Anand, Preetha et al. Cancer is a Preventable Disease that Requires Major Lifestyle Changes...

Anand, Preetha et al. Cancer is a Preventable Disease that Requires Major Lifestyle Changes Pharmaceutical Research, Vol. 25, No. 9, Sept 2008

BBC NEWS – Cancer

Jack Andraka & Pancretic Ca

Practice Questions

Autocoid

Pharm. Practice QuestionsPharm. Practice Questions1 – A 57-year-old Caucasian male is being evaluated for hyperlipidemia. He has a history of unstable angina and long-standing hypertension. As you prescribe the appropriate medications to this patient, you explain that he will likely experience skin flushing and warmth after taking his pills. Which of the following mediates the side effect you describe?

AnswerAnswer

A. Histamine

B. Serotonin

C. Prostaglandin

D. Substance P

E. Platelet-activating factor (PAF)

Pharm. Practice QuestionsPharm. Practice Questions

2 – A 75-year-old Caucasian male is brought to your office with a pruritic rash. He has poor vision and a history of frequent falls. Which of the following would be the most appropriate medication considering this patient’s past medical history?

AnswerAnswer

A. Hydroxyzine

B. Promethazine

C. Fexofenadine

D. Chlorpheniramine

E. Diphenhydramine

Pharm. Practice QuestionsPharm. Practice Questions

3 – A An 18-year-old woman presents to her primary care physician after experiencing a one-sided headache for the fourth time in the last 2 years. Her headaches have all been similar in nature. She says the pain is worst right behind her eye and that she feels nauseous and cannot stand bright lights or loud noises while she is having a headache. The physician prescribes sumatriptan. What is the mechanism of action of this medication?

AnswerAnswer

A. Blocking cyclooxygenase enzymes in the CNS

B. Blocking serotonin-mediated nociceptive signaling

C. Blocking synthesis of pro-inflammatory prostaglandins around nerve endings

D. Stimulating -receptors in the brain

E. Stimulating -receptors in the brain

TOXICOLOGY

Defined:•Is the study of the adverse effect of chemicals on living organisms.•All chemicals and drugs have some degree of toxicity.

Toxicology

CHEMICAL ROUTE OF CONTACT

• Inhalation• Oral• Topical• Self-injection

TARGET ORGANS

• Lungs via inhalation for gases, vapors

• Liver for ingested chemical by mouth

• Brain

• Kidney

• Heart

TOXIC ACTIONS

• Nonselective action

• Selective action: e.g., warfarin inhibiting specific clotting factors

• Immediate actions: e.g., OP poisoning

• Delayed action: e.g., exposure to asbestos

OCCUPATIONAL & SPECIFIC ENVIRONMENTAL TOXINS

• A. Halogenated hydrocarbons: exposure is through ingestion or inhalation.

Carbon tetrachloride ( CCl4 ):

•contracted by consumption of contaminated

drinking water, inhalation (low levels) →→ leads

to ???

• Toxic effects: irritation of the eye & respiratory

system at low levels. (High levels ??) →→

•Nausea, vomiting, stupor, convulsion, coma & death

from CNS depression at high levels

•Kidney & liver damage.

• Chloroform: by ingestion or inhalation• Toxic effect: hepatotoxicity, nephrotoxicity,

arrythmias, nausea, vomiting, dizziness,

headaches & stupor + CNS depression.

AROMATIC HYDROCARBONS

• Benzene: half of exposure is via tobacco smoke,

combustion of fossil fuels including automobile

gasoline, consumption of contaminated water.

• Toxic effect: are hematopoietic particularly

leukemia (AML), agranulocytosis.

AROMATIC HYDROCARBONS

• Toluene: by automobile emissions, use of toluene-like degreasers, certain paints & furniture polish.

• Toxic effect: CNS depression, drowsiness, ataxia, tremors, impaired speech, hearing , vision, liver, kidney damage & death.

ALCOHOLS

• Methanol & Ethylene glycol: are oxidized to toxic

products. Formic acid ↔ methanol

• Glyoxylic, glycolic and oxalic acid- ethylene glycol

• Toxic effects: coma, seizures, hyperpnea, visual loss

(esp with methanol), hypotension & nephrotoxicity

(ethylene glycol).

• Antidote: fomepizole, IV ethanol

PESTICIDES

• Organophosphates & carbamate insecticides:

toxicity is via inhibition of AchE resulting in

accumulation of excess acetylcholine.• Antidote: atropine + pralidoxime

A 60-year-old farmer is brought to the emergency department due to confusion, muscle cramps and difficulty breathing. His past medical history is insignificant. He currently takes no medications. Physical examination reveals excessive sweating, wheezing and bradycardia. His pupils are constricted, Symmetric and reactive to light. Intravenous atropine is administered and he gradually improves. Which of the following is still a risk for this patient?

A. BradycardiaB. BronchospasmC. Intestinal obstructionD. Muscle paralysisE. Urinary incontinence

RODENTICIDES

• Exposure is by accidental ingestion or suicidal ingestion e.g., warfarin.

• Warfarin mechanism ???• Antidote: ?

HEAVY METALS

• Lead (Pb): old paint chips, drinking H2O,

industrial pollution, food & contaminated dust• Distributed to soft tissues, teeth, hair & bone

where it is detected by X-ray examination.• Blood = 1 - 2 months • Bone = 20 - 30 years.

HEAVY METALSToxic effects:

•CNS: headache, confusion, clumsiness, convulsion coma & rarely death if treated with chelation therapy.

•GIT: constipation, intestinal spasm

•BLOOD: hypochromic, microcytic anemia.

•Still birth, decrease fertility.

•Antidotes: dimercaprol, succimer

• IRON (Fe): used as prenatal supplements &

also for the treatment of anemias• Fe poisoning: severe GI distress leading to

necrotizing gastroenteritis with hematemesis

and bloody diarrhea, dyspnea, shock, coma• Antidotes: deferoxamine IV, phlebotomy

Mercury (Hg): (elemental, IO, O)

•1. Elementary mercury: exposure is usually occupational by inhalation of the vapor.

•SE: depression, tremors, memory loss, inflammation of the kidneys, decreased verbal skills & pulmonary toxicity.

•2. inorganic mercury: e.g., mercuric chloride, exposure is usually occupational.

•Toxic effect: renal damage.

Mercury: (elemental, IO, O)

•3. organic mercury: exposure is by ingestion of fish

contaminated with methylmercury, dyes, fireworks,

photography

•SE: visual loss, loosening of teeth, paresthesias, ataxia,

hearing loss, tremors, mental deterioration & movement

disorders.

•Can be misdiagnosed as Parkinson's disease in the elderly.

•Org Hg most toxic of the 3 forms.

Antidotes: activated charcoal, succimer & dimercaprol

• Arsenic: seen as wood preservatives, pesticides,

ant poisons• SE: gastroenteritis, hypotension, garlic scented

breath, torsades, rice water stool, stocking

glove neuropathy, skin pigmentation (raindrop

pattern)• Antidotes: activated charcoal, dimercaprol,

penicillamine or succimer

GASES• Carbon monoxide: colorless, odorless & tasteless gas.

• Source: combustion of C- materials, automobiles,

poorly vented furnaces, fireplaces, wood-burning stoves,

charcoal grills & kerosene space heaters.

• Toxic effects: is related to hypoxia within brain & heart.

Dyspnea, lethargy, confusion, headache, drowsiness,

seizures, coma & death.• Antidote: removal from source + 100% O2 by face

mask or endotracheal tube.

• Cyanide: toxicity is as a result of inactivation of the enzyme cytochrome oxidase (where is this?)

• Toxic effect: death due to respiratory arrest .

• Antidote: nitrite, thiosulfate

• Asbestos: exposure is by inhalation of fibers.

• Abestosis, mesothelioma & lung cancer associated with exposure.

• Symptom: pain in the vicinity of the lesion, dyspnea and cough.

• Silica: occupational, seen in mine workers, construction sites & stone cutting.

• Is currently incurable.

ANTIDOTES• Atropine: for intoxication by OP

• Pralidoxime: for OP poisoning by reactivation of AcHE.

• N-acetylcysteine: for acetaminophen toxicity.

• Sodium nitrite and sodium thiosulfate: for cyanide toxicity.

• Fomepizole: for methanol or ethylene glycol toxicity.

CHELATORS:

• Dimercaprol: to chelate Hg , Pb & As

• Succimer: for mild Pb, Hg intoxication.

• EDTA: back up for Pb intoxication.

• Penicillamine: Cu, Fe, Pb, Hg

A Toxicology Question

Pharm. Practice QuestionsPharm. Practice Questions

1 – A A 35-year-old male presents to the physician’s office with a several day history of colicky abdominal pain, constipation irritability and headaches. He works at a battery manufacturing factory. His past medical history is significant for iron deficiency anemia depression and occasional illicit drug use. Which of the following is the most likely cause of this patient’s current condition ?

AnswerAnswer

A. Lead poisoning

B. Iron poisoning

C. Fluoxetine overdose

D. Methanol ingestion

E. Cocaine abuse