TOXIDROMES AND DIETARY SUPPLEMENTS Flashcards
CLINICAL DIAGNOSIS
collect
assess
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TOXIDROMES
5 main toxidromes
toxidromes based on…
5 main
- sympathomimetic
-anticholinergix
-cholinergic
-sedative/hypnotic
- opioid
- never ones (neuroleptic malignany syndrome, serotonin syndrome
2 larger classes toxidromes
- fast and furious: sympathomimetic and anticholinergic
- downers: sedative-hypnotics, opioids
TOXIDROMES – VITAL SIGNS
bp, pulse, RR, temp, pupils, skin, peristalsis
other signs
Sympathomimetics ↑ ↑ ↑ ↑ Dilated Wet −/↑ Tremors, seizures diaphoresis
Anticholinergic +/- ↑ +/- ↑ Dilated Dry ↓ Dry mucous, flush, urinary retention
Cholinergic +/- +/- - - Small Wet ↑ Salivation, lacrimation, urination,
diarrhea, bronchorrhea,
fasciculations, paralysis
Opiates ↓ ↓ ↓ ↓ Small - ↓ Hypoflexia
Sedative/Hypnotic ↓ ↓ ↓ ↓ +/- - ↓ Hypoflexia, ataxia
Withdrawal** ↑ ↑ −/↑ −/↑ Dilated Wet ↑ Tremors, seizures diaphoresis
TOXICOLOGY MNEUMONIC
bradycardia PACED
tachycardia FAST
P - propanolol (BB), poppies (opioids)
A - anticholinesterase drugs
C - clonidine, CCB
E - ethanol, other alcohols
D- digoxin
Tachycardia (FAST)
F - freebase (cocaine)
A - anticholinergics, antihistamines, amphetamines
S -sympathomimetics, solvent abuse
T - theophylline
TOXIDROMES - SYMPATHOMIMETIC
causes
key signs/symptoms
common agents
tx/antidote
slide 10
TOXIDROMES - ANTICHOLINERGIC
causes
key signs/symptoms
mnemonics
common agents
tx/antidote
slide 11-12
TOXIDROMES - CHOLINERGIC
causes
key signs/symptoms
common agents
tx/antidote
slide 13
TOXIDROMES – SEDATIVE/HYPNOTIC
causes
key signs/symptoms
common agents
tx/antidote
slide 14
TOXIDROMES - OPIOID
causes
key signs/symptoms
common agents
tx/antidote
slide 15
TOXIDROMES - Serotonergic (Serotonin Toxicity)
causes
key signs/symptoms
common agents
tx/antidote
slide 16
TOXIDROMES - Withdrawal Syndromes
alcohol, sedative-hypnotic, opioid
slide 17
SALES AND REGULATION….
, Supplements
Natural Health Products
Under the Natural Health Products Regulations, which came into effect on
January 1, 2004, natural health products (NHPs) are defined as:
q Probiotics
q Herbal remedies
q Vitamins and minerals
q Homeopathic medicines
q Traditional medicines such as traditional Chinese medicines
q Other products like amino acids and essential fatty acids
PROBLEMS
Key Issues
§ Poorly characterized (ie., ADME)
§ Not been rigorously studied – lack of good scientific data
§ Inadequately regulated manufacturing
§ Contamination or tampering of the products
§ Potential interaction with prescription drugs
§ Narrow therapeutic range (eg. warfarin and digoxin) highest risk
§ Products decrease concentrations of daily medications such as
immunosuppressants to prevent organ rejection
PHARMACOLOGICAL PRINCIPLES
5
- Volatile oils – Aromatic plants (ethereal or essential oils), evaporate at RT, odor, many
are mucus membrane irritants, CNS activity, eg., catnip, chamomile, garlic - Fixed oils – Esters of long-chain fatty acids and alcohols, used as emollients,
demulcents, bases of other products, generally least dangerous, eg., olive and peanut oils - Resins – Complex mixtures of acrid resins, resin alcohols, resinol, tannols, esters,
resenes, strong GI irritants, eg., dandelion, elder - Alkaloids – Heterogenous group of alkaline and nitrogenous cmpds, found throughout plants, many active and toxic compds, eg., acotnium, goldenseal, Jimson weed
- Glycosides – Esters that contain a sugar component (glycol) and a nonsugar (aglycone)
- Saponins: licorice, ginseng (mucus membrane irritants, cause hemolysis, steroid activity)
- Anthraquiones: senna, aloe (irritant cathartics)
- Cyanogenic glycosides: apricot, cherry, peach pits (release cyanide)
- Lactone glycosides: tonka beans (anticoagulant activities)
- Cardiac glycosides: foxglove and oleander (cardioactive steroids – digoxin)
CONTAMINATION
Metal and mineral poisonings from lead,
cadmium, mercury, copper, selenium, zinc,
arsenic…
Mineral Clay Products
* Products used to relieve joint pain,
muscle or other chronic diseases
(osteoarthritis)
* Clay acidic extracts suppress nitric
oxide production and reduce
inflammation
* Rich in essential mineral but may also
contain arsenic, cadmium lead
DIETARY SUPPLEMENT-DRUG INTERACTIONS
St. John’s Wor
q Common herbal remedy promoted to treat anxiety, depression, gastritis,
insomnia, promote healing, HIV
q Interacts >20 different pharmaceutical products – clinical implications
A) Chronic use – induces P-gp activity, leads decrease absorption and increased
excretion
B) Induces CYP3A4, CYP2E1, CY2C19
C) Inhibits monoamine reuptake, increasing levels of serotonin, norepinephrine,
dopamine – precipitates serotonin toxicity
D) Inhibits COX-1 in platelets decreasing TxA2 (additive effect with antiplatelet
agents)
vitamins
concerns
- Consistently among the top most common categories of poisonings
- Two general classes:
- Water-soluble
- Minimal toxicity -thiamin, riboflavin, pantothenic acid, folic acid, biotin, Vit B12
- Associated toxicity - Ascorbic acid (Vit C), nicotinic acid (Vit B3) and
pyridoxine (Vit B6) - Fat-soluble
- Bioaccumulate and may have toxicity
- Vitamins A, D and E (but not K) toxicity large overdose or chronic use
- Adverse effects secondary to Vit K – severe/fatal anaphylactoid reaction
Vitamin A
RDA
Adult male 900 mcg RAE/day (3,000 IU/day)
Adult female 700 mcg of RAE/day (2,300 IU/day)
pathophys
- Two forms – retinol (storage form) and carotenoid (precursor)
- Essential for growth and differentiation of epithelial cells in mucus-secreting or keratinizing tissues
- Primarily stored in the liver
Pathophysiology
* Toxic effects at the nuclear level as retinoic acid influences gene expression (hormones, growth factors)
* Hepatoxicity (Ito cells) – hypertrophy, hyperplasia transdifferentiation -obstruction
* Evidence of idiopathic intracranial hypertension
vitamin a
clinical manisfestations
management
dlinical Manifestations
* Toxic effects more frequent with chronic ingestions
* Acute O/D – hrs-2days-
* Chronic – affects skin, hair, bones, liver, brain – dry/fragile skin (yellow-orange discoloration); hair thinning/curly; nails shiny/brittle; cirrhosis/portal hypertension; severe headache/visual disturbances
Management
* Acute – GI decontam (activated charcoal)
* Discontinuation and supportive care
Vitamin D
pathophys
- Deficiency – historical problems (Rickets disease)
lack of dietary or sunshine - Excessive fortification of foods (milk) led to
poisonings – balance - VitD must be metabolized (liver) into active form
- Circulates, binds to receptors – regulates calcium
Pathophysiology - Toxic doses – varies, no consensus
- Hallmark toxicity is hypercalcemia, serum concentrations 25(OH)D 20x normal
vitamin d
clinical manisfestations
management
Clinical Manifestations
* Early manifestations – weakness, fatigue, somnolence, irritability, muscle and bone pain,
nausea/vomiting, abdominal pain
* Chronic – polyuria and polydipsia, nephrolithiasis (kidney stones)
* Severe hypercalcemia – ataxia, confusion, psychosis, seizures, AKI, cardiac dysrhythmias
Management
* Discontinuation and supportive care, oral or IV fluids, calcitonin
Vitamin E
pathophys
clinical manisfestations
management
- Eight naturally occurring compounds 2 classes (tocopherols and tocotrienols)
- Antioxidant properties, protects polyunsaturated FA from oxidation, binds to
peroxyl radicals
Pathophysiology - High doses it acts as prooxidant (ie., alpha-tocopheroxyl radical)
Clinical Manifestations - GI symptoms – nausea, diarrhea, abdominal cramps >2000mg/day
- Antagonizes the effects of vitamin K by increasing epoxidation to inactive form
Management - Discontinuation and supportive care
Vitamin C
clinical manisfestation
pathophys
Ascorbic acid, reported antioxidant properties, scurvy (reducing agent)
* Popular use for wound healing, cataracts, aging, mental attentiveness decrease
stress
* Little to no objective data to support these benefits (500mg/day supplements)
* Absorption occurs by a saturable active transport system in intestine, large
ingestions get eliminated via kidney (occurs ~3g/day)
* Co-factor in several hydroxylation and amidation reactions
* Prooxidant properties at high concentrations
Clinical Manifestations
* Conflicting data suggesting association with oxalosis and kidney stones
* GI effects at high doses (>1g/day) – localized esophagitis (prolonged mucosal
contact) and diarrhea
Vitamin B6
pathophys
clinical manisfestations
management
- Pyridoxine absorbed in intestinal tract, rapidly metabolized, renal excretion
- Pyridoxal phosphate (PLP) is the active form – coenzyme for synthesis of γaminobutyric acid (GABA)
- Treatment of nausea and vomiting of pregnancy
Pathophysiology - Both deficiency and toxicity are characterized by neurologic effects, peripheral
sensory system
Clinical Manifestations - Chronic overdose – progressive sensory ataxia and severe distal impairment of
proprioception and vibratory sensation - Reflexes diminished of absent but touch, pain, temp minimally effected
Management - Discontinuation and supportive care
Vitamin B3
pathophys
Nicotinic acid, or niacin, converted into nicotinamide (incorporated into cofactor NAD)
* Reduces TG synthesis and VLDL production
* Increases HDL-C and decreases LDL-C
Pathophysiology
* Deficiency causes pellagra (dermatitis, diarrhea, dementia)
* Most common ADR vasodilatory cutaneous flushing (sense of warmth) last ~1-3h,
caused by production PGD2 and PGE2
Vitamin B3
clinical manisfestations
management
linical Manifestations
* Immediate release formulations develop flushing more, dyspepsia
* Extended release more GI effects and hepatoxicity (>2-3g/day)
* Elevated aminotransferases, fatigue, anorexia, nausea, vomiting, jaundice
* Severe cases fulminant hepatic failure and hepatic encephalopathy
Management
* NSAID (aspirin) prior to administration inhibit COX, take with food (avoid EtOH, spicy),
gradual increment of dosing
* Tolerance to flushing will develop – take several weeks
