Doxirubucin

(Adriamycin)

1. inadequate monitoring

2.improper adherence

3.overprescribing

4.drug-drug or drug-dz/food interactions

5.allergic rxns

6.inadequate atn

7.med errors

8.ADRs

a rxn that is noxious, unintended, and occurs at doses normally used in man for the prophylaxis, dx, or therapy of dz.

(NOT when physician mistakenly gives larger dose, or when pt makes mistake).

1.stabilize pt(remove source and ABCs)

2.Clinical Eval(full history, exam, stat labs/tests, followup)

3.Prevention of further absorption or exposure

4.Enhance elimination

5.Admin antidote

6.supportive care and maintenance

Therapeutic Index

(margin of safety)

calculated by LD50 or TD50/ED50

The larger the therapeutic index the greater safety margin

Acceptable Daily Limit

(ADL)

Threshold Limit Value

(TLV)

1)Polycyclic aromatic hydrocarbons (soot, tar, burned meat, cigs)

2) Aromatic Amines

3)Nitrosamines

4)Aflatoxin(from aspergillus growing on corn, peanuts)

5)Safrole

1)Cyclophosphamide

2)Melphalan

3)Nitrogen Mustard

4)Ethylene Oxide

Contraindicated in pregnant women.

animal and human data reveal fetal impacts or there is evidence or fetal risk based on human experience or both, use of drug clearly outweighs any possible benefit.

Ethanol

diphenylhydantoin(phenytoin)

cig smoke

retinoic acid(tretinoin, retin-A)

thalidomide

pO2 in air

pO2 in alveolar space

160mmHg

100mmHg(b/c water vapor in alveolar sacs)

binding of oxygen to hemoglobin demonstrates this, with each molecule that is bound, the structure of hemoglobin changes slightly. cooperativity allows saturation to occur more rapidly

1.the affinity of hemoglobin for oxygen increases with each molecule of oxygen that is bound.

2.the affinity of hemoglobin for oxygen decreases with each molecule of oxygen that is lost(it takes the least amunt of energy to release the last O2 molecule).

used as internal combustion fuel

odorless, tasteless, colorless, non-irritating

silent killer

a way to get CO poisoning

an idustrial solvent(paint thinner)

fire extinguisher

it's highly lipid soluble

it's metabolized by mixed function oxidases to CO and released in the body

decreases ability of blood to carry oxygen

forms carboxyhemoglobin (COHb)

hemoglobin has a 240-fold greater affinity for CO than O2

**small concentrations of CO can be lethal**

LEFT

hemoglobin becomes fully saturated at a lower pO2, increases the apparent affinity of hemoglobin for O2 and hemoglobin can't release O2 as easily

so, less oxygen transported to the cells and the O2 that is transported is not as readily available to the cells.

1.tightness across forehead (due to cerebral edema potentiated by increase in ICP)

2.dilation of cutaneous vessels

3. labored breathing with exertion

4.throbbing in temples

5. easily fatigued

6.dizziness

7.weakness

8.confusion

9.N/V

10. collapse/fainting

cherry red skin color

(pt with pre-existing heart dz are at special risks)

1. relieve cerebral and cardiac ischemia

2. promote the dissociation of COHb

3. ADMINISTER OXYGEN=direct antidote

4.reduce oxygen demand

5.elevate head and admin mannitol(if cerebral edema)

not a widespread pollutant in environment, most exposures are accidental or suicidal exposures.

bitter almond smell

most rapid acting form of CN

(CN poisoning)

most frequent encoutered form

LD50 is apx 2mg/kg

irritating gas

produce pulmonary edema, tearing,and excessive salivation

found in apple, peach, plum, apricot, cherry, almond seeds

hydrolyzed to form hydrogen CN

CN combines with ferric form of iron (Fe3+) in alot of enzyme systems

most imp=cytochrome a3, it blocks the electron transfer from cytochrome a3 to molecular oxygen (stops ETC, all aerobic respiration stops and no ATP)

reduces celluar utilization of O2 resulting in increased venous pO2

it has the same affect of complete lack of O2

the amount of oxygen reaching the cell is normal, but the cell can't use the delivered O2.

gas is most rapid acting

salts are slowest(must be absorbed through GI)

initially pt dosen't appear cyanotic b/c still have O2

conscious,flushed, rapid pulse, HA, stuporous, tachycardia, tachypnea, comatose, unresponsive, hypotension, respiration slow, gasping, dilated pupils, cyanotic skin color, death due to respiraton arrest.

contains:

1.amyl nitrite inhalant

2.sodium nitrite solution

3.sodium thiosulfate solution

inhalant given first followed by sodium nitrite by iv and then sodium thiosulfate iv

amyl nitrite and sodium nitrite are administered to produce methemoglobin, methemoglobin removes CN from cytochrome a3.

the thiosulfate removes CN from the methemoglobin resulting in formation of thiocynate which is nontoxic and can be excreted in the urine.

Hydroxocobalamin

(cyanokit)

2 vials of lyophilized hydroxocobalamin

MOA: hydroxocobalamin combines with CN to form cyanocobalamin (vit. B12) which is then cleared by the kidney.

coadmin. of sodium thiosulfate is said to have synergistic effects.

adverse effects: transient HTN, reddish-brown skin, mucuous membranes and urine discoloration, rate anaphylaxis type rxns.

Airway, Breath(ventilation), Circulation

ABCs

Cholinergic or Anticholinesterase Syndrome

poisoning from Organophosphates, carbamate insecticides

Cholinergic Excess:

Peripheral-Muscarinic effects: sweating, pupillary contriction, lacrimation, sialorrhea, wheezing, abd. cramps, vomiting, diarrhea, bradycardia, hypotension, blurred vision, urinary incontinence.

Nicotinic effects: fasciculations, cramps, weakness, paralysis, respiratory compromise,mydriasis

peripheral effects:mydriasis, tachycardia,HTN, hyperthermia, flushing, abd. distention, urinary retention, dry skin.

central effects: lethargy, excitement, seizures, confusion, delirium,hallucinations, delusions, etc.

Extrapyramidal Syndrome

extrapyramidal motor system smoothes out otherwise coarse, voluntary muscle motions so when this system is blocked it produces movement disorders by disrupting the balance b/t central cholinergic and dopaminergic tone.

dysphonias, dysphagia, oculogyric crisis, rigidity, tremor, torticollis, opisthotonus, trismus, laryngospasm

non-physiological carboxy hemoglobinemia-most common, CO poisoning, dosen't cause early cyanosis despite sever hypoxia

non-physiological methemoglobinemia develops when toxicants oxidize excessive amounts of ferrous (+2) iron of hemoglobin to the ferric (+3) state.

hypoxia, HA, disoriention, coma, nausea, vomiting, cardiac dysfunction, acidosis, and death.

(HIV pts on dapsone{oxidizing drug} or pts getting endoscopy)

diaphoresis, lack of urinary retention, presence of bowel sounds=adrenergic toxicity

check bed side sugar for hypoglycemic

anxious individuals displaying drug seeking behavior.

opioid withdrawal-mydriasis, piloerection, rhinorrhea, lacrimantion

overdose from sodium channel blockers, TCAs, phenothiazines, and group IA antiarrhythmics

TX-alkalization of urine

toxicity from aspirin, methanol, ethylene glycol

problems from diabetic ketoacidosis, lactic acidosis, uremia

Rattle snake

cotton mouth

copper head(red/brown head)#1 in Arkansas

red on yellow kills a fellow,

red on black, venom lack

bites from coral snakes may appear to be nothing more than scratches belying their often delayed and dramatic toxic potential

venom is like ketamine blocker

weakness, nausea, restlessness, vomiting, diarrhea, sweating, confusion, visual changes, salivation, hypotension, sob, myoglobinuric renal failure may develop (so alkalize the urine).

dramatic decreases in plts, fibrinogen, elevations in INR, PT, PTT, DIC

anaphylactic rxns

Polyvalent Fab crotaline antivenom

(CroFab)

Non-essential metals

(heavy metals)

are less effectively handled b/c the body lacks pharmacokinetic machinery.

toxicity comes from displacement of essential metals from various biomolecules and alteration of their function. related toxicities often involve multiple organ systems.

no life form can synthesize these metals, all required minerals come from dietary sources.

iron, copper, zinc, chromium, selenium, cobalt, magnesium, manganese, and molybdenum(these have known biological functions)

metals which have no known biological role

cadmium(toxic at v. low levels, lack of adequate handling and excretion pathways)

imp ones: lead, mercury, arsenic, cadmium, aluminum

**gastrointestinal and neurological symptoms**

thorough history is important!

can detect arsenic, lead, and mercury

(acute exposure)

Total Body iron(3-5g),ingestion of more than 20mg/kg is likely to cause problems(prenatal vitamins risk for kids)

usually prescribed for occult bleeding and pregnant pts.

Acute iron toxicity

(5 stages)

1.N/V/D(present in 6 hrs)

2.pts appear to improve transiently

3.systemic toxicity recurs w/shock,acidosis, CNS dysfunction

4.Frank liver failure

5.gastic outlet obstruction or stenotic sm bowel

absorbed=oral and inhalation

99% in blood is bound to RBCs

t1/2=1-2months, steady state reached in 6m

slowly accumulates in bone

acute ingestion=nausea, vomiting, abd pain,damage cenral/peripheral NS=encephalopathy, seizures, coma, pailledema,dev. problems, peripheral neuropathy...

*metaphyseal arrest of growth in children produces radiographically evident lead lines in bone. children are at greater risk

removal, supportive,

chelation with BAL, EDTA,(related to pts age,presence of symptoms,whole blood levels)

elementary-inhalation(readily crosses BBB, ionized and trapped)

ingested-concentrate in kidneys(b/c long chain alkyl and aryl mercury cmpds, rapidly oxidized.

short chain alkyl-very lipid soluble, after absorbing through gut, move rapidly in brain, rbcs, liver,kidney,fetus, excreted in bile, undergo enterohepatic recirculation

gastrointestinal decontamination

chelationw/BAL or succimer

d-penicillamine

acute: w/i 30 min. to few hrs, severe cholera like diarrhea, N/V=dehydration, hypotension, myocardial dysfunction, pulm edema, acute renal failure, rhabdomyolysis, mee's lines, alopecia, pancytopenia, chest sympt., black foot dz,palmoplantar keratoses, melanosis, basal cel squamous cell carcinomas

gas-garlic odor-profound hemolysis

have their own inherent toxicities(BAL-peanut oil)

bind only ionic forms of metals, water soluble are more readily excreted in urine or bile.

Organometallic cmpds unreactive toward metals

**the choice of which chelators to use depends upon variables including identity of the metal, form, length of exposure, pts condition**

**for maximum benefit all chelators should be given asap after absorption of toxic dose**

Calcium disodium EDTA-binds calcium, magnesium,zinc (toxic metals displace calcium from chelate)

**nephrotoxic**

chelates lead, mercury, copper

(Wilson's dz-aplastic anemia, agranulocytosis, renal and pulm prob)