Pharm Topic 28: Toxin Recognition And Overdose Management

Front 1

What is the most common ingestant?

Back 1

Analgesics

Front 2

What is the number 1 cause of death due to pharm ingestion?

Back 2

Sedative/Hypnotic/Antipsychotics.

Front 3

Salicylates (pKa, protein, dialyzable, tox half life)

Back 3

pKa = 3.5 (weak acid)
90% protein bound
Easily Dialyzable
Tox Half life = 20hrs.

Front 4

Salicylates Elimination

Back 4

Mainly via conjugation but becomes overwhelmed and becomes Michaelis-Menten elim in OD.

Front 5

Sialicylates TOX mech

Back 5

Uncouple ox phos leading to increased metabollic rate, hyperventillation, heat production and acidosis. Increased glycolysis leads to hyperglycemia. Kids get hypoglycemia.
Also Interfere with coagulation factors leading to hypoprothrombin, capillary fragility, decreased platelet adhession, and throbocytopenia.

Front 6

Salicylates antidote

Back 6

Vit K for coagulation
Sodium bicarbonate for the acidosis and to decrease absorbtion and increase secretion.

Front 7

Salicylates and Fetus

Back 7

Crosses placenta. May cause metabolic acidosis in newborn, possible teratogen, contraindicated in 3rd trimester.

Front 8

Sodium Bicarbonate

Back 8

Used to correct metabollic adicosis from ethylene glycol poisoning or when there are high loads of acid. Can also fix wide complex ventricular rythems from tricyc antidepressant poisons and other drugs that block Na channel. Used to alkalinize urine, increaseing excretion of weak acids. Also used to decrease crystalization of -globins in renal tubules.

Front 9

Acetominophen Elimination

Back 9

Mostly by glucuronidation, but some by CYP 2E1 > NAPQI. NAPQI is detoxed by glutathione.
Peak plasma levels may be delayed if co-ingested with narcs and GI slowing drugs.

Front 10

Acetominophin TOC mech

Back 10

If there is insufficient glutathione, NAPQI binds to macromolecules causing hepatic damage.

Front 11

NAC

Back 11

Used for acetaminophen TOX. Promotes glutathione synth and offers a harmless substitute for active metabolites of acetaminophen to bind to.

Front 12

NSAIDs types

Back 12

-Salicylates
-Propionic acids (ibuprofen, naproxen, ketoprofen, oxaprozin)
-Acetic acids
-Oxicams
-Pyrazolones
-Fenamates

Front 13

Symptoms of an NSAID overdose

Back 13

-CNS depression
-Resp depression
-Metabolic acidosis
-Renal Insuficiency

Front 14

NSAID treatment

Back 14

If 200-400 mg/kg are ingested, should treat with activated charcoal and gastric emptying. >400 is a serious tox risk.

Front 15

CAD toxicity

Back 15

-Excessive NE reuptake blockade
-Direct quinidine-like effect (blocks fast inward Na influx in hert)
-Central plus peripheral anticholinergic effects.
NE excess can lead to NE depletion. May see arrhythmias, bradycardia, hypotension, cap collapse.

Front 16

Tricyclic antidepressants

Back 16

Direct inward fast sodium and potassium rectifier channel blockers

Front 17

Cyclic Antidepressant treatment

Back 17

Alkalinization with NaHCO3 and +/- hyperventillation
NA bolus to overcome sodium channel blockade.

Front 18

Iron Tox

Back 18

Free iron is catalyzes redux reactions > lipid peroxidation + free rad formation. Get hypotension, hypovulemia, cellular damae from free radicals. Get acidosis via:
-tissue hypoperfusion and lactate formation
-hydration of ferric ions
-disruption of ox phos.

Front 19

Deferoxamine

Back 19

Chealates iron. Turns urine, sweat, skin red. Adverse effects include hypotension, acute lung injury, anaphylaxis.
Chronic use correlated with hearing and visual loss. Also associated with yersinia sepsis and mucormycosis.

Front 20

Anticonvulsants names

Back 20

carbamazepine, valproic acid, phenobarbital, and phenytoin.

Front 21

Anticonvulsant OD symptoms

Back 21

Nystagmusm ataxia, depressed sensorium, convulsions, coma.

Front 22

Carbamazepine (CBZ) TOX

Back 22

Respiratory depression, apnea, decreased GI motility (causing delay in Cmax)
Crosses placenta and is a terat.
Major metabolite, CBZ-E is toxic and takes a while to peak.

Front 23

Anticonvulsant mechs and treatment

Back 23

CBZ is an NA channel blocker. Treat with supportive care and multi dose activated charcoal.
Valproic acid enhances GABA. May consume carnitine and affect mito FA oxidation.
Phenytoin blocks Na channels.
Phenobarbital is GABAergic. Supportive care plus charcoal.

Front 24

Opiates types

Back 24

-Morphine
-Codine
-Heroin
-Oxycodone
-Hydrocodone
-Propoxyphene
-Meperidine
-Methadone

Front 25

Opiate TOX

Back 25

-CNS depression/coma
-Seizures (esp. meperidine)
-Miosis
-Resp depression and pulmonary edema.

Front 26

Naloxone

Back 26

Opiate antagonist. works on mu-1,2, kappa, and sigma.

Front 27

Coaine mech

Back 27

CNS stimulant, blocks repuptake of nori and promotes release. Blocks presynaptic monoamine transporter.
Slow on/off sodium channel blocker, fast on off potassium rectifier.
Early stim, late depression

Front 28

Cocaine TOX

Back 28

-CNS hemorrhage
-MI
-Pul edema
-pneumothorax
-seizures
-rhabdomyolysis

Front 29

Cocaine / metabolite ratios

Back 29

A ration of BE:cocaine > 100:1 means use was more than 10 hours prior (cocaine detected 24-36 hours)

Front 30

Psychostimulant types

Back 30

Cocaine, amphetamines and derrivatives, and methylphenidate.

Front 31

Psychostimulant mechs

Back 31

Induce catecholamine release and block transporters (DAT)

Front 32

Amphetamine elimintaion

Back 32

Resistant to COMT and MAO. Metabolized via p450. Polymorphisms of CYP2D6 are important.

Front 33

Amphetamine tox

Back 33

-Rhabdomyolysis
-Tachycardia
-Hypertension
-Hyperthermia
-Agitation
-Seizures
-CNS hemorrhage

Front 34

PCP mech and tox

Back 34

Antagonizes effect of glutamate on NMDA receptor by blocking calcium influx. Can cause tachycardia, hypertension, and rhabdomyolysis

Front 35

7 qualifiers for substance abuse (need 3 or more within a 12 month period)

Back 35

1) Tolerance leading to more drug needed for effect
2) Diminished effect from continued use of same amount
3) Withdrawal involving tachycardia, tremors, NV, anxiety, hallucinations.
4) Substance taken in larger amounts of for a linger period than intended or an unsuccessful attempt to cut down.
5) SIgnificant time spent obtaining and doing drug.
6) Social/occupational/recreational activities are reduced because of drug
7) Use is continued despite knowledge of it causing a physical or psychological problem.

Front 36

SSRIs examples and tox

Back 36

Fluoxtine, paroxetine, sertraline, and fluoxamine. Less toxic than CADs but can cause seritonin toxicity when combined with other drugs.

Front 37

Sedative/hypnotic mechs

Back 37

Barbituates cause excess GABA leading to CNS depression and resp. depression.
Benzo increases GABA tone.

Front 38

Flumazenil

Back 38

Competitive antagonist of benzo at the GABA-a receptor. Dont use if there is possibility of mixed OD leading to seizures (CAD, cocaine, unknown)

Front 39

Atypical antipsychotics

Back 39

Safer than conventional. Can cause, hypotension, tachycardia, prolonged QT and widened QRS. Possible hepatotox and electrolyte imbalance.

Front 40

Ariprazole

Back 40

Atypical antipsychotic with a novel mech. Stabalizes dopamine by causing a D2 blockade in excess but maintains a basal D2 level if at shortage.
OD effects include somnolence, anxiety, ataxia, and dystonia. NMS possible.

Front 41

Digitoxin mech and tox

Back 41

In overdose poisons the Na/K ATPase pump. Get increased intracellular calcium, brady cardia, arrhythmias, hyperkalemia.

Front 42

Cardiac glycosides examples

Back 42

Digoxin, oleander

Front 43

Digoxin antidote

Back 43

Digoxin specificc antibody fragment. Abs reach cardiac sites where digoxin is inhibiting ATPase, binding it and removing it from the tissue.