Oral
Parenteral
Another name for Thiazides and related diuretics
Benzothiadiazides
Effects of Thiazides and related diuretics
Similar to those of loop diuretics:
- Increase renal excretion of sodium, chloride, potassium, and water
- Elevate levels of uric acid and glucose
How is diuresis of Thiazides and related diuretics compared to loop diuretics
Considerably lower than that produced by loop diuretics
Not effective when urine flow is scant (unlike loop diuretics)
Prototype for Thiazides and related diuretics
Hydrochlorothiazide (HydroDIURIL)
How long does it take for hydrochlorothiazide to peak?
4-6 hours
Therapeutic uses for hydrochlorothiazide
HTN
Edema
Diabetes insipidus
Adverse effects of hydrochlorothiazide
Hyponatremia, hypochloremia, and dehydration
Hypokalemia
Hyperglycemia
Hyperuricemia
Impact on lipids, calcium, and magnesium
Effects of hydrochlorothiazide on pregnancy
During lactation, enters breast milk
Drug interactions with hydrochlorothiazide
- Digoxin
- Augments effects of hypertensive medications
- Can reduce renal excretion of lithium (leading to accumulation)
- NSAIDs may blunt diuretic effect
- Can be combined with ototoxic agents without increased risk of hearing loss
Potassium-sparing diuretics compared to other diuretics
Most modest increase in urine production
Decrease in potassium excretion
Rarely used alone for therapy
Two groups of potassium-sparing diuretics
Aldosterone antagonist
Nonaldosterone antagonist
Prototype drug for aldosterone antagonist potassium-sparing diuretics
Spironolactone (Aldactone)
Mechanism of action for Spironolactone
Blocks aldosterone in the distal nephron
Retention of potassium
Increased secretion of sodium
Therapeutic uses of spironolactone
HTN
Edematous states
Heart failure (decreased mortality in severe failure)
Primary hyperaldosteronism
Can be used for hormonal issues:
Premenstrual syndrome
Polycystic ovary syndrome
Acne in young women
Adverse effects of spironolactone
Hyperkalemia
Benign and malignant tumors
Endocrine effects
Drug interactions of spironolactone
Thiazide and loop diuretics
Agents that raise potassium levels
Prototype of osmotic diuretics
Mannitol (Osmitrol)
Action of Mannitol
Promotes diuresis by creating osmotic force within lumen of the nephron
Pharmacokinetics of mannitol
Drug must be given parenterally
Therapeutic uses of mannitol
Prophylaxis of renal failure
Reduction of intracranial pressure
Reduction of intraocular pressure
Adverse effects of mannitol
Edema
Headache
Nausea and vomiting
Fluid and electrolyte imbalance
How much does one liter of fluid weigh?
2.2 lbs
How much of the total body water is in intracellular fluid?
2/3
Where is extracellular fluid located?
Outside the cells:
Divided into the vascular compartment (blood vessels) and the interstitial space (the gaps between the cells)
Explain the renin-angiotensin-aldosterone system
Decreased renal perfusion initiates release of aldosterone.
Aldosterone is a mineral corticoid that retains sodium and where sodium goes, water goes.
Aldosterone also retains potassium.
Lab value for potassium
3.5-5.0 mEq/L
Lab value for sodium
135-145 mEq/L
Lab value for chloride
95-105 mEq/L
Lab value for magnesium
1.5 to 2.5 mEq/L
Lab value for serum creatinine
0.6 to 1.2 mg/dl
Lab value for BUN
10 to 20 mg/dl
Lab value for glucose
70 to 100
Lab value for platelets
150,000 to 400,000
Lab value for hemoglobin (Hgb)
F 12-16 g/dl
M 14-18 g/dl
Lab value for hematocrit (Hct)
F 37-47%
M 42-52%
What can cause an abnormal loss of fluids? And what symptoms would they have?
Vomiting, diarrhea, hemorrhage
Dehydration
Weak, low BP
Dry skin
What can cause someone to have fluid volume excess? And what symptoms would they have?
CHF, kidney failure
Crackles, dyspnea, edema
How would a pt be treated who has fluid volume excess?
Diuretics
What nursing interventions would be done for pts who have abnormal fluid volume?
Assess the pt
Daily weights
I & O
IV fluids
Types of drugs that act on the Renin-Angiotensin-Aldosterone System
Angiotensin-converting enzyme inhibitors (ACE inhibitors)
Angiotensin II receptor blockers (ARBs)
Direct renin inhibitors
Aldosterone antagonists
Main functions of the RAA system
All involved with blood pressure
Many involved with fluid volume
Many involved with electrolytes
How is the RAAS involved with blood pressure?
Actions of angiotensin II
Vasoconstriction
Release of aldosterone
Actions of aldosterone
Regulation of blood volume and blood pressure
Pathologic cardiovascular effects
How does aldosterone regulate blood pressure and blood volume?
When aldosterone is released form adrenal cortex, it acts on the distal tubular of the kidneys, causing release of sodium and potassium
Because of this BP and blood volume go down
How does the RAAS elevate BP?
Angiotensin II formed by renin and angiotensin-converting enzyme
- renin speeds up formation of angiotensin I from angiotensinogen
- Regulation of renin release
- Angiotensin-converting enzyme (kinase II) converts angiotensin I (inactive) to angiotensin II (highly active)
Main part of RAAS to increase BP or blood volume
Renin (its main purpose is to elevate BP)
Where are ACE enzymes (AKA kinase II) located?
On the surface of many blood vessels
In the lining of the vasculature of the lungs
(Even though we typically only think of it being involved with the renals)
Situations the RAAS helps to regulate BP in
Hemorrhage
Dehydration
Sodium depletion
When someone is experiencing low BP, how does the RAAS act on the body to fix it?
Constricts renal blood vessels
Acts on the kidney to promote retention of sodium & water, and the excretion of potassium
How do ACE inhibitors work?
By preventing Angiotensin II, which lowers the levels of angiotensin II, which can dilate vessels
Therapeutic uses of ACE inhibitors
Hypertension
Heart failure
MI
Diabetic and non diabetic nephropathy
Prevention of MI, stroke, and death in pts at high cardiovascular risk
How do ACE inhibitors help MI and heart failure?
By remodeling the heart and preventing more damage from happening
Adverse effects of ACE inhibitors
First dose hypotension (fall risk!)
Fetal injury (can’t take during pregnancy)
*Cough (due to increased bradykinin)
Angioedema (swollen face, need to be taken off)
Hyperkalemia
Dysgeusia and rash
Renal failure or **bilateral renal artery stenosis (contraindicated)
Neutropenia
Drug interactions for ACE inhibitors
Diuretics
Antihypertensive agents
Drugs that raise potassium levels
Lithium (b/c some cause lithium to accumulate in the body)
Nonsteroidal anti-inflammatory drugs
How should ACE inhibitors be administered?
- All administered orally, except for Enalapril (Vasotec) which is given IV
- May be administered without regard to meals, except for Captopril (capoten) and Moexipril
List 3 ACE inhibitors
Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil)
Pharmacologic effects of ARBs
- Block access of angiotensin II
- Cause dilation of arterioles and veins
- Prevent angiotensin II from inducing pathologic changes in cardiac structure
- Reduce excretion of potassium
- Decrease release of aldosterone
- Increase renal excretion of sodium and water
- Do not inhibit kinase II
- Do not increase levels of bradykinin
Difference between ACE inhibitors and ARBs
ARBs do not increase bradykinin release in vasculature of the lungs. Because of this, they do not cause cough
Therapeutic uses of ARBs
HTN, heart failure, MI
Diabetic nephropathy
If unable to tolerate ACE inhibitors, next best protection against MI, stroke, and death from cardiovascular causes in high-risk patients
Adverse effects of ARBs
Angioedema
Fetal harm in pregnancy
Renal failure (**bilateral renal artery stenosis)
Administration of ARBs
All are given PO
List 3 ARBs
Losartan (Cozaar)
Valsartan (Diovan)
Telmisartan (Micardis)
Function of direct renin inhibitors
Binds tightly with renin and prevents the division of angiotensinogen to angiotensin I
Side effects of direct renin inhibitors
Angioedema
Cough
GI effects
Hyperkalemia
Fetal injury
Only drug approved for HTN in direct renin inhibitor class
Aliskiren (Tekturna)
Mechanism of action of aldosterone antagonists
Selective blockade of aldosterone receptors
Therapeutic uses of Eplerenone (Inspra)
HTN
Heart failure
Administration considerations for Eplerenone (Inspra)
Absorption is not affected by food
Adverse effects of Eplerenone (Inspra)
Hyperkalemia (can be severe)
Drug interactions of Eplerenone (Inspra)
Inhibitors of CYP3A4
Drugs that raise potassium levels
Use with caution when combined with lithium
Prototype for aldosterone antagonists
Spironolactone (Aldactone)
Mechanism of action for spironolactone (Aldactone)
Blocks aldosterone receptors, binds with receptors for other steroid hormones
Therapeutic uses of Spironolactone (Aldactone)
HTN
Heart failure
Adverse effects of Spironolactone (Aldactone)
*Hyperkalemia (b/c it is also a potassium sparing diuretic)
Gynecomastia
Menstural irregulatrities
Impotence
Hirsute said
Deepening of the voice
How do calcium channel blockers work?
*Prevent calcium ions from entering cells
Which parts of the body to calcium channel blockers have the greatest impact on?
Heart
Arteries
Arterioles
What are calcium channel blockers used to treat?
*HTN
*Angina pectoris
*Cardiac dysrhythmias
Other names for calcium channel blockers
Calcium antagonists
Slow channel blockers
What do calcium channels do?
Regulate the entry of calcium ions into cells
What are the 2 groups of CCBs?
Verapamil and diltiazem
Dihydropyridines
What are verapamil and diltiazem?
Agents that act on the vascular smooth muscle and the heart
What are dihydropyridines?
Agents that act mainly on vascular smooth muscle
How do calcium channel blockers work on vascular smooth muscle when they are open vs. blocked?
Open = contractile process
Blocked = *vasodilation
What do therapeutic doses of calcium channel blockers do?
Work selectively on peripheral arterioles and arteries, and arterioles of the heart
Do not have significant effect on veins
Why does blocking calcium channels cause vasodilation?
Calcium causes forceful contractions of the heart. If we relax the muscle by blocking some of the calcium, it makes contractions less forceful and allows smooth muscle to relax
Which receptor are calcium channels highly intertwined with?
Beta1 adrenergic receptors in the heart
Classifications of calcium channel blockers
Dihydropyridines
Non-dihydropyridines
Example of dihydropyridines group of calcium channel blockers
Nifedipine (Procardia)
Examples of non-dihydropyridines group of calcium channel blockers
Verapamil, Diltiazem (Cardizem)
Site of action for Dihydropyridines
Act primarily on arterioles
Site of action for verapamil and diltiazem
Act on arterioles and on the heart
Function of Verapamil (Calan, Covera-HS)
Agent that blocks calcium channels in blood vessels and acts on vascular smooth muscle and the heart
Hemodynamic effects of Verapamil
Direct effects on the heart and blood vessels (relaxes)
Reflex effects
Five direct hemodynamic effects of verapamil
- Block at peripheral arterioles (reduces arterial pressure)
- Block at arteries and arterioles of heart (increases coronary perfusion)
- Block at SA node (reduces heart rate)
- Block at AV node (decreases AV nodal contraction)
- Block in the myocardium (decreases force of contraction)
Indirect (reflex) hemodynamic effects of Verapamil
Baroreceptor reflex (may cause BP to jump back up)
Net effects of verapamil
Little or no net effect on cardiac performance
*Vasodilation accompanied by reduced arterial pressure and increased coronary perfusion
Administration of Verapamil
Can be given PO or IV
Therapeutic uses of Verapamil
Angina pectoris (vasopastic angina and angina of effort)
Essential hypertension (first line agent)
Cardiac dysrhythmias
Types of cardiac dysrhythmias verapamil can be used for
Atrial flutter
Atrial fibrillation
Paroxysmal supraventricular tachycardia
How does verapamil help with dysrhythmias
If dysrhythmias are really fast, verapamil slows down contractions causing rhythm to be more regular
Adverse effects of Verapamil
*Constipation (most common complaint)
*Dizziness, facial flushing, headache (from lowered BP/HR)
Edema of ankles and feet
Gingival hyperplasia
Heart block
Drug interactions of Verapamil
Digoxin (doesn’t work well with other drugs)
Beta-adrenergic blocking agents (could lower BP too much or cause dysrhythmias)
When is Verapamil given IV?
Only for dysrhythmias and Pt must be on cardiac monitor with resuscitation equipment immediately available
Actions of Diltiazem
*blocks calcium channels in heart and blood vessels (similar to verapamil)
Lowers blood pressure
How does Diltiazem lower blood pressure?
Arteriolar dilation
Direct suppressant/reflex cardiac stimulation = little net effect on heart
Therapeutic uses for diltiazem
Angina pectoris
HTN
Cardiac dysrhythmias (atrial flutter, atrial fibrillation, paroxysmal tachycardia)
Adverse effects of diltiazem
(Similar to verapamil, but less constipation)
Dizziness
Flushing
Headache
Edema of ankles and feet
*Exacerbates bradycardia, sick sinus syndrome, heart failure, second- or third-degree heart block
Drug interactions of diltiazem
Digoxin
Beta-adrenergic blocking agents
What are Dihydropyridines?
Agents that act mainly on vascular smooth muscle
Create a significant blockade of calcium channels in blood vessels
And *Minimal blockade of calcium channels in the heart
Prototype of dihydropyridines
*Nifedipine (Procardia)
Actions of Nifedipine
Vasodilation by *blocking calcium channels
Blocks in vascular smooth muscle
Very little blockade of heart Ca channels
Cannot be used to treat dysrhythmias
Less likely than verapamil to exacerbate pre-existing cardiac disorders (used more for BP)
Direct effects of nifedipine
Limited blockade of Ca channels in vascular smooth muscle (no direct suppressant effects on: automaticity, AV conduction, or contractile force)
Indirect effects of nifedipine
Lowered BP activates baroreceptor reflex
(Primarily with fast-acting vs. sustained release)
Net effect of nifedipine blocking calcium channels and causing vasodilation
*Lowered BP
*Increased heart rate
*Increased contractile force
(HR and contractile force not affected as much as BP)
Therapeutic uses of nifedipine
Angina pectoris
HTN
Adverse effects of nifedipine
Flushing
Dizziness
Headache
Peripheral edema
Gingival hyperplasia
Chronic eczematous rash in older patients
Reflex tachycardia (= increased cardiac O2 demand)
- & can increase pain for anginal patients
What can nifedipine be combined with to prevent reflex tachycardia?
Beta blocker
(This is ok b/c nifedipine does not lower HR as much as beta blockers do)
Vasodilator that works selectively to dilate arterioles
Hydralazine
Vasodilator that works selectively to dilate veins
Nitroglycerin
Vasodilator that works to dilate both arterioles and veins
Prazosin
What occurs when a drug dilates resistance vessels (arterioles)?
Cause a decrease in cardiac Afterload
What occurs when a drug dilates capacitance vessels (veins)?
Decreased force with which blood is returned to the heart, so decreased preload
Therapeutic uses of vasodilators
*Essential HTN
*HTN crisis
*Angina pectoris
Heart failure
MI
Pheochromocytoma
Peripheral vascular disease
Pulmonary arterial hypertension
Production of controlled hypotension during surgery
Main adverse effects related to vasodilation
- Postural hypotension
- Reflex tachycardia
- Expansion of blood volume
What should you tell a patient who first starts taking vasodilators?
*They may faint, feel dizzy or fatigued
Action of Hydralazine (Apresoline)
Selective dilation of arterioles
(Postural hypotension is minimal)
Therapeutic uses of Hydralazine (Apresoline)
Essential hypertension (PO)
Hypertensive crisis (IV)
Heart failure
Adverse effects of Hydralazine (Apresoline)
Reflex tachycardia
Increased blood volume
Systemic lupus erythematous-like syndrome
Headache
Dizziness
Weakness
Fatigue
Drug interactions of Hydralazine (Apresoline)
Other antihypertensive agents
Avoid excessive hypotension
(Combined with beta blocker to protect against reflex tachycardia and diuretics to prevent sodium and water retention and expansion of blood volume)
Action of Minoxidil (Loniten)
Selective dilation of arterioles
(More intense dilation than Hydralazine, but causes more adverse reactions)
Uses of minoxidil (Loniten)
Severe HTN that is unresponsive to safer drugs
Adverse effects of minoxidil (Loniten)
Reflex tachycardia
Sodium and water retention
Hypertrichosis (hair growth b/c can also be used topically as rogane)
Pericardial effusion
Fastest acting antihypertensive agent
Sodium Nitroprusside (Nitropress)
Action of sodium nitroprusside (Nitropress)
Causes venous and arteriolar dilation
Administration of Nitropress
*IV infusion (CCU)
Onset of Nitropress
Immediate (but BP returns to pretreatment level in minutes when stopped)
When is Nitropress used?
For hypertensive emergencies
(Pt must be hooked up to monitor b/c vasodilation effects are so strong)
Adverse effects of Nitropress
Excessive hypotension (Must lower pt’s bp slowly)
Cyanide poisoning (b/c of how it breaks down in body, creates cyanide build up)
Thiocyanate toxicity
Other vasodilators
ACE inhibitors
Angiotensin II receptor antagonists
Direct renin inhibitors
Organic nitrates
Calcium channel blockers
Sympathy lyrics
Nesiritide
What are nesiritides?
Drugs for pulmonary arterial hypertension
Prehypertension BP
120-130 / 80-89
Two categories of HTN
Primary (essential) HTN
Secondary HTN
Difference between primary and secondary hypertension
Primary (essential) HTN:
- no identifiable cause
- chronic, progressive disorder
- can be treated but not cured
Secondary HTN:
- identifiable primary cause
- possible to treat the cause directly
- some individuals can actually be cured
Who is more likely to have primary (essential) HTN?
Older adults
African Americans
Mexican Americans
Post menopausal women
Consequences of hypertension
Heart disease
- MI
- heart failure
- angina pectoris
Kidney disease
Stroke
Free lifestyle modifications for pts with HTN
Sodium restriction
DASH diet (fruits, veggies) & alcohol restriction
Aerobic exercise, smoking cessation
Maintenance of K+ and Ca+ intake
Formula for arterial pressure
Arterial pressure = cardiac output X peripheral resistance
What causes changes in cardiac output?
Heart rate
Myocardial contractility
Blood volume
Venous return
Systems that help regulate blood pressure
Sympathetic baroreceptor reflex
Renin-angiotensin-aldosterone system
Renal regulation of blood pressure
Patient education for taking BP medications
They must take them faithfully to bring BP down
If they don’t get BP under control, may have stroke or MI
Encourage them to get a BP cuff to check at home
Can cause impotence in men and makes them not want to take it
Drugs for hypertensive emergencies
Fenoldopam
Labetalol
Diazoxide
Clevidipine
Which BP meds are contraindicated during pregnancy?
ACE inhibitors
ARBS
Direct renin inhibitors (DRIs)
Which medications should be used for preeclampsia and eclampsia?
Labetalol
Magnesium sulfate (anticonvulsant)
Patho of heart failure
Cardiac remodeling (gets out of shape & bigger)
Physiologic adaptations to reduced cardiac output
Physiologic adaptations to reduced CO
Cardiac dilation
Increased sympathetic tone
Water retention and increased blood volume
Natriuretic peptides
Drugs that are used to treat heart failure
Diuretics
Drugs that inhibit the renin-angiotensin-aldosterone system
Beta blockers
Inotropic agents (Digoxin- cardiac glycoside, dopamine)
Vasodilators
Drugs that inhibit the RAAS
ACE inhibitors
ARBs (if ACE inhibitors are not tolerated)
Aldosterone antagonists
Direct renin inhibitors
What are inotropic agents?
Sympathomimetics
Types of sympathomimetics
Dopamine (Intropin)
Dobutamine
Phosphodiesterase inhibitors
How does dopamine work for heart failure?
Catecholamine
Activates beta1 adrenergic receptors in heart, kidney, and blood vessels
Increases heart rate
Dilates renal blood vessels
Activates alpha1 receptors
How does dobutamine work for heart failure?
Synthetic catecholamine
Selective activation of beta1 adrenergic receptors
Intravenous vasodilators used for acute care
*Nitroglycerin
*Sodium nitroprusside (Nitropress)
Nesiritide (Natrecor)
Principle adverse effects of nitroglycerin
Hypotension
Resultant reflex tachycardia
Principal adverse effect of Nitropress
Profound hypotension
Principle adverse effect of Nesiritide (Natrecor)
Sympatomatic hypotension
Functions of digoxin and cardiac glycosides
Positive inotropic actions:
- increase myocardial contractile force
- alter electrical activity of the heart
- favorable affect neurohormonal systems
What is Digoxin
A cardia (Digitalis) Glycoside
Naturally occurring compound
*Effects of Digoxin
Profound effects on the mechanical and electrical properties of the heart
Increases myocardial contractility
Increased cardiac output
Adverse effect of Digoxin
Can cause severe dysrhythmias
Relationship of potassium to inotropic action
Potassium levels must be kept in normal physiologic range
Hemodynamic benefits of Digoxin
Increased cardiac output
- decreased sympathetic tone
- increased urine production
- decreased renin release
*Heart rate of a pt taking digoxin that would cause you to hold the drug and call the provider
- <60
Drug interactions of Digoxin
Diuretics
ACE inhibitors
ARBs
Sympathomimetics
Quinidine
Verapamil
Half life of digoxin
About 1.5 days
Stage A of heart failure
No symptoms of HF
Management directed at reducing risk
Stage B of heart failure
TX is same as for stage A with the addition of ACE inhibitors or ARBs
Stage C of heart failure
Relieve symptoms
Diuretics
BB
digoxin
Stage D of heart failure
Worse
Multiple drugs
Diuretics
Repeated hospitalizations
Fluid management is constant
What does ASCVD stand for?
Atherosclerotic Cardiovascular Disease
What is cholesterol?
A component of all cell membranes and membranes of intracellular organelles
What is cholesterol required for?
Synthesis of certain hormones and bile salts
Where does cholesterol come from and what is it manufactured by?
Comes from dietary sources
Manufactured by cells, primarily in the liver
What are apolipoproteins?
Recognition sites for cell-surface receptors
Function of apolipoproteins
Activate enzymes that metabolize lipoproteins
And increase the structural stability of lipoproteins
What are the 3 classes of plasma lipoproteins that are relevant to coronary atherosclerosis?
Very-low-density lipoproteins (VLDLs)
Low-density lipoproteins (LDLs)
High-density lipoproteins (HDLs)
Which class of lipoprotein are triglycerides in?
VLDLs
Which category of lipoproteins is the greatest contributor to CHD?
LDLs
Which class of lipoproteins is cholesterol in?
HDLs
What happens with the inflammatory process of atherogenesis?
Infiltration of macrophages, T lymphocytes, and other inflammatory mediators
How old/often should you have cholesterol screened?
Every 5 years for adults over 20
What do we want HDL cholesterol levels to be?
> or equal to 45 mg/dL
What do we want LDL cholesterol levels to be?
< 100 mg/dL
What do we want triglycerides levels to be?
< 90 mg/dL
Factors in risk assessment of cholesterol
Identifying CHD risk factors
Identifying CHD risk equivalents:
- diabetes, atherosclerotic disease other than CHD
Identifying an individual’s CHD risk category
Therapeutic lifestyle changes for High-LDL cholesterol
Smoking cessation
Diet
Exercise
Three medication categories for high cholesterol
HMG-CoA reductase inhibitors
Bile-acid sequestration
Fibrates
Secondary treatment targets of cholesterol medication
Metabolic syndrome (increases risk for CHD & T2DM)
High triglycerides (levels above 150 mg/dL)
Factors of metabolic syndrome
High blood glucose
High triglycerides
High apolipoprotein B
Low high-density lipoprotein (HDL)
Prothrombotic state
Proinflammatory state
Hypertension
Treatment goals for metabolic syndrome
Reduce the risk for atherosclerotic disease
Reduce the risk for T2DM
Increase physical activity
(Want to make sure pts know that they have to turn this disease around otherwise they will have diabetes and heart problems)
Most effective drugs for lowering LDL
HMG-CoA Reductase Inhibitors (Statins)
What do Statins do?
Lower LDL cholesterol
Raise HDL cholesterol
Lower triglyceride levels
Nonlipid beneficial cardiovascular actions of statins
Promote plaque stability
Reduce the risk for cardiovascular events
Increased bone formation
Prototype for statins
Lovastatin/Mevacor
When is the best time to take a drug that lowers cholesterol?
In the evening
Because a lot of cholesterol synthesis takes place at night while sleeping
What happens if you stop taking statins?
Cholesterol goes back up to where it was before starting the drug
Mechanism of action for statins
Cholesterol reduction
Therapeutic uses of statins
Hypercholesterolemia
Primary and secondary prevention of CV events
Post MI therapy (bc it helps prevent plaque from building up in vessel walls)
Diabetes
Another popular statin drug
Rouvastatin (Crestor)
Nursing consideration for patients taking Crestor
If pt is Asian, may get very high levels of this drug and have to decrease dose to lower levels
Adverse effects of statins
Common:
- headache
- rash
- GI disturbances
Rare:
- *Myopathy/rhabdomyolysis
- hepatotoxicity
What is myopathy and rhabdomyolysis?
A rare side effect of stating drugs
Myopathy - injured muscle tissue and can develop into:
Rhabdomyolysis - muscle tissue breaks down and increased levels of creatinine kinase floats around and could get into renals
Which severe side effects should you watch for in a pt taking statins?
Muscle tenderness and weakness (could indicate myopathy/rhabdomyolysis
Jaundice, pt saying they don’t feel good (could indicate hepatotoxicity)
Need to draw liver enzymes to see if they’re elevated
Drug interactions of statins
Most other lipid-lowering drugs (except bile acid sequestration)
Drugs that inhibits CYP3A
*Use in pregnancy (Category X = contraindicated)
Dosing of statins
*should be once daily, in the evening
What should the patient have done before they start taking a cholesterol lowering medication?
We need to get a lipid profile on them
Function of Bile-Acid sequestrants
Primarily used as adjuncts to statins
Lowers LDLs
Prototype bile-acid sequestrant
Colesevelam/Welcol
Difference between Colesevelam/Welchol and other bile-acid sequestrants
Does not increase uptake of fat-soluble vitamins as other bile sequestrants do
Does not significantly reduce the absorption of statins, warfarin, digoxin, and most other drugs studies
Two other drugs in the bile-acid sequestrants group
Cholestyramine
Colestipol
Function of Colesevelam (Welchol)
Decrease in LDL cholesterol
(Increased VLDL levels in some patients)
Mechanism of action of Colesevelam (Welchol)
Increases LDL receptors on hepatocytes
Prevents reabsorption of bile acids
Use of Colesevelam (Welchol)
Reduces LDL cholesterol (with modified diet and exercise)
Adverse effects of Colesevelam (Welchol)
Constipation
Function of Ezetimibe (Zetia)
Inhibits cholesterol absorption
Which type of cholesterol drug is Ezetimibe (Zetia)?
Bile-Acid Sequestrant
Uses of Ezetimibe (Zetia)
Lower total cholesterol
LDL cholesterol
Apolipoprotein B
Adverse effects of Ezetimibe (Zetia)
Myopathy
Rhabdomyolysis
Hepatitis
Pancreatitis
Thrombocytopenia
Drug interactions of Ezetimibe (Zetia)
Statins
Fibrates
Bile-acid sequestrants
Cyclosporine
Most effective type of drug available for lowering TG levels
Fabric Acid Derivatives (Fibrates)
Main functions of Fibrates
Most effective drug for lowering TG levels
Can raise HDL cholesterol
Little or no effect on LDL cholesterol
Drug interactions for Fibrates
Warfarin (can increase risk for bleeding)
Statins (can increase risk for rhabdomyolysis)
3 Fibrates used in the United States
*Gemfibrozil (Lopid)
Fenofibrate (Tricor)
Fenofibric acid (TriLipix)
Prototype for Fibrins
Gemfibrozil (Lopid)
Effects of Gemfibrozil (Lopid) on plasma lipoproteins
Decreased plasma TG content
Decreased VLDL levels
Can increase HDL cholesterol
How does Gemfibrozil (Lopid) interact with warfarin?
Displaces warfarin from plasma albumin
Must measure INR frequently
Uses of Gemfibrozil (Lopid)
Reduces high levels of plasma triglycerides (VLDLs)
(Treatment reserved for pts who have not responded to diet modification)
Less effective than statins in reducing LDL
Can raise HDL but not approved for this use
Adverse of Gemfibrozil (Lopid)
Rashes
GI disturbances
Gallstones
Myopathy
Liver injury (hepatotoxic)
Other products that are used to alter plasma lipid levels
Lovaza - omega 3 acid
Fish oil - diet
Plant stanol and sterol esters
Cholestin
What are GP2B3A receptors?
Receptors on platelets (50,000-80,000 on each platelet)
Where anticoagulation medications go in and attach to decrease platelet aggregation
Stage 1 of hemostasis
Formation of platelet plug
Platelet aggregation
Stage 2 of hemostasis
Coagulation
Intrinsic and extrinsic coagulation pathways
Three major groups of drugs for thromboembolic disorders
Anticoagulants
Antiplatelets
Thrombolytics
What do anticoagulants do?
Reduce the formation of fibrin
Two mechanisms of action of anticoagulants
Inhibit the synthesis of clotting factors
Inhibit the activity of clotting factors
Two drugs in anticoagulant group of drugs for thromboembolic disorders
Heparin
Coumadin
Function of heparin
Enhances antithrombin
Rapid-acting anticoagulant
How is heparin administered?
By injection only (Cannot be absorbed so can’t be PO)
IV (Continuous and intermittent)
Deep SubQ
Therapeutic uses of Heparin
Preferred anticoagulant during pregnancy when rapid anticoagulation is required
Pulmonary embolism
Stroke evolving
Massive DVT
Open heart surgery
Renal dialysis
Low-dose therapy postoperatively
Disseminated intravascular coagulation (DIC)
Adjunct to thrombolytic therapy
Adverse effects of heparin
Hemorrhage
Heparin-induced thrombocytopenia
Hypersensitivity reactions
What is heparin-induced thrombocytopenia?
HIT syndrome: wipes out pt’s platelets
How do we know HIT syndrome is occuring?
Get a base line lab value before starting pt on the drug and compare after starting. If platelets keep decreasing, will know they are being wiped out
When is heparin contraindicated?
Thrombocytopenia, uncontrolled bleeding
During and immediately after surgery of the eye, brain, or spinal cord (could cause hematomas and put too much pressure in these areas)
*Antidote for overdose of Heparin
*Protamine sulfate
What is aPTT? When is it drawn, and why?
Activated partial thromboplastin time
Gives an indication of how effective the heparin is working.
Need to draw pt’s levels every 6-8 hours while they’re taking heparin
Normal levels of aPTT and what happens to the levels when a pt is taking heparin?
Normal is around 40 seconds. Want it to increase when they are on heparin
Difference between unfractioned heparin and low-molecular-weight heparins
Unfractioned heparin has a different molecular structure and can be given IV
Low-Molecular-Weight heparins are composed of molecules that are shorter than those found in unfractioned heparin
Therapeutic uses of Low-Molecular-Weight heparins
Prevention of DVT after surgery (including replacement of hip, knee)
Treatment of established DVT
Prevention of ischemic complications
What types of ischemic complications does Low-Molecular-Weight heparin prevent?
Pts with unstable angina
Non-Q wave MI
STEMI
How is Low-Molecular-Weight heparin administered?
SubQ
Dosage is based on body weight
Antidote for toxicity of Low-Molecular-Weight heparin
Protamine sulfate
Benefits and down-sides of Low-Molecular-Weight heparin
Costs more than unfractionated heparin
Does not require monitoring, can be given at home
Adverse effects and interactions of Low-Molecular-Weight heparin
Bleeding (but less than with unfractionated heparin)
Immune-mediated thrombocytopenia
Severe neurologic injury for pts undergoing spinal puncture or spinal epidural anesthesia
Types of Low-Molecular-Weight heparins
*Enoxaparin (Lovenox)
Dalteparin (Fragmin)
What is *Warfarin (Coumadin)?
*An oral anticoagulant
Uses of Warfarin (Coumadin)
Oral anticoagulant with delayed onset
Vitamin K antagonist
Blocks biosynthesis of factors 7, 9, 10 and prothrombin in coagulation cascade
Not useful in emergencies (since it’s PO)
Long term prophylaxis of thrombosis
Which patients would use Warfarin as a long-term prophylaxis of thrombosis?
For prevention of:
- Venous thrombosis and associated pulmonary embolism
- prevention of thromboembolism (in pts with prosthetic heart valves)
- prevention of thrombosis during atrial fibrillation
How to monitor treatment with warfarin:
*Prothrombin time (PT) - normal is 12 seconds
* Internal normalized ratio (INR)
Adverse effects of warfarin
Hemorrhage (give Vitamin K for toxicity)
Fetal hemorrhage and teratogenesis during pregnancy
Pts will bruise easily
Drug interactions of warfarin
Drugs that increase anticoagulant effects
Drugs that promote bleeding
Drugs that decrease anticoagulant effects
Heparin
Aspirin
Acetaminophen
Antagonist for Coumadin
Vitamin K
What should you educate a pt on when they begin taking Warfarin?
Don’t want them to eat too much vitamin K in their diet to cancel it out
Should wear a bracelet that says they’re on Coumadin
Will bruise easily
Difference between how direct thrombin inhibitors and heparin work
Direct thrombin inhibitors directly inhibit thrombin and heparin enhances the activity of antithrombin
Drugs that are direct thrombin inhibitors
Dibigatran etexilate (Pradaxa) (not important)
Hiruden Analog: Bivalirudin (Angiomax)
Lepirudin (Refludan)
Function of Angiomax
Prevents clot formation (combined with aspirin) in pts with unstable angina who are undergoing coronary angioplasty
Mechanism of action of Angiomax
Facilitates the actions of antithrombin
Prevents conversion of fibrinogen to fibrin
Prevents activation of factor XII
Adverse effects of Angiomax
Bleeding
Back pain
Nausea, headache
Use of lepirudin (Refludan)
Prophylaxis and treatment of thrombosis in pts with HIT
(Direct inhibition of thrombin)
Drug that is a selective factor Xa inhibitor
Rivaroxaban (Xarelto)
Function of Xarelto
Binds directly with factor Xa to cause inactivation
Use of Xarelto
Retention of DVT and PE after ortho surgery
Prevention of stroke in pts with atrial fibrillation
Adverse effects of Xarelto
Bleeding
How does aspirin function as an anti platelet drug?
Inhibition of cyclooxygenase
Adverse effect of aspirin
Increases risk for GI bleeding
How does Clopidogrel (Plavix) work as an anti platelet drug?
P2Y12, adenosine diphosphate receptor antagonist
How does Vorapaxar (Zontivity) work as an antiplatlet drug?
Protease-activated receptor-1 (PAR-1) antagonist
Therapeutic uses of aspirin
Ischemic stroke
Transient ischemic attack
Chronic stable angina
Unstable angina
Coronary stunting
Acute MI
Previous MI
Primary prevention of MI
Adverse effects of aspirin
Bleeding
GI bleeding and hemorrhagic stroke
(Enteric coated tablets may not reduce risk for GI bleeding)
Therapeutic uses of plavix
Prevents blockage of coronary artery stents
Reduces thrombotic events in pts with acute coronary syndromes:
- MI
- Ischemic stroke
- Vascular death
Adverse effects of Plavix
Similar to those of aspirin
How does Vorapaxar (Zonitivity) work as an antiplatlet drug?
Protease-activated receptor-1 PO
Emergency drugs used in chest pain situations via IV
Aggrastat
Integrilin
How does Eptifibatide (Integrilin) work?
Small peptide that causes reversible and highly selective inhibition of GP IIb/IIIa receptors
Effects reverse within 4 hours of stopping the infusion
Which type of drug is Alteplase (tPa)?
Thrombolytic Fibrinolytic Drug
Therapeutic uses of Alteplase (tPa)
Strong emergency critical care drug
MI
Ischemic stroke
PE
Major adverse effects of Alteplase (tPa)
*Bleeding
(Minor oozing to life-threatening amount)
Risk for intracranial bleeding higher than with streptokinase
Likely sites of bleeding in pts taking Alteplase (tPa)
Recent wounds
Needle puncture sites
Invasive procedure sites
What increases the risk of bleeding for a pt taking Alteplase (tPa)?
Anticoagulants increase risk for hemorrhage
(Blood replacement may need to be considered)
How can nurses minimize the risk of bleeding in pts taking Alteplase (tPa)?
Minimizing physical manipulation of the pt
Avoiding subQ and IM injections
Minimizing invasive procedures
Minimizing concurrent use of anticoagulants
Minimizing concurrent use of anti platelet drugs
How is Alteplase (tPa) administered?
IV
Pt must be hooked up to 2 IVs. One for the tPa and one for a regular drip (like NS)
Weight based and requires careful assessment
Where does pain from angina occur?
Sudden pain beneath the sternum, often radiating to left shoulder and arm
What causes angina?
*Oxygen supply to the heart is insufficient to meet oxygen demand
Two goals of angina drug therapy
Prevention of MI and death
Prevention of myocardial ischemia and anginal pain
What controls cardiac oxygen demand
Heart rate
Myocardial contractility
Intramyocardial wall tension (preload/Afterload)
What controls oxygen supply?
Myocardial blood flow
Myocardial perfusion only in diastole
Three forms of angina pectoris
Chronic stable angina (exertional angina)
Variant angina (Prinzmetal’s or vasospastic angina)
Unstable angina
Three families of antianginal agents
*Organic nitrates
*Beta blockers
*Calcium channel blockers
What can cause chronic stable angina?
Emotional excitement
Large meals
Cold exposure
CAD
Treatment strategy for chronic stable angina
Increase cardiac oxygen supply
Decrease oxygen demand
Therapeutic agents for chronic stable angina
Organic nitrates
Beta blockers
Calcium channel blockers
Ranolazine (newer drug with limited indications, can be combined with other drugs)
Non drug therapy for chronic stable angina
Avoid factors that can precipitate angina
Decrease risk factors
What causes variant angina?
Coronary artery spasm
Treatment for variant angina
Increasing cardiac oxygen supply
Therapeutic agents for variant angina
Calcium channel blockers
Organic nitrates
How can you tell if someone is having unstable angina?
Symptoms of angina at rest
New onset of exertional angina
Intensification of existing angina
Treatment strategy of unstable angina
Maintain oxygen supply
Decrease oxygen demand
Therapeutic agents for acute management of unstable angina
Anti-ischemic therapy
Antiplatelet therapy
Anticoagulant therapy
Types of angina nitroglycerin is used for
Stable and variant angina
Action of nitroglycerin
Vasodilator
Adverse effects of nitroglycerin
Headache
Orthostatic hypotension
Reflex tachycardia
Drug interactions with nitroglycerin
Hypotensive drugs
Phophodiesterase type 5 inhibitors (Viagra)
Beta blockers, verapamil, and diltiazem
Which group of antianginal meds does nitroglycerin fall into?
Organic nitrates
What should you know about a pt’s tolerance to nitroglycerin?
Can develop rapidly, and will cause cross tolerance to all other nitrates
To minimize, use the lowest effective dose
For long acting formulas, do 8 drug-free hours per day
Preparations and routes of nitroglycerin
Sublingual tablets
Sustained release oral capsules
Transdermal delivery systems
Translingual spray (most common)
Topical ointment
IV infusion
What should a pt do if they are having chest pain and have nitro with them at home?
Take one sublingual nitro and wait 5 mins. If they are still having chest pain, call 911 and take another tablet
Nursing considerations for nitroglycerin
If using long acting preparations, they should be discontinued slowly
All uses for nitroglycerin
Acute anginal therapy
Sustained anginal therapy
IV for perioperative control of BP
Treatment of heart failure with MI
Unstable angina
Uncontrolled exacerbations of chronic angina
Critical care organic nitrates
Isosorbide mononitrate (Imdur) & isosorbide dinitrate (Isordil)
Amyl nitrate
Beta blockers that can be used for angina
*Propranolol (Inderal)
*Metoprolol(Lopressor)
Function of propranolol and metoprolol for anginal pain
Decrease cardiac oxygen demand
Adverse effects of propranolol and metoprolol
Bradycardia
Decreased AV conduction
Reduction of contractility
Asthmatic effects
Use with caution in pts with diabetes
Insomnia
Depression
Bizarre dreams
Sexual dysfunction
Calcium channel blockers that can be used for angina
*Verapamil
*Diltiazem
*Nifedipine
Function of calcium channel blockers for angina
Block calcium channels in vascular smooth muscle
Types of angina calcium channel blockers can be used for
Stable and variant angina
Adverse effects of calcium channel blockers
Dilation of peripheral arterioles
Reflex tachycardia
Hypotension
Beta blockers
Bradycardia
Heart failure
AV block
Drug in new class of antianginal agents
Ranolazine (Ranexa)
How does Ranexa work?
Benefits are modest, works better in men
Does not reduce heart rate, BP, or vascular resistance
Side effects of Ranexa
Can prolong QT interval, and can lead to Vtach
Multiple drug interactions
Drugs used to prevent MI and death
Antiplatelet drugs
Cholesterol-lowering drugs
Angiotensin-converting enzyme (ACE) inhibitors
Antianginal agents
(All of these can be used in combination to help with angina or to prevent MIs, etc.)
Risk factors for angina
Smoking
High cholesterol
Hypertension
Diabetes
Physical inactivity
Management of variant angina
Calcium channel blocker, or long acting nitrate
If either of these alone is inadequate, add a nitrate
If combination fails, CABG may be indicated
(Beta blockers not effective with vasospastic angina)
Antiplatelet therapy for angina:
Aspirin (indefinitely)
- Clopidogrel (Plavix)
- Abciximab (ReoPro)
- Eptifibatide (Integrilin)
Anticoagulant therapy for angina
Subcutaneous LMW heparin or IV
Unfractionated heparin
Anti-ischemic therapy for angina
Nitroglycerin
Beta blockers
Supplemental O2
IV morphine
ACE inhibitor
Revascularization therapy for angina
Coronary artery bypass graft (CABG) surgery
Percutaneous transluminal coronary angioplasty (PTCA)
Comparison of CABG surgery with percutaneous coronary intervention (PCI)
Two types of myocardial infarctions
MI
STEMI (ST-Elevation MI)
Difference between a MI and a STEMI
MI: necrosis of the myocardium resulting from ischemia
STEMI: acute IM, causes elevation of the ST segment on the ECG
Pathophysiology of a STEMI
- Blood flow to a region of myocardium is stopped (by platelet plugging and thrombus formation)
- Hydrogen ions accumulate
- Local metabolic changes occur
- Myocardial injury triggers ventricular remodeling
- Degree of residual cardiac impairment depends on amount/location of damage
Pain symptoms of STEMI
Severe sub sternal chest pain
Crushing/constricting pain
Radiates down arm and jaw
Things to look for to determine if someone has had a STEMI
Chest pain
Characteristic ECG changes
Sweating, weakness, sense of impending doom
(But 20% of pts experience no symptoms)
Biochemical markers for MI
Routine drug therapy for management of STEMI
Oxygen
Aspirin (not NSAIDs) (have pt chew it)
Morphine (IV to relieve pain & decrease anxiety)
Beta blockers (give right after)
Nitroglycerin (to vasodilate)
What is reperfusion therapy for when managing STEMI
Pt will go to cath lab for reperfusion therapy.
To dissolve clots, and convert plasminogen to plasmin
Types of reperfusion therapy to manage STEMI
Primary percutaneous coronary intervention
Fibrinolytic (thrombolytic) therapy
Adjuncts to reperfusion therapy when managing an MI
Heparin
Antiplatelet drugs
What type of Fibrinolytic drugs are used for management of STEMI?
Alteplase (a tissue plasminogen activator)
Reteplase
Tenecteplase
What is primary percutaneous coronary intervention?
Primary = use of angioplasty rather than fibrinolytic therapy
Stents may be placed
What is the goal of primary percutaneous coronary intervention?
Primary PCI within 90 minutes of patient contact
What should all patient undergoing PCI receive?
An anticoagulant (IV heparin, bivalirudin) combined with
Antiplatelet drugs: aspirin plus either Clopidogrel, ticagrelor, or prasugrel
Function of fibrinolytic (thrombolytic) therapy?
Dissolves clots
How does fibrinolytic therapy dissolve clots?
Converts plasminogen to plasmin (proteolytic enzyme)
1. Alteplase, a tissue plasminogen activator
2. Reteplase
3. Tenecteplase
When is fibrinolytic therapy most effective?
When patient presents early
(Best for patients younger than 75 years)
Goal of fibrinolytic therapy
To improve ventricular function and reduce mortality
Adjuncts to reperfusion therapy when managing a STEMI
- Unfractionated heparin (used for treatment lasting less than 48 hours)
- Low-molecular-weight heparin (used for treatment lasting longer than 48 hours)
- Antiplatelet drugs:
- Low dose aspirin
Types of Antiplatelet drugs used adjunct to reperfusion therapy when managing a STEMI
Clopidogrel (plavix)
Glycoprotein (GP) IIb/IIIa inhibitors
Considerations when giving a pt aspirin adjunct to reperfusion therapy when managing a STEMI
May use aspirin concurrently with clopidogrel
Should take indefinitely
Higher dose should be given for PCI patients
How should ACE inhibitors and ARBs be used while managing STEMI
They decrease short-term mortality in all patients
Start treatment within 24 hours
Why should calcium channel blockers be used when managing STEMI
Antianginal, vasodilation, and antihypertensive actions
Complications that can occur due to STEMI
Ventricular dysrhythmias
Cardiogenic shock
What occurs with ventricular dysrhythmias after STEMI
Develop frequently and are major cause of death after MI
Prophylactic antidysrhythmics not successful
What causes cardiogenic shock after a STEMI
Results from tissue perfusion reduction
7-15% of post MI patients develop shock in first few days
How can patients who have had a STEMI improve their chances of having another one
Cholesterol control
Smoking cessation
Exercise
Blood pressure control
Diabetes control
*Which medications should post MI patients take?
Beta blocker
ACE inhibitor
Antiplatelet drug or anticoagulant
Symptoms of Diabetes Melkite’s
Sustained hyperglycemia
Polyuria
Polydipsia
Ketonuria
Weight loss
Other names for T1DM
Insulin dependent
Juvenile onset
Primary defect of T1DM
Destruction of pancreatic beta cells
What percentage of diabetes cases is type 1?
5-10%
Another name for T2DM
*Non-insulin dependent diabetes
Adult onset
What causes type 2 diabetes?
Insulin resistance and impaired insulin secretion
Short term complications of diabetes
Hyperglycemia and hypoglycemia
Long term complications of diabetes
Macrovascular damage
- Heart disease
- HTN
- Stroke
Hyperglycemia
Altered lipid metabolism
What can Macrovascular damage from diabetes cause?
Retinopathy
Nephropathy
Neuropathy
Gastroparesis
Amputation secondary to infection
What causes gestational diabetes?
Placenta produces hormones that antagonize the actions of insulin
Glucose can pass freely from the maternal to the fetal circulation (fetal hyperinsulinemia)
What can happen if proper glucose levels are not maintained during pregnancy?
To prevent teratogenic effects
How is someone diagnosed with diabetes?
Excessive plasma glucose is diagnostic of diabetes.
Patient must be tested in two separate ways, and both tests must be positive
Tests that can be used to diagnose diabetes
Fasting plasma glucose (FPG)
Casual plasma glucose
Oral glucose tolerance test (OGTT)
*Hemoglobin A1C
What does glucose level have to be to diagnose diabetes from a fasting plasma glucose test?
126 mg/dL or higher
What does glucose level have to be to diagnose pt with diabetes for a casual plasma glucose test?
200 mg/dL or greater
What does a pt’s glucose level have to be to diagnose with diabetes during an oral glucose tolerance test?
200 mg/dL or higher
What does hemoglobin A1C measure?
Measures the glucose that’s bound to the hemoglobin molecules in the blood
Gives snapshot of what glucose levels have been over last 3 months
What level of A1C is indicative of diabetes?
6.5% and above
Criteria for pts to be diagnosed with pre diabetes
Impaired fasting glucose between 100 & 125 mg/dL
Impaired glucose tolerance test
What happens when someone is diagnosed with pre diabetes
They are at an increased risk for developing T2DM
(Many people who meet prediabetes criteria never develop diabetes)
May reduce risk with diet changes and exercise and possibly with certain oral anti diabetic drugs
Primary goal of diabetes treatment
To prevent long-term complications
What needs to be controlled during diabetes treatment?
Tight control of blood glucose level
Control blood pressure
Control blood lipids
Treatment plan for T1DM
Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement
Dietary measures for T1DM
Total number of carbohydrates is more important than the type
Glycemic index
Treatment plan for T2DM
Requires comprehensive plan:
- modified diet and exercise
- drug therapy
Should be screened and treated for:
- HTN
- Nephropathy
- Retinopathy
- Neuropathy
- Dyslipidemias
Common target values while self monitoring blood glucose:
*80-130 mg/dL before meals
*<180 mg/dL 1-2 hours after meals
Goal for A1C for diabetic patients
Below 7%
But below 8% may be appropriate for pts with a history of severe hypoglycemia
How is insulin synthesized?
In the pancreas by beta cells within the islets of langerhans
What stimulates insulin release
A rise in blood glucose, usually by eating food
*Types of rapid acting insulins
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
*Types of short acting insulin
Regular insulin: Humulin R
Regular insulin: Novolin R
*Type of intermediate duration insulin
Neutral Protamine Hagedorn (NPH) insulin
*Types of long duration insulin
Insulin glargine (Lantus)
Insulin detemir (Levemir)
*Types of ultra long duration insulin
Insulin glargine (toujeo)
Insulin degludec (Tresiba)
Prototype for short-duration, rapid-acting insulin
Insulin lispro (Humalog)
Time frames of Humalog
Rapid onset (15-30 mins)
Peak: .5-2.5 hrs
Short duration (3-6 hrs)
When should Humalog be administered
Before (or even after eating)
Should be injected 5-10 minutes before meals
Routes of Humalog
Usually subQ
Or insulin pump
Time frames of NovoLog
Rapid onset 10-20 minutes
Peak: 1-3 hours
Short duration 3-5 hours
When should NovoLog be administered?
5-15 minutes before meals
Time frames of Apidra
Rapid onset 10-15 minutes
Peak: 1-1.5 hours
Short duration 3-5 hours
When should Apidra be administered
Close to the time of eating
Routes for regular insulin
SubQ injection
SubQ infusion
IM injection (used rarely)
IV
Time frames for regular insulin
Onset: 30-60 mins
Peak: 1-5 hours
Duration: 10 hours
Color of regular insulin
Clear
Time frames of NPH insulin
Onset: 60-120 hours
Peak: 6-14 hours
Duration: 16-24 hours
What can NPH insulins be mixed with?
Short acting insulins (to give more coverage)
What color are NPH insulins?
Cloudy
And must be rotated before admin
Administration of NPH insulin
SubQ injection only
Must be rotated before admin
Time frames of lantus
Onset: 70 minutes
Duration 18-24 hours
Time frames of levemir
Onset 60-120
Duration: 12-24 hours
Color of long duration insulin
Clear solutions
How long does Toujeo last?
24 hours
(Very concentrated)
How are toujeo and tresiba typically administered?
Usually come in prefilled pens
*Rules for mixing insulin
NPH with short-acting insulins
Short-acting insulin is drawn first (clear to cloudy)
How can insulin be administered through subcutaneous infusion?
Portable insulin pumps
Implantable insulin pumps
How should insulin be stored?
*unopened vials should be refrigerated until needed
Not frozen!
Can be used until expiration date if refrigerated.
Keep out of direct sunlight and extreme heat
How should mixtures of insulin be stored?
Mixtures in vials: stable for 1 month at room temp and for 3 months under refrigeration
Mixtures in pre-filled syringes: stored in refrigerator for at least 1 week, stored vertically with needle pointing up
*Therapeutic uses of insulin?
Principle use: diabetes mellitus
(Required by all type 1 and some type 2 pts)
IV insulin for DKA
Hyperkalemia (can promote uptake of potassium)
AIDS in the diagnosis of GH deficiency
Complications of insulin treatment
Hypoglycemia
Lipohypertrophy (lumpy looking skin from injecting in same spot)
Allergic reactions
Hypokalemia
Drug interactions with insulin
Hypoglycemic agents
Hyperglycemic agents
Beta-adrenergic blocking agents
Glucose level of hypoglycemia
*below 70 mg/dL
Treatment for a pt who has a blood glucose below 70
Rapid treatment for hypoglycemia is mandatory
Conscious pts: fast-acting oral sugar (OJ, glucose tabs, soda)
If swallowing or gag reflexes are suppressed: IV glucose or parenteral glucagon
Medication group for T2DM
Oral hypoglycemics
Prototype of oral hypoglycemics
Metforman (Glucophage)
What type of oral hypoglycemic is metformin?
Biguanides
Most common side effects of metformin
GI disturbances
Lactic acidosis (potentially fatal but rare)
Uses of metformin
T2DM
Prevention of T2DM
Gestational diabetes
PCOS
What are Sulfonylureas used for?
Oral hypoglycemic for T2DM only
Promote insulin release
Major side effects of Sulfonylureas
Hypoglycemia
Weight gain
Why does rosiglitazone (Avenida) have restricted use?
Can cause cardiac side effects
How do alpha-glucosidase inhibitors work?
Oral hypoglycemics that act on the intestine to delay absorption of carbohydrates
Two alpha-glucosidase inhibitors
Acarbose (Precose)
Miglitol (Glyset)
Adverse effects of alpha-glucosidase inhibitors
Flatulence
Cramps
Abdominal distention
Diarrhea
Liver dysfunction
How do DPP-4 inhibitors (AKA gliptins) work?
Oral hypoglycemics that promote glycemic control by enhancing the actions of incretin hormones
Adverse effects of DPP-4 inhibitors
Upper respiratory infection
UTI
Headache
Types of drugs other than insulin that can treat T2DM
GLP-1 receptor agonists (incretin mimetics)
Amylin mimetics
2 GLP-1 receptor agonists
Exenatide (Byetta)
Liraglutide (Victoza)
1 drug that is a amylin mimetic
Pramlintide (Symlin)
Acute complications of poor glycemic control
Diabetic ketoacidosis (DKA)
Hyperglycemic hyperosmotic nonketotic syndrome (HHNS)
*Characteristics of DKA
Hyperglycemia
Water loss
Altered fat metabolism
Ketoacids
Hemoconcentration
Acidosis
Coma
Treatment for DKA
*Insulin replacement
Bicarbonate for acidosis
Water and sodium replacement
Potassium replacement
Normalization of glucose levels
Symptoms of HHNS
- Large amount of glucose excreted in urine
- Dehydration and loss of blood volume
- Increases blood concentration of electrolytes and non electrolytes (particularly glucose)
- Increases hematocrit (blood thickens and becomes sluggish)
How does HHNS occur?
With T2DM with acute infection, acute illness, or other stress
What happens if HHNS is left untreated?
Can lead to coma or death
Management of HHNS
Correct hyperglycemia and dehydration with IV insulin, fluids, and electrolytes
Difference between DKA and HHNS
HHNS has little or no change in ketoacid levels and has little or no change in blood pH
HHNS also has no sweet or acetone smell to urine/breath
Difference between treating DKA and HHNS
HHNS does not get treated with bicarbonate because there is no acidosis to treat
How is severe hypoglycemia treated?
IV glucose to immediately raise blood glucose level is preferred
*Glucagon can be used if IV glucose is not available
How does *glucagon work for treating hypoglycemia?
Delayed elevation of blood glucose (promotes glycogen breakdown)
Will not work in starvation (b/c malnourished have little glycogen left to break down)
Patient teaching for pts with diabetes
Self glucose checks
Medications
Care of insulin
All the supplies
Syringes - put used ones in a container
Nutrition
S & S of hypo- and hyper- glycemic
If they’re sick, have surgery, run marathons, etc, will all require adjusting doses
Age of pt and family support
What functions do thyroid hormones have a profound effect on?
Metabolism
Cardiac function
Growth (promotes maturation in infancy and childhood development)
Hormones produced by the thyroid
Triiodothyronine (T3)
Thyroxine (T4, tetraiodothyronine)
Synthetic T3
Liothyronine
*Synthetic t4
*Levothyroxine
What is a serum TSH test used for?
Screening and diagnosis of hyperthyroidism
(Elevated TSH is indication of hyperthyroidism)
What are serum T3 or T4 tests used for?
Can measure total T4 or free T4
(Or total T3 or free T3)
What is hypothyroidism called in adults?
And in infants?
Myxedema in adults
Congenital hypothyroidism in infants
How is hypothyroidism treated in adults?
Replacement therapy with thyroid hormones
In almost all cases, treatment must continue lifelong
How is hypothyroidism treated in infants?
Replacement therapy with thyroid hormones
Clinical presentation of hypothyroidism in adults
Pale, puffy, and expressionless face
Cold and dry skin
Brittle hair or loss of hair
Lowered heart rate and temperature
Lethargy and fatigue
Intolerance to cold
Impaired mentality
Causes of hypothyriodism
Malfunction of the thyroid (usual cause)
Hashimoto’s disease (Chronic autoimmune thyroiditis)
Insufficient iodine in diet
Surgical removal of thyroid and destruction of thyroid with radioactive iodine
Insufficient secretion of TSH and TRH
Lifelong medications that are used to treat hypothyroidism
Levothyroxine (T4) (standard treatment)
*Liothyronine (T3) option
What can occur if someone has hypothyroidism during pregnancy?
In first trimester can result in permanent neuropsychological defects in the child
What can occur in infants who have hypothyroidism
May be permanent or transient
Can cause mental retardation and derangement of growth if not diagnosed and treated
Two forms of hyperthyroidism
Graves’ disease (most common form)
Toxic nodular goiter (Plummer’s disease)
Who does Graves’ disease most typically affect?
Women 20-40 years old
Notable symptom of Graves’ disease
Exophthalmos
Cause of hyperthyroidism
thyroid-stimulating immunoglobulins (TSIs)
Treatment of hyperthyroidism
Surgical removal of thyroid tissue
Destruction of thyroid tissue
Suppression of thyroid hormone synthesis
Beta blockers (ex: propranolol)
Nonradioactive iodine
Causes of thyrotoxic crisis (thyroid storm)
Patients with thyrotoxicosis who undergo significant stress (surgery, illness, etc.)
High levels of thyroid hormone
(Cannot be identified by laboratory testing)
Signs of thyrotoxic crisis
Hyperthermia (105° or higher)
Severe tachycardia
Restlessness
Agitation
Tremor
Unconsciousness
Coma
Hypotension
Heart failure
*Treatment of thyrotoxic crisis
*Potassium iodide, *Methimazole, and *Beta blocker
Sedation, cooling, glucocorticoids, IV fluids
Prototype thyroid hormone preparation for hypothyroidism
*Levothyroxine (Synthroid)
What is Levothyroxine (Synthroid)?
Synthetic preparation of thyroxine (T4) and drug of choice for *all types of hypothyroidism
Conversion to T3
Half life of Levothyroxine (Synthroid)
7 days
When should Levothyroxine be taken?
In the morning at least 30-60 minutes before breakfast
Adverse effects of Levothyroxine
Tachycardia
Angina
Tremors
Can intensify effects of warfarin
Drug interactions of Levothyroxine
Drugs that reduce Levothyroxine absorption
Drugs that accelerate Levothyroxine metabolism
Warfarin
Catecholamines (too much stimulation)
First-line drug for hyperthyroidism
Methimazole (Tapazole)
What type of drug is Methimazole (Tapazole)?
Thionamides
How long does it take for Methimazole to work?
May take 3-12 weeks for euthyroid state (may need to add something to help sooner)
Pros and cons of Methimazole
Does not cause liver damage associated with PTU
Does not destroy existing stores of thyroid hormone
More dangerous than PTU during lactation and during the first trimester of pregnancy
Considered a hazardous agent, handle with caution
Applications of Methimazole in hyperthyroidism
- Can be used alone for Graves’ disease
- Adjunct to radiation therapy until the effects of radiation manifest
- Suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy)
- Patients experiencing thyrotoxic crisis (although PTU is preferred)
Function of propylthiouracil (PTU)
Inhibits thyroid hormone synthesis
Second line drug for Graves’ disease
Half life of PTU
90 minutes
How long does it take PTU to work?
6-12 months for full benefits
Therapeutic uses of PTU
Graves’ disease
Adjunct to radiation therapy
Preparation for thyroid gland surgery
Thyrotoxic crisis
Adverse effects of PTU
Agranulocytosis (most serious)
Hypothyroidism
Pregnancy and lactation
Can cause *severe liver damage
PTU vs. Methimazole
PTU can cause severe liver injury, meth does not
PTU has shorter half life, hence it requires 2-3 daily doses
PTU crosses placenta less readily than meth and achieves lower concentrations in breast milk
PTU blocks conversion of T4 to T3 in the periphery, meth does not
What is Radioactive Iodine-131?
Radioactive isotope of stable iodine
Emits gamma and beta rays
Half life of radioactive iodine 131
8 days
How long does it take radioactive iodine to work?
2-3 months for full effect
When is radioactive iodine used?
In Graves’ disease
Cannot be used in children or during pregnancy
Type of nonradioactive iodine
Lugol’s solution
What is Lugol’s solution used for?
Strong iodine solution used to suppress thyroid function in preparation for thyroidectomy
Adverse effects of Lugol’s solution
Brassy taste
Burning sensation in mouth and throat
Soreness of teeth and gums
GI injury
(These could all also be symptoms of mild toxicity)
How can beta blockers be used for thyroid issues?
For hyperthyroidism
Can suppress tachycardia and other symptoms of Graves’ disease
(Benefits derive from beta-adrenergic blockade, not from reducing levels of T3 or T4)
Also beneficial in thyrotoxic crisis
