4- Endocrine Pharm

Endocrine pharmacology general function

• Replacement

• Increase hormonal effect

• Treat excessive endocrine function

• Regulate/manipulate normal endocrine function

4

What are the 4 types of insulin?

- rapid acting

- regular

- intermediate-acting

- long acting

Regular insulin

- Synthetic or pork

- Absorption slower than endogenous insulin released from the pancreatic beta cells

Rapid acting insulin

- Biosynthetic insulin that is slightly different than human insulin to allow rapid absorption

Intermediate-acting insulin

- Absorbed slower and have a prolonged effect

- Created by adding other agents to insulin

Long-acting insulin

Absorbed slower and has a prolonged effect

• Used when less stringent control of blood sugar is needed such as person controlling condition with diet & weight control

• May be used if person has problems with hypoglycemia overnight

Biosynthetic

A combination of insulin is used to

provide optimal control of blood sugar

Intensive insulin therapy goal

maintain blood glucose in the normal physiologic range

• Frequent monitoring of blood glucose level and self-administration of insulin

• Decreases long-term complications due to “tighter control”

Insulin therapy ADR

Immunologic reaction

– Allergic reaction (rash, wheezing, bronchoconstriction, etc)

– Usually associated with animal forms of insulin

Hypoglycemia

• Dose greater than patient’s needs

• Missed or delayed meal

• Exercise – accelerates the movement of glucose out of bloodstream into skeletal muscle

What are the initial s/s of Hypoglycemia?

- Headache

- Fatigue

- Hunger

- Tachycardia

- Sweaty/Clammy

- Pale

- Anxiety

- Confusion

What are the later s/s of Hypoglycemia?

- Loss of consciousness

- Seizures

- Death

What are the consideration of Insulin therapy?

• Insulin needs to be refrigerated

• Need sterile syringes

• Rotate sites (abdomen, upper thighs, upper arms, back, buttocks)

• Glucose monitoring

Oral antidiabetic drugs

Control blood glucose levels in type 2 DM

- increases the release of insulin from pancreatic beta cells

- increases sensitivity of peripheral tissues to insulin

What are the types of oral antidiabetic drugs?

- Sulfonylureas

- Biguanides

- Alpha-glucosidase inhibitors

- Thiazolidinediones

- Benzoic acid derivatives

Sulfonylureas MOA

- increase insulin release

- decrease hepatic glucose production

- variable efficacy and effects decrease with time

Sulfonylureas ADR

- Hypoglycemia (most common)

- GI disturbances

- Headache

Biguanides MOA

- decreases hepatic glucose production

- increase tissue sensitivity to insulin

*Metformin (Glucophage) is a

Biguanides

Biguanides ADR

- GI disturbances

- Lactic acidosis (rare, but can be fatal)

Sulfonylureas vs Metformin

• Sulfonylurea use associated with 21% increase in cardiovascular events (stroke, MI) & deaths

• Confirms use of metformin as first-line drug for treatment of diabetes

• Strengthens the evidence about the cardiovascular benefits of metformin

Alpha-Glucosidase Inhibitors MOA

Inhibit glucose absorption from the GI tract

• Inhibit enzymes that break down sugars in the GI tract which slows the entry of glucose into the bloodstream

Examples of alpha glucosidase inhibitors

- Acarbose (Precose)

- Miglitol (Glyset)

Alpha-glucosidase inhibitors ADR

- GI disturbances

Thiazolidinediones MOA

- decrease hepatic glucose production

- increase tissue sensitivity to insulin

Examples of Thiazolidinediones

- Pioglitazone (Actos)

- Rosiglitazone (Avandia)

Thiazolidinediones ADR

- Headache

- Dizziness

- Fatigue/weakness

- Back pain

- Hepatic toxicity (rare)

Benzoic acids MOA

- increase insulin release

Benzoic acids examples

- Repaglinide (Prandin)

- Nateglinide (Starlix)

Benzoic acids ADR

- Hypoglycemia

- Bronchitis

- Upper respiratory tract infections

- Joint & back pain

- GI disturbances

- Headache

Glucagon is used to manage Hypogycemia. It is used to

treat hypoglycemia associated with insulin or oral hypoglycemic agents

– Mobilizes release of glucose from liver: Sufficient glycogen needed in the liver to be effective

Glucagon ADR

nausea, vomiting, allergic reaction (skin rash, difficulty breathing)

Glucagon-like Peptide agonist (GLP-1)

hormone that is normally released from the GI tract after eating

• Stimulates insulin release from pancreas

• Decreases glucagon release, delays absorption of food, & reduces appetite

GLP-1 agonists

• Manage BS

• Lower A1C

• Weight loss

GLP-1 Agonists

• Exenatide (Byetta): Injected before morning and evening meals to prevent BS spikes

• Tirzepatide (Mounjaro): Once weekly injection

• Semaglutide

– Injection (Ozempic, Wegovy)

– Rybelsus

What are the side effects of GLP-1 agonists?

• GI symptoms: Nausea, Vomiting, Diarrhea

• Hypoglycemia

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

- Inhibits enzyme that breaks down GLP-1 to prolong effects

- Example: Sitagliptin (Januvia), Vildagliptin (Galvus)

Immunosuppressants

- Used in Type 1 DM

- Limits beta cell destruction & decreases need for exogenous insulin

Immunosuppressants ADR

severe side effects when used at high doses for long time

What are rehab considerations for pts taking drugs for DM?

• Have foods containing glucose available in case of hypoglycemia

• Can patient or other person self-administer insulin appropriately?

• Insulin absorption affected by: Physical agents (heat, cold), Massage, Exercise

• Patient education: Diet, Exercise, Signs & symptoms of low blood sugar

• Ask patient about most recent blood sugar level

A 75 y/o patient is receiving outpatient physical therapy for gait & balance impairments. They come to PT at 9 am 2x/wk. They c/o feeling shaky and have a headache. Their pulse is 100 bpm. They are sweating and pale. PMH includes a h/o DM & hypertension. Meds: Humalog 75/25, Furosemide, Atenolol.

– What are considerations when working with this patient?

– What is your next step?

– Other considerations

- what their blood sugar

- vital signs

- dehydration (furosemide may cause this)

- atenolol is a beta blocker, monitor RPE

Antithyroid agents for hyperthyroidism

inhibit synthesis of thyroid hormones

- Temporary measure

- Examples: Propylthiouracil (Propyl-Thyracil), Methimazole (Tapazole)

Antithyroid ADR

skin rash, itching agranulocytosis (↓ WBC), aplastic anemia (↓ RBC), excessive inhibition will cause symptoms resembling hypothyroidism

Beta blockers for Hyperthyroidism

Used to treat symptoms of tachycardia, palpitations, etc

Iodide for hyperthyroidism

- Large doses to cause a rapid decrease in thyroid function

- Effects diminish ≈ 2 weeks of use

- May be used prior to thyroidectomy

- ADR: severe hypersensitivity (allergic) response

Radioactive iodine for hyperthyroidism

- Radioactive isotope selectively destroys thyroid tissue (follicle)

- Grave's Disease

- Ablates thyroid gland & need to have thyroid replacement therapy

Hormone replacement therapy for hypothyroidism

- Debate about whether to replace T4 only or both T3 & T4

- Used after thyroidectomy, pharmacologic ablation, treatment of goiter, other hypothyroidism

What are rehab considerations of thanking thyroid disorders

- monitor pt for s/s related to dosing

- differentiate between disease process and ADR

- watch for treatment interactions

- vital signs

hyperparathyroidism is usually managed with:

surgical resection

• Alternative pharmacological management of hypercalcemia: Biphophonates, Calcitonin

Pharm management for Hypoparathyroidism

Calcium supplements: used to ensure adequate calcium is present for physiologic processes and encourage bone formation

Signs of hypercalcemia

- Constipation

- Drowsiness

- Fatigue

- Headache

- Confusion

- Irritability

- Cardiac arrhythmias

- Hypertension

- Nausea & vomiting

- Skin rash

- Pain in bones & muscle

Vitamin D for hypoparathyroidism

Fat-soluble vitamin

Used to ↑ blood calcium & phosphate levels to enhance bone mineralization

• ↓ renal excretion of calcium & phosphate

• ↑ intestinal absorption of calcium & phosphate

Signs of vitamin D toxicity

- Headache

- Increased thirst

- Decreased appetite

- Metallic taste

- Fatigue

- GI disturbances (nausea, vomiting, constipation, diarrhea)

- Hypercalcemia

- Hypertension

- Cardiac arrhythmias

- Renal failure

- Mood changes

- Seizures

- Death due to cardiac & renal complications

What are rehab considerations for pts taking drugs for parathyroid disorders

• Monitor patient for signs & symptoms related to toxicity

• Weight bearing activities to stimulate bone formation

• Avoid stress to bones that may be weak

• UV light promotes endogenous Vitamin D synthesis & bone formation

Male and female hormone

*see pic

Androgens

Testosterone replacement: small doses to counteract effects of aging in men

Anabolic steroids

- Used to ↑ muscle size & strength

- Use several anabolic steroids together: Known as "stacking"

ADR associated with high doses of anabolic steroids

• Liver damage

• Cardiovascular disease

• Affect bone metabolism

- Accelerate closure of epiphyseal plates leading to impaired skeletal growth in children

- Avascular necrosis of femoral heads

• Aggression & severe mood swings

• Testicular atrophy & impaired sperm production

There are no problems if anabolic steroids taken at physiologic doses. T/F?

True

Hormonal contraceptives

Estrogen replacement therapy

Hormone therapy for persons with gender dysphoria

Rehab considerations for pts taking drugs male and female hormones

25 y/o patient is receiving outpatient PT for a whiplash injury during a motor vehicle accident. They smoke ½ pack per day & drink 3-4x/mo. Meds: Flexeril (muscle relaxant), oral contraceptive with Estrogen & Progesterone, Acetaminophen as needed.

- Today, the patient reports an increase in headaches. Additional questions reveal c/o a dull ache & tightness in the right calf. What are your concerns & why?

- How do you proceed?

- possible DVT: smoking and estrogen contraceptive

- refer, wells criteria to pass along to PCP