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AbstractStatistics show that 1 in 4 myocardial infarctions (MI), also known as heart attacks, in people between the ages of 18 and 45 can be linked to cocaine use (Qureshi, A., Suri, F., Guterman, L., & Hopkins, N., 2001). Cocaine is not the only illicit and recreational drug to have adverse affects on the cardiovascular system. The primary sources of data used for this study will be reports and studies completed in the health care field. The secondary source of data will be statistical data from local hospitals regarding cardiac complications in patients with documented drug use and history. This study should pull the various pieces together of the many non-associated studies into the subject. The selection of specific participants used in this study and the other studies examined are random. The control group for the study will be the statistical information regarding cardiac complications in individuals with no history of recreational drug use. The age group of the study is individuals between the ages of 18 and 45. The individuals examined come from all ethnic and socioeconomic groups. There is no disclosure of personal health care information and all patient information is held at the highest confidentiality.
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Running head: CARDIOVASCULAR EFFECTS OF DRUG 1
Cardiovascular Effects of Drug Use:
Focusing on Recreational and Illicit Drugs
Daniel Jones
Skagit Valley College
CARDIOVASCULAR EFFECTS OF DRUG 2
Abstract
Statistics show that 1 in 4 myocardial infarctions (MI), also known as heart attacks, in
people between the ages of 18 and 45 can be linked to cocaine use (Qureshi, A., Suri, F.,
Guterman, L., & Hopkins, N., 2001). Cocaine is not the only illicit and recreational drug
to have adverse affects on the cardiovascular system. The primary sources of data used for
this study will be reports and studies completed in the health care field. The secondary
source of data will be statistical data from local hospitals regarding cardiac complications
in patients with documented drug use and history. This study should pull the various
pieces together of the many non-associated studies into the subject. The selection of
specific participants used in this study and the other studies examined are random. The
control group for the study will be the statistical information regarding cardiac
complications in individuals with no history of recreational drug use. The age group of the
study is individuals between the ages of 18 and 45. The individuals examined come from
all ethnic and socioeconomic groups. There is no disclosure of personal health care
information and all patient information is held at the highest confidentiality.
CARDIOVASCULAR EFFECTS OF DRUG 3
Cardiovascular Effects of Drug Use:
Focusing on Recreational and Illicit Drugs
I. Introduction
According to the National Survey on Drug Use and Health (NSDUH),
approximately 21.8 million Americans, ages 12 or older, in 2009 consumed illicit drugs
(“Health, United States,” 2010.) Of the 21.8 million illicit drug users, approximately 5.1
million in total used drugs other than marijuana (“Health, United States,” 2010). Statistics
show that 1 in 4 myocardial infarctions (MI), also known as heart attacks, in people
between the ages of 18 and 45 can be linked to cocaine use (Qureshi, A., Suri, F.,
Guterman, L., & Hopkins, N., 2001).
Recreational and illicit drug use has a profound effect on the central nervous
system but studies also show acute effects to the heart and circulation system. Drug-related
morbidity has a strong link to their cardiovascular effects due to their significant and
profound changes to the cardiovascular system. According to Paramedic Kelly Grayson
(2011), most, if not all, emergency medical technicians (EMT), paramedics, nurses and
physicians will likely encounter patients with cardiovascular complications related to illicit
and recreational drug use. Medical professionals are required to have an awareness of the
pathophysiological and pharmacological effects of these substances in order to diagnose the
complications that are originated form their use.
The purpose of the study is to show and educate the present and forthcoming
facts and evidence of the link between recreational drug use and their effects on the
cardiovascular system. The more that recreational drugs are used; therefore, recreational
drugs will be linked to cardiovascular complications and disease.
CARDIOVASCULAR EFFECTS OF DRUG 4
II. Methods
I carefully searched the MEDLINE, EMBASE, PROQUEST and EBSCOHOST
databases for all relevant articles, published until July 2011, using the following keywords:
‘marijuana’, ‘atrial fibrillation’, ‘arrhythmias’, ‘tachycardia’, ‘pcp’, ‘narcotic’, ‘inhalant’,
‘volatile substance’, ‘hallucinogen’, ‘palpitations’, 'recreational drug', 'cocaine', 'khat',
'MDMA', 'stimulants', 'barbiturates', 'illicit drug', 'myocardial infarction', ‘heart’ and
‘cardiovascular’. A manual search of reference lists from identified reports, to find
additional sources, was also performed. Finally, I identified all relevant articles dealing
with the cardiovascular effects and complications of recreational and illicit use.
III. Medical Effects
The majority of cardiovascular complications from drug use are from their
sympathetic nervous system activation (Ghuran, A., Nolan, J., 2000). Sympathetic nervous
system activation can cause vasoconstriction, tachycardia, arrhythmias and erratic and
unpredictable blood pressure changes (Ghuran et al., 2000). Due to spiking catecholamine
levels and sympathetic nervous system activation hypertension is very common, but
hypotension is also possible (Delvin, R., Henry, J., 2008). Amphetamines are primarily
responsible for myocardial infarction and ischemia, which is a result of increased oxygen
requirement, thrombus formation and platelet aggregation from elevated catecholamine
concentrations.
Recreational and illicit drugs interact with various central nervous system
neurotransmitters. A general understand of these neurotransmitters is required to
understand how each drug effects the body and can have an effect on the cardiovascular
system. The primary neurotransmitters are GABA, Glycine, Glutamate, Aspartate,
CARDIOVASCULAR EFFECTS OF DRUG 5
Acetylcholine, Catecholamines (Dopamine, Norepinephrine and Epinephrine) Serotonin,
Histamine, Vasopressin, Oxytocin, Tachykinins, CCK, NPY, Neurotensin, Opiod peptides,
Somatostatin and Purines (Goodman, L., Brunton, L., Chabner, B., Knollmann, B., 2008).
GABA (γ-‐amino butyric acid) is the primary and major neurotransmitter
with an inhibitory effect in the central nervous system (Goodman et al., 2008). GABA
facilitates inhibitory actions of interneurons in the brain and presynaptic inhibition
within the spinal cord (Goodman et al., 2008). GABA receptors are divided into 3
types, A, B and C. GABAA being the most important to this study as it is the most
prominent subtype (Goodman et al., 2008). GABAA is a ligand gated Cl-‐ ion channel,
which is an inotropic receptor that opens after release of GABA by presynaptic neurons
(Goodman et al., 2008). GABAA is the binding site of neuroactive drugs such as
barbiturates, benzodiazepines, ethanol (alcohol), volatile anesthetics and anesthetic steroids
(Goodman et al., 2008).
Catecholamines are fight or flight hormones that are released by the adrenal
glands (Goodman et al., 2008). There are three different hormones released by the adrenal
glands (Goodman et al., 2008). Norepinephrine, sometimes called Noradrenaline,
Epinephrine, also known as adrenaline, and dopamine all have strong links to stimulant use
and have great effect on the cardiovascular system (Goodman et al., 2008).
Dopamine is the most predominant catecholamine hormone constituting for
over half its content. Within the CNS Dopamine plays a large part in the limbic zones of
the cerebral cortex, which is responsible for controlling the autonomic nervous system and
gives the high associated with many recreational drugs (Goodman et al., 2008). Dopamine
CARDIOVASCULAR EFFECTS OF DRUG 6
receptors have been linked to the pathophysiology of schizophrenia and Parkinson’s
disease (Goodman et al., 2008).
Norepinephrine is mostly located in the hypothalamus and in specific zones of
the limbic system, which include the central nucleus of the amygdala and dentate gyrus of
the hippocampus. Norepinephrine has three different androgenic receptors (α1, α2 and β)
characterized by their pharmacologic properties and distribution (Goodman et al., 2008). β
adrenergic receptors are coupled to stimulation of adenylyl cyclase activity. α1 is primarily
associated with neurons, where α2 are more characterized with vascular and glial elements
and functions (Goodman et al., 2008).
Epinephrine is found in the medullary reticular formation. Epinephrine makes
connections on a restricted level to a few pontine and diencephalic nuclei. The
physiological properties have yet to be identified for epinephrine.
Serotonin (5-Hydroxytryptamine, 5-HT, 3-[β-aminoethyl]-5-hydroxyindole) is
found in enterochromaffin cells in the gastrointestinal (GI) tract, broadly throughout the
central nervous system and in storage granules in platelets (Goodman et al., 2008).
Serotonin, or 5-HT, is synthesized from tryptophan by a two-step process, which is then
actively transported to the brain (Goodman et al., 2008). Serotonin’s cardiovascular system
response is blood vessel contraction (Goodman et al., 2008). The blood vessel contraction
is primarily in the pulmonary, renal, splanchnic and cerebral vasculatures (Goodman et al.,
2008). Serotonin in increased levels can cause notable bradycardia and hypotension
(Goodman et al., 2008).
CARDIOVASCULAR EFFECTS OF DRUG 7
Gilman Manual of Pharmacology and Therapeutics (2008) (p. 193)
Aggregation triggers the release of 5-HT stored in platelets. Local actions of 5-HT include
feedback actions on platelets (shape change and accelerated aggregation) mediated by 5-HT2A
receptors, stimulation of Nitric Oxide production mediated by 5-HT1-like receptors on vascular
endothelium, and contraction of vascular smooth muscle mediated by 5-HT2A receptors. These
influences act in concert with many other mediators (not shown) to promote thrombus formation
and hemostasis (Goodman et al., 2008).
IV. Recreational and Illicit Drugs
The majority of recreational and illicit drugs have an effect on the
cardiovascular system (Ghuran et al., 2000). Sedatives (Benzodiazepines, benzodiazepine
agonists, barbiturates, alcohol, gammahydroxybutyrate, GBL, 1,4-butandiol), Stimulants
(Amphetamines and cocaine), Narcotics (Full opiod agonists, partial, selective or mixed
opiod agonists), Cannabis (delta-4-tetrahydrocannabinol and cannabidiol), Psychedelics
(Phenethylamines, tryptamine and ergolines), Dissociative anesthetics (Phencyclidine
(PCP), dextromethorphan and ketamine), Inhalants (Diethyl ether (starter fluid),
chloroform, toluene, gasoline, glue, paint, xenon, cyclopropane, Freon, halothane,
CARDIOVASCULAR EFFECTS OF DRUG 8
sevoflurane, nitrous oxide, nitrites, isoamyl nitrite, isobutyl nitrite and Other (Salvinorin A
(salvia divinorum), muscimol, nicotine, caffeine, methaqualone, khat, thalidomide,
meprobamate, carisoprodol, glutethimide, chloral hydrate, ethchlorvynol, methyprylon and
primidone) substances have direct (primary) and indirect (secondary) adverse effects on the
cardiovascular system (Fallows, Z., 2009).
i. Sedatives
Sedative abuse is
very common among
recreational drug users.
Medically, sedatives are
normally prescribed and
used to treat anxiety,
insomnia, muscle tension,
drug and alcohol withdraw,
seizures and sometimes
hypertension (high blood
pressure) (Goodman et al.,
2008). Sedatives, such as
benzodiazepines and
barbiturates, act at benzodiazepine receptors that are located closely to ϒ-aminobutyric
acid (GABA1) receptors (Goodman et al., 2008). When benzodiazepines bind to the
1 GABA receptors (GABAA, GABAB and GABAC) are located on chloride ion channels at the inhibitory synapses within the central nervous system (CNS), which includes the reticular activating system (RAS).
Ashton, H., from http://www.benzo.org.uk/manual/bzcha01.htm
CARDIOVASCULAR EFFECTS OF DRUG 9
receptors and the chloride channels open the chloride ions flow inward causing the
neuronal membrane to hyperpolarize (Goodman et al., 2008). This causes a reduction
in anxiety and wakefulness because benzodiazepines enhance the effects of GABA at
their receptors (Goodman et al., 2008). Benzodiazepines primarily target the CNS and
only have two effects that act on the peripheral nervous system (PNS) (Goodman et
al., 2008). Coronary vasodilation, causing hypotension, observed after intravenous use
and blockade of neuromuscular receptors, only seen in very high doses, are the only
two PNS actions known of benzodiazepines (Goodman et al., 2008).
Benzodiazepine, along with other narcotic analgesic and sedative,
intoxication and withdraw can cause hypotension and bradycardia (Goodman et al.,
2008). Adverse cardiovascular effects due to histamine release from mast cell
degranulation can also induce cardiac arrhythmias including premature ventricular and
atrial ectopic activity, idioventricular rhythms, atrial fibrillation and ventricular
tachyarrhythmias (Ghuran, A., Nolan, J., 2000). Many of the sedatives are commonly
taken intravenously which is known to cause cardiac complications such as bacterial
endocarditis, which is sometimes associated with pulmonary abscesses (Goodman et
al., 2008).
Barbiturates, derivatives of 2,4,6-trioxohexahydropyrimidine, reversibly
reduce the activity of all excitable tissues (Goodman et al., 2008). The action of
barbiturates takes place by decreasing nerve impulses traveling to the cerebral cortex
by potentiating gamma-aminobutyric acid (Lisanti, P., 1998). The mechanisms in
which barbiturates act on GABAA receptors are markedly distinct from GABA or
benzodiazepines (Goodman et al., 2008). Barbiturates promote with the binding of
CARDIOVASCULAR EFFECTS OF DRUG 10
benzodiazepines to GABAA receptors and potentiate GABA induced chloride by
lengthening periods where bursts of channel opening occur instead of making bursts
more frequent as of benzodiazepines (Goodman et al., 2008). Also, α and β subunits
of the channel are required for barbiturate action unlike benzodiazepines (Goodman et
al., 2008). Because of these actions, barbiturates produce depression of the CNS
varying from mild sedation to anesthesia clinically (Goodman et al., 2008).
Barbiturates normally cause bradycardia and hypotension due to their
depression of the CNS (Goodman et al., 2008). In cases of barbiturate abuse and
intoxication, mixed with alcohol, and overdose have caused cardiovascular collapse
from extreme CNS depression (Goodman et al., 2008). Intravenous use of barbiturates
has an increased incidence of ventricular arrhythmias, particularly, but not required,
when epinephrine and halothane2 are present (Goodman et al., 2008). Serious and
sometimes-extreme deficits in cardiovascular functions occur after acute barbiturate
intoxication, which is why barbiturates have mostly been replaced by somewhat safer
benzodiazepines (Goodman et al., 2008).
ii. Stimulants
Stimulant use is among the top of the list in recreational and illicit drug users.
Most stimulants commonly abused have analogous adverse effects on the
cardiovascular system (Ghuran et al., 2000). The majority of adverse effects of
stimulants are related to sympathetic nervous system activation (Ghuran et al., 2000).
Cocaine inhibits reuptake of norepinephrine and dopamine at sympathetic nervous
2 Volatile liquid anaesthetic that has growing levels of abuse as many barbiturates and benzodiazepines are increasing more difficult to obtain due to tighter drug control regulations.
CARDIOVASCULAR EFFECTS OF DRUG 11
system terminals as well as stimulating release of norepinephrine from the adrenal
medulla oblongata (Goodman et al., 2008). Amphetamines, including
methylenedioxymethamphetamine (MDMA), cause indirect activation of the
sympathetic nervous system by releasing dopamine, norepinephrine and serotonin from
central and autonomic nervous system (ANS) terminals (Goodman et al., 2008). The
toxicity of amphetamines is exemplified when administered with alcohol (Ghuran et al.,
2000). The sympathetic activation by both cocaine and amphetamines causes
vasoconstriction, tachycardia, hypertension, hypotension and cardiac arrhythmias
(Ghuran et al., 2000). Cocaine is also commonly known for causing myocardial
infarction (Aslibekyan, S., Levitan, E., Mittleman, M., 2008).
Cocaine can raise catecholamine levels as high as five times their normal
level (Ghuran et al., 2000). At extremely high doses, cocaine impairs myocyte
electrical activity as well as blocking fast sodium and potassium channels and
inhibiting the entry of calcium into myocytes (Goodman et al., 2008). The serum half-
life of cocaine is relatively short, being approximately 30-80 minutes (Goodman et al.,
2008). Ninety percent of cocaine is metabolized and excreted in urine within two
weeks (Goodman et al., 2008). The period of excretion provides a means of diagnosing
recent ingestion in the hospital environment (Goodman et al., 2008). When cocaine is
consumed alongside alcohol, a metabolite is formed called cocaethylene (Goodman et
al., 2008). Cocaethylene is an extremely cardiotoxic metabolite that is much more
toxic than its parent, cocaine (Goodman et al., 2008). A study also revealed that
marijuana use with cocaine increases plasma cocaine levels and concentrations of the
drug (Goodman et al., 2008).
CARDIOVASCULAR EFFECTS OF DRUG 12
Amphetamine and MDMA both produce indirect sympathetic activation by
releasing norepinephrine, serotonin and dopamine from CNS and ANS terminals
(Ghuran et al., 2000). Compared to cocaine, amphetamine inhibits monoamine oxidase
and does not contain a local anaesthetic effect (Goodman et al., 2008). Alcohol
potentiates amphetamine when taken concurrently with each other (Goodman et al.,
2008). Ecstasy and amphetamine plasma half-life are similar, as ecstasy is a derivative
of amphetamine (Goodman et al., 2008).
iii. Narcotics (Opioid Analgesics)
Opiod is a term that refers to all compounds that have a relation to opium,
which is a derivative of the poppy (Goodman et al., 2008). The drugs that are derived
from opium are opiates that include morphine, thebaine, codeine and a large amount of
semi- and synthetic derivatives (Goodman et al., 2008). Opiates work by mimicking
endogenous opiod peptides, also known as endorphins that are the naturally occurring
ligands for opiod receptors (Goodman et al., 2008). Opiod receptors, or endogenous
opiod receptors, have the known sensory role, which is inhibiting painful response from
painful stimuli (Goodman et al., 2008).
Opioids primarily act through three different receptor types. The three
receptor types are the µ, δ and κ, which have been studied thoroughly (Goodman et al.,
2008). Similar to morphine, the majority of clinical used opioids select µ receptors
(Goodman et al., 2008). High doses possibly change the pharmacological profile of the
opioid taken and become especially true when doses are increased to overcome
tolerance, which is very common with recreational opioid use (Goodman et al., 2008).
CARDIOVASCULAR EFFECTS OF DRUG 13
Tolerance occurs when a decrease in effectiveness of a drug due to repeated
administration (Goodman et al., 2008).
Clinically used opiates exert themselves through the µ receptors affecting
numerous systems (Goodman et al., 2008). The effects most commonly seen are
alterations of respiratory, gastrointestinal, neuroendocrine and cardiovascular system
function (Goodman et al., 2008). Morphine-like opioids produce many CNS effects as
well (Goodman et al., 2008). The effects most likely encountered are drowsiness,
analgesia, mental clouding and mood changes (Goodman et al., 2008). In addition to
these effects, euphoria is commonly reported which is one of the factors that make
opioids a commonly abused recreational and illicit drug (Goodman et al., 2008). As
doses increase the effects of the drugs increase including respiratory and cardiovascular
depression (Goodman et al., 2008).
The specific cardiovascular effects of opioids vary according to the dose
taken. When a patient or user is supine, the majority of cardiovascular effects of
opioids are negligible (Rea, R., Thames, M., 1993). Orthostatic hypotension and
fainting generally occur when a supine patient assumes the upright position (Rea et al.,
1993). Much of these effects are provoked by the concurrent release of histamine when
taking opioids (Rea et al., 1993).
Goodman & Gilman’s Manual of Pharmacology and Therapeutics (2008) shows that:
Effects on the myocardium are not significant in normal individuals. In patients
with coronary artery disease but no acute medical problems, 8–15 mg morphine
administered intravenously produces a decrease in oxygen consumption, left
ventricular end-diastolic pressure, and cardiac work; effects on cardiac index
CARDIOVASCULAR EFFECTS OF DRUG 14
usually are slight. In patients with acute myocardial infarction, the
cardiovascular responses to morphine may be more variable than in normal
subjects, and hypotension may be more pronounced.
Morphine may exert its well-known therapeutic effect in the treatment of
angina pectoris and acute myocardial infarction by decreasing preload, inotropy,
and chronotropy, thus favorably altering determinants of myocardial O2
consumption and helping to relieve ischemia. Morphine can mimic the
phenomenon of ischemic preconditioning, where a short ischemic episode
paradoxically protects the heart against further ischemia. This effect appears to
be mediated by d receptor modulation of a mitochondrial ATP-sensitive K+
channel in cardiac myocytes.
Morphine-like opioids should be used with caution in patients who have a
decreased blood volume because the drugs can aggravate hypovolemic shock.
Morphine should be used with great care in patients with cor pulmonale because
deaths after ordinary therapeutic doses have been reported. The concurrent use of
certain phenothiazines may increase the risk of morphine-induced hypotension.
(p. 355)
iv. Ethanol (Alcohol)
Ethanol is a sedative and CNS depressant but has a different structure and
action than the pharmacological sedatives listed earlier (Goodman et al., 2008).
Ethanol is the only legal, non-prescription recreational drug that is as widely accepted
and as much of a societal problem as it is. The disturbance between the inhibitory and
excitatory influences in the brain causing disinhibition, sedation and ataxia are some of
CARDIOVASCULAR EFFECTS OF DRUG 15
the adverse effects of ethanol (Goodman et al., 2008). Unlike most drugs, exceedingly
large amounts of ethanol are required to cause physiological effects (Goodman et al.,
2008).
Studies regarding the epidemiology of alcohol consumption show that 20-30
grams ethanol/day confers a cardioprotective effect (Goodman et al., 2008).
Paradoxically consumption of larger amounts of alcohol daily infer a much greater and
increased risk of cardiovascular failure including, cardiomyopathy, arrhythmias and
stroke (hemorrhagic) (Whicker, S., Sayer, G., Saltman, D., 2006). Large amounts of
alcohol use can cause hypertension by raising diastolic and systolic blood pressure
(Goodman et al., 2008). Ethanol causes numerous effects pharmacologically on cardiac
conduction, which includes sympathetic stimulation and ventricular repolarization
(Goodman et al., 2008). The ventricular repolarization is indicated by a prolonged QT
interval (Goodman et al., 2008).
Goodman & Gilman’s Manual of Pharmacology and Therapeutics (2008) shows that:
Atrial arrhythmias associated with chronic alcohol use include
supraventricular tachycardia, atrial fibrillation, and atrial flutter. Some
15–20% of idiopathic cases of atrial fibrillation may be induced by
chronic ethanol use. Ventricular tachycardia may be responsible for the
increased risk of unexplained sudden death that has been observed in
persons who are alcohol-dependent. During continued alcohol use,
treatment of these arrhythmias may be more resistant to cardioversion,
digoxin, or Ca2+-channel blocking agents. (p. 376)
CARDIOVASCULAR EFFECTS OF DRUG 16
Alcohol is known to cause cardiomyopathy by having a toxic dose-related
effect on cardiac and skeletal muscles (Goodman et al., 2008). Various studies show
the depression of cardiac contractility by alcohol, which leads to cardiomyopathy
(Goodman et al., 2008). Statistics show that half or more of patients with idiopathic
cardiomyopathy are alcohol dependent (Goodman et al., 2008). 40-50% of all patients
with cardiomyopathy that is ethanol/alcohol induced will die within 3-5 years as an
effect of their alcohol dependence (Goodman et al., 2008).
v. Cannabis and Khat
Cannabis, also known as Marijuana, is the 2nd most used drug in America
right behind ethanol (Health, United States, CDC, 2010). Δ-9-tetrahydrocannabinol
(THC) is the primary psychoactive chemical in cannabis. (Ghuran et al., 2000) THC is
only one of 61 cannabinoids and approximately 340 other chemical compounds in
cannabis not including the same carbon monoxide, tars, carcinogens and irritants found
in tobacco smoke (Hall, W., Solowij, N., 1998).
The action of THC is on at least two types of cannabinoid receptors, CB1 and
CB2. CB1 receptors are primarily present in the cognitive, memory, reward, anxiety,
pain, endocrine function, sensory perception and motor co-ordination regions of the
brain (Goodman et al., 2008). CB2 can be found in the spleen and other tissues and can
possibly but culprit for the immunosuppressive activities of cannabis (Goodman et al.,
2008). Outside of the psychoactive effects of cannabis it also has cardiovascular and
respiratory effects that can be notable (Hall, W., Solowij, N., 1998). The
cardiovascular effects of cannabis have a biphasic effect based off of dose taken
(Ghuran et al., 2000). Cannabis in acute doses is responsible for tachycardia and
CARDIOVASCULAR EFFECTS OF DRUG 17
vasodilation resulting in hypotension and increased core temperature (Ghuran et al.,
2000). The cardiac output due to the effects of cannabis has been noted to increase as
high as 30%, which is normally accompanied by and increased cardiac work and O2
demand (Goodman et al., 2008). At higher doses the actions of cannabis reverse
commonly causing bradycardia and hypotension (Caldicott, D., Holmes, J., Roberts-
Thompson, K., Mahar, L., 2005). Along with these higher dose effects there have been
ECG abnormalities affecting the P & T waves as well as the ST segment (Goodman et
al., 2008). The onset of the physiological effects of cannabis is seen very shortly after
absorption (Hall, W., Solowij, N., 1998). The plasma half-life of cannabis is between
20-30 hours (Goodman et al., 2008).
Catha edulis, also known more commonly as khat, is one of the more
common and popular drugs in the Arabian Peninsula and horn of Africa (Al-Motarreb,
A., Al-Kebsi, M., Al-Adhi, B., Broadley, K., 2002). It is estimated that there are
between 5-10 million khat users in the world (Al-Motarreb et al., 2002). Khat has
various pharmacologically active constituents but S-(-)-Cathinone [S-(-)-α-
aminopropiophenone] is the most significant (Widler, P., Mathys, K., Brenneisen, R.,
Kalix, P., Fisch, H., 1994). Cathinone is an alkaloid that is closely related to
amphetamines, which raises concern for cardiovascular complications (Wilder et al.,
1994). Much of these complications are caused by marked hypertension due to
cathinone metabolizing into norephedrine and norpseudoephedrine (Apps, A., Matloob,
S., Dahdal, M., Dubrey, S., 2011). There have been reported cases of khat use linked
with myocardial infarction and ischemia (Al-Motarreb et al., 2002).
vi. Psychedelics
CARDIOVASCULAR EFFECTS OF DRUG 18
Lysergic acid diethylamide (LSD) and psilocybin (Shrooms) are the primary
recreationally used psychedelics (Ghuran et al., 2000). Both LSD and psilocybin
chemically resemble serotonin so their actions are similar (Ghuran et al., 2000). LSD is
an ergot alkaloid that is a nonselective 5-HT agonist (Goodman et al., 2008). LSD
primarily acts through the 5-HT2 receptors inhibiting the firing of raphe neurons (5-HT)
(Goodman et al., 2008). The cardiovascular effects of LSD can include increased pulse
and hypertension (Ghuran et al., 2000). Serotonin abnormalities may result in atypical
clotting and reduced clot retraction (Goodman et al., 2008). Although rare, myocardial
infarction and supraventricular tachyarrhythmias have occurred as a result of LSD use
(Ghuran et al., 2000).
vii. Dissociative anesthetics
Phencyclidine (PCP) and Ketamine and are the primary dissociate anesthetics
abused (Goodman et al., 2008). Ketamine clinically is used for conscious sedation and
anesthesia and has some very unique properties (Goodman et al., 2008). Ketamine is in
the same drug class as phencyclidine (PCP) and is water-soluble (Goodman et al.,
2008). Administration and induction of ketamine normally causes hypertension,
tachycardia and an increase in cardiac output (Goodman et al., 2008). These
cardiovascular effects are most likely due to the inhibition of central and peripheral
catecholamine reuptake making this an indirect effect (Goodman et al., 2008).
Ketamine does have direct adverse cardiovascular effects including inotropic and
vasodilation activity (Goodman et al., 2008). Ketamine also increases myocardial O2
consumption that can cause severe cardiac complications in users with myocardial
ischemia (Goodman et al., 2008).
CARDIOVASCULAR EFFECTS OF DRUG 19
viii. Inhalants or Volatile Substances
Recreationally used inhaled substances are common among adolescents and
non-selective drug seekers (Ghuran et al., 2000). These volatile substances are
normally cheap, legal and can easily be obtained which make this very concerning and
hard to control (Ghuran et al., 2000). Varied and extremely detrimental cardiovascular
effects can occur from inhalant use, including sudden death (Ghuran et al., 2000).
Tachyarrhythmias from sympathetic nervous system activation are a common
occurrence from volatile substance use (Ghuran et al., 2000). Myocardial sensitivity to
circulating catecholamines may also cause lethal tachyarrhythmias (Ghuran et al.,
2000). Some of the notable cardiovascular complications from volatile substances
include bradyarrhythmias, supraventricular arrhythmias, ventricular arrhythmias,
hypotension, cardiac ischemia and cardiomyopathy (Ghuran et al., 2000).
ix. Synthetics and Analogues
Spice, K2 and bath salts are among the top of the list of the most popular
“legal” drugs available on the street (“HDAP,” 2011; “Office of,” 2011). Spice and K2
are synthetic cannabinoids, which belong in the same drug class as cannabis (“HDAP,”
2011). Bath Salts are a stimulant being sold as a legal cocaine and ecstasy substitute
that contains Methylenedioxypyrovalerone (MPDV), which is also known as
mephedrone (Wehman, J., 2011; O’Malley, P., 2011). MPDV has no known clinical
medical value therefore information is extremely limited on it’s pharmacodynamic,
pharmokinetic and pharmacological properties (O’Malley, P., 2011).
Spice being like cannabis has many similar effects. One frightening
difference between spice and cannabis is that the potency has been found to be upwards
CARDIOVASCULAR EFFECTS OF DRUG 20
of 5 times more potent than the strongest marijuana (“HDAP,” 2011). The effects of
the synthetic cannabinoids have not been fully tested yet but many adverse effects have
been seen. Spice has been associated with adverse effects such as heart palpitations,
respiratory complications, paranoia and aggression (“HDAP,” 2011).
V. Statistics
Drug use and abuse is growing in massive proportions from year to year and is causing
an overwhelming and increasing workload on emergency rooms and prehospital providers
around the globe. The Drug Abuse Warning Network (DAWN) monitors drug-related
emergency room/department visits and deaths as a public health surveillance system in order to
track the impact of drug use in the United States. Each year data is compiled from hospitals
across the country about drug-related emergency department visits and death and made available
to the public.
According to the National Survey on Drug Use and Health (NSDUH), approximately
21.8 million Americans, ages 12 or older, in 2009 consumed illicit drugs (“Health, United
1,619,054 1,616,311 1,742,887 1,883,272 1,999,861 2,070,439
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
Annual Estimated Visits
Total ED Visits
DAWN Drug Related ED Visits
Estimates 2004 Estimates 2005 Estimates 2006
Estimates 2007 Estimates 2008 Estimates 2009
CARDIOVASCULAR EFFECTS OF DRUG 21 States,” 2010.) Of the 21.8 million illicit drug users, approximately 5.1 million in total used
drugs other than marijuana (“Health, United States,” 2010). Between 2004 and 2009 there have
been a staggering 10,931,824 drug-related ED visits (DAWN, 2009). Not all of these drug-
related have cardiovascular complications associated with them. Of these 10.9 million visits 3.7
million can alone be contributed to alcohol consumption, which is commonly in combination
with other recreational drugs (DAWN, 2009). Statistics show that 1 in 4 myocardial infarctions
(MI), also known as heart attacks, in people between the ages of 18 and 45 can be linked to
cocaine use (Qureshi, A., Suri, F., Guterman, L., & Hopkins, N., 2001). A total of 2.966,511
visits can be attributed to cocaine use that means nearly 741,627 of those cocaine related visits
had a non-fatal myocardial infarction (DAWN, 2009). Dependence of the various recreational
and illicit drugs is a contributing factor to cardiovascular complications (DAWN, 2009).
Goodman and Gilman’s 2008
VI. Conclusion
CARDIOVASCULAR EFFECTS OF DRUG 22
Recreational and illicit drug use across the board has some varying effect on the
cardiovascular system. More information and studies are required to find definitive links to
some drugs and their cardiovascular effects, such as marijuana, but evidence does exist that even
the drugs viewed as harmless are far from it. Every year there is an increasing number of pre-
hospital and emergency room cases showing and linking cardiovascular complications to drug
use. Cardiovascular effects are not the only concern of recreational and illicit drugs but ranks
high on the list.
CARDIOVASCULAR EFFECTS OF DRUG 23
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