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

http://www.bbc.com/future/story/20150306-the-mystery-of-vanishing-cancer BBC NEWS – Cancer

Jack Andraka & Pancretic Ca

Autocoid Practice Questions

Pharm. Practice Questions 1 – 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?

Answer Histamine Serotonin Prostaglandin Substance P Platelet-activating factor (PAF)

Pharm. 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?

Answer Hydroxyzine Promethazine Fexofenadine Chlorpheniramine Diphenhydramine

Pharm. 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?

Answer Blocking cyclooxygenase enzymes in the CNS Blocking serotonin-mediated nociceptive signaling Blocking synthesis of pro-inflammatory prostaglandins around nerve endings Stimulating -receptors in the brain Stimulating -receptors in the brain Sumatriptan monoamine oxidase

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 CHEMICAL ROUTE OF CONTACT

TARGET ORGANS Lungs via inhalation for gases, vapors Liver for ingested chemical by mouth Brain Kidney Heart TARGET ORGANS

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 TOXIC ACTIONS

OCCUPATIONAL & SPECIFIC ENVIRONMENTAL TOXINS A. Halogenated hydrocarbons: exposure is through ingestion or inhalation. OCCUPATIONAL & SPECIFIC ENVIRONMENTAL TOXINS

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. CCl4 was formerly used in fire extinguisher and currently used as a cleaning agent

Chloroform: by ingestion or inhalation Toxic effect: hepatotoxicity, nephrotoxicity, arrythmias, nausea, vomiting, dizziness, headaches & stupor + CNS depression. Used for producing dyes and pesticide and was formerly used as an anesthetic

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

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. AROMATIC HYDROCARBONS

Methanol & Ethylene glycol: are oxidized to toxic products 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 ALCOHOLS

Organophosphates & carbamate insecticides: toxicity is via inhibition of AchE resulting in accumulation of excess acetylcholine. Antidote: atropine + pralidoxime PESTICIDES

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. Bradycardia B. Bronchospasm C. Intestinal obstruction D. Muscle paralysis E. Urinary incontinence

Exposure is by accidental ingestion or suicidal ingestion e. g Exposure is by accidental ingestion or suicidal ingestion e.g., warfarin. Warfarin mechanism ??? Antidote: ? VKER – Factors II, VII, IX, X, protein C & S … Antidote: Packed Red Blood cells, Fresh Frozen Plasma… IV or Oral Vit K1… RODENTICIDES

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 METALS Toxic effects: Antidotes: dimercaprol, succimer 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. Clinical Presentation is?

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 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 ?

Answer Lead poisoning Iron poisoning Fluoxetine overdose Methanol ingestion Cocaine abuse