Drugs Affecting the Body

System: Endocrine System

Presented by: Javier, Magallanes, Oppus, Tuparan

Endocrine System
● Endocrine system regulates essential activities of the body including:

➢ Metabolism of nutrients
➢ Reproduction
➢ Growth and development
➢ Adapting to change in internal and external environments
➢ Body defenses
➢ Regulation of cellular metabolism and energy balance
Hormones
- Chemical substances secreted by the cells into the extracellular fluids that
stimulate or regulate metabolic activity of other cells in the body.
Endocrine Drugs
- Hormones are pharmacologically classified as drugs
- Can be natural (from animals), semi-synthetic or synthetic compounds
Indications:
a. Replacement therapy
b. Treatment for certain disorders
c. Diagnostic purposes
 Pituitary
● The pituitary gland is located in the skull in the bony sella
turcica under a layer of dura mater.
● It is divided into three lobes: an anterior lobe, a posterior lobe,
and an intermediate lobe.
● anterior lobe produces stimulating hormones in response to
hypothalamic stimulation.
● pituitary lobe stores ADH and oxytocin.
● Intermediate lobe produces endorphins and enkephalins to
modulate pain perception.
● Drugs that affect anterior pituitary hormones mimic or
antagonize the effects of specific pituitary hormones.
● The anterior pituitary hormone that is most commonly used
pharmacologically is growth hormone (GH).
ANTERIOR PITUITARY HORMONE
DRUGS
Growth Hormone Agonists

● Growth Hormone Agonists skeletal growth, growth of internal organs, protein

synthesis, and stimulation of processes required for normal growth.
● Disease Spotlight: GH Deficiency
● Hypopituitarism i It occurs as a result of the following: developmental abnormalities,
congenital defects of the pituitary, circulatory disturbances (e.g. hemorrhage), acute
or chronic inflammation of the pituitary, and pituitary tumors.
● Dwarfism is the GH deficiency in children which results to short stature.
● Somatotropin deficiency syndrome (SDS) is a condition in adults with
hypopituitarism caused by pituitary tumors or trauma, or may have been treated for
GH deficiency as children, resulting in a shutdown of the pituitary production of
somatotropin.
SOMATROPIN

- Somavert selectively binds to growth hormone receptors on cell surfaces,

where it blocks the binding of endogenous GH. this leads to normalization of
serum IGF-1 levels.

Therapeutic Action:

- Somatropin is used to treat growth failure in children and adults who lack
natural growth hormone. This includes people with short stature due to
Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature at
birth with no catch-up growth, and other causes.
SOMATROPIN

Indications:

● Short stature due to growth hormone deficiency

● Turner’s syndrome
● Prader Willi syndrome
● Noonan syndrome
● Homeobox containing gene
● Small for gestational age
SOMATROPIN

Contraindications:

● Hypersensitivity to drug/class/component
● Caution if hepatic impairment, elevated lfts, gh secreting tumors, diabetes
mellitus.
SOMATROPIN
Side Effects:

● pain, itching, or skin changes where the medicine was injected;

● swelling, rapid weight gain;
● muscle or joint pain;
● numbness or tingling;
● stomach pain, gas;
● headache, back pain; or
● cold or flu symptoms, stuffy nose, sneezing, sore throat, ear pain.

Available Forms: Injection

SOMATROPIN
Nursing Considerations/ Responsibilities:
● Assess bone age annually in all patients and especially those also receiving concurrent
thyroid or androgen treatment, since these drugs may precipitate early epiphyseal
closure. Urge parent to take child for bone age assessment on appointed annual dates.
● Lab test: Periodic serum and urine calcium and plasma glucose.
● Hypercalciuria, a frequent adverse effect in the first 2–3 mo of therapy, may be
symptomless; however, it may be accompanied by renal calculi, with these reportable
symptoms: flank pain and colic, GI symptoms, urinary frequency, chills, fever, hematuria.
● Test for circulating GH antibodies (anti somatropin antibodies) in patients who respond
initially but later fail to respond to therapy.
● Observe diabetics or those with family history of diabetes closely. Obtain regular urine
for glycosuria or fasting blood glucose and HbA1C.
● Examine patients with GH deficiency secondary to intracranial lesion frequently for
progression or recurrence of underlying disease.
SOMATROPIN

Teaching Point:

● Instruct patient and parents on correct procedure for reconstituting medication, site
selection, technique for subcut injection, and disposal of needles and syringes.
Review dose schedule. Parents should report persistent pain or edema at the
injection site.
● Advise parents to monitor blood glucose closely in children with diabetes mellitus.
Parents should also be advised to report persistent severe abdominal pain; may be
a symptom of pancreatitis, and signs and symptoms of hypersensitivity reactions
(rash, facial swelling, difficulty breathing) immediately to health care professional.
● Emphasize need for regular follow-up with endocrinologist to ensure appropriate
growth rate, to evaluate lab work, and to determine bone age by x-ray exam.
Growth Hormone Antagonists

● Growth Hormone antagonists are used in treating GH hypersecretion

(hyperpituitarism) caused by pituitary tumors.

Disease Spotlight: Hyperpituitarism

● GH hypersecretion is usually caused by pituitary tumors and can occur at any time of
life.
● Gigantism occurs before the epiphyseal plates of the long bones fuse and cause
acceleration in linear skeletal growth. Individuals with gigantism can reach 7 to 8 feet
in height with fairly normal body proportions.
● Acromegaly is a form of hyperpituitarism after epiphyseal closure (adults). As linear
growth is impossible, hypersecretion of GH causes enlargement in the peripheral
parts of the body such as hands and feet as well as internal organs (heart).
BROMOCRIPTINE
- Being a dopamine agonist, it stimulates dopamine receptors, inhibits anterior
pituitary prolactin secretion.

Therapeutic Action:
- Relief of rigidity and tremor in parkinsonism. Restoration of fertility in
hyperprolactinemia. Decreased growth hormone in acromegaly.

Indication:
- Hyperprolactinemic states.
BROMOCRIPTINE
Contraindications:
- Uncontrolled hypertension and sensitivity to any ergot alkaloids, uncontrolled
hypertension.
- Avoid abrupt withdrawal of the drug
Side Effects:

● Blurred vision ● feeling, seeing, or hearing things that are not there
● chest pain or discomfort ● feeling of constant movement of self or surroundings
● difficulty in speaking ● feeling that others are watching you or controlling your
● dizziness or lightheadedness, behavior
● double vision ● feeling that others can hear your thoughts
● headache
BROMOCRIPTINE
Available Forms: Tablets and Capsules

Nursing Considerations/ Responsibilities:

● Monitor vital signs closely during the first few days and periodically throughout
therapy.
● Lab tests: Periodic CBC, liver functions and renal functions with prolonged therapy.
● Monitor for and report psychotic symptoms and other adverse reactions in
Parkinson's patients because larger doses are used.
● Improvement in Parkinson's disease may be noted in 30–90 min following
administration of bromocriptine, with maximum effect in 2 h.
BROMOCRIPTINE
Teaching Point:

● Make position changes slowly and in stages, especially from lying down to
standing, and to dangle legs over bed for a few minutes before walking. Lie
down immediately if light-headedness or dizziness occurs.
● Do not drive or engage in other potentially hazardous activities until response
to drug is known.
● Avoid exposure to cold and report the onset of pallor of fingers or toes.
● Note: Patients may have temporary rebound breast enlargement and pain
following drug withdrawal.
BROMOCRIPTINE
Teaching Point:

● Advise patients being treated for amenorrhea and galactorrhea to use

barrier-type contraceptive measures until normal ovulation cycle is restored.
Oral contraceptives are contraindicated.
● Inform physician immediately, if pregnancy occurs during therapy.
Bromocriptine should be discontinued without delay.
● Do not breastfeed while taking this drug.
POSTERIOR PITUITARY HORMONE
DRUGS
Drugs Affecting Posterior Pituitary Hormones
● The posterior pituitary stores two hormones produced by the
hypothalamus (antidiuretic hormone or vasopressin [ADH] and oxytocin).
● ADH possesses antidiuretic, hemostatic, and vasopressor properties. It is
the hormone affected in diabetes insipidus, a condition characterized by
production of a large amount of dilute urine containing no glucose.
CONIVAPTAN
Therapeutic Action:
- Conivaptan is used to treat hyponatremia (low sodium levels). Conivaptan improves
urine flow without causing the body to lose too much sodium as you urinate.
Indications:
- Conivaptan is an arginine vasopressin receptor antagonist, prescribed for
hyponatremia (low blood sodium level).
Contraindications:

- Contraindicated in patients with anuria (absence of urination), severe kidney

problems who are taking CYP3A inhibitors, electrolyte disturbances, and
hypersensitivity.
Side Effects:
● Blood - Anemia.
● Heart - Abnormal heart rhythm and high/low blood pressure.
● Gastrointestinal - Constipation, diarrhea, nausea and vomiting.
● General - Swelling in the extremities, injection site reactions such as redness,
pain, inflammation, fever and thirst.
● Infections - Pneumonia and urinary tract infection.
● Metabolic - Decrease in blood minerals.
● Central Nervous system - Headache, confusion and sleeplessness.
● Respiratory - Throat pain.
● Skin - Itching.
Available Forms:
Nursing Considerations:
● Monitor neuromuscular signs of fluid and electrolyte imbalances, including low levels of
sodium (hyponatremia), potassium (hypokalemia), and magnesium (hypomagnesemia).
Signs of imbalances include headache, confusion, lethargy, irritability, weakness, muscle
cramping, and muscle hyperexcitability and tetany. Notify physician immediately if these
signs occur.
● Assess blood pressure (BP) and compare to normal values. Report changes in BP, either
a problematic decrease in BP (hypotension) or a sustained increase in BP (hypertension).
● Monitor IV injection site for pain, swelling, and irritation. Report prolonged or excessive
injection site reactions to the physician.
Teaching Point:
● Instruct patient and family/caregivers to maintain adequate fluid intake and
avoid dehydration.
● Instruct patient and family/caregivers to report other troublesome side effects
such as severe or prolonged headache, sleep loss, fever, increased urination,
or diarrhea.
Thyroid and Antithyroid Drugs

THYROID GLAND
● Produces hormones Thyroxine and Triiodothyronine which
influence growth, development and metabolism.
● Production of this hormones depends on the thyroid gland
receiving iodine from the body
● THYROXINE (T4)
● TRIIODOTHYRONINE (T3)
THYROID-STIMULATING HORMONE
The TSH released from the anterior pituitary and is stimulated when the blood
levels of T3 and T4 are low.

HYPOTHYROIDISM
A condition characterized by diminished production of the thyroid hormone.
● Primary hypothyroidism stems from an abnormality in the gland itself
● Secondary hypothyroidism begins at the level of the pituitary gland and the
result from the reduced levels of TSH
● The third type is caused by reduction in the amount of TRH of thyrotropin
releasing hormone by the hypothalamus
HYPOTHYROIDISM- ADULTS
CLINICAL MANIFESTATIONS

● Weight Gain
● Constipation
● Fatigue
● Edema
Hypothyroidism
● All newborns are tested birth for thyroid function
● If untreated it can lead to retardation due to effects on brain development.
EXAMPLE OF DRUGS

THYROID DRUG SUCH AS:

● LEVOTHYROXINE SODIUM- is the drug of choice for replacement therapy for
the treatment hypothyroidism. It increase the level of T4 and metabolically
deiodinated to T3. it is also used to treat simple goiter and chronic lymphocytic.
● LIOTHYRONINE- is a synthetic T3 with a biologic half-life 2.5 days with rapid
onset use of action (within a few hours).
THERAPEUTIC ACTION
To treat hypothyroidism, myxedema,goiter, thyroid cancer.

INDICATIONS:
LEVOTHYROXINE SODIUM- indicated as replacement therapy in primary
(thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired
hypothyroidism
LIOTHYRONINE- is indicated for use as replacement or supplemental treatment for
hypothyroidism of an etiology.
Available forms for Levothyroxine
It comes by tablet or liquid that swallow.
Contraindications:

Absolute Contraindications- Thyrotoxicosis and myocardial infarction.

Caution: adrenal insufficiency, cardiovascular disease including cardiac arrhythmias,

hypertension, and angina pectoris; diabetes, mellitus, osteoporosis;
hypopituitarism; dysphagia

Side effects: Nausea, Vomiting, anorexia, diarrhea cramps,

tremors, insomnia, weight loss.

Adverse reactions:

● Tachycardia, hypertension, palpitations, osteoporosis, and seizures; usually

due to overmedication. Other adverse reactions include urticaria, rash, and
alopecia
Available forms for
Liothyronine

Liothyronine sodium hard capsules

are qualitatively similar in
biological action to thyroxine but
the effect develops in a few hours
and lasts for 24 to 48 hours after
stopping the treatment
Therapeutic actions
Liothyronine sodium may be preferred for treating severe and acute hypothyroid
states because of its rapid and more potent effect, but thyroxine sodium is normally
the drug of choice for routine replacement therapy.

Contraindications
Hypersensitivity to any components of Liothyronine sodium hard capsules.
Patients with angina of effort or cardiovascular diseases and thyrotoxicosis.
Side Effects
● Anxiety.
● arm, back, or jaw pain.
● blurred or double vision.
● chest pain or discomfort.
● chest tightness or heaviness.

Nursing considerations/ responsibilities

● Monitor symptoms related to BMR
● Monitor heart rate, reporting tachycardia and palpitations
● Education re life long treatment of deficient hormones
HYPERTHYROIDISM
Is an increase in circulating T3 and T4 levels which usually results from an
overactive thyroid gland or excessive output of thyroid hormones from one or more
thyroid nodules.

Causes:

Graves disease

Thyroid storm caused by stress or infection

Antithyroid Drugs
Methimazole and propylthiouracil (PTU) act by inhibiting the incorporation of iodine
molecules into the amino acid tyrosine

Propylthiouracil has the added ability to inhibit the conversion of T4 to T3 in the

peripheral circulation.

PTU OR PROPYLTHIOURACIL
● Most common drug used in hyperthyroidism
● Will take about two weeks before the client will see change
Nursing Considerations- Antithyroid drugs
Determine baseline vital signs including weight changes for future comparison

Signs and Symptoms of thyroid crisis or thyroid storm

● Fever
● Tachycardia
● Heart failure
● Flush skin
● hypotension
Teaching points
General:

● Instruct patients that certain foods can interfere with the absorption of thyroid
hormones such as soy products, broccoli and cabbage, iodized salt, coffee
● Follow-up is important to monitor dosing and therapeutic effects of the drug
therapy.
Anti-diabetic Drugs
Pancreas

- Is a mixed gland

Exocrine portion

- Releases pancrealipase and chymotrypsin

Endocrine portion

- 1 million islets of Langerhan

- Have at least 4 hormonal cells.
Antidiabetic Drugs / Drugs used in Pancreas disorders
● When the pancreas no longer secrete sufficient effective insulin, the
glucose cannot enter the cells.
● Diabetes Mellitus - metabolic disorder in which glucose levels in the
blood are too high and begins to spill in the urine because the
kidney tubule cells cannot reabsorb it rapidly.
● NIDDM - Non-Insulin Dependent Diabetes Mellitus
● IDDM - Insulin Dependent Diabetes Mellitus
● Glucagon - acts on the liver to increase blood glucose levels by
stimulating the breakdown of glycogen into glucose, and amino
acids and free fatty acids.
Insulin
- Is the storage and anabolic hormone of the body.
- Principal hormone required for proper glucose use in normal metabolic
processes.

Therapeutic Actions:

❏ Facilitates transport of glucose across cell membrane

❏ It promotes glycogenesis and gluconeogenesis in the liver.
❏ It increases amino acid transport, protein synthesis, and glycogenesis in the
muscles
❏ It increases triglyceride storage in adipose tissues
Indications of Insulin
● Diabetes Mellitus Type 1
● Diabetes Mellitus Type 2 that cannot be controlled by diet, exercise and oral
hypoglycemic agents
● Ketoacidosis
● Diabetic coma

Types of Insulin

● Rapid-short insulin
● Intermediate insulin
● Long -acting insulin
Contraindications of Insulin
● No contraindications as it is a replacement hormone. However, close
monitoring is needed among pregnant and lactating women to adjust the dose
accordingly.
● Hypersensitivity to drug/class/component
● Dosage may need to be reduced in severe renal impairment

Side Effects of Insulin

● Redness, swelling, and itching at the injection site
● Changes in the feel of your skin, skin thickening (fat build-up), or a little
depression in the skin (fat breakdown)
● Weight gain
● Constipation
● Insulin overdose can result in shock and possible death
Available forms of Insulin
Nursing Considerations/Responsibilities:
● Nursing Assessment
❏ Assess for the contraindications or cautions so that appropriate monitoring and
adjustments can be completed.
❏ Perform a physical assessment to establish a baseline before beginning
therapy.
❏ Assess skin lesions; orientation and reflexes; blood pressure, pulse,
respiration, and adventitious breath sounds.
❏ Inspect skin areas that will be used for injection; note any areas that are
bruised, thickened, or scarred.
❏ Obtain blood glucose levels as ordered.
❏ Assess activity level
❏ Monitor the results of laboratory tests.
● Nursing Diagnoses and Care Planning
❏ Risk for unstable blood glucose related to ineffective dosing of antidiabetic
agents.
❏ Imbalanced nutrition
❏ Risk for infection related to glucose levels

● Nursing Implementation
❏ Monitor nutritional status
❏ Gently rotate the vial containing the agent and avoid vigorous shaking
❏ Rotate injection sites
❏ Monitor response carefully to avoid adverse effects.
● Evaluation
❏ Monitor patient response to therapy
❏ Monitor for adverse effects
❏ Evaluate patient understanding on drug therapy
❏ Monitor patient compliance to drug therapy

Teaching Points:
❏ How to administer insulin
❏ Review insulin pen administration
❏ Blood glucose monitoring
❏ Diabetes supplies
Oral Hypoglycemic Drugs Classification
● Insulin secretagogues
● Biguanides
● Alpha-glucosidase inhibitors
● Thiazolidinedione derivatives
Examples of Insulin Secretagogues
● Sulfonylureas
- Stimulate pancreatic release of insulin
- Inhibit pancreatic release of glucagons
- Increase insulin receptor binding
- Decrease hepatic extraction of insulin

Examples:

Chlorpropamide, Tolbutamide, Acetohexamide, Tolazamide (1st Generation)

Glibenclamide, Gliclazide, Glipizide, Glimepiride (2nd Generation)

Indications: Type 2 diabetes

Contraindications:

● Allergy to sulfonylureas
● Type 1 diabetes
● Pregnancy and lactation

Side Effects:

● Hypoglycemia
● GI distress ( nausea, vomiting, epigastric discomfort)
● Allergic skin reactions

Nursing Considerations:

● Assess for contraindications or cautions

● Perform a complete PA to establish baseline status begging therapy and evaluate
effectiveness.
Biguanide (Metformin)
- Acts by promoting glucose uptake into cells
- Used in precaution with renal disorders
- Reducing hepatic glucose output and enhances insulin sensitivity in hepatic and
peripheral tissues
- decreases the amount of glucose (a type of sugar) released into the
bloodstream from the liver and increases the body's use of the glucose.

Therapeutic Actions:
helps to control the amount of glucose in the blood.

Indications:
Type 2 diabetes prevention, gestational diabetes, treatment and prevention of PCOS
Contraindications:
Renal dysfunction, Hypersensitivity to metformin, impaired hepatic function,
Congestive cardiac failure needing drug treatment, and acute or chronic metabolic
acidosis. Pregnancy, lactation

Side Effects of Metformin

- Gastrointestinal including a metallic taste in the mouth, mild anorexia, nausea,
abdominal discomfort, and soft bowel or diarrhea.
Potentially Fatal: Lactic acidosis in presence of renal failure and alcoholism
Available forms of Metformin

❏ Liquid or Solution
❏ Tablet

Nursing Considerations

● Assessment: history and physical status

● Interventions:
❏ Monitor Urine or serum glucose levels
❏ Arrange for transfer to insulin therapy during periods of high stress
❏ Use IV glucose if severe hypoglycemia occurs as a result of overdose
Teaching points
● Do not discontinue this medication without consulting your healthcare
provider.
● Monitor urine or blood for glucose and ketones as prescribed.
● Swallow extended-release tablets whole; do not cut, crush, or chew.
● Do not use this drug during pregnancy; if you become pregnant, consult with
your physician for appropriate therapy.
● Avoid using alcohol while taking this drug.
● Report fever, sore throat, unusual bleeding or bruising, rash, dark urine,
light-colored stools, hypo- or hyperglycemic reactions.
Hormones of the Adrenal Cortex:
1. Adrenocorticosteroids
a. Mineralocorticoids. Electrolyte and water balance. Natural occurring is
aldosterone.
b. Glucocorticoids. Affect fat, protein, and carbohydrate metabolism and also
have an anti-inflammatory effect.

2. Adrenal Androgens
Adrenal cortex
-is the outer region and also the largest part of an adrenal gland.

-it consist of three layers:

1. zona glomerulosa (outer layer)

- Produces mineralocorticoids
2. zona fasciculata (middle layer)
- Produces glucocorticoids
3. zona reticularis (innermost layer)
- Produces adrenal androgens
Mineralocorticoids
- Possess sodium-retaining and potassium-secreting effects
- Essential for fluid and electrolyte balance
- endogenous : aldosterone desoxycorticosterone
- Synthetic: fludrocortisone

Glucocorticoids
- Endogenous: Cortisol, Cortisone, Corticosterone, Hydrocortisone
- Essential for the metabolism of carbohydrates, fats, and proteins
- They enhance response of the vascular and bronchial smooth muscles to
catecholamines
Glucocorticoids
Therapeutic uses: Allergy, Inflammation of joints and bones, skin disease, organ
transplant immunosuppression, Pulmonary Diseases - Bronchial Asthma & COPD.
Adverse Effects: Cushing’s syndrome, adrenal suppression, osteoporosis, PUD,
impaired wound healing, cataract, hyperglycemia
Addison’s Disease
- Hypersecretion of andrenocorticosteriods
- Characterized by: anorexia, dehydration, weakness and lethargy, hyper
pigmentation
Addison’s disease:
Cushing’s Syndrome
- Hypersecretion of
adrenocorticosteroids

- Characterized by: moon face,

buffalo hump, pendulous
abdomen, hypertension
Parathyroid Glands
● Two pairs of small, oval-shaped glands. They are located next to the two
thyroid gland lobes in the neck. Each gland is usually the size of a pea.
● Produces parathyroid hormones or PTH

Disorders:

● Hypoparathyroidism - decrease in PTH

● Hyperparathyroidism - increase in PTH
Hypoparathyroidism
Calcitriol - active form of Vitamin D3

Drug class: Antihypocalcemic Agents

Therapeutic actions:

● used to treat and prevent low levels of calcium and bone disease in patients whose
kidneys or parathyroid glands are not working normally.
● it is also used to treat secondary hyperparathyroidism.

Indications:

● Management of hypocalcemia in patients on chronic renal dialysis.

● Management of hypocalcemia associated with hypoparathyroidism and with
sustained systemic glucocorticoids therapy.
Contraindications:

● Allergy to any component of the drug

● Hypercalcemia or Vitamin D toxicity
● Pregnancy and lactation

Side effects: The most common side effect of calcitriol include headache,
drowsiness, as well as a dry mouth and a metallic taste.

Available forms: capsule, oral solution, and tablet

Nursing considerations:

● Make sure patient receives enough calcium.

● Store drug at room temperature and protect from heat and direct sunlight.
● In high-dose or long-term calcitriol therapy, be alert for vitamin D toxicity.

Teaching point:

● Warn patient not to take other forms of vitamin D while taking calcitriol.
● Instruct patient to take a missed dose as soon as possible.
● Advise patients to notify prescriber immediately if signs of toxicity develop.
Hyperparathyroidism
Calcitonin

Drug class: Antihypercalcemic Agents

Therapeutic actions:

● Inhibits bone resorption and lowers elevated serum calcium. It also increases the
excretion of filtered phosphate, calcium, and sodium by the kidney.

Indications:

● Used to treat Paget’s disease, postmenopausal osteoporosis, and emergency

treatment of hypercalcemia.
Contraindications:

● Allergy to any component of the drug

● Hypocalcemia
● Pregnancy and lactation
● Renal dysfunction
● Allergy to salmon or fish products
● Pernicious anemia

Side effects: headache, bronchospasm and flu-like symptoms, as well as vomiting

and diarrhea.

Available forms: nasal spray and injection

Nursing considerations:

● Perform a skin test before administering drug.

● Monitor serum calcium level
● Assess for nausea, especially with the first dose
● Check for antibody formation

Teaching point:

● Tell patient to refrigerate injection or unopened nasal spray container

● Explain how to activate the nasal pump
● Instruct patient to report nasal symptoms
Thank you for listening!