MedChem 1 Herbal Meds

Doctrine of Signatures

natural products that were used because they resembled human anatomy or mimicked a disease state

i.e. Walnut for brain health, Red juice of bloodwort for blood disorders, Kidney-shape leaves of Hepatica to treat kidney diseases

Artemisia annua L. (wormwood)

used to treat fevers, malaria

Why were toad skins used?

their action is similar to Digitalis cardiac glycosides

Importance of Ebers Papyrus in Egypt

22 therapeutic formulations, included products derived from animals

Importance of Snakeroot in Ayurveda

root of this plant resembles the shape of snakes, and therefore was used to treat snakebites

it was also used for mental diseases

Reserpine (hypertensive) was isolated from the dried root of snakeroot

What did Hippocrates say were the four humors of the body? Why are these important?

black bile, yellow bile, phlegm and blood

imbalance of these humors was responsible for disease and the temperament of the individual

De Materia Medica

contains over 600 species of natural products with medical value, 500 of which are plants

includes approx. 1000 natural product drugs (mostly plant-based), 4,740 medicinal usages for drugs, and 360 medical properties such as antiseptic and anti-inflammatory

Mandrake

once believed to have magical powers because its root resembles the human body (doctrine of signature)

Now know its root contains hallucinogenic tropane alkaloids (i.e. atropine, scopolamine, apoatropine, hyoscyamine)

Used as a pain killer, anesthetic before operations

What was the importance of the Islamic World?

separated the arts of apothecary (pharmacy) and physician

Black Seed

was used in treatment of different diseases including asthma, bronchitis, rheumatism

now used as a dietary supplement that helps prevent disease and slow down aging process

What did Paracelsus contribute?

Investigated the use of opium

Introduced dose-response concept

Held that illness was the result of external agents attacking the body rather than imbalances within

18th Century Contributions

William Withering investiagted folk remedies, from which we discovered we can study natural products using a chemical approach

19th Century Contributions

isolation of drugs from natural products

i.e. opium from poppy, anti-malarial compound quinine from cinchona tree bark

20th Century Contributions

Direct use of plant extracts continue to decrease

Use of semi-synthetic or wholly synthetic ingredients originally isolated from plants

21st Century Contributions

renewed interest in investigating plants for medically useful compounds

wide range of therapies outside the mainstream of Western medicine

Herbal Medicine vs. Western Medicine

herbals - whole natural products, broader effects

western - isolated chemicals, more specific targets

Why patients refer to CAM and natural products?

Dissatisfaction with Western medicine

More active in own healthcare

Philosophical orientations

Regulatory Problems with Dietary (herbal) Supplements

labeling problems, lack of quality control and a plethora of advocacy literature leading to misinformation

Challenges with Herbal Meds

Supply issue: unable to culture on production scale

Quality issue: the type (climate, bugs, soil quality) of environment a plant grows; how and when an herb is harvested and processed.

Safety issue: herbal-drug-food interactions; contamination; unknown mechanisms according to modern medicine; allergic reactions

Ephedra

weight loss supplement

can raise BP, cause arrhythmias, lead to seizures

Miracle Burn

blend of 16 different vitamins, minerals, and herbal products

no established dietary allowance

contains ephedra

Apple Cider Vinegar (ACV)

promotes weight loss, lowering blood pressure, reducing cholesterol, fighting arthritis pain, relief of sore throat

caution: avoid if you have gastritis, ulcers, or GERD

L-Carnitine

Naturally produced from lysine and methionine

Transports long chain fatty acids to the mitochondria

Helps increase energy

Coenzyme Q10

Natural product and also found in our body

FDA Orphan Drug for mitochondrial encephalomyopathies

Possible treatment for CHF, but not diabetes and exercise tolerance

Melatonin

naturally occurring hormone

used for insomnia, jet lag, anti-aging, and dementia

FDA Orphan Drug for circadian rhythm problems in the blind

Possibly unsafe in children, affects gonadal development

Ginko Biloba

Dilates arteries, capillaries and veins; increase peripheral blood flow

Inhibits platelet activating factor; use caution with anti-coagulants and anti-platelet drugs

use caution with stimulants, caffiene may increase risk of subdural hematomas

Inhibition of CYP3A4, Inducer of CYP2C19

Echinacea

used internally as an immunostimulant and anti-infective or topically as a wound-healing agent

produces nonspecific immune system activation

safe for short-term use (up to 12 weeks)

not recommended for auto-immune diseases, may be immunosuppressive

Inhibition of CYP3A4 in the intestine, as an inducer in long-term use

Garlic

lowers blood lips, inhibits platelet formation

possibly effective in decreasing cholesterol and BP

ineffective against H. Pylori

can cause GI upset, risk of hemorrhagic complications in surgery

May be an inhibitor of CYP3A4, as an inducer in very high doses, P-glyprotein

GInseng

produces increased resistance to stress and depression, and strengthens normal body functions

may increase BP

interacts with Lasix, decreases diuretic action

Moderate hepatic CYP3A4 inhibitor

Soybean

used for effect in postmenopausal symtopms, bone loss prevention, cardiovascular disease

Saw Palmetto

relieves symptoms of BPH, increases urine flow

may interfere with hormone therapies (i.e. contraceptive pill or HRTs)

St. John’s Wort

used in nervous restlessness, mild/moderate depression; externally for contusions and burns

contraindications: suicidal tendencies, severe agitation, hypersensitivity

Potent inducer of CYP3A4 and drug efflux transporter P-gp, PXR Activator, CYP3A4 inhibitor (short-term)

contains hyperforin, a ligand for PXR

can cause serotonin syndrome (SSRI and MAO inhibitor) and adrenergic crisis

Valerian

mild sedative, tranquilizer, sleep aid, anti-spasmodic

may potentiate CNS depressants

Inhibition of CYP3A4, Inhibition of CYP2D6

Cranberry

used for treatment and prophylaxis of UTIs

Milk Thistle

used as an antihepatotoxic, generally non-toxic

Ginger

anti-emetic, anti-motion sickness, digestive aid

Black Cohosh

estrogen-like effects

relieve symptoms of PMS and painful menstruation

Drugs discovered from natural products

Aspirin - pain, fever, headache

Purple foxglove (Digitalis purpurwa) - dropsy (edema)

Penicillin - anitbiotic

Morphine - pain

Privileged Structure Hypothesis

selected by evoluutionary pressure, to provide chemical scaffolds that binding to multiple target proteins

What toxic substances are contained by herbal meds?

Pyrrolizidine alkaloids

Phorbol Esters 

Aristolochic acids

Borage

diuretic, expectorant and antidiarrheal

contains pyrrolizodine alkaloids, which are potentially teratogenic, carcinogenic and hepatotoxic

Sweet Flag

a remedy for a variety of  digestive upsets and colic

some contain a carcinogen known as cis-isoasarone

Chaparral

wide variety of diseases including arthritis, cancer, venereal disease, tuberculosis, rheumatism and colds

contains ordihydroguaiaretic acid (NDGA), an antioxidant; used as an anticancer agent

NDGA has been shown to be nephrotoxic and hepatotoxic

Coltsfoot

folk remedy for coughs and bronchial congestion; used as demulcent and antitussive

contains carcinogenic, hepatotoxic pyrrolizidine alkaloids

Germander

Used as an anorectic

Contains hepatotoxic diterpenoids

Licorice

expectorant and demulcent in treatment of coughs and colds; anti-ulcer activity

over time causes pseudoaldosteronism (Na, H2O retention + K depletion → high BP, heart failure, cardiac arrest)

Poke Root

alternative (tonic), anti-rheumatic and anticancer product

contains triterpenoid saponins, carcinogenic

Sassafras

spring tonic and blood purifier; used as a stimulant, antispasmodic, antirheumatic and tonic

contains safrole, a carcinogenic

What is the interaction between Ritanovir and garlic?

possible interaction with garlic PK or PD, resulting in garlic toxicity to GI tract

Grape seed

In high doses, as an inducer of CYP3A4

Kava

Pregnane X receptor (PXR) activator

Grape fruit

Potent CYP3A4 inhibitor in the intestine

Inhibitor of P-gp and the uptake drug transporter OATP

Black Pepper

Inhibitor of CYP3A4 and P-gp

Seville Orange

Inhibition of CYP3A4, P-gp and OATP

Goldenseal

Inhibition of CYP3A4 and CYP2D6