Pharmaco Toxicology

7/22/2019 Pharmaco Toxicology

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TOXIC SUBSTANCES AND

TREATMENT

PHARMACOLOGY

BLOCK OF CHEM 3

MEDICAL SCHOOL UNSOED


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Aluminum

Symptoms:

Acuteconstipation, nausea, anorexia, colic,gastrointestinal irritation, skin problems

Chronicmuscle twitching, numbness, paralysis,fatty degeneration of kidney and liver

May reduce absorption of Selenium andphosphorousosteomalacia?

Alzheimers and Parkinsons disease

Hyperactivity and learning disorders in children

Amounts:

Best measured by hair analysis

10-20ppm

High Risk Population:

Diets high in refined foods, flours, baked goods,processed cheeses and common table salt

Those using antacids, antiperspirants or cookwith aluminum foil or kitchenware

Treatment: Use chelation therapy (EDTA, desferrioxamine)

Support with Calcium, Magnesium and zinc

Prevention:

Avoid sources


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Arsenic

May be functional in humans in small amounts

Sources: Small amounts in food - Higher in filtering molusks

Environmental toxin from burning fuel oils and coals

Weed killers

Methods of toxicity:

May displace phosphorous and phosphates in somereactions in the body

Symptoms of toxicity:

Possiblyhair loss, dermatitis, diarrhoea, fatigue,

headaches, confusion, muscle pains, red and white

blood cell problems, neurologic symptoms, and liver

and kidney damage. Amounts:

7-10ppm in hair analysis

High risk population:

Miners, smelters and vineyard workers

Treatment: Dimercaprol (given 24 hours after exposure)

Can be supported with Vitamin C

Prevention:

Avoid sources


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Cadmium

Sources:

Cigarette smoke1 mcg/cigarette, 70% exhaled Refined foods and root vegetables

Water pipes - galvanised

Coffee and tea

Coal burning

Shellfish Ceramics, dental materials, storage batteries

Methods of toxicity:

Competes with zinc for binding sites

May catalyse oxidation reactions

Symptoms: Kidney damage (concentrated storage)

Hypertension and Kidney stones

Cardiac hypertrophy

Progressive atherosclerosis

Depressed immunity

Prostate enlargement

Bone deformities

Emphysema

Anemia


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Cadmium

Amounts leading to toxicity:

Relative to zinc status

2ppm in hair analysis

High risk population:

Industrial and metal workers, zinc miners,

smokers and passive smokers, coffee and tea

drinkers, diets with refined flours and sugars(white rice)

Treatment:

EDTA chelation

High intake of zinc and selenium will prevent

further absorption

Iron, copper, selenium and C will help elimination

Prevention

Minimise exposure

Ensure adequate zinc levels (15-30mg/day)

Strengthen kidney function


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Lead

Sources:

Batteries

Solder

Pottery

Pigments - cosmetics

Gasoline

Paint

Foodgrown near industrial areas

Methods of toxicity

Interferes with calcium, iron, copper, and zinc

Interrupts erythrocyte enzymes Inactivates metalloenzymes in brain

chemistry

Can react with cell membranes

Inactivates cysteine-containing enzymes

Immunosuppressant May have some affect on gastrointestinal

function


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Lead


Acuteheadache, fatigue, muscle pains,anorexia, constipation, vomiting, pallor, anemia.

Agitation, irritability, restlessness, memory loss,

poor coordination, vertigo and depression (lead

encephalopathy)

Low levelaffect intelligence, attention span,language and memory. Insomnia and

nightmares, hyperactivity and retardation, and

senility

Amounts:

0-30ppm may be normal High risk population:

Anyone working directly with lead

Work in zinc or vanadium mining

Childrenbetter absorption and smaller bodies

Pregnant women


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Lead

Treatment:

EDTA

Calcium and vitamin D and C supplementation

Cysteine and methionine250mg twice daily

Prevention:

Do not exercise along freeways or in heavy traffic

Do not allow children to play near busy streets

Do not store food in pottery

Avoid soldered cans

Evaluate for lead levels any questionable

substances (ie water)


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Mercury

Sources:

Fungicides and pesticides Cosmeticsantibacterial additive

Dental fillings

Medicines

Coal burning

Fish Methods of toxicity:

Affects the inherent protein structure

Inactivates enzymes

Damages cell membranes

Immunodepressant May interfere with selenium


Inhalation

Acutefever, chills, coughing, and chestpain

Chronicfatigue, headache, insomnia,nervousness, impaired judgement andcoordination, emotional lability, loss of sexdrive


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Mercury

Ingestionfatigue, insomnia, irritability, anorexia,

loss of sex drive, headache, forgetfulness or poormemory. Dizziness, tremors, uncoordination, and

depression.

May cause multiple sclerosis

Amounts leading to toxicity:

>5ppm hair levels High risk population:

Farmers

Those with amalgam fillings

Treatment:

Drinking milkmercury acts on protein in milk

Penicillamine (potentially toxic)

EDTA

Vitamin C, Selenium, pectin and alginates

Prevention: Avoiding contact

High fibre diet

Selenium 100-20mcg


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Caffeine

Sources

Effects on the Body

Benefits

Detoxification and Nutrients


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Sources of Caffeine

Coffee

Tea

Chocolate

Cocoa

Guarana root

Some soft drinks Kola nut

Diet supplements

OTC e.g. NoDoz, Awake


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Toxic Effects of Caffeine

Nervousness

Anxiety

Irritability and Agitation

Tremor/shakes

Insomnia

Depression Headache

GIT irritation

Bed wetting

Heart burn

Fatigue and dizziness

or irregular heart rate Elevated blood pressure

cholesterol Nutritional deficiencies

Poor concentration

Diarrhoea


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Negative Effects of Caffeine

1. Common side effects as before

2. Acid irritant to GIT and liver - hydrochloricacid which can irritate ulcers as well as causeulcers

3. Diuretic effectloss of potassium,magnesium, calcium, iron, zinc, B vitaminsespecially B1, vitamin C etc

4. Relaxes the smooth muscle in the coloncausing a laxative effect

5. Fibrocystic breast disease & Oesteoporosis

6. Cardiovascular effects - Bp and cholesterol,risk of atherosclerosis and heart disease,

heart rhythm disturbance

6. Birth defects and spontaneous abortions

7. risk of certain cancers e.g. Bladder cancer,pancreatic cancer

8. risk of kidney stones9. Adrenal

exhaustion/stress/fatigue/hypoglyceamiasyndrome

10. Anxiety and panic disorders


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Caffeine Interferes With These

Substances

1. Lowers phenylalanine and tyrosine

levels2. Melatonin production

3. Testosterone levels

4. Absorption of calcium, iron,

magnesium, potassium. Phosphorous,zinc, vitamin C, B vitamins

5. Depletes biotin, inositol, vitamin A andvitamin B1


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Benefits of Caffeine

1. Hypochlorhydria

2. Diuretic effect

3. Improves athletic performanceadrenergiceffect, vasodilatation, BMR. Optimal level isconsidered 9mg/kg of body weight. (Careful ofbanned limit)

4. Can aid weight loss

5. Stimulates brain functionalertness and

concentration6. Boosts moodalleviates mind depression

7. Stimulates respiratory systemaids asthmasufferers

Rapidly absorbed when consumed orally fromintestines

Significant serum levels reached 30-45 mins after

ingestion Complete oral ingestion effect occurs in about 90mins

Peak plasma levels occurs in approximately 2 hours

Half life = 3-55 hours

Metabolised by the liver prior to excretion in thekidneys

Bioavailability of Caffeine


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Detoxification of Caffeine

Slow detoxification is recommended rather than cold

turkey to withdrawal effects Aim is to support the detox with a good diet and

adrenal support

Alkalising the diet is helpful in detoxification

Some people start by switching to lower caffeine

sources e.g. tea or trying coffee substitutes e.g Eco,

dandelion root

Withdrawal symptoms of Caffeine

Nutrient Dosage

B vitamins Complex 1-2 tabs / day

Magnesium 600mg/day

Calcium 800mg/day

Iron 10-20mg/day

Zinc 50mg/day

Vitamin C 2000-6000mg/day

Tyrosine 1000-2000mg/day

Potassium 600-1000mg/day


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Withdrawal Symptoms of Caffeine

Headache

Dizziness Cravings

Drowsiness

Irritability

Inability to concentrate

Insomnia Runny nose

Fatigue

Nausea

Depression

Vomiting Apathy

Cramps

Constipation

Ringing in ears

Anxiety

Feeling hot and cold

Nervousness

Tachycardia

Shakiness


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Tobacco

Toxic effects

Interference of Substances

Detoxification and Nutrients


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Toxic Effects of Tobacco

1. risk of atherosclerosis2. risk of abnormal blood clotting3. risk of CVD4. Can cause cerebral insufficiency

5. risk of hypertension6. risk of intermittent claudation7. risk of ischemic heart disease8. risk of stroke9. Can cause halitosis

10. Impairs hearing

11. risk of age-related macular degeneration12. risk of risk of cancers e.g. Lung, cervical,bladder, oesophagus etc13. Can cause leukoplakia (pre-cancerous lesions

in the mouth)

14. number of free radicals15. risk of oesteoporosis16. Can impair taste and mental function

17. Can cause coughs, bronchitis and emphysema

18. risk of infertility and genital problems


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Tobacco Interferes with these

Substances

1. Carotenoids

2. Testosterone

3. Calcium

4. Selenium

5. Vitamin A

6. Vitamin E

7. fibrinogen levels8. Can cause cross linking of DNA

mutations9. homocysteine10. cholesterol


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Symptoms Associated with Tobacco

Heart burn

Surgical complications

Allergies

Nutritional deficiencies

Angina pectoris

Stains on teeth and fingers

Hoarseness

pregnancy risk Coughs

caffeine use Headaches

alcohol use Memory loss

Higher insurance rates

Anxiety

Fatigue

Lowered immunity

Low sexuality

Cold hands and feet

Leg pains


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Cigarettes and Appetite

Cigarettes suppress appetite

Interferes with hunger response in brain

Supplementation with zinc required

especially if they suffer from eating

disorders as well


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Nutrients and Foods that help Decrease Damage from

Cigarettes

1. Arginineinhibits the adhesions of monocytes to

the endothelium2. Cysteineprecursor to glutathione which helpsprevent damage to the bronchial tubes

3. Seleniumcounteracts many toxic effects

4. Zincstrengthens the mucus membranes oflungs and boosts levels depleted from tobacco

5. Vitamin Astrengthens mucus membranes

6. Vitamin C - oxidation7. Vitamin Ecounteracts many toxic effects

8. B vitaminsaids nervous system

Aggressiveness

Anxiety

appetite

Poor concentration Impatience

Insomnia

Irritability

Cravings

Withdrawal symptoms of Tobacco


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Suggestions for Cessation of Smoking

Cut down on other addictive substances e.g.

Caffeine, sugar, alcohol Get a partner or another smoker to stop with them

Work on psychological factors first e.g. Dontsmoke at the normal times like after dinner sochange daily patterns

A smoker wont quit unless they definitely reallywant too

Learn stress management techniques

Start exercising or exercising more

Stay busy to prevent boredom

Set small goals along the way

Get plenty of rest Keep a positive attitude

Find oral substitutes

use quitting substitutes

When cravings arise, develop a behaviour to

counteract them


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Alcohol

Toxic effects on the Body

What it Interferes with

Detoxification Processes

Nutrients to assist Detoxification


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Alcohol Interferes with:

1. Amino acidsSAMe

2. Carbohydratestolerance to Galactose3. Carotenoids

4. Enzymesacetylcholine production and fatbreakdown

5. Hormonesi. hGH and prolactin

ii. melatonin and testosterone

6. Lipidsinterferes with the absorption of CetylMyristoleate (CMO)

7. Minerals:i. calcium

ii. magnesium

iii. Excretes potassiumiv. selenium

v. zinc

8. Neurotransmitters:i. Inhibits acetylcholine

ii. Reduces GABA receptor sites

iii. Inhibits Nitric Oxide

iv. Prevents vasopressin release


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Alcohol Interferes with:

9. Organic acids: lactic acid & uric acid10. Peptides - glutathione11. Polyphenols - rutin12. Quinones

13. Second messengerscyclic AMP

14. Sexual hormones - testosterone15. Micro-organisms: destroys gut bacteria

16. Vitaminsdecreases/destroysi. Biotin

ii. Choline

iii. Folic acid

iv. Inositol

v. PABA

vi. Vitamin Avii. Vitamin B1

viii. Vitamin B2

ix. Vitamin B6

x. Vitamin B12

xi. Vitamin C

xii. Vitamin D

xiii. Vitamin Exiv. Vitamin K


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Sugar Response and Alcohol

There is a theory that involves 3 parts:

1. Reactive blood sugar

2. Low serotonin

3. Low beta endorphins

These factors can be seen in alcoholics and siblings

of alcoholics. All can lead to cravings for

sugar, depression, mood swings and low

impulse control.

Sugar can act like a drugaddiction

Affects same area in brain as heroin and

morphine

Drug detox increases sugar cravings as it

gives them a similar high or feelingfills a gap

Withdrawal symptomsblood sugar drops so

they crave either the drug (e.g. alcohol) orsugar

Biochemistry of sugar sensitivity is very

similar to alcoholism


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Baby stepsDrugs & Sugar

Allow sugar for the first 2 days

After 2 days start to the amount of sugarconsumed

Suggestions:

1. Frozen yoghurt instead of ice-cream

2. Can still have Milo, drinking chocolate, Akta-Vite

3. Mineral water or natural cordial instead of softdrink

4. Use raw sugar

5. Helgas white bread, turkish bread,

bagels,wholemeal muffins etc6. No lollies/sweets


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Effects of Illegal Drugs on the Body


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Teenage Community Drug Abuse

Drug and Demographics 1995 1998

Users % Users

%

Tobacco males 14-19 14.5 16.3

Tobacco females 14-19 13.2 15.8

Regular alcohol male 14-24 55.1 48.7

Regular alcohol female 14-24 33.3 34.1

Marijuana male and female 14-24 32.8 37.9

Barbituates male and female 14-24 0.1 0.5

Heroin male and female 14-24 0.6 1.3

Amphetamines male and female 14 - 24 5.6 9.8

Cocaine male and female 14-24 1.8 1.9


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Toxic Effects of Amphetamines

Nervous System

1. Depression

2. Excessive stimulation of dopamine D2

receptors

3. Drug dependence

4. A decrease in intelligence

5. Impairs memory

Immune System

Interferes with thymus gland via norepinephrine

deficiency

Metabolism

Lack of energy, motivation and willpower.


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Amphetamines Interfere with:

1. Enzymes - tyrosine2. Neurotransmitters:

(I) Inhibits dopamine

(ii) norepinephrine and vasopressin3. Metabolismincreases it

4. Nervous system:

(I) Suppresses emotion(ii) Increases alertness temporarily

(iii) Used in ADD treatment

(iv) Alleviates fatigue temporarily

(v) Improves intelligence temporarily

(vi) Improves learning, attention span and memorytemporarily

Substances that Increase Potency

1. Amino acidstyrosine prolongs life of drug

2. Smart Drugs

Substances Counteracts the toxic Effects1. Tryptophan counteracts the cravings for

amphetamines

2. Tyrosine corrects norepinephrine deficiency


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Toxic Effects of Marijuana

Eyes/Vision

Can cause persistent blood shot eyes

Immune System

1. Can cause cancer e.g. long term use can causetesticular cancer

2. Suppresses T-lymphocytes

Respiratory System

Can cause emphysema-like changes in lung

Nervous System

1. Anxiety

2. Unpaired coordination

3. Hallucinations

4. Decreased learning abilities

Marijuana temporarily and reversibly causes:

1. Short-term memory loss2. Mental retardation in offspring

3. Paranoia

4. Can trigger or exacerbate psychotic episodes(trigger for schizophrenia)


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Toxic Effects of Marijuana

Sexual systems

Female: suppresses lactation (prolactin-blocker)Male: Infertility by decreasing sperm count and

testosterone

Marijuana interferes with:

1. Hormonestestosterone2. Neurotransmitterssuppresses vasopressin

3. Nucleic acidsinterferes with synthesis ofDNA and RNA

Digestive systemcan prevent vomiting fromchemotherapy

Eyes/Eyesightalleviates glaucoma by loweringintraocular eye pressure

Nervous systemstimulates the appetite, sedates theCNS and alleviates pain by influencing the painreceptors in the brain

Health Benefits of Marijuana


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Toxic Effects of Ecstacy

1. Excretory system: can cause urinary retention

2. Nervous system: produces amphetamine likefeelings of euphoria with fewer hallucinationsand less sense of disembodiment. Can causehyperpyrexia.

Ecstacy Interferes with:

Neurotransmitterscauses release of large amountsof serotonin so therefore subsequent depletion

Serotonin levels are significantly lower in animals giventhe equivalent quantity of ecstasy as that found inone pill of MDMA. This occurs because the cellsthat produce ecstasy are unable to keep up withdemand (as serotonin is released in large amountsby ecstasy). Ecstasy users have fewer serotoninreceptors compared to non-users.

Ecstasy. The happiest diet pill on earth?Romano, J. Muscular Development. 37(12):158-162, 2000


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Toxic Effects of LSD

Cardiovascular System

Increases blood pressure

Nervous System

1. Extreme anxiety (temporary)

2. Extreme confusion (temporary)

3. Impairs coordination4. Potent hallucinations

5. Inhibition of acetylcholineserotonin

6. Temporary panic disorder

Neurotransmitterscauses hallucinatory effects byfunctioning as a general 5-HT antagonist: blocksserotonin receptors, thereby inhibiting its function andallowing acetylcholine to cause excessive stimulation.

Also causes release and destruction of vasopressin.

Reduces Detrimental Effects: Vitamin B3

LSD interferes with:


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Toxic Effects of Inhalants

Long term Effect

The most toxic type of drugs that young people canabuse, as it can cause irreversible damage.

Nervous System

1. Brain damage resulting in movement disordersand possible intellectual impairment (esptoluene)

2. Peripheral nervous damage: arms and legstrembling uncontrollably, numbness, weaknessand muscle paralysis

3. Gasoline toxicitylead poisoning causingdementia and muscle paralysis

4. Tinnitus

Kidneys

1. Severe kidney damagekidney failure

2. Serious electrolyte imbalancesmuscleweakness, nausea, vomiting and mentalconfusion

3. Glomerulonephritis

Liver: Abnormal liver function


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Toxic Effects of Inhalants

Lungs

Lung inflammation Pneumonia and other infections

Asphyxia = death

Heart & Blood Vessels

1. Abnormal rhythms of the heart2. Sudden sniffing death syndromeif individual

exercises or gets excited

Bone Marrow & Blood

1. Benzenecan cause severe anemia andleukemia

2. Methylene chloride is converted to carbonmonoxide resulting in brain damage. Heartpatients and cigarette smokers have anincreased risk if use simultaneously.


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Aim of Nutrition in Detoxification of Drugs & Alcohol

Assist the body to detoxify the drug(s)

out of the body as quickly as possible

which lessens the severity and length of

withdrawal

Repair some of the damage done to their

body by the drugs, bad eating habits andlifestyle

Alkalise the body and reduce acidity

Educate people on proper nutrition


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Nutrients that counteract Drug

Dependence

1. SAMe (S-Adenosylmethionine)

counteracts anxiety and depression

2. Tryptophancounteracts cravings for

amphetamines, decreases physical

pain

3. Lipidsreduces withdrawal symptoms

4. Vitaminsvitamin C reduces

withdrawal symptoms


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Beneficial Foods for Alcohol & Drug

Detoxification


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Beneficial Foods for Alcohol and Drug

Detoxification

1. WaterEspecially filtered, helps to flush out

toxins2. Fibreaids in absorption and removal of

toxins

3. Fresh vegetable juicesalkalises the body,contains natural antioxidants and helps liverand kidney detox functions

4. Protein foodscontains tryptophan, tyrosine,glutamine, methionine, cysteine, and taurineetc. These are precursors to neurotransmittersand detox processes.

5. Fresh fruit and vegetablesexcellent form offibre, nutrients and help to alkalise the body

6. Whole grainscontain essential nutrients fordetox. Also required for serotonin production.

7. Garlicblood cleanser, lowers blood fats andis a natural antibiotic

8. Gingernatural anti-inflammatory, reducesnausea, stimulates circulation and sweating


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Beneficial Foods for Alcohol and Drug

Detoxification

9. Raw foodsincreases number of nutrients in

foods

10. Glutamine foodsassists alcohol withdrawale.g. GABA receptors, also heals mucousmembranes and decreases cravings for CHOand sugars.

11. Foods that assist kidney functione.g.asparagus, watermelon, parsley, wheat grass,beetroot, fennel etc

12. Foods that assist liver functionlemons,pears, grapes, cherries, wheat grass,

artichokes, dandelion tea, turmeric, broccolietc


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Essential Nutrients and Supplements

Glutamine Glutamine2-3 grams a day (empty

stomach)

Magnesium Magnesium600mg per day

B complex

(esp B3)

B complex - 1 tablet every 4 hours

Vitamin C Vitamin C250 mg every 3 hours

Alcohol

Acetaldehyde

Acetate

Aldehyde Dehydrogenase

(B3 Dependant Enzyme)

Alcohol Dehydrogenase

(B3 Dependant Enzyme)


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Essential Nutrients and Supplements

Zinc 30mg a day

Essential fats EPA/DHA3g per day after food

Carnitine Carnitine & Acetyl-L-Carnitine400mg

1g per day

Lipotropenes Liver Tablets including taurine,methionine, choline, vitamins, St Marys

Thistle, Globe artichoke etc

Documents

Pharmaco Toxicology