orthomolecular compounds and medicinal mushrooms€¦ · adverse effects • dangerous or life...

Nutritional Pharmacology

©CNM 2011

Learning outcomes

• Explain factors affecting variability of responses to drugs, including pharmacokinetic and pharmacodynamics.

• Classify the major classes of pharmaceutical medications, their general actions, possible side effects, and contraindications.

• Analyse information and research from standard reference sources of common pharmaceutical medications.

• Explain possible drug-nutrient (food and nutraceuticals) and drug-herb interactions for a specified list of common drugs.

Basics of Pharmacology

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MHRA Definition of a Drug

• Any substance or combination of substances presented as having properties for treating or preventing disease in human beings

• Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis”

• Supplements fall outside this definition provided they don’t make medicinal claims!

• Since the EU Herbal Medicine Directive (THMPD) 2004/24/EC, many herbal products are being transferred from food supplement status to medicine status. This means companies that make them are have to provide lots of evidence on their manufacturing processes and ingredients, efficacy or traditional use in order to register their products with the MHRA. Herbal products not properly registered will be illegal.

• Read more (cut and paste into your browser): http://www.mhra.gov.uk/Howweregulate/Medicines/Herbalmedicinesregulation/

MHRA (2008) Borderline products: What is a medicine? Available at:

http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Borderlineproducts/index.htm (Accessed: 21 August 2009)

http://www.mhra.gov.uk/Howweregulate/Medicines/Herbalmedicinesregulation/

http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Borderlineproducts/index.htm

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The Medicines Act 1968 (UK)

Medicines are divided into 3 categories:

• General Sale List (GSL) medication

– Able to be sold anywhere

– Limits on pack size and strength that can be sold

• Pharmacy Only Medication (PO)

– Only able to be sold in pharmacy

– Sale must be supervised by a pharmacist who will check for any medical conditions/ other medicines to make sure it is safe to take the drug

• Prescription Only Medication (POM)

– Only able to be sold on prescription

– There are some exceptions to this law e.g. Midwives may be able to obtain POM

NHS (2007) What is the law regarding the sale of medicines? Available at:

http://www.nhs.uk/chq/Pages/1325.aspx?CategoryID=73&SubCategoryID=101 (Accessed: 21 August 2009)

http://www.nhs.uk/chq/Pages/1325.aspx?CategoryID=73&SubCategoryID=101

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Controlled Drugs

Some prescription only medicines are further classified as Controlled drugs, such as morphine, pethidine and methadone.

There are controls on:

• Who may prescribe these medicines,

• How the prescription is written,

• How much may be prescribed, and

• How the medicines are stored in the pharmacy.

• Also, the pharmacist must make a record of the prescription in the controlled drugs register.

NHS (2007) What is the law regarding the sale of medicines? Available at:

http://www.nhs.uk/chq/Pages/1325.aspx?CategoryID=73&SubCategoryID=101 (Accessed: 21 August 2009)

http://www.nhs.uk/chq/Pages/1325.aspx?CategoryID=73&SubCategoryID=101

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Misuse of Drugs Act 1971

• Prohibits certain activities in relation to controlled drugs e.g. their manufacture, supply and possession. gives a list of substances, including some medicines, that it is illegal to possess, supply or manufacture without proper authority such as a prescription written by a registered medical practitioner that was dispensed by a registered pharmacist.

• It divides substances into three legal categories known as class A, B and C

• Class A: e.g. Morphine • Class B: e.g. Codeine, Dexamphetamine • Class C: e.g. Anabolic steroids, Diazepam

British Medical Association (2007) Controlled Drugs and Drug Dependence. In: British National Formulary 54.

London: BMJ publishing group and RPS publishing. p7

Drug Naming

The naming of drugs follows a standard nomenclature.

All drugs have three names.

a) Proprietary, brand or trade name

b) Generic name: Simple official name for a specific drug

c) Chemical name

Example:

• Trade name:

– Panadol

– Calpol

– Disprol

• Generic name:

– Paracetamol

– Acetaminophen (USA)

• Chemical name:

– Acetyl-para-aminophenol

British Medical Association (2007) How to Use the BNF. In: British National Formulary 54. London: BMJ

publishing group and RPS publishing. p vi

http://images.google.com/imgres?imgurl=http://upload.wikimedia.org/wikipedia/commons/thumb/5/5e/Paracetamol-skeletal.png/180px-Paracetamol-skeletal.png&imgrefurl=http://en.wikipedia.org/wiki/Portal:Chemistry/Featured_article/20&h=98&w=180&sz=6&hl=en&start=3&um=1&tbnid=HrloopijB6boHM:&tbnh=55&tbnw=101&prev=/images%3Fq%3Dparacetamol%2Bstructure%26um%3D1%26hl%3Den%26rls%3Dcom.microsoft:en-us:IE-Address

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BNF: British National Formulary

• Necessary for every therapist

• Used throughout NHS

• Lists drug indications, cautions,

contra-indications, side-effects and dosages

• Drugs are listed under their various classifications: Lipid regulating, Anxiolytics etc

• Both generic and brand names are given

• Often obtainable second hand (from Pharmacy, Amazon etc)

• Updated biannually

• Specific BNF for Children

Indications: The

approved uses or

diseases for which the

drug has been proved

effective

Contra-indications:

Circumstances under

which the drug should

usually not be taken.

Often listed at the start of

the chapter on each type

of drug

Side-Effects: Additional

effect on the body even at

the recommended dose

Generic Name

Classification: Drugs are

classified by their primary

pharmacological action

and effect

Dose

Brand Names British Medical Association (2007)Lipid

regulating drugs. In: British National Formulary

54. London: BMJ publishing group and RPS

publishing. p 140

©CNM 2011

Practice!

• Please use your BNF to look up the indications of the following drugs:

• Alendronate

• Captopril

• Lorazepam

• Furosemide

• Isosorbide

• Benzotropine – can you find it?

• Nexium

• Montelukast

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Adverse Effects

• Dangerous or life threatening additional effects. • Drug should be discontinued or dosage reduced

• Adverse effects can be classified as: • Predictable:

– Exaggerated physiological effect – Side Effect – Toxicity – Cumulative toxicity – Iatrogenic – Induced by physician e.g. wrongly prescribed

medication or dose

British Medical Association (2007) Adverse reactions to drugs. In: British National Formulary 54. London: BMJ publishing group and

RPS publishing. p 11

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Adverse Effects

• Unpredictable:

– Allergy – Hypersensitivity reaction to a particular drug – Idiosyncratic reaction – Specific to the sufferer Commonly,

this is caused by a disturbance in enzyme function, congenital or acquired, so that the triggering substance cannot be processed properly

Example: Patients with a genetic deficiency of the glucose-

6-phosphate dehydrogenase enzyme cannot take oxidant drugs such as aspirin because this would result in haemolysis

Dawson JS (2002) Introduction to pharmacology. In: Pharmacology. London. Elsevier . pp.18

Examples

Teratogenic effects

of the anti-emetic

thalidomide were

not discovered until

years later

Reye’s syndrome

Potentially fatal disease

associated with brain and liver

damage. Associated with aspirin

consumption by children with

viral illnesses.

Symptoms are similar to viral

illnesses and are often missed

Current advice in the United

Kingdom by the Committee on

Safety of Medicines is that

aspirin should not be given to

those under the age of 16 years

Alternative: Paracetamol NOT

ibuprofen

Penicillin

hypersensitivity

Mega doses of vitamin A.

Husky’s in the arctic have died

from eating polar bear liver

British Medical Association (2007) Non-opioid

analgesics. In: British National Formulary 54.

London: BMJ publishing group and RPS

publishing. p 224

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Pharmacology 2 areas of pharmacology of importance:

• PHARMACOKINETICS – How drugs are absorbed and moved about the body

• PHARMACODYNAMICS – How drugs exert their effects

Absorption Distribution Metabolism Excretion

Via blood,

lymph

Breakdown by

liver using

enzymes

Diffuses from site

of application

Via kidneys, GIT,

skin, lungs

Pharmacokinetics

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Administration Methods

• Considerations: – Cheap and convenient – Easy to administer – Good patient compliance – Speed of onset – Bioavailability – Safe – Bypasses the liver – Food interactions – Commercial availability – Volume needed to dose – Availability of slow release (if needed)

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Enteral Administration

• Oral – E.g. Tablets, capsules, powers, liquids, chewing gums etc

– Absorbed from stomach and intestines

– Bioavailability depends on the release of active form, the dosage form, destruction in the gut, absorption and loss of active via the first pass effect

• Sublinguals – E.g. Nitroglycerin, homeopathy, B12

– Bypass first pass effect

• Enemas/Suppositries – Bypass first pass effect

– Useful if vomiting prevents oral administration

Dale MM & Haylett DG (2004) Absorption and distribution of drugs. In: Pharmacology Condensed. Edinburgh. Churchill Livingstone. pp.21

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Parenteral Adminstration

These routes are useful for

– Rapid effects

– Drugs that are poorly absorbed from the gut

– Irritants

– Localised action

Dosage forms include

• Injections – Intravenous,Intra-arterial Intramuscular, Subcutaneous

• Inhalation – e.g. Bronchodilators used for asthma

• Topical – Application of drug to the skin. Requires drug to lipid

soluble E.g. Creams, gels, ointment, patches etc


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Injections

Sub cutaneous • Good for slower release • Examples: Adrenaline (vasoconstriction), Contraceptive rod, Depot (oil

based) Intra muscular • Usually into gluteus maximum – Large muscle can inject up to a few

millilitres! • Exercise increses absorptions • Depots Intravenous • Absorption not required, very fast. • Can be stopped if there is an adverse reaction. Intraarterial • Can direct treatment at a particular organ. E.g. Chemo, local anasthetic


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Drug Absorption

• Very dependent on drug properties: – Large vs. small molecules – Lipid soluble vs. water soluble – Acid vs. alkaline – Chemically reactive vs. chemically inert – Formulation – Quick dissolving versus slow release oral

preparations. The use of oil based slow releasing depot formulations for injections

• For oral drug gastrointestinal motility will also affect absorption

• Drugs can also interact with other substances in the gut such as foods


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Drug Distribution

• Most drugs entering the body do not spread evenly and rapidly through the whole body.

• Drug distribution depends on the individual properties of the drug

• Drugs may or may not: – Bind to plasma proteins in the blood – This reduces the active

concentration of the drug

– Bind to other tissues e.g. Tetracycline binds to calcium in bones and teeth

– Accumulate in lipids – e.g. General anaesthetics

– Cross the blood brain barrier – Needs to be a rapidly absorbed lipid soluble drug

– Cross the placenta


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Barriers to Distribution

Blood brain barrier • Protective mechanism that stops harmful substances from reaching the

brain. • The endothelium cells of the capillaries in the brain are much closer

together than in normal tissue • Astrocytes in the CNS help to maintain tight junctions that create a barrier

between the capillaries and the brain tissue • This means only very lipophilic substances or those which are actively

transported can enter the CNS • Note: Placenta is much less effective than the BBB so many drugs cannot

be used in pregnancy

• Certain areas of the body inhibit movement of drugs e.g. placenta and blood-

brain barrier

• This can make treating some disease very difficult. E.g. The BBB can block HIV antiretroviral drugs, leaving a virus reservoir in the CNS

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Drug Metabolism

• The effect of a drug depends not only on it’s action, but how it is handled by the body

• The liver is the main site of drug metabolism. Other sites of metabolism include the small intestine, kidneys and lungs

• If drugs are administered orally they are absorbed into the portal circulation and go directly to the liver

• This means drug concentration is often drastically reduced before it reaches general circulation– This is known as the first pass effect

• This reduces the bioavailability

• Injections, inhaled, topical and sublingual drugs bypass the first pass effect, however all circulating drugs will be metabolised by the liver eventually

Dale MM & Haylett DG (2004) Drug metabolism and excretion. In: Pharmacology Condensed. Edinburgh. Churchill Livingstone. pp.22

©CNM 2011

First Pass Effect

• Some drugs are metabolised so completely by the liver they cannot be dosed orally.

• E.g. The angina drug glyceryl trinitrate is 96% destroyed by the liver • Termed as having a high hepatic first

pass effect. • Dosed sublingually instead

Galbraith A et al. (2007) Fundamentals of pharmacology: an applied approach for nursing and health. Harlow. Pearson. p112

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Liver Detox Pathways

• Metabolism in the liver involves 2 processes

• Phase I - The drug is made more lipophobic to reduce the chance of reabsorption by the kidneys

• Phase II - It is conjugated to reduce it’s effects and aid excretion

Liska D et al. (2004) Environment and toxicity. In:Clinical Nutrition: A Functional

Approach. Washington. Institute of functional medicine. pp.254


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Drug Metabolism

• Metabolism can have a variety of different effects on a drug

• Some drug metabolites share the action of the parent compound e.g. diazepam

• Some drug metabolites are toxic e.g. paracetamol

• Some drugs are pro-drugs and only become activated when they are metabolised e.g. enalapril

• Some drugs can interfere with certain liver enzymes interfering with their own metabolism and that of other drugs. This is an important consideration for drug interactions

• Smokers can also show increased metabolism of certain drugs due to induction of cytochrome P448 by a component of tobacco smoke



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P450 Enzyme System

• The activity of the P450 enzyme system can be markedly increased by exposure to certain drugs or dietary factors

• This can reduce the effect of the drug and is an important consideration in durg interactions

• Other drugs may inhibit the P450 enzyme system

• This leads to a potentiation of drug effects that can lead to toxicity

Cytochrome P450 3A4


http://opm.phar.umich.edu/images/proteins/1tqn.gif

©CNM 2011

Renal Excretion

The kidneys are the main site of excretion, though the liver and lungs may also play a role.

Renal excretion involves the following processes

• Glomerular filtration – Small drug molecules are filtered out through the glomerulus

• Active tubular secretion – Larger drugs and metabolistes are actively transported into the kidney tubules. Drugs may have to compete for transport proteins – this can change their excretion rate

• Drugs that are lipid soluble or unionised can be reabsorbed.

• This changes the excretion rate of the drug

• Urinary pH can affect whether a drug is ionised or not and therefore its excretion rate


©CNM 2011

Hepatic Excretion

• Bile is the major excretion route for some drugs e.g. Cromoglycate and rather more drug metabolites e.g. morphine glucuronide

• Drug excreted in the bile may be reabsorbed from the intestines via the enterohepatic circulation

• This can lead to longer excretion times

• Reabsorption rates may be affected by gut flora and competition with other drugs/substances


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Dosage

• Amount of drug required to produce the desired effect.

• Usually expressed by a weight or measure and time factor

• For example: 2 BD, 3 TDS, 1 Nocte

• Needs to be based on patient parameters:

– Weight

– Age

– Sex

– Nature of the drug

– Drug’s half-life

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Half Life

• The time it takes for a drug’s concentration in the body to fall by half

• Very dependant on rate of elimination

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Dosage Regimens

• Drugs are administered in a certain dose pattern to ensure that a therapeutic concentration is maintained for the time period required to address the problem

• Dosage frequency based on:

– Absorption

– Transport

– Half life

• Can reduce frequency via:

– With/without food

– Slow-release formulae (e.g. Vit C)

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Dosing Regimens

• Toxic dosing – Drug given too frequently or at too high dose

• Sub-optimal dosing – Drug given too infrequently or in too low doses

• Therapeutic dosing – Dosing regime maintains drug concentration within the therapeutic range

Golan DE & Kashjian AH (2008) Principles of pharmacology: the

pathophysiologic basis of drug therapy. Balmitmore. Lippincott Williams

& Wilkins pp.46

©CNM 2011

Loading Dose

• A larger dose or an injection may be given initially, followed by smaller ‘maintenance doses’

• This allows the drug to rapidly reach therapeutic levels in the body • Can only be done when there are no adverse effects from taking a larger

dose of the drug! • Also a common practice in sport with creatine and with some herbal

medicines

Normal Dosing Loading Dose

Golan DE & Kashjian AH (2008) Principles of pharmacology: the pathophysiologic basis of drug therapy. Balmitmore. Lippincott

Williams & Wilkins pp.46

©CNM 2011

Compliance

• To order for some drugs to be effective they must be taken at regular intervals for a certain period of time

• Patient compliance is essential to maintain effective concentrations of the drug

• If dosing regimens are not followed properly it can lead to drug resistance or toxicity

• Practical dosage forms and regimens are vital for improving patient compliance

• Dosing with meals is often easier to remember but consider that 3 times a day requires the person to remember to take their medication to work

Dosage

Regime

Compliance

4 times/day 51%

3 times/day 65%

2 times/day 69%

Once daily 79%


Claxton AJ, Cramer J, Pierce C (2001) A systematic

review of the associations between dose regimens

and medication compliance. Clinical Therapy 23(8)

pp.1296-310

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Pharmacodynamics

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Mode of Drug Action

• In many cases the detail of the mode of action is not known

• Hence a lot of side effects (short or long term) are not known

3 common types of action are:

• Specific – Chemical structure of the drug is of paramount importance. E.g. Lock and key hypothesis to explain drugs action on a particular receptors or enzymes.

• General - The chemical structure of the drug is not as important as its physical and chemical properties. E.g. General anaesthetics are fat-soluble and accumulate in the membranes of neurons, rendering the individual unconscious. Antacids neutralise stomach acid

• Placebo - The tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work

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Receptors as Drug Targets

• Receptors are protein in or on a cell that can respond to hormones, neurotransmitters, inflammatory mediator, immune mediators

• Some receptors are very specific, others more general

• Many drugs make use of these endogenous receptors

• A drug that binds to a receptor and stimulates a response is called an agonist

• A drug that binds to a receptors and blocks or reduce the effect of a agonist is called an antagonist

• Antagonism is a generally a reversible competitive process between the drug and bodies natural chemical. The more drug that is present the less chance of the natural transmitter having an action.

• However, some antagonist drugs bind irreversibly and the action occurs until the drug is broken down

Dale MM & Haylett DG (2004) General principles of drug action. In: Pharmacology Condensed. Edinburgh. Churchill Livingstone. pp.2-6

Agonist and Antagonists

Aderis Pharmaceuticals (2003) Science technology. Available at: http://www.aderis.com/science/tech.htm (Accessed: 27 August 2009)

http://www.aderis.com/science/tech.htm

©CNM 2011

Other Drug Targets

• Some drugs target carriers, these include:

– ATP-powered ion pumps

– Transporters – Channels which use the electrochemical gradient of one ion e.g. sodium to transport another ion or molecule

• Others interact directly with ion channels that cross the plasma membrane

• Drugs can also produce effects by interacting directly with enzymes, either by competing with the natural substrate or by binding elsewhere on the enzyme and reversibly or irreversibly modifying the enzyme active site

Dale MM & Haylett DG (2004) Molecular aspects of drug action. In: Pharmacology Condensed. Edinburgh. Churchill Livingstone. pp.7-11

©CNM 2011

Biochemical Individuality

• Every single one of us is unique

• The way we process food, supplements and drugs varies

• Our needs for different nutrients are different depending on our genetics, environment as well as health

• For example it has been shown that people with ‘normal’ serum levels of vitamins B6, B12 and folic acid can still have raised levels of homocysteine

• Biochemical individuality is an important consideration for dosing in nutritional therapy

Liska D et al. (2004) Nutrition from a functional perspective. In:Clinical Nutrition: A Functional Approach. Washington.

Institute of functional medicine. pp.6

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Biochemical Individuality

• Differences in metabolism can also be important in toxicity, for example:

– Inborn errors in metabolism due to genetic mutations

– Imbalances in metabolism e.g. one step in a metabolic pathway is less efficient

– Differences in gut flora that can affect metabolism and give rise to toxins

– Environmental exposure to agents which interfere with certain metabolic pathways

Liska D et al. (2004) Environment and toxicity. In:Clinical Nutrition: A Functional Approach. Washington. Institute of functional

medicine. pp.240-248

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Drug Interactions

Drugs can interact with other drugs, supplements, herbs and even foods

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Pharmacokinetic Interactions

• These interactions occur when absorption, distribution, metabolism, or elimination of a drug is altered.

• For example, when calcium binds and decreases absorption of a quinolone antibiotic, a pharmacokinetic interaction has occurred.

• Or when drug levels are increased because another drug or supplement inhibits a metabolizing enzyme (e.g. cytochrome P450 isozymes)

Natural Medicines Comprehensive Database (2009) Drug-Supplement Interactions. Available at:

http://www.naturaldatabase.com/(S(xfqte4iaxf3tfs55ocygbnaa))/ce/ceCourse.aspx?s=ND&cs=&pc=07%2D34&cec=1&pm=5 (Accessed:

27/08/09)

http://www.naturaldatabase.com/(S(xfqte4iaxf3tfs55ocygbnaa))/ce/ceCourse.aspx?s=ND&cs=&pc=07%2D34&cec=1&pm=5

©CNM 2011

P450 (CYP) Enzyme system • The CYP 3A4 enzyme is involved in the metabolism of over

50% of all drugs

• The human body has over 30 CYP enzymes, but only six of them are known to be relevant for interactions: 1A2, 2C19, 2E1, 2C9 2D6 3A4

• Over 78 dietary supplements and herbs have some effect on a CYP enzyme, and therefore the potential to interact with drugs metabolized by these enzymes.

• Supplements such as St. John's Wort, Garlic, DHEA and others that alter this enzyme can interact with a very long list of conventional drugs.



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Pharmacodynamic Interactions

• Can often be predicted based on the pharmacology of a drug or supplement.

• These interactions occur when the pharmacological effects of two products are additive or oppositional.

• Example: When a drug and a supplement both have hypoglycemic activity, then there is a chance for an additive pharmacodynamic interaction. E.g. Chromium and Metformin

• When a drug lowers blood pressure and a supplement increases it, there is a chance for an oppositional or antagonistic pharmacodynamic interaction. E.g. Antihypertensive drugs and liquorice



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©CNM 2011

Drugs and Alcohol

• Alcohol can inhibit a drug's metabolism by competing with the drug for the same set of metabolizing enzymes

• Long-term alcohol ingestion may activate drug-metabolizing enzymes, thus decreasing the drug's availability and diminishing its effects

• Enzymes activated by chronic alcohol consumption transform some drugs into toxic chemicals that can damage the liver or other organs

• Alcohol can magnify the inhibitory effects of sedative and narcotic drugs at their sites of action in the brain.

• Some drugs affect the metabolism of alcohol, thus altering its potential for intoxication and the adverse effects.

• Alcohol can also force certain drugs out of their depot resulting in overdose

The People’s Pharmacy (2002) Drug and Alcohol Interactions. Available at: http://www.healthcentral.com/static/pp/pdf_guides/alcohol-

02.pdf (Accessed 27/08/09)

http://www.healthcentral.com/static/pp/pdf_guides/alcohol-02.pdf



©CNM 2011

Drug Interaction Resources

• A-Z Guide to Drug-Herb-Vitamin Interactions by Alan R. Md Gaby

• BNF – Appendix 1

• www.nutripeople.co.uk - Free access to Health Notes for students

• www.naturaldatabase.com – Subscriber site that allows you to check specific supplement company products against clients medications

http://www.amazon.com/exec/obidos/search-handle-url/002-8597343-1010434?%5Fencoding=UTF8&search-type=ss&index=books&field-author=Alan%20R.%20Md%20Gaby

http://www.nutripeople.co.uk/

http://www.naturaldatabase.com/

http://www.amazon.com/gp/reader/0761515992/ref=sib_dp_pt

Common Food-Drug Interactions

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Grapefruit Juice

• Grapefruit furanocoumarins, specifically bergamottin and dihydroxybergamottin, selectively inhibit CYP3A4 in the gut wall.

• Therefore, grapefruit significantly increases gastrointestinal absorption of CYP3A4 substrates and increases peak levels.

• Since grapefruit doesn't inhibit hepatic CYP3A4, the half-life of drugs metabolized by this enzyme is not increased.

• However, consuming large amounts of grapefruit or consuming grapefruit repeatedly for an extended period might also result in some inhibition of hepatic CYP3A4

• The inhibition of CYP3A4 by grapefruit can last for up to 24 hours...so separating administration of grapefruit and drugs won't help.



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©CNM 2011

Partner Work

• Using appendix I in your BNF please identify 10 drugs that interact with grapefruit juice

©CNM 2011

Pomegranate Juice

• Pomegranate juice appears to cause interactions in a manner similar to grapefruit juice based on preliminary evidence.

• But there isn't as much research yet on the interactions caused by pomegranate.

• Until more is known, err on the side of caution. Advise patients not to drink pomegranate juice if they are taking drugs metabolized by CYP3A4



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©CNM 2011

Noni Juice

• Noni juice contains significant amounts of potassium, about 56 mEq/L.

• This isn't a problem for most people, but could result in hyperkalemia in people with renal dysfunction or in people taking other drugs that increase potassium levels such as ACE inhibitors.



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Green Vegetables

• Large amounts of green vegetables such as broccoli, spinach, cabbage, brussel sprouts etc seem to reduce the effect of anticoagulants such as Warfarin

• These vegetables contain substances called indoles which increase the rate warfarin is metabolised and eliminated

• They are also rich in vitamin K

• Anticoagulants compete with vitamin K to decrease production of blood clotting factors

• If vitamin K levels are boosted anticoagulant effects are reduced

Mason P (2002) Food and Medicines. The Pharmaceutical Journal. 269 pp. 571-573

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Soya

• Ingestion of soy foods simultaneously with thyroid hormones can reduce their absorption

• People taking thyroid hormones should not consume soy products within 3 hours of taking their medication

• The effects of warfarin may also be reduced by large amounts of soya bean products

• Soy may interfere with the effects of oestrogen blocking drugs such as tamoxifen


Gaby, AR (ed.) (1999) A-Z Guide to Drug-Herb-Nutrient Interactions. New York. Three Rivers

Press pp. 206

Natural Medicines Comprehensive Database (2009) Tamoxifen interactions. Available at:

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=97&fs=ND (Accessed:

27/08/09)

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=97&fs=ND

©CNM 2011

Dairy

• Calcium can bind antibiotics like the quinolones and tetracycline, and also bisphosphonates reducing their absorption.

• It can also bind and reduce absorption of levothyroxine.

• To avoid this interaction, advise patients to take levothyroxine and calcium supplements or calcium rich foods at least four hours apart.



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©CNM 2011

Tyramine Containing Foods

• Tyramine containing food and drink can precipitate a hypertensive crisis in people taking MAOI anti-depressants

• Food to avoid include: – Eggplant, avocado

– Figs, grapes, oranges, pineapples, plums, prunes, and raisins

– Matured cheeses

– Processed foods

– Fermented soy products

– Processed, cured or pickled meats

– Chocolate

– Nuts


©CNM 2011

Effects of Different Diets

• Dramatic changes in diet may also affect someone’s medication, for example:

• High protein diets may reduce the effects of theophylline and L-Dopa

• High fibre diets can reduce serum levels of tricyclic antidepressants

• Salt restriction can increase serum lithium to toxic levels


©CNM 2011

Nutrient Depletions

• Some medications can affect the levels of certain

nutrients in the body.

• This is an important consideration when assessing nutrient status.

• Often nutritional supplements can be used to counteract these drug-induced depletions

• Both www.nutripeople.co.uk and www.naturaldatabase.com contain information on drug nutrient depletions

http://www.nutripeople.co.uk/

http://www.naturaldatabase.com/

Nutrient Depletion: The Worst Offenders

Drug Nutrients affected Mechanism

Statins

CoQ10 Block synthesis of mevalonic acid, which is a precursor of cholesterol and coenzyme Q10

Antibiotics Biotin, Pantothenic Acid (B5), Pyridoxine (B6)

Riboflavin (B2), Thiamine (B1), Vitamin B12

Vitamin K

Destruction of normal intestinal microflora may lead to decreased production of various B vitamins and vitamin K.

Metformin Vitamin B12

Folic Acid

Malabsorption of B12 and folic acid

Natural Medicines Comprehensive Database (2009) Drug Influences on Nutrient Levels and Depletion. Available at:


27/08/09)




Diuretics Calcium, Magnesium

Potassium, Folic Acid

Vitamin B1, Vitamin B6

Vitamin C

Increased urinary loss

Antacids Calcium

Iron

Chromium

Folic Acid

Increased gastric pH may reduce solubility and absorption

Aluminium containing antacids can bind to calcium preventing absorption



27/08/09)




Thyroxine Calcium Increased bone turnover may lead to increased urinary calcium losses

Bile Acid Sequestrants

Beta-Carotene, Vitamin A

Vitamin E, Vitamin K

Folic Acid, Iron

Vitamin B12, Vitamin D

Magnesium, Phosphate

Reduced absorption



27/08/09)




Oral contraceptive pill

Folic acid

Magnesium

Vitamin B6

Vitamin B2

Vitamin B1

Vitamin A

Vitamin B12

Vitamin C

Zinc

Reduced absorption, increased excretion, increased protein binding and induction of liver enzymes which use folate

Shift from plasma to tissues

Interference with metabolism

Reduced absorption or interference with conversion to active form

Reduction in activity of the thiamine-dependent enzyme

Reduce liver storage of vitamin A

Reduced B12 protein binding

Reduced absorption, increased excretion and increased requirement



27/08/09)




Proton Pump Inhibitors

Beta-carotene, Calcium

Chromium, Folic Acid

Vitamin B12, Vitamin C

Zinc

Reduced gastric acid levels inhibit the absorption of these nutrients

Steroids Calcium, Vitamin D

Chromium, Folic Acid

Magnesium, Potassium

Strontium, Zinc

Steroids can increase urinary excretion of these nutrients, often this is accompanied by losses from the bone tissue



27/08/09)


Common Drugs & Key Interactions

A review of some of the common classes of drugs and nutraceuticals they may

interact with

Gastrointestinal System

©CNM 2011

Antacids

• Examples: Mucogel, Maalox • Usually contain aluminium or magnesium compounds • Indication: Dyspepsia, esp. Ulcer-based • Mode of action: Neutralise stomach acid • Interactions: Should not be taken with other drugs, may impair

absorption • Magnesium-containing antacids tend to be laxative • Aluminium-containing antacids may be constipating. • Mg carbonate and aluminium hydroxide often combined to cancel

out GI effects! • NB Al hydroxide can bind to other drugs reducing their effectiveness

e.g. warfarin and digoxin. Dose may need to be altered or drugs dosed separately

• NB Overuse of antacids – Acid rebound

British Medical Association (2007) Antacids and simethicone. In: British National Formulary 54. London: BMJ

publishing group and RPS publishing. p38

©CNM 2011

Interaction: Vitamin D

• The protein which transports calcium across the intestinal wall can also bind and transport aluminum.

• This protein is stimulated by vitamin D, which may therefore increase aluminum absorption

• This mechanism may contribute to increased aluminum levels and toxicity in people who use antacids long term or those with kidney problems

Natural Medicines Comprehensive Database (2009) Antacid Interactions. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=&sh=69&fs=ND&sid=929&searchid=1

6522179#pshow (Accessed: 28/08/09)



©CNM 2011

Antimotility Drugs

• Examples: Codeine phosphate, Imodium, Lomotil, Loperamide

• Mode of action: Acts on opioid receptors in the muscles lining the walls of the intestines.This reduces peristalsis allowing more time for water and electrolytes to be reabsorbed

• Indication: Uncomplicated acute diarrhoea in adults

• Contraindication: Young children, abdominal distension, active/acute ulcerative colitis

• Cautions: Liver disease and pregnancy

• Side Effects: Nausea, constipation, drowsiness

• N.B. In dehydration, fluid/electrolyte replacement are the primary concern. It is also important to address the underlying cause.

British Medical Association (2007)Anti-motility drugs. In: British National Formulary 54. London: BMJ publishing group and RPS

publishing. pp.51

©CNM 2011

Antispasmodics

• Examples: Mebeverine, Buscopan • These compounds act directly on the gut muscles at the

cellular level to relax them • Indications: IBS, Diverticular disease • Mode of action: Antimuscarinics: block acetylcholine

receptors • Contra-indications: Mysthenia gravis, prostate enlargement,

pyloric stenosis • Cautions: Down’s syndrome, children, elderly, GERD,heart

problems • Side effects: Constipation, palpitations, reduced bronchial

secretions, urinary retention

British Medical Association (2007) Antimuscarinics. In: British National Formulary 54. London: BMJ publishing group and RPS

publishing. p41

Antimuscarinics – Mode of Action

Society for Continence (Singapore) (2009) Changing Treatments for Overactive Bladder. Available at:

http://www.sfcs.org.sg/medi_page/site_web_sfcs/common_page.asp?pg=66 (Accessed: 21 August 2009)

http://www.sfcs.org.sg/medi_page/site_web_sfcs/common_page.asp?pg=66

©CNM 2011

Interaction: Calcium-D-Glucarate

• Calcium D-glucarate can be used to help prevent hormone-related cancers.

• It is thought to decrease oestrogen levels by affecting oestrogen's elimination.

• Oestrogen is normally metabolized through the glucuronidation phase II pathway in the liver.

• It's then excreted in the bile, but a bacterial enzyme in the intestine called beta-glucuronidase normally breaks the oestrogen-glucuronide bond, allowing oestrogen to be reabsorbed.

• Calcium D-glucarate works at this step by inhibiting beta-glucuronidase, decreasing the amount of oestrogen that is reabsorbed.

Natural Medicines Comprehensive Database (2009) Calcium-D Glucarate. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&sh=76&id=136 (Accessed:

28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&sh=76&id=136

©CNM 2011

Interaction: Calcium-D-Glucarate

• Theoretically, calcium D-glucarate might increase the clearance of drugs that undergo glucuronidation.

• This includes some antispasmodics as well as acetaminophen, atorvastatin, diazepam, digoxin, entacapone, therpautic oestrogens, irinotecan, lamotrigine etc

Glucuronidation of

Oestrogen

Natural Medicines Comprehensive Database (2009) Glucuronidated drugs. Available at:


6522179#pshow (Accessed: 28/08/09)



©CNM 2011

H2-Receptor Antagonists

• Examples: Zantac, Ranitidine, Tagamet, Pepcid

• Aid healing of gastric and duodenal ulcers by reducing gastric acid output

• Indications: Gastric/duodenal ulcers, reflux oesophagitis

• Mode of action: Used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells

• Most antihistamines have no effect on H2 receptors

• Caution: Liver and/or kidney-impaired patients as these drugs can compromise detoxification pathways.

• Side effects: Diarrhoea, headaches, dizziness, rashes, fatigue

• Mostly replaced by helicobacter eradicating drugs and PPIs (more effective)

British Medical Association (2007) H2-receptor antagonists. In: British National Formulary 54. London: BMJ publishing group and

RPS publishing. pp.44-47

H2 Antagonists - Mode of Action

Konturek S J; Brzozowski T; Konturek P C; Schubert M L; Pawlik W W; Padol S; Bayner J (2008) Brain-gut and appetite regulating hormones in the

control of gastric secretion and mucosal protection. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 59

Suppl 2 pp.7-31.

©CNM 2011

Proton Pump Inhibitors (PPIs)

• Examples: Zoton, Nexium, Losec

• Block the ‘proton pumps’ of gastric cells

• Indications: Short term treatment of gastric/duodenal ulcers, H Pylori in combination with 2 antibiotics other drugs, GERD, prevention of NSAID-associated ulcers

• Mode of action: Block hydrogen-potassium adenosine triphosphate enzyme system (the proton pump) of gastric parietal cells

• Caution: Liver disease, pregnancy, breast-feeding, gastric cancer (masking sx)

• Side effects: Nausea, vomitting, diarrhoea,flatulence constipation, abdominal pain, headache, dizziness

British Medical Association (2007) Proton pump inhibitors. In: British National Formulary 54. London: BMJ publishing group and


PPI – Mode of Action

AstraZeneca (2009) Acid reflux-Treatment-Medicine. Available at:

http://www.astrazeneca.com.ph/1027897/1027901/522976?itemId=1517321 (Accessed: 21 August 2009)

http://www.astrazeneca.com.ph/1027897/1027901/522976?itemId=1517321

©CNM 2011

Corticosteroids

• Examples Prednisolone, hydrocortisone

• Indications: Inflammatory bowel disease, asthma, eczema, hypersenstivity reactions, autoimmune conditions

• Mode of action: Block the production of substances that trigger inflammatory actions

• Can be taken as pills or sometimes enema, suppositories and topical creams if only the lower part of the GI tract is affected

• In severe cases, some corticosteroids are given intravenously • Contraindications: Active infection, live virus vaccination • Cautions: Adrenal and immune suppression. Growth retardation in

children. Heart, liver or kidney problems. Diabetes or osteoporosis. Pregnancy and breastfeeding.

• Side effects: Numerous: GIT problems, osteoporosis, adrenal suppression, Cushings syndrome, skin thinning etc

British Medical Association (2007) Corticosteroids. In: British National Formulary 54. London: BMJ publishing group and RPS

publishing. pp.376-381

©CNM 2011

Laxatives

• Bulk forming laxatives:

– E.g. Bran, Fybogel, Normacol

– Increase faecal mass to stimulate peristalsis

– Must be taken with water

• Stimulant laxatives:

– E.g. Senna, Sennacot

– Increase intestinal motility

– Side-effects: May cause diarrhoea, hypokalaemia, Senna can irritate the colon and long term use has been linked to colon cancer

British Medical Association (2007) Bulk forming laxatives. In: British National Formulary 54. London: BMJ publishing group and

RPS publishing. pp.58

British Medical Association (2007) Stimulant laxatives. In: British National Formulary 54. London: BMJ publishing group and RPS

publishing. pp.59

©CNM 2011

Laxatives

• Osmotic laxatives:

– E.g. Lactulose, Magnesium salts (Mg sulfate)

– Increase water in colon by drawing fluid from the body or retaining fluid

– Caution: Mg salts are often abused. May cause dehydration

• Side effects of any laxative: Colic, “Lazy bowel”

British Medical Association (2007) Osmotic laxatives. In: British National Formulary 54. London: BMJ publishing group and RPS


Cardiovascular System

©CNM 2011

Cardiac Glycosides

• Examples: Digoxin, Lanoxin

• Indications: Atrial fibrillation, heart failure

• Mode of action: Increase myocardium force of contraction by increasing Ca influx into the heart muscle.

• Interactions: Ca (agonistic- increases effect)

• Contraindications: Heart block ventricular arythmias

• Caution: Low Mg, K increases toxicity, pregnancy, kidney problems

• Side effects (usually in overdose): Nausea, vomiting, diarrhoea, anorexia, abdominal pain, visual disturbance, arrhythmias

British Medical Association (2007) Cardiac glycosides. In: British National Formulary 54. London: BMJ publishing group and RPS


©CNM 2011

Digoxin - Mode of Action

Pharmacorama (2007). Inhibitors of Na+/K+-ATPase: Cardiac glycosides – Effects. Available at:

http://www.pharmacorama.com/en/Sections/NAK-ATPase-Digoxin-1.php (Accessed: 21 August 2009)

http://www.pharmacorama.com/en/Sections/NAK-ATPase-Digoxin-1.php







©CNM 2011

Interaction: Hawthorn

• Theoretically, concomitant use of digoxin with hawthorn might potentiate the effects, requiring digoxin dose reduction

• Hawthorn preparations act on the myocardium by increasing force of contraction and lengthening the refractory period, increasing coronary blood flow and cardiac output, and reducing oxygen consumption

• Hawthorn's cardiotrophic properties are attributed to increased membrane permeability for calcium and phosphodiesterase inhibition, which increases intracellular cAMP. Increased cAMP leads to increased coronary blood flow, vasodilation, and positive inotropic effects

• Preliminary research suggests that hawthorn also has antiarrhythmic activity

• Hawthorn also seems to have hypotensive activity, according to preliminary research. It seems to cause peripheral vasodilation and to induce endothelium-dependent arterial relaxation. The proantocyanidin constituents seem to cause this effect

Natural Medicines Comprehensive Database (2009) Hawthorn. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=527&ds= (Accessed:

28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=527&ds

©CNM 2011

Diuretics

• Examples: Furosemide, Lasix

• Indications: Hypertension, pulmonary oedema, chronic heart failure, oedema

• Mode of action: Diuretics reduce reuptake of primary filtrate from the loop of Henle/distal tube = Decrease blood volume and therefore pressure

• First line Rx for elderly, unless contraindicated

• Contraindications: Hypokalaemia, hyponatraemia, hypercalcaemia, liver impairment,renal failure, dehydration

• Caution: Diabetes, gout, liver/kidney problems, SLE, pregnancy, breastfeeding

• Side effects: Mineral loss especially hypokalaemia, hypotension, GIT effects, impotence

British Medical Association (2007) Diuretics. In: British National Formulary 54. London: BMJ publishing group and RPS publishing.

pp.71-77

©CNM 2011

Thiazide Diuretic - Mode of Action

Baylor College of Medicine (2009). Diuretics for the Treatment of Hypertension. Available at:

http://www.hypertensiononline.org/slides2/slide01.cfm?q=site+of+action&dpg=1 (Accessed: 21 August 2009)

http://www.hypertensiononline.org/slides2/slide01.cfm?q=site+of+action&pg=1

http://www.hypertensiononline.org/slides2/slide01.cfm?q=site+of+action&dpg=1

http://www.hypertensiononline.org/slides2/slide01.cfm?q=site+of+action&pg=1

©CNM 2011

Interaction: Calcium

• Thiazide diuretics reduce calcium excretion by the kidneys

• Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome = hypercalcemia, metabolic alkalosis, renal failure

• Advise patients to consult their physician about appropriate calcium doses, and to have their serum calcium levels and/or

parathyroid function monitored regularly.

Natural Medicines Comprehensive Database (2009) Calcium. Available at:

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&s=ND&pt=100&sh=157&id=781 (Accessed:

28/08/09)

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&s=ND&pt=100&sh=157&id=781

©CNM 2011

Beta-Blockers

• Examples: Propranolol, Atenolol, Tenormin, Lopressor • Indications: Hypertension, angina, heart attacks, arrhythmias ,

heart failure, thyrotoxicosis, anxiety, migraine prophylaxis • Contraindications: Asthma, certain heart conditions • Caution: Avoid abrupt withdrawal, liver/kidney problems,

diabetes, pregnancy, breastfeeding • Side effects: GIT disturbance, bradycardia, hypotension,

shortness of breath, headaches, fatigue, dizziness, sexual dysfunction, cold extremeties, sleep disturbance, exacerbation of psoriasis

British Medical Association (2007) Beta-adrenoreceptor blocking drugs. In: British National Formulary 54. London: BMJ publishing

group and RPS publishing. pp.83-89

©CNM 2011

Beta-Blockers Mode of Action

• Block noradrenaline receptors in arteries and on the heart muscle.

• Noradrenaline causes arteries to narrow and the heart to beat faster. By blocking its action, beta-blockers can cause arteries to widen, slow down the heart and decrease its force of contraction.

• This results in a drop in blood pressure and less work for the heart to do.

• Can be cardio selective or general

American College of Physicians (2009). Medical management following myocardial infacrtion. Available at:

http://www.acpinternist.org/archives/2006/12/extra/drug.htm (Accessed: 21 August 2009)

http://www.acpinternist.org/archives/2006/12/extra/drug.htm

©CNM 2011

ACE Inhibitors

• Examples: Captopril, Imidapril hydrochloride, Ramipril

• Indications: Heart failure, Hypertension, CVD prophylaxis

• ACE inhibitors stop conversion of angiotensin I to angiotensin II (Vasoconstrictor)

• First-line Rx for young Caucasians

• Often need diuretic use at same time

• Contra-indications: Individuals sensitive to ACE inhibitors, pregnancy

• Cautions: Concomitant use with diuretics (need to monitor BP and electrolytes), breastfeeding

• Side-effects: Hypotension, persistent dry cough, nausea, vomiting, diarrhoea, reduces glomerular filtration (In renal impairment kidney function must be monitored), electrolyte imbalance

British Medical Association (2007) Angiotensin-converting enzyme inhibitors. In: British National Formulary 54. London: BMJ

publishing group and RPS publishing. pp.98-103

©CNM 2011

Angiotensin II Antagonists

• Examples:Candesartan, Eprosartan, Losartan potassium

• Indications: Heart failure, Hypertension

• Block the action of angiotensin II at the angiotensin II receptor

• Less side effects than ACE inhibitors.

• Often need diuretic use at same time

• Contra-indications: Pregnancy and breastfeeding

• Cautions: Renal impairment, aortic or mitral valve stenosis.

• Side-effects: Hypotension, dizziness electrolyte imbalance

British Medical Association (2007)Angiotensin II Receptor Antagonists. In: British National Formulary 54. London: BMJ publishing


©CNM 2011

Mode of Action

NHS Education for Scotland (2009). Mechanism of action and side-effects of angiotensin converting enzyme (ACE) inhibitors. Available

at: http://www.nes.scot.nhs.uk/prescribing/topics/Hypertension/page10.htm (Accessed: 26 August 2009)

http://www.nes.scot.nhs.uk/prescribing/topics/Hypertension/page10.htm

©CNM 2011

Calcium-Channel Blockers

• Examples: Amlodipine, Diltiazem hydrochloride, Nifedipine, Plendil, Zanidip

• Indications: Angina, hypertension • Block influx of calcium to heart and vascular muscle • Dual effect – heart contraction force is reduced and

coronary artery dilate • First-line Rx for Afro-Caribbeans • Contraindications: Unstable angina, heart failure, aortic

stenosis, pregnancy and breastfeeding (some types) • Caution: Do not withdraw suddenly, liver/kidney

impairment

British Medical Association (2007) Calcium channel blockers. In: British National Formulary 54. London: BMJ publishing group and


©CNM 2011

Calcium Channel Blockers

• Calcium floods into heart cells through the calcium channel at each beat which releases internal stored calcium (blue arrows).

• This causes the muscle to contract.

• The diagram show three calcium channel blockers acting at different sites in the calcium channel.

Association of the British Pharmaceutical Industry (2009). Heart disease and the pharmaceutical industry. Available at:

http://www.abpi.org.uk/publications/publication_details/targetHeartDisease/hd&thepharm2c.asp (Accessed: 26 August 2009)

http://www.abpi.org.uk/publications/publication_details/targetHeartDisease/hd&thepharm2c.asp

©CNM 2011

Alpha-Adrenoceptor Blockers

• Examples: Doxazosin, Phenoxybenzamine, Phentolamine

• Indications: Resistant Hypertension, BPH

• Stop adrenaline causing vasoconstriction in the blood vessels and act as vasodilators

• Contra-indication: Most types can’t be used when there is a history of myocardial infarction, stroke or heart failure.

• Cautions: First dose may cause hypotension, pregnancy, breastfeeding

• Side Effects: Hypotension, tachycardia, dizziness, GIT disturbance, drowsiness, urinary incontinence

British Medical Association (2007) Alpha adrenoceptor blocking drugs. In: British National Formulary 54. London: BMJ publishing


©CNM 2011

Interaction: CoQ10

• Preliminary evidence suggests that coenzyme Q-10 might enhance arterial relaxation and improve vasodilation, helping to lower blood pressure.

• This effect seems to be caused by increased endothelial production of prostacyclin (PGI2) or increased sensitivity of arterial smooth muscle to PGI2, or both.

• Since Coenzyme Q-10 can decrease blood pressure it might have additive blood pressure lowering effects when used with antihypertensive drugs and should be used with caution

Natural Medicines Comprehensive Database (2009) Co-enzyme Q10. Available at:


28/08/09)


©CNM 2011

Nitrates

• Examples: Glyceryl trinitrate, Isosorbide mononitrate

• Indications: Angina, left ventricular failure

• Decompose to form nitric oxide a rapid, potent vasodilator

• Contraindications: Hypotension, hypovolemia

• Caution: Tolerance develops rapidly in continual use

• Side effects: Hypotension, tachycardia, headache, flushing, dizziness

Dawson JS (2002) Cardiovascular system. In: Pharmacology. London. Elsevier . pp.132

©CNM 2011

Interaction: L-Arginine

• L-arginine is a substrate for the nitric oxide synthase (NOS) enzyme.

• NOS in vascular endothelial cells converts L-arginine to nitric oxide (NO)

• NO is also known as endothelium-derived relaxation factor (EDRF) and causes vasodilation.

• The production of NO from L-arginine may be responsible for it blood pressure reducing properties.

• Theoretically, concomitant use with nitrates or antihypertensives might cause additive vasodilation and have a hypotensive effect; use with caution

Natural Medicines Comprehensive Database (2009) L-arginine. Available at:


28/08/09)


©CNM 2011

Antihypotensive Drugs

• Sympathomimetic amines • Examples: Phenylephrine, ephadrine • Indications: Shock, Hypotension. Acts on alpha-adrenergic

receptors (constricts peripheral vessels) and beta-adrenergic receptors (accelerates heart rate)

• Contra-indications: Pregnancy, Breast feeding, Hypertension • Caution: Diabetes, elderly • Side effects: Tachycardia, arrhythmia, NVD, dyspnoea,

anxiety/restlessness/insomnia, changes in blood glucose level, dizziness

British Medical Association (2007) Vasoconstrictor sympathomimetics. In: British National Formulary 54. London: BMJ publishing


©CNM 2011

Anti-Coagulants • Examples: Warfarin, Phenindione, Acenocoumarol • Indications: DV thrombosis, pulmonary embolism, Prophylaxis

in those with prosthetic heart valves • Block the action of vitamin K an important cofactor in the

clotting pathway • Contra-indications: Haemophilia, cerebral thrombosis, peptic

ulcers, hypertension, pregnancy • Caution: Surgery, liver/kidney impairment, breastfeeding • Side effects: Haemorrhages • May require concomitant use of other anticoagulants such as

heparin as onset of action is slow Dawson JS (2002) Cardiovascular system. In: Pharmacology. London. Elsevier . pp.146

©CNM 2011

Warfarin - Mode of Action

• Warfarin blocks vitamin K activation

Mayo Medical Laboratories (2008). Warfarin: Genotyping and improving dosing. Available at:

http://www.mayomedicallaboratories.com/articles/communique/2008/08.html (Accessed: 26 August 2009)

http://www.mayomedicallaboratories.com/articles/communique/2008/08.html

©CNM 2011

Interaction: Vitamin E

• Large doses of vitamin E seems to inhibit platelet aggregation and interfere with vitamin K-dependent clotting factor production

• These effects appear to be dose-dependent, and are probably only likely to be clinically significant with 800 IU/day or more

• Mixed tocopherols such as those found in food and some supplements seem to have a greater effect on platelet aggregation than alpha-tocopherol alone.

• Mixed tocopherols seem to increase nitric oxide (NO) release and superoxide dismutase (SOD) protein content in platelets reducing aggreagation.

• Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

• Anticoagulant and antiplatelet drugs that might interact with vitamin E include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

Natural Medicines Comprehensive Database (2009) Vitamin E Drug Interactions. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=954&ds=interdrug

(Accessed: 28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=954&ds=interdrug

©CNM 2011

Brain Storm

• How many foods and supplements can you think of that may interact with warfarin

• Appendix I in the BNF will give you a starting point

©CNM 2011

Statins • Examples: Atorvastatin, Pravastatin Lipitor, Zocor, Simvastatin,

Lipostat

• Inhibit HMG CoA reductase - an enzyme involved in cholesterol synthesis.

• Indication: Hypercholesterolaemia, hypertriglyceridaemia – First choice drug

• Often combined with antihypertensives, aspirin, diabetes management and/or diet/lifestyle

• High insulin stimulates the action of this enzyme so diabetics often have high cholesterol

• Contraindications: Pregnancy, breastfeeding, liver disease

• Caution: Alcoholism, hypothyroidism

• Side effects:GIT distrubance, headaches, fatigue, insomnia, myositis

Dawson JS (2002) Cardiovascular system. In: Pharmacology. London. Elsevier . pp.142

Statins – Mode of Action

Davidson MH & Jacobson TA (2001). How Statins Work: The Development of Cardiovascular Disease and Its Treatment With 3-

Hydroxy-3-MethylglutarylCoenzyme A Reductase Inhibitors. Available at:

http://www.geocities.com/Heartland/Ridge/4839/statins.html (Accessed: 26 August 2009)

http://www.geocities.com/Heartland/Ridge/4839/statins.html

©CNM 2011

Interaction: Red Yeast

• Red yeast supplements are manufactured by culturing M. purpureus on rice at carefully-controlled temperature and growing conditions to increase the concentration of mevinic acids

• Red yeast contains ten mevinic acids, also known as monacolins, the highest concentration of which is constituted by lovastatin

• These compounds competete with HMG-CoA reductase, blocking cholesterol biosynthesis

• Red yeast also contains sterols

• The overall cholesterol-lowering effect of red yeast is likely a result of the combination of lovastatin, mevinic acids, and other constituents

• Theoretically, taking red yeast with other statins might increase the risk of potential adverse effects

Natural Medicines Comprehensive Database (2009) Red Yeast. Available at:


28/08/09)


Respiratory System

©CNM 2011

Bronchodilators

• Examples: Salbutamol AKA Ventolin (Immediate action, short duration) Salmeterol (Delayed, longer action)

• Work by acting on receptors in the lungs called beta-2 receptors. Stimulation of these receptors causes the muscles in the airways to relax, allowing the airways to open.

• Indications: Symptomatic relief of bronchoconstriction (Asthma)

• Cautions: Hyperthyroidism, CVD, arrhythmias

• Side effects: Tremor, anxiety, headache, palpitation, muscle cramping, hypokalemia

Dawson JS (2002) Respiratory system. In: Pharmacology. London. Elsevier . pp.153

©CNM 2011

Xanthines

• Examples: Theophylline, Nuelin, Amoinphylline

• Indications: Asthmatic children that can’t use inhalers, noctural asthma, COPD

• Increase the levels of cAMP in bronchial smooth muscle leading to bronchodilation

• Contraindications: Cardiac disease, hypertension, liver impairment

• Cautions: Interact with a lot of other drugs

• Side effects: Nausea, vomiting, tremor, insomnia, tachycardia

Dawson JS (2002) Respiratory system. In: Pharmacology. London. Elsevier . pp.153-154

©CNM 2011

Interaction: Thuja

• The applicable parts of thuja are the leaf and oil from the leaf.

• Some evidence suggests polysaccharides in thuja might have antiviral and immunostimulating

• However, thujone, a constituent of thuja, is a neurotoxin that can cause convulsions

• Theoretically, patients taking drugs that lower the seizure threshold might be at greater risk of seizure if they also take thuja

• This include drugs such as theophylline, antiarrhythmics (mexiletine), antibiotics (amphotericin, penicillin, cephalosporins, imipenem), antidepressants (bupropion, others), antihistamines (cyproheptadine, others), immunosuppressants (cyclosporine) and others

Natural Medicines Comprehensive Database (2009) Thuja. Available at:


28/08/09)


©CNM 2011

Corticosteroids

• Examples: Becotide, Pulmicort, Beclometasone, Flucticasone, Budesonide, Prednisolone

• Indications: Asthma prophylaxis, COPD

• Depress inflammatory response in bronchial mucosa which reduce airway inflammation, oedema and mucus secretion

• Onset 3-7 days, regular use required

• Cautions: Children who are still growing, respiratory infections

• Low dose: Usually minimal systemic effects

• Side effects: Adrenal suppression, Oral candidiasis, Respiratory tract infection, Cushings (If used is large oral doses)


©CNM 2011

Interaction: Liquorice

• The glycyrrhetinic acid component in liquorice inhibits renal 11-beta-hydroxysteroid dehydrogenase, reducing conversion of cortisol to inactive cortisone in the kidneys Cortisol has equal affinity to aldosterone for mineralocorticoid receptors in the distal portion of the renal tubules, promoting sodium and water retention and potassium excretion and increasing blood pressure.

• Response to liquorice is highly variable

• Theoretically, concomitant use of liquorice with steroids might potentate the duration of activity of corticosteroids e.g. hydrocortisone

• This combination might also increase potassium loss and increase the risk of potassium depletion.

• Overuse or misuse of liquorice can cause potassium depletion

Natural Medicines Comprehensive Database (2009) Liquorice. Available at:


28/08/09)


©CNM 2011

Leukotriene Receptor Antagonists

• Examples: Montelukast, zafirlukast • Indication: Non-steroidal asthma

prophylaxis • Latest asthma drugs • Block the action of leukotriene at the

leukotriene receptors in the bronchiolar muscle inhibiting brochoconstriction

• Also work well alongside steroids • Contraindications: Liver impairment

breastfeeding • Cautions: Elderly, pregnancy • Side effects: GIT disturbance, dry mouth,

headache


©CNM 2011

Mast Cell Stabilisers

• Example: Sodium cromoglicate, Nedocromil sodium

• Indication: Hayfever, allergies etc • Stabilises mast cell membranes, prevents

histamine release • Needs to be taken before symptoms occur,

preventative only (not for acute attack)

• Not as effective as steroids (but fewer side-effects), ineffective in some patients

• Side-effects: Throat irritation, cough, nausea, vomiting, diarrhoea

Dawson JS (2002) Respiratory system. In: Pharmacology. London. Elsevier . pp.154-155

©CNM 2011

Antihistamines

• Indications: Allergies, Hayfever, Pruitus

• Work by antagonising H1 histamine receptors

Sedating

• Examples: Tavegil, Piriton, Vallergan, Phenergan

• Cautions: BPH, urinary retention, liver disease, renal impairment, epilepsy, children, elderly

• Side effects: Drowsiness, dry mouth, headaches, GIT disturbance, blurred vision

Non-Sedating

• Examples: Telfast, Neoclarityn, Loratadine, Zirtek, Claritin

• Cautions: Liver /renal impairment, epilepsy, children, elderly

• Side effects: Rare – muscle pain, drowsiness, arrhythmias


Antihistamine - Mode of Action

Sorrenson L (2008). Making an Impact On Allergies. Available at: http://www.optometric.com/article.aspx?article=101729

(Accessed: 26 August 2009)

http://www.optometric.com/article.aspx?article=101729

©CNM 2011

Interaction: Quercetin

• Preliminary evidence suggests that quercetin might work similarly to cromolyn, inhibiting antigen-stimulated histamine release from mast cells of patients with allergic rhinitis

• However, there is evidence that quercetin inhibits CYP3A4

• Theoretically, concurrent use of quercetin and drugs metabolized by these enzymes might result in reduced drug elimination, increased serum levels, and increased effects.

• Drug affected include some antihistamines, calcium channel blockers, chemotherapeutic agents, antifungals, glucocorticoids, prozac, citalopram and numerous others

Natural Medicines Comprehensive Database (2009) Quercetin. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=294&ds=&name=QUERCETI

N&searchid=16522179 (Accessed: 28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=294&ds=&name=QUERCETIN&searchid=16522179

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=294&ds=&name=QUERCETIN&searchid=16522179

©CNM 2011

Adrenaline/Epinephrine

• Examples: EpiPen, Anapen

• Indication: Allergic emergencies, anaphylaxis, angioedema, cardiac resuscitation

• Often used in combination with steroids and/or antihistamines (slower acting)

• Cautions: Heart disease, hypertension, cerebrovascular disease, arrhythmias, diabetes, hyperthyroidism, glaucoma, elderly

• Side effects: Nausea, vomiting, tachycardia, arrhythmias, hypertension, anxiety, tremor, restlessness, headache, weakness, dizziness, hyperglycemia, sweating

British Medical Association (2007) Allergic emergencies. In: British National Formulary 54. London: BMJ publishing group and


©CNM 2011

Decongestants

• Example: Ephedrine

• Indication: Nasal congestion

• Epherdrine constricts nasal blood vessels limiting oedema and nasal secretions

• Contraindications: Diabetes, hypertension, hyperthyroidism

• Caution: Use in children

• Side effects: Local irritation, headaches, rebound congestion on withdrawal


©CNM 2011

Interaction: Caffeine

• Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects.

• There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death

• Tell patients to avoid taking caffeine containing foods and drinks with ephedrine

• This includes tea, coffee, green tea, cocoa, guarana etc

Natural Medicines Comprehensive Database (2009) Ephedrine. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=233&fs=ND (Accessed:

28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=233&fs=ND

Central Nervous System

©CNM 2011

Parkinson’s Disease Drugs

• Dopamine precursors – L-Dopa

• Dopamine agonists – Bromocriptine, ropinirole, pergolide, lisuride

• Drugs that stimulate dopamine release – Amantadine

• MAOB inhibitors (inhibit breakdown of dopamine) – Selegiline

• COMT inhibitors (inhibit breakdown of dopamine) – Entacaptone

• Anticholinergics (reduce symptoms) – Benzotropine, procyclidine, orphenadrine

Dawson JS (2002) Central Nervous system . In: Pharmacology. London. Elsevier . pp.90-92

Parkinson’s Drugs

Dawson JS (2002) Central Nervous system . In: Pharmacology. London. Elsevier . pp.90

©CNM 2011

Interaction: B6

• Levodopa is biotransformed into dopamine by the enzyme aromatic amino acid decarboxylase

• This enzyme that utilizes vitamin B6 as a co-factor.

• Supplemental B increases levodopa metabolism in the peripheries

• This reduces the anti-parkinsonism effect because the dopamine formed in the peripheries inhibits further absorption of levodopa in the GI tract and cannot cross the blood brain barrier into the CNS site of action.

• People taking L-dopa should therefore avoid all B6 containing supplements (dietary B6 has no effect)

• This interaction does not occur when carbidopa is used concurrently with L-dopa e.g. Sinemet

Mason P (2002) Nutritional supplements and drugs. The Pharmaceutical Journal. 269 pp. 609-611

Okereke CS (2002) Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of

Parkinson's disease patients experiencing motor fluctuations with levodopa. J Pharm Pharmaceut Sci. 5(2) pp.146-161

Interaction: B6

Okereke CS (2002) Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of

Parkinson's disease patients experiencing motor fluctuations with levodopa. J Pharm Pharmaceut Sci. 5(2) pp.146-161

©CNM 2011

Benzodiazepines

• Examples: Diazepam (Vallium), Xanax, Lorazepam

• Indications: Muscle relaxant e.g. whiplash (low dose), minimising drug withdrawal, severe/disabling insomnia/anxiety (short term only)

• Act on GABA (CNS inhibitory) receptors

• Contraindications: Bronchopulmonary disease, concomitant use with alcohol, barbiturates and antihistamines

• Caution: Tolerance/dependence, withdrawal causes anxiety, insomnia, anorexia, tremor, perspiration, tinnitus, perceptual disturbance

• Side effects: Drowsiness/confusion, muscle weakness, dependence


©CNM 2011

Benzodiazepines - Mode of Action

• Benzodiazepines bind to a sub-unit of the GABA-A receptor.

• Their binding causes a structural change that results in an increase in GABA A receptor activity

CNS Forum (2005). Mechanism of action of the benzodiazepines Available at:.

http://www.cnsforum.com/imagebank/item/drug_benzo/default.aspx (Accessed: 26 August 2009)

http://www.cnsforum.com/imagebank/item/drug_benzo/default.aspx

©CNM 2011

Antidepressants - SSRIs

• Selective Serotonin Reuptake Inhibitors

• SSRI’s are much more widely prescribed than other antidepressants (MAOI’s, TCA’s) as they have less side effects

• Examples: Prozac, Citalopram, Sertraline

• Indications: Chronic and major depression, nerve pain

• Inhibit the reuptake of serotonin from the synaptic cleft

• Contraindications: Concomitant use with MAOI antidepressants, use in manic phase

• Caution: Withdrawal should be tapered over a few weeks

• Side effects: GIT disturbance, insomnia, anxiety, agitation, sexual dysfunction


©CNM 2011

SSRI - Mode of Action

• SSRIs restore the levels of serotonin (5-HT) in the synaptic cleft by binding at the 5-HT re-uptake transporter

• This blockade leads to the accumulation of 5-HT in the synaptic cleft and the concentration of 5-HT returns to within the normal range

CNS Forum (2005). The mechanism of action of specific 5-HT re-uptake inhibitors. Available at:

http://www.cnsforum.com/imagebank/item/Drug_SSRI_2/default.aspx (Accessed: 26 August 2009)

http://www.cnsforum.com/content/pictures/imagebank/hirespng/Drug_SSRI_2.png

http://www.cnsforum.com/imagebank/item/Drug_SSRI_2/default.aspx

©CNM 2011

Interaction: 5-HTP

• Combining serotonergic antidepressants with 5-HTP can have an additive effect might increase the risk of serotonin syndrome.

• These drugs include the SSRIs such as Prozac, Paxil, Zoloft, and others; as well as tricyclic and atypical antidepressants such as amitriptyline, clomipramine, imipramine and others.

5-HTP

Serotonin

Biotin, B6, Zinc

Natural Medicines Comprehensive Database (2009) Prozac Drug Interactions. Available at:

http://www.naturaldatabase.com/(S(xfqte4iaxf3tfs55ocygbnaa))/nd/Search.aspx?cs=&s=ND&pt=&sh=15&fs=ND&sid=794&searchid=1650

5629#pshow (Accessed: 27/08/09)

• 5-HTP is a natural extract from the seeds of the Griffonia plant.

• Precursor to serotonin • More direct source than tryptophan which can be

incorporated into proteins or used to make vitamin B3 • 5-HTP also crosses the blood brain barrier more easily

than tryptophan.



©CNM 2011

Interaction: St John’s Wort

• Concomitant use with SSRIs can lead to additive effects which can increase the risk of serotonergic side effects, including serotonin syndrome

• Although this effect has only been reported with nefazodone, paroxetine, and sertraline, it might also occur with other antidepressants.

• Use of St. John's Wort with other antidepressants should only be done with close supervision.

• Active constituents are believed to be hypericin and hyperforin

• Modulate the effects of serotonin, dopamine, and norepinephrine

and may inhibit reuptake of these neurotransmitters making them

more available to the brain

Natural Medicines Comprehensive Database (2009) Prozac Drug Interactions. Available at:


5629#pshow (Accessed: 27/08/09)



©CNM 2011

Antiepileptic Drugs

• Anticonvulsants

• Examples: Phenytoin, Sodium Valproate, Carbamazine

• Indications: Epilepsy

• Inhibit sodium ion channels in neurons preventing the spread of a seizure

• Contraindications: These drugs have a lot of interactions due to their ability to induce certain liver enzymes, should not be used in cases of liver impairment

• Side effects: GIT disturbance, insomnia, dizziness, headaches, gum tenderness, hirsuitism, acne, allergic reactions, ataxia, sedation


©CNM 2011

Interaction: Folic Acid

• Antiepileptics can cause folate deficiency by decreasing intestinal absorption and inducing hepatic enzymes that increase folic acid metabolism

• However, folic acid supplementation can reduce serum anticonvulsant levels and seizure control

• Folic acid supplements should only be given to people on antiepileptics who can be monitored (preferably by their GP)

• Women on anticonvulsants who are planning pregnancy should seek medical advice as they may need high dose (5mg) folic acid supplementation to reduce the risk of neural tube defects

Mason P (2002) Nutritional supplements and drugs. The Pharmaceutical Journal. 269 pp. 609-611

©CNM 2011

Nausea & Vertigo Drugs

• Example: Prochlorperazine

• Indications: Menieres Disease, nausea, vomiting, vertigo, psychosis

• Block dopamine, histamine and acetylcholine receptors

• Contraindications: May exacerbate Parkinson’s symptoms

• Side Effects: Sedation, hypotension, increased prolactin levels

Dawson JS (2002) Gastrointestinal System. In: Pharmacology. London. Elsevier . pp.173

©CNM 2011

Interaction: Phosphatidyl Choline

• Phosphatidylcholine is a phospholipid and a major component of lecithin

• Phosphatidylcholine is the largest reservoir of choline in the body and choline is a precursor to acetylcholine

• Since phosphatidylcholine might increase acetylcholine, there is interest in using it for improving memory and for conditions such as Alzheimer's disease.

• Theoretically phosphatidylcholine may decrease the effectiveness of drug such as prochlorperazine and antimuscarinic which work by blocking acetylcholine receptors

Natural Medicines Comprehensive Database (2009) Phosphatidylcholine. Available at:


27/08/09)


Inflammation & Pain

©CNM 2011

NSAIDs

• Examples: Aspirin, Ibuprofen

• Indications: Pain relief, inflammation, fever

• Inhibit the enzyme cycloxygenase which is involved in metabolism of arachadonic acid to inflammatory mediators

• Contraindications: Peptic ulcers, hypersensitive people

• Cautions: Asthma, impaired renal function

• Side effects: Dyspepsia, nausea, vomiting, ulcer formation, renal damage, liver damage, bronchospasm, allergic reactions

Dawson JS (2002) Inflammation, pain and immunosuppression. In: Pharmacology. London. Elsevier . pp.57-58

NSAID – Mode of Action

Stovitz SD & Johnson RJ (2003). NSAIDs and Musculoskeletal Treatment. Available at:

http://www.chiro.org/LINKS/DISCONTINUED/NSAIDs_and_Musculoskeletal_Treatment.html (Accessed: 26 August 2009)

http://www.chiro.org/LINKS/DISCONTINUED/NSAIDs_and_Musculoskeletal_Treatment.html

©CNM 2011

Interaction: Gingko

• Gingko has antiplatelet effects

• It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation

• Combining ginkgo with NSAIDs might have additive antiplatelet effects and increase the risk of bleeding.

• In one case, a 71-year-old man had taken a specific ginkgo extract 40 mg twice daily for 2.5 years experience a fatal intracerebral hemorrhage after about 4 weeks of taking ibuprofen 600 mg daily

• Short-term use of ginkgo leaf might not significantly reduce platelet aggregation and blood clotting.

• It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation

• Use ginkgo cautiously or avoid in patients who are taking NSAIDs or anticoagulant drugs.

Natural Medicines Comprehensive Database (2009) Ibuprofen Interactions. Available at:

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=18&fs=ND (Accessed:

27/08/09)

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&drg=1&s=ND&pt=&sh=18&fs=ND

©CNM 2011

Serotonin Agonists

• Examples: Sumatriptan, Rizatriptan

• Indication: Migraine relief

• Believed to reverse blood vessel dilation in the brain

• Contraindications: Ischemic heart disease, hypertension

• Cautions: Coronary heart disease, liver impairment, pregnancy and breastfeeding

• Side effects: Sensations of tingling, heat, chest tightness

Dawson JS (2002) Inflammation, pain and immunosuppression. In: Pharmacology. London. Elsevier . pp.66

Endocrine & Reproductive Drugs

©CNM 2011

Thyroid Hormone Replacement

• Examples: Levothyroxine, Liothyronine

• Indication: Hypothyroidism

• The drugs are converted into T3 in vivo

• Contrainidcations: Thyrotoxicosis

• Caution: CVD

• Side effects: Arrhythmias, tachycardia, anginal pain, cramps, headaches, restlessness, sweating, weight loss

Dawson JS (2002) Endocrine and Reproductive Systems. In: Pharmacology. London. Elsevier . pp.184

©CNM 2011

Anti-Thyroid Drugs

• Examples: Carbimazole, methimaxole, propylthiouracil

• Indications: Hyperthyroidism

• Inhibit thyroid peroxidase which results in reduced thyroid hormone synthesis

• Contraindications: Patients with a large goitre

• Cautions: Renal impairment

• Side effects: Nausea, headaches, allergic reactions, hypothyroidism

Dawson JS (2002) Endocrine and Reproductive Systems. In: Pharmacology. London. Elsevier . pp.182-183

©CNM 2011

Interaction: Iodine

• Iodine is essential for the synthesis of the thyroid hormones T3 and T4

• However, excess iodine can actually lower serum thyroid hormones

• In fact high doses of iodine can be used to treat thyrotoxicosis

• For this reason iodine should not be used with levothyroxine or anti-thyroid drugs as it may increase hypothyroidism

Natural Medicines Comprehensive Database (2009) Iodine. Available at:

http://www.naturaldatabase.com/(S(33wuc145gtlecx45otdrwbyi))/nd/Search.aspx?cs=&s=ND&pt=100&id=35&ds=&name=IODINE&search

id=16523174 (Accessed: 28/08/09)

http://www.naturaldatabase.com/(S(33wuc145gtlecx45otdrwbyi))/nd/Search.aspx?cs=&s=ND&pt=100&id=35&ds=&name=IODINE&searchid=16523174

http://www.naturaldatabase.com/(S(33wuc145gtlecx45otdrwbyi))/nd/Search.aspx?cs=&s=ND&pt=100&id=35&ds=&name=IODINE&searchid=16523174

©CNM 2011

Thinking Exercise

• You have a 54 year old female client who presents with hypothyroidism and the early stages of osteoporosis. She is also suffering with menopausal hot flushes. She is taking 100mcg thyroxine daily and the statin Lipotor

• What considerations need to be taken into account when making dietary suggestions for this client?

• What supplements may benefit this client?

• Are there any important considerations regarding the timing of particular foods or supplements?

• What supplements would not be advised for this client?

Diabetes Drugs

Drug Mechanism Side effects

Insulin

Used for Type I (and Type II when endogenous insulin production fails)

Mimics endogenous insulin action Local reaction, hypoglycemia in overdose

Sulphonylureas e.g. gliclazide, tolubutamide

Used for Type II

In the membrane of pancreatic beta-cells, blocks potassium channels opening calcium channels, calcium influx increases insulin release from the cell

Weight gain, GIT disturbance, allergic reaction, headaches, hypoglycemia

Metformin

Used for Type II

Decreases gluconeogenesis and increases glucose uptake by activating AMP - an important enzyme in GLUT4 translocation

Anorexia, headaches, nausea, vomiting, decreased B12 absorption


©CNM 2011

GLUT4

• GLUT4 is the insulin-regulated glucose transporter found

in fat and muscle tissue.

• In the absence of insulin, GLUT4 is kept within the lipid

bilayer of muscle and fat cells.

• Insulin causes a redistribution of GLUT4 from

intracellular storage sites to the plasma membrane

allowing diffusion of circulating glucose down its

concentration gradient into muscle and fat cells.

Kulkarni A (2009) Insulin Action on Myo1C Mediated Movement of GLUT4. Available at:

http://dolly.biochem.arizona.edu/Bioc462b_Honors_Spring_2009/abhik/insulin.html (Accessed: 27/08/09)

http://dolly.biochem.arizona.edu/Bioc462b_Honors_Spring_2009/abhik/insulin.html

GLUT4

Kulkarni A (2009) Insulin Action on Myo1C Mediated Movement of GLUT4. Available at:

http://dolly.biochem.arizona.edu/Bioc462b_Honors_Spring_2009/abhik/insulin.html (Accessed: 27/08/09)

http://dolly.biochem.arizona.edu/Bioc462b_Honors_Spring_2009/abhik/insulin.html

©CNM 2011

Interaction: Chromium

• Chromium causes an increase in GLUT4 on the plasma membrane resulting in improved glucose trafficking in response to insulin.

• This is thought to be mediated by the fact that chromium increases membrane fluidity by reducing plasma membrane cholesterol levels.

• It may activate p38 MAPK, another enzyme thought to play a role in insulin-stimulated glucose uptake.

• Chromium is therefore particularly useful when insulin resistance is present, especially if accompanied by an abnormal lipid profile.

• Theoretically, concomitant use of chromium and diabetes drugs might increase the risk of hypoglycemia and blood sugar should therefore be carefully monitored

Chen G, Liu P, Pattar GR, Tackett L, Bhonagiri P, Strawbridge AB et al. (2006) Chromium activates glucose transporter 4 trafficking and

enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism. Mol Endocrinol. 20(4)

pp.857-70

©CNM 2011

Oral Contraceptive Pill

• Indications: Contraception, menstrual symptoms

• Contain oestrogen and progesterone

• High level of steroids suppress gonadotrophins. As a result follicular maturation and ovulation do not occur

• Contraindications: Pregnancy, breastfeeding, CVD, diabetes, migraine, breast or genitourinary cancer, liver disease

• Caution: Antibiotics can reduce the effectiveness of the pill

• Side effects: nausea, vomiting, headaches, weight gain, breast tenderness, impaired liver function, impaired glucose tolerance, thrombosis, hypertension, increased risk or cervical and breast cancer


©CNM 2011

Oestrogen Agonists

• Used as part of HRT

• Indications: Management of menopausal symptoms

• Contraindications: Pregnancy, oestrogen dependent cancers, history of blood clots

• Side effects: Increased risk of endometrial and breast cancer


©CNM 2011

Interaction: Vitamin C

• Increases in plasma oestrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with OCP or HRT, including topical products

• It's suggested that vitamin C prevents oxidation of oestrogen in the tissues, regenerates oxidized oestrogen, and reduces sulfate conjugation of oestrogen in the gut.

• When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C doesn't have any effect on oestrogen levels.

• Increases in plasma oestrogen levels may occur when women who are deficient in vitamin C take supplements

• These clients should be monitored for oestrogen-related side effects.

Natural Medicines Comprehensive Database (2009) Vitamin C Drug Interactions. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=1001&ds=interdrug&name=Vit

amin+C+(VITAMIN+C+(ASCORBIC+ACID))&searchid=16522179 (Accessed: 28/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=1001&ds=interdrug&name=Vitamin+C+(VITAMIN+C+(ASCORBIC+ACID))&searchid=16522179

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=1001&ds=interdrug&name=Vitamin+C+(VITAMIN+C+(ASCORBIC+ACID))&searchid=16522179

©CNM 2011

Oestrogen Antagonists

• Example: Tamoxifen, clomiphene

• Indications: Breast cancer, female infertility

• Block oestrogen receptors in oestrogen sensitive tissues and feed back to pituitary antagonising endogenous oestrogens

• Contraindications: Liver disease, ovarian cysts, endometrial cancer

• Side effects: Multiple pregnancies, hot flushes, withdrawal can cause visual disturbance and ovarian hyperstimulation


©CNM 2011

Progestogen Agonists

• Examples: Progesterone, hydroxyprogesterone

• Indications: PMS, Period pain, heavy menstrual bleeding, endometriosis, contraception (mini pill), part of HRT

• Contraindications: Pregnancy, arterial disease, liver disease, breast or genitourinary cancer

• Side effects: Menstrual irregularities, nausea, vomiting, headaches, weight gain, breast tenderness


©CNM 2011

Androgens

• Examples: Testosterone, mesterolone

• Indications: Castrated men, pituitary or testicular disease causing hypogonadism, breast cancer

• Contraindications: Men with breast or prostate cancer, hypercalcaemia, pregnancy, breastfeeding

• Side effects: Oedema, hypercalcaemia, reduced male fertility, virilism in women, increased risk of prostate cancer

156© CNM 2009

Dawson JS (2002) Endocrine and Reproductive Systems. In: Pharmacology. London.

Elsevier . pp.198

©CNM 2011

Anti-Androgens

• Example: Cyproterone

• Indications: Male hyper-sexuality, prostate cancer, acne, female hirsutism, precocious puberty

• Contraindications: Liver disease, severe diabetes, children

• Side effects: Fatigue, lethargy, liver damage

Dawson JS (2002) Endocrine and Reproductive Systems. In: Pharmacology. London.

Elsevier . pp.198

Musculoskeletal System

©CNM 2011

Bisphosphonates

• Examples: Disodium etidronate, Alendronate (Fosamax)

• Indications: Prevention of post menopausal and corticosteroid induced osteoporosis, management of hypercalcaemia in bone cancers

• Bisphosphonates inhibit and destroy osteoclasts

• Contraindications: Renal impairment, hypocalcaemia

• Side effects: Nausea, oesophageal reactions, hypocalcaemia

Dawson JS (2002) Endocrine and Reproductive. In: Pharmacology. London. Elsevier . pp.200

©CNM 2011

Interaction: Iron

• Most of the iron in the body is found in the haemoglobin of red blood cells and in the myoglobin of muscle cells where it is required for oxygen and carbon dioxide transport

• Iron also functions in the electron transport chain as an electron carrier in cytochromes. It is also found in the functional groups of most enzymes in the Krebs cycle.

• Iron is an essential cofactor in the synthesis of neurotransmitters such as dopamine, norepinephrine, and serotonin.

• Iron and other divalent cations (magensium, calcium) can decrease absorption of bisphosphonates by forming insoluble complexes

• Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron

Natural Medicines Comprehensive Database (2009) Iron. Available at:

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&s=ND&pt=100&id=912&ds=&name=IRON&searchi

d=16523573 (Accessed: 28/08/09)

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&s=ND&pt=100&id=912&ds=&name=IRON&searchid=16523573

http://www.naturaldatabase.com/(S(wgt54jf1ay1uiw55tzlaqgva))/nd/Search.aspx?cs=&s=ND&pt=100&id=912&ds=&name=IRON&searchid=16523573

©CNM 2011

Calcitonin

• Indications: Hypercalcaemia, Paget’s disease

• Inhibits osteoclast action and reduce reabsorption of calcium by the kidneys

• Caution: Allergies, renal impairment

• Side effects: Nausea, vomiting, flushing, diarrhoea, tingling

Dawson JS (2002) Endocrine and Reproductive. In: Pharmacology. London. Elsevier . pp.201

©CNM 2011

Gold Salts

• Examples: Auranofin

• Indications: Rhematic disease

• Side effects: Rashes, proteinuria, ulceration, diarrhoea, bone marrow suppression


©CNM 2011

Gout Drugs

Colchicine

• Inhibits migration of white blood cells into the inflammed joint

• Side effects: GIT toxicity and disturbance, bone marrow suppression, renal failure

Allopurinol

• Inhibits xanthine oxidase – the enzyme involved in uric acid synthesis

• Side effects: Headaches, dyspepsia, diarrhoea, rash, hypersensitivity


©CNM 2011

Antibacterial Drugs

• 3 main types

• Drugs that inhibit bacterial cell wall synthesis – E.g. Penicillin, cefixime, vancomycin

• Drugs that inhibit bacterial nucleic acids – E.g. Sulfadiazine, ciprofloxacin

• Drugs that inhibit bacterial protein synthesis – E.g. Streptomycin, tetracycline, minocycline, chloramphenicol, erthyromycin

• Side effects: The most common side effects arfe hypersensitivity reactions and GIT disturbances due to changes in gut microflora

• Note: The development of antibiotic resistance is common

Dawson JS (2002) Infectious diseases. In: Pharmacology. London. Elsevier . pp.31-39

©CNM 2011

Interaction: Magnesium

• Magnesium can form insoluble complexes with quinolone antibiotics and tetracyclines decreasing their absorption

• Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

• Use of an aminoglycoside antibiotic and magnesium concurrently can lead to neuromuscular weakness and possible paralysis.

• Both agents reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade.

• This is most likely to occur with high doses of magnesium given intravenously

Natural Medicines Comprehensive Database (2009) Magnesium. Available at:

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=998&ds=interdrug&name=MA

GNESIUM&searchid=16522179 (Accessed: 27/08/09)

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=998&ds=interdrug&name=MAGNESIUM&searchid=16522179

http://www.naturaldatabase.com/(S(u1uu5rbs32p1nm55tghn1ar4))/nd/Search.aspx?cs=&s=ND&pt=100&id=998&ds=interdrug&name=MAGNESIUM&searchid=16522179

©CNM 2011

Antiviral Drugs

• Drugs that inhibit attachment or penetration of host cells. E.g. Amantadine, zanamivir, immunoglobulins

• Drugs that inhibit viral replication. E.g. Aciclovir, ribavarin and the reverse transcriptiase inhibitors - AZT, efavirenz and nevirapine.

• Protease inhibitors – Saquinavir, ritonavir, nelfinavir

• Immunomodulators - Interferons


©CNM 2011

Antifungal Drugs

• 3 mains classes

• Polyene macrolides e.g. nystatin – Punch holes in fungal cell membranes

• Imidazoles e.g. miconazole – Inhibit fungal lipid synthesis and interfere with fungal enzymes

• Triazoles e.g. fluconazol - Inhibit fungal lipid synthesis and interfere with fungal enzymes

• Caution: All the above have a significant impact on the liver


©CNM 2011

Interaction: Garlic

• There is some evidence that garlic may have an affect on cytochrome P450 3A4 (CYP3A4) isoenzymes particularly those containing allicin, research is however contradictory.

• Until more is known about this potential interaction, use caution when considering concomitant use of garlic and other drugs affected by (CYP3A4) .

• Drugs that may be affected include; antifungals, some calcium channel blockers, chemotherapeutic agents, and glucocorticoids among others.

Natural Medicines Comprehensive Database (2009) Garlic. Available at:


28/08/09)


Antihelminthic Drugs

Drug Worm Mechanism Side effects

Niclosamide Tapeworm Blocks the worms glucose uptake damaging its attachment

Mild GIT disturbance

Praziquantel Schistosome infection

Increases worm permeability to calcium

Mild GIT disturbance, headache, dizziness

Piperazine Roundworm

Threadworm

Paralyses the worm GIT disturbance

Dizziness


Cancer

©CNM 2011

Drugs for Cancer

• Cytotoxic therapy

• Drugs that kill rapidly dividing cells by interfering with the replication process

• Side effects: Bone marrow suppression, GIT symptoms, loss of hair, impaired wound healing, sterility, secondary cancers

Dawson JS (2002) Cancer. In: Pharmacology. London. Elsevier . pp.24

©CNM 2011

Drugs for Cancer

• Hormones and antihormones. E.g. Oestrogen antagonists, progesterones, androgen antagonists

• The growth of some cancers is hormone dependent

• Immunotherapy

• Immunostimulation

• Use of tumour specific antibodies to target drugs at cancer cells

Dawson JS (2002) Cancer. In: Pharmacology. London. Elsevier . pp.28

Miscellaneous

©CNM 2011

Skin Treatments

• Steroids – Topical, oral or intravenous for the relief of inflammatory skin conditions e.g. eczema

• Dithranol – Topical psoriasis drug

• Vitamin D analogue – Used topically in psoriasis

• Tar preparations – Used topically in psoriasis and occassionally eczema

• Salicylate – Used topically in eczema, psorasis, acne, wart and callus eradication

• Emollients – Used to soothe and hydrate the skin

Dawson JS (2002) Eyes and skin. In: Pharmacology. London. Elsevier . pp.209-210

©CNM 2011

Immuno-suppressants

• Used to suppress immune response in autoimmune conditions and organ transplant or skin grafts

Examples

• Cyclosporin – Inhibits T-cells.

• Azathioprine – Impairs DNA synthesis

• Glucocorticoids – Suppress inflammation and immune response

Dawson JS (2002) Inflammation, pain and immunosuppression. In: Pharmacology. London. Elsevier . pp.67-69

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