PHARMACODYNAMICS AND PHARMACOKINETICS IN AYURVEDA

•      Pharmacodynamics—what drug does to the body??

•      Pharmacokinetics----what body does to drug??

That means…

•         Physiological & biochemical effects of drugs & their mechanism of action at macromolecular/a sub cellular/organ system level is PD.

•        Movements of the drug in & alteration of drug by the body includes ADME, binding/localisation/storage, biotransformation & excretion of the drug is PK.

DRAVYA (DRUGS)

 

PADARTHAVIJNANA     DRAVYAVIJNANA

(Physical properties)         (Pharmacological)

 

NAMARUPA                  KALPANA                  YOGA

                (Pharmacognosy)              (Pharmacy)       (Clinical pharmacology)

 

GUNA KARMA vij                  PRAYOGA vij

(Pharmacodynamics)             (Therapeutics)

 

GUNA                  KARMA

(Study of props)       (Study of effects)

The pharmacological , toxicological & clinical efficacy of a drug are attributed to 5 qualities of a drug broadly classified as rasa ,guna,veerya,vipaka & prabhava.the pharmacodynamic & kinetic actions of ayurvedic drugs  (single & compound ) are difficult to explain in terms of modern pharmacology. It is not the single chemical entity as in case allopathic drugs, acts as a receptor & elicits a response. Moreover the drug therapy is not generalized as ijn the case of allopathic drugs. The drug selectivity is according to doshas and to see the panchabhouthik compatibility of the drug & individual. Classification of drugs into mrudu, madyama & teekshna is an eye-opener to modern therapeutics on the rationale of selection of drugs for the treatment of various diseases.

Conceptualization

Ø  Concept of Panchamahabhuthas.

Ø  Concept of Dravya,Guna,Rasa,Veerya,Vipaka,Karma & Prabhava.

Ø  Concept of Vriddhi,Saamya & Kshaya.

Ø  Concept of Samanya,Vishesha,Samavaya.

Ø  Concept of Karana & Karya dravyas.

Ø  Concept of Dosha,Dhathu & Malas.

Ø  Concept of Shat kriya kalas.

Ø  Concept of Srothas.

Ø  Concept of Pramanas.

Charakaacharya defines

     rÉiÉç MÑüuÉïÎliÉ iÉiÉç MüqÉï |            (action of the drug)

•      rÉãlÉ MÑüuÉïÎliÉ iÉiÉç uÉÏrÉï |             (potency of the drug)

•      rÉ§É MÑüuÉïÎliÉ iÉiÉç AÍkÉMüUhÉqÉç |   (site of action)

•      rÉSÉ MÑüuÉïÎliÉ xÉ MüÉsÉ: |           (time for bioavailability)

•      rÉjÉÉ MÑüuÉïÎliÉ xÉ EmÉÉrÉ: |          (  mode of action)

•      rÉiÉç xÉÉkÉrÉÎliÉ iÉiÉç TüsÉqÉç |        (therapeutic effect)

Concept of Panchamahabhoothas

q  The PANCHAMAHABHOOTHA theory is important as Medicinal chemistry is for modern medicine.

q “BHOOTHA” is defined as the minutest matter which will prove its existence through certain charecteristic features or it is the factor which produces all the organic and inorganic materials. ( pÉÔ xɨÉrÉÉqÉç )

q  Vaisheshikas explained on the basis of Paramanu & trisrenu.

q  Sankhyas proved it on basis of Pancha tanmathras & mahabhuthas.

q  PMB’s related to elements H,O,N,P,S,C.etc

q  Panchatanmatras means the physical properties of matter while Panchabhuthas are indicators of chemical properties of atom along with physical properties. Therefore PTM’s have horizontal expansion in periodic table while PMB’s have linear/ vertical expansion like groups in periodic table.

q  Sthavara and jangama act as good medicines.

Three kinds of activities

v  Bhutatma –activity in the micro matter.

v  Jeevatma– activity in organic matter.

v  Paramatma—activity in the galaxy.(imperceivable.)

Ayurveda describes the dravya on the basis of bhootha predominance in it. The QSAR (quantity structure activity relationship) of a drug is quite similar to pharmacological action of dravya resulting from its panchabhouthik configuration.

Concept of Samanya,Vishesha,Samavaya.

• Similar properties enhance qualities. (ekavrutthi and ubhaya vrutthi)

• Opposite properties reduce or the most powerful will overcome the others.

• Factors involved are samyoga,samskara desha ,kaala.
• Dravya samanya,guna samanya,karma samanya.

• Athyantha samanya,madhya samanya,eka desha samanya.

• Dravya vishesha,guna vishesha,karma vishesha.

•      pÉÔrÉxÉÉ urÉmÉSãvÉ lrÉÉrÉ | (with some exceptions)

Basics of Ayurveda

Pharmacology

               The materia medica of the Ayurveda, composed of the five basic elements, has been categorized according to the derivatives o f these elements. They include: taste (rasa), potency (virya), taste of the digestion product (vipaka), properties (guna), specific properties (prabhava) and action (karman).

       Taste (rasa) is six fold: sweet (madhura), sour (amla), salty (lavana), sharp (tikta), bitter (katu) and astringent (kasaya). Each taste is composed of two of the five elements. The condition of the food substances after digestion is also expressed in terms of taste (vipaka), however it can only be sweet, sour or sharp.

        The properties (guna), are grouped in 10 pairs, each one complementary to the other: heavy and light, cold and hot, fat and dry, slow and sharp, stable and labile, soft and hard, clear and slimy, smooth and raw, fine and massive and viscous and liquid.

        The potency (virya) of a drug is defined as its capability to express its property. Sometimes, potency is grouped in the same way as the property, but for practical reasons, it is usually expressed in terms of hot (ushna) and cold (shita).

        The specific property (prabhava) distinguishes two drugs that have the same taste, taste after digestion and potency. This might be due to the composition of the drug or the location in the body where the drug acts.

        Finally the action (karma) of a drug on the body is expressed in terms of the three doshas. A drug can increase or decrease the vata dosha, the pitta dosha and the kapha dosha.

       The drugs used in Ayurveda are made by several processes from vegetable and mineral raw materials. Mostly plant alkaloids are the active ingredients.

 

Concept of DRAVYA

• Seat for rasa guna virya and vipaka.
• Medium of existence.
• Vyvasthitatwa (stability)
• Nityatwa (eternity)
• Swajaati avasthana (geno-specificity)
• Panchendriya grahyatva(perception)
• Ashrayatva (host for properties )
• Arambha samarthya(initition of action.)
• Sastra pramanya (classical references)
• Kramaapekshitatva(degree of maturity)
• Ekadesha sadyatva (utility of part used)
• Taratama yoganupalabdhi( avail for grading)
• Vikalpa samarthya (possibility of pharmaceutics)
• Pratighatha samarthya (malleability )

Dravyas when classified

•      Antah chethana dravyas.

•      Bahirantah chethana dravyas.

•      Achethana rasa dravyas.

•      Jangama                                           Mridu

•      Oudhbidha                                        Madyama

•      Parthiva                                           Teekshna

•      Dosha shamana (shamana)

•      Dhathu pradhushana (kopana)

•      Swasthavrittha. (swastha)

On basis of major bhutas dravyas are….

•         Akashiya-mridu,laghu,sukshma,vyavayi,slakshna,visada,viviktha,avyaktha rasa.

•         Vayavya-laghu,sheetha,ruksha,khara,visada,sukshma,kashaya rasa.

•         Agneya-ushna,teekshna,sukshma,ruksha,khara,visada,katu rasa with slight amla & lavana.

•         Apya-drava,snigdha,sheetha,manda,mridu,sheetha,sandra,guru,picchila,madhura and kashyamla rasa.

•         Parthiva-Guru,khara,katina,manda,sthira,visada,sandra,sthula,madhura kasaya rasa.

Concept of Gunas

•      MüÉUhÉqÉç aÉÑhÉ mÉÔuÉïMü: ,MüÉrÉï aÉÑhÉÉã SìÓvrÉiÉã |

o   Denote the common properties of dhatus and dravyas.

o   Gurvaadi gunas----41

o   Paradi gunas (chikithsopayogi gunas) -------10

o   Sushrutha adds vyavayi and vikasi gunas.

o   Badantha nagarjuna adds sugandha ,durgandha,aasukari,suchi,vimala,visra,prasanna.

o   Paradi gunas were also called vishishta samarthya sampanna gunas.

Paradi gunas

Paratwa

•         Priority and superiority

•         Pradhaanatwam

•         Sannikrushtathwam

•         Specificity

•         Drug of choice.

Eg:Agryoushadhas

Aparatwa

•         Posteriority

•         Inferior quality

•         Ahitha padarthas

•         Apradhana

Viprakrushta

•         To know about the harmful effect.

•         Eg:ahitha dravyas.

•         Samyoga

•         Integration

•         Combination

•         Nitya or anitya

•         Combn of dravya & guna is nitya.

•         Combn of dravya &dravya is always anitya.

•         SìurÉÉhÉÉÇxÉÇWûiÉÏpÉÉuÉ:

Vibhaga

•         Disintegration

•         Division of combination

•         Vibhakthi

•         Viyoga

•         Bhagashograha

•         Not only samyogaabhava.

•      mÉëÉÎmiÉmÉÔÌuÉïMüÉ AmÉëÉÎmiÉ: |

Prithaktwa

•         Separateness

•         Severality

•         Diffrentiation

•         Asamyoga lakshana

Parimaana

•         Measurement

•         Maana

•         Dairghya

•         Gurutwa etc.

•         Vailakshanya roopa

•         Anekata roopa

Samskaara

•         Changing the original quality.

•         Enhancement

•         Gunaantharaadhaana

•         Vega

•         Sthitisthapaka

•         Bhaavana

Abhyasa

•         Vriddhi & hrasa hetu.

•         Practice

•         Habituate.

•         Samaana guna –vriddhi

•      xÉiÉiÉ Ì¢ürÉÉvÉÏsÉlÉ|

•         Paratwa        Drug of choice

                                    

•         Aparatwa     Contra-indication

•         Yukthi    Careful assessment

•         Sankhya   How many times  ?

•         Samyoga   Possible combination

•         Vibhaga   What should be avoided  ?

•         Pruthaktva :Selection of specific thing.

•         Parimaana   Dose.

•         Samskaara  Modification

•         Abhyasa: Administration.

Pharmaco-activities of guna

•         Effect can be assessed with the help of inference.

•         Guna cannot perform any action of its own.

•         Human body & drug constituents are all having similar composition of PMB’s.

•         Vriddhii kshaya samya depend on these factors.

Role of physical properties (Vaisheshika gunas)

•         Colour: responsible for variation in response in trials observed with placebos.

•         Taste: local and systemic effect.

•         Smell: useful in unconscious states.

Other gunas

Vyavayi guna

Vikaasi guna

Aashukaari

Sugandha

Durgandha.

Concept of rasas

•         7 rasas -----shadrasas+kshara says Nimi.

•         8 rasas------7 above+avyaktha says Dhamargava.

•         Rasas are different in different dravyas.

•         Tara tama bhavas

•         According to panchamahabhutha configuration.

•         Vital forces of the body.

                  As mentioned earlier also every thing in this universe are composed of panch mahabhoot hence rasa are also no exception to it. 

             Rasa plays a very important role in body therapeutically and also in diagnosing a certain disease. It has a great significance in determining the vata, pitta and kapha’s involvement in the actual cause of a disease. As it has been know to you that any kind of vitiation of dosha causes disease in body. Hence excess of in take of certain rasa or deficiency of rasa causes imbalance in are tridosha.

Rasopalabdhi :

ü  From the moment of exposure of a substance to organ of taste.

ü  Tastes perceived through pramanas

ü  Action of bodhaka shleshma.(first chemical change.

Limitations

o        Purely subjective

o        Abnormality or disease

o        Insolubility

o        ethical/psychological

o        fatal

Transformation of rasas

• Sthana
• Samyoga
• Agni
• Aathapa
• Bhavana
• Desha
• Kaala
• Parinaama
• Upasargaja
• Vikriya.

Rasas are divided as

• Dosha prakopa
• Dosha shaamaka
• Vidaahi rasas
• Avidahi rasas

Also rasas are eka,dwi,tri,chathuh,pancha & shadrasa.

Characters of rasas

1. Madhura rasa----tempting and attracts
2. Amla----------------produces secretions
3. Lavana-------------scrapes doshas.
4. Katu-----------------spreads,secretions.
5. Tiktha---------------helps in taste perception.
6. Kashaya------------causes discomfort.

Pharmaco-actions of rasas

Madhura-                                      aaswada,ahlada,aksha                                                                                                             prasadaka,tarpana,jeevana,kaphakara.

Amla-                                             kshaalana,harshana,mukasraava

                                                        Kantavidaaha,jihwadwejana.

Lavana-                                         syandana,kapola gala daha,kapha                                                                               praseka,vishyandana,mardava janana.

Katu-                                              jihwagraudwejana,chimachimaayana,

                                                        akshinaasasrava,udwegajanana,shirograha.

Tiktha-                                           vishada,mukhavaishadya,bhakthaaruchi,

                                                        kanta vishoda,rasanapratihanti.

Kashaya-                                        jadatwa,kanta & srotho bandha,jihwa                             sthambhana,vakra shoshana,hridaya                                             karshana.

                                                                                                                                   

Effects of rasas

Madhura                                                                 

•         Vata pittashamaka

•         Dhatu ojovardhaka,

•         Jeevaniya,

•         Ayushya,

•         Indriya prasadana,

•         Kantya,

•         Sandhaniya,

•         Varnya etc

Amla

•         Pitta kapha vardhaka

•         Vatanulomana

•         Deepana

•         Pachana

•         Koshta vidahi

•         Vyavayi

•         Hridya

Lavana

v  Vata hara

v  Pachana

v  Kledana

v  Deepana

v  Chedana

v  Bhedana         

v  Vikasi

v  Samshodhana

v  Dhathu shaithilyakara

Katu

v  Kapha hara

v  Mukha shodyakara

v  Vrana ropana

v  Kandu hara

v  Srotho vivarana

v  Krimi hara.

v  Agni vardhaka

Tiktha

v  Pitta kapha hara

v  Vishahara

v  Krimi hara

v  Reduces Daha

v  Lekhana

v  Dhatu soshana

v  Kushtaghna

Kashaya

v  Pitta vata hara

v  Samsamana

v  Sangrahi

v  Sandhana kara

v  Lekhana

v  Twachya

v  Vishtambhi

v  Ropana

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Conclusion:One should not advise about the drug based on its rasa b’coz even when rasa of drugs is similar actions may differ.

Vipaka

                             When we eat or drink a substance it comes in the contact with jathar Agni (digestive fire). If the jatharagni is in its normal state it is able to digest (pachana) the substance eaten. During this digestion the food undergoes many bio transformational changes. In this process of paak (physiological condition of digestion) due to different degrees of digestion, the transformation of rasa takes place. This changing of rasa of the substance into a certain similar or dissimilar rasa is called vipaka. After completion of digestion, the substance or the food ingested would produce certain action by which we can know the process under which the substance has undergone. Hence vipaka is judged by anumana (inference made after observation). The effects of vipaka commences after the full digestion is completed. These vipaka are of there types.

Madhura vipaka

Aamla vipaka

Katu vipaka 

•         Visheshasya paka

•         Endproduct of any dravya.

•         Final transformation state

•         Parinaama lakshana

•         Yakrith is the site .(dr.dwarakanath)

•         Respective bhuthagni helps in metabolism

•         Karma nishta/karma parisamapthi

•         Acts through distribution.

Assessing vipaka

•         Known only after complete digestion

•         End phase of biotransformation

•         Cannot be perceived directly

•         Absence of pratyaksha

•         Cannot be assessed only on basis of rasa & virya.

•         Rasa effects manas whereas vipaka effects body.

•         Responsible for various other pharmacological actions.

Superiority

•         Nimittatwa.

•         Dhathupadehath.

•         Vipakakshepatwa.

•         Sastra pramanya.

Concept Of virya

•         Unmetabolized active principle of a drug.

•         Powerful/ potency.

•         Characterized by drug action.

•         Virya is shakthi.

•         Sahaja & kritrima

•         Karma nishtaya.

•         Ushna virya(kinetic energy)

•         Sheetha veerya(potential energy)

Concept of prabhava

•         Peculiar action of dravya

•         Non specific effects of a drug.

•         Guna vishesha.

•         Vichitra pratyarabdha.

•         Achintya virya,daiva prathighatha.

•         Vikruthi vishama samavetha.

•         Avadharaniya

•         Adbhutha karma

•         Aagama.

Concept of Karma

•         Final target achieved by drug.

•         Uddesya or sadhya.

•         Factors responsible for the association and dissociation.

•         Karma is the cause and karya is effect.

•         Dravya karma is due to dravya,karma,and in combination.

•         Initial consequence of a drug-cell interaction.( action of the drug)

•         Remaining are the effects.

Samprapti & mode of action

•         Rasa and vipaka---koshta---chaya prakopa

•         Guna--------------rasa samvahana—prasara

•         Virya & prabhava—dushyas & srothas-----sthana samshraya.

•         Oushadha dravya is concerned with bhuthagni paka.

•         Dosha pratyanika or vyadhi pratyanika.

Drug absorption

•         Amashaya is the place for kapha & snigdha sheetha & guru are absorbed.

•         Grahani is the place for pitta & snigdha ushna &laghu are absorbed here.

•         Pakwashaya is the site of vata & thus ruksha sheetha and laghu are absorbed here.

•         Adhikarana is the site of action.

•         Based on site of action /receptors different actions like twachya,pleehagna,varnya,medhya are seen.

Karma is classified as..

•         Effect on srothas

•         Effect on doshas

•         Effect on dhathus

•         Effect on malas

•         Effect on upadhathus.

•         Effect on ashayas.

•         Effect on vyadhi / lakshana.

•         Effect on agni.

Mode of drug action can beanalyzed by Pratyaksha,Anumaana,Aptopadesha+ yukthi

Some Of Pharmacological Actions.

•          Deepana

•         Pachana

•         Samshodhana

•         Samshamana

•         Anulomana

•         Bhedhana

•         Rechana

•         Chedana

•         Grahi

•         Sthambhana

•         Madakari

•         Pramaathi

•         Vyavayi

•         Vikasi

•         Abhishyandi

•         Asukaari

•         Yogavahi

•         Sukshma

•         Pranahara

•         Vidahi

•         Jeevaniya etc.

Some Of Pharmaco-Properties.

•         Avasadana

•         Upaga

•         Upachayakrit

•         Uttejaka

•         Tarpana

•         Dushana

•         Vivarana

•         Nivarana

•         kopana

•         Pravarthana

•         Prabhodhana

•         Nigrahana

•         Baddha

•         Mardana krit

•         Vardhana

•         Soshana

•         Prashamana

•         Sangrahi  etc

Summarizing.

Pharmacodynamics

•         Structure related activity i.e panchabhouthik configuration is the base.

•         The ingredients of a dravya are proved with individual activities.

Pharmacokinetics

•         Rasa vipaka virya supersede one another in order.

•         Vipaka is always a process and not the active ingredient.

•         Synergistic actions & direct action differ.

Conclusion 

•         Rasa, guna & virya karmas can be considered under PD whereas vipaka under PK.

•         There is a concept of rasena karma,vipakena karma,gunena karma,viryena karma,prabhavena karma.

•         Ayurveda advocates the concept of pharmacotherapeutics and clinical pharmacology but not pharmacology & therapeutics separately.

“A good physician should be a good                        pharmacologist too”