cardio diabetic pres 3

Presented by : Mohammad Maddah –R3

Why?

u  The metabolic syndrome is a cluster of interrelated risk factors for the development of Cardiovascular disease CVD

u  Once the criteria of metabolic syndrome is there, the prevalence of coronary heart disease (CHD) is doubled.

u  CHD Risk Increases with Increasing Number of Metabolic Syndrome Risk Factors .

CHD Risk Increases with Increasing Number of Metabolic Syndrome Risk Factors

Sattar et al, Circulation, 2003;108:414-419 Whyte et al, American Diabetes Association, 2001 Adapted from Ridker, Circulation 2003;107:393-397

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1.52

2.53

3.54

4.55

5.56

6.57

one two three four

Rel

ativ

e R

isk

Cardiovascular risk factors

BMI = body mass index; TC = total cholesterol; DM = diabetes mellitus; HTN = hypertension. Wilson PWF et al. Circulation. 1998;97:1837–1847.

0 2 4 6 8

10 12 14

HTN DM Smoking BMI >27 TC >220

Single Risk Factors

Multiple Risk Factors

Odd

s ra

tios

Smoking + BMI

2

Smoking + BMI

+ TC >220

3

Smoking + BMI

+ TC >220 + DM

4

Smoking + BMI

+ TC >220 + DM + HTN

5 The Framingham Study

u  Which one of the following meds cause fatal myocarditis and cardiomyopathy:

1.  Ziprisdone

2.  Risperidone

3.  Clozapine

4.  Sertraline

5.  citalopram

u  What is the average range of QTC in female?

1.  440 msec.

2.  470 msec

3.  490 msec

4.  500 msec

Case

u  A 62-year-old woman is brought to the emergency department by paramedics for chest pain that has been present for 5 hours. Medical history is notable for DYSLIPEDIMIA . Medications include atorvastatin, and aspirin.

u  On physical examination, she appears comfortable. She is afebrile, BP is 190/90 mm Hg, PR is 88/min and respiration rate is 16/min. Cardiac examination shows no murmurs, extra sounds, or rubs. The lungs are clear and pulses are equal bilaterally. Neurologic examination is normal.

u  The electrocardiogram shows 2-mm ST-segment elevation in leads I,V2, and V3.

u  A coronary catheterization Iis done witin 1 hour.

u  Current medications are aspirin, clopidogrel, metoprolol, atorvastatin, and sublingual nitroglycerin.

u  4 weeks later patient started to be isolated , low mood with frequent guilt feeling and death wishes

u  according to the family she had these sx for the last 2 weeks.

u  How will you appaoach this case?

HX,MSE,IX,File review,D\D.

u  What is your management?

u  Will you start medications? Why?

u  How will you follow up?

u  In patients with CHD, the prevalence of major depression is nearly 20% and the prevalence of minor depression is approximately 27%.

u  Francois Lesperance 25% of pt had an MI also gave hx of MDD.

u  7% occurred in the year prior to the MI.

u  15% started after the MI.

u  MDD rates higher around 6 months following MI and gradually decrease around 1 year.

u  Detailed hx and physical examination.

u  Detailed meds HX

u  rehabilitation programs include exercise training, risk factor modification, education, medical surveillance, vocational rehabilitation, and psycholog- ical counseling

Approach

u  Earlier prescription of antidepressants in the hospital (in coordination with cardiology) is recommended in the following circumstances (Huffman et al. 2004).

u  Depression with suicidal ideation .

u  Development of sx during hospitalization.

u  History of severe depression.

u  Severe depression that inhibits participation in rehabilitation or self-care

u CREATE u SADHART u  ENRICHD u MIND-IT

u  In SADHART, the depression scale ratings did not improve significantly in the total study population with sertraline therapy compared with placebo [95]. However, the subset of patients who had a history of major depression prior to their MI did have significant improvements in depressive symptoms with sertraline.

Clinical Management Only n=142

Clinical Management + IPT n=142

Citalopram

n=67

Placebo

n=75

284 Patients with CAD from 9 Canadian academic centers, meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression > 4 weeks duration and

had baseline 24-item Hamilton Depression Rating Scale (HAM-D) > 20 2X2 Factorial. Randomized. Controlled. Parallel-Group. Double-blinded.

Mean age 58.2 years, 25% women

!  Primary Endpoint Change in 24-item HAM-D from baseline. !  Secondary Endpoint: Self-reported Beck Depression Inventory II (BDI-II)

score

12 weeks

R

R R

Citalopram

n=75

Placebo

n=67

Lespérance et al., JAMA 2007; 297(4): 367-79

u  In CREATE, citalopram or placebo [ 89]. After 12 WK of therapy, the citalopram group had a statistically significant greater decline in a standard measurement of depression compared with placebo.

u  However, the United States FDA issued warnings that citalopram causes dose-dependent QT interval prolongation that can lead to arrhythmias, and thus recommends avoiding citalopram in patients with recent acute MI.

u  compares psychotherapy (CBT) to treatment-as-usual in patients with depression and/or reduced social support following an MI.

u  The intervention did not increase event free survival.

u  improved depression and social isolation.

u TCAs: u Orthostasis, Type 1A antiarrhythmic

effects u Generally safe in selected pts with

stable ht.disease u Contraindicated after MI

u SSRIs: u Safety shown for sertraline in SADHRT

and citalopram in CREATE u Uncommonly cause bradycardia

u Mirtazapine: Safety shown in MIND-IT

u Stimulants: generally safe u But there is a Black Box warning; PDR

says contraindicated in structural heart disease.

u No ↑ CV risk in minors. N Engl J Med 2011; 365:1896

u No ↑ CV risk in adults? Am J Psychiatry 2012; 169:178

(small absolute↑ in VT, RR 1.8 but inverse dose relationship

SSRIs and bleeding

SSRIs and bleeding

u  Risk is increased still further in those also receiving aspirin, NSAIDs or oral anticoagulants.

u  Try to avoid SSRIs in patients receiving NSAIDs, aspirin or oral anticoagulants or with history of cerebral or GI bleeds.

u  If SSRI use cannot be avoided, monitor closely and prescribe gastroprotective proton pump inhibitors.

u  ECG monitoring is essential for all patients prescribed antipsychotics. An estimate of QTC interval should be made on admission to in-patient units (note that this is recommended in the NICE schizophrenia guideline13) and at least yearly thereafter.

u  Measure QTC in all patients prescribed antipsychotics.

u  On admission :if previous abnormality or known additional risk factor, at annual physical health .

u  Consider measuring QTc within a week of achieving a therapeutic dose of a newly prescribed antipsychotic that is associated with a moderate or high risk of QTc prolongation or of newly prescribed combined antipsychotics.

u  In general, a QTc of 440 ms is considered the average upper limit of normal.

u  • An interval of 500 ms or more is a signal to change the treatment method (Glassman 2002).

u  antipsychotics block cardiac potassium channels and are linked to prolongation of the cardiac QT interval .

u  440msec for men, 470msec for women.

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u  Hypotension: avoid low-potency agents and clozapine (due to α1-adrenergic blockade)

u  All antipsychotics may ↑ QT u  Higher risk with pimozide, thioridazine, mesoridazine,

droperidol, and ziprasidone

u  Lowest risk with aripiprazole and olanzapine

u  Screen for already ↑QT, other QT prolonging drugs, personal or family Hx of unexplained syncope or sudden death

u  Estimated rates of clozapine-associated myocarditis range from 1/500 to 1/10,000 .

u  Eighty-five percent of the cases develop during the first 2 months of therapy.

u  Usually a dilated cardiomyopathy .

u  Benzodiazepines, buspirone—safe

u  Mood stabilizers u  Lithium generally safe at nontoxic doses, but avoid in heart

failure

u  Valproic acid generally safe

u  Cholinesterase inhibitors u  May have vagotonic effects on the heart (e.g. bradycardia)


u  What is the average range of QTC in male?

1.  440 msec

2.  470 msec

3.  490 msec

4.  500 msec

u  35 YO male schizopherinic pt well managed on amisulpride 600 mg once daily ECG showed flatened T - wave with QTC 460 msec:

1.  Reduce dose and refer to cardiologist.

2.  Change to olanzpine.

3.  No need for intervention.

4.  Reassure the pt and repeat ECG later.

u  48 YO male 6 weeks post MI and recent hemorrhigic stroke on aspirin presented with Depressive SX :

1.  Start on 20 mg of citalopram.

2.  Start on lorazepam 1mg then taper down.

3.  No need for intervention.

4.  Reassurance as these SX will fade by time.

5.  Start on mirtazapine 30 mg .

Case

u  39 YO female pt k\c of schizopherenia well controlled on halloperidol 5 mg twice daily, cogentin 2mg once daily admitted on the medical ward as case of MI recently.

u  The medical team change the AP to quetiapine 200 mg twice daily and the regimen of the MI meds including aspirin,clodepigrol and metapronolol.

u  3 days later the patient started to be agitated thinks that the nurses want to harm him and hearing voices commanding him to leave the hospital.

u  The medical team consult you regarding his agitation.

u  How will you appaoach this case?

HX,MSE,IX,File review,D\D.

u  What is your management?

u  When will you start treatment?

Summary

u  ECG must be done in cardiac patient as baseline and follow up when reaching theraputic dose or introducing new agent to avoid sudden cardiac death.

u  Average QTC range for male: 440msec, female: 470mse.

u  Safest ADs : sertraline,citalopram,mirtazapine and bupropione.

u  All benzodiazepine cosider safe.

Summary

u  Avoid IV AP and always go with low effect of AP like olanzapine and resperidone .

u  Aripaprizole is the safest AP.

u  In polypharmacy always look for drug drug interactions.

u  Consult cardiologist if the patint condition unstable.

u  Almost all SSRIs have antiplatelet effect and interact with warfarin which increse bleeding time.

CASE

u  Mr. x 29 YO saudi male k/c of CHD and DM 2 presented to your clinic with disorganised behavior and audiatory hallucination for the past 9 months you diagnosed him as schizophrenia .

u  Regardless to the medication he is taking for CHD and DM 2 .

u  What’s the most important work up before starting AP?

u  What is the best AP regarding his condition?

PREVELENCE

u  6.4 percent in adults WORLD WIDE

u  Saudi Arabia 890,000 , 2,523,000 (WHO).

u  KSA, adults: 17.6%.

u  prevalence in mentally ill is two to three times higher than that found in the general population .

Prevelence in KSA Al-Qurashi, et al., (2011)

u  Epidemiological study in 6024 individuals

u  D.M. 34.1% in males & 27.6% in females.

u  Mean age :- 55.3 yrs. u  BMI > 25 :-

In general :- 72.5 % In diabetics :- 85.7 % (females > males)

(p. = < .0001)

DIAGNOSTIC CRITERIA:

u  Diabetes mellitus can be diagnose according WHO either by one of the followings:

u  Random blood sugar more than 200mg\dl with symptoms.

u  Fasting blood sugar more than 126mg\dl.

u  HbA1c more than 6.5.

u  OGTT 2hour more than 200mg\dl.

METABOLIC SYNDROME

u  Current Adult Treatment Panel III (ATP III) criteria the metabolic syndrome as the presence of any 3 of the following :

u  Abdominal obesity, as a waist circumference in men >102 cm (40 in) and in women >88 cm (35 in.)

u  Serum triglycerides ≥150 mg/dl (1.7 mmol/L) or drug treatment for elevated triglycerides .

u  Serum high-density lipoprotein (HDL) cholesterol <40 mg/dl (1 mmol/L) in men and <50 mg/dl (1.3 mmol/L) in women, or drug treatment for low HDL cholesterol (HDL-C) .

u  Blood pressure ≥130/85 mmHg or drug treatment for elevated blood pressure.

u  Fasting plasma glucose (FPG) ≥100 mg/dl (5.6 mmol/L), or drug treatment for elevated blood glucose (9)

CATIE Trial Design

1493 patients with

SCZ Comorbidity Other meds

Participants who discontinue Phase 2 choose one of the

following open-label treatments

• ARIPIPRAZOLE

• FLUPHENAZINE DECANOATE

• PERPHENAZINE

• RISPERIDONE

• OLANZAPINE

• ZIPRASIDONE

• QUETIAPINE

• 2 of the antipsychotics above

Phase 3 Phase 1*

R

OLANZAPINE

QUETIAPINE

RISPERIDONE

ZIPRASIDONE

PERPHENAZINE

Double-blind, random treatment assignment.

Phase 2

CLOZAPINE (open-label)

OLANZAPINE, QUETIAPINE or RISPERIDONE

OLANZAPINE, QUETIAPINE or RISPERIDONE

ZIPRASIDONE

R

R

No one assigned to same drug as in Phase 1

Participants who discontinue Phase 1 choose either the

clozapine or the ziprasidone randomization pathways

*Phase 1A: participants with TD do not get randomized to perphenazine; phase 1B: participants who fail perphenazine will be randomized to an atypical (olanzapine, quetiapine, or risperidone) before they are eligible for phase 2.

Stroup TS et al. Schizophr Bull. 2003;29:15-31.

• CLOZAPINE

CATIE ( Metabolic Results )

Drug Average Weight Gain (lbs)

Weight Gain >7%

Fasting Blood Sugar (mg/dl) /HgbA1c (%) Change

Olanzapine 9.4 30% 15.0/0.41

Quetiapine 1.1 16% 6.8/0.05

Risperidone 0.8 14% 6.7/0.08

Perphenazine -2.0 12% 5.2/0.10

Ziprasadone -1.6 7% 2.3/-0.10

Citrome et al,2005

> 50% of patients on Olanzapine & Clozapine will

gain more than 10% of their body weight

within 14 weeks

Newcomer,2006 meta-analysis

Wt. Gain after 1 year

Drug

< 1kg Aripiprazole & Ziprasidone

2 - 3 kg Quetiapine & Risperidone

> 6 kg Olanzapine (< 12.5 mg)

> 10 kg Olanzapine ( >12.5 mg )

+ = increased effect; - = no effect; D = discrepant results.

Drug Weight Gain Diabetes Risk Dyslipidemia

Clozapine + + + + + Olanzapine + + + + + Risperidone + + D D Quetiapine + + D D Aripiprazole +/- - - ziprasidone +/- - -

American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity - Diabetes Care 27:596-601, 2004

Effect on glucose homstasis and weight


SSRIs


SNRIs

Mirtazpine and trazadone


Agomelatine

MCQ

u  Mr. x 29 YO saudi male k/c of CHD and DM 2 presented to your clinic with disorganised behavior and audiatory hallucination for the past 9 months you diagnosed him as schizophrenia . Regardless to the medication he is taking for CHD and DM 2 .

u  Best AP is:

1.  Olanzapine.

2.  Amisulpride.

3.  Aripiprizole.

4.  Clozapine.

summary

u  All depressed patient should should be screened for diabetes.

u  Monitoring of metabolic syndrome is a must.

u  SSRIs as 1st line : fluoxetine.

u  ziprasidone and aripiprazole showing the least effect.

u  clozapine and olanzapine shows the most effect.

u  SNRIs ( deluxtine) use for diabetic neuropathy.

u  avoid TCAs and MAOIs if possible due to their effects on weight and glucose homeostasis .

cardio diabetic pres 3

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