Glucocorticoid	Approximate Equivalent dose (mg)	Half-life (Biologic) hours
Short-Acting
Cortisone	25	8-12
Hydrocortisone	20	8-12
Intermediate-Acting
Methylprednisolone	4	18-36
Prednisolone	5	18-36
Prednisone	5	18-36
Triamcinolone	4	18-36
Long-Acting
Betamethasone	0.6 - 0.75	36-54
Dexamethasone	0.75	36-54

Last updated 07/18/2002 13:09:00

Calculator at: http://www.globalrph.com/corticocalc.htm

Glucocorticoid Comparison*

*Approximate Equivalent may vary with disease state

Agent	Equivalent Dose (approx. mg)	Route of Administration	Relative Antiinflammatory Potency	Relative Mineralocorticoid Potency	Biologic Half-Life (hours)
Betamethasome	0.6-0.75	IM,IV,PO	20-30	0	36-54
Dexamethasone	0.75	IM,IV,PO	5-30	0	36-54
Hydrocortisone	20	IM,IV,PO	1	2	8-12
Methylprednisolone	4	IM,IV,PO	5	0	18-36
Prednisolone	5	PO	4	1	18-36
Prednisone	5	PO	4	1	18-36

Dexamethasone to Methylprednisolone Conversion
Dr Bleck's Neurosurgery Service

Dexamethasone	Methylprednisolone
Dose in mg	Dose in mg
0.5	2
1	4
2	9
3	13
4	18
5	22
6	27
7	31
8	36
9	40
10	44
11	49
12	53
13	58
14	62
15	67
16	71
17	76
18	80
19	84
20	89

Last Updated on 5/14/01
By Medical Center User

1. Dosing: Adult
1. Betamethasone (Celestone) 0.5 to 0.9 mg IM/PO qd
2. Cortisone (Cortone) 25-300 mg PO qd
3. Dexamethasone (Decadron) 0.75-9 mg PO/IM/IV divided q6h
4. Hydrocortisone (Cortef)
1. Parenteral: 100 to 150 mg IV/IM q2-6 hours prn
2. Oral: 20 to 240 mg/day PO in divided dosing
5. Methylprednisolone
1. Parenteral (Solu-Medrol) 10 to 125 mg IV/IM
2. Oral (Medrol) 4 to 48 mg PO qd
3. Medrol Dose pack: tapers from 24 to 0 PO over 7 days
6. Prednisolone (Prelone) 5-60 mg PO/IV/IM qd
7. Prednisone (Deltasone) 5-60 mg PO qd
8. Triamcinolone (Aristocort, Kenalog) 4 to 48 mg PO/IM qd
2. Dosing: Child
1. Methylprednisolone (Solu-Medrol)
1. Dose: 1-2 mg/kg/dose PO/IV/IM q6h up to 125 mg/dose
2. Prednisolone (Prelone)
1. Dose: 1-2 mg/kg/dose PO qd to bid up to 60 mg/day
2. Maximum: 60 mg per day
3. Preparations
1. Syrup: 15 mg/5 ml
2. Liquid: 5 mg/5 ml
3. Agents: Overall potency (equivalent dosages)
1. High potency
1. Betamethasone 0.6 to 0.75 mg
2. Dexamethasone 0.75 mg
2. Medium potency
1. Methylprednisolone 4 mg
2. Triamcinolone 4 mg
3. Prednisolone 5 mg
4. Prednisone 5 mg
3. Low potency
1. Hydrocortisone 20 mg
2. Cortisone 25 mg
4. Agents: Relative anti-inflammatory potency
1. High anti-inflammatory potency
1. Betamethasone 20-30
2. Dexamethasone 20-30
2. Medium anti-inflammatory potency
1. Methylprednisolone 5
2. Triamcinolone 5
3. Prednisolone 4
4. Prednisone 4
3. Low anti-inflammatory potency
1. Hydrocortisone 1
2. Cortisone 0.8
5. Agents: Relative Mineralocorticoid Potency
1. Mineralocorticoid Activity
1. Cortisone 2
2. Hydrocortisone 2
3. Prednisolone 1
4. Prednisone 1
2. No Mineralocorticoid Activity
1. Betamethasone
2. Dexamethasone
3. Methylprednisolone
4. Triamcinolone
6. Agents: Half Life
1. Long half-life (36-54 hours)
1. Betamethasone
2. Dexamethasone
2. Medium half-life (18-36 hours)
1. Methylprednisolone
2. Prednisolone
3. Prednisone
4. Triamcinolone
3. Short half-life (8-12 hours)
1. Cortisone
2. Hydrocortisone

Pharmacodynamics / Pharmacokinetics (Primary)

1. 90% of glucocorticoid protein bound
• Receptors for CBG-steroid complex on cell surface.
• Corticosteroid Binding Globulin "delivers drug to cells"
• Albumin binding restricts volume of distribution
2. Active transport of bound steroid into cell
3. Binding of glucocorticoid to receptor in cytoplasm (complex)
4. Active transport of complex to nucleus
5. Tight binding of complex to "regulatable" gene sequences.
• Cell type determines which sequences.
6. Binding causes an increase in DNA transcription
7. A variety of proteins may be produced (depending on specific genes activated)

Concequences of Glucocorticoid pharmacology

• Strength of binding (steroid to CBG, steroid to receptor, steroid-receptor to DNA) determines potency and duration.
• Pharmacokinetics of circulating glucocorticoid have little effect on potency or duration.
• Ultimate activity of glucocorticoids depends on the nature and quantity of the proteins produced. Pharmacokinetics of the new protein (amount produced and half-life) ultimately determines the potency and duration of the response. Proteins may interact with each other and with DNA to alter binding.
• Gluconeogenesis enzymes
• Lipocortin
• Decreased phospholipase A₂ activity

Pharmacodynamics (Secondary)

Glucocorticoids appear to have activities that are mediated through alternate pathways. These are are probably NOT mediated through the regulation of DNA transcription. Specific receptors have not been clearly identified. The "kinetics of these effects are different than those mediated through cell nuclei.

• increased sensitivity to adrenergic drugs
• direct vascular effects
• activity in spinal cord trauma

Systemic Effects of Glucocorticoids

Central Nervous System	Euphoria and behavioral changes Maintenance of alpha rhythm Lower Seizure Threshold
Autonomic Nervous System	Required for normal sensitivity of adrenergic receptors
Gastrointestinal Tract	Decreased calcium and iron absorption Facilitation of fat absorption Increased acid, pepsin, and trypsin Structural alteration of mucin
Skeletal Muscle	Weakness (excess and deficiency) Muscle atrophy (chronic excess)
Skin	Atrophy and thinning (chronic excess) Calcinosis Cutis
Hematopeoietic system	Involution of lymphoid tissue (species dependent) Decrease in peripheral lymphocytes, monocytes, eosinophils Increase in peripheral neutrophils, platelets, RBCs Decreased Clotting Time Decreased phagocyte competence
Cardiovascular system	Positive inotropic effect Increased blood pressure (increased blood volume)
Kidneys	Increased reabsorption of water, sodium, chloride Increased excretion of potassium, calcium Increased extracellular fluid
Bone	Inhibition of collagen synthesis by fibroblasts Acceleration of Bone resorption Antagonism of Vitamin D
Cells	"Stabilization" of liposomal membranes Inhibition of macrophage response to migration inhibition factor Lymphocyte sensitization blocked Cellular response to inflammatory mediators blocked Inhibition of fibroblast proliferation
Reproductive Tract	Parturition induced during the latter part of pregnancy in ruminants and horses Less reliable in dogs and cats Teratogenesis during early pregnancy.

Glucocorticoids as Drugs

Potency is primarily determined by the glucocorticoid base. The ester may control the amount of drug released into the circulatory system which would also control the magnitude of effect.

Table 2. Comparison of Glucocorticoid Bases.
Base	Relative Potency^1	K/Na Effect	Equivalent Dose^2	Duration (HPA)^3	Structural Difference
Short Acting
Hydrocortisone	1	++	20	12
Cortisone^4	0.8	++	25	12	11 ketol
Intermediate Acting
Prednisone^4	3.5	+	6	12 - 36	1 ketol; 1=2
Prednisolone	4.0	+	5	12 - 36	1=2
Methylprednisolone	5.0	0	4	12 - 36	6-me; 1=2
Triamcinolone	5.0	0	4	12 - 36	9-F;16-OH;1=2
Long Acting
Paramethasone	10	0	2	> 48	6-F;16-me;1=2
Betamethasone	25	0	0.8	>48	9-F;16-bme;1=2
Dexamethasone	30	0	0.7	>48	9-F;16-me;1=2
^1. Glucocorticoid potency ^2. Dose suggested is replacement therapy for a 20 kg. dog ^3. Durations for other effects are likely to be different (see mechanism of action notes) ^4. pro-drug, activated by conversion to hydrocortisone or prednisolone.

Duration is controlled by the base UNLESS the base is attached to an ester that makes it "long-acting" (Table 3). Even then, the base will have some effect. (e.g. dexamethasone acetate injection will have a longer duration of effect than prednisolone acetate).

Glucocorticoid Products (Esters and dose forms)

Selection of a glucocorticoid ester is based on the route of administration and the desired duration and intensity of effect.

Oral

• the ester is irrelevant. All are separated from the base in the GI tract. The base drugs are well absorbed.

IM, SubQ, Intralesional

• Rapidly absorbed products can be used as substitutes for oral preparations. Their absorption and duration are roughly equivalent to the oral base products (and salts).
• Slowly absorbed (Depot) products are designed to provide either low concentrations of glucocorticoids for extended periods of time or high concentrations in a local area (e.g., tumor injections).

IV

• Water soluble salts. These reach sites of action 1/2 - 1 hour faster than oral but are otherwise similar in potency.
• This is the most appropriate route of administration for "EXTREME-DOSE" glucocorticoid therapy (e.g., CNS trauma, shock, etc.)

Table 3. Available Glucocorticoid Products
Base	Oral	Intravenous Rapid IM, SC Absorption	Intralesional Slow IM, SC Absorption	Topical
Betamethasone	Free base	Na phosphate	Na phosphate + Acetate	Free base Benzoate Dipropionate Valerate
Cortisone	Acetate		Acetate
Dexamethasone	Free base	Na phosphate	Acetate	Free base
Fluprednisolone	Free base
Hydrocortisone	Free base Cypionate	Na phosphate Na succinate	Acetate	Free base Acetate
Meprednisone	Free base
Methylprednisolone	Free base	Na succinate	Acetate	Acetate
Paramethasone	Acetate
Prednisolone	Free base	Na phosphate Na succinate	Acetate Tebutate Na phosphate + Acetate	Free base Acetate Na succinate
Prednisone	Free base
Triamcinolone	Free base Acetonide Diacetate		Acetonide Diacetate Hexacetonide	Free base Acetonide

Glucocorticoid Replacement Therapy

Control clinical signs of Primary Hypoadrenocorticism

Categories

• Idiopathic (Destruction of Adrenal Cortex)
• Iatrogenic (o,p'-DDD)

Treatment - Emergency

• Mineralocorticoid deficiencies
• Normal Saline
• Hydrocortisone
• Glucocorticoid deficiencies
• Hydrocortisone
• Prednisolone

Treatment - Maintenance

• Mineralocorticoid deficiencies
• Desoxycorticosterone Pivalate (monthly injections)
• mineralocorticoid only - VERY reliable
• 9-fluorohydrocortisone acetate (Florinef®)
• mixed activity - VARIABLE
• Glucocorticoid deficiencies
• Prednisone or prednisolone
  Daily oral or daily injection with rapidly absorbed (non-depot) form.

Control clinical signs of Secondary Hypoadrenocorticism

Categories

• Idiopathic (Destruction or dysfunction of pituitary)
• Iatrogenic (Chronic glucocorticoid administration)

Treatment - Emergency

• Fluid therapy
• Glucocorticoid (Intravenous glucocorticoid products)

Treatment - Maintenance

"Axis Recovery"

• Slow reduction in dose over extended period of time
• change dose rate every 3-4 weeks, change to EOD for first reduction
• No ACTH (maintains negative feedback on hypothalamus)
• Remember extra pred. for "stress"

• Daily replacement therapy
• Prednisone or prednisolone preferred
• 1 mg/kg of hydrocortisone activity each day (dog)
• 0.2 - 0.25 mg/kg prednisone, prednisolone "normal" secretion rate not known for other species
• "Stressful" Situations
• additional prednisone or prednisolone

Anti-inflammatory and Anti-immunologic Therapy

Steroids are potent drugs for interrupting events triggered at the cell membrane (prostaglandins, phospholipase, etc.), and cell mediated immunity (antigen recognition, cell migration, etc.)

Steroids are NOT effective inhibitors of antibody synthesis.

Reduce inflammation

Dosing

• approximately 4 x replacement dose
• usually 1 mg/kg prednisone or prednisolone
• various "protocols" lead to success

Discontinuing therapy

• Cold turkey if glucocorticoid therapy of less than 2 weeks duration
• Taper off if Glucocorticoid therpy of greater than 2 weeks duration. Rate of taper should be proportional to duration of prior therapy. The longer the original therapy, the slower the rate of dose reduction.

Inhibit immunologic responses

Dosing

• approximately 16x replacement dose (daily)
• usually initiate with 4 mg/kg prednisone or prednisolone per day in two doses (2 mg/kg q12H)
• avoids relatively remote potential for acute adverse effects
• possibly reduces initial efficacy (versus one single daily dose)
• Acute "psychosis" POSSIBLE with these doses (especially in one 4 mg/kg daily dose)

Reducing dose rates

• Goal is to "acheive the lowest dose that will control the disease."
• Disease break may require returning to original remission doses (or higher).

Alternate day therapy (Anti-inflammatory OR Anti-immunologic)

Administration of a single dose of an intermediate-acting glucocorticoid on alternate days in a dose equivalent to that being employed over a 48 hour period.

200 mg given every other day has the same efficacy as 90 mg given every day.

200 mg given every other day produces the same adverse effects as 25 mg given every day.

When?

• any patient who is dosed with glucocorticoids for longer than 14 days

How?

• can be used as one step in "tapering" protocol but with greater risk of disease "breakthrough"
  1 mg/kg SID (change to) 1 mg/kg EOD
• can convert to EOD with SMALL loss of efficacy
  1 mg/kg SID (change to) 2 mg/kg EOD

Which drugs?

• Prednisone, prednisolone, methylprednisolone OK.
• Triamcinolone ????
• Dexamethasone, betamethasone inappropriate
• Substitute rapidly absorbed (non-depot) IM or SC forms for oral

Why?

• Greater reduction in side effects than can be acheived by dose reduction alone.
• Does NOT eliminate side effects, merely minimizes them.

Intravenous use

• Shock: Methylprednisolone sodium succinate (Solu Delta Cortef®) vs. dexamethasone Na phosphate
• Spinal cord trauma: Methylprednisolone sodium succinate

Topic Summary (Glucocorticoids)

1. All glucocorticoid drugs act by the same basic mechanism. (Altering relative production of various mRNA's). Cells control the specific response by controlling specific DNA sequences that can be regulated. Anti-inflammatory (and anti-immunologic) activity cannot be separated from metabolic side effects.
2. Differences between glucocorticoid drugs are potency, duration of action of the base, and pharmacokinetic behavior of the salts.
3. Salts of glucocorticoids do not effect the duration of action following oral administration.
4. Injectable replacements for oral glucocorticoids (given daily or on alternate days) include bases for injection, succinate, hemisuccinate, and phosphate salts.
5. Alternate day therapy limits the (metabolic and adrenal axis) toxicity of glucocorticoids while efficacy is maintained.