Exam I: Corticosteroids, Asthma and COPD Drugs Flashcards
Endocrine glands are ductless. What does this mean?
Secrete hormones directly into the bloodstream
Corticosteroids used in drugs are derived from or structurally similar to what?
Derived from or structurally similar to endogenous hormones from the adrenal cortex portion of the two adrenal glands
Corticosteroid hormone drugs are synthetic versions of what?
Synthetic versions of the endogenous steroid hormones in the body
Adrenocorticotropic Hormone (ACTH) is secreted by the?
Anterior pituitary gland
Another name for ACTH is what? Is this hormone inhibitory or stimulatory?
Corticotropin
Stimulate adrenal gland
ACTH causes what effects in the body?
Production and release of corticosteroid hormones which influence:
- Carb and electrolyte metabolism
- Sex glands associated with estrogenic and androgenic hormones
Name the two glucosteroids. They are secreted by?
Cortisol and Cortisone
Cortisone is metabolically converted to Cortisol in the body
Secreted by the adrenal glands
Name the major mineralocorticosteroid. Secreted by?
Aldosterone
Secreted by the adrenal cortex
Glucocorticosteroids effects/functions? (3)
- Regulate glucose (gluconeogenesis)
- Lipid and protein metabolism (anabolism and catabolism)
- Affect immune response and inflammation.
Mineralocorticoids effect/functions?
- Water and electrolyte metabolism and balance
- Promotes Na+ retention and K+ excretion
- Na+/K+ balance - regulates blood volume and pressure
What is the basic structure of corticosteroids? Chemical class - steroids.
4-ring structure
3 - 6-membered rings
1 - 5-membered ring
Pharmacological class of corticosteroids.
Hormone Replacement Therapy (HRT)
Anti-inflammatory and immunosuppressive effects
What is bursitis?
Indication for corticosteroid
Inflammation of fluid filled sacs that help cushion bones and tendons
What is Ankylosing spondylitis?
Indication for corticosteroid
Refers to an inflammatory skin condition
What is Rheumatoid arthritis ?
Indication for corticosteroid
Serious autoimmune and inflammatory disease of the joints
What is Reyes syndrome?
Indication for corticosteroid
Rare but serious condition that causes swelling of the brain and liver after a person acquires a viral infection
What is dermatoses?
Indication for corticosteroid
Refers to an inflammatory skin condition
ex. Contact dermatitis, Psoriasis
Corticosteroids are used when the typical anti histamines are not effective. Name three indications.
Anti-allergic effects
- Erythema multiforme - skin condition that can occur secondary to a hypersensitivity reaction to infection or drugs
- Serum Sickness - Reaction that can occur when a nonhuman protein enters the body (ex. Vaccination, monoclonal antibody).
- Allergic conjunctivitis - eye inflammation
Name 4 respiratory indications for corticosteroids.
- Asthma
- Status Asthmaticus - asthma attack
- Chronic Obstructive Pulmonary Disease (COPD) exacerbations
- Allergic Rhinitis
How are corticosteroids immunosuppressive?
Glucocorticoids inhibit cell-mediated immunologic functions, especially those dependent on lymphocytes
Delay rejection reactions in patients with organ transplants
Name 4 collagen-related indications for corticosteroids.
- Systemic Lupus Erythematosus (SLE) - autoimmune, inflammatory disease
- Rheumatic Heart Disease - inflammatory disease that affects connective tissue especially in the heart, joints, skin and brain
- Tendonitis - inflammation in tendons (tissues that connects muscle to bone)
- Polymyostitis - type of inflammatory myopathy (weakness, muscle disease)
How are corticosteroids used in neoplastic diseases?
Used primarily in advance stage cancers
- Used to reduced spinal cord compression
- Help relieve pain such as bone pain
- Increase appetite
Corticosteroids affect insulin secretion and muscle protein catabolism.
True/False
True
“OLONE” steroids are anabolic or catabolic? ex. Oxandrolone Tablets
Anabolic
Involved in the synthesis and build-up of protein
Other steroids are catabolic
Anabolic (“OLONE”) steroids are C-III drugs why?
Illicit use by athletes since they mimic the effects of testosterone
Long term adverse effects of corticosteroid therapy.
- Osteoporosis
- Muscular atrophy
- Thinning of the skin,
- Development of cataracts
- Adrenal suppression and insufficiency
Contraindications for steroid use.
Avoid use with:
- Systemic fungal infections
- Administration of live or live attenuated vaccines with immunosuppressive doses
Corticosteroid pregnancy classfication.
Category C
Should only be given if the benefits outweigh the risks
Warnings for steroid use:
- Can mask acute infections
- Exacerbate a viral infection
- Cause psychiatric disturbances like euphoria, depression etc.
True/False
True
Primary Adrenocortical Insufficiency (deficit in both adrenocorticoids) - name disease.
Addison’s Disease
Addison’s Disease symptoms
- Lethargy
- Weight Loss
- GI problems
- Hyperpigmentation
- HYPOnatremia or HYPERkalemia
- HYPOtension
How can hypotension be treated in patients with Addison’s disease?
Fludrocortisone, an aldosterone substitute to help the retention of sodium in water to increase blood pressure
Metabolic disorder caused by excess secretion of adrenocortical steroids - name the disease.
Cushing’s Syndrome
Cushing’s Syndrome symptoms.
- Hypertension
- Weight gain
- “Moon Face” – recall that fat deposits in neck, back and shoulder areas
- Hirsutism – unwanted hair growth
- Hyperglycemia
- Osteoporosis
- Thinning of the skin
Cushing’s disease vs syndrome
Disease - specific type of Cushing’s syndrome that occurs when a pituitary tumor causes the body to make too much cortisol
FDA approved drugs for Cushing’s disease.
- Pasireotide diaspartate (Signifor®) - SubQ for Cushing’s disease
- Osilodrostat (Isturisa®) - po, Cushing’s disease cannot get surgery or unsuccessful surgery
- Mifepristone (Korlym®) - control hyperglycemia in patients with Type II diabetes + Cushing’s syndrome
Corticosteroids have a narrow therapeutic index.
True/False
False
Most problems are associated with long-term use, not the initial or individual maintenance doses
Why is tapering of steroids necessary?
Never discontinue corticosteroid therapy abruptly after long-term therapy
Tapering-down is necessary because abrupt withdrawal → Addison’s syndrome (adrenocorticoid deficit)
Categorize corticosteroids by short-acting, intermediate-acting and long-acting.
Short-acting - Cortisone, hydrocortisone
Intermediate-acting - Prednisone/prednisolone, triamcinolone, methylprednisolone
Long-acting - Dexamethasone, betamethasone
Half life increments for short-acting, intermediate-acting, and long-acting corticosteroids.
Short-acting – 8-12 hour half life
Intermediate-acting – 12 – 36 hour half life
Long acting – 36-54 hour half life
Name oral corticosteroids. (8)
- Cortisone
- Betamethasone,
- Hydrocortisone
- Prednisone
- Prednisolone
- Methylprednisolone
- Dexamethasone
- Triamcinolone
Only soluble versions of drugs can be given IV - how can you determine if a drug is soluble by its name?
Sodium within the name
ex. Hydrocortisone Sodium Phosphate
Hydrocortisone Sodium Succinate
What is an epidural? (3)
- Injection into the spaces surrounding the spinal column (epidural spaces)
- Useful in treating back pain associated with arthritis
- Last resort treatment after a patient has undergone back surgery
Common topical uses for hydrocortisone
Pruritis (itching), burns, dermatoses
Fungal infections in conjunction with an antifungal
Eczema
Hydrocortisone Acetate can be given IV and IM.
True/False
False
Not soluble - can be given IM
Prednisone vs Prednisolone
Prednisone (prodrug) - po only
Prednisolone (active form)
Methylprednisolone Acetate vs Dexamethasone Sodium Phosphate (solubility and release effects)
Methylprednisolone Acetate (Depo-Medrol) - Not soluble, provides a repository effect (allows it to have a long acting release effect)
Dexamethasone Sodium Phosphate - Soluble, Will not provide a “depot” (repository) effect (due to it being in its soluble form)
Corticosteroid that can be given as an Intravitreal injection (into the eye).
Triamcinolone
Corticosteroid that can come as a rectal foam used in ulcerative colitis.
Budesonide
One of the strongest topical agents that is a corticosteroid.
Halobetasol Propionate
Corticosteroids with a dermal formulation. (4)
- Triamcinolone
- Beclomethasone
- Fluticasone
- Mometasone
Fludrocortisone Acetate (Florinef®) - dosage form, indication and effects
PO only - 0.1 mg tablets
Very potent mineralocorticoid
Indicated in Addison’s disease - help promote reabsorption of sodium and help provide fluid retention to control blood pressure
ADR from prolonged use of a ophthalmic corticosteroid.
Can cause glaucoma due to increased intraocular pressure
Name Common Ophthalmic and Otic corticosteroids. (6)
- Dexamethasone
- Difluprednate
- Fluocinolone acetonide
- Fluorometholone
- Loteprednol Etabonate
- Prednisolone
What is asthma?
Chronic inflammatory disease
Affects many different cells (ie. leukocytes, epithelial cells)
Partial or complete airway obstruction
Asthma is the most common chronic disease.
True/False
True
Onset of asthma in males vs females.
Males - more vulnerable pre-puberty
Females - more vulnerable post-puberty
Other differences are not dramatic
Drugs that can triggers asthma symptoms.
NSAIDs (including aspirin)
Unlike asthma, COPD is fully reversible.
True/False
False
Asthma typically goes away in adulthood
COPD is not fully reversible
What is COPD?
A chronic, progressive disease characterized by airflow limitations
What are the two major manifestations of COPD? What damage do these disorders cause?
Chronic bronchitis and pulmonary emphysema
Alveoli (the air sacs in the lung) become enlarged and damaged
This results in a reduced surface area and capacity for the exchange of CO2 and O2
COPD is usually diagnosed in its early stages.
True/False
False
Symptoms for COPD is most evident after the patient has had a severe deterioration
COPD can cause cachexia (extreme weight loss and muscle wasting)
True/False
True
Name the 4 types of delivery devices for asthma medication.
Pressurized Metered Dose Inhaler (pMDI) - Uses chemical propellant
Dry Powder Inhaler (DPI)- Capsule or blister foil with powder breaks inside device to release powder
Soft Mist Inhaler (SMI) - “Respimat”, Compressed spring rather than chemical propellant.
Nebulizer - Turns liquid medication into a mist
What are National Asthma Education and Prevention Program (NAEPP) Asthma Guidelines?
Treatment algorithm to treat asthma – stepwise approach
Describe the 2019 Global Initiative for Asthma (GINA) Asthma Guidelines.
Stepwise process
For patients 12+
Personalized Asthma Management: Assess, adjust, review response
Controller vs reliever medication for asthma
Controller - Taken daily to maintain control of asthma
Reliever - “Rescue”, as needed to treat acute symptoms
Describe GOLD Guidelines for COPD.
Testing measures used to determine the best treatment option for a patient with COPD
Uses CAT (questionnaire) and mMRC (characterize dyspnea)
Describe SABA “TEROL” drugs. Onset, peak, full duration, mode of action.
Short-acting beta2 agonists (SABA)
Onset ~ 5 minutes
Peak ~ 30 minutes
Duration ~4-6 hours
Cause bronchodilation
Are SABA (“TEROL”) typically controller or reliever medications? What is the most common delivery device?
Typically reliever medications
All MDI except respiclick and digihalers which are dry powder inhalers
Albuterol is a(n) _____ of levalbuterol. (Hint: structure)
Isomer
Why should patients wait 30-60s between each puff when using an MDI?
This gives the medicine and propellant enough time to mix together
Common adverse effects of SABA (“TEROL”).
- Anxiety
- Tremors
- Hypokalemia and hypomagnesemia
- Tachycardia – dose dependent, sympathomimetic type side effect
Describe LABA (“TEROL”) drugs. Duration, Safe to use alone?
Long-term bronchodilation (Lasts about 12 hours)
Asthma: Only safe for used with Inhaled Corticosteroids (ICS) (“SONE”)
COPD: LABAs can be used alone
Name the two SABA (“TEROL”).
Albuterol
Levalbuterol
LABA side effects, any DDI or food-drug interactions?
Similar side effects as SABA
Tachyphylaxis (effectiveness of the drug may diminish after long term continuous use)
No major DDI or food-drug interactions
When are LABAs used for asthma?
Added to therapy when ICS alone is not effective
Usual dose frequency of LABAs and name the exceptions.
Usually twice daily
Indacaterol and olodaterol –> dosed once daily
What are the muscarinic antagonists mode of action? Name two types?
Involves the acetylcholine system at the type III muscarinic receptors located in the bronchial smooth muscle (also referred to as antimuscarinics)
Short-acting muscarinic antagonists –> SAMA
Long-acting muscarinic antagonists –> LAMA
LAMAs are mostly used to treat what disorder? What is the exception?
Mostly treat COPD
Ipratropium bromide (Atrovent) can treat COPD and asthma
ICS are only prescribed for asthma not COPD.
True/False
False
Can be used in severe cases of COPD
Name the SABA/SAMA combo drug.
Albuterol/Ipratropium – Respimat inhaler or Duoneb solution
All SABA/SAMA and LAMA/LABA products are BID except?
Vilanterol and Olodaterol products - once daily
What is the fairly new triple therapy inhaler for COPD?
ICS/LABA/LAMA
Fluticasone/Vilanterol/Umeclidinium (Trelegy Ellipta) - once daily
Leukotriene Modifiers. Route of admin, m of a. Name the three drugs.
Leukotriene Receptor Antagonists (LTRA)
Work by blocking the action of leukotrienes at the cysteinyl leukotriene receptors - anti inflammatory bc leukotrienes promote inflammation
Montelukast, Zafirlukast and Zileuton - po only
Are LTRAs better rescue agents than ICS?
LTRAs cannot be rescue agents - they are for mild asthma especially when inhalation is not possible
ICS typically produce better outcomes for asthma
What type of drugs inhibit action of LTRAs? (name the enzyme these drugs metabolize)
Drugs that are metabolized via CYP3A4
Warnings for LTRAs.
Montelukast - agitation, aggression, depression, sleep disturbances, SI
Zafirlukast and Zileuton - hepatoxicity
Name all functions/effects of LTRAs. (Hint: what does it decrease)
Decreases inflammation
Decreases edema and mucous secretion
Decreases bronchoconstriction of the airway
Are LTRAs indicated for short or long term use?
Long term use
Monoclonal Antibodies (-LIZUMAB) indication, m of a, high or low cost?
Target IgE pathway (allergic asthma) or Interleukin (IL) pathways (relevant to eosinophilic disorders)
For severe, persistent asthma
High cost - can excess $10,000 a year
Monoclonal Antibodies (-LIZUMAB) precautions and dangers?
May cause an anaphylactic reaction due to foreign antibodies
Dispensed only at specialty pharmacies
Can be given every 2-4 weeks.
Phosphodiesterase-4-Inhibitor. Indication, side effects, contraindication?
Indicated in severe COPD
Side effects: Headache, dizziness, insomnia, weight loss (discontinue if persists)
Contraindication: Severe hepatic impairment (Child-pugh class B or C)
What are the two OTC asthma products
Racepinephrine (epinephrine (racemic)) – Asthmanephrin™ inhalation solution
Ephedrine Sulfate + Guaifenesin (Primatene™) Tablets
Theophylline & Aminophylline in treating asthma and COPD. Is it a recommended therapy?
Narrow therapeutic index
Many adverse effects
- Treatment of asthma exacerbation with theophylline is not recommended
- Management of acute COPD with IV theophylline is not recommended
Steps to use pMDI? (5)
- Shake
- Remove “dust cap”
- Prime - 2 puffs in the air, especially after prolonged storage
- Press down and inhale slowly and deeply over 5 seconds.
- Hold breath for 4-10 secs then exhale gently
Why did Hydrofluoroalkane (HFA) propellant replace chlorofluorocarbon (CFC) propellants in inhalers?
CFC is bad for the environment and depletes the ozone layer
Benefits of spacers for inhalers.
- Aerosol slowed less need for hand to mouth coordination
- Reduces drug impinged on oropharynx. Increases drug inhaled into lower airways.
- Reduce side effects caused by oropharyngeal deposition of ICS
Spacers can be used with DPIs
True/False
False
Cannot use a spacer with a Dry Powder Inhaler
Soft mist inhalers are breath-actuated like Dry powder inhalers.
True/False
False
Soft mist inhalers are not breath-actuated. They use a compression spring to push out medication.
