Endocrine Disorders - Part Of Pharm Exam 2

Front 1

Endocrine system

Back 1

• Responsible for homeostasis
• Involves synthesis and secretion of hormones
• Feedback mechanisms between organs

Front 2

Hormone

Back 2

•

Chemical substances secreted into the bloodstream with specific
effects at target organs
Classified as amines, peptides, or steroids - this describes the hormone STRUCTURE

Front 3

Review of Diabetes, and Insulin Physiology

Back 3

• Disorder of carbohydrate and lipid metabolism
• Due to a deficiency of insulin – absolute versus relative
• Significant clinical consequences if untreated
o Acute
o Chronic
§ Microvascular – retinopathy, nephropathy, neuropathy
§ Macrovascular – HTN, IHD, stroke, associated death

Front 4

Diabetes – Type 1

Back 4

o Insulin-dependent
o Auto-immune destruction of pancreatic β-cells
o Presentation: polyuria, polydipsia, polyphagia, weight loss
o Patients: < 30 yo, lean
o 5-10% patients

Front 5

Diabetes – Type 2

Back 5

o Non-insulin dependent
o Insulin resistance
o Increased hepatic glucose production
o Impaired insulin secretion
o Polyuria, polydipsia, fatigue, weight gain
o Patients: > 40 yo, obese
o 90-95% of patients

Front 6

Diabetes Assessment - what are the different FBG levels?

Back 6

Fasting Plasma Glucose

Normal - < 100 mg/dL or < 5.6 mmol/L
Pre-Diabetic - 100-125 mg/dL or 5.6-6.9 mmol/L
Diabetes - 126 mg/dL or 7 mmol/L

Front 7

What are the Goals of Glycemic Control?

Back 7

Index
FPG (mg/dL) - normal:< 100 Goal:90-130
Postprandial (mg/dL) - normal: < 140 Goal: < 180
Bedtime (mg/dL) - normal: < 120 Goal: 100-140
Hemoglobin A1C (%) - normal: <6
Goal: <7

Front 8

What does the pancreas make?

Back 8

insulin
glucagon
somatastatin

Front 9

What is the treatement for type 1 diabetes?

Back 9

o Healthy diet, physical activity, BG monitoring
o Insulin
o Pramlintide

Front 10

What is the treatment for type 2 diabetes?

Back 10

o Lifestyle modifications – diet, physical activity
o Adjunctive pharmacologic therapy
§ Sulfonylureas – tolbutamide, glipizide
§ Meglitinides – repaglanide, nateglinide
§ Biguanides – metformin
§ -Glucosidase inhibitors – acarbose, miglitol
§ Thiazolidinediones – pioglitazone, rosiglitazone
§ Insulin
§ Dipeptidyl peptidase-4 inhibitors – sitagliptin
§ Other – exenatide

Front 11

What tells the pancreas to secrete insulin?

Back 11

- hormones from GI after meal
- vagus nerve

Front 12

What does the insulin do?

Back 12

- helps glucose, amino acids and fatty acids get into cells
- not just glucose

Front 13

What are the drugs for diabetes?

Back 13

- insulin
- glipizide
- metformin
- repaglinide
- acarbose
- rosiglitazone
- pramlintide
- sitagliptin
- exenatide

Front 14

What is HgbA1c?

Back 14

- your hemoglobin becomes glycocerated.
- this indicates glucose control over a longer period of time than just a FBG

Front 15

What are the drugs for type 1 DM?

Back 15

Insulin
Adjunctive amylin analog

Front 16

Insulin (100 units/mL)

Back 16

Indication – DM1, DM2, acute hyperglycemia
MOA – binds to insulin receptor…
Dose – individualized to patient
Example: 0.1-1 unit/kg (DM1); 0.2-0.6 unit/kg (DM2) SC

Onset/Peak/Duration – (depends on insulin type)
Elimination – renal
Adverse effects – hypoglycemia, allergic reaction, lipodystrophy;
interactions ethanol, oral hypoglycemic agents, -blockers

Front 17

Give the different types of insulin that act over a variety of times.: - know these!!!

Back 17

Rapid – aspart (NovoLog®), lispro (Humalog®), glulisine (Apidra®)
Short – regular (Humulin® R, Novolin® R)
Intermediate – NPH (Humulin® N, Novolin® N), detemir (Levemir®)
Long – glargine (Lantus®)

Front 18

What is the duration of the different types of insulin?

Back 18

- Aspart, lispro - 4-6 hrs
- regular (6-10 hrs)
- NPH (12-20 hrs) - normal insulin
- Extended zinc insulin (18-24 hrs)
- Glargine (20-24 hrs)

Front 19

What is the difference between rapid and short acting insulin?

Back 19

- rapid - aspart - acts in 10-20 min
- Short - regular - 30 -60 min

Front 20

Does the pancreas give short or long acting insulin? A combo of the two?

Back 20

Endogenous (pancreas)
- basal 50% (.5-1 units/hour)
- parandial - 50%

Front 21

What do we base our exogenous insulin treatment on? What are we mimicking?

Back 21

Basal
- initiate at 10 unites once daily sc
Parandial
- 1 unit for 10 g CHO when eating

- we're trying to mimic what the pancreas does, with a basal level and then quick acting types when you eat

Front 22

What are the different regular human insulin mixtures?

Back 22

70% NPH / 30% Regular (Humulin® 70/30, Novolog® Mix

50% NPH / 50% Regular (Humulin® 50/50)

70/30)

Front 23

What are the different Insulin Analog Mixtures?

Back 23

–
75% NPLispro / 25% Lispro (Humalog® 75/25)
–
70% NPAspart / 30% Aspart (NovoLog® Neutral 70/30)
–
50% NPLispro / 50% Lispro (Humalog® 50/50)
–
50% NPAspart / 50% Aspart (NovoLog® Mix 50/50)

Front 24

Pramlintide (Symlin®)

Back 24

Indication – insulin-using DM1 & DM2 patients
Mechanism – analog of amylin which targets postprandial hyperglycemia - slows gastric emptying, suppresses post meal glucagon release, increases satiety (targets PP hyperglycemia)
Dose – DM1 – 15 g SC ac; DM2 – 60 g SC ac (don’t mix with insulin)
Adverse effects – nausea, hypoglycemia, caution: gastroparesis, hypoglycemia, unawareness

Front 25

what is a difference between gen 1 and gen 2 drugs for DM2?

Back 25

- second generation agents have shorter half-lives and are generally safer

Front 26

Glipizide (Glucotrol®, Glucotrol® XL)

Back 26

Indication – DM2
Mechanism – promotes pancreatic insulin release
Dose – 5 mg daily, max 10-20 mg bid (XL: 5-20 mg daily)
Duration – 12-24 h (XL: 24 h) - note: has short half life, but works a long time, b/c it isn't working in the bloodstream, it's workin at the cells in the liver and muscles
Elimination – hepatic metabolism, renal excretion
Adverse effects – hypoglycemia, weight gain; avoid in pregnancy/lactation;
interactions ethanol, β-blockers

Front 27

Repaglinide (Prandin®)

Back 27

Indication – DM2
Mechanism – promotes pancreatic insulin release
Dose – 0.5-2 mg just before meal (max 4 mg qid)
Onset/Duration – rapid acting, postprandial BG
Elimination – hepatic metabolism, biliary excretion
Adverse effects – hypoglycemia

Front 28

Metformin (Glucophage®, Glucophage® XR, Riomet®)

Back 28

Indication – DM2
Mechanism – glucose production, glucose uptake
Dose – 500 mg bid 850 mg bid-tid (XR: daily in eve)
Onset/Duration – slow abs, basal & postprandial BG
Elimination – excreted renally (unchanged)
Adverse effects – ANV; avoid in hepatic or renal
(CrS 1.4-1.5 mg/dL)
dysfunction; interactions ethanol, sulfonylureas, vitamin B12 and folic acid
- gets used a lot because hypoglycemia is NOT one of the side effects

Front 29

Acarbose (Precose®)

Back 29

Indication – DM2
Mechanism – carbohydrate absorption at GI tract
Dose – 25 mg tid, titrate q1-2mo (max 50 or 100 mg tid)
Onset/Duration – postprandial BG
Adverse effects – abdominal distension, cramps, borborygmus, and
diarrhea; hepatic dysfunction; interactions metformin, iron supplements

Front 30

Rosiglitazone (Avandia®)

Back 30

FDA restricts access - it can actually cause heart failure!!
Indication – DM2
Mechanism – reduces insulin resistance
Dose – 2 mg bid or 4 mg daily,
titrate up in 3 mo if poor response (4 mg bid)
Onset/Duration – takes weeks for full effect
Elimination – hepatic metab, renal and GI excretion
Adverse effects – fluid retention, edema, LDL-C, risk for CV events;
caution in HF; interaction insulin

Front 31

Sitagliptin (Januvia®)

Back 31

Indication – DM2 (monotherapy ± metformin/glitizone)
Mechanism – DPP-4 (dipeptidyl-peptidase-4) inhibitor
Slows the inactivation of incretin hormones?
Dose – 25-100 mg daily
Elimination – renal (dose-adjust in renal impairment)
Adverse effects – headache, nasopharyngitis, upper respiratory infection;
caution renal failure; interaction digoxin

Front 32

Exenatide (Byetta®)

Back 32

Indication – as an add-on to metformin or a sulfonylurea in DM2
Mechanism – an incretin mimetic that improves insulin secretion
Dose – 5 μg SC bid ac
Adverse effects – NVD, jitters, dizziness, hypoglycemia

Front 33

What are thy hypothyroid diseases?

Back 33

hashimoto's Dz
myxedema
cretinism

Front 34

What are the hyperthyroid diseases?

Back 34

- graves Dz
- plummers Dz
- Thyrotoxic Crisis

Front 35

What is the name for normal thyroid function?

Back 35

Euthyroid

Front 36

How do we treat hypothyroidism?

Back 36

TH replacement
Levothyroxine

Front 37

How do we treat hyperthyroidism?

Back 37

decrease TH production
Propylthiouracil
Methimazole
(Propranolol) - a beta blocker
Non-pharmacologic
•
Surgical resection
•
Radioactive iodine

Front 38

Levothyroxine (Levothroid®, Levoxyl®, Synthroid®)

Back 38

Indication – hypothyroidism
Mechanism – conversion to T3 as replacement
Dose – 50-100 g daily, titrate to target TSH
IV Dose – ~½ PO dose daily; ~4 g/kg for myxedema
Onset – starts within hours, but weeks to full effect
Elimination – t½ ~7 days
Adverse effects – thyrotoxicosis (tachycardia, angina, tremor,
nervousness, insomnia, hyperthermia, heat intolerance)
Adverse effects – interactions:
o Decrease levothyroxine absorption – aluminum-containing
antacids, calcium, cholestyramine, colestipol, iron supplements,
sucralfate
o Increase levothyroxine metabolism – carbamazepine,
phenobarbital, phenytoin, rifampin
o Levothyroxine influences other meds – inc warfarin effect,
inc catecholamine effect

Front 39

which drugs are enzyme inducers?

Back 39

- carbamazepine
- phenobarbital
- phenytoin
- rifampin

Front 40

Propylthiouracil

Back 40

Indication – hyperthyroidism
Mechanism – inhibits thyroid hormone synthesis
Dose – 100-300 mg tid initially, 50 mg tid maintenance
Onset/Duration – within 1 h…but 3-12 wks to euthyroid
Adverse effects – hypothyroidism, rash, nausea, headache, arthralgia,

parasthesias, agranulocytosis; caution in pregnancy, avoid in lactation

Front 41

Testosterone (DepoTestosterone®, Androderm®, AndroGel®, TestoPel®)

Back 41

Indication – hypogonadism, delayed puberty
Mechanism – testosterone replacement
Dose – 50-400 mg IM q2-4wk; 5 mg/d patch daily, 50-100 mg/d gel
Adverse effects – virulization, gynecomastia, edema, hepatotoxicity, LDL-
C, HDL-C, premature epiphyseal closure

Front 42

What are the indications for taking estrogens?

Back 42

Indications – menopausal hormone therapy, contraception

Front 43

Conjugated Estrogen (Premarin®, others)

Back 43

Indication – alleviation of peri-menopausal symptoms; prevention of
osteoporosis in high risk patients
Mechanism – estrogen replacement; decreases osteoclast activity via ER
Dose – 0.3-0.625 mg PO daily; 12.5 μg TD
(± progestin)
Adverse effects – headache, depression, GB disease, N, V, abd cramps,
↑ BP, TED, BTB, edema, breast tenderness, breast cancer

Front 44

what are the indications for progestins?

Back 44

Indications – menopausal hormone therapy, contraception

Front 45

What is contraception?

Back 45

prevention of conception or impregnation

Front 46

What are contraceptives?

Back 46

an agent for the prevention of conception; relating to any
measure or agent designed to prevent conception

Front 47

What are the desired contraceptive properties?

Back 47

Highly effective
o Prolonged duration of action
o Rapidly reversible
o Privacy of use
o Protection against STDs
o Easily accessible

Front 48

How do you decide who gets which contraceptive drug?

Back 48

Effectiveness (theoretical,
actual)
o Health status and habits
o Frequency of intercourse
o Importance of not being
pregnant
o Age
o Perceptions, risk, benefit
o Side effects

Front 49

What are the different methods of contraception?

Back 49

Non-hormonal
o Abstinence, withdrawal, sterilization, barrier methods
o Spermicides
Mechanism of Action – surface active agent that immobilizes sperm;
barrier to sperm (gels and foams)
Agents – nonoxynol-9 (foam, gel, suppository, film); octoxynol-9 (gel)

Hormonal
o Drug classes – estrogens, progestins
o Routes – oral, transdermal, injectable, intravaginal

Front 50

What are the product types of oral contraceptives?

Back 50

monophasic, biphasic, triphasic, progestin only

Front 51

What is monophasic oral contraception?

Back 51

Dosing – fixed continuous dose estrogen and progestin
Administration – one tablet by mouth daily
Considerations – equal efficacy compared with multiphasic products;
products with < 20 g ethinyl estradiol may cause less bloating and breast
tenderness;
Extended cycle (contains 91 tablets)
Continuous cycle

Front 52

What is biphasic oral contraception?

Back 52

Dosing – fixed dose of either estrogen or progestin, with variable (2) doses
of the other hormone at different time in cycle
Administration – one tablet by mouth daily
Considerations – no good evidence for any advantage or fewer side
effects than monophasic products

Front 53

What is triphasic oral contraception?

Back 53

Dosing – fixed constant dose of estrogen with phasic progestin doses (3)
at different time in cycle
Administration – one tablet by mouth daily
Considerations – no good evidence for any advantage or fewer side
effects than monophasic products

Front 54

What is the progestin only type of oral contraception?

Back 54

Dosing – low dose of a progestin only, no estrogenic component
Administration – take one tablet orally every day; start 1st day of menses
Considerations – the “minipill” tends to be less effective than combination
OC products with typical use; irregular menstrual cycles indicates inhibited
ovulation; nearly 40% continue to ovulate normally

Front 55

What are the disadvantages across all combination OCs?

Back 55

§ Increased risk of hepatocellular adenoma
§ Mild increased risk of thromboembolism and stroke
§ May elevate BP
§ Estrogenic and progestin side effects

Front 56

What are general considerations for oral contraceptions?

Back 56

§ No data to support lower risk of DVT with 20 g
§ All products lower free testosterone levels, but only a select few
products carry FDA-labeling for treatment of acne vulgaris
§ For best lipid profile consider norgestimate, desogestrel or low dose
norethindrone acetate, or lowest dose norethindrone or ethynodiol
diacetate; drospirenone may increase serum potassium

Front 57

What are counselling points for oral contraceptives?

Back 57

No STD protection
§ Many symptoms occur in the first cycle and improve over next 2-3
cycles (follow initial use closely for 3-6 mo)
§ Take the first tablet on the first Sunday after beginning
menstruation (or alternatively on first day of menses)
§ Start new pack immediately (28-day), or in 1 wk (21-day)

Front 58

What are options for emergency contraceptions?

Back 58

Dosing
Plan B® – levonorgestrel 0.75 mg (2 tabs)
§ Administration
Plan B® – take 1 tab ASAP, follow by 2nd tab 12 h later
§ Considerations
Efficacy (Plan B® – 89%)
Nausea, vomiting; doesn’t disrupt an established pregnancy

Front 59

What are the different rountes of contraceptive meds?

Back 59

oral, transdermal, injectable, intravaginal

Front 60

Transdermal Contraceptives

Back 60

Dosing – patch delivers ethinyl estradiol 20 μg/d, and norelgestromin 0.15
mg/d (Ortho Evra®)
Admin – apply 1 patch weekly (low abd, buttocks, upper arm, torso)
Use for 3 weeks, followed by a patch-free week before resuming the patch
Considerations – less effective in patients > 90 kg

Front 61

What happens if you miss taking a pill?

Back 61

§ Use an additional form of contraception first cycle, or if miss more than one tab in a cycle, or if experience severe vomiting or diarrhea lasting for more than one day
§ If 2 pills missed in weeks 1-2, use additional contraception for remainder of the cycle
§ If 2 pills missed in week 3, continue 1 pill daily until the next Sunday, throw out remainder of the pack, and begin a new pack that day, use additional contraception for duration of old pack and first week of new pack
§ If 3 or more pills are missed, continue 1 pill daily until the next Sunday, throw out remainder of the pack, and begin a new pack that day, use additional contraception for duration of old pack and first week of new pack