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medical implications of substa
4.05.07
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04/07/2007

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Term
EtOH complications of pancreatitis?
Definition
Pancreatitis –
acute (abdominal pain, vomiting, pancreatic necrosis, pseudocyst formation). Dx – elevated serum amylase and lipase.
chronic (chronic abdominal pain, malabsorption due to exocrine failure, hyperglycemia due to islet cell failure)
Term
What is most common cause of pancreatitis?
Definition
EtOH
Term
EtOH and the liver?
Definition
Hepatic toxicity – proposed mechanisms:
reactive oxygen species (ROS) -> reduced levels of antioxidants -> oxidative stress -> cell injury
acetaldehyde and oxygen radicals -> interact with cellular proteins and macromolecules -> hybrid compounds (‘adducts’) -> impedes the function of the original proteins
the adducts may also induce harmful immune responses Alcoholic hepatitis –
acute inflammation of the liver, often after period of heavy EtOH use
abdominal symptoms, sometimes fever
lab -> incr hepatic transaminases
AST(SGOT) > ALT(SGPT) (maybe by ~2x)
increased bilirubin
Term
What is AST/ALT pattern seen wtih EtOH hepitisis?
Definition
AST>ALT
Term
EtOH and hepatic steatosis?
Definition
Hepatic steatosis
deposition of fat within liver parenchyma.
Vs. ‘NASH’ (non-alcoholic steatohepatitis).
can cause hepatic inflammation, elevated liver-associated tests which then generate more testing, anxiety, etc.
Term
EtoH and Cirrhosis?
Definition
Cirrhosis
eventual fibrosis, portal hypertension, leading to numerous potential complications
esophageal varices
ascites
coagulopathy due to diminished clotting factor synthesis
hepatocellular carcinoma
Term
What is EtOH/Hep C synergy?
Definition
Alcohol use in the setting of hepatitis C virus (HCV) infection can accelerate the progression toward cirrhosis
Term
EtOH and FAS?
Definition
Pregnancy
Fetal Alcohol Syndrome
broad range of physical, cognitive, and behavioral disabilities
neuroimaging -
reduced size of basal ganglia
reduced size of the cerebellum
impaired development or agenesis of the corpus callosum
Term
What are the effects of inhalents?
Definition
Nitrous oxide, nitrites –
mechanism:
vasodilation, increase in heart rate
smooth muscle relaxation
mainly used in context of sexual activity
potential interaction with PDE-inhibitors
(e.g. sildenafil) -> severe hypotension
Nitrous oxide
whipped cream canisters
Amyl nitrite, isobutyl nitrite, butyl nitrite
‘poppers’ – implicated in AIDS circa 1983
Term
EtOH and withdrawl?
Definition
Withdrawal syndromes
agitation
delirium tremens (‘D.T.’s)
Epidemiologic association with cancers of the mouth, throat, esophagus, liver, prostate, and in women, breast
Term
acute/chronic tox with huffing?
Definition
Acute toxicity:
129 inhalant abuse deaths were reported to a national data system in 1999
cardiac dysrhythmias
‘sudden sniffing death syndrome’
interference with oxygenation
seizures
Chronic toxicity:
peripheral neuropathy
hepatic injury (esp. hydrocarbons)
behavioral and cognitive impairment
Term
Amphet and CV/Neurbehva complications?
Definition
CNS stimulants, includes (crystal) methamphetamine, methylphenidate
Cardiovascular complications
relate mainly to alpha- and beta-adrenergic agonist properties
Neurobehavioral complications
relate mainly to dopaminergic (over)release and nerve terminal injury at the synapse
Term
Amphet and acute tox?
Definition
Acute toxicity:
systemic
hyperthermia
cardiovascular
tachycardia (beta)
hypertension (alpha and beta)
myocardial infarction
Term
Acute Amphet Neuro?
Definition
Acute toxicity, contin.
Neurologic
seizures
example: hemorrhagic stroke risk from OTC sympathomimetic amine - PPA
“.. we estimate that 1 woman may have a stroke due to phenylpropanolamine for every 107,000 to 3,268,000 women who use products containing phenylpropanolamine as an appetite suppressant within a three-day window ..” NEJM 12/21/00
Term
chronic tox amphet?
Definition
Chronic toxicity:
Cardiovascular
dilated cardiomyopathy (reduced ventricular function)
Neurobehavioral
memory/learning impairment
anxiety, paranoia, psychosis
formication – sense of bugs crawling
anorexia
Term
Derma chronic amphe
Definition
Dermatologic
burns from fires during home manufacturing
Infectious
‘party and play’ (PnP) – behavioral disinhibition leading to transmission of HIV etc.
Term
Amph and preg?
Definition
suggestion of increased rates of
premature delivery
placental abruption
fetal growth retardation
heart and brain abnormalities
Term
barbituates?
Definition
Sedative-hypnotics, includes pentobarbital, secobarbital, phenobarbital, thiopental
Complications relate to the inhibition of neuronal depolarization
potentiating, prolonging, and mimicking GABA, the inhibitory neurotransmitter
blocking glutamate receptors
Term
barb, actue tox?
Definition
Acute toxicity:
narrow therapeutic index – small increment in dose can yield toxicity
depression of the respiratory drive(s) - neurogenic and hypoxemic
Term
chronic tox to barb?
Definition
Chronic toxicity:
tolerance; withdrawal syndrome
neonatal withdrawal
Term
what is main concern with barbs?
Definition
respiratory depression
Term
What happens with acute tox with benzos?
Definition
Acute toxicity:
uncommon to require medical care for acute toxicity
anterograde amnesia
confusion (esp. elderly pts)
Term
what happens with chronic tox with benzos?
Definition
Chronic toxicity:
rebound insomnia
withdrawal syndrome
Term
what does coke do?
Definition
Blocks reuptake of norepi and norepi by the preganglionic neuron
thus excess signal to the postganglionic neuron
sympathomimetic
alpha- and beta-adrenergic
Term
coke acute cardiac complications?
Definition
Acute cardiac complications:
increased myocardial oxygen demand
via increased heart rate, systemic arterial pressure, and LV contractility
coronary artery vasoconstriction
incr alpha-adrenergic stimulation
incr endothelin production
decr nitric oxide production
incr platelet activation
accelerated atherosclerosis, Acute cardiac complic, contin:
cocaine-assoc chest pain
In 2000, 175,000 U.S. E.R. visits
myocardial ischemia
tx: O2, aspirin, nitroglycerin, benzodiazepines
avoid: beta-blockers
myocardial infarction (MI)
supposed 24-fold increase in MI risk within first hour after cocaine use, Acute cardiac complic., contin.:
arrhythmia
aortic dissection
tx: beta-blockers
avoid: aspirin
Chronic cardiac complications
accelerated atherosclerosis
dilated or hypertrophic cardiomyopathy (from chronic sympathetic stimulation)
Term
what tx for aortic dissection?
Definition
beta blockers
Term
what tx for myocardial ischemia?
Definition
oxygen, aspirin, nitroglyercin, bezos. NO beta blockers
Term
coke and respiratory tract?
Definition
Respiratory Tract:
Nasal septal perforation
‘Crack lung’
Acute – hypersensitivity reaction with fever
Chronic - unclear diagnosis
tobacco use a possible confounder
Term
coke: acute neurological complications
Definition
Acute neurologic complications:
seizures
at high doses
intracranial hemorrhage
aneurysmal
( could -> subarachnoid bleed)
hypertensive
( could -> intracerebral bleed)
Term
Coke: systemic problems?
Definition
Acute systemic complications:
hyperthermia
hypermetabolic state
dopaminergic pathways ?involved
impaired heat dissipation
impaired sweating and vasodilation
impaired behavioral response to heat
mimics fever, creating need for eval
rhabdomyolysis
muscle ‘breakdown’
may be consequence of hyperthermia
renal failure from ‘muscle pigment’ may develop
Term
coke and pregnancy?
Definition
Pregnancy
cocaine crosses placenta
fetal plasma esterase activity low vs. adult
maternal
hypertension increased risk of fetal growth retardation, premature delivery
reports of increased risk of congenital malformations
neonatal irritability
controversy re: longer-term neurobehavioral problems (‘crack babies’)
decreased uterine blood flow
spontaneous abortion
placental abruption
Term
MDMA tox?
Definition
MDMA (3,4-methylenedioxymethamphetamine)
increased serotonin release and inhibition of reuptake
Toxicities:
hyperthermia, seizures, rhadomyolysis, fluid/electrolyte imbalance
‘rave’ setting
hepatic injury
cardiovascular effects
incr HR, BP, myocard O2 consumption
Term
liquid ecstacy tox?
Definition
Liquid ecstasy – GHB
reported toxicity includes:
confusion, hallucination
coma, from which pt may rapidly awaken
respiratory depression (esp with concurrent EtOH)
fulminant hepatic failure requiring transplantation
Term
what are acute tox opiates?
Definition
Acute toxicity:
mainly relates to overdose
CNS depression to coma
reduced rate of respiration
reduced brainstem responsiveness to rising CO2
impaired pontine/medullary regulation of breathing rhythm
Term
what are key mech leading to death?
Definition
respiratory and CNS depression are key mech leading to death
Term
chronic tox of opiates?
Definition
Chronic toxicity:
dependence
risk of pneumonia
prolonged Q-T interval on EKG
high-dose methadone
constipation
risks related to IDU (injection drug use)
Withdrawal
Pregnancy
neonatal abstinence syndrome
potential confounding issues re: low birthweight, small head circumference etc.
Term
dissolving agents?
Definition
Inert/particulate matter
sugar, flour, quinine, starch
example: talc (white powder)
lodges in alveolar capillaries
development of ‘talc granulomas’; appear as small nodules on CXR
example: soil; shredded paper dyed with shoe polish (in black tar heroin) -> microbes
Term
what is major IDU related pathogen?
Definition
staph aureus. and MRSA
Term
what viruses from drugs?
Definition
HIV
HBV – hepatitis B virus
HCV – hepatitis C virus
HDV - hepatitis D superimposed on HBV
GBV-C – a flavivirus
HTLV-I and II – human T-cell lymphotropic virus I and II
Term
what do you get HepC from?
Definition
HepC transmission is more closely linked to IDU than sexual contact
Term
why might the host be immunolgoicall supressessed?
Definition
May be malnourished or living in poor conditions
Vitamin deficiencies may be present
The humoral immune system may be polyclonally activated
elevated IgM and IgG
Term
what are ways of drug admin?
Definition
Not limited to the well-known routes
can inject cocaine, snort heroin
Oral (p.o)
Nasal insufflation (intranasal/snort)
sinusitis
epidemiologic association of HCV infection with sharing straws used for snorting cocaine; Smoking or inhalation
‘huffing’, ‘bagging’ etc.
‘hotboxing’ in a car
transmission of M. tuberculosis
Transrectal
‘keistering’, ‘booty bumping’
Term
What does IDU stand for?
Definition
IDU – ‘injection drug use’
development of injection equipment circa 1855
intravenous (IVDU)
intramuscular (IM)
subcutaneous (SC)
a.k.a. ‘skin-popping’
‘shooter’s patch’
Term
what is edogenous endophthalmitis?
Definition
Eye/ear/nose/throat:
endophthalmitis – infection of the ocular cavity (vitreous)
endogenous endophthalmitis –
seeded hematogenously (via IDU or
other unrelated bacteremia)
Staphylococcus aureus
Candida species

differs from ‘exogenous’ endophthalmitis – stick/paperclip etc. into eye, or ocular surgery complication
Term
what are major problems with bloodstream?
Definition
Bloodstream:
air embolism – injection/entry of air into the vascular system
bacteremia/fungemia – transient or sustained circulation of bacteria or yeast (can be a hallmark of endocarditis as well - next slide)
Staph. aureus
Pseudomonas aeruginosa, others
Term
what are major cardiac problems?
Definition
Cardiac:
endocarditis – organism in blood develops a nidus of infection on heart valve or other endocardial structure.
usually a predisposing valvular abnormality (congenital or acquired)
IDU (especially intravenous) can over time create damage to valves, especially TV, PV (but also MV, AoV)
infective endocarditis (IE) – can categorize
by presentation
acute bacterial (ABE)
subacute bacterial (SBE)
by location
R-sided (TV, PV) vs. L-sided (MV, AoV)
native (NVE) vs. prosthetic (PVE)
by organism
bacterial vs. fungal
‘culture negative’; most common organism - Staph. aureus
increasingly beta-lactam resistant (MRSA)
Tx: prolonged antibiotic therapy (weeks), almost always IV
valve-replacement surgery sometimes indicated
quasi-ethical debate re: performing if ongoing IDU, since high risk of developing future PVE
previous endocarditis is a risk factor for future episodes (if survives the first episode)
Term
what are peripheral vascular problems?
Definition
Peripheral vascular:
arterial occlusion/vasospasm
inadvertent intraarterial injection e.g. cocaine
vasculitis
rare - cocaine, amphetamines
loss of medically-useful venous access due to overuse; septic thrombophlebitis
infected vein wall/clot
often accompanied by fever, bacteremia
mycotic aneurysm
seeding of vessel wall or vaso vasorum ->
infection and weakening of arterial wall -> ‘mushroom-like’ (‘mycotic’) aneurysmal dilation
Term
what are pul infectious problems?
Definition
Cigarette use associated with ~four-fold increased risk of invasive pneumococcal disease (meningitis, bacteremia) (NEJM 3/9/00)
Pneumothorax – air introduced from environment (or by lung puncture) during attempted injection into jugular vein
Term
what are renal complications?
Definition
Renal:
sclerosing glomerulonephritis,
a.k.a. ‘heroin nephropathy’
inflammatory process in glomeruli, presumably an immunologic reaction to circulating drug or contaminants
Term
what are major GI problems?
Definition
Gastrointestinal:
splenic abscess
complication of bacteremia
hepatitis b, c, delta –
acute liver failure
cirrhosis
hepatocellular carcinoma
Term
what are major derma problems?
Definition
Dermatologic:
‘Track marks’
carbon particles (?and hemosiderin), scarring
Soft tissue infection
cellulitis – infection of skin and subcutaneous tissues
abscess – from skin-popping or IV use
example: ‘speedball’ = cocaine + heroin
local tissue ischemia from cocaine-induced vasoconstriction, plus microbes from unsterile agent/procedure -> risk for abscess

Dermatologic, contin.:
Soft tissue infection, contin.
fasciitis – infection of superficial or deep fascia
soft-tissue pathogens:
gram positives (staph/strept)
rise in methicillin-resistant Staph. aureus (MRSA) among non-hospitalized persons
aerobic gram negative rods
from environment/water
Pseudomonas, Serratia, Proteus, etc.
Dermatologic, contin.: soft tissue pathogens
anaerobes
clostridial skin/subcut infectn
skin-popping black tar heroin
C. tetani - tetanus
C. botulinum – wound botulism
C. perfringens - gas gangrene
C. sordellii - shock-like syndrome
C. novyi – local infection and circulatory collapse
Term
musculoskeleton problems?
Definition
Hematogenous route more likely the cause than direct inoculation
sternoclavicular joint involment after using jugular vein
(Pyo)Myositis – focal infection within skeletal muscle
usually Staph. aureus ; septic arthritis – infection of joint space
Staph. aureus most common
Pseudomonas
Candida species
osteomyelitis – infection of bone
Staph. aureus most common
Term
Neurologic problems?
Definition
Neurologic:
Vertebral osteomyelitis
Spinal epidural abscess
Staph. aureus most common in IDU
may result in paraplegia or paralysis
Brain abscess
usu. subsequent to bacteremia/endocarditis
Clostridial syndromes
see dermatologic
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