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Therapeutics II > Exam 3 > Flashcards

Exam 3 Flashcards

1
Q

National Organ Transplant Act

A

Passed by congress in 1984 to address the nations critical donor shortage and improve the organ matching process.
Established OPTN

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2
Q

Indications for renal transplant (RTx)

A

End stage renal disease (ESRD) regardless of the cause.

Diabetes is the primary cause

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3
Q

Absolute contraindications to RTx

A

Severe cardiovascular or pulmonary disease
Chronic illness with short life expectancy
Active or recently treated cancer
Active sepsis or life threatening infectious disease
Active substance abuse
Poorly controlled mental illness

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4
Q

Relative contraindications to RTx

A 
Current tobacco use
BMI
Age
Dementia
Lacking social support
Non-Adherence
Limited or no health insurance
Pharmacologic
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5
Q

RTx- Donor evaluation

A

Must be at least 18 years old in good physical and mental health
Must be willing to donate (do not feel like you must)
Be well informed and have a good grasp on the risks and benefits.
Have a good support system

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6
Q

DBD: Donation after brain death

A

Death declared by physician (Not OPO)
Once, declared, OPO involved
Pt remains on ventilator throughout organ recovery which takes 3-4 hours

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7
Q

DCD: Donation after cardiac death

A 
Family/NOK decide to withdrawal care 
Once decided, OPO involved
Ventilator support withdrawn and death declared by physician 5 minutes after ceased circulation. 
Organ recovery in 1-2 hours 
Lack of blood flow may damage organs
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8
Q

Donor/ recipient Compatibility

A
  1. ) Blood type matching
  2. ) Tissue type matching
  3. ) Crossmatching
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9
Q

Blood type A matching

A

antibodies- anti-a
antigens-A

Compatible blood types- A and O

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10
Q

Blood Type B matching

A

Antibodies- anti B
Antigens- B

Compatible blood types- B or O

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11
Q

Blood Type AB matching

A

Antibodies- none
Antigens- A and B
Compatible blood types- A, B, AB, O

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12
Q

Blood Type O matching

A

Antibodies- anti-a, anti-b
antigens-none
compatible blood type- O

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13
Q

Tissue type matching

A

Determines the number of antigens the donor and recipient share
The more antigens matched, the more successful the transplant

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14
Q

Cross matching

A

Used to identify the presence of preformed antibodies against a donor (events: pregnancy, blood transfusion, prior transplant)
Panel Reactive Antibody (RBA)- recipient serum is tested against donor lymphocytes contained from a panel of about 100 donors.
%PRA=0= donor not sensitized, donor and recipient cells do not react together.

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15
Q

Desensitization

A

Process (plasmapheresis +/- medication therapy) to reduce harmful donor specific antibodies

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16
Q

Acute transplant rejection

A

Can occur at any time post-transplant and may lead to allograft loss.
Diagnosis: biopsy, decline in function, organ-specific factors
Kidney- rise in SCr
Liver- Elevated LFTs
Heart- no specific symptoms

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17
Q

Risk factors for rejection (kidney)

A 
Number of HLA mismatches
Younger recipient age
Older donor age
AA ethnicity 
Panel reactive antibody (>40%)
Cold ischemia time >24 hours
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18
Q

General concepts of immunosuppressants

A

Lifelong immunosuppression is required after transplant
Risk of rejection is higher in the beginning
Induction immunosuppression- potent drugs given at time of transplant to quickly resolve immune response. Not always necessary
Maintenance immunosuppression- Started within the 1st week and continued long term. Higher doses in first 6-12 months
Infections are common
PTLD, tumors, and skin cancer common

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19
Q

BBW for most immunosuppressants

A

Increased risk of infection that may lead to hospitalization or death
May be associated with the development of malignancies that can lead to hospitalization or death

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20
Q

How to take immunosuppressants

A

No missed doses
Take on a fixed schedule
Take the same way each day (with or w/o food)

Must be up to date in vaccines prior to transplant, avoid live vaccines after transplant

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21
Q

The three signal model of T cell activation

A

Signal 1: Activation of T cell receptor (TCR)

  • Located on T lymphocyte surface
  • Recognizes foreign antigen presented by antigen-presenting cells

Signal 2: Co-Stimulation: Interaction between cell surface markers between the APC and T cell

Signal 3: Activation of IL-2 receptor on the T cell surface. Stimulates T cell proliferation

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22
Q

Classes of immunosuppressant drugs

A 
Calcineurin inhibitors
Costimulation inhibitors
Antimetabolites
m-TOR inhibitors
Corticosteroids
Monoclonal and polyclonal antibodies
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23
Q

Calcineurin inhibitors

A

Cyclosporine
Tacrolimus

Inhibit T cell activation by preventing the phosphatase enzyme calcineurin from acting on the nuclear factor of activated T cells (NFAT), the function of which is to upregulate the expression of IL-2

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24
Q

Cyclosporine varieties, absorption, and metabolism

A

Available in different dosage forms that are no bioequivalent.
Cyclosporine USP- oral and injectable
Cyclosporine USP modified- a microemulsion, oral only

Absorption-
Cyclosporine USP- poor and erratic, bile dependent
Cyclosporine modified- Improved not bile-dependent

Metabolism- Gut and hepatic CYP3A4, p-glycoprotein

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25
Q

Cyclosporine (CSA) major adverse events

A

Nephrotoxicity

  • Acute- reversible and dose-dependent vasoconstriction of afferent arteriole
  • chronic- irreversible damage to the nephrons

Neurotoxicity- tremor, HA, insomnia, confusion, PRES
Cosmetic effects- acne, hirsutism, gingival hyperplasia
Hyperkalemia
Hyperlipidemia
Hypertension

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26
Q

Cyclosporine dosing

A

Initial doses are weight-based and dosed Q12H
Titrated to achieve target trough levels of 100-400ng/mL

IV- 33-50% of oral dose as continuous infusions or in 2 divided doses

  • Must be non-PCV bags.
  • Associated with anaphylaxis and additional nephrotoxicity
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27
Q

Tacrolimus dosage forms, absorption, and metabolism

A

Calcineurin inhibitor
Available in different dosage forms-not bioequivalent
IR and ER formualtions
Absorption- variable, not bile-dependent, decreased by food (take consistently with regard to food)

Metabolism- CYP3A4 and p-glycoprotein

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28
Q

Tacrolimus AE

A

Same as cyclosporine, but more tolerable
More common- hyperglycemia, neurologic effects
Less common- HTN, hyperlipidemia, cosmetic effects

Additional AE- diarrhea, alopecia

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29
Q

Tacrolimus dosing

A

Initial doses are weight based and dosed Q12H
Titrated to achieve target trough values of 5-20ng/mL

IV- 25-33% PO dose as continuous infusion, must uses non-PCV bags, risk of anaphylaxis

Sublingual- open capsule contents under tongue and allow to dissolve. 50% PO dose.

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30
Q

Cyclosporine VS Tacrolimus

A

Study done in 1998

Three year graft and treatment failure significantly in the tacrolimus group

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31
Q

DDI with CNIs

A

Enzyme inducers lower CSA/TAC levels

  • This increases the risk of rejection
  • Phenytoin, carbamazepine, phenobarbitol, Rifampin, St. Johns wort

Enzymes inhibitors raise CSA/TAC levels

  • Increases risk of toxicities
  • Erythromycin, clarithromycin, azole antifungals, diltiazem, verapamil, nifedipine, metoclopramide, grape fruit juice
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32
Q

Trough levels

A

Whole blood concentrations drawn immediately before next dose

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33
Q

Belatacept

A

Costimulation inhibitor (Signal 2)
Binds CD80 ad CD86 receptors on APCs
-Blocks the binding to CD28 on T cells

Approved for kidney transplant only
IV infusion given monthly
Major benefit over CNIs- Decreased nephrotoxicity

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34
Q

Belatacept vs Cyclosporine

A

Belatacept is superior in kidney transplant

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35
Q

Antimetabolites

A

Azathioprine
Mycophenolate

Inhibit purine nucleotide synthesis which is necessary for T cell proliferation
Signal 3

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36
Q

Azathioprine

A

Prodrug, converted to 6-MP which competes with other purines to inhibit purine nucleotide synthesis

  • prevents proliferation
  • Acts within de novo and salvage pathways

6-MP is metabolized by several pathways, one of which is xanthine oxidase

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37
Q

Azathioprine AE

A

Hematologic- leukopenia, anemia, thrombocytopenia
N/V (take with food)
Alopecia, hepatotoxicity, pancreatitis

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38
Q

Azathioprine dosing

A

Oral- initial doses are weight based and dosed QD
Doses decrease with time away from transplant
IV=PO
Titrated to WBC count 3500-6000 (low-normal)

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39
Q

Mycophenolate

A 
Mycophenolate mofetil (MMF)
Enteric-coated mycophenolate sodium (EC-MPS)

Both are prodrugs for mycophenolic acid (MPA)
MMF is rapidly converted into MPA by 1st pass metabolism (desterification)
EC-MPS is released in small intestine

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40
Q

Mycophenolate MOA

A

MPA inhibits inosine monophosphate dehydrogenase (IMPDH)
-This inhibits lymphocyte proliferation

More specific than AZA for lymphocytes

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41
Q

Mycophenolate metabolism and elimination

A

After oral intake there is a rapid hydrolysis to MPA, seen as first peak concentration
MPA is converted back into MPAG in liver and some of it goes into enterohepatic recirculation appearing as a “second peak”
Complex metabolism=no trough levels

Excreted by the kidneys as either MPA or MPAG
Both metabolites may accumulate with renal insufficiency

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42
Q

Mycophenolate AR

A

GI: N/V/D, abdominal pain, peptic ulcers
-Take on an empty stomach (decreases Cmax with food) but food does not affect the overall AUC so you can take with or w/o food
Leukopenia, anemia

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43
Q

Mycophenolate dosing

A

Given BID, can split up more frequently prn for GI AE

MPA AUC equations are available

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44
Q

mTOR inhibitors

A

Sirolimus and Everolimus

Structurally related to macrolide abx and tacrolimus
-Diff MOA as TAC so can be used together

MOA: Inhibit mammalian target of rapamycin and inhibit vascular endothelial growth factor

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45
Q

Sirolimus

A

Poor absorption
Variably affected by food- take consistently with regard to food
Metabolism- CYP 3A4 and p-glycoprotein substrate
Mean 1/2 life of 60hrs
Time to steady state- 2 wks
Trough concentrations 1-2 weeks after dose changes

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46
Q

Sirolimus AE

A 
Leukopenia, anemia, thrombocytopenia (dose related)
Hyperlipidemia (particularly TGs)
Delayed wound healing
Mouth ulcers
Interstitial pneumonitis
Hepatic artery thrombosis after OLTXP
Proteinuria
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47
Q

Sirolimus dose

A

Loading doses may be given if needed to get to therapeutic levels quickly
Dosed QD
Titrated to trough levels 5-25ng/mL
No IV formulations

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48
Q

Everolimus

A

2 types: kidney and liver transplant (tab), oncology (tabs and tabs for suspension)

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49
Q

Everolimus metabolism, ARE, dosing

A

Metabolism- Substrate of CYP3A4 and P-glycoprotein
1/2 life- 30 hours
Similar AE to sirolimus, but slightly better
Dosed BID
Titrated to trough levels 3-8ng/mL

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50
Q

Corticosteroids

A

Methylprednisolone and prednisone

Broad spectrum immunosuppressants
Decrease adhesion molecule synthesis
Inhibit transcription factors

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51
Q

Corticosteroids metabolism

A

Hepatic, active metabolite- prednisolone

Long biologic 1/2 life- give QD

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52
Q

Corticosteroids AE

A

Hyperglycemia, osteoporosis, cataracts, acne, CNS stimulation, HPA axis suppression, acid reflux, GI ulceration

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53
Q

Corticosteroids dose

A

Initially given in very high doses
Gradually tapered
Usual maintenance doses <10mg/day
Combination with other IS agents for lower doses

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54
Q

Monoclonal and Polyclonal antibodies

A

Target various immune cell surface markers, particularly on B and T lymphocytes
Indications vary- induction agents and acute rejection

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55
Q

Alemtuzumab

A

Mech- Anti-CD 52 monoclonal antibody
-causes antibody-dependent cellular-mediated lysis
Uses- B-cell chronic lymphocytic leukemia
Txp- induction therapy and acute rejection

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56
Q

Alemtuzumab dosing and AE

A

One dose IV injection on day of transplant

AE: neutropenia, anemia, thrombocytopenia, infusion reactions

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57
Q

Basiliximab

A 
Chimeric- mouse-human monoclonal antibody
Mechanism- IL-2receptor antagonist
Use for induction therapy only
Given IV x 2 doses
AE- infusion reactions rare
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58
Q

Additional MABs used in kidney transplant

A

Rituximab-anti CD20 antibody, eliminates B lymphocytes
Use to treat rejection

Eculizumab- binds to compliment protein
Prevents compliment-mediated damage that can occur with rejection

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59
Q

Rabbit antithymocyte Globulin (rATG)

A

Polyclonal
Manufactured by introducing human lymphoid tissue into rabbits
Causes T cell depletion
Used in induction therapy and for tx of acute T cell-mediated rejection

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60
Q

Antithymocyte Globulin

A

Given in slow IV infusion for 3-14 days

AE: neutropenia, anemia, thrombocytopenia, infusion rxns, thrombophlebitis, serum sickness

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61
Q

ATG (equine) and IV immune globulin polyclonal antibodies

A

ATG- similar to rATG but less effective

IVIG0 multiple mechanisms to reduce circulating HLA antibody levels

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62
Q

Proteosome inhibitors

A

Bortezomib and Carfilzomib
Reversibly (B) or irreversibly (C) bind to intracellular proteasomes
Causes cell death in a variety of cell types that are dependent on proteasome function (plasma cells)
Elimination of plasma cells reduces antibody function

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63
Q

Hyperacute rejection

A

occurs minutes to hours after organ reperfusion
Requires preformed circulating antibodies
Crossmatch and blood matching techniques make this very rare

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64
Q

Acute rxn

A

3 subtypes: T cell-mediated (cellular), antibody mediated, or mixed

Can occur any time 1 week or longer
Diagnosed via biopsy
May or may not be reversible

65
Q

Creating IS regimens

A

Combine drugs that act in different areas of the 3-signal model
+/- induction therapy- varies by organ
Maintenance therapy- CNA (CSA/TAC) or belatacept + antiproliferative (AZA, MMF, mTOR) + prednisone

Most common: TAC+ MMF+ Pred

66
Q

Gluconeogenesis

A

Production of glucose from noncarbohydrate precursors

67
Q

Glycogenesis

A

Conversion of glucose to glycogen for storage

68
Q

Glycogenolysis

A

Breakdown of stored glycogen to glucose

69
Q

Glycolysis

A

Breakdown of stored glycogen to glucose

70
Q

Pancreatic islet cells

A

The pancreatic islet cells and their endocrine precursors:
alpha- glucagon
beta- insulin, amylin
delta- somastatin

The exocrine pancreas is involved in digestion

71
Q

How does glucagon raise blood glucose

A

It stimulates glycogenolysis and gluconeogenesis

It also stimulates fat breakdown

72
Q

How does insulin lower blood glucose?

A

Insulin is anabolic (a builder)
It stimulates glucose uptake
It suppresses glucose produced by the liver
It suppresses free fatty acids (FFA) release from fat cells. FFAs inhibit uptake of glucose and stimulate gluconeogenesis. Chronic FFa release will cause insulin resistance
Insulin suppresses glucagon release

73
Q

Fasting state

A

Glucose-disposal
Non-insulin dependent tissues (75%)
Liver and muscle (25%)
Glucose production primarily in liver

74
Q

Non-insulin dependent tissues

A 
Beta cells
Red blood cells
Intestines
Central nervous system
Kidney
75
Q

Fed state

A

Glucose disposal
Muscle- 80-85%
Adipocyte- 4-5%
Do mild physical activity after eating to stimulate glucose disposal

76
Q

Pathogenesis of Type 1 Diabetes

A

Autoimmune disease with progressive beta cell destruction, resulting in physiologic dependence on exogenous insulin

77
Q

Stage 1 Type 1 Diabetes

A

Characteristics- autoimmunity, normoglycemia, presymptomatic

Diagnostic criteria- Multiple antibodies, no IGT or IFG

78
Q

Stage 2 Type 1 diabetes

A

Characteristics- autoimmunity, dysglycemia, presymptomatic
Diagnostic criteria- Multiple antibodies, Dysglycemia: IFG and/or IGT
FBG: 100-125mg/dL
A1C: 5.7-6.4% or greater than 10% increase

79
Q

Stage 3 Type 1 Diabetes

A

Characteristics- New-onset hyperglycemia, symptomatic

Diagnostic criteria- Clinical symptoms, diabetes from normal criteria

80
Q

Coexistent autoimmunity in type 1 diabetes

A

Celiac disease- have gluten free diet

Thyroid disease, generally hypothyroidism

81
Q

Pathogenesis of Type 2 diabetes

A

Caused by multiple defects:

  • Impaired insulin secretion
  • Insulin resistance involving muscle, liver, and adipocytes
  • Excess glucagon secretion
  • Deficiency and resistance to insulin hormones
  • Sodium0glucose cotransporter upregulation in the kidney
82
Q

Insulin secretion

A

Glucose gets into the cells and closes the ATP-K channel, this opens the Ca channel and insulin is released
Insulin is not involved in glucose getting into beta cells

83
Q

What phase of insulin response is impaired in T2DM?

A

Phase 1- insulin is not being stored completely

84
Q

Impaired insulin secretion T2DM

A

Beta cell mass and function is reduced
This failure is progressive, there is a 5-7% loss of beta cells per year
-Caused by glucose toxicity, age, lipotoxicity, insulin resistance, genetics, incretin deficiency

85
Q

Glucose toxicity

A

As glucose increases insulin increases. Glucose is toxic to beta cells and they can’t keep up with chronically high levels of glucose, causing loss of cells and function

86
Q

Insulin Resistance T2DM

A

Liver- Hepatic glucose production increased in mild to moderate fasting hyperglycemia.
-Failure to suppress glucagon in response to a meal (two sources of glucose production in fed state)

Peripheral (skeletal muscle)- major site of postprandial glucose disposal. Onset of insulin action is delayed for about 40 minutes. Glucose uptake reduced by 50%

Peripheral (adipocyte)- Fasting plasma FFA levels increased and fail to suppress after glucose ingestion. FFAs stored as TGs in adipocytes and insulin is a potent inhibitor of lipolysis

87
Q

Obesity and insulin resistance

A

Weight gain leads to insulin resistance
Visceral adipose tissue (VAT)
-fat cells located w/in abdominal cavity
-correlates with insulin resistance
-waste circumference is good marker
-Higher rate of lipolysis means increased FFA production
-Produces adipocytokines, increased FFA production
-Produces adipocytokines, causing insulin resistance, HTN, and hypercoagulability

88
Q

Glucagon secretion T2DM

A

Failure to suppress glucagon after a meal

Paradoxical rise in glucagon levels because of insulin resistance and GLP-1 resistance

89
Q

The incretin effect

A

Glucagon-like peptide-1 (GLP-1) is secreted by L cells

  • Levels decreased in T2DM
  • Stimulated insulin secretion and suppresses glucagon secretion.
  • Slows gastric emptying
  • Reduces food intake by increasing satiety

Glucose-dependent insulinotropic peptide (GIP)- secreted by K cells

  • Insulin secretion during near-normal glucose levels
  • insulin sensitizer in adipocytes
90
Q 
Characteristics of diagnosis for Type 1 Diabetes
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
A 
Age- <35
C-peptide- Very low
ICA, GAD65, IA-2, IAA- Often positive
Circulating Insulin- Rapidly deficient
Time to requiring insulin- At onset
91
Q 
Characteristics of diagnosis for Type 2 Diabetes
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
A

Age- >35
C-peptide- Normal to high
ICA, GAD65, IA-2, IAA- Negative
Circulating Insulin- Excessive and resistant
Time to requiring insulin- Can be many years

92
Q 
Characteristics of diagnosis for LADA
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
A 
Age- >/= 30
C-peptide- Low
ICA, GAD65, IA-2, IAA- Can be positive 
Circulating Insulin- Gradually resistant
Time to requiring insulin- Within 6 months (variable)
93
Q

Gestational Diabetes Mellitus (GDM)

A

Any degree of glucose intolerance with on set or first recognition during pregnancy

  • Test for GDM at 24-48 weeks of gestation in pregnant women not previously known to have diabetes (A)
  • Test for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors (B)

If first trimester, it is T2DM not GDM
Second trimester, GDM unless clearly otherwise

94
Q

Screening for GDM

A

75g glucose load, check fasting levels 1 hr and 2 hr after.

Diagnosis if fasting- 95mg/dL
1hr- 180mg/dL
2 hr- 155mg/dL
3hr- 140mg/dL

95
Q

Long term risk of GDM

A

Strongest known predictor of T2DM- 50% diagnosed 10 years postpartum

Test women with GDM for prediabetes or diabetes at 4-12 weeks postpartum

2/3rds chance of GDM in future pregnancies

Increased lifetime risk of HTN and stroke

96
Q

Medications related to hyperglycemia

A 
Fluoroquinolones (cipro)
Atypical antipsychotics (Risperidone, quetiapine, olanzapine)
Beta-blockers
Glucocorticoids
Calcineurin inhibitors
Protease inhibitors
Thiazides and thiazide like diuretics
97
Q

Criteria for diabetic testing in asymptomatic adults

A 
Testing should be considered in overweight or obese adults who have one or more of the following risk factors:
-1st degree relative with diabetes
-History of CVD
-HTN
-Hyperhcolesterolemia
-Women with PCOS
- Physical inactivity
-High risk ethnicity
Begin testing at 45 for all patients 
Test q 3 years for women that have had GDM
Prediabetics should be tested yearly
All other patients should be tested q 3 years
98
Q

Clinical presentation of diabetes

A 
Polyuria
Polydipsia
Polyphagia
Lethargy/fatigue
Weight loss
Blurred vision
99
Q

Diagnostic criteria for diabetes

A

A1C- >/= 6.5%
FPG- >/= 126mg/dL
2-hr PG- >/= 200mg/dL during an OGTT

Classic symptoms of hyperglycemia and random PG >/= 200mg/dL

100
Q

Diagnostic criteria for prediabetes

A

A1C- 5.7-6.4%
FBG- 100-125mg/dL
2-h PG- 140-199mg/dL

101
Q

Hemoglobin A1C

A

Glucose enters erythrocytes and glycates amino terminals of hemoglobin

  • Represents glycemic exposure over 2-3 months
  • Does not require fasting
  • Levels may vary with race/ethnicity
  • Hemoglobinopathies/RBC turnover
102
Q

Estimated average blood glucose (eAG) eqn

A

eAG= 28.7 x A1C -46.7

103
Q

Strengths of A1C

A

Reflects chronic hyperglycemia
Less biologic variability than 1-2h glucose
Eliminates need for fasting
Unaffected by acute illness or recent activity
Used as a guide to adjust treatment
Better predictor of complications that fasting BG

104
Q

Limitations of A1C

A

Certain conditions interfere with the interpretation of results (hemolytic anemia, recent transfusion, pregnancy, loss of blood)
Lack of standardization in other countries
Cost

105
Q

Symptoms of hypoglycemia

A

Tremor, nervous/anxious, diaphoresis, tachycardia, hunger, lightheaded/HA, irritable, confusion, drowsiness

106
Q

Hyperglycemic crisis

A

Type 1- diabetic ketoacidosis

Type 2- Hyperglycemic hyperosmolar state

107
Q

Microvascular complications of diabetes

A

Retinopathy
Nephropathy
Peripheral neuropathy
Autonomic neuropathies (gastroparesis, erectile dysnfunction)

108
Q

Macrovascular complications of diabetes

A

CAD, cerebrovascular disease, peripheral artery disease

109
Q

DCCT trial

A

Intensive treatment of decreasing A1Cs decreases the risk of microvascular complications but not macrovascular

110
Q

ADA glycemic targets

A

A1C- <7%
Preprandial- 80-130mg/dL
Peak postprandial PG- <180mg/dL

111
Q

Monitoring for diabetes

A

Perform the A1C test at least 2 times a year in patients who are meeting treatment goals and who still have glycemic control
-Perform A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic control

112
Q

Self-monitoring of blood glucose

A

Intensive insulin regimen- prior to meals/snacks, bedtime, occasionally postprandially, prior to exercise, when hypoglycemia expected, after treating hypoglycemia, prior to critical tasks (driving)

113
Q

Continuous glucose monitoring

A

Measures interstitial glucose
Real-time CGM- continuously report glucose levels. Alarms for hypo and hyperglycemia

Intermittently scanning CGM (isCGM)- adult use only, no alarms, lower cost, does not communicate continuously

Limitations- Invasive, some require daily calibrations, requires very motivated pts

114
Q

CGM- based targets

A

Goal target range 70-180 and be in this range >/= 70% of the time

115
Q

Risks of uncontrolled diabetes in pregnancy

A 
Spontaneous abortion
Fetal anomalies
Preeclampsia 
Fetal demise
Macrosomia
Neonatal hypoglycemia
Neonatal hyperbilirubinemia
116
Q

Pregnancy diabetes recommendations

A

A1C- <6.5%
Preconception counseling
Medication evaluation

117
Q

Preeclampsia and aspirin

A

Women with type 1 and type 2 diabetes should be prescribed low dose aspirin from the end of the first trimester until the baby is born in order to lower risk of preeclampsia

118
Q

Childrens and adolescents with diabetes

A

Mainly Type 1

Insulin doses may need to change based on sexual maturity and physical growth
Assess the ability to provide self-care
Supervision in childcare/school
Neurological vulnerability to hypoglycemia/hyperglycemia
Less stringent A1C goals than other pts due to risk of hypoglycemia

119
Q

Older adults diabetes

A

Less stringent A1C goals

120
Q

Cystic fibrosis related diabetes (CFRD)

A

Associated with worse nutritional status, more severe inflammatory lung disease, greater mortality.

Primary defect is insulin insufficiency related to partial fibrotic destruction of the islet mass

Annual screenings should begin at age 10 with OGTT
Do not use A1C

Patients should be treated with insulin!

121
Q

Posttransplantation Diabetes Mellitus (PTDM)

A

Describes presence of diabetes in posttransplant setting irrespective of timing to diabetes onset

OGTT= gold standard test

122
Q

Angioplasty

A

Damage of blood vessels

123
Q

Microvascular disease

A

Damage to small blood vessels

124
Q

Macrovascular disease

A

Damage to the arteries

125
Q

Macrovascular complications of diabetes

A

Cerebrovascular disease, CAD, peripheral vascular disease

126
Q

Microvascular complications of diabetes

A

Retinopathy, Nephropathy, autonomic neuropathy, peripheral neuropathy

127
Q

What is the mechanism behind complications in diabetes?

A

Chronic exposure to hyperglycemia
-Interaction of glucose with proteins causes advanced glycosylation end products and leads to tissue damage and injury

-Accumulation of metabolic products of aldose reductase system affects cellular energy metabolism and contributes to cell injury and death

128
Q

ASCVD

A 
Acute coronary syndromes
H/O MI
Stable or unstable angina
Coronary or other arterial revascularization 
Stroke
Transient ischemic attack
Peripheral arterial disease
129
Q

ASCVD and HTN

A

HTN is a major risk factor for ASCVD and microvascular complications

Type 1 diabetes- often underlying nephropathy

Type 2 diabetes- coexists with other cardiometabolic risk factors

130
Q

BP goals for diabetes patients

A

ACC/AHA- <130/ <80
ADA
Diabetes + HTN+ 10-year risk >15%- <130/<80
Diabetes + HTN + 10 year risk <15%- <140/<90

131
Q

Diabetes + BP <160/100 treatment

A

Lifestyle management
Start with one agent
Albuminuria? Yes- ACE/ARB
No- ACE/ARB/CCB/Thiazide

132
Q

Diabetes + BP >160/100 treatment

A

Lifestyle management
Start with 2 agents
Albuminuria? Start ACE or ARB + thiazide or CCB
no- Any 1st line agents

133
Q

ASCVD lipid management

A

Increased prevalence of lipid abnormalities in T2DM
Low HDL associated with high TG
Use statin

134
Q

Statin benefit groups

A
  1. ) Clinical ASCVD
  2. ) Primary elevation of LDL >190mg/dl
  3. ) 40-75 yo w/ diabetes w/ LDL 70-189mg/dL
  4. ) W/O clinical ASCVD or diabetes aged 40-75 w/ LDL 70-189mg/dL and 10 year risk >7.5%
135
Q

What intensity statin should be recommended for statin benefit groups?

A

Moderate to high intensity

136
Q

ADA statin recommendations primary prevention

A

40-75= moderate intensity statin
20-39 w/ ASCVD risk factors= may be reasonable Multiple ASCVD risk factors or 50-79= High-intensity statin
ASCVD risk >20% and LDL reduction <50%= add ezetimibe

137
Q

ADA statin recommendations secondary prevention

A

High-intensity statin

Very high risk and LDL>70= add ezetimibe or PCSK9 inhibitor

138
Q

ASCVD risk factors

A 
LDL >100mg/dL
HTN
Smoking
CKD
Albuminuria
Family h/o premature ASCVD
139
Q

Vascepa

A

Icosapent ethyl (Vascepa)
FDA approval in 2019 for pts with controlled LDL on a statin but elevated TG (135-499)
REDUCE-IT trial

140
Q

Fibrates and Niacin

A

Combination therapy with statin has not been shown to improve ASCVD outcomes or provide additional CV benefit and is generally not recommended

141
Q

ASCVD antiplatelet agents

A

Everyone should be on an aspirin for secondary prevention

Primary prevention based on risk factors

142
Q

Diabetic nretinopathy

A

Prevalence strongly related to duration of diabetes and glycemic control
Chronic hyperglycemia, nephropathy, HTN, dyslipidemia all increase risk

143
Q

Nonproliferative diabetic retinopathy (NPDR)

A

Hyperglycemia contributes to changes in the integrity of blood vessels within the retina
Alterations in blood-retinal barrier and vascular permeability
Release of angiogenic factors related to hypoxia and ischemia
Occlusion of retinal capillaries

144
Q

Proliferative diabetic retinopathy (PDR)

A

Neovascularization and accumulation of fluid within the retina (macular edema) contribute to vision impairment

145
Q

Stages of diabetic retinopathy

A

Mild nonproliferative- microaneuryisms
Moderate nonproliferative- some blood vessels in retina become blocked
Severe nonproliferative- many blood vessels blocked. New blood vessels begin to form.
Proliferative- New BV have thin and weak walls and leak. This causes severe vision loss and potential blindness.

146
Q

Screening for diabetic retinopathy

A

Type 1- at least w/in 5 years of onset
Type 2- at onset

After onset screen yearly

147
Q

Diabetic nephropathy

A

Leading cause of ESRD

Caused by hemodynamic alterations in renal microcirculations and structural changes in glomerulus

148
Q

Screening for diabetic nephropathy

A

Assess UACR and eGFR annually

Twice annually if UACR >30 and/or eGFR <60

149
Q

Treatment for diabetic kidney disease

A

Glycemic and BP control
ACE/ARB not recommended for primary prevention
ACE/ARB recommended for UACR >30
Non-dialysis pts protein intake should be 0.8g/kg/day

150
Q

Diabetic neuropathy

A

Distal symmetric polyneuropathy (DSPN)

other autonomic neuropathies

151
Q

DSPN

A

Symptoms vary
small fibers- pain, burning, tingling
large fibers- numbness and loss of protective sensation
Screen annually

152
Q

DSPN treatment

A

Pregabalin, duloxetine, gabapentin all 1st line

153
Q

Diabetic foot care

A

Annual food exam
therapeutic footwear
screen for PAD
Do Ankle-brachial index testing

154
Q

Ankle-brachial index testing (ABI)

A 
Normal: 0.9-1.30
Mild obstruction- 0.7-0.9
Moderate obstruction- 0.40-0.69
Severe obstruction- <0.40
Poorly compressible >1.3
155
Q

Peripheral artery disease

A

Needs to be on antiplatelet therapy (clopidogrel or aspirin)

Preventative foot care

156
Q

Autonomic neuropathies

A

Cardiovascular autonomic neuropathy- resting tachycardia (>100bpm)
Orthostatic hypotension

GI- constipation, gastroparesis

GU- erectile and bladder dysfunction

157
Q

Gastroparesis

A

Food stays in a diabetic pts stomach longer
Tx- small meals, low-fat, low-fiber, 4-5 times per day
Prokinetic agents- metoclopramide and erythromycin

158
Q

Immunizations for diabetes pts

A

Influenza
Pneumoccocal
Hep B

Therapeutics II (5 decks)

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