Prof.  Dr.  S.S.  Savrikar                            M.D.  (Ayu.),  Ph.D.      R.  

A.  Podar  Medical  College  (Ayu)    Worli,  Mumbai  (India)  

A report from

New York City Dept of Health and Mental Hygiene (DOHMH) 2011-12

Six pregnant women used Ayu medications

Blood lead levels (BLLs) 16 to 64 μg/dL.

Lead concentrations of medications as high as 2.4%

several medications also contained mercury or arsenic Published in Center for Disease Control and Prevention MMWR Morbidity and Mortality Weekly Report

Weekly / Vol. 61 / No. 33 August 24, 2012

A detailed study w. r. t. indications and duration of consumption of the drugs

reveals that

drugs - misused by the patients

for much longer than

prescribed duration and for a wrong indication

Name of Medicine Prescribed indication Used for Prescribed duration

Consumed Duration

Cap Pregnita Pregnancy nausea vomiting

Nausea & Vomiting 7 days

4 months

Vatavidhwa nsan Rasa

Gastric Disorder

Skin Problems 7 days 3 monhs

Kankayan vati

Lump Pregnancy 7 days 3 months

Garbhapala Rasa Pregnancy Diseases To keep fetus healthy 7 days 6 months

Cap Ovarin

Amenorrhea    dysmenorrhea  

Miscarriage & to promote fertility

4 to 6 weeks 5 months

Garbhdharak Yoga Promo.ng    concep.on  

Promote fertility

3 days following menstruation for three menstrual cycles

Daily for 4 months

Ayurvedic drug - Drug or Food supplement ? Heavy metal limits for food and drug - different No limits applicable for drug products containing elements intentionally included for therapeutic benefit

Prescribed limits of dose and duration of metallic/ mineral drugs

Daily dose Max Cumulative dose

Duration

Gold 60 mg 1 g 1 5 days

Silver , Copper

120 mg 2 g 30 days

Other metals

180 mg 3 g 45 days

There is no such thing as a safe drug. Adverse Reactions

integral part of drug Pharmacology

Ayurvedic drugs- Not an exception

Uppsala Monitoring Centre (UMC) ADR reports from over 100 countries around the world

in 2010 database contained over 4 million reports, of which approx. 21,000 included herbal or natural products >158 million Americans  

some US$ 17 billion spent in 2000

> 70% German population using herbal medicinal products - first choice in the t/t of minor diseases or disorders

Indian Scenario  Incidence of ADRs leading to hospitalization - 2.85%

ADR developed during hospitalization- 6.34%

Fatal ADR incidence - 0.08%

Fourth to sixth leading cause of death among hospitalized patients

Hospitalized patients - a significant burden of ADRs Patel TK1, ’ Patel PB. ‘Incidence of Adverse Drug Reactions in Indian Hospitals: A Systematic Review of Prospective Studies. Curr Drug Saf. 2016;11(2):128-36.

ADRs in Ayu. Hospital

Total - 60,000 patients screened

IPD 4196 patients Female 2260 Male 1936

Adverse Events 84 from IPD and OPD

Confirmed ADR 52 OPD- 04 Developed during Hosp stay 48

Overall incidence 1.143%. Females 28 (1.3%) Males 20 (1.03%)

Ajanal MN, Nayak SU, Kadam AP, Prasad B S. Pharmacovigilance study of Ayurvedic medicine in Ayurvedic Teaching Hospital: A prospective survey study. AYU 2015;36:130-7

Toxicity and adverse events, unwanted reactions of Ayu drugs can be due to

(i) Side effects

(ii) Reactions due to overdose, overuse (iii) Hypersensitivity, allergic

and idiosyncratic reactions

(iv) Mid-term and long-term toxic effects including liver, renal, cardiac and neurotoxicity, genotoxicity and teratogenicity

Ongoing problems in preparation of Ayu drugs-

Use of poor quality material

Incorrect or misidentified material

Incorrect processing methods

Adulterated or contaminated material

Issues in Ayurvedic drug administration

1. Dose of the drug

2.  Duration of administration

3.  Indication of administration

Edible material

Wholesome or Unwholesome

Usually or persistently or

Wholesome and unwholesome by nature or due to effect of associated factors - Caraka Samhita

Usually Wholesome - Water Ghee Milk

Usually Unwholesome Acrid material Poisons

May prove useful in some diseased states

Wholesome and Unwholesome - Lemon juice

Wholesome as a promoter of digestion

Unwholesome as augmenter of acidity

Wholesome - Health promoter Unwholesome - Health destructive However Unwholesome used regularly in diseased states

Ghee (Clarified butter)

Usually Wholesome in character

Unwholesome when consumed in Overdose Spring Marshy lands With non-compatible materials Obese individuals

Poisons Unwholesome in nature Can prove life saving

when used in appropriate dose

Characteristics of best drug

Produces expected therapeutic effects Life saving

May cause little discomfort

Not causing any permanent damage

when processed appropriately and used in appropriate dose

Manifestations of drug being metabolized (Kashyap Samhita)

Yawning Irritability

Dryness of mouth Restlessness

Fatigue Drowsiness

Cramps in thighs

Reduction in disease symptoms

Concept of non-compatibility

Non compatible Combinations Actions Proportions in taste temperament metabolic products

Some times Non-compatible drugs need to be used in diseased conditions with ref to disease state habitat period of drug administration body type digestive status -Susruta Samhita

Unwholesome dietary combinations Cucumber + Milk Mushroom + Milk Sprouts + Milk Meat, Fish, Alcohol + Milk

Non –compatible practices lead to

Disease

Debility

Death

Non-compatible practices – Compared with

consumption of Poison - Susruta Samhita

Drug-food interaction

Consumed food affects the ingredients in a medicine so the medicine can't work the way it should

Interaction of grapefruit with medicines?

Grapefruit juice can cause higher levels of some medicines in the body, leading to side effects

Interactions can happen up to 3 days after eating or drinking grapefruit

Guggulu (Comiphora weightii)

with Anticoagulant drugs:

Aspirin, warfarin Potentiates the effects

Thyroid medications:

Stimulates the thyroid gland1

Propanol and Calcium channel blockers

diltiazem 2 may reduce absorption

1*Tripathi YB, et al. Thyroid stimulatory action of (Z)-guggulsterone: mechanism of action. Planta Med 1988;54(4):271-7. *Panda S, Kar A. Gugulu (commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci 1999;65(12):PL137-41. 2*Dalvi SS, et al. Effects of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India 1994;42(6):454-5.

Garlic – Alium Sativum

Modulates activity of drug-metabolizing enzymes

Cytochrome p450 isozymes and/or

Drug transporter P-glycoprotein

May have potential pharmacokinetic interactions with anticancer drugs - Sparreboom 2004

Raw garlic has high antioxidant potential

Higher doses may be toxic to the heart, liver and kidney -Banerjee 2003

Garlic supplements can impede HIV medication

Curcuma longa

0.2 or 1% of turmeric ethanol extract for 14 days

showed hepatotoxicity in mice - Deshpande 1998

Dietary turmeric (0.2%, 1.0%, 5.0%) or

Ethanol extract (0.05%, 0.25%) for 14 days,

reported to be cancer preventive,

found to be hepatotoxic in mice

with coagulative necrosis and a zone of regeneration of Parenchymal cells - Kandarkar 1998

Piper nigrum

10 mg/kg piperine for 30 days to rats

decrease in testis weight, testicular testosterone, seminiferous tubular and Leydig cells

damage to seminiferous tubules, desquamation of spermatocytes and spermatids and increased serum gonadotropins -Malini 1999

CCl4-induced hepatotoxicity

Potentiated by piperine, dose-dependently in ra - Piyachaturawat 1995