20100225-kbk-controlsystem-drugs affecting endocrine functions.ppt

8/10/2019 20100225-kbk-controlsystem-Drugs affecting Endocrine Functions.ppt

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Drugs affectingEndocrine Functions

Dep. Farmakologi dan Terapeutik,

Fakultas Kedokteran

Universitas Sumatera Utara

Februari 2010, KBK, FK USU, Medan


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Endocrine System

Endocrine system includes the pituitary,thyroid, parathyroids, pancreas, adrenals, andreproductive organs

Endocrine system secretes hormones directlyinto the bloodstream to function in growth,development, and maintenance of bodyfunctions

Abnormal production of hormones can belife-threatening


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Pituitary Dysfunction

Pituitary can malfunction due to injury,

surgery, tumors, or damage from radiation

Undersecretion or oversecretion

Hypofunction: Hypopituitarism What will occur when there is a complete absence

of pituitary function?

Anterior pituitary hyperfunction most commonly involves ACTH or GH Posterior pituitary hypofunction

Most commonly deficient secretion of ADH


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Drugs Affecting the Pituitary Gland

Anterior Pituitary Gland

1. Conditions treated are those of abnormal

growth, specifically:

* Dwarfism

* Acromegaly

* Gigantism


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Posterior Pituitary Drugs

Two posterior hormones are oxytocin and

antidiuretic hormone (ADH).

Antidiuretic analogues are used to treat diabetes insipidus, nocturnal

enuresis (bedwetting).

can cause vasoconstriction and increased BP.

Other names: Vasopressin (pitressin), desmopressin (stimate),

lypressin (diapid)


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Syndrome of Inappropriate ADH

Secretion

Excess secretion of ADH even with subnormal

serum osmolality

Can not excrete a dilute urine

Retain fluids and develop dilutional hyponatremia

Usually nonendocrine cause

Typical interventions: treat underlying cause and

restrict fluids

May use diuretics (furosemide) is severe Na


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Drugs Affecting the Parathyroid &

Thyroid Glands Parathyroid glands regulate calcium levels.

Hyperparathyroidism, results from a tumor and

treatment is surgical removal of all or part of theglands.

Thyroid gland produces thyroid hormones.

Play a role in regulating growth, maturation,and metabolism. Hyperthyroidism

Hypothyroidism


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Parathyroid Glands

Secrete parathormone in response to lowered serumcalcium levels

Symptoms of parathormone deficiency can includeincreased muscular irritability and psychiatric

disorders Manifestations: Tetany

Latent: numbness, tingling, cramps in extremities, stiff hands and feet

Overt: bronchospasm, laryngeal spasm, carpopedal spasm, dysphagia,seizures, photophobia, cardiac dysrhythmias

Dx: Positive Chvosteksand Trousseaus sign Acute hypoparathyroidismIV parathormone

Chronicdiet high in calcium and low in phosphorus

Oral Ca gluconate, aluminum carbonate, vitamin D


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Acute Hypercalcemic Crisis

Extreme serum calcium elevation

Increased serum calcium levels can be lifethreatening

> 15 mg/dL neurologic, cardiovascular, andrenal symptoms that can be life threatening

Treatment: Rehydration

Diuretics Phosphate treatment

Emergency treatment to lower calcium


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Thyroid Dysfunction


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Hypothyroidism

Treatment is aimed at thyroid hormone

replacement.

Prototype drug: levothyroxine (Synthroid)

No significant side effects in therapeutic

doses.

Overdose could lead to thyrotoxicosis or

thyroid storm.


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Goiter

Not common in developed countries.

AKA Hashimotos disease

Chronic autoimmune disease Treatment is aimed at supplementing the

inadequate iodine.


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Hyperthyroidism

Typically a result of tumors

Most common cause is Graves Disease

Treatment is typically surgical removal of allor part of the gland.

Radioactive iodine may be given

Propylthiouracil(PTU), may be given alone orin conjunction with radiation


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Antithyroid Hormones

Inhibits the synthesis of thyroid hormones by

decreasing iodine use; does not inactivate or

inhibit T3 or T4

Commonly used to treat hyperthyroidism

May increase the effect of anticoagulants


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Drugs Affecting the Adrenal Cortex

Adrenal cortex secretes 3 classes of hormones:

1. Glucocorticoids

2. Mineralocorticoids3. Androgens

Two diseases associated with the adrenal cortex:1. Cushings Disease

2. Addisons disease


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Cushings Disease

Treatment is typically surgical.

Pharmacologic intervention with a

antihypertensives:1. Spironolactone (Aldactone)

2. ACE inhibitorsCaptopril (Capoten)


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Drugs Affecting the Pancreas

Insulin Preparations

Three Sources:

1. Beef

2. Pork

3. Human

Differprimarily in their onsetand duration

of action and incidence of allergic reaction.

Preparations may be short acting,intermediate acting or long acting.


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Oral Hypoglycemic Agents

Used to stimulate insulin secretion from

the pancreas is patients with NIDDM.

Four Pharmacologic classes:1. Sulfonylureas

2. Biguanides

3. Alpha-glucosidase inhibitors

4. Thiazolidinediones


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Hyperglycemic Agents

Two agents:

1. Glucagon

2. Diazoxide (proglycem) Increase blood glucose levels.


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Glucagon

Given IM when IV live is unobtainable

Converts glycogen stores into glucose

Side effects: N/V, allergic reactions (rare)


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Diazoxide

Inhibits insulin release

Typically used for patient with

hyperinsulin secretion from pancreatictumors

Not indicated for treating diabetes-

induced hypoglycemia


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D50 (Dextrose 50%)

Sugar solution given intravenouslyfor acutehypoglycemia.

Primary side effect is local tissue necrosis if infiltrationoccurs

Action Rapidly increases serum glucose levels

Provides short-term osmotic diuresis

Indication Coma of unknown origin

Hypoglycemia

Status Epilepticus


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DEXTROSE 50%

Contraindications Intracranial hemorrhage

Delirium tremens

Use with caution in acute alcoholism - ineffective without

thiamine; may make thiamine deficiency more severe

Severe pain (paradoxical excitement may occur)

Know or suspected CVA unless hypoglycemia is

documented

Adverse reaction Extravasation leads to tissue necrosis

Incompatible Reactions Sodium bicarbonate

Coumadin


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GLUCOSE

Actions

A quickly absorbed form of glucose to increase

blood glucose levels

Indications Hypoglycemia

Conscious patients

Contraindications

Decreased level of consciousness Nausea/vomiting

Precautions

Assure that the airway is patent


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Glucagon

Insulin antagonist used in the management ofsevere hypoglycemia Increases blood glucose levels by increasing the

breakdown of glycogen to glucose and inhibitsglycogen synthesis

Mechanism of Action: binds on Glucagon receptors(GPCR type) on

hepatocytes increased cAMP PK A glycogen phosphorylase release of glucose from

glycogen Metabolic effects:

catabolic hormone - increased glycogenolysis andgluconeogenesis result in increased plasma glucose

levels


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GLUCAGON

Actions Protein secreted by the alpha cells of the pancreas (islets

of Langerhans)

Causes a breakdown of stored glycogen to glucose

(glycogenesis); increases circulating blood glucose Unknown mechanism of stabilizing cardiac rhythm in beta-blocker overdose

Positive inotropic and chronotropic

Decreases GI motility and secretions, pancreatic

secretions, and blood pressure Incompatible/Reactions

Incompatible in solution with most other substances


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GLUCAGON

Indications Hypoglycemia

Beta-blocker overdose

Contraindications

Hyperglycemia Known hypersensitivity

Adverse Reactions Hypersensitivity (protein-based drug)

Nausea/vomiting Precautions

Caution with administration to patients with a history ofcardiovascular or renal disease


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Proglycem

Hyperglycemic agent that may be used in the

treatment of hypoglycemia associated with

hyperinsulinism or other causes

Inhibits pancreatic-insulin release


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THIAMINE

Actions Required for carbohydrate metabolism

Deficiency leads to anemia, polyneuritis,

Wernickes encephalopathy, cardiomyopathy

Administration may reverse symptoms ofdeficiency, but effects are dependent upon

duration of illness and severity of disease

Indications

Coma of unknown origin, especially if alcohol may

be involved

Delirium tremens

Other thiamine deficiency syndromes


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THIAMINE

Contraindications Known hypersensitivity

Adverse Reactions Rare

Incompatible/Reactions Alkaline solutions

Barbiturates

Bicarbonate Cephalosporins

Other antibiotics


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INSULINActions Protein secreted by beta cells of the Islets of

Langerhans Responsible for promoting the uptake of glucose by

the cells (muscle, cardiac, CNS, and all other tissue)

Necessary for carbohydrate, fat and proteinmetabolism

Converts glycogen to fat Allows glucose storage in the liver

Promotes fat and protein synthesis whileantagonizing fat breakdown Produces intracellular shift of potassium and

magnesium to reduce elevated serum levels of thoseelectrolytes


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INSULIN

Indications Rarely used in the field - blood glucose levels are necessary

before administering in an emergency situation

In-hospital use: diabetic ketoacidosis or other

hyperglycemic state Hyperkalemia

Contraindications / Adverse Reactions Hypoglycemia

Hypokalemia Incompatible/Reactions

Incompatible in solution with all other drugs

Antagonizes actions of epinephrine, steroids, estrogens,

thyroid hormones, diazoxide, dilantin


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Insulin receptors

Insulin receptors are cell surface

receptors with protein kinase activity

They are responsible for bothphysiological and pharmacological

action of insulin and its analogues


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INSULIN

Notes Usually refrigerated

Oral hypoglycemics, such as Orinase,

Diabinese and Dymelor, are not substitutesfor insulin, they stimulate the release of

insulin from a sluggish pancreas


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Adrenal Gland Dysfunction:

Pheochromocytoma

Tumor of the adrenal gland

Usually benign

Peak incidence between 40 and 50

Symptoms triad: headache, diaphoresis andpalpitations

Hypertension and cardiac disturbances common

Acute, unpredictible onset with gradual resolution ofsymptoms


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Adrenal Insufficiency

Adrenal cortex function

is inadequate to meet

the needs for cortical

hormones Primary: Addisons

Secondary

What is the most

common cause of Acute

Adrenal Insufficiency?


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Adrenal Crisis


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Adrenal Crisis

Medical Management

Immediate

Reverse shock

Restore blood circulation

Antibiotics if infection

Identify cause Supplement glucocorticoids during

stressful procedures or significant illness


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Cushings Syndrome

Excessive adrenocortical

activity

Most often due to

corticosteroid use Overnight

dexamethasone

suppression test

Indicators: Na+

glucose K+


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Cushings Syndrome

Medical Management

Pituitary tumor

Surgical removal

radiation

Adrenalectomy

Adrenal enzyme inhibitors

Metyrapone, glutethimide, ketoconzole

attempt to reduce or taper corticosteroid

dose


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Primary Aldosteronism

Profound K+ and H+

ions, pH and HCO3

Near normal or Na

Universal sign: HTN Dx:

Measurement of aldosterone

excretion rate after salt

loading Renin-aldosterone

stimulation test and bilateral

adrenal venous sampling

Symptoms:

Muscle weakness

Cramping

Fatigue Nonacid urine

Polyuria

serum osmolality

Polydypsia

Arterial HTN


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Primary Aldosteroninsm

Medical Management

Surgical removal

Spironalactone for persisitent HTN

Monitor for fluctuations in adrenal hormones

Corticosteroids, fluids, agents to maintain BP and

prevent complications

Maintain normal serum glucose


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Common endocrine complications

type 2 (NIDDM) diabetes,

hypertension,

dyslipidaemia, and cardiovascular diseases including AMI, AP,

PVD & stroke.

Why are these now considered

complications of endocrine disorders?

b l d f


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Metabolic dysfunction

drug-induced hyperprolactinemia

20100225-kbk-controlsystem-drugs affecting endocrine functions.ppt

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