codeine

Metabolism of codeine is highly variable

Max 4 gacetaminophen daily

Landmark Emergency Medicine Trials

Trial Name Reference Clinical Trial Details

DIVERTICULITIS

DINAMO AnnSurg.2021:274|5):e435 Title:Efficacy and Safety of NonantibioticOutpatient Treatmentin Mild Acute Diverticulitis

Purpose:fo support that uncomplicated acute diverticulitis can be treated using outpatient care withoutantibiotics.

Methods:A Prospective, multicentre, open-label,RCT trial was conducted with 480 patients diagnosed with uncomplicated mild diverticulitis

using CT.Patients were randomized to the classical treatment with antibiotics and without antibiotics.The outcome of interest was hospital

admission.

Results:14/238 patients treated with antibiotics were admitted to hospital and 8 /242 patients treated without antibiotics were admitted to

hospital.

Conclusion:The results show that treatment of uncomplicated mild diverticulitis can be effectively conducted as an outpatient without use of

antibiotics.

CONCUSSION

NCT03S64210 JAMA Pediatr.

2021;175(11):1124

Title:Effect ofScreen Time on Recovery from Concussion

Purpose:To determine if screen time during the first 48 h after injury has an impact on the duration of concussive symptoms.

Methods:RCT consisting of 125 patients who were permitted to engage in unrestricted screen time or advised to abstain from screen time for 48 h

after injury.The primary outcome of concern was days needed for resolution of concussive symptoms (<3on Post concussive symptom scale).

Results:The treatment group with unrestricted screen time had a significantly longer recovery time when compared to the group advised to

abstain from screen time - 8 d and 3.5 d, respectively.

Conclusion:The results of this study show that abstention from screen time during the first 48 h may reduce the duration of concussive symptoms.

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References

American College olEmergency Physicians. Clinical policy lorthe initial approach to patients presenting with altered mentalstatus.Ann Emerg Med 1999:33{2):2S12SO.

AndradeJG. AguilarM.AUemaC. elal.The 2020Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelinesfor the Management olAtrial fibrillation.Can JCardio. 2020 Dec

1:36(12):1847-948.

Andrcoli IE.Carpenter Ci.Cecil Rl.el al.Andrcob and Carpenter'

sCecil essentials ol medicine.81h ed.Philadelphia: Saunders:2010.

Alii ME.Brambrink AM. Healy 0W, elal.Success of intubation lescue techniques alter failed direct laryngoscopy madulls: A retrospective comparative analysisfrom the multicenler perioperative outcomes group.

Anesthesiology 2016:125:656 666.

Bachmann LM. Kolb E.Roller Ml.el at. Accuracy olOttawa ankle rules toexclude fractures of theankfe and mid - foot:systematic review. BMJ 2003:326:411.

Barash PC. Cullen Bf.Sloellmg RK.Clinical anesthesia.5th cd.Philadelphia:lippincotl: 2005.

Bauer G.Pyne J. Ftancino MC.et al.SuKidafily among trans people in Ontario: Implicationsfor social work and social lustice/lasulcidabilitc parmi les personnesIransen Ontario:Implicationsen tiavailsocial ct en

lustice sociale.ServSoc 2013:59:35 62.

Barrueto Jr F. Beta blocker poisoning [Internet]. UploDatc: 2018[updated 2017 April11; cited 2018 July 30].Available from: hltps://www,uploddle.com/contcnts/beta- blKker-poisOfling.

Boulanger J, Lindsay M.Gubitc 0. el al.CanadianStroke Best Practice Recommendationslor Acute Stroke Management: Prehospital. Emergency Department, and Acute Inpatient Stroke Caie.6th Edition. Update 2018.

IntJ Stroke. 2018 Dec1:13(91:949-84.

Boyer EW,Serotonin syndrome (serotonin toxicity)[Internet]. UploDatc:2018 [updated 2018 March 12:cited 2018 July 30]. Available from: htlps://www.uploddle.com/contents,

soiolonin syndrome serotonin toxicity.

Bullcr HR. Prins MH. Lensin AWA. et al.Oral tivaroxaban lor the treatment of symptomatic pulmonary embolism. NEJM 2012:366:1287-1297.

Bullcr HR. Prins MH. lensin AWA. ct al.Oral tivaroxaban lor the treatment of symptomatic venous thromboembolism. NEJM 2010:363:2499 2510.

Chandy 0. WeinhouseGL Drownmg (submetsion injuries)[Internet]. UploDatc: 2022|updated 2021August 19: cited 2022 May17].Available from: htlps:/ /www.uptodate.com contents, drowning submeision- injuries.

Channa AB. Video laryngoscopes.Saudi JAnaesUi 2011;5(4):357 359.

Chu P.Blunt abdominal trauma:current concepts.Curt Orthopaed 2003;17|4):254 259.

DarganP,WallaceC,JoitesAl.An evidence based flowchart toguide the management ol acute salicylate (Aspirin ( overdose.Emerg Med J 2002:1913);206 209.

Oesimone ME.Weinstock RS.Hypoglycemia.[Updated 2018 May 5].In:Femgold KR. Anasvalt B, Boyce A , et al.,editors.Endotexl [Internet].South Dartmouth (MA): https:7Twmv.endoteit.otg/,lnc.:2000-.Available from:

https://www.ncbi.nlm.nih.gov.

|

books/N8K2791377

Duchesne JC.HuntJP.Wahl G.etal.Reviewof current blood transfusionsstrategiesina mature level I trauma centre:were we wrong lor the last 60 years? J Trauma 2018:65(21:272-276.

Ell iott WJ. Hypertensive emergencies.Cnt CareQm 2001:17[2):435-451.

FarkasJD.Long B.KoyfmanA.etal.BRASH Syndrome:Bradycardia.Renal Failure, AV Blockade,Shock,and Hyperkalemia.J Emerg Med.2020 Aug:59(2):216-223.

FramptonA.Reporting of gunshot wounds bydoctorsin emergency departments:A duty or a right? Some legaland ethical issuessurrounding breaking patient conridenhality.Emerg Med J 2005:2212):84 86.

Hanania NA.Zimmerman JL.Accidental hypothermia.CrrtCare Oin.1999 Apr;15(2):235-49. doi:10.1016i

's0749-0704(05]70052-x.PMID:10331126.

Jaff MR.McMurtry MS.Archer Sl.et al.Management ol massrve andsubmassive pulmonary Eembolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension.Circulation. 2011 Apr

26;123(16):1788-830.

Jalota R.Sayad E.Tension Pneumothorax.[Updated 2021Jan 23].In:StatPearls[Internet], Treasure Island|Fl):SlatPearls Publishing:2021Jan-.Available from:htlps-J/vmvr.ncbi.nlm.nih.gov/books;NBK559090l

.

Kalant H,Roschlau WH.Principles of medical pharmacology.7lhed.Hew York:Oxford University Press,2006.

Keim S.Emergency medicineon call.New York:McGraw Hit;2004.

Kline JA.Mitchell AM.KabrhelC.etsf.Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.J Ihromb Haemost 2004:2(8):1247-1255.

LeSauxH.Guidelinesfor the management of suspected and confirmed bacterial meningitis in Canadian children older than one month of age [Internet].Canadian Paediatric Society:2014 Mar 3[ig>dated 2018 Dec 20:

cited 2020Jun 18].Available from:https://www.cps.ca/en/documents'position/management- of-bacterial-meningitis.

LeSauxH.RobinsonJL.Managemerit of acute obbsmediain children six months ol age and older [Internet],Canadian PaediatricSociety;2016 Feb 5[cited 2020Jun18].Available lrom:hltps://www.cps.ca/en/

docu ments/position,1

acute-oti tis- media.

Lotfollahradeh S.Seligson MI.Marx WH.Aorbc rupture.[Updated 2021 Dec 3].In:StatPearls[Internet].Treasure Island (FL):StatPearls Publishing; 2022 Jan-.Availablefrom:hUpsJ/www.ncbi.nlm.nih.gov/books/

NBK459138/

Marx J. Hockberger R, Walls R.Rosen’s emergency medicine:concepts and clinical practice.8th ed. Philadelphia:Saunders/Mosby, 2013.

Mokin M.Ansari SA. McTaggart RA.etal.Indicationsfor thrombectomy in acute ischemic strokefrom emergent large vessel occlusion (ELV0):report of the SKIS Standards and GuidelinesCommittee.J Neuromterv Surg.

2019 Mar 1:11|3):215-20.

Moscati RM,Mayrose J.Reardon RF.et al.A multicenler compaiissnof tapwater versussterile saline for wound irrigation. Acad Emerg Med.2007 May;14[5):404-9.

Munro PI.Management edampsiain the accident and emergency department. Emerg Med J 2000;17(1):7-11.

Nilsson 1.Johannesson E. ForbergJU elal. Diagnostic accuracy of the HEART Pathway and EDACS ADP when combined with a 0- hour/1-hour hs- cTnT protocol for assessment of acute chest pain patients. Emerg Med J.

2021 Nov 1;38(11):808-13.

Osmond MH, Klassen TP.WeiIs GA,etal.CATCH: a clinical decision rule for the use ol computed tomography in children with minor head injury.CMAJ 2010:132(4):341 348

Panchdl AR . Bartos JA.CabanasJG. etal. Part 3:Adult Basic and Advanced life Support: 2020 American Heart Association Guidelinesfor Cardiopulmonary Resuscitation and EmergencyCardiovascular Care.21Oct 2020.

Circ.2020;142:S366-S468.

Passman R. Radish A. Polymorphic ventricular tachycardia,long 0-1syndrome,and torsades de pointes. Med Clin N Am 2001:85(2):321.

Paritel PM. van der Zijdcn I. GaudknoS.cl al.Trauma ol the spine and spinal cord:Imaging strategies. Eur Spine J 2010;19:8-17.

Perry JJ.Sliell IG.Siviloltr MA. ct al.Clinical decision rulesto rule out subarachnoid hemoirhage for acute headache. JAMA 2013:310(12):1248 1255.

Perry JJ. Sliell IG.Sivilotti MA, ct al.Sensitivity ol computed tomography performed within six hours of onset of headache lot diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ 2011:343:d4277.

Righini M. Van EsJ, Den Ex ter PL,etal.Age adjusted d dimciculoll levelslorulc out pulmonary embolism: The AOJUST- I

’E Study. JAMA 2014;311|11):11171124.

Roberts JR. Hedges JR.Clinical proceduresin emergency medicine. 5lhed. Philadelphia:Saunders. 2009,

Robinson Jl. Finlay JC. Lang ME. el at.Ur maty tract infection in infants and children: Diagnosis and management [Internet].Canadian Paediatric Society: 2014 Jun13|updatcd 2020 Jan 1; cited 2020 Jun18], Available

from: htlps://www.cps.ca/en/documents/position/urinaiy-tiact-inlections-ln -childien.

Rodrigue!RM. Greenwood JC. Nucklon TJ. etal.Compansonof qSOFAwilh current emergency department tools lor scieeningol patients with sepsis lor critical illness. EmergMcd J. 2018 Jun;3S|6):350 356. doi:

10.1136/emermed 2017-207383. Epub 2018 May 2. PMID: 29720475.

Sabatine MS.Cannon CP,Gibson M.etal.Addition of clopidogrclloAspiiin '

and fibrinolytic therapy loi myocardial infarction with Si-segment elevation. NEJM 2005:352(2):1179 1189.

Sarlelli M, Kluger Y.Ansaloni l.et al.Raising concerns about theSepsis 3definitions.World J Emerg Surg. 2018:13:6.Published 2018Jan 25.d«:10.1186/s13017 018 0165-6.

Schulman S, Kearon C. Kakkar AK. etal.Extended use of dabigatran.warfarin, or placebo in venous thromboembolism. NEJM 2013:368:709-718.

Shaker MS. Wallace DV.Golden DBK.et al.Anaphylaxis a 2020 ptacbce parameter update,systematic review.andGrading of Recommendations.Assessment.Oevelopmentand Evaluation (GRADE ) analysis.J AllergyClin

Immunol. 2020Apr;145|4):1082-123.

Sigmon DF.An J. Nasogastric tube.[Internet].[Updated 2022 May 22). In:StatPearls[Internet].Treasure Island (FL):StatPearls Publishing:2022 Jan .Available front https:/ /www.ncbi.nlm.nih .gov,lbooks' NBK556063'

Singer M,Oeutschman CS.Seymour CW.etal.The Third InternationalConsensus Definitionsfor Sepsis and Septic Shock (Sepsis-3).JAMA. 2016:315(8):8O1-810. doi:10.1001/jama.2016.0287.

Soar J, Pumphrey R.Cant A.etal.Emergency treatmentof anaphylactic reactions:guideline for healthcare providers.Resuscitation 2008;77(2):157-769.

Shell IG,WellsGA,Vandemheen KL.etal.The Canadian CT head rule for patients with minor head injury,lancet 2001:357(92661:1391-1396.

Shell IG,WeiIs GA,Vandemheen KL.etal.TheCanadian C-spine rule for radiography inalert and stable trauma patients.JAMA 2001:286(15):1841-1848.

Thompson M.Street Opioid Resuscitation Recommendations:For Pre-Hospital and Hospital Care [Internet]. Ontario Poison Centre 2018 Aug1[cited 2020 Jun18].Available from:http://www.ontariopcksoncentre.ca/

pdf/76897-Hopsitalg uidelines_ naloxone _ Aug18.pdf.

Tintinalli JE, KelenGE.Emergency medicinecacomprehensivestudy guide.7th ed. NewYork:McGraw-Hill; 2004.

Topjian AA , Raymond IT.AtkinsD.etal.Part 4:Pediatric Basic andAdvanced Life Support: 2020 American Heart Association Guidelinesfor Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.21 Oct

2020.Circ.2020:142:S469-S523.

Tran A.YatesJ,LauA.etal.Permission hypotension versus conventional resuscitation strategiesin ad ult trauma patientswith hemorrhagic shock:Asystemabc reviewand meta-anatysis ol randomized controlled trials.

J Trauma Acute CareSurg 2018:84(5):802-808.

Varon J, Marik PE.The diagnosis and management of hypertensivecrises.Chest 2000;118:214-227.

Vidt DG.Emergency room management of hypertensive urgencies and emergencies.J Clin Hypertens 2004;6:520-525.

Walls RM.Hockberger RS.GauscheHill M.Rosen'semergency medicine:concepts and clinical practice.9th ed.Philadelphia:Saunders/Elsevier; 2018.

Warden CR.Zibulewsky J.Mace S.el al.Evaluation and management of febrile seiiuresin the out-of-hospital and emergency departmentsettings.Ann Emerg Med 2003:41(2):215-222.

Wells PS. Anderson DR. Rodger M.elal.Derivation of a simple clinical model to categorize patients probability of pulmonary embolism:increasing the models utility with IhesimpfiRED d-dimer.J Ihromb Haemost

2000;83:416-420.

Wells PS.Anderson DR. Rodger M.elal.Excluding pulmonary embolism althe bedside without diagnostic imaging:management of patients with suspected pulmonary embolism presenting to theemergency

department by using asimple clinical model.Ann Intern Med 2000:135(2):98-107.

YaoX.Skinner R, McFaull St.etal.At-a-glance:Injury hospitalizations in Canada 2018/19.[Internet],Available from https://doi.Org/10.24095/hpcdp.40.9.03

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E Endocrinology

Miski Dahir, Maria Sarny, and Claire Sethuram, chapter editors

Karolina Gaebe and Alyssa Li, associate editors

Wei Lang Dai and Camilla Giovino, HBM editors

Dr. Angela Assal, Dr.Jeremy Gilbert, Dr.Adrian Lau, and Dr. Maria Wolfs,staff editors

Acronyms

Basic Anatomy Review

Major Endocrine Organs

Dyslipidemias

Overview of Lipid Transport

Primary Dyslipidemias (rare)

Secondary Dyslipidemias

Dyslipidemia and the Risk for Coronary Artery Disease

Treatment of Dyslipidemias

.E2 Calcium Homeostasis ...

„ Hypercalcemia

Hypocalcemia

E3

Metabolic Bone Disease

Osteoporosis

Osteomalacia and Rickets

Renal Osteodystrophy

Paget’s Disease of Bone

Male ReproductiveEndocrinology

Androgen Regulation

Tests of Testicular Function

Hypogonadism and Infertility

Erectile Dysfunction

Gynecomastia

Female ReproductiveEndocrinology.

Paraneoplastic Syndrome

Common Medications

Diabetes Medications

Thyroid Medications

Metabolic Bone Disease Medications

E18 Adrenal Medications

Landmark Endocrinology Trials.

References

E42

E46

E51

Disorders of GlucoseMetabolism..

Overview of Glucose Regulation

Pre-Diabetes (Impaired Glucose Tolerance/Impaired Fasting

Glucose)

Diabetes Mellitus

Treatment of Diabetes

Acute Complications

Macrovascular Complications

Microvascular Complications

Other Complications

Hypoglycemia

Metabolic Syndrome

E7

E55

E56

E57

Obesity.

E62 Pituitary Gland.

Pituitary Hormones

Growth Hormone

Prolactin

Thyroid Stimulating Hormone

Adrenocorticotropic Hormone

Luteinizing Hormone and Follicle Stimulating Hormone

Antidiuretic Hormone

Pituitary Pathology

Thyroid.

Thyroid Hormones

Tests of Thyroid Function and Structure

Thyrotoxicosis

Graves’ Disease

Subacute Thyroiditis (Thyrotoxic Phase)

Toxic Adenoma/Toxic Multinodular Goitre

Thyrotoxic Crisis/Thyroid Storm

Hypothyroidism

Hashimoto’s Thyroiditis

Myxedema Coma

Non-Thyroidal Illness (Sick Euthyroid Syndrome)

Thyroid Nodules

Thyroid Malignancies

Adrenal Cortex

Adrenocortical Hormones

Adrenocortical Functional Workup

Mineralocorticoid Excess Syndromes

Cushing’s Syndrome

Congenital Adrenal Hyperplasia

Hyperandrogenism

Adrenocortical Insufficiency

Adrenal Medulla

Catecholamine Metabolism

Pheochromocytoma/Paraganglioma

Disorders of Multiple Endocrine Glands.

Multiple Endocrine Neoplasia

....E66

E24

E33

..E40

E41

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Acronyms

hemoglobin Ate

abdominal aortic aneurysm

antibodies

ABCA1 ATP-binding cassette

transporter A1

ACEI angiotensin converting enzyme

inhibitor

albumin-creatinine ratio

antidiuretic hormone

anion gap

ApoA1 alipoprotein A1

ApoB apolipoprotein B

ApoC2 alipoprotein C2

ApoE4 alipoprotein E4

ARB angiotensin receptor blockers

absolute risk reduction

arginine vasopressin

blood glucose

BMD bone mineral density

CAH congenital adrenalhyperplasia

CHO carbohydrates

creatine kinase

CKD chronic kidney disease

CMV cytomegalovirus

CNS central nervous system

CrCI creatinine clearance

CVD cardiovascular disease

DDAVP desmopressin (1-deamino8-D-arginine vasopressin)

A1c DHEA dehydroepiandrosterone

diabetes insipidus

DKA diabetic ketoacidosis

OXM dexamethasone

DVT deep veinthrombosis

ECF extracellular fluid

ECFV extracellular fluid volume

FFA free fatty acids

FNA fine needle aspiration

FPG fasting plasma glucose

GFR glomerular filtrationrate

GHRH growth hormone releasing

hormone

glucagon-like peptidel

gonadotropin releasing

hormone

hemoglobin

hCG human chorionic gonadotropin

HDL high density lipoprotein

HHS hyperosmolar hyperglycemic

state

HLA human leukocyte antigen

HMG-CoA3-hydroxy-3-methylglutaryl

-

coenzyme A

HPA hypothalamic pituitary adrenal

Hs-CRP highly-sensitive C-reactive

protein

HVA homovanillic acid

ICF intracellular fluid

IDL intermediate density lipoprotein PTU

impaired fasting glucose

insulin-like growth factor 2

impaired glucose tolerance

juxtaglomerular apparatus

lecithin-cholesterol

acyltransferase

low density lipoprotein

low density lipoproteincholesterol

propylthiouracil

RAAS renin-angiotensin-aldosterone

system

radioactive iodine

RAIU radioactive iodine uptake

RANKL receptor activator of nuclear

RH releasing hormone

factor-xB ligand

RRR relative risk reduction

AAA Dl IFG

Ab IGF2

IGT RAI

JGA

LCAT

ACR LDL

ADH LDL-C

AG SA secondary aldosteronism

low density lipoprotein receptor SGLT2i sodium/glucose cotransporter-2

inhibitor

LDL-R

LP lipoprotein

lipoprotein (a)

LPL lipoprotein lipase

MEN multiple endocrine neoplasia T4

methimazole

MTC medullary thyroid cancer

normal saline

OGTT oral glucose tolerance test

primary aldosteronism

PAD peripheral arterial disease

PCOS polycystic ovary syndrome

PCSK9 Proprotein convertase subtilisin/ TSI

kexin type 9

POMC pro-opiomelanocorticotropin

PRL prolactin

PTH parathyroid hormone

PTHrP parathyroid hormone-related

protein

LP(a) SHBG sex hormone-binding globulin

T3 triiodothyronine

thyroxine

TBG thyroid-binding globulin

TC total cholesterol

TG triglycerides

TgAb thyroglobulin antibodies

TPOAb anti-thyroid peroxidase

antibodies

TRAb TSH receptor antibodies

thyroid stimulating

immunoglobulin

VIDl very low density lipoprotein

VMA vanillylmandelic acid

WC waist circumference

GLP-1

GnRH

ARR MMI

AVP Hb

BG NS

PA

CK

Basic Anatomy Review

Major Endocrine Organs

HYPOTHALAMUS PITUITARY GLAND

Corticotropin-RH ICRHI

Gonadotropin-RH (GnRH)

Thyrotropin-RH (TRH)

Growth hormone-RH(GHRH)

Antidiuretic hormone (ADH)*

Oxytocin*

Anterior pituitary

Growthhormone (GHI

Prolactin (PRL)

Thyroid-stimulating hormone (TSH)

Luteinizing hormone ILH)

Follicle-stimulating hormone (FSH)

Adrenocorticotropic hormone (ACTH)

Posterior pituitary

Antidiuretic hormone (ADH)*

THYROID GLAND

Triiodothyronine (T3I

Thyroxine(T4)

Oxytocin*

PARATHYROID GLANDS

Parathyroid hormone (PTH)

ADRENALGLAND

Cortex

Aldosterone

Cortisol

Androgens

Medulla

Catecholamines

PANCREAS

Insulin

Glucagon

Somatostatin

OVARIES

Estrogen

Progesterone TESTES

Testosterone

’ADH and oxytocin are produced in the hypothalamus and storedinthe posterior pituitary gland © Stefania Spano 2012

Figure1.Endocrine system

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Dyslipidemias

Definition

• metabolic disorders characterized by elevations of fasting plasma LDL-C and/or TG, and/or low HDLcholesterol

Overview of Lipid Transport

• lipoproteins are spherical complexes that consist of a lipid core surrounded by a shell of water-soluble

cholesterol, apolipoproteins, and phospholipids

• lipoproteins transport lipids within the body

• apolipoproteins serve as enzyme cofactors, promote clearance of the particle by interacting with

cellular receptors, and stabilize the lipoprotein micelle

Table 1. Lipoproteins

Lipoprotein Function

Chylomicron

VIOL

Transports dietary TG from gut loadipose tissue and muscle

Transports hepatic synthesized TG from liver to adipose tissue and muscle

Product of hydrolysis of TG inVLDLby lipoproteinlipase resulting in depletion of TG core

Enriched incholesterol esters

Cholesterol rich atherogenic particles

Formed by further removal of residual TG from I0L core by hepatic lipase

Transports cholesterol from peripheral tissues to liver

Acts as a reservoir for apolipoproteins

IDL

LDL

HDL

CW

CM

EXOGENOUS PATHWAY

Dietary

ENDOGENOUS PATHWAY

=

TGs Oxidized LDLoccurs in

subendothelial space of

arterial bloodvessels

3

Dietary Bile Acids

Cholesterol =a

Endocytosis through

LDLReceptor

A A

*

MACROPHAGE

[h

Cholesterol

absorption

inhibitors

SMALL

BOWELv

Bile acid Acetyl-CoA |

X

~

| sequestrants

"T1

(resins) I

HMG-CoA 1

Statin

W

Statin m LIVER EXTRAHEPATIC

TISSUES

Cholesterol

N

— Endogenous B-100 FOAM I

cholesterol %

- apoE \ f

- TG

CELL @

Dietary

cholesterol

I

JUNiacin

TOLIVER Endocytosis through

Remnant Receptor

EARLY

ATHEROSCLEROSIS

C-ll Hepatic Lipase

.1

B-48 C-ll AI^AII

E

^

f

-48 E

^

B-IDO E

^

B-1!

I

Chylomicron N

^**

,,

*

, jVLDL T'DL

\ _ TRemnant l

B

^

BCAPILLARY^

BB B

^

BCAPILLARY^

BB

Fibrate I -I- I I Fibrate I + I I

FreeFatty Acids LPLipase* 4

—* Free FattyAcids

degrades TG

HDL

PLASMA LCAT

IIDL givesphospholipids and

TG toHDLandreceives

cholesterol esters fromHDL)

ICholesterol

Triglyceride

*LP Lipase requires activationbyApoC-ll

LP Lipase*

degradesTG i i

Adipose Tissue and Muscle Adipose Tissue andMuscle

Figure 2. Exogenous and endogenous biosynthetic lipid pathways

Primary Dyslipidemias (rare)

Definition

• caused by a genetic defect in lipid metabolism

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Table 2. Primary Dyslipidemias

Condition Main Lab Abnormality Mechanism Clinical Features Treatment

t Total cholesterol

» LOL cholesterol

Genetic defect in LDLR (most common).

PCSK9.orApoB

Tendinous xanthomatosis (achilles. patellar. Maximally tolerated Stalin as initial drug

therapy,addition of second drug leietimibe

and/or PCSK9 inhibitor) as second line,third

line for homocygotes is portacaval shunt or

Heterozygotes: premature CAD.50% risk of LDL aplieresis:potential liver transplant

Ml in men by age 30

Homocygotes:manifest CAD and other

vascular disease early in childhood which

can be fatal (in <20 y/o)

Premature coronary heart disease,

xanthelasma,and obesity

Familial

Hypercholesterolemia and extensor tendons of hand)

An autosomal dominant condition that can be Arcus cornealis

homorygous or heterozygous

Impacts liver's ability lo clear LDL from the

circulation

Xanthelasmata

Refer to lipid specialist indrug-resistant

hypercholesterolemia

Familial Combined

Hyperlipidemia

t ApoB Increased production of ApoB-100-

containing lipoproteins from the liver

Statins as initial drug therapy

Addition of ecetimibe and/or PCSK9 inhibitor

if LDLIowering is not achieved. May consider

fibrate if elevated TG

t TGs

t LDL

t LDL Mild defects in multiple genes responsible

for IDLmelabolism: LDL-R.ApoB.ApoE4

Higher risk of cardiovascular disease similar Statins as first line

to familial hypercholesterolemia for patients Use ecetimibe,bile acid sequeslranls. PCSK9

older than 40

Polygenic Familial

Hypercholesterolemia

inhibitor,or nicotinic acid as alternatives (if

not tolerated) or in addition

<10-15% of calories from fat

Supplement with essential fatty acids,fatsoluble vitamins

Plasmapheresis may help individuals with

ApoCx mutation

Hereditary

Chylomicronemia

Familial lipoprotein

lipase deficiency

(e.g.Familial

Hypertriglyceridemia/type

IV familial dyslipidemia)

ApoC2 deficiency

Familial

Hypoalphalipoproteinemia

t TG from excess

chylomicron particles

Lipoprotein lipase deficiency:prevents Presents at infancy (LPL),adolescence to

proper digestion and storage of fats leading adulthood (ApoCr)

to massive accumulation of triglyceride rich Abdominal complaints (pain,

hepatosplenomegaly.pancreatitis)

Lipemia retinalis

Eruptive xanthomata

chylomicron particles

ApoCz deficiency:prevents activation

of lipoprotein lipase leading to massive

accumulation of triglyceride rich chylomicron

particles

Autosomal dominant inheritance of a

mutation in the A8CA1or the ApoAr gene

Reduce the risk of atherosclerosis

with lifestyle changes,management

of concomitant hypercholesterolemia,

hypertriglyceridemia, and metabolic

syndrome if present

Reduce the risk of atherosclerosis

with lifestyle changes,management

of concomitant hypercholesterolemia,

hypertriglyceridemia, and metabolic

syndrome if present

*

HDL cholesterol Premature atherosclerosis

Cerebrovascular disease

Tangier Disease

*

HDLcholesterol Autosomal recessive inheritance of

mutations in the ABCA1gene

Impaired HDL-mediated cholesterol

efflux from macrophages and impaired

intracellular lipid trafficking

Mild hypertriglyceridemia

Neuropathy

Enlarged,orange-coloured tonsils

Premature atherosclerosis

Splenomegaly

Hepatomegaly

Corneal clouding

T2DM

Secondary Dyslipidemias

Definition

• caused by acquired medical conditions or lifestyle factors that affect lipid metabolism

Familial Hypercholesterolemia and

Cardiovascular Risk Calculators

• Risk calculators such as Framingham

and SCORE do not apply to patients

with familial hypercholesterolemia

• Consider all adults with familial

hypercholesterolemia as “high-risk"

Table 3. Etiology of Secondary Dyslipidemias

Hypercholesterolemia Low HDL Hypertriglyceridemia

Endocrine:hypothyroidism (small dense LDL Endocrine:obesity/metabolic syndrome.DM

with T 2DM and obesity,with normal LDL level)

Renal:nephrotic syndrome, CKD

Immunologic:monoclonal gammopalhy

Hepatic:cholestatic liver disease (e.g.primary

biliary cirrhosis)

Nutritional:anorexia nervosa

Drugs:cyclosporin, carbamazepine, steroids

Lifestyle: smoking, obesity

Endocrine:obesity/metabolic syndrome, DM

Renal:nephrotic syndrome.CKD

Drugs:corticosteroids,estrogen,

hydrochlorothiazide,retinoic acid,P-blockers

without intrinsic sympathomimetic action

(ISA), anti-retroviral drugs,atypical

antipsychotics, oral contraceptive pills

Lifestyle:alcohol,high carbohydrate/high

fat diet

Other:pregnancy

Drugs:p-blockers.anabolic steroids

Other:acute infections,inflammatory

conditions

Treatment Effect

• Each 1.0 mmol/L decrease in LDL

corresponds to approximately

20-25%relative risk reduction in

cardiovascular disease

• Statins lower LDL by about 30-40%

• Ezetimibe lowers LDL by about 18%

• PCSK9 inhibitors lowers LDL by

Dyslipidemia about 50% and the Risk for Coronary Artery Disease

•increased LDL is a major risk factor for atherosclerosis and CAD

•increased HDL is associated with decreased CVD and mortality

•moderate hypertriglyceridemia (triglyceride level 2.3-9 mmol/L) is an independent risk factor for

CAD,especially in people with DM and in post-menopausal women

Screening

•screen men and women >40 yr or post-menopausal women

•if the following risk factors are present, screen at any age:

DM

current cigarette smoking or COPD

H'

l

'

N (sBP >140, dBP >90), hypertensive diseases of pregnancy

obesity (BM1 >30 kg/m )

6% Rule

• If the dose of a statin is doubled,

there is approximately a 6% increase

in the LDL lowering efficacy

r n

L J

+

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E5 Endocrinology Toronto Notes 2023

family history of premature CVD or dyslipidemia

clinical signs of hyperlipidemia (xanthelasma, xanthoma, arcus cornealis)

clinical or radiological evidence of AAA

• clinical evidence of atherosclerosis

• inflammatory disease ( rheumatoid arthritis, SLE, psoriatic arthritis, ankylosing spondylitis,

inflammatory bowel disease)

HIV infection on highly active antiretroviral therapy (HAART)

CKD (estimated GPR <60 mL/min/1.73 m -

1

)

• erectile dysfunction

high-risk ethnicity: South Asian, Indigenous peoples

•screen children with a family history of hypercholesterolemia or chylomicronemia

•components ofscreening:

• history and physical examination,lipid panel (total cholesterol, LDL-C, HDL-cholesterol, TG),

non-HOLcholesterol, B(> , eGFR

optional: urine ACR, ApoB

For Statin Follow- Up

• Liver enzymes and lipid profile: liver

enzymes measured at the beginning

of treatment, then once after therapy

initiated.Lipids (once stabilized)

measured annually.Order both if

patient complains of jaundice, right

upper quadrant pain, dark urine

• CK at baseline and if patient

complains of myalgia

• Discontinue statin if CK >10x upper

limit of normal or patient has

persistent myalgia

•ApoB

each atherogenic particle (VLDL, IDL, LDL, and lipoprotein A) contains one molecule of ApoB

serum (ApoB) reflects the total number of particles and may be useful in assessing cardiovascular

risk and adequacy of treatment in high-risk patients and those with metabolic syndrome

• I.p(a) levels may help stratify those at intermediate risk, but is not recommended for routine

measurement (only measured once in a patient'slifetime)

•coronary artery calcium (CAC) may help stratify those at intermediate risk

•CRP levels

2021Canadian Cardiovascular Society

Guidelines on the Management of

Dyslipidemia for the Prevention of

Cardiovascular Disease in the Adult

Can J Cardiol 2021:S0828-282X(21)00165-3

• Patients with clinical atherosclerosis.

AAA, LDL-C £5.0 mmoLL, and most

with diabetes or CKD should be

started on statin therapy

• Lipid/llpoprotein screening Is

recommended in patients >40 yr or at

any age for those at increased risk

• Non-HOL cholesterol or Apo8

are preferred to LDL-C aslipid

parametersfor screening in patients

with TG >1.5 mmol/L

• LP(a) should be measured once in a

person'

slifetime as part of initial lipkl

screening to assess cardiovascular

highly sensitive acute phase reactant (non-specific)

may be clinically useful to identify those at a higher risk of CVD than predicted by the global risk

assessment

CVD Risk Assessment

•Framingham Risk Score ( IRS): I0 yr risk of major CVD event.Calculated based on gender, age, total

cholesterol, HDL-cholesterol,sBRand smoking (>20%: high-risk; 10- 19%: moderate risk; <10%:lowrisk)

•Reynolds Risk Score: 10 yr risk of major CVD event. Calculated based on age,sBP, total cholesterol,

HDL-cholesterol, high sensitivity CRP,family history of Ml

Treatment of Dyslipidemias

Approach to Treatment

risk

• Lipid-lowering therapy should be

intensified with ezetimibe and/or

PCSK9 inhibitors in patients with

LDL-C remaining >1.8 mmol/L (or nonHDL cholesterol >2.4 mmol/L or ApoB

20.7 g/l) on a maximally tolerated

statin dose

Primary Prevention

Low-Risk Intermediate- Risk High- Risk

FRS <10% FRS 10-19 9% and FRS >20%

LDL C>

_3 5mmol/L or

Non HDL C >$ 2mmol/L or

ApoB > 1.2 g/Lor

Mon>50 and women >60 withone additional risk

factor ,