Environmental diseases 2 Bianchi Flashcards
__________ is the leading exogenous cause of human cancers, including 90% of lung cancers
tobacco, responsible of 4 million deaths annually, worldwide
Smoke contains a complex mixture of _______ chemicals
7000, At least 60 are carcinogens
describe Nicotine
- strongly addictive
- binds to nicotinic acetylcholine receptors
- stimulates the release of catecholamines from
sympathetic neurons
acute effects of Nicotine:
-increase in heart rate
-increase in blood pressure
-elevation of cardiac contractility and
output
__________ - directly involved in the development of lung cancer in humans
- activated by cytochromes P-450
Polycyclic hydrocarbons and nitrosamines
smoking and the diseases associated with it:
- associated with cancers of the esophagus, pancreas, bladder, kidney, cervix, and bone
marrow but also liver and colon (US Surgeon General) - irritant effect on the tracheobronchial mucosa
- inflammation and increased mucus production (bronchitis)
- recruitment of leukocytes → injury to lung tissue → obstructive pulmonary disease
- strongly linked to the development of atherosclerosis
___________:
- harms the developing fetus → intrauterine growth
retardation
- increases the risk of type 2 diabetes, rheumatoid
arthritis, age-related macular degeneration, ectopic
pregnancy, and erectile dysfunction
smoking
________ is a CNS depressant:
Ethanol
________ mg/dL = Drowsiness
200
_________ mg/dL = Stupor
300
_________ = Coma,
respiratory arrest
> 300mg/dL
where does alcohol mainly get metabolized?
liver
which enzymes metabolize ethanol in the liver?
1- alcohol dehydrogenase (constitutive)
2- cytochromes P-450 (Inducible = ↑expression)
3- catalase
All of them produce acetaldehyde
4- acetaldehyde dehydrogenase → acetic acid (activated to acetyl-CoA for Krebs cycle)
toxic effects of Acetaldehyde?
lipid accumulation in the liver, inflammation of the liver, fibrosis of the liver, carcinogenesis of the liver, inhibition of protein synthesis.
in 50% of japanese and indians the Aldehyde Dehydrogenase varies ALDH21 → ALDH22
which causes ?
lower metabolic activity and thus lower tolerance to alcohol.
how does alcohol damage the liver?
the Alcohol dehydrogenase causes the depletion of NAD which is responsible for the malfunction of the Beta oxidation and thus causes the fat accumulation in the liver and causes acidosis.
effects of alcohol on CNS?
-affects subcortical structures
that modulate cerebral cortical
activity
-disordered cortical, motor, and
intellectual behavior.
-cortical neurons and lower
medullary centers are depressed
-respiratory arrest may follow.
effects of alcohol on gastrointestinal tract?
acute gastritis and ulceration
effects of alcohol on the liver?
-multiple fat droplets accumulate in
the cytoplasm of hepatocytes
-fatty change or hepatic steatosis
The adverse effects of ethanol can be classified as _______ or _______
acute or chronic
fetal alcohol syndrome lead to?
microcephaly, growth retardation, and cognitive defects (advanced aging)
Acetaldehyde and ROS can cause?
cancer of the oral cavity, esophagus, and liver
ALDH2*2 mutation is the risk for developing ?
esophagus cancer
what is Menopausal Hormone Therapy?
-consists of the administration of estrogens together with a progestagen → reduce the number of
fractures in women due to postmenopausal osteoporosis and other menopause-associated
disorders
-MHT increase the risk of breast cancer, stroke, and venous thromboembolism (VTE) after 5 years
of treatment
Risks and benefits of the MHT depend on?
- MHT effects depend on the type of hormone therapy used (combination estrogen-progestagen
versus estrogen alone) - the age and risk factor status of the woman at the start of treatment
- the duration of the treatment
- hormone dosage, formulation, and route of administration
Risk and benefits of MHT?
- Combination estrogen-progestagen increases the risk of breast cancer: RISK
- MHT may have a protective effect on the development of atherosclerosis and coronary disease
in women younger than age 60 years: BENEFIT - MHT increases the risk of stroke and VTE including deep vein thrombosis and pulmonary
embolism: RISK
_________ almost always contain a synthetic estradiol (now low doses) and a variable amount of a
progestin, but some preparations contain only progestins (act by inhibiting ovulation or preventing
implantation)
oral contraceptives
Risks and benefits of Oral Contraceptives?
Breast carcinoma: do not increase breast cancer risk.
Endometrial cancer and ovarian cancers: protective effect against these tumors
Cervical cancer: may increase risk in women infected with human papillomavirus
Thromboembolism: even low-dose (less than 50 µg of estrogen) twofold to fourfold increased risk
of venous thrombosis and pulmonary thromboembolism, particularly in women who are carriers
of the factor V Leiden mutation. lower than the risk of thromboembolism associated with
pregnancy.
Cardiovascular disease: no appreciable risks in nonsmokers but double in smoker women
Hepatic adenoma: association between the use of OCs and this rare benign hepatic tumor
especially in older women who have used OCs for prolonged periods
__________ is the most common used analgesic in the United States (responsible for about 50% of acute
liver failure, with 30% mortality)
paracetamol
in some cases paracetamol might cause damage to the liver:
hepatocellular injury necrosis and progress to
liver failure
effects due to the chronic exposure to the Aspirin?
- CNS changes: hearing impairment, mental confusion, drowsiness
- nonspecific symptoms: nausea, vomiting, and diarrhea
- erosive gastritis: gastrointestinal bleeding and gastric ulceration
- bleeding: inhibits platelet COX1 (constitutive) and then irreversibly blocks the production of
thromboxane A2, the main activator of platelet aggregation
injuries due to the aspirin?
- accidental poisoning or in chronic use for analgesic purposes
- salicylate overdose causes alkalosis because of the stimulation of the respiratory center
- followed by metabolic acidosis and accumulation of pyruvate and lactate
effects of Cocaine?
Produces intense euphoria and neurologic stimulation, making it one of the most addictive drugs
how does the cocaine work?
it blocks the dopamine transporters in the CNS, thus causing them to accumulate in the synaptic cleft and overstimulate the receptors on the receiving neurons.
effects of Cocaine on human health?
hypertension, cardiac arrhythmia, myocardial infarction, cerebral hemorrhage and infarct
other effects of cocaine on human health?
CNS: the most common acute effects on the CNS are hyperpyrexia (thought to be caused by
aberrations of the dopaminergic pathways that control body temperature) and seizures
The acute and chronic effects of cocaine on various organ systems are
Effects on pregnancy: In pregnant women, cocaine may cause acute decreases in blood flow to the
placenta, resulting in fetal hypoxia and spontaneous abortion. Neurologic development may be
impaired in the fetus of a pregnant woman who is a chronic drug user.
Other effects: Chronic cocaine use may cause:
(1) perforation of the nasal septum in snorters → ischemic necrosis
(2) decreased lung diffusing capacity in those who inhale the smoke
(3) dilated cardiomyopathy.
what do cocaine users experience?
- increase in alertness
- feelings of well-being
- euphoria
- increased energy and motor activity
- increased feelings of competence
- Increased sexuality
examples of Opioids:
natural and synthetic, include heroin and prescription drugs such as oxycodone,
hydrocodone, fentanyl, tramadol, and methadone
what is the agonist of endorphin receptors?
Morphine
infections due to the heroin use:
-The sites most commonly affected are:
-the skin and subcutaneous tissue,
-heart valves, liver, and lungs.
In a series of addicted patients more than 10% had endocarditis. Most cases are caused
by Staphylococcus aureus
-Viral hepatitis (HBV, HCV) is the most common infection among addicted persons and is
acquired by the sharing of dirty needles. This practice has also led to a very high
incidence of human immunodeficiency virus (HIV) infection in intravenous drug users.
examples of Opiates:
morphine and codeine, derived from poppy plants
what is heroin?
Heroin (opioids):
Street drug derived from the poppy plant that is closely related to morphine.
The use of Heroin is even more harmful than cocaine. It is cut (diluted) with an agent (often talc or
quinine) thus the size of the dose is not only variable but also usually unknown to the buyer.
effects of Heroin ?
Effects on the CNS
euphoria, hallucinations, somnolence, sedation, rapid addiction
Other adverse effects
Physical effects related to:
(1) the pharmacologic action of the agent
(2) reactions to the cutting agents or contaminants
(3) hypersensitivity reactions to the drug or its adulterants (quinine itself has neurologic,
renal, and auditory toxicity)
(4) diseases contracted due to the use of contaminated needles
sudden death due to heroin:
- Sudden death, usually related to overdose, is an ever-present risk because drug purity
is generally unknown (ranging from 2% to 90%). Addition of very potent synthetic
opioids such as fentanyl and carfentanyl to heroin, greatly increases the chances of
fatal overdose - Sudden death can also occur if heroin is taken after loss of tolerance for the drug built
up over time. - The mechanisms of death include profound respiratory depression, arrhythmia and
cardiac arrest, and severe pulmonary edema.
pulmonary injury due to the Heroun use:
- moderate to severe: edema, septic embolism from endocarditis, lung abscess,
opportunistic infections, and foreign-body granulomas from talc and other adulterants - granulomas occur principally in the lung but they are sometimes found in other organs
(spleen, liver, and lymph nodes that drain the extremities) - examination under polarized light often highlights trapped talc crystals, sometimes
enclosed within foreign-body giant cells
damage to kidneys due to the heroin use:
-Kidney disease is a relatively common hazard. The two forms most frequently
encountered are amyloidosis and focal and segmental glomerulosclerosis; both induce
proteinuria and nephrotic syndrome.
effects of methamphetamine?
feeling of euphoria, which is followed by a
“crash.” Long-term use leads to violent
behavior, confusion, and psychosis marked
by paranoia and hallucinations
what is methamphetamine?
This addictive drug is closely related to amphetamine but has stronger effects in the CNS.
Use started in the early 2000 peaking in the year 2005 but has fallen steadily since that
time
Use of methamphetamine fell to approximately 560,000 users in 2017, a decrease of more
than 50% since 2006
mechanism of methamphetamine?
Methamphetamine acts by
releasing dopamine in the brain, which
inhibits presynaptic neurotransmission at
corticostriatal synapses, altering
glutamatergic transmission
what is tetrahydrocannabinol (THC)?
Agonist of endocannabinoid receptors
Characteristics of Marijuana?
-It is estimated that worldwide 192 million people used marijuana → most widely used
illicit drug globally
-Extracted from Cannabis sativa plant, which contain the psychoactive substance
tetrahydrocannabinol (THC)
effects of Marijuana?
- euphoria and a sense of relaxation, heightened sensory perception (e.g., brighter colors),
laughter, altered perception of time, and increased appetite - beneficial effects of marijuana:
- use to treat nausea after cancer chemotherapy
- use to decrease pain in some chronic conditions that are otherwise difficult to treat
- chronic use is associated to motor cognitive disorders as well as cardiovascular
impairments - other disorders associated to the carcinogens introduced with the smoke
- marijuana addiction remains controversial
- In adults with multiple sclerosis (MS)-related spasticity, short-term use of oral
cannabinoids improves patient-reported spasticity symptoms
For some of these conditions, the effects of cannabinoids are modest; for all other
conditions evaluated there is inadequate information to assess their effects
