Bush Medicine 22/05/14 6:42 PM

Objectives

1. Gain an appreciation for indigenous people and their culture

2. Describe indigenous health with reference to

a. Health beliefs

b. Health before colonization

3. Describe he purpose, preparation and administration methods of bush

medicines

4. Identify some plants used in bush medicines and describe their use

Who are Indigenous Australians?

The capital I in indigenous refers to the actual aboriginal person, whereas

the things associated with aboriginals are named with a lower case ‘I’.

There are different traditional indigenous nations in Australia.

There are more aboriginals than Torres Straight Islanders and most of

them inhabit western Sydney.

2.4% of Australians are aboriginal (approx. 600,000)

There are 38 registered pharmacists Indigenous pharmacists in Australia.

Barriers for pharmacists to Indigenous Australians

1. Language barriers

2. Cultural issues; traditionally, Indigenous Australians have very

segregated roles for men and women. It is almost impossible for a

female pharmacist to cater for a male aboriginal and vice versa.

Furthermore, there are trust issues that arise as aboriginals find it

easier to trust indigenous Australians; people native to their own

cultures.

3. Remoteness and Location: Weather affects medicines, hard for

pharmacists or patients to migrate to a suitable location

4. Health Beliefs (causation and effect)

Categories of illness

causation

Causes of Illness Examples of illness

Natural Emotions, diet, physical

assault and trauma

Weight loss, suicide,

diarrhea, injury

Environmental Winds, moon, climate Pain, epilepsy, colds

and headaches

Direct supernatural Breach of taboo e.g. sacred

site, relationship

Swellings, vomiting,

pneumonia

Indirect supernatural Sorcery e.g. Boning, singing Death, serious injury

Emergent/ Western Post colonization Alcohol related illness,

diabetes, measles

What was their health like before colonization?

Before colonization:

Health was at a much better state than before white Australians showed

up

Possibly better than white settlers

The main conditions suffered were:

Their were problems in physical injuries such as cuts, bruises, broken

bones

Joint and muscle pain

Headaches

Skin infections/itchy skin

“women’s” problems

Diet

Before colonization:

Bush foods

Full use of food in region

Variety, especially fertile areas

Wide variety of fruits, vegetables and animal meat

Diet balanced and healthy (sufficient vitamins, fats and proteins)

Healthy lifestyle (5-6 hour exercise per day)

Changes in diet now

Modern indigenous diet a function of

Loss of land

Disruption of traditional lifestyle

Introduced flour and sugar

Occasional meat or offal

Handed out to Indigenous station hands

Nutritionally much poorer

Increase in disease

Raised blood pressure/cholesterol

Diabetes

Ranges of treatments and what they are used for

Traditionally medicines have been used for

Skin conditions

Pain

Infection

Joint and muscle pain

Coughs and colds

Stomach problems

Childbirth

“women’s problems”

Where do they get the medicines from?

Plants

Animals

Steam baths

Clay pits

Activated Charcoal and mud (GI problems, absorb gas for

bloating, and poisons)

Massages

String amulets

Secret chants

How are the treatments given?

No measured doses

No specific times of treatment

Mostly applied externally, when you rub into the skin it isn’t effectively

taken into the blood stream

-Sometimes

Vapour or steam inhaled

Inserted into the nose

Made into a pillow

Made into an infusion and drunk

The medicines where

Crushed and inhaled

Heated

Infusion: soak a product in water for a certain amount of time, and strain

the pulp. E.g. tea

Decoction: Boiled in water and drink the whole liquid

Decoction is different than an infusion, the boiled liquid has high temp will

release the ingredients however may damage the activeness of the

ingredient.

Plants used in tradition bush medicines

Caustic Vine

Botanical name: Sarcostemma australe

Therapeutic use: antiseptic, caustic

Application: the milky sap from the crushed plant is dabbed onto skin

Regions: western Australia, Queensland, South Australia, central southern

and central northern NT

Headache Vine

Botanical name: Clematis glycinoides

Therapeutic use: analgesic

Application: aroma from the crushed leaves is inhaled

Regions: Eastern coast of Australia

Bunch spear grass

Botanical name: Heteropogon contortus

Therapeutic use: expectorant(cough medicine), mosquito repellant

Application: Leaves cut up and soaked or boiled in water, liquid drunk

Whole plant burnt

Regions: North Western WA, Queensland, Northern Territory

Post childbirth

Botanical name: Eremophila Iongfolia

Therapeutic use: After childbirth and to bring on lactation

Application:

Pit is dug, leaves placed over (not in) a small fire

Leaves placed over fire

Steam is given off

More myth than medicine

Some cures and treatments are ineffective

view with skepticism because

o disease will run its natural course (correlation does not

equal causation) and patient will recover anyway

o conditions today are more complex

Some treatments may be dangerous

o Not necessarily because of toxicity

o They may prevent or delay detection of the underlying

cause of the disease

o May interact with modern medicines

Drug Discovery and development 22/05/14 6:42 PM

Today

What is a drug

Where do the drugs come from

Plants as sources of drugs

The story of opium

What are drugs

Molecule/pharmaceutical agent that benefits humanity

Substance with narcotic of stimulant effects

Penicillin – a good drug?

Heroin – a bad drug?

Definition of a perfect drug

Have defined and wanted effect on the human body

No toxicity

No side effects

Easy to take; 100% bioavailability

Penicillin

One of the most effective anti-bacterial agents

Very safe

HOWEVER

Doesn’t kill all bacteria

Many strains become resistant wit the time

Many people are allergic to penicillin e.g. anaphylactic shock

Therefore, penicillin is not an ideal drug

Heroin

Best painkiller identified so far, marketed in 1898 for 5 years

Name origins “heroic”

Withdrawn due to the highly addictive properties

Reduces pain and produces euphoric effect

Therefore, heroin is not a “bad” drug. In terms of the analgesic effect is

Good but the euphoric and addictive effects are bad

Best definition

Drugs are compounds which interact with a biological system to produce a

biological response

Morphine – reacts with the body to bring pain relief

Snake venom – reacts with the body to cause death

LSD – reacts with the body to produce hallucinations

Coffee – reacts with the body to wake you up

How safe is a safe drug?

Every drug has the potential to become poison

Morphine

Small doses – pain killer

High doses – kills by suffocation

Therapeutic index: determine how safe a drug is

Therapeutic index

Indicate safety of a particular drug

Measure of drug’s beneficial effects at low dose vs. its harmful effects at

high dose

Therapeutic index = TD50/ED50

TD50 Toxic dose leading to toxic effect in 50% of cases studied

ED50 Effective dose leading to max therapeutic effect in 50% of cases

Studied

High therapeutic index – TD >> ED

Large safety window between beneficial and toxic doses

Summary

Drugs are compounds that interact with a biological system to produce a

biological response

No drug is totally safe

The dose level determines whether it will act as a medicine or a poison

Therapeutic index indicates the safety of a drug – the higher the value,

the safer the drug

Origin of drugs

Nature (plants, marine, microorganisms etc.)

Chemical space

Serendipity (good luck)

Plans as Drug sources

Definitions

Herbal remedies (phytomedicines)/ herbal medicines

Extracts of plant material that are used to prevent and treat

illness.

Pharmacologically active constituent/ pure active agents

Component of the herbs responsible for biological activity

Natural Product

Plant derived pure compounds

extraction

Crude plantcontaining drug

isolation

unrefined preparation containing active agents - galenical

identificati

on

Chemical synthesis of pure drug

modificatio

n

new drugs

Herbal Medicines

Herbal medicine Pharm. Active constituent

St. John’s wort

Hypericum perforatum

Hypericin, hyperforin

Chamomile

Matricaria recutita

Levomenol, chamazulene,

flavonoids (reduce anxiety)

Gingko leaves

Gingko biloba

Ginkolides A, B, C; gingektin

Most herbal medicines contain a variety of biologically active

constituents.

The Story of Opium

Opium – Papaver somniferum

The unripe seed capsules are cut and the latex (milky fluid) collected and

dried to produce raw opium

Development of drugs from opium

Raw opium further processed to produce a range of galenicals including:

Opium dry extract

Opium liquid extract (dissolved dry extract in alcohol)

Opium tincture (laudanum) (concentrated)

The purified active ingredients – morphine and codeine – obtained from

raw opium.

Treatment for hysterical women and to induce sleep (tincture)

Morphine

Main constituent: 4 – 21%

One of the most effective drugs known for the relief of pain

Morphine – the standard against which new analgesics are measured

Dosage forms include: oral solutions, sustained-release tablets,

suppositories and injectable preparations

Most morphine synthetically converted into codeine and other derivatives

Codeine

Concentrations 0.7 – 2.5%

Most codeine synthesized from morphine

Codeine produces less analgesia, sedation and respiratory depression

Codeine usually taken orally

Codeine proscribed for the relief of moderate pain, and suppression of

cough

Difference between morphine and codeine is a hydroxyl group

Semi-synthetic drug development

Semi-synthetic drug preparation

Why develop new drugs?

Mode of action

Side effects

Enhance targeting ( if a drug activates many targets, one may be

for side effects, so by enhancing particular targets may reduce

side effects)

Improve pharmacodynamics/kinetics

In the case of morphine

Retain analgesic activity

Decrease/lose addictive properties

Heroin

Both the –OH groups replaced with OCOCH3 (acetyl)

The acetyl groups make it much easier for the drug to pass through the

blood brain barrier, and affect the opioid receptors in the brain. Once

heroin enters the brain, the acetyl groups are removed and the drug

works like morphine. The only difference is that the effect is a lot faster.

It is called Diacetylmorphine – palliative care

Heroin is semi-synthetic and its manufacture is legally prohibited

More potent painkiller than morphine

Shows considerably stronger euphoric effect

At the same time, aspirin was being discovered however went through

more rigorous testing before released on the market

Heroin used as a substitute for morphine but turned out to be more

addictive

Other derivatives

OXYCODONE – agonist

Analgesic for treatment of moderate to severe pain

Good oral bioavailability

Still very addictive

NALOXONE – antagonist(block effects of agonist)

Reverses the effects of morphine and its derivatives

For the treatment of morphine overdose; immediately effective

Antitussives

Structural modifications result in the production of the antitussives (cough

suppressants)

Pholcodine and dextromethorphan

Synthetic drugs

Synthetic drugs (new) from opium

Identify important functional groups

Synthesis new compounds which may appear different

Selective activity may be produced

Analgesics, anti-diarrheal drugs, drugs for the treatment of addiction

Good analgesics include FENTANYL and DEXTRO-PROPOXYPHENE which

are derivatives of morphine.

Methadone (non-analgesic)

Methadone structurally different

Retains the appropriate shape and size for action at the same receptor

Used in the treatment of addiction as it prevents feelings of craving and

other symptoms of withdrawal.

Acts as a partial agonist

Antidiarrheal drugs

Poor absorption, first-pass metabolism and P-gp mediated efflux prevent

BBB permeability

Reduced

Euphoria

Analgesia

Respiratory depression

E.g. LOPERAMIDE

SUMMARY

Antitussives (cough suppressants)

Opioid agonists (reversing addiction)

poppy seeds opium

codeine

Morphine

analgesics

antitussives

anti-diarrheal drugs

opioid agonists

drugs for treatment of

addiction

PART 2

Ephedra Sinica (Ma Huang)

Small plant, with slender green stems

Dried young branchlets

Stimulant; increases body’s metabolic rate and therefore increases body

temperature

Chinese: antipyretic and antitussive

Russian: Joint pain

S. America: Venereal diseases

Ephedra alkaloids

Alkaloids 1.3 – 2%

Ephedrine (50-90%)

Pseudoephedrine (diastereoisomer of ephedrine)

Methyl ephedrine

Methyl pseudoephedrine

Norephedrine

Norpseudoephedrine

The established pharmacological action attributed to ephedrine and its

diastereomer pseudoephedrine.

Alkaloid: Nitrogen containing, naturally occurring compounds with cyclic

structure

Diastereomers: pair of isomers that have opposite configurations at one or

more chiral centers but are non-superimposable.

Main Ephedra alkaloids

Ephedrine Pseudoephedrine

CNS stimulant Constricts blood vessels

Decongestant Primarily decongestant

Appetite suppressant Side effects (increase heart rate and

blood pressure)

Serious side effects (increase heart

rate and blood pressure)

In many countries replaced by

phenylephrine

CNS stimulants

Ephedrine and pseudoephedrine is a precursor for the synthesis

of amphetamines

Removal of the –OH groups allows entry into the brain

Amphetamine displace stores of adrenaline from nerve cells

Indirectly stimulate CNS

Lipophilic

Reduced activity in receptors

o Heart

o Lungs

o Vasculature

Synthetic drugs of ephedrine origin

CLONIDINE

Antihypertensive agent

Centrally acting alpha adrenergic agonist (the chlorine groups make

uptake of the drug in the receptor more selective

Reduces heart stimulation and blood pressure

Increasingly used for the treatment of ADHD

ATENOLOL

Beta adrenergic receptor agonist (high blood pressure)

Antihypertensive agent

Minimizes cardiac stimulation

Reduces blood vessel constriction (vasodilation)

SALBUTAMOL

Short acting beta adrenergic receptor agonist

Salbutamol used in asthma to relieve breathlessness by opening airway

passageways

Reduces vasoconstriction and causes cardiac stimulation

Summary of Ephedra

Ephedra ephedra extracts

pseudoephedrine

Ephedrine

Drugs for treatment of hypertension

Drugs for treatment of

asthma

Designer drugs of abuse

opioiDrugs for treatment of

ADHD

Atropa Belladonna

Atropos - Greek for mythology

Used by the Greeks and Romans as a poison

Belladona – beautiful women

Either the roots or the leaves are used

Belladonna tincture BP: Alcoholic percolation

Belladonna dry extract BP: dried tincture

Datura stramonium

Used by Indians and central Americans for ceremonial purposes

Indians used to smoke the leaves to treat asthma

Extracts can be made from the leaves, flowering tops and seeds

Stramonium Dry extract

Stramonium liquid extract (ethanolic extract)

Stramonium tincture (45% ethanol)

Can cause delirium

Contains toxic chemicals

A. Belladonna and D. Stramonium

Yield: 1%

Agonist of the cholinergic system

Used as an anti-spasmodic in the gastrointestinal tract

Atropine – racemic

Dialates the pupil – used in ophthalmology for treatment of

glaucoma

Both are antagonists of the muscarinic acetylcholone receptors

(mAChRs)

Decreases motion of the stomach (prevention of motion sickness)

Drugs derived from Hyoscoyamine

IPRATROPIUM BROMIDE

(similar structure to Hyoscoyamine)

agonist of the cholinergic system (mAChRs)

prevents airway constriction – used to treat asthma

the charge prevents BBB permeability – no central side effects

Synthetic anticholinergic agents

new structure but the same activity

oxybutynin, solifenacin and tolterodine – agonists of the

cholinergic system

mainly used to control incontinence

similar agents are used in eye examinations and surgery

Hyoscoyamine derived drugs

Salicylates

Naturally occurring in various plants such as myrtle leaves,

willow bark, willow leaf, wintergreen, black birch

Extract of dried bark from the young branches Salix species

(>1.5% salicylate derivatives)

Used for the treatment of pain and reduce fever

Examples: Salicyl alcohol, Salicin, Methyl Salicylate

Synthetic Salicylates

The addition of the acetyl group

o Reduces salicylic acids toxicity

o Retains its analgesic activity

o Retains its anti-pyretic activity

Trademark of Bayer, most widely used drug

Anticoagulant at low doses (<50 mg)

Anti-inflammatory at high doses (>500 mg)

Acts via inhibiting cyclooxygenase (COX inhibitor)

Synthetic non-steroidal anti inflammatory drugs

Structurally dissimilar to salicylates

Atropa/ Datura extracts/tinctures

atropine

Hyoscyamine

drugs for treatment of

glaucoma

drugs for treatment of

asthma

drugs for treatment of incontinence

Drugs for treatmetn of

motion sickness

Retain anti-inflammatory and analgesic activity

Some retain anti pyretic activity

Examples include ibuprofen, paracetamol, indomethacin, piroxicam

Selective NSAIDs

CELECOXIB

First marked selective COX2 inhibitor

Osteoarthritis, rheumatoid arthritis

Structurally dissimilar to previous non steroidal anti inflammatory

drugs

Retains anti-inflammatory activity

Developed to reduce NSAIDs side effects

Increased risk of stroke and heart attack (Vioxx, Refecoxib)

withdrawn

Hypericum perforatum

St John’s Wort: Prozac from the plant kingdom

top selling herbal preparation in recent years

outselling fluoxetine (Prozac) by a factor of four in Germany

Myrtle leavesWillow BarkWillow Leaf

extracts/tinctures

salicaylalcoholmethylsalicylate

Salicilin

anti-pyretic drugs

analgesic drugs

anti-inflammatory drugs COX inhibitors

Treatment of mild to moderate depression

Hypericin and hyperforin are the main active constituents

Makes skin extremely sensitive to sunlight

Commercial extracts standardized to of 3-6% hyperforin and

0.3% Hypericin.

Hypericum perforatum

ACTIVE CONSTITUENTS

Naphtodoanthrones Hypericin and pseudohypericin

Prenylated phloroglucinol hyperforin

Flavonoids (quercetin, rutin), amino acids, phenylpropanes,

xantones, tannins etc.

MECHANISM OF ACTION

Monoaminooxidase (MAO) inhibition by Hypericin (“old” data)

Mechanism of action

“New” findings

reuptake inhibition of %-HT, DA, NA, GABA and glutamate by

Hypericum extracts

Hyperforin being the most important constituent

Monoamines transport inhibitor

Increased 5-HT turnover in the brain

Binds to GABA-A and B receptors causing inhibition of GABA

reuptake

5-HT: 5-hydroxytryptamine = serotonin

DA: Dopamine

NA: Noradrenaline

GABA: gamma aminobutyric acid

Neurotransmitter: molecule that mediates the signal transport between

brain cells.

Hypericum perforatum

Other activities

β-secretase inhibition activity (treatment of Alzheimer’s disease)

Antiretroviral and bactericidal activity (unknown mechanism)

Anti-inflammatory activity

Antitumoral activity of both hypericin & hyperforin

Antidepressant activity observed with st johns wort extracted but

not with isolated products

Summary of Hypericum

Potent anti-depressive effects

Some clinical trials state no improvement

Placebo-effect?

Not all herbal medicines provide a good lead structure for development of

new drugs, however they are still a very important part of healthcare.

Hypericum perforatu

mExtracts

Hypericin

Hyperforin

22/05/14 6:42 PM