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PHAR 253 - Therapeutics (2) > Corticosteroids / Endocrine Physiology > Flashcards

Corticosteroids / Endocrine Physiology Flashcards

1
Q

Main hormone secreted by Zona Glomerulosa?

A

Aldosterone

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2
Q

Main hormone secreted by Zona Fasciculata?

A

Cortisol

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3
Q

Main hormone secreted by Zona Reticularis?

A

Testosterone

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4
Q

Primary functions of Cortisol?

A

-Mediate stress response

-Regulate carb / lipid / protein metabolism

-Regulate inflammatory & immune responses

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5
Q

What bodily responses are generated due to Cortisol release?

A

-Increase HR & BP

-Liver conversion of Glycogen to Glucose

-Bronchiolar Dilation

-Reduced digestion & urine production

-Metabolic Rate goes up

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6
Q

Long term stress responses of the body… What are they?

A

Mineralocorticoids: Retain Na+ & H2O, increased BV & BP

Glucocorticoids: Protein / fat conversion to glucose, immunosuppression

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7
Q

Explain the HPA Axis.

A

1) Stressors (ie. Low Blood Sugars or BP, Fever, Injuries) trigger Hypothalamic release of CRH.

2) CRH targets Pituitary (along with Vasopressin & Cytokines) & ACTH is released.

3) ACTH targets Adrenal Gland, Cortisol is released.

4) Persistent Cortisol negatively feeds back on the loop, suppressing further CRH & ACTH release / production.

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8
Q

The two primary functions of Glucocorticoids?

A

-Inflammatory Suppression

-Suppressed Immune Response

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9
Q

How do Glucocorticoids suppress inflammation?

A

-Reduce Cytokine release

-Reduced vasoactive substance release

-Inhibit leukocyte / macrophagic migration & adhesion to capillary surfaces

-Interfere with phagocytosis

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10
Q

How do Glucocorticoids suppress Immune Responses?

A

-Alter gene / cell function

-Affect WBC function

-Inhibit T cell activation

-Inhibit Interleukins, Cytokines, Gamma Interferon, TNF-alpha synthesis

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11
Q

How might Corticosteroids be of use to somebody with Plaque Psoriasis?

A

-Reduce epidermal cell turnover & inhibit cellular DNA synthesis

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12
Q

How do Corticosteroids infer anti-tumor effects?

A

-Inhibit cellular glucose transport

-Induce cell death to immature lymphocytes

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13
Q

Major issue with Ophthalmic / Otic Corticosteroid formulations?

A

-How to properly administer the drug

Punctal Pinch being done? Getting any drug in the eye / ear? Closing eye after drug admin?

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14
Q

Indications for Nasal Corticosteroids?

A

-Rhinitis
-Nasal Polyps
-Sinusitis

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15
Q

Issue with Nasal Corticosteroids?

A

Delivery Techniques (same as Drops)

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16
Q

Pros & Cons of Metered Dose Inhalers?

A

Pros: Portable

Cons: Inhalation Technique, # of Doses Left Not Displayed

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17
Q

Pros & Cons of Diskus Inhalers?

A

Pros: Portable & Display Remaining Doses

Cons: Powder Deposition, Age Restrictions (young kids lower lung capacity)

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18
Q

Generic name of the Nebular product used as a Corticosteroid?

A

Budesonide (brand name is Pulmicort)

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19
Q

Pros & Cons of Nebulizers?

A

Pros: Good lung delivery for those who cannot generate sufficient respiratory flow rate. Also easy to use the mask on young kids.

Cons: Time Consuming, $$$, Not Portable, False Security.

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20
Q

Rank the following Corticosteroid Creams by potency (from least to greatest):

-Betamethasone Dipropionate

-Betamethasone Valerate

-Hydrocortisone

-Clobetasol Propionate

A

Hydrocortisone (7)

Betamethasone Valerate (5)

Betamethasone Dipropionate (3)

Clobetasol Propionate (1)

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21
Q

Rank the following Corticosteroid Ointments by potency (from least to greatest):

-Betamethasone Dipropionate

-Hydrocortisone

-Clobetasol Propionate

-Betamethasone Valerate

A

Hydrocortisone (7)

Betamethasone Valerate (5 @ 0.05%; 3 @ 0.1%)

Betamethasone Dipropionate (2)

Clobetasol Propionate (1)

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22
Q

Rank the following Corticosteroid Lotions by potency (least to greatest):

-Betamethasone Valerate

-Clobetasol Propionate

-Betamethasone Dipropionate

A

Betamethasone Valerate (5 to 6 depending upon product)

Betamethasone Dipropionate (3 to 5 depending upon product)

Clobetasol Propionate (1)

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23
Q

High potency topical steroid use should be limited to what therapeutic duration?

A

< 2-4wks (followed by usage of less potent agents)

-Should also never be applied more than twice daily.

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24
Q

Maximum topical corticosteroid dose per week (for Ultra Potent Agents)?

A

50g / wk

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25
Factors that affect topical corticosteroid absorption?
-Moisture (increases absorption 4-5x) -Potency -Dosage Form -Concentrations -Formulation -How You Apply It -Occlusion (decreases by up to 10x) -Site of Admin -Condition of Skin
26
IM vs. IV vs. Intra-Articular: Rank them by onset of action.
1) IV (fastest & best for high dosing) 2) IA (quicker & short duration) 3) IM (slowest & prolonged duration)
27
How many times per year can Intra-Articular injections be administered?
3-4x / yr
28
T or F: IV Corticosteroid doses are equivalent to Oral Corticosteroid doses?
True!
29
List the generic oral dosage forms of corticosteroids.
Betamethasone Cortisone Dexamethasone Hydrocortisone Methylprednisolone Prednisone Triamcinolone
30
Oral Solution form of Corticosteroids we discussed in class?
Prednisolone
31
What is a physiologically normal amount of Cortisol production per day?
10 - 20mg / day
32
What is the daily Prednisone equivalency that mimics endogenously produced Cortisol amounts?
5mg / day
33
What would be considered a "low or maintenance dose" of Prednisone?
5 - 15mg / day
34
What would be considered a "moderate dose" of Prednisone?
0.5mg / kg / day
35
What would be considered a "high dose" of Prednisone?
1 - 3mg / kg / day
36
What would be considered a "massive dose" of Prednisone?
15 - 30mg / kg / day
37
What are the Short Acting Corticosteroids?
Cortisone & HC
38
What are the Intermediate Acting Corticosteroids?
-The "Preds" (Prednisone & Prednisolone) -Methylprednisolone -Triamcinolone
39
What are the Long Acting Corticosteroids?
Dexamethasone & Betamethasone
40
Short Acting Corticosteroids have a half life of how many hours?
8 - 12h
41
Intermediate Acting Corticosteroids have a half life of how many hours?
12 - 36h
42
Long Acting Corticosteroids have a half life of how many hours?
36 - 72h
43
Which Corticosteroids have Na+ Retaining Potencies? What are their relative potencies?
Cortisone & HC: 1 The "Preds": 0.8 Methylprednisolone: 0.5
44
Anti-Inflammatory Potencies of the Corticosteroids... List them all.
Cort: 0.8 HC: 1 Preds: 4 Methylpred: 5 Triam: 5 Dexa: 25 Beta: 25
45
Cortisone equivalent dose?
25mg
46
HC equivalent dose?
20mg
47
Prednisone / Prednisolone equivalent dose?
5mg
48
Methylprednisolone / Triamcinolone equivalent dose?
4mg
49
Dexamethasone / Betamethasone equivalent dose?
0.75mg
50
Ophthalmic CS side effects?
-Stinging & Redness -Tearing & Burning -Secondary Infection -Cataract Development
51
Inhaled CS side effects?
-Thrush -Hoarseness -Dry Mouth -Dysphoria (altered voice) -Swallowing Difficulties
52
Nasal CS side effects?
-Runny Nose -Bloody Nose -Burning -Sneezing
53
How can we minimize Nasal / Inhaled CS side effects?
-Rinse Mouth (ICS) -Point Device away from Septum (NCS)
54
Topical CS side effects?
-Burning -Irritation -Skin Atrophy -Tachyphylaxis (effects wear off with LTU) -Telangiectasia (spider veins)
55
Systemic side effects attributed to Oral CS?
-Hypertension -Skin Thinning -Muscle Wasting -Moon Face -Cataracts -Abdominal Fat -Bruise Easy / Slowed Wound Healing
56
Psychological side effects of Systemic CS?
-Euphoric -Insomnia / Restlessness -Memory Impairment
57
Long term psychological side effects of Systemic Corticosteroids?
-Depression -Mania -Psychosis
58
What do we recommend long term corticosteroid users do (regarding exams)?
Routine Eye Exams (as Cataract damage is irreversible)
59
CS's can cause GI upset & dyspepsia... It also can increase one's risk of developing Peptic Ulcer Disease if taken concurrently with what medications?
NSAIDs
60
Blood Glucose increases due to CS usage typically take place above what Prednisone dose? How long after d/c do effects persist?
> 15mg / day -Effects can persist for months after.
61
T or F: Na+ / H2O retention doesn't normally resolve itself upon CS d/c.
False... Normally does resolve itself.
62
T or F: High Dose CS therapies can increase appetite.
True.
63
Suggest mechanisms of action in which CS's suppress childhood growth.
-Suppress Osteoblastic activity. -Suppress Growth Hormone secretion. -Inhibition of Insulin Receptors.
64
What CS formulation do we see the most pronounced effects on childhood growth?
Oral CS Therapies
65
T or F: Short term CS use in kids for acute reasons will permanently affect growth.
False... Can maybe stunt growth, but more so for chronic use & d/c of the medication sees a catch-up growth period.
66
When are Cortisol levels highest during the day?
AM (7 - 8 in the morning)
67
Why must we taper CS's gradually (rather than a complete stop)?
-Continual Corticosteroid use completely suppresses the HPA... Means that produced levels of CRH & ACTH are basically null & body cannot respond to stressor events.
68
Bodily effects of complete HPA Axis Suppression?
-Hypotension / Hypoglycemia -Flu Like Symptoms (NV / Fatigue / Chills / Fever / Muscle Aches) -Weight Loss -Confusion
69
Factors that predict HPA Axis Suppression?
-Type of Steroid Used -Dose Used -ROA -Duration -Admin Time (Hypotensive / Hypoglycemic crashes more likely with PM dosing) -Intervals of Dosing (more with QID than OD dosing)
70
Length of time that it may take the HPA Axis to restore normal functioning once CS's are d/c?
Weeks to over a year (sometimes even as long as 1 - 3yrs)
71
What is the SST (Short Synacthen Test) used for?
-To determine degree of HPA Axis Supression... ACTH given & plasma Cortisol levels measured at 0, 30, 60min intervals in order to determine Cortisolic responsiveness to ACTH release.
72
Describe the trends of Adrenal Insufficiency risk as it pertains to the following dosage forms: Nasal Intra-Articular Oral
Nasal: Least risk (around 5%) Intra-Articular: Somewhat high risk (around 42%) Oral: Highest risk (around 49%)
73
Low dose, medium dose, high dose: What are the relative risks of suffering from Adrenal Insufficiency while on these CS dosing regimens?
Low Dose: Very low risk (around 2%) Medium Dose: Relatively low risk (around 8-9%) High Dose: Moderate risk (around 22%)
74
As dosing regimens on CS's go on for longer periods of time (ie. Beyond a year), how does the relative risk of suffering from Adrenal Insufficiency change?
Increases dramatically (less than a month 1.4%; over a year in length risk increases to beyond 27% of suffering from Adrenal Insufficiency)
75
Susceptibility to viral, bacterial, and fungal infections increase when one takes a CS dose of > ____mg / day of Prednisone.
Over 10mg / day -Typically does not occur in doses < 10mg / day.
76
Because of the nature of how CS's inhibit cell division, what skin-related condition might people see an increased risk of obtaining when taking these medications?
Acne
77
Gladys is a middle aged woman (52yrs) with arthritis. She comes to your pharmacy complaining of recent foot fractures. You probe deeper and determine she's been recently put on corticosteroids about 2 months ago. Explain mechanistically how her steroid therapy may be contributing to her recent run of fractures.
-Reduced Ca2+ absorption from the diet and reabsorption from the Kidneys. -Inhibition of Osteoblast activity (no bone regeneration). -Length of therapy itself contributing to increased fracture risk ( >2-3 months of therapy greatly increases risk). -Potential Osteoporosis (30-50% on chronic therapy develop it).
78
Fracture Risk Assessments should be conducted on all adults initiating or continuing GC therapies above a dose of ____ mg / day and beyond a therapy length of > ___ months.
> 2.5mg / day ; > 3 months in duration
79
What add-on therapy / therapies are strongly recommended for high risk GIOP adults on Corticosteroids?
-Bisphosphonate (to enhance Ca2+ absorption and promote bone health). -Vitamin D (to enhance Ca2+ absorption from diet). -Potential Ca2+ supplementation.
80
Why can muscle wasting occur in patients on high dose CS's?
-CS's have catabolic effects (as well as suppress protein synthesis).
81
Above a Prednisone dose of ___ mg / day is when myopathy becomes more common.
> 10mg / day
82
Amongst kids on short term CS therapies (< 14d duration), what was the most common reason for discontinuing the therapy?
Vomiting (due to bitter taste)
83
T or F: Short term CS use (< 2 wks) outright eliminates the risk of side effects.
False... Risk is quite small of obtaining things such as Sepsis / Venous Thromboembolism / Fracture, but there is still a risk.
84
What is the recommended short term corticosteroid therapy regimen for COVID treatment?
Dexamethasone 6mg OD (for up to 10 days duration of therapy)
85
CS treatment in COVID patients saw an increase in ______ _______ and a decrease in ________ in those requiring oxygen.
increase in clinical outcomes ; decrease in mortality
86
T or F: CS dosing has set guidelines for all individuals.
False... Very patient specific (want to bring inflammation & immunological responses under control via the MED).
87
Order the following dosing regimens by their immunosuppressive potentials: TID OD BID
OD < BID < TID -More frequent the dosing, the more potent immunosuppression is.
88
What is the most typical weight based maintenance dose for those on CS's?
0.5 - 1mg / kg / day
89
Is a taper necessary to conduct with a patient on CS's for < 2 weeks length?
Probably not.
90
Beyond what length of time on CS therapies should we begin to consider taping a patient?
> 3wks... Dependent upon cumulative dose, dosing frequency, physiological circumstances, etc.
91
When desiring a CS taper, what is a good rule of thumb to follow?
5 - 10% / wk as a desired dose reduction.
92
"Every Other Day" (EOD) dosing is typically done with what class of CS's?
Intermediate Acting CS's... Long Acting work too long & Short Acting work for too short of a duration.
93
What situations would warrant EOD Corticosteroid dosing?
-Chronic Admin -Kids needing maintenance doses
94
What are the three systems / molecules in charge of regulating Aldosterone secretion?
1) RAAS 2) Potassium 3) ACTH
95
What three things stimulate Aldosterone release?
1) Drop in BP 2) Salt Depletion 3) CNS Excitation
96
What condition arises due to the actions of Aldosterone (as it pertains to Na+ / K+)?
Hypokalemia... Na+ retention is increased, and thus K+ excretion in the Distal Collecting Tubules of the Kidneys increases.
97
What is Cushing's Syndrome?
Persistent exposure (either Exogenous or Endogenous in nature) to excessive Glucocorticoids.
98
T or F: Men are more affected by Cushing's Syndrome than Women.
False... Women > Men (incidence is 5:1 W to M).
99
T or F: Exogenous GC use raises Cushing's incident rates by a substantial amount (relative to Endogenous overexposure).
True.
100
What causes Endogenous overproduction of Cortisol in Cushing's Syndrome?
1) Pituitary Tumors (overproducing ACTH, leading to more Cortisol secretion from Adrenals). Incidence is 80% of Endogenous cases. 2) Tumors on the Adrenal Gland itself (leading to more Cortisol production). Incidence is 20% of Endogenous cases.
101
What are the clinical features of Cushing's?
Face: Moon Face, Facial Plethora, Acne Abdomen: Weight Gain / Obesity Systemic: Hypertension, Bruise Easy, Glucose Intolerance, Muscle Weakness, Thinning Skin / Striae, Fatigue Bones: Osteopenia / Increased Fractures Miscellaneous: Irregular Periods, Reduced Sex Drive, ED, Depression / Emotional Instability, Reduced Linear Growth (kids)
102
How does the prognosis of Cushing's change when therapeutic goals are achieved (signs / symptoms resolved)?
Untreated: 5yr Survival Rates of 50% Treated: 20yr Survival Rates of 87%
103
What treatment is sometimes required upon surgical removal of Pituitary Adenomas in Cushing's patients?
Supplemental CS therapies (as Cortisol levels will be dropping too pronouncedly).
104
If surgical removal of Pituitary Adenomas is unsuccessful, what else can we do?
1) Repeat surgery 2) Medication Therapies 3) Radiation Therapies 4) Bilateral Adrenalectomy
105
In cases of Drug-Induced Cushing's Syndrome, what is our treatment option?
Taper off of the medication (no shit Sherlock).
106
What pharmacological agents can be used as therapies for treating Cushing's Syndrome patients?
1) Steroidogenesis Inhibitors -Ketoconazole -Metyrapone -Mitotane 2) ACTH Secretion Inhibitors -Pasireotide
107
What is our DOC for Cushing-oid pharmacotherapies?
Ketoconazole (effective drug & lesser adverse effects profile).
108
S/E's of Ketoconazole?
-Stomach Upset -Boobies (gynecomastia) -Headaches -Sedation -ED (dick don't work) -Sex Drive like Adam :( -Increased LFT needed
109
Other things to look out for with Ketoconazole?
LOTS OF DRUG INTERACTIONS!!! -CYP1A2 Drugs -CYP2C9 Drugs -CYP3A4 Drugs
110
What use does Metyrapone have in treating Cushing-oid symptoms?
-Often used concurrently with Ketoconazole (to offset individualistic s/e's).
111
S/E's of Metyrapone?
-Androgenic side effects (ie. Hirsutism, Acne) -N/V, Abdominal Discomfort -Dizziness & Headaches -Allergic Rashes
112
What is Mitotane's indication in Cushing's treatment regimens?
Inoperable Adrenal Carcinomas
113
Why is Mitotane initiated in hospital?
-Because of its Cytotoxic nature (kills both cancerous cells & healthy cells) & s/e profile. -Substantially drops Cortisol levels (can drop dangerously low & requires quick hospital team response).
114
S/E profile of Mitotane?
-NVD (80%) -Depression -Lethargic / Somnolence (40-80%) -Hypercholesterolemia -Rash -Hepatotoxicity
115
MOA of Pasireotide?
-Binds Somatostatin receptors, which inhibits ACTH secretion from producing Adenomas.
116
Pasireotide s/e's?
-Hepatotoxic -CV events (Bradycardia / QT Prolongation) -Hyperglycemia -Gall Bladder Events
117
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PHAR 253 - Therapeutics (2) (8 decks)

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