Steroids

Steroids do not have a mechanism for _____

Pain management

• no analgesic properties

Steroids inhibits ______ pathways

• clyclooxygenase

• Lipoxygenase

Steroids have better ______ effects than NSAIDs

Anti-inflammatory

2 types of Steroids

1. Sex steroids

2. Corticosteroids

Types of Steroids - Sex steroids

1. Estrogen

2. Progesterone

3. Androgen (testosterone)

• for sexual characteristics

• Reproductive functions

Types of steroids - Corticosteroids

1. Mineralocorticoids

2. Glucocorticoids

• fluids and electrolytes

• Metabolism

• Immune function

Sex steroids - estrogen + progesterone

Responsible for enlargement of breasts/hips, menstruation, ovulation (production of egg cells)

Sex steroids - Androgen

• Responsible for the voice of males, bigger body mass, and bones, more hair growth, production of sperm cells

Corticosteroids - Mineralocorticoids

Fluids and electrolytes (sodium - potassium exchange in urine, electrolytes in the plasma and in the cell, amount of urine output)

Corticosteroids - Glucocorticoids

For metabolism and immune function

HPA Axis

Starts with the hypothalamus→ releases the corticotropin releasing hormone (CRH)→ stimulates the anterior pituitary gland→ releases adrenocorticotropic hormone (ACTH)→ stimulates the adrenal cortex lodged above the kidneys → releases cortisol

Controls and provides a list every year on the banned substances in sports

World Anti-Doping Administration

Cortisol

• Naturally occurring in our body; controls our immune processes

• If present in excessive amounts → sends negative feedback to stop the hypothalamus from releasing CRH and the anterior pituitary gland from releasing ACTH → decreased amount of cortisol

Cortisol: Immunosuppression

• Decreased lymphocytes, eosinophils, monocytes, basophils

  • The immune response is suppressed

• Increased RBC, neutrophils, platelets

AAS - Androgenic

• enhance sexual characteristics

AAS - Anabolic

Increases muscle mass

AAS - Ergogenic

enhances sports performance

Evidence: AAS

• Increase in muscle mass

  • Hypertrophy (increase in bulk)

  • Hyperplasia (increase in # of muscle cells)

• Increase in strength

  • Enhanced calcium release from SR and/or increased calcium sensitivity of the contractile proteins

• Anti catabolic effects

  • No breakdown is happening in the muscles

• Endpoints (size and strength) are enhanced by training

  • Not allowed to take steroids without training

Examples of AAS

Which athletes use AAS?

• contact sports

• Body builders

Adverse Effects - Cardiovascular

• increased LDL

• Decreases HDL

• Hypertension

• Elevated triglycerides

• Atherosclerotic heart disease

1. Adverse Effects - Male reproductive

• testicular atrophy

• Gynecomastia

• Impaired spermatogenesis

• Altered libido

• Male pattern baldness

Adverse Effects - Reproductive Female

• menstrual dysfunction

• Altered

• Clitoral enlargement

• Deepening of the voice

• Male pattern baldness

Adverse Effects - Hepatic

• elevated liver enzymes

• Jaundice

• Hepatic tumors

• Peliosis hepatis

Adverse Effects - Endocrine

• altered glucose tolerance

• Decreased FSH, LH

• Acne

Adverse Effect - MSK

• premature epiphyseal closure

• Tendon degeneration

Adverse Effects - CNS

• mood swings

• Violent behavior

• Depression

• Psychosis

Irreversible Adverse effects of AAS

• atherosclerotic heart disease

• Male pattern baldness

• Clitoral enlargement

• Deepening of voice

• Hepatic tumors

• Peliosis hepatis

• Premature epiphyseal closure

• Tendon degeneration (??)

AAS - Is gynecomastia reversible?

Possible

• Direct Measures of AAS

• Gas chromatography - mass spectrometry

• Liquid chromatography - mass spectrometry

• Metabolites may be present up to 30 days depending on agent, dose, route

Why are steroids prohibited in sporting events

• Competitive advancement, inc performance - cheating

• Tested by blood or urine

• Adverse health effects

  • In the long run, heart attack can happen

• If found positive = strip of medals, suspended (depends on federation)

• Therapeutic-use exemptions

  • E.g. asthma

  • Even if tested positive = exempted, no sanctions will be given

Cortisol physiologic effects - list

1. Increase in blood glucose / increase in liver glycogen

2. Anti-inflammatory

3. Immunosuppression

4. Enhances sodium and water reabsorption

5. Behavioral and mood changes

1. Cortisol - Increase in Blood Glucose / Liver Glycogen

Increase in Liver

• Protein synthesis

• Glycogen synthesis

• Glycogen storage

• Gluconeogenesis

• Makes sure that you have enough blood sugar in the system

Other tissues

• Increase in uptake and utilization of glucose

• Increased Lipolysis

• Increased Proteolysis

• Increased fat deposition in abdominal adipose tissue

Cortisol - Anti-inflammatory

• Inhibits eicosanoids biosynthesis

• Inhibits chemotaxins

• Stabilizes lysosomes

  • Cells responsible for the immune/inflammatory response

  • Allows lesser cells to attack the area of inflammation

• Vasoconstriction

  • Vasodilation: ↑ blood/cells in the area = ↑ swelling, redness, warmth

  • Vasoconstriction = limiting inflammatory response

• Inhibits both the cyclooxygenase and lipoxygenase pathways

  • Leukotrienes are also inhibited

  • Steroids have better anti-inflammatory properties because they inhibit both pathways

  • NSAIDs only target the cyclooxygenase pathway

Cortisol - Immunisuppression

• Decreased lymphocytes, eosinophils, monocytes, basophils

• The immune response is suppressed

• Increased RBC, neutrophils, platelets

Routes - List

1. Topical

2. Inhalational

3. Oral

4. IV

5. Injection

6. Epidural

Routes - Topical

• Simple mosquito bites, psoriasis, skin allergies, eczema, etc.

• Eye drops for conjunctivitis

  • Too much inflammation, too much redness

Routes - Inhalational

Inhaled steroids are given if bronchodilators aren’t effective in addressing the bronchoconstriction for wheezing

Routes - Oral

• E.g. prednisone, dexamethasone, and methylprednisolone

  • Some steroids prescribed to patients

• Any anti-inflammatory management

  • Severe OA

  • Chronic diseases not responsive to topical (e.g. eczema and psoriasis)

  • Cancer (as part of the chemotherapeutic management)

• If topical is not working, you can shift to oral.

Routes - IV

• If pt cannot tolerate oral routes or refused to drink and the patient needs to be admitted to the hospital

• E.g. methylprednisolone, dexamethasone

  • Can also be given IM

  • IV is preferred for less incidence

Routes - Injection

• Inject steroids in joints

  • Shoulder inflammation (e.g. adhesive capsulitis, rotator cuff syndrome)

  • Knees (e.g. torn ligaments, chronic/severe OA)

• Can use US to identify structure

Routes - Epidural

• E.g. for chronic low back pain

• Done under x-ray, image intensifier

  • See exact level of the vertebra

Adverse Effects - Cushing’s Syndrome

• Centripetal/Truncal Obesity- fat deposition is on the trunk/abdomen

• Moon facie (cheek/face enlargement)

• Buffalo hump (fat on the back)

• Hyperglycemia (↑ blood sugar)

• Hypertension (↑ blood pressure)

• Cardiac hypertrophy (heart enlargement)

• Adrenal: hyperplasia and tumor formation

• Muscle wasting (weakness and thin extremities)

• Thinning of scalp hair

• Increased facial hair

• Osteoporosis

• Striae of the skin- skin becomes stretched out forming striae

• Acne

Adrenocortical Suppression is caused by?

• Prolonged steroid use leading to the hypothalamus and pituitary gland to stop secreting.

• If there are high levels of cortisol in the blood → signals the hypothalamus and pituitary gland to stop secreting

Adrenocortical Suppression - Effects

• Anorexia (loss of appetite)

• Nausea/vomiting

  • Nausea - feel of vomiting

  • Vomiting - the actual expulsion of gastric contents

• Weight loss (d/t muscle loss)

• Lethargy (inactive, feeling lazy and sleepy)

• Headache

• Fever

• Muscle and joint pains

• Postural hypotension (when assuming the upright position from supine, they are not able to tolerate changes in position

If patient already benefited from steroids →

• gradually decrease the dose (do not abruptly stop the treatment)

• E.g. 50 mg 2x/day → 50 mg q morning for 2 wks → 25 mg q other day for 2 wks

• Allows the hypothalamic-pituitary axis to recover

• Takes a while to recover

Adverse Effects of Chronic Steroid use - Catabolism

• Muscle wasting

• Muscle weakness

• Osteoporosis

• Vertebral compression fractures (common)

Adverse Effects of Corticosteroids - Ulcers

• Peptic ulcers (irritant to the gastric mucosa)

  • Give antacids and proton pump inhibitors along with steroids to prevent gastric irritation or peptic ulcers

  • Proton pump inhibitors will aid in preventing the secretion of excessive gastric juices

Adverse Effects of Corticosteroids - Infections

• Increased susceptibility to infections

  • Ex: when you see cancer pts, they are wearing masks because they are immunosuppressed

  • Reverse isolation

Adverse Effects of Corticosteroids - Growth

• Growth retardation especially in children who were given steroids before their growth spurt.

  • Premature closure of long bones (epiphysis)→ inhibits ideal height

Adverse Effects of Corticosteroids - Eyes

• Glaucoma, cataracts

  • Increased pressure in the eye that can lead to blindness

Adverse Effects of Corticosteroids - Mood

• Nervousness, mood swings, psychosis (behavioral changes)

  • Nervous, jittery, irritable

  • Mood swings - happy and the next moment, they are sad; part of the imbalance of hormones

Adverse Effects of Corticosteroids - Psychosis

• Psychosis - extreme; have both delusions, and hallucinations

  • Delusions of grandeur - you feel as though you are the best

  • Delusion of persecution - worse behavioral effect of steroids; nobody likes you

Steroid Preparations - Biologic Half-Life

• Different from elimination half-life

• Certain amount of steroids is still left after stopping the medication, exerting its biological effect

• Focused on how long the half-life will still be

Steroid Preparations - Short Acting

• Biologic half-life = 8-12 hrs

• Cortisol (Cortef, Hydrocortone)

• Cortisone (Cortone)

• Not on how fast they are eliminated but on how long the half-life will still be

Steroid Preparations - Intermediate Acting

• Biologic half-life = 12-36 hrs

• Prednisone (Prednisone, Decortisyl)

• Prednisolone (Histacort)

• 6-Methyprednisolone (Solumedrol)

• Triamcinolone (Kenacort, Ledercort)

Steroid Preparations - Long Acting

• Biologic half-life = 36-72 hrs

• Paramethasone (Haldrone)

• Betamethasone (Celestamine, Betnovate)

• Dexamethasone (Oradexone, Decilone, Maxitrol)

Neuropathic pain

Neuropathic pain - pathologic type of pain where there is damage to the spinal cord, nerve roots, peripheral nerves, sensory pathways, nociceptive pathways

Adjuncts for Neuropathic pain - Tricyclic Antidepressants

Amitriptyline

• Increases descending inhibitory signals in the spinal cord

• The DHC has descending signals that can regulate the release of nociceptive impulses → where the action of these antidepressants happen

• (Amitriptyline + Chlordiazepoxide) Limbitrol

  • Anticholinergic side effects

    • Tachycardia

    • Drying of the secretion

Tricyclic Antidepressants - Anti-cholinergic side effects

• Drowsiness

• Dry mouth

  • E.g. pt asks to drink again

• Blurring of vision (secondary to the pupillary vasodilation)

• Constipation

• Difficulty in urinating

• Weight gain

Adjuncts for Neuropathic pain - Anticonvulsants

• For seizures (epilepsy)

• Membrane stabilizers

  • Able to stabilize the neuronal membranes so that it prevents the transmission of nociceptive impulses.

  • Pregabalin (Lyrica)

  • Carbamazepine (Tegretol)

  • Na Valproate (Epilim)

  • Gabapentin (Neurontin)

    • Mostly prescribed nowadays

• Anticonvulsants side effects

  • Fatigue

  • Stomach upset/discomfort

  • Dizziness

  • Blurring of vision

    • May be prone to falls or accidents if you ask them to do an activity alone

  • Important to note these side effects to know when to defer physical therapy.