Topic review G lucocorticoids - PowerPoint Presentation

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Topic reviewGlucocorticoids

By Dr Barakat Shahin

Phamacology lect5 By Dr Barakat Shahin

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Phamacology lect5 By Dr Barakat Shahin

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Glucocorticoids + Mineralocorticoids + Sex hormoneCorticosteroid = Cortex + Steroid

GlucocorticoidsPhamacology lect5 By Dr Barakat Shahin3

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Adrenal glandPhamacology lect5 By Dr Barakat Shahin

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IntroductionCortisol is the predominant corticosteroid secreted from the adrenal cortex in humansS

ecreted according to a diurnal pattern under the influence of ACTH from the pituitary gland under the influence of CRH from the hypothalamus

Review article: Corticosteroid Insufficiency in

Acutely

Ill Patients

N

Engl

J Med 2003;348:727-34

.

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Regulation of Cortisol Secretion3 major mechanisms

1. Negative feedback mechanism 2. Diurnal variation 3. Stress physical psychological

physiological

Review Article :

Applications

of Steroid in Clinical

Practice

International

Scholarly Research

Network ISRN

Anesthesiology

Volume

2012

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Phamacology lect5 By Dr Barakat Shahin

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Glucocorticoids: Physiological EffectMetabolism - R

egulator of carbohydrate, protein, lipid, and nucleic acid metabolism - Stimulate gluconeogenesis - Promote mobilization and oxidation of fatty acids - Excess cortisol causes “buffalo hump”

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buffalo humpPhamacology lect5 By Dr Barakat Shahin

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Blood Pressure Control - Increase vascular smooth muscle sensitivity

to pressor agents - Reduce nitric oxide-mediated endothelial dilatation - Increase filtration fraction and glomerular hypertension - Synthesis

of angiotensinogen and atrial natriuretic peptide

- Decrease

prostaglandin

synthesis

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cardiovascular system - influence on myocardial responsiveness, arteriolar tone, and capillary permeability

- Hypocorticism increased capillary permeability inadequate vasomotor response decrease in cardiac output and cardiac size- Hypercorticism leads to chronic arterial hypertensionPhamacology lect5 By Dr Barakat Shahin

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Blood Pressure Control - increases vascular smooth muscle sensitivity to pressor

agents - reduces nitric oxide-mediated endothelial dilatationPhamacology lect5 By Dr Barakat Shahin

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Anti-Inflammatory Effects - Stabilize lysozyme membranes

- Decrease the release of inflammation - Decrease capillary permeability - Interfere with complement pathway activation - Interfere with formation

of inflammatory mediators

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Bone and Calcium Metabolism - Inhibit osteoblast function

- Excess glucocorticoid causes osteopenia and osteoporosisPhamacology lect5 By Dr Barakat Shahin19

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CNS and Mood - depression

- euphoria - psychosis - apathy - lethargyPhamacology lect5 By Dr Barakat Shahin

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Developmental Changes - maturing of number of systems in 3rd trimester

- pulmonary surfactant - enzyme in the liver - phenylethanolamine N-methyltransferasePhamacology lect5 By Dr Barakat Shahin

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Eye -raise intraocular pressureGut

- Chronic steroid used increases the risk of peptic ulcer - Pancreatitis with fat necrosisPhamacology lect5 By Dr Barakat Shahin

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Endocrine Effects - suppress thyroid axis

- inhibit GRH pulsatility Phamacology lect5 By Dr Barakat Shahin23

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Effect of Anaesthesia and SurgeryPlasma cortisol levels typically increase from 2-10 foldsMaximum ACTH and cortisol levels are reached in the early postoperative period

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Cortisol return to normal within 24 hrs postoperatively May remain elevated as long as 72 hrs

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Anesthetic drugs VS HPA response Etomidate

Large doses of opioid Volatile anestheticsPhamacology lect5 By Dr Barakat Shahin

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glucocorticoidAnti-inflammatory potency

Na-retaining potencydurationEquivalent doseCortisol11

<12 hr

20

Prednisolone

Methyl-P

4

5

0.8

0.5

12-36 hr

5

4

Dexa

-

methasone

25

0

>36 hr

0.75

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Adverse Drug Effects of

Steroid SupplementationPhamacology lect5 By Dr Barakat Shahin29

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Risks with Short-Term (Perioperative) Supplementation aggravation of hypertension

fluid retention delayed wound healing hypokalemia increased susceptibility to infection decreased glucose

tolerance

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Risks with Long-Term Supplementation HPA axis suppression

hypokalemia metabolic alkalosis edema weight gain hyperglycemia

osteoporosis peptic ulcer & GI bleeding

buffalo hump

proximal skeletal muscle

myopathy

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Application of Steroids in anesthesia

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Perioperative steroid replacement therapyNormal circulating Cortisol level: -highest at 6-8 a.m. : 6-23 mcg/dL

-lowest at midnight : 2.9-13 mcg/dLMean cortisol production rate is 5.7 mg/m2/day or about 10 mg/dayIn severe surgical stress: 75-150 mg/day

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Adrenal insufficiencyPrimary adrenal insufficiency:  impairment of the adrenal glandsglucocorticoid ,mineralocorticoid and sex hormone are lost

Secondary adrenal insufficiency : secondary to hypothalamic-pituitary disease or suppression of the HPA axisSheehan’s syndrome, long continued exogenous steroidPhamacology lect5 By Dr Barakat Shahin34

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Recovery time of normal HPA axis varies from 2 days to 12 months after discontinuation of steroid therapyAbility to respond to stress returns by 2 months after discontinuation of steroid therapy

Review Article:Applications of Steroid in Clinical PracticeSafiya Shaikh, International Scholarly Research Network ISRN Anesthesiology,Volume 2012, Article ID 985495

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Degree of HPA suppression is related to choice of steroid preparation , duration and dose of steroid therapy

A. S. Krasner, “Glucocorticoid-induced adrenal insufficiency,”Journal of the American Medical Association, vol. 282, no. 7, pp.671-676,1999.

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Glucocorticoid potency correlates with risk for adrenal insufficiency The equivalence of 15 mg/day of prednisolone for more than 3 weeks should be suspected of having HPA suppression

A. S. Krasner, “Glucocorticoid-induced adrenal insufficiency,”Journal of the American Medical Association,

vol. 282, no. 7, pp.671-676,1999

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Patient currently taking steroids

<10 mg/dAssume normal HPA responseAdditional steroid cover not required>10 mg/dMinor

Sx

25mg of hydrocortisone at induction

Moderate

Sx

Usual

periop

. steroid

+25mg of hydrocortison

e at induction

+100 mg/d for 24 hr

Major

Sx

Usual

periop

. steroid

+25mg of hydrocortison

e at induction

+ 100 mg/d for 48-72hr

Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem

M. Salem

Annals of Surgery, vol. 219, no. 4, pp. 416–425, 1994

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Patient stopped taking steroid

Stopped < 3 moTreat as if on steroidsStopped > 3 moNo periop. steroid necessary

Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem

M. Salem

Annals of Surgery, vol. 219, no. 4, pp. 416–425, 1994

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Retrospective, prospective and randomised studies all methodologically flawed Continuation of the basal glucocorticosteroids is sufficient to stress

Perioperative glucocorticosteroid supplementation is not supported by evidenceDylan W. de Lange :

European Journal of Internal Medicine 19 (2008) 461–467

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Current and rather defensive strategy of perioperative supraphysiological glucocorticosteroid supplementation is not embedded in medical evidenceHigh doses of glucocorticosteroids have disadvantages that should not be ignored

Perioperative glucocorticosteroid supplementation is not supported by evidenceDylan W. de Lange : European Journal of Internal Medicine 19 (2008) 461–467Phamacology lect5 By Dr Barakat Shahin

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Patients receiving therapeutic doses of corticosteroids undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroid

Requirement of Perioperative Stress Doses of CorticosteroidsA Systematic Review of the Literature

Paul E. Marik, MD; Joseph Varon, MD

Arch Surg. 2008;143(12):1222-1226

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Patients receiving physiologic replacement doses of corticosteroids owing to primary adrenal insufficiency require supplemental doses of corticosteroids in the

perioperative periodAdrenal function testing is not required in these patientsRequirement of Perioperative Stress Doses of Corticosteroids

A Systematic Review of the LiteraturePaul E.

Marik

, MD; Joseph

Varon

, MD

Arch Surg. 2008;143(12):1222-1226

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There is currently

inadequate evidence to support the use of supplemental perioperative steroids in patients with adrenal insufficiencyAdministration of the patient’s daily maintenance dose of corticosteroid may be sufficient and supplemental doses are not required

Supplemental perioperative steroids for surgical patients with adrenal insufficiency (Review)

prepared and maintained by The Cochrane Collaboration and published in

The Cochrane Library

2012, Issue 12

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There is a need for high quality RCTs in various surgical settings to assess the requirement for supplemental perioperative steroids when patients with adrenal insufficiency undergo surgery

Supplemental perioperative steroids for surgical patients with adrenal insufficiency (Review) prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 12Phamacology lect5 By Dr Barakat Shahin

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Thank you

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Postoperative nausea and vomitingDexamethasone

inhibit the synthesis of prostaglandin and various other inflammatory mediators acting on chemoreceptor trigger zonePhamacology lect5 By Dr Barakat Shahin53

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may and cause emesisPhamacology lect5 By Dr Barakat Shahin

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Post Intubation Laryngeal Oedemacommonly given after multiple attempts at intubation Dexamethasone 0.1-0.2 mg/kg ivits efficacy has not been confirmed

Dexamethasone 0.6 mg/kg orally is effective treatment for children with mild croupPhamacology lect5 By Dr Barakat Shahin55

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Post Extubation Stridortypically occurs in people who have been intubated for several daysadministered at least 12 hrs prior to extubation for patients who have been intubated for more than 3 days or who are at increased risk of reintubation

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multiple doses of steroids reduce the risk for edema and reintubation, whereas a

single dose only shows a non significant trend toward effectivenesssteroids were most useful when administered in high risk patients, as determined by a cuff-leak test, and when the steroids were

administered at least 4 hrs

before

extubation

. Benefits were less clear

if patients

were not selected according to risk

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Epidural Steroid Injection (ESI)treat back pain (mainly due to nerve root irritation) in patients with a wide variety of spine pathologies including radiculopathy, spinal stenosis, diskspace narrowing, annular tears, spondylosis, spondylolisthesis,vertebral fractures, and postlaminectomy syndromeeffective alternative to surgical treatment and is best for patients with lumbar disc disease who have not improved after 4 weeks of conservative medical therapy

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Steroids in Traumatic SpinalCord Injuryremains controversial for cord injuries because improvement is minimal and difficult to documenthigh dose methyl prednisolone with an IV bolus of 30 mg/Kg followed by 5.4 mg/kg/hr infusion for 23 hrs

Clinicians should consider AI in patients with spinal cord injury receiving glucocorticoidsPhamacology lect5 By Dr Barakat Shahin59

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Sepsis and Steroidsevere sepsis or in septic shock were found to have occult or unrecognized adrenal insufficiency incidence may be as high as 28% in seriously ill

patientssignificantly higher rate of success in withdrawal of vasopressor therapymay result from suppression of overexuberant and dysregulated immune responses, suppression of inflammatory responses through a variety of mechanisms, and upregulation of adrenoreceptor

function

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Nosocomial infection, reactivation of latent infection, hyperglycaemia, bone metabolism, and psychosis as well as intensive care associated paresis must also be consideredThe current evidence does not support the use of hydrocortisone doses above 200 mg/dayPhamacology lect5 By Dr Barakat Shahin

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Steroids and There Applications asAnalgesic Adjunctsmediated by anti-inflammatory and immune suppressive effect

decreased production of various inflammatory mediators that play a major role in amplifying and maintenance of pain perceptionDexamethasone microspheres have been found to prolong the block duration in animal and human studies, and adding methylprednisolone to local anesthetic increases the duration of axillary brachial block

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glucocorticoids act on the prostaglandin system differently than NSAIDs and have other antiinflammatory effects, there may be better analgesia when glucocorticoids are added to NSAIDsPhamacology lect5 By Dr Barakat Shahin

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Adverse Drug Effects ofSteroid Supplementation

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Risks with Short-Term (Perioperative) Supplementation aggravation of hypertension

fluid retention stress ulcers & GI bleeding psychiatric disturbances delayed and abnormal wound healing hypokalemia

osteoporosis

increased

susceptibility to

infection

decreased glucose

tolerance

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Risks with Long-Term Supplementation HPA axis suppression hypokalemia

metabolic alkalosis oedema weight gain hyperglycemia redistribution

of body fat

buffalo hump

proximal skeletal muscle

myopathy

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