Topic 7: Cardiovascular System & Phytomedicines Cardiovascular Disease, Lipids and & phytomedicines Flashcards
Thrombus
a soft gel-like coagulated phase of blood resulting from conversion of fibrinogen to fibrin that may or may not be occlusive to the vessel
Thrombosis
clotting in a blood vessel that can result in infarction of tissues supplied by the vessel
Hypertension
high arterial blood pressure
Coronary Arteries
arteries that provide oxygenated blood to the heart
Coronary Artery Disease (Ischemic Heart Disease)
plaque deposition in the coronary arteries which over time can result in a reduction or blockage of the arterial blood supply and oxygen supply to cardiac muscle
if blood supply is reduced or interrupted for a long enough time the cardiac muscle becomes ischemic (low in blood supply) resulting in infarction and death of the muscle tissue supplied by the clogged artery
Angina Pectoris
ischemia to the heart from coronary artery disease results in constricting pain in the chest that sometimes radiates to the shoulder and down the inside of the arm
Infarction
sudden blood supply insufficiency due to thrombus, emboli, or vascular torsion resulting in a macroscopic area of necrosis due to tissue death
Myocardial Infarction (MI) (Heart Attack)
infarction of an area of the heart muscle secondary to coronary artery occlusion
death may result if infarction is sufficiently large and/or in a vulnerable area of the heart muscle
Environmental Triggers that Modulate Genetic Predisposition to Cardiovascular Disease
- diet/overall caloric intake
- obesity
- level of physical activity
- stress, physiological/social
Nutrition Constituents
- protein
- fats
- carbohydrates
- vitamins
- minerals
- phytochemicals/secondary metabolite compounds
Plant Constituents in Human Nutrition
- vitamins: carbon containing organic substances present in minute amounts in food plants that are essential to normal metabolism
- minerals: inorganic substances that contain elements other than carbon and are present in minute amounts in food plants
- phytochemicals/secondary metabolite compounds: organic substances present in minute amounts in food and medicinal plants that may have beneficial effects for humans
Chemical Classes From Plants
- carbohydrates and lipids: intermediates or products of primary plant metabolism
- alkaloids: nitrogen atom in heterocyclic ring; major source is flowering plants but also found in toads, ants, birds
- nitrogen-containing compounds (excluding alkaloids): amino acids, proteins, peptides, amines, cyanogenic glycosides, purines, pyrimidines
- phenolics, polyphenols: aromatic ring containing at least one hydroxyl group, flavonoids, lignins, tannins, melanin, coumarins, quinones
- terpenoids: largest group of natural plant compounds, derived from 5-carbon precursor isoprenes, camphor, digitalin, gossypol, carotenoids, cucurbitacins
Protein
- macromolecules with carbon, hydrogen, and nitrogen-containing amino acids in peptide linkages
- there are 20 amino acids of which 9 are essential in the human diet and all 9 of these are found in plant foods
Carbohydrates
-small molecules (mono- and disaccharides):
mono: glucose, fructose, galactose
di: sucrose (glucose + fructose = table sugar), lactose (glucose + galactose = milk sugar
-larger molecules
polysaccharides: starch, glycogen, cellulose
refined grain polysaccharides: much of fiber, phytochemicals and vitamins have been removed
unrefined whole grain polysaccharides: rich in fiber, phytochemicals, vitamins
-inverse relationship between level of fiber in diet and risk for death
Exogenous Fatty Acids (Fat, Saturated Fatty Acids, Trans Fatty Acids)
fat: oily or greasy components that contain glycerol esters
saturated fatty acids: possess no double bonds and are solid at room temperature
trans fatty acids: mono- or polylunsaturated vegetable oils are hydrogenated which results in them becoming solid at room temperature; these fats are worse than saturated fats on cardiovascular health
Exogenous Fatty Acids (Unsaturated Fatty Acids, Omega-3 Fatty Acids, Essential Fatty Acids)
- unsaturated fatty acids: possess one or more double or triple bonds and are liquid at room temperature (mono- and polyunsaturated)
- omega-3 Fatty Acids: polyunsaturated fatty acids with double bond three carbons from methyl moiety (flaxseed oil, walnut oil, hemp oil, salmon oil)
- essential fatty acids: unsaturated fats from plants essential in human diet (linoleic and linolenic acids found in soy oil)
Dietary and Coronary Artery Disease
problem: saturated fat is main dietary factor that influences LDL cholesterol levels; high LDL cholesterol levels contribute to coronary artery disease
dietary solution: reduce saturated fat in diet to high insulin and high triglycerides (not desirable)
protein -> high insulin and high triglycerides (not desirable)
healthy fat -> monounsaturated/polyunsaturated (desirable)
Monounsaturated Oils
- olive oil
- canola oil
- peanut oil
- avocado oil
- sesame oil
- almond oil
Omega-3 Fatty Acids
- polyunsaturated fatty acids with double bond three carbons from methyl moiety
- rich sources of omega-3-fatty acids: flaxseed, walnut, hemp, salmon, and black current oil
- omega-3-fatty acids reduce risk for cardiovascular disease and have antiinflammatory effects
Endogenous Lipids in Humans
- cholesterol
- TG = triglycerides
- LDL = low density lipoprotein
- HDL = high density lipoprotein
- desirable to have low cholesterol, TG, and LDL
- desirable to have high HDL
Coronary Artery Disease (Ischemic Heart Disease)
- plaque deposition in the coronary arteries which over time can result in a reduction or blockage of the arterial blood supply and oxygen supply to cardiac muscle
- if blood supply is reduced or interrupted for a long enough time the cardiac muscle becomes ischemic (low in blood supply) resulting in infarction and death of the muscle tissue supplied by the clogged artery
Dietary Fat and Cardiovascular Health
replacing saturated and hydrogenated trans fatty acids with non-hydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary artery disease in women than reducing overall fat intake
Syndrome X
-cluster of metabolic abnormalities secondary to insulin resistance and compensatory elevated insulin levels: high triglycerides low HDL cholesterol high blood clotting high blood pressure high coronary artery disease
Oxidative Stress on Vascular System
-clinical endpoints: TG level and LDL oxidation
high TG level -> high LDL oxidation -> high atherogenesis -> high CAD (coronary artery disease)
low TG level -> low LDL oxidation -> low atherogenesis -> low CAD (coronary artery disease)
Diet and Coronary Artery Disease
-problem: saturated fat is main dietary factor that influences LDL cholesterol levels; high LDL cholesterol levels contribute to coronary artery disease
-dietary solution: reduce saturated fat in diet to high insulin and high triglycerides (not desirable)
protein -> high insulin and high triglycerides (not desirable)
healthy fat: mono-/polyunsaturated (desirable)
Diet and Coronary Artery Disease Optimum Nutrient Ratios to Reduce Insulin Resistance
15% protein
45% complex carbohydrates
40% fat with majority monounsaturated and polyunsaturated sources
<10% of total calories as saturated fat
Coronary Artery Disease Development
- low-density lipoproteins (LDLs) can be oxidized by free radicals (molecular fragments) and become part of artery clogging plaque
- flavonoids in tea and other plant foods are thought to cause an antioxidant effect as: free-radical scavengers and/or act on enzymes that influence blood clot formation
Lycopersicum esculenta
- antioxidants/coronary artery disease
- from Solanum
- active ingredient: lycopene
- plant pigment carotenoid found in tomato paste and also in watermelons and grapefruit
- consumption of lycopene-rich foods work as potent antioxidants to reduce the risk of heart attacks
Vitamin E
- antioxidants/coronary artery disease
- daily vitamin E intake resulted in an angiographic reduction in coronary artery lesion progression
Phytoestrogen Compounds
- isoflavones from Glycine max (soybeans), lignans from Linum usitatissimum (flaxseed), and coumestans in Helianthus annuus (sunflowers)
- non-steroidal estrogens in foods that contain a phenyl substitute like estradiol
- have affinities for estrogen receptors in humans
Phytoestrogens and Atherogenesis
-at the site of arterial injury genistein reduces the development of atherogenesis through the following actions:
inhibits platelet activation/aggregation
inhibits thrombin formation
prevents activation of thromboxane A2
prevents activation o fcollagen-induced platelets
inhibits growth factors
enhances vasodilation
Aspirin (Overview)
-from Filipendula (=Spiraea) ulmaria in Rosaceae and Salix alba in Salicaceae
-common name: meadowsweet from Eurasia
-habitat/habit: small tree in meadows and swamps
-part used: bark
-ethnomedical use: inflammation, pain, fever
-pharmaceuticals: salicylic acid
-chemical class: glycoside
-chemical derivatives: salicylic acid-> acetylization -> acetylsalicylic acid (aspirin)
-
Aspirin (Administration)
taken orally as: analgesic antiinflammatory antipyretic antiplatelet (makes platelets less sticky which reduces likelihood of clot formation)
Aspirin (Chemistry)
antiimflammatory mechanism of action:
aspirin blocks cyclooxygenase (proostaglandin synthase) which ->
low conversion of arachidonic acid to endoperoxide -> low formation of thromboxane A2
low prostaglandin synthesis/inflammation and inhibits platelet hemostasis (makes platelets less sticky which reduces likelihood of clot formation)
plasma C-reactive protein concentrations may be reduced
Aspirin (Antiinflammatory Effects on CV Disease)
- C-reactive protein marker for systemic inflammation
- base-line plasma C-reactive protein concentrations are higher among men who went on to develop myocardial infarction or ischemic stroke compared to men who did not develop vascular events
- aspirin consumption -> reduction of plasma C-reactive protein, reduction in myocardial infarctions
Aspirin Effect on Platelet Aggregation, Arterial Thrombosis, and Isochemic Heart Disease
- inhibition of platelet aggregation by aspirin reduces the incidence of acute and chronic ischemic complications of atherothrombotic diseases
- after acute myocardial infarction, aspirin lowers rates of recurrent infarction and death by 20%
- aspirin reduces myocardial infarctions by 30% in patients with unstable angia
- best antiplatelet agent for the chronic protection of patients with ischemic heart disease
Coumadin
- anticoagulant
- Melilotus officinalis in the Fabaceae
- common name: sweet clover
- geography: Eurasia, naturalized in North America
- habitat/habit: open fields; herb
- plant part used: aerial parts
- ethnomedical uses: carminative, spasmolytic
Coumadin (Chemistry)
-active compounds: dicoumarol
-chemical derivatives: coumadin (=warfarin Na), phenprocoumon, acenocoumarol
-mechanism of action: antagonizes vitamin K, results in inhibition of formation of prothrombin in the liver which is dependent on vitamin K to form
modern medical use: anticoagulant
Antihyperlipidemics
Allium sativum in Alliaceae (garlic)
-geography: Eurasian origin, now worldwide
-therapeutic use: fresh garlic taken in diet as an antihyperlipidemic
Avena sativa in Poaceae (oats)
-geography: mediterranean origin, now worldwide
-mechanism of action: oat bran in diet binds lipids in GI tract and reduces its absorption
Pinus spp. in Pinaceae (pine)
-geography: northern hemisphere
-habitat: forests of scandinavia
-active compound: sitostanol (benecol) is a sterol compound
-therapeutic use: benecol margarine is eaten as a food to lower cholesterol
Congestive Heart Failure
- cardiac glycosides from plants
- digoxin (lanoxin) from leaves of Digitalis lanata from Europe
- digitoxin (chrystodigin) leaves of Digitalis purpurea from Europe
- ouabain (= G-strophanthin) from seeds of Strophanthus gratus from Africa
Digitalis lanata and D. purpurea
- plant family: Scrophulariaceae
- common name: foxglove
- geography: europe
- habitat/habit: gardens, open fields, herb
- plant part used: leaves
- ethnomedical uses: cardiac stimulant, congestive heart disease
Digitalis lanata
-active compounds: digoxin (lanoxin), digitoxin (chrystodigin)
-chemical class: cardiac glycoside steroid
-modern medical uses:
digoxin (lanoxin): congestive heart disease, atrial tachyarrhythmias
digitoxin (chrystodigin): congestive heart disease
Digitalis purpurea
-active compounds: digitalin, digitoxin
-modern medical uses:
digitoxin (chrystodigin): congestive heart disease
digitalin: cardiotonic
gitalin: cardiotonic
Cardiac Glycosides (Mechanisms of Action)
-potent and selective inhibitors of the active transport of sodium and potassium across cell membranes
-site of binding is on:
extracytoplasmic surface alpha subunit of Na+, K+, ATPase
equivalent of an enzymatic cellular “Na+ pump”
-inhibition of alpha subunit of Na+, K+, ATPase results in:
increase of cytosolic Ca+ availability to interact with contractile proteins during systole
increase the force of the cardiac muscle contraction resulting in slower but stronger heart beat
-regulates conduction of electrical impulse through AV (atrial-ventricular) node
Cardiac Glycoside Arrow Poisons from Africa
Acokantheran oppositifolia
- plant family: Apocynaceae
- geography: east and southern Africa
- ethnomedical use: arrow poison from wood
Strophanthus gratus
- plant family: Apocynaceae
- geography: africa
- ethnomedical use: arrow poison from seeds
active compound: ouabain (=G-strophanthin)
therapeutic use: cardiotonic, congestive heart failure
Anti-arrythmic Cardiac Drugs
- verapamil: derived from papaverine extracted from Papaver somniferum from southeastern europe
- lidocain, procainamide, and tocainide derived from cocaine extracted from Erythroxylum coca from South America
- quinidine: derived from Cinchona officinalis from teh amazon rainforest of south america
- atropine: extracted from Atropa belladonna from europe
Papaver somniferum
- found in Papaveraceae
- common name: opium
- geography: southeastern europe
- chemical derivative: papaverine -> verapamil
- mechanisms of action: verapamil: vasodilator of coronary and other arteries, Ca2+ channel blocker
- modern medical use: verapamil: hypertension, cardiac arrhythmias
Cardiac Arrhythmias and Local Anesthesia
Erythroxylum coca
- plant family: Erythroxylaceae
- common name: coca
- geography: andes mountains, south america
- habit: shrub, small tree
- ethnomedical uses: leaves used as stimulant, cardiac stimulant, enhance endurance, appetite suppressant
Cocaine and Derivatives (Mechanisms of Action)
local anesthetic
-procain HCl -> blockade of nerve impulses (short duration of action)
-tetracaine -> blockade of nerve impulses (long duration of action)
-lidocaine -> blockade of nerve impulses (intermediate duration of action)
anti-arrhythmic cardiac activity
-lidocaine, tocainide, and procainamide -> block open and inactivated cardiac Na+ channels -> slows conduction
Cocaine and Derivatives (Modern Medical Uses)
cocaine
- applied topically by dentists and nose and throat experts
- local anisthetic
- local vasoconstrictor that shrinks mucosal tissue
tetracaine
-topical anesthetic applied to cornea by ophthalmologists
procain HCl
- infiltrative anesthetic used by dentists for nerve blocks
- local anesthetic and tx of ventricular arrhythmias
tocainide (Tonocard)
-tx of ventricular arrhythmias
procainamide
-tx of supraventricular arrhythmias and ventricular arrhythmias
Cinchona officinalis and C. ledgeriana (Overview)
- geography: native to south america, introduced to africa and asia
- habitat/habit: forest, trees, shrubs
- plant part used: bark of stem and root
- ethnomedical use: fever
- active compounds: alkaloids quinin, quinidine, cinchonidine, cinchonine (over 20 different alkaloids found in bark)
- chemical derivatives: chloroquine, mefloquine
Cinchona officinalis and C. ledgeriana (Chemistry)
- mechanisms of action: antiplasmodial, cardiac antiarrhythmic (quinidine) by blocking Na channels -> block cardiac Na+ channels -> slows conduction
- modern medical uses: treatment of malaria, cardiac arrhythmias, prevention and treatment of nocturnal recumbancy leg muscle cramps
Cardiac Arrhythmias
Atropa belladonna
- plant family: Solanaceae
- common name: belladonna
- geography: europe
- habit: herb
- plant parts used: leaves, roots
- pharmaceuticals: atropine, scopolamine (hyoscine)
- chemical class: alkaloid
Atropine for Cardiac Arrhythmias
- mechanisms of action: anticholinergic, at muscarinic type cholinergic receptors
- modern medical uses:
atropine: cardiac stimulant, treatment of ventricular bradycardia and premature ventricular contractions associated with a slow atrial rate
Angina Pectoris (Crataegus monogyna, C. laevigata, C. oxyacantha, C. spp. (hawthorne) in Rosaceae)
- ethnomedical uses: leaf and flower preparations of this small tree taken to treat coronary artery disease, angina, circulatory disorders
- mechanisms of action: dilation of coronary arteries
- modern medical uses: coronary artery disease, angina, circulatory disorders
Angina Pectoris (Ammi visnaga in Apiaceae)
- geography: mediterranean environments in southern europe, north africa, naturalized in north america
- cultural origins: berber in north america
- ethnomedical use: fruit extract from this herb taken orally to treat angina pectoris and asthma
- mechanisms of action: increased blood flow to coronary arteries to treat angina pectoris
- therapeutic use: friend extracts taken orally to treat angina pectoris
Angina Pectoris (Theobroma cacao in Malvaceae)
- common name: chocolate
- principle active compound: theobromine
- therapeutic uses: smooth muscle relaxant, angina pectoris, coronary artery dilator, myocardial stimulant, diuretic
Anti-hypertension Drugs
- metoprolol (lopressor) and atenolol (tenormin) are beta-blockers derived from ephedrine extracted from Ephedra sinica from china
- verapamil derived from papaverine extracted from Papaver somniferum from southeastern europe
- dark chocolate and theobromine from Theobroma cocoa from south america
Ephedra sinica
- plant family: Gnetaceae
- common names: E. sinica (Ma Huang)
- plant part used: aerial parts
- ethnomedical uses: asthma, sinusitis, stimulant
- pharmaceutical: ephedrine
- chemical class: alkaloid
Adrenergic Alpha-1 Receptors
high arteriole constriction
low gland secretion
low instestinal motility
Adrenergic Alpha-2 Receptors
low secretion of insulin from beta-islet cells in the pancreas
Adrenergic Beta-1 Receptors
high heart rate high heart contractility high cardiac conduction velocity high cardiac automaticity high renin secretion by kidney which increases blood pressure
Adrenergic Beta-2 Receptors
high tracheal and bronchiole relaxation and dilation
Ephedrine Derivatives That Are Beta Blockers
B1 and B2 competitive blockade
-nadolol (corgard): tx hypertension
-timolol (timoptic): tx hypertension and glaucoma
both these medicines can cause bronchospasm in some patients which results in difficulty breathing, so they can not be used in these patients
B1 competitive blockade: tx hypertension
-metoprolol tartate (lopressor)
-atenolol (tenormin)
Rauvolfia serpentina
- plant family: Apocynaceae
- common name: rauvolfia
- geography: India, Indomalasia
- habit: climbing shrub
- plant parts used: root
- ethnomedical uses in Ayuverdic medicine: antihypertensive, sedative, tranquilizer, antipsychotic
Rauvolfia serpentina (Active Compound)
resperine
- mechanism of action: reduce catecholamine and 5-hydroxytrytomine levels in the CNS and peripheral tissues
- therapeutic uses: psychosis, mania, hypertension
Papaver somniferum
- in Papaveraceae
- common name: opium
- geography: southeastern europe
- chemical derivative: papverine -> verapamil
- mechanism of action (verapamil): vasodilator of coronary and other arteries, Ca2+ channel blocker
- modern medical use (verapamil): hypertension, cardiac arrhythmias
Theobroma cacao
- plant family: Malvaceae
- ethnomedical uses: dark chocolate taken orally as antihypertensive, reduces coronary artery disease, aphrodisiac
- active molecule: theobromine
- mechanism of action: smooth muscle relaxant cause blood vessels to dilate
Migrane Headache (tx with caffeine + ergotamine)
sources of caffeine: -Coffee robusta (coffee) -Camellia sinensis (tea) -Theobromacacao (chocolate) -Cola (cola nut) source of ergotamine: -Claviceps purpurea (ergot fungus)
Migraine Headache (tx with Tanacetum parthenium)
Tanacetum parthenium found in Asteraceae
- common name: feverfew
- geographical: SE europe
- plant part used: inflorescence decoction
- ethnomedical therapeutical use: migraine headaches, fever
Varicose Veins and Chronic Venous Insufficiency
- Aesculus hippocastanum in Hippocastanaceae
- common name: horse chestnut
- geography: eurasia
- habitat: temperate forest tree
- ethnomedical use: seeds used in europe to treat varicose veins and chronic venous insufficiency
Aesculus hippocastanum (Peripheral Vascular Disease tx)
- active compound: aescin
- mechanism of action: inhibits capillary permeability to protein
- modern medical use: seed extract applied topically to treat varicose veins and chronic venous insufficiency
Theobroma cacao (Peripheral Vascular Disease tx)
- pentoxifylline derived from theobromine
- common names: chocolate, cacao
- geography: andes foothills in south america
- habitat: tropical forest tree
- plant part used: seeds
- ethnomedical uses: stimulant, euphoriant
Pentoxifylline
- active compounds in Theobroma cacao: alkaloids theobromine, caffeine, theophylline
- chemical derivative: theobromine -> pentoxifylline
- thereapeutic uses (theobromine): smooth muscle relaxant, coronary artery dilator to treat angina pectoris, myocardial stimulant, diuretic, CNS stimulant
- therapeutic uses (pentoxyfylline): peripheral vascular disease, treats chronic occlusive arterial disease with claudication
Ginkgo biloba (Peripheral Vascular Disease tx)
- origin: China
- ethnomedical use: increases blood circulation of brain and extremeties
- modern therapeutic use: peripheral vascular disease, Raynaud’s disease (poor circulation of hand and feet)
Pausinystalia johimbe (Impotence tx)
- common name: Yohimbine
- plant part used: bark
- origin: west africa
- ethnomedical use: taken orally as aphrodisiac in west africa by mny different ethnolinguistic groups
- active compound: yohimbine taken orally as pharmaceutical
- mechanism of action: competitive blockade on adrenergic alpha receptors
- therapeutic use: taken orally as an aphrodisiac and to tx impotence
Papaver somniferum (Impotence tx)
- active compound: papaverine (alkaloid) from Papaver somniferum
- mechanism of action: vasodilator, smooth muscle relaxant
- therapeutic use: penis injections of papaverine produce prolonged penile erections to treat impotence and as an aphrodisiac
