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Cardiac Medications
Hypericum perferatum
Stops angtiogensin II: most vasoactive product of renin- Capsicum frutescens Cough. Slowed progression of chronic renal faulure (captopril
antiogensin. Lower renin in African's, therefore less only)
ACE Inhibitors - PRLIS effective. Dec systemic arteriolar resistance, diastolic
BP, systolic BP, HT rate; INC HT output, stroke volume,
stroke work. Ferrous sulfate DEC by captopril
KCl (Pottasium) Inc by captopril, trandolapril
Ephedra sinica May antagonize ACE inhibitors
DEC Na, Cl, K, H
Cardiac Therapy -
Congestive Heart Failure Glycyrrhiza glabra Leads to hypo-K, may antagonize amiloride
Crateagus Increased exercise tolerance, dec adverse effects
Inc Iodide (KI) amiloride, spironolactone
Diuretics: Loop. Furosimide/ Inhibit Na reabsorption in ascending loop of Henle, Antacids dec by ethacrynic acid
Lasix. proximal and distal tubules. Dec B1
Dec Folic acid
Nicotiana tabacum vasoconstrictive nicotine --> dec furosemide
Effect on rat uterus antagonized by amiloride, interfere alpha 1A
Serenoa repens
antagonist
Gossypium herbaceum hypo K
Bile acid sequestrants - Exchanges Cl for bile acid --> insoluble complex, feces. Dec Vit A, B3, B12, folic acid, D3, E, K, Ca carbonate, Fe
cholestyramine (Questran), Elevated cholesterol, LDL. No drugs 1 hr before, 4-6 sulfate
colestipol hours post use (particularly fat soluble) Given with B3 --> INC colestipol efficiency
Mechanism unknown- Dec LV extraction free fatty acids
Fibrates - clofibrate, benzafibrate,
--> dec TG. With statin: sever myostitis, acute renal Dec vit A, B12, E, Fe sulfate
fenofibrate, gemfibrozil
failure, dec vitamin E
Dec CoQ10
Cardiac Therapy -
Dyslipidemias B3 inc statin toxicity or additive clinical effect
HMG-CoA reductase inhibitors -
Rate limiting step in cholesterol synthesis Dec simvastatin (p=glycoprotein, CYP 3A4. Pravastatin has no p-
statins (atorvastatin/lipitor). Hypericum perferatum
glycoprotein so unaffected.
Citrus paradisi Inc bioavailability
Ananas comosus Inc cholesterol reduction
Gastrointestinal lipase inhibitors- GI lipase absorption inhibitor. Used in obesity, fatty liver, Plantago psyllium Dec GI flatulence
orlistat NIDDM. SE: Gi upset, diarrhea
Dec Vit A, D, E, K, B12
Loop Diuretics - bumetanide,
ethacrynate, enthancrynic acid,
furosemide
Osmotic Diuretic - mannitol
Edema Potassium Sparing Diuretids:
amiloride, spironolactone,
triamterene, hydrochlorothiazide
Thiazides and Related agents
Various Diuretics
Antiadrenergic Agents - Alpha 1,2
Dec Total peripheral resistance. SE: orthostatic
Adrenergic Blocking agents. Serenoa repens Inhibit alpha 1A antagonist cloned human receptors
hypotension, tachycardia
Prazosin/minipress
Antiadrenergic Agents - Alpha 1,2
Short duration, positive inotropic, chronotropic. Vascular
Adrenergic Blocking agents. Pausinystalia yohimbe Due to alpha 2A antagonisms from phenolamine
smooth muscle dilator. Prevent HT episodes.
Phentolamine mesylate/ rogitine
alpha adrenergic agnoist/antagonist. Dec peripheral
Centrally Acting Antiadrenergic
resistance, diastolic & systolic BP, HT rate, postural Pausinystalia yohimbe Inc BP. Clonidine dec anxiety induced by yohimbe.
Agents - Clonidine/ catapres
reflexes intact. SE: dry mouth (inc dental caries)
Centrally Acting Antiadrenergic
Fe sulfate dec drug effect. KCl decreased by drug.
Agents - Methyldopa
Epedra sinica Reserpine dec epedrine induced catecholamines
Pausinystalia yohimbe
Lithium carbonate Induced head twiches sig decreased
Depletes brain NE, serotonin depletes NE at peripheral Hypericum perferatum antagonized reserpine effect
Centrally Acting Antiadrenergic sympathetic nerve terminal, peripheral vasodilation.
Hypertension Agents - Reserpine Used in HT and anxiety, Raynaud's. SE: hypotension, GI Camellia sinensis (green/ black tea) Dec GI ulcer
upset. Curcuma longa Dec GI ulcer
Vaccinium myrtillius Dec GI ulcer
Dec orofacial dyskinesia, poor memory, brain lipid peroxidation.
Withania somnifera
SE: memory problems. Withania helps with this.
Arteriolar Smooth Muscle Agents
- Ca Channel Blockers Citrus paradisi Inc bioavailability
(Felodipine)
Arteriolar Smooth Muscle Agents
- Vasodilators. Sodium Dec B12
nitroprusside.
Diuretics - Osmotic (mannitol) Dec Mg oxide, KCl
Diuretics - Thiazides and related Induce Na, water excretion by inhibiting sodium, Cl co- Dec KCl, Zn
agents transporter. SE: inc chol, TG, LDL
Crataegus spp Inc exercise tolerance, dec adverse effects
Renin-Angiotensin System Agents
Metabolized by P450 3A4. SE: syncope, hypotension. Citrus paradisi, hypericum perforatum May use p-glycoprotein, CYP 450
(losartan potassium)
CYP 450 1A2 Caffeine, Ginkgo bilboa, Hypericum perforatum, quercetin
Phase 1 CYP450 Update CYP 450 2E1 Hypericum perforatum, Allium sativum
CYP 450 3A4 Amiodarone, quinidine, verapamil, hypericum perforatum, Camellia sinensis, Allium sativum, Citrus paradisi, Hydrastisi canadensis
Glutathione s-transferase Larrea tridentata, Gossypium herbaceum, G hirsutum, Cinchona spp, Nicotiana tabacum, Allium sativum, Coriandrum sativum, Zingiber officinale
UDP -
glucuronosyltransferases Larrea tridentate, Allium sativum, A cepa
Phase II Update (UGT)
NADPH - quinone
Vaccinium myrtillus, V. macrocarpus, Allium sativum, A. cepa, Zingiber officinale
reductase
Epoxide hydrolase Allium sativum, A. cepa
LOOK AT SUMMARY SLIDES
Caffeine 4 cup/d dec LI, withdrawl --> tremors, inc LI levels.
Plantago Psyllium Dec 14% therefore > 1hr
Cydonia vulgaris quince seed
Astragalus gummifer, Ulmus fulva (slippery elm)
Na transport. Inc K, Na in urine. Dec catecholamine Oenothera Biennis Dec tremor SE (2-3g/day)
clearance. Inhibit intracellular c-AMP formation. Low Fucus vesiculosus
Bipolar Disorder Lithium Carbonate May be beneficial for thyroid
NaCl diet inc LI reabsorption. Thyroid - block T3 Laminaria digitans
release (hypoT) Asparagus officinalis
Barosma betulina
Diuresis
Camellia sinensis
Coffea arabica
Oenothera Biennis latent temporal lobe epilepsy (seizures)
Areca catechu Inc. SE.
Silybum marianum 400 mg bid DEC Liv toxicity.
Borago officinalis
Phenothiazine / Fluphenazine /
Schizophrenia Dopamine-block receptor. Catecholamine - hepatotoxic. Linum usitatissimum
thiodazine
Coffea arabica tannin Dec GI
Camellia sinensis + high tannin: Geranium maculatum
(Quercus spp.)
Reserpine (Rauwolfia) Inc. seretonin, NE
L-tryptophan, L-Tyrosine, L-phenylalanine URI (allergies/cold meds)
food (fermented), fava bean Seretonin; Thyroid hormones
Kaolin Dec absorption
retention ephedrine, pseudoephedrine => tremor, insomnia,
MAO - brain, GI, LIV; Dec BP, inhibit breakdown Na bicarbonate (tums, IV)
tachycardia
catecholamines: seretonin, NE. MAO-A-5HT, MAO-B -
Coffea arabica, OTC amine, L, Dopa, Tricyclic
phenylethylamine. Inc. catecholamines => BP,
MAOI (Monoamine oxidase Phenelzine, moclobemide, nardil, antidepressants, Theobroma cacao (chocolate), Camellia
tachycardia, occipital HA, intracranial bleed. 98%
inhibitors) manerix sinensis, Ephedra sinensis, E. vulgaris, Panax Ginseng,
absorbed. 55% bioavail. 90% w/ repeat use.Slow
Rauwolfia serpentina, potentiate hypoglycemics - B blocker,
metabolizers => 2% caucasians, 15% ASIANS.
Hydrazine sulfare (anti-CA therapy)
Washout 2 weeks post use.
Passiflora incarnata alk act on MAO pathway. Potentiate hexobarbital
Selenicereus grandiflorus alk, amines
Sarotharmnus scoparius tyramine
Eleuthercoccus senticosus potentiate hexobarbital
Hypericum perforatum weak in-vitro MAOI effect
Psychiatric Disorders
effect norepinephrine, dopamine; nor adrenergic, NSAIDS, ASA (GI bleed), warfarin
histaminergic, muscarinergic, GABA, benzodiazepine Gingko biloba dec sex dysfunction
receptor. Well absorbed, CYP450-1A2, 2C19, 2D6, 3A4; elderly, mild serotonin syn after 8 months SSRI => insomnia,
Citalopram, Fluoxetine, 98% metabolized. KI 64%, BM 36%; slower in elderly. Hypericum perforatum
SSRI (Selective serotonin groggy, incoherent, weak, lethargic
Fluvoxamine maleate, paroxetine Enters breast milk. 2-5 wk washout MAOI => SSRI. W/
(5HT) reuptake inhibitors) Hypericum perforatum Hyperforin Inhibits uptake serotonin, NE
(paxil), Sertraline MAOI => Serotonin Syndrome: agitation,
hyperreflexia, tremor, diarrhea, hyperthermia, Tanacetum (Chrysanthemum) pathenium Inhibit serotonin release
seizure, DIC, vent. arrhythmia. SE = inc suicide < Salix alba, S. nigra, Filipendula ulmaria, Gaultheria
18yo. dermatologic, hypoglycemia in diabetes, procumbens, Melilotus officinalis,
Tricyclic: Amitriptyline, Ephedra sinica Amitriptyline blocked inc. BP
clomipramine, desipramine, Alter transport, storage, release catecholamine. Inhibit
Gingko biloba offset sex dysfunction
doxepin, imipramine, nortripyline, histamine, 5HT, acetylcholine. CI: MAOI
trimipramine Nicotiana tabacum speeds tricylic elimination
Anticholinergic. CI: Seizure, seizure risk, children, post-
Dec orthostatic hypotension of climipramine, NE & BP of
Tetracyclic: Maptotiine acute MI, LV/KI damage, blood dyscrasias, tricyclic Pausinystalia yohimbe
desipramine
sensitivity.
Antidepressants
Mechanism unclear. 60-70% KI, 9-29% BM. SE: MAOI, digitalis, phenytoin, EtOH
Other: Trazodone
priapism, arrhythmia if HT Dz, latent seizures Hypericum perforatum serotonin syndrome
Humulus lupulus additive
Hypericum perforatum Hyperforin Inhibits uptake serotonin, NE
Tanacetum (Chrysanthemum) pathenium Inhibit serotonin release
Valeriana officinalis
Citrus paradisi Inc. Bioavailability, CYP-3A4
Hypericum perforatum midazolam dec 60% after 12d tid vs levels pre-SJW, CYP-3A4
Piper methysticum Enhanced sedation, GABA-A affinity, alprazolam
EtoH
counteracted diazepam 22%, clonazepam, antagonized
GABA & Benzodiazepine receptors, chloride channels. Coffee arabica
Benzodiazepines: Alprazolam, triazolam
Anxiolytic => anticonvulsant => Dec. muscle tonus => Valeriana officinalis
bromazepam, chlordiazepoxide, Aids withdrawl
CNS Depressants, sedation => hypnosis=> death?. Well absorbed. Protein
clobazam, clonazepam, Melatonin
Anesthetics bound 80-99%. Concentrate in lipids: CNS, adipose
clorazepate, diazepam, Cola nitida, C.acuminata, Puallina cupana, Ilex
tissue. Elimination KI, Highly addictive. CI: Myasthenia Caffeine effect
flurazepam….PAM paraguayensis, Camellia sinensis, Theobroma cacao
gravis, acute-angle closure glaucoma
Eleuthercoccus senticosus potentiate hexobarbital (diazepam)
Panax ginseng pentobarbital
Passiflora incarnata hexobarbital
Morphine alkaloid of papaver somnifera
Withania somnifera (mice) tolerance to morphine analgesia inhibited & dependence blocked
Glucocorticoid - primary, inc. protein catabolism,
glucaneogenesis; anti-inflammatory. Adipose redistribution
=> central from periphery. Ca2+ dec. GI absorption, inc.
Antidiabetic (eg. Insulin), cyclosporine, digoxin, estrogen, isoniazid,
urine excretion, inhibit macrophages, dec. immune
oral anticoagulants, K losing diuretics, ASA, NSAIDS
response, stimulate erythoid of bone marrow, inc survival
rbc & platelets. mineralcorticoid - 2o, Na reabsorption, K,
H excretion; salt retention.
Bethamethasone, cortisone, interfere with aldosterone, cortisol breakdown => inc half life; acid
Glycyrrhiza glabra
dexamethasone, fludrocortisone, => potentiated topical hydrocortisone
Metab LV => urine, bile. CI: fungal infection, live viral Riges nigrum oil
Corticosteroids hydrocortisone, RA - dec. joint tenderness # & score vs placebo
vaccine.
methylprednisolone, Borago officinalis
prednisolone, triamcinolone DBPC, cataract surgery, post-op => dec. lid edema, conjunctival
Anamas comosus
edema, mild hemorrhage
Aloe spp., Rhamnus frangula, R.purshiana, Rheum
Anthraquinones, potassium depletion => arrhythmia
palmatum, R. officinale, Cassia acutifolia
Astragalus membranaceus, Echinacea spp., Tabebuia
Immune
avellandae
Estrogen, progesterone, pregnenolone, testosterone, DHEA
ASA Dec. clearance => increase methotrexate toxicity
Folic acid Dec. therapeutic response
Vit A, glutathione Dec. toxicity
Folic acid analog. Competes w/, irreversibly binds Vit E, Selenium Increased Tx effect
dihydrofolate reductase; blocks active form: Panax quinquefolium Inc. Tx effect Est+ Breast CA
Antimetabolites Methotrexate
tetrahydrofolate; Inc. glycine, inc. homocysteine. 93% Cannibus sativa Dec nausea in 78% (unresp. To antiemetics)
bioavailable IV, 36% oral. 80% urine excretion Matricaria recutita resolved mucositis, oral ulcers
Betula lenta, actea racemosa, Filipendula ulmaria,
Gaultheria procumbens, Populus balsamifera, P.
tremuloides, salix alba, S. nigra
prevented myelosuppresion - rbc, wbc. Chemotherapeutic effect
Cyclophophamide (Nitrogen
Alkylating agents Withania somnifera unknown. Delayed hypersensitivity rxn induced by cyclo
mustard analogs)
suppressed at 1000 mg/kg.
May bind DNA => interstrand , intrastrand crosslinks
=> apoptosis. Post-IV - KI, LV, prostate; bladder,
muscle, testicle, pancreas; later: bowel, adrenals, HT,
Cisplatin (Platinum compounds) Diuretics Increase ototoxicity
LU, brain. Platinum persists in tissues => 180 days.
Excretion: 90% urine, 10% bile, 10-40% in urine @ 24h.
SE: nephrotoxicity, ototoxicity.
Vit A, E, glutathione, quercerin inc. tx effect
VIT C; B-Carotene+A+C+E; genistein, quercetin Inc. cytotoxicity
Cannibus sativa Dec nausea in 78% (unresp. To antiemetics)
stage II ST CA - doubled survival time, improved CD3, CD4 while
Panax ginseng
on 5FU+Cisplatin
non-small cell LU CA - reduced death risk, inc proliferation SP
Astragalus membranaceus
cells, B cell IgG, cytotoxic T cells, macrophage IL-6 & TNF
Pyrimidine analogs
B-carotene, melatonin Dec Tx effect
Blocks methylation of deoxyuridylic acid => thymidylic
Fluorouracil Vit C, glutathione Inc Tx effect
Antimetabolites acid therefore interferes w/ DAN, RNA synthesis
Vit A, CoQ10, gluthathione Dec. toxicity
Metabolized to 5FU by thymidine phosphorylase in tumor Melilotus officinalis coumarin anti-coagulants
Capecitabine
and normal cells => cell damage; colorectal => LV CA CYP450 2C9
CoQ 10, Vit A, C, E, Selenium, Melatonin Dec Toxicity
Vit A, C, E, Selenium, B-Carotene, quercetin, green tea Inc Tx effect
Bind DNA, inhibit nucleic acid synthesis, 4-5% Panax quinquefolium Inc Tx effect Est+ Breast CA
excreted in urine in 4-5d. 40-50% in bile/feces in 7d, Cannibus sativa Dec nausea in 78% (unresp. To antiemetics)
Chemotherapeutic Agents (Antracyclines) Doxorubicin,
slowed if impaired LV function. SE: progressive Rosmarinus officinalis methanol extract Inc DOX in Breast CA cells via P-glycoprotein transport pump
Cytotoxic Antibiotics Daunorubicin, epirubicin,
diverse cardiac toxicity (permanent). Disposal - Inc DOX in ovarian sarcoma, Dec. DOX in normal tissue, Dec.
idarubicin, valrubicin Camellia sinensis extract
anything that contacts if must be labelled & treated as tumor size (mice)
hazardous waste. Actea racemosa Inc. cytotoxicity (mice) also MCF-7
Digitalis spp., Rauwolfia serpentina, Selenicereus
Direct herbal regulation of cardiac function
grandiflorus…
Chemotherapeutic Agents
Anti-androgens - bicalutamide,
sypoterone, flutamide, nilutamide
Non-steroidal aromatase
inhibitors - anastrozole,
exemestane, letrozole
Competes w/ estrogen binding sites in breast, uterus.
Anti-estrogen - Tamoxifen Displays estrogen-like effect on endometrium, bone, Citrus sinensis peel Dec Tx effect
blood lipids
Vit A, melatonin Inc. Tx effect
Vit. C, tocotrienols (?) Inc. Cytotoxicity
Hormone Antagonists DEC Magnesium
Increase Zinc
Panax quinquefolium
Inc Tx effect Est+ Breast CA
Oenothera Biennis
Silybum marianum prevented KI damage
Actea - 58% EtOH extract HOT FLUSHES in post-meno breast CA survivors
Ribes nigrum faster response to tamoxifen
Induces apoptosis via inhibition NK kappaB, stabilization Human CA cells lines w/ anti-oxidants => not induce apoptosis. DO
Protease Inhibitor - Velcade
protoapoptotic proteins. Promotes chemo & radio- Vitamin C NOT GIVE VELCADE & VIT C TOGETHER => velcade does not
bortezmii PS-341
sensitization. Relapsed multiple myeloma generate intracellular reactive oxygen species.
Estrogen & progesterone B12, B2, B6, Vit C, Magnesium, ASA (Salix alba/nigra,
marvelon, cyclen, ovral-21 Inhibit ovulation Dec Folic Acid
monophasic Filipendula ulmaria…)
Estrogen & progesterone
Synphasic, ortho 7/7/7 Suppress gonadotropins Citrus paradisi, Vit C may Inc. ethinyl estrogen
biphasic
Estrogen & progesterone Suppress gonadotropins => Dec ovarian androgens =>
Oral Contraceptives Alesse-21, Triphasil-21 Hypericum perforatum Dec. contraceptive activity
triphasic Dec testosterone
Theobroma cacao, coffee arabica, cola nitida, paullinia
Androgen dependent acne Diane-35 Block androgen receptors Inc sereum Vit A, Vit K, calcium, zinc, caffeine
cupana (guarana), Ilex paraguayensis, Camellia sinensis
Glycyrrhiza glabra hypertension
gaviscon, Aluminum-magnesium Nicotiana tabacum clots, strokes, MI
preparations - mylanta diovol, Digitalis spp. Dec. phosphorus, iron, folic acid
Antacids Antacid foam, coating agent. Acid absorption.
Calcium preparations - tums, Vit C Inc. Al absoprtion
Magnesium preparations - phillips
Histamine H2 Receptor Cimitidene, famotidine, nizatidine, Onset 15-60 min, duration 4-8h, clearance 30-48h.
Antagonists ranitidine Inhibits CYP450-1A2, 2C9, 2D6, 3A4. Bind H2 receptors
Dec B12, Ca, Mg, Fe
Gastroesophageal Reflux Peak plasma 2h, duration 24h. 95% plasma protein
Iansoprazole, Omeprazole,
Proton Pump Inhibitors bound. Excretion: urine 80%, feces 20%. CYP450-2C19.
Pantoprazole, Rabeprazole
70% reduction in peak HCl after 5d @ 20mg/d.
Antacids
H2 Hypericum perforatum, citrus paradisi Dec acid dependent nutrients
Proton pump
Inhibits purine synthesis: esp leukocytes, lymphocytes.
Cyclosporin + azathioprine Used in KI transplant, RA. SE: susceptible fungal, viral Cordyceps sinesis Dec nephrotoxicity
infection, cunvulsion, GI ulcer
Immunosuppressants
Used 6 wek acute KI rejection after 16 y. Serum
Medicago sativa + Actea
cyclosporine unaltered. T cell activation via L-
racemosa
canacanine?
Pneumococcal vaccine
Vaccines Uncaria tomentosa - H2O extract enhanced immune response by elevating
w/o oxindole alk lymph:neutrophil ratio in blood & dec serotype decay
Dec Fe absoption
Ephedrine Increase thermogenesis
MAOIs, propranolol, metropolol, pheylpropanolamin Inc. BP reaction via Inc. Norepinephrine
Inhibits adenosine
Clozapine Supraventricular Tachycardia
Pentobarbital, diazepam, triazolam, zopiclone, clonazepam Antagonizes
Caffeine Increases ASA absorption
Dec. Lithium levels
Fluvoxamine, oral contraceptive, cimetidine, verapramil,
disulfiram, fluconazole, mexiletine, phenylpropanolamine, Inc. caffeine stimulation
idrocilamine, methoxsalen, phenacetin, furafylline
Quinolone antibiotics (enoxacin, pipemidic acid),
Caffeine inhibited
norfloxacin, ciprofloxacin
Phenytoin Increase caffeine metabolism & loss
H2 blockers, acetaminophen, B12 Dec blood levels
Benzodiazepines, heparin, pentazocine, TCAs, caffeine,
Speeds elimination
amobarbital, Vit C
Phenylbutazone, quinine, estradial, flecainide, haloperidol,
Speeds metabolism
ligncaoine, tacrine, thiothixene, zolpidem, phenothiazines
Nicotiana tabacum Furosemide, insulin, dextropropxyphene, B-Blocker Renders less effective
Glutethimide Enhances drug effect
Oral Contraceptives Inc. stroke risk in women > 30
Adenosine Inc. circulatory effect
Theophylline (green tea) Inc. Metabolism
Cimetidine, ranitidine (H2 antagonists) Dec. breakdown of nicotine
Nifedipine Inc. BP effect
Felodipine, amlodipine, verapamil, nitrendripine, nisoldipine,
Inc. bioavailability 3X
nimodipine (Inhibit CYP450-3A$
Terfenadine Increase bioavailability => fatal arrhythmia
Coumarin, benzodiazepines, simvastatin, lovastatin,
saquinavir, quinidine, estradiol, ethinylestradiol (inhibit Inc. bioavailability
Citrus Paradisi CYP450-3A4)
Cyclosporin (P-Glycoprotein inhibition) Inc. Plasma concentration
Caffeine metabolism inhibited: Inc. AUC + dec 1/2life + Dec.
Naringin (inhibits CYP450-1A2)
caffeine clearance
Clarithromycin, 14-hydroclarithromycin Dec. absorption
Fexofenadine Dec. bioavailability
Paroxetine Inc. sedation w/ surgery
Nefazodone, sertaline, trazodone Serotonin syndrom (in elderly pts)
Cyclosporine, Indinavir, ethinyestradiol, desogestrel,
warfarin, phenprocoumon, midazolam, statins (HMG-Co- Dec. Plasma
reductase), digitozin, B-Blockers
Hypericum Perforatum
Dec. Resperine (mice)
Inc. EtOH effect (mice)
MAOIs enhanced
Opiod anesthetics, tamoxifen, taxol, etopisine,
Induce CYP450-3A4, P-glycoprotein reduced
pseudoephedrine, naloxone, proxicam, tetracycline