ItisanUPHILLtasktomonitordrugsofISM - Pharmacovigilance · Herbal drugs have been used in India for more than 4000 years

It is an UPHILL task to monitor drugs of ISM

Prof. K. C. Singhal M.D., Ph.D. (Medicine), D.Sc., F.I.A.N., F.I.P.S., F.I.A.M.S.

Consultant WHO Center for International Drug Monitoring, Uppsala, Sweden

Ex-Vice - Chancellor,

NIMS University

Jaipur

ccessible

ffordable

ssured safety

About 70% Indian population (60-70 crore) depends on alternative system of medicine.

WHO

Herbal drugs are cheaper than generic drugs !!??

Herbal drugs have been used in India for more than 4000 years.

Tradi7onal medicines

•  Middle of 19th century, 80% of all medicines were herbal

•  Even today 25% of drugs are derived from plant source

•  Most of these drugs came from tradi7onal lead, folk knowledge etc.

•  Some of these s7ll could not subs7tuted despite the enormous advancement in synthe7c chemistry eg. Reserpine, taxol, vincris7ne etc.

Ø  Medicinal Plants for Primary Care Ø  65 to 80% world population use safety

traditional Medicine Ø  Use based on historical and anccdotal

evidence Ø  Little data with regard to efficacy

Health care system in India

•  Allopathy – Disease oriented •  Ayurveda -‐ (Holis7c system) •  Unani -‐ (Holis7c system) •  Siddha -‐ (Holis7c system) •  Homeopathy Symptom based •  Conference

Principals of Treatment are different

•  Ayurveda -‐ VATA •  -‐ PiCa •  -‐ Kafa

•  Unani -‐ Mijaz ( temperament) •  Hot, Cold, Dry, Moist •  Hot + Dry •  Hot + Moist •  Cold + Dry •  Cold + Moist

Fundamental of Unani Medicine

• Unani Medicine-‐concept of elementary i.e groups of four elements, air, water fire and earth. • HippocraAc theory of four humors i.e blood phlegm, bile and black bile

HYPOTHESIS

•  Disease is caused by the impairment of Temperament ( Mijaz )

•  Drugs of opposite temperament provide beneficial response

Selec7on of Pa7ents Posi7ve response

10 to 15 percent increase in FEV1 (forced Expiratory volume in one second)

Ibn Sina The Author of Al Qanoon Fil Tibb (Canon of Medicine)

Abu Bakr Mohammad bin Zakariyya al Razi (Rhazes)

•  Born in Iran 240 hijri •  Studied Indian Medicine •  Chief Medical Officer in hospital of Baghdad •  Became blind at 60 •  29 books wri[en by Rhazes are available

Maqala Fi Abdal Al-Adwiya Al Mustamala Fi

Al-Tib wa Al-Ilaj (Kitab Al-Abdal)

" All the drugs required for the treatment are not available everywhere. So, if the physician is unaware of substitutes which may be used in place of the original drug, the objectivity and benefaction of this medical profession would cease".

Examples of compound drugs along with substitutes

Drug Substitute Dawa al-‐Qust Dawa ul-‐Kurkum

Dawa al-‐Luk

Roghan-‐e-‐hina Roghan-‐e-‐Marzanjosh

Roghan-‐e-‐gul Roghan-‐e-‐Banafsha

Principles of substitutions Avicenna -‐ Subs7tute should only be used when original drug

meant to be used is not available.

Avicenna -‐ No drug can be a complete subs7tute for another drug in all respects.

Rhazes -‐ Drug should be subs7tuted for original drug for specific ac7vity

-‐ Different drugs may be subs7tuted for different ac7on

-‐ Subs7tuted drug should match the original in mijaz (Temperament)

Mijaz (Temperament)

• Drug could be

Hot + Dry

Hot + Moist

Cold + Dry

Cold + Moist

• Hot, Cold, Dry, Moist -‐ each has degrees from 1-‐3

• A drug hot and dry in 1st degree be subs7tuted with hot and dry 1st degree

Subs7tu7on (Abdal al-‐adviya)

Drug of one origin can be replaced with drug of another origin. Example :

Drug Subs7tute

Jund Bedastar (Animal) Black pepper (1/2 by weight) (Plant)

Calcinated & washed egg Tarasis (Gummiferum)

shell

One species of plant may subs7tute for another species

Podina kohi (Mentha) Podina Nahri (Panny Royal)

Another part of same plant may serve as subs7tute

Margosa flower Margosa leave or bark

Sosan leaves (Lilly) Sosan Root

Banafsha

Factors influencing quality of herbal drugs

♦ Collec7on in proper season and not during rains

♦ Authen7ca7on, nomenclature

♦ Collected material dried in sheds under proper ven7la7on

♦ Pes7cide residue

♦ Foreign material (mixture of other species)

♦ Fungal contamina7on

♦ Pack properly dried herbs in air/ water proof bags

Major constraints in herbal drug standardiza7on and guidelines for strengthening quality control

* Dependence on wild source

* Adultera7on and subs7tu7on

* Mul7lingual nomenclature

* Public test house for herbal drugs

* Prepara7on of herbal drug manual or pharmacopoeia

* Poor investment in R & D for establishing standards of herbal drugs

* Lack of safety evalua7on facili7es

* Absence of herbal drug regula7ons

* Lack of trained manpower

Tradi7onal Medicine

Why ADR Monitoring Difficult

♦ Theories of applica7on are different

♦ Too many products to monitor

♦ Mul7ple ingredient formula7ons -‐numerous

♦ Herbal and allopathic drugs taken together

♦ Formula7ons change keeping same brand name

♦ Methods of prepara7ons differ

♦ Quality checking is ambiguous

Repor7ng Herbal ADR's A long, tedious and unending

journey ahead..............

although it must happen

Why is ADR Monitoring of Herbal drugs more difficult

There are single and mul7ple ingredient formula7ons


To many products to monitor

Scien7fic Observa7ons

♦ Overdose -‐ produce minimal toxicity

♦ Intoxica7on may cause life threatening events

♦ Mechanism of toxicity not well understood

♦ ADR analysis difficult


The formula7ons can be changed at will keeping the same brand name

Table 2: Following formula was started with 52 ingredients and now it has 8 cons7tuents. Each tablet contains powders of

Himsra 65 gm

Kanasi 65 gm

Madur Bhasm 33 gm

Kaka machi 32 gm

Arjuna 32 gm

Kasamarda 16 gm

Biramjasipha 16 gm

Jharuka 16 gm

Some Facts

* Only 5% of the 500,000 species of plants have been screened for biological acAvity.

[Farnsworth NR & Bingel AS. In New Natural products and plant Drugs with pharmacological, biological or therapeuAc acAvity. Wagner H. & Wolff, P.., Ed. New York. Springer P.I. (1977).

* Plant products consAtute 25% of the prescribed drugs.

[ Ref: Zenk, MH. In proceedings of IV Ist Cong. In plant Tissue and Cell Culture. Thorpe TA., cd. Calgary University of

Calgary P.I. (1998)]

Contd..

Pharmacovigilance

•  Any thing herbal is safe!!????? •  Adverse drug reacAons (ADR) •  Drug-‐drug interacAons •  Herb-‐Drug interacAons •  Toxicity of the isolated ingredients •  TradiAonal process (Shodhana)

Tradi7onal Medicine: Threats

•  Poor positioning on a global level

•  Ignored by the global scientific community

•  Very little scientific research validations

•  Very little publications in peer-reviewed

science Journals

•  Deliberate negative propagandas

Why is ADR monitoring of ‘Herbal’ drugs even more

difficult?

There are single and mul7ple ingredient formula7ons

The formulaAons can be changed at will keeping the

same brand name

Why is ADR monitoring of ‘Herbal’ drugs even more difficult?

The ADR reporting terminology of multiple specialties can differ

Why is ADR monitoring of ‘Herbal’ drugs even more difficult?

23/11/16 38

C. S., Su.- 1:124

Pharmacovigilance !

All drugs are dangerous some may also be useful

N Moore, BMJ,2005,330, 539-‐40

Wednesday, 23 November 16

39

What is Pharmacovigilance !

C. S., Su.- 1:124

All drugs are dangerous some may also be useful Moore, BMJ,2005,330, 539-‐40

"No drug which is pharmacologically effec7ve is en7rely without hazard. The hazard may be insignificant or may be acceptable in rela7on to the drug's therapeu7c ac7on. Furthermore, not all hazards can be known before a drug is marketed... “A report by EU experts”

Wednesday, 23 November 16 40

No medicinal product is en7rely or absolutely safe for all people, in all places, at all 7mes. We must always live with some measure of uncertainty.

23/11/16

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ItisanUPHILLtasktomonitordrugsofISM - Pharmacovigilance · Herbal drugs have been used in India for more than 4000 years