toxines and cardiovascular medicine and implications

toxins in cardiovascular medicine

1. Cardiovascular toxins

2. CNS Stimulants
I.Cocaine, Crack (free base or hydrochloride).
II.Amphetamines:
D-Amphetamine, Methamphetamine,
methylphenidate (use to treat attention deficit
disorders in children), phenmetrazine (Preludin)
- used to treat obesity,
(hallucinogens = MDA, MDMA, DOM;
methylenedioxymethamphetamine, "ecstasy,"
dimethoxyamphetamine).
III. Khat: Cathinone, methcathinone.

3. Cocaine

4. Cocaine Overview
•Alkaloid from Erythroxylon coca
•Indigenous to western South America
•Coca leaves used for religious, mystical,
social, stimulant, and medicinal purposes
•Main stimulant uses: endurance, feeling of
well-being, alleviate hunger
•Medical uses: local anesthetic,
vasoconstrictor

5. Cocaine Production
•Coca paste extracted from soaked and mashed leaves
(60-80% cocaine)
•Freebase/crack extracted from powder with baking soda
•Cocaine powder made by mixing paste with hydrochloric
acid (cocaine HCl)

6. Epidemiology
•In 1997:
- 25 million Americans admitted using cocaine at
least once
-3.7 million had used it within the previous year
-1.5 million were current users
•Cocaine was mentioned in 30% of all drug related
ER visits the same year
•Between 1994 and 1998, the number of new users
per year increased 82%

7. Pharmacology
•Cocaine is an alkaloid extracted from the leaf of
Erythroxylon Coca bush
•Available in the two forms:
-alkaloid dissolved in HCL to make hydrochloride salt:
-PO, IV, intranasal
-not heat stable so cannot be smoked
-“free base”, alkaloid dissolved in ammonia or sodium
bicarb (baking soda) to make ‘crack’;
-heat stable so can be smoked

8. Pharmacology
•Cocaine hydrochloride is well absorbed through all
mucous membranes
•As compared to the intravenous route, mucosal
administration results in slower onset of action,
later peak effect and a longer duration of action
•Euphoria is almost immediate after crack cocaine is
smoked
•Crack cocaine is considered the most addictive
form of the drug

9. Pharmacology
• Principal metabolites (benzoylecgonine and ecgonine
methyl ester) are excreted in urine
• Serum half life of cocaine is 45-90 minutes
• However, the metabolites are detectable in blood or
urine for 24 to 36 hours post use

10. Pharmacology

11. Mechanism of action
Cocaine acts as a powerful
sympathomimetic agent:
blocks the presynaptic
reuptake of
norepinephrine and
dopamine; results in an
excess of these
neurotransmitters at the
site of the postsynaptic
receptor

13. Cocaine cardiac
action
Cocaine cardiac
complications

14. CV effects of cocaine:
Ischemia
•Risk of AMI increases 24 fold during the 60
minutes following cocaine use
•There is NO dose-response relationship between
cocaine use and AMI
•Six percent of patients with cocaine-related chest
pain have cardiac enzyme elevation
•Most patients with cocaine-related AMI have no
risk factors except concomitant use of tobacco

16. Pathogenesis of cocaine related ischemia

17. Cocaine and atherosclerosis
Cocaine has been shown
to cause disruption in
platelet cytoskeleton, as
well as structural injury to
the endothelium
Normal
endothelium
Cocaine-induced
injury

18. Cocaine and Atheroclerosis
In vitro studies have shown cocaine can cause
damage to endothelial lining that enhances
permeability to LDL
Also, promotes leukocyte migration to
endothelium which may further accelerate
premature atherosclerosis.

19. Cocaine and atherosclerosis
Kollodgie et al, JACC 1991:
-Review of 5871 autopsies, 495 subjects with evidence of
cocaine use
-studied degree of atherosclerosis and mean number of
adventitial mast cells per coronary segment
-Results:
-significantly more mast cells in subjects with cocaine-
associated thrombosis than in the other age matched
groups
-subjects with cocaine-associated thrombosis also had
significant coronary atherosclerosis without plaque
hemorrhage despite a mean age of 29 +/- 2 years

20. Cocaine and Cardiomyopathy
Proposed mechanisms:
1) Myocardial ischemia or infarction
2) Microscopic changes of subendocardial contraction band
necrosis possibly through profound repetitive sympathetic
stimulation

3) Animal studies have shown that cocaine alters cytokine
production in the endothelium, changes the composition of
myocardial collagen and myosin, and induces myocyte
apoptosis

21. Cocaine and Dysrhythmias
•Cocaine has been shown to cause VT/VF in presence
of ischemia
•Also thought to:
-increase ventricular irritability and lower VF
threshold
-increase QRS and QT through Na-channel
blocking properties
-increase intracellular Ca
++
leading to
afterdepoloarizations
-reduces vagal activity thereby increasing
sympathomimetic effects

22. Cocaine and Endocarditis
•IVDU is associated with endocarditis
•Cocaine use is a greater independent risk factor for
SBE than other IV drugs
-reasons unclear
-perhaps tachycardia and hypertensive effects induce
valvular injury
-known immunosuppressive effects through
inhibition of IL-8
•Most often effects left-sided valves, unlike other IV
drugs.

23. Cocaine and Aortic Dissection
•Aortic dissection or rupture has been
temporally related to cocaine use
•Dissection probably results from the
substantial increase in systemic arterial
pressure induced by cocaine.
•Also, the cocaine-related rupture of mycotic
and intracerebral aneurysms has been
reported

24. Treatment
•Treatment of acute cocaine-induced ischemia and MI is
directed towards inhibition of platelet aggregation and
reversal of vasoconstriction/ spasm
•Aspirin should be administered to all patients with
suspected cocaine-induced ischemia
•There is little experience with fibrinolytic therapy in this
setting and it should be considered as a last resort

25. Treatment
•Cocaine-induced vasoconstriction is mediated
through the α-adrenergic receptors
•β-adrenergic blocking agents can exacerbate cocaine-
induced vasoconstriction
•Nitroglycerin and verapamil reverse cocaine-induced
vasoconstriction and are first-line agents in this
setting
•Labetolol reverses cocaine-induced hypertension, but
doesn’t reverse vasoconstriction
•Benzodiazepines also help with reduction of blood
pressure and pulse rate

26. Therapeutic and diagnostic recommendations in cocaine-associated chest pain.
James McCord et al. Circulation. 2008;117:1897-1907
Copyright © American Heart Association, Inc. All rights reserved.

28. 2008
2011

29. 2014

30. Amphetamines

31. Amphetamine Overview
(poor man’s cocaine, crystal meth, ice, glass, speed)
•Synthetic analog of ephedrine,
active ingredient in mahuang
•Mahuang used in China for asthma
–Chinese (Mandarin) má huáng : má,
hemp + huáng, yellow
•Methamphetamine and
Methylphenidate (Ritalin) are very
similar
•Medical uses: obesity, ADHD,
narcolepsy

32. Amphetamines - Background
•Used for over 60 years therapeutically for
numerous disorders
–Schizophrenia
–Addictions (morphine and nicotine)
–Head Injury
–Hypotension
–Severe hiccups
–Others

33. Amphetamines - Background
•Used in WW II to fight fatigue and enhance
performance
•Widespread abuse began in 1940’s with
students and truck drivers to stay awake and
increase alertness
•Were used as appetite suppressants

34. Mechanism of Action
•All CNS effects caused by the release of
newly synthesized NE and dopamine from
presynaptic storage sites
•Behavioral stimulation and increased motor
activity result from stimulation of dopamine
receptors in the mesolimbic system

35. Pharmacological Effects
•Physiological Effects
–Increased BP
–Decreased HR
–Increased alertness
–Psychomotor stimulant
–Loss of appetite

36. Pharmacological Effects
•Psychological Effects
–Euphoria
–Excitement
–Mood elevation
–Increased motor/speech activity
–Feeling of power

37. Pharmacological Effects
•More effects
–Task performance may improve
–Dexterity deteriorates

38. Pharmacological Effects
•At moderate doses
–Respiratory stimulation
–Slight tremors
–Restlessness
–Greater increase in motor activity
–Insomnia
–Agitation

39. Pharmacological Effects
•At high doses
–Repetitive purposeless acts
–Sudden outbursts of aggression/violence
–Paranoid delusions
–Severe anorexia
–Overall psychosis and abnormal mental conditions
–Amphetamine Psychosis: paranoid ideation
•Primarily with meth users

40. Pharmacological Effects
•In addition to the direct effects of the
drug….
–Infections from neglected health care
–Poor eating habits
–Use of unsterile equipment
–Great deterioration in social, personal,
occupational affairs

41. Pharmacological Effects
•Long Term evidence shows...
–Psychometric deficits
–Poor academic performance
–Behavioral problems
–Cognitive slowing
–General maladjustment
•The effects on this list are permanent.

42. Cathinones
Bind to monoamines transporters for
dopamine ,serotonin,and norepinephrine , which
accounts for their sympathomimetic properties.
Like cocaine and amphetamins ,these substances
produce stimulant effects .

43. khat

44. Khat Khat
A green leaf with ‘amphetamine-like’ effects
Chewed mainly for social interaction by Yemenis,
Ethiopian and Somalis in homeland.
Types: Yemeni, Ethiopian, Kenyan and other different
brands with different levels of cathinone, Cathedulins and
other unexplored components
Illegal in many countries
5 and the UK is
more likely to enforce its illegalization
6
on
24/6/2014

45. On average around 100–300g of khat can be chewed in a 3-4
hour khat session .
The mucosa of the mouth is thought to be the first absorption
segment, where most of the active constituents are absorbed
59 ± 21% for cathinone and 84 ± 6% for cathine).
Peak plasma levels of cathinone are obtained 1.5–3.5 h after
the onset of chewing khat
Cathamines are excreted in breast milk and detected in the
urine of breast-fed babies 2-4 hours after ingestion
Pharmacology
Khat Khat

46. Pharmacology
Cathinone has markedly stronger effects than cathine and
norephedrine. For example, cathinone has been reported to be
7-10 times more potent than cathine on a behavioral measure
of food intake
Blood pressures are elevated for about 3 hours after 1 hour of
chewing of 0.6 g/kg, about one quarter of the amount
consumed in a traditional khat session
.
Khat Khat

47. Pathogenesis of Khat-Induced
Cardiovascular Complications
Cathinone, the most active khat alkaloid, has been shown
to increase heart rate and blood pressure in animal and
human studies,
This effect was mediated by 1-adrenergic receptors.
blood pressure remains elevated for about 3 hours after 1
hour of chewing about one quarter of a traditional khat-
session dose.
These effects might increase myocardial oxygen demand
and precipitate ACS in susceptible patients and worsen
the outcome
Khat Khat

48. Khat is also believed to induce coronary artery spam.
increase of hypercoagulable state. Due to
the induction of tissue factor with amphetamine,
increase in endothelial tissue factor
a reduction in tissue factor pathway inhibitor
Premature coronary atherosclerosis is another potential
mechanism. About 5 of 6 patients with amphetamine-
associated MI had obstructive coronary artery disease in
amphetamine-associated MI.
Pathogenesis of Khat-Induced
Cardiovascular Complications
Khat Khat

49. Khat Chewing and ACS
One study showed :
79% prevalence of khat chewing among patients hospitalized with MI in
Yemen in 2002, which was significantly higher than in control subjects
(20.8%; P0.001).
Furthermore, the vast majority of events (70.1%) occurred either during
or immediately after completion of a khat-chewing session.
The peak period of presentation among khat chewers was between 3 and
11 PM, coinciding with the timing of khat-chewing sessions, whereas in
non–khat chewers, the peak time was between 3 and 9 AM.
Khat Khat

50. Khat and cardiovascular effects Khat Khat

51. Cannabis and the
Cardiovascular
Effects

52. Cannabis
History of use
•Material from the Cannabis plants
–Cannabis sativa and Cannabis indica
•Known to have been cultivated for approx.
12,000 years (beginning in China)

53. Marijuana: What is it?Marijuana: What is it?
•Dry, shredded mix of leaves,
flowers, stems, and seeds,
usually from Cannabis sativa
or Cannabis indica plant
•Both are common subspecies of
the hemp plant, which is
common throughout the world
•Contains over 400 chemical
compounds
•Common names: grass, weed,
pot, reefer, Mary Jane, ganja
SOURCE: SAMHSA, 2012 (reference list).
53

54. Cannabis
Pharmacology
Primary Cannabinoids from Cannabis are:
•Cannabinol (CBN), Cannabidiol (CBD) and
Tetrahydrocannabinol (THC)
•THC (-9-THC ) is the only one with
significant psychoactive properties
•CBN - 1/10
th
activity of THC; CBD - none

55. Cannabis
Pharmacology & Toxicology
•Primary routes of administration are:
oral or smoking
•Smoked marijuana or inhaled hash (much more potent)
provides the highest delivery
•Typical joint weighs 0.5 - 1 gram and contains 20 + mg of
THC

56. Cannabis

57. How is Marijuana Used?How is Marijuana Used?
57
SOURCE: University of Utah, 2013 (reference list).

58. Cannabis
Onset & duration of effects
•Physical and psychological effects commence
within minutes of finishing a joint
•Psychological effects can persist from 4 to 8
hours depending upon route of administration
(oral, slower onset, longer duration)

59. Different Kinds of Marijuana-Based Different Kinds of Marijuana-Based
MedicineMedicine
•Synthetic THC medications available in U.S. for nausea/appetite
stimulation:
–Dronabinol (Marinol®) (FDA approved for HIV)
–Nabilone (Cesamet®) (FDA approved for cancer; HIV off-
label)
•Other medications not available in U.S.:
–Nabiximols (Sativex®) THC/cannabidiol mouth spray for pain
relief, muscle spasms; currently being investigated by FDA
–Rimonabant (Accomplia®, Zimulti®) for treatment of obesity
and nicotine dependence
(selective cannabinoid receptor-1 blocker)
59

60. Cannabis and the Cardiovascular
system
60
Comparatively little research has been done in this area, but there
are sufficient published scientific papers to raise concern .
Cardiovascular disorders represented 2% of the reports related
to cannabis, classified into cardiac, cerebral, and peripheral
complications

61. Mechanisms of cardiovascular
effects
61
a) proarrythmic effect mediated by catecholamines
b) cardiac ischemia due to an increase in heart rate and cardiac
workload in susceptible individuals
c) postural hypertension
d) delay in seeking medical care for acute coronary events due to
analgesic properties of cannabis
e) impaired oxygen supply to the heart secondary to increased
blood carboxyhemoglobin levels
f) production of oxidant gases by marijuana smoking resulting in
cellular stress, which may highten cardiovascular risk through
activation of platelets, increased oxidized LDL formation,
enhanced factor VII activity and induction of an inflammatory
response

62. 62
During cannabis smoking the concentration of Δ9- tetrahydrocannabinol
in the bloodstream reaches peak levels even before the end of the
smoking period and then it is rapidly distributed to the tissues
Its use leads to dose-dependent tachycardia, raised blood pressure and
cardiac output, for which tolerance rapidly develops.
Decreased peripheral vascular resistance and postural hypotension
frequently occur .
Electrocardiographic effects of cannabis are sinus tachycardia, sinus
bradycardia, second degree heart block, atrial flutter and fibrillation
Mechanisms of cardiovascular
effects

64. Despite the known underreporting, the rate of cannabis-related
cardiovascular complications reported steadily rose during the past
5 years.
Cardiovascular disorders represented 2% of the reports related to
cannabis

Published reports describe a temporal relation between marijuana
use and the development of
acute myocardial infarction,
cardiomyopathy ,
and sudden cardiac death.

65. Marijuana use and myocardial
infarction
Marijuana use may also precipitate the development of myocardial
infarction in patients with coronary artery disease.
After myocardial infarction, mortality is significantly higher in
marijuana users than in the general population.
In a study of 1,913 adults after hospitalization for myocardial
infarction, Mukamal et al found :
a 4.2-fold increased risk for mortality in marijuana users who
reported consuming the drug more than once per week before the
onset of the infarction compared with nonusers.

66. In 2001, Mittleman et al addressed the question by interviewing 3,882
patients with acute myocardial infarctions about marijuana use and
found that the risk for developing myocardial infarction was
4.8 times higher than average in the hour immediately after
marijuana use.
Marijuana use and myocardial
infarction

67. Most case reports describe relatively:
young patients in their second or third decades
with normal coronary arteries or minimal atherosclerosis,
suggesting that marijuana does not lead to the development or
acceleration of atherosclerotic damage in healthy adults.
Marijuana use and myocardial
infarction

68. Currently unknown.
But marijuana use is known to increase heart rate and enhance
sympathetic tone.
It is possible that cannabis has a deleterious effect on coronary
microcirculation.
(CARDIA) study showed that patients who used marijuana tended
to have a high caloric diet and were more likely to smoke tobacco
and use other illicit drugs.

The mechanism underlying the association
between marijuana use and myocardial infarction

69. Marijuana use and cardiomyopathy
Reports of an association between marijuana use and cardiomyopathy
are rarer than those of myocardial infarction.
Two case reports describe left ventricular dysfunction associated with
marijuana smoking.

70. However, Bachs and Mørland reported 6 cases of probable cardiac
death in young adults ranging from 17 to 43 years of age that appeared
to be related solely to marijuana use.
Potential mechanisms for sudden cardiac death after marijuana use
could be related to the development of acute myocardial infarction
and or arrhythmias, the no-reflow phenomenon, or increased
catecholamine levels.

Marijuana use sudden cardiac death

71. Marijuana-induced atrial fibrillation
During the past few years an increasing number of case reports
indicate an association between marijuana smoking and the
development of AF
AF occurrence, especially in young people without structural heart
disease or other precipitating factors for AF.
 It should also be borne in mind that because of social or legal
reasons most users of illicit drugs avoid seeking medical attention.
In addition, many short episodes of AF may pass without
symptoms. Taking into consideration all these notions, it could be
reasonable to conclude that the burden of the problem is possibly
underestimated.

73. Cerebrovascular Effects of Marijuana
Use
Cases of clear, documented stroke during marijuana use have been
previously reported.
Later reports confirmed this association, finding that strokes tend to
occur during actual marijuana inhalation in episodic and heavy
marijuana users.
Mouzak et al reported classic transient ischemic attacks in 3 patients
during marijuana use that resolved with normal full neurologic
workup, suggesting a reversible effect of cannabis inhalation on the
blood vessels of the brain that may be attributable to a spasm or, less
likely, a temporal increase in blood pressure

74. In 5 patients, reexposure to cannabis resulted in recurrent stroke
despite the absence of other vascular risks.
There have been 2 additional case reports published describing stroke
after myocardial infarction related to heavy marijuana use.
Cerebrovascular Effects of Marijuana
Use

75. Peripheral Effects of Marijuana Use
Several case reports describe peripheral atherosclerotic disease,
known as:
cannabis arteritis, that is a very rare peripheral vascular disease
similar to Buerger's disease,There were about 50 confirmed cases
from 1960 to 2008, all of which occurred in Europe.
Cannabis arteritis presents with claudication, Raynaud’s phenomenon,
and ischemic ulcers or digital necrosis.
Angiography usually shows atherosclerotic changes ranging from mild
atherosclerotic plaques to total occlusion. Some patients improved with
marijuana cessation

76. J Am Heart Assoc. 2014;3:e000638 doi: 10.1161/JAHA.113.000638)

77. They identified all spontaneous reports of cardiovascular
complications related to cannabis use collected by the French
Addictovigilance Network from 2006 to 2010.
- 1.8% of all cannabis-related reports (35/1979) were
cardiovascular complications,

78. -with patients being mostly men (85.7%) and of an average age of
34.3 years.
-There were 22 acute coronary syndromes),
-10 peripheral complications (lower limb or juvenile arteriopathies
and Buerger-like diseases),
-- 3 cerebral complications (acute cerebral angiopathy, transient
cortical blindness, and spasm of cerebral artery).
-In 9 cases, the event led to patient death.

79. ,

81. American Journal of Cardiology 
2014 113, 187-190DOI: (10.1016/j.amjcard.2013.09.042)
Copyright © 2014 Elsevier Inc. Terms and Conditions
Summary

82. Ethanol
- two thirds of Americans occasionally consume ethanol,
- 10% are considered to be heavy consumers.
Although the ingestion of a moderate amount of ethanol (usually
defined as three to nine drinks/week) is associated with a reduced
risk of cardiovascular disease, the consumption of excessive
amounts has the opposite effect.

83. Effects of Ethanol on Cardiac Myocyte
Structure and Function
First, ethanol and its metabolites, acetaldehyde and acetate, may exert
a direct toxic effect on the myocardium.
Second,
deficiencies of certain vitamins (e.g., thiamine), minerals (e.g.,
selenium), or electrolytes (e.g., magnesium, phosphorus, potassium)
may adversely affect myocardial function.
Third, certain substances that sometimes contaminate alcoholic
beverages, such as lead (often found in moonshine) or cobalt, may
damage the myocardium.

85. Effects of Ethanol on Cardiac Myocyte
Structure and Function
Diastolic dysfunction, interstitial fibrosis of the myocardium,
About 50% of asymptomatic chronic alcoholics have
echocardiographic evidence of left ventricular hypertrophy with
preserved systolic performance
As many as 30% of asymptomatic chronic alcoholics have
echocardiographic evidence of left ventricular systolic dysfunction.
With continued heavy ethanol ingestion, these subjects often develop
symptoms and signs of congestive heart failure, which is caused by a
dilated cardiomyopathy

86. Ethanol-induced dilated cardiomyopathy
Most men who develop an ethanol-induced dilated cardiomyopathy
have consumed more than 80 g of ethanol/day (i.e., 1 liter of wine, 8
standard-sized beers, or 0.5 pint of hard liquor) for at least 5 years.
Women appear to be even more susceptible to ethanol’s cardiotoxic
effects,
Complete abstinence may manifest a substantial improvement in left
ventricular systolic function and symptoms of heart failure with or a
dramatic reduction in ethanol consumption
Although most of this improvement occurs in the first 6 months of
abstinence, it often continues for as long as 2 years of observation.

87. Ethanol and Systemic Arterial Hypertension
Ethanol is a causative factor in up to 11% of men with hypertension
Individuals who consume more than two drinks daily are 1.5 to 2
times more likely to have hypertension when compared with age-
and sex-matched nondrinkers.
The mechanism is poorly understood,
studies have demonstrated that ethanol consumption increases
plasma levels of catecholamines, renin, and aldosterone .
Abstinence often normalizes systemic arterial pressure.

88. Ethanol and Lipid Metabolism
Ethanol inhibits the oxidation of free fatty acids by the liver, which
stimulates hepatic triglyceride synthesis and the secretion of (LDL)
cholesterol.
Most commonly,
therefore, ethanol consumption causes hypertriglyceridemia.
In addition,
heavy ingestion may cause an increase in the serum concentrations
of total and LDL cholesterol. Regular ethanol consumption
increases the serum concentration of high-density lipoprotein (HDL)

89. Coronary Artery Disease
Conversely, light to moderate ethanol intake (two to seven
drinks/week) is associated with a decreased risk of cardiovascular
morbidity and mortality in men and women
Heavy ethanol use is associated with an increased incidence of
atherosclerotic CAD
This rise may result at least in part, from:
systemic arterial hypertension, an increased left ventricular
muscle mass (with concomitant diastolic and/or systolic
dysfunction), and hypertriglyceridemia

90. Coronary Artery Disease
Moderate consumption exerts several beneficial effects, including the
following:
(1) an increase in the serum concentrations of HDL cholesterol and
apolipoprotein A-I;
(2) inhibition of platelet aggregation;
(3) a decreased serum fibrinogen concentration;
(4) increased antioxidant activity (from the phenolic compounds and
flavonoids contained in red wine);
(5) anti-inflammatory effects (with lower concentrations of white
blood cells and C-reactive protein);
(6) improved fibrinolysis resulting from increased concentrations of
endogenous tissue plasminogen activator and a concomitant decrease
in endogenous plasminogen activator inhibitor activity

91. Moderate consumption
exerts several beneficial
effects

92. Even in men already at low risk for cardiovascular disease on the
basis of body mass index, physical activity, smoking, and diet,
moderate alcohol
intake is associated with a reduced risk of myocardial infarction (MI)

93. Arrhythmias
Ethanol consumption is associated with a variety of atrial and
ventricular arrhythmias, most commonly the following:
(1)atrial or ventricular premature beats;
(2) supraventricular tachycardia;
(3) atrial flutter;
(4) atrial fibrillation;
(5) ventricular tachycardia;
(6) Ventricular fibrillation.
The most common ethanol-induced arrhythmia is atrial
fibrillation
holiday heart

94. - The presence of myocardial interstitial fibrosis,
ventricular hypertrophy, cardiomyopathy, and autonomic
dysfunction also may enhance the likelihood of
dysrhythmias.
Arrhythmogenic :
- concomitant factors may predispose to arrhythmias, including :
cigarette smoking, electrolyte disturbances, metabolic
abnormalities, hypertension, or sleep apnea.
Acute ethanol ingestion induces a diuresis, which is accompanied
by the concomitant urinary loss of sodium, potassium, and
magnesium.

95. Sudden Death
In subjects without known cardiac disease, the decrease in cardiovascular
mortality associated with moderate ethanol intake
Of the more than 21,000 men in the Physicians Health Study, those who
consumed two to four drinks/week or five to six drinks/week had a
significantly reduced risk of sudden death when compared with those who
rarely or never drank
In contrast, heavy ethanol consumption (i.e., six or more drinks/day)
or binge drinking was associated with an increased risk of sudden
Death independent of the presence of coronary artery disease

96. Sudden death in alcoholics

97. Environmental Exposures
Cobalt
fulminant form of dilated cardiomyopathy was described in heavy
beer drinkers.
It was suggested that the cobalt chloride that was added to the beer as
a foam stabilizer was the causative agent; therefore, its addition was
discontinued. Subsequently, this acute and severe form of
cardiomyopathy disappeared.

98. Lead
Mainly gastrointestinal and central nervous systems.
On occasion, subjects with lead poisoning have ECG abnormalities,
atrioventricular conduction defects, and overt congestive heart failure.
Rarely, myocardial involvement may contribute to or be the principal
cause of death
Arsenic
Arsenic exposure typically occurs from pesticide poisoning.
Its cardiac manifestations include:
pericardial effusion, myocarditis, and various ECG abnormalities,
including QT interval prolongation with T wave inversion.
Environmental Exposures

99. Mercury
Occupational exposure to metallic mercuric vapors may cause
systemic arterial hypertension and myocardial failure.
Although some studies have suggested that a high mercury content
of fish may counteract the beneficial effects of its omega-3 fatty
acids, thereby increasing the risk of atherosclerotic cardiovascular
disease, more recent assessments have not supported an association
between total mercury exposure and the risk of coronary artery
disease
Environmental Exposures

100. Carbon monoxide
Carbon monoxide has a higher affinity for hemoglobin than oxygen;
to reduced tissue oxygen delivery.
cardiac toxicity may delayed for several days by:
myocardial hypoxia or
a direct toxic effect on myocardial mitochondria.
Sinus tachycardia and various arrhythmias, including ventricular
extrasystoles and atrial fibrillation, are common; bradycardia and
atrioventricular block may occur in more severe cases.
Angina pectoris or MI may be precipitated by carbon monoxide
exposure in patients with or without underlying
coronary artery disease.
The administration of 100% oxygen or treatment in a hyperbaric
oxygen chamber usually results in rapid resolution of the
cardiac abnormalities.

101. Cardenolides
Cardenolides are naturally occurring plant toxins
second- or third degree heart block—and cardiac arrest.
Poisoning with the digitalis cardenolides (digoxin and digitoxin) is
reported worldwide. Cardiotoxicity from other cardenolides, such as
the yellow, pink, or white oleander and sea mango tree, is a major
problem in South Asia.
In India and Sri Lanka, yellow oleander has become a popular means
of self-injury, with tens of thousands of ingestions annually and a
case fatality ratio of 5% to 10%.
Prolonged hospitalization and observation is recommended, because
the occurrence of dangerous dysrhythmias may be delayed up to 72
hours after ingestion

102. “Mad Honey”
Honey produced from the nectar of rhododendrons growing on the
mountains of the eastern Black Sea region of Turkey may contain
grayanotoxins, which bind to voltage-dependent sodium channels in
the heart and lead to bradycardia and atrioventricular block.
Symptoms of “mad honey” poisoning (e.g., nausea, vomiting,
hypotension, syncope) occur a few minutes to several hours after
honey ingestion, with the severity of the poisoning dependent on the
amount ingested.
Grayanotoxins are metabolized and excreted rapidly, so the toxic
effects of honey poisoning are rarely fatal and typically resolve in 2
to 9 hours.

103. Scombroid
Acute severe myocardial dysfunction caused by histamine poisoning
has been reported within 1 hour of the ingestion of spoiled scombroid
fish, such as tuna or bonito.
The flesh of these fish is rich in histidine, which is metabolized by
gastrointestinal flora to histamine.
The diagnosis is mainly based on clinical findings, but can be
documented by the determination of histamine concentrations in the
ingested fish or increased plasma histamine levels in the patient
within 4 hours of fish ingestion.

104. Envenomations
Black widow spider, bee, wasp, jellyfish, cobra, and scorpion
envenomation have been associated with cardiac complications,
including:
MI, acute cardiac failure, myocarditis, bradyarrhythmias, heart
block, ventricular
tachyarrhythmias, and sudden death
The mechanisms include:
the systemic release of catecholamines,
cardiac ion channel modulation,
coronary arterial vasoconstriction, and direct myotoxic effects.