Unit 2 – Clinical Pharmacology Including the Effects of Co-morbidity

Absorption, Distribution, Metabolism and Excretion,
including adverse drug reactions and interactions


To appreciate how drugs are affected within the body, and how factors such as age, enzyme induction and inhibition affect a drug, it is necessary to have an understanding of absorption, distribution, metabolism and excretion.

Reading

Reading

Greenstein, B. (2004) Trounce's Clinical Pharmacology for Nurses (17th Edition). Edinburgh: Churchill Livingstone.
Chapter 1, The use of pharmaceuticals, 5-18

Cossey, M. (2004) Applied Pharmacology (Chapter 7) in Courtenay, M. and Griffiths, M. (Eds) Independent and Supplementary Prescribing: An Essential Guide. 75-96.

McKinnon, J. (2004) A painless introduction to pharmacology for nurses: part 1. Nurse Prescribing. 2 (1) 16-19.

Make Notes

Take notes on absorption, first-pass effect, distribution and elimination.

Make notes on factors that influence the dosage regime and factors that may modify drug response.

Please pay particular attention to the role and function of the liver and kidneys. It is extremely important that you understand absorption and distribution of drugs as this has utmost relevance to your responsibility as a prescriber.

On page 14 of Chapter 1, Greenstein discusses the factors that may modify the efficacy and choice of dose of the drug in patients with particular reference to:

  • patient age and size
  • genetic factors
  • nutritional factors
  • ethnicity
  • intercurrent illness
  • drug interactions
  • psychological factors
Make Notes

Make notes on each of the above factors with particular reference to the action of enzymes. The drug examples will help you to understand the importance of considering these factors in practice.

 

Reading

Reading

Greenstein, B. (2004) Trounce's Clinical Pharmacology for Nurses (17th Edition). Edinburgh: Churchill Livingstone.
Chapter 32, Adverse reactions to drugs, testing of drugs and pharmocovigilance, 407-418.

Medicines Resource (1999) Drug interactions in primary care: Part I, Principles and management. Medicines Resource Issue 54.

Medicines Resource (1999) Drug interactions in primary care: Part II, Selected drug interactions. Medicines Resource Issue 55.

It is also important to consider interactions between over-the-counter (OTC) medication and medication that is prescribed. Therefore, when prescribing for a patient, knowledge of any OTC medication they may be taking is useful.

Reading

Reading

Nathan, A. (1992) Interactions between prescribed and over-the-counter medication. Pharmaceutical Journal 249: 6707, 428-430.

Make Notes

Identify the common and potentially serious interactions that feature in the article.

Adverse drug reactions and Yellow Card reporting to the Committee on Safety of Medicines

The Medicines and Healthcare products Regulatory Agency (MHRA) defines an adverse drug reaction (ADR) as 'an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the medicine'.

In 1964, the UK introduced the Yellow Card scheme for reporting suspected ADRs, following the thalidomide tragedy. The scheme relies on voluntary reporting of suspected ADRs and many safety issues can be identified through vigilant use of the scheme.

In autumn 2002, the Committee on Safety of Medicines (CSM) and the Medicines Control Agency (which was replaced by the MHRA in April 2003) extended the responsibility of reporting ADRs via the Yellow Card scheme to nurses, with the advent of extended nurse prescribing.

Further information about the Yellow Card scheme is available at:
http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=286

Link to another Unit

You will find more information on reporting and documentation of ADRs in Unit 4. Prescribing Partnerships and in Unit 5. Prescribing in Practice.

Direct and indirect interactions arising from smoking

Smoking, similarly to OTC medications, can interact with prescribed medication. This is generally because cigarette smoke causes an increase in the rate of drug elimination, inducing the production of liver metabolising enzymes in smokers.

The various headings below explore direct and indirect interactions of drugs in smokers:

Direct interactions with smoking

Tricyclic antidepressants
Smokers tend to have lower plasma levels of these antidepressants therefore therapeutic response may be decreased. Look for signs of inadequate response — the patient may need larger dose of drug.

Benzodiazepines: diazepam and chlordiazepoxide
– May have lesser sedative effects
– May need a larger dose for appropriate sedation.

Dextropropoxyphene
– May be less effective
– A different analgesic may be more appropriate.

Heparin
– Eliminated more quickly in smokers
– May need a larger dose.

Oral contraceptives
– Risk of serious cardiovascular reactions is increased in smokers
– Risk is increased in those aged over 35
– Inform the patient of the increased risk and encourage her to stop smoking.

Pentazocine
– Smokers tend to require higher doses of a drug
– Look for signs of inadequate response — the patient may need a larger dose.

Phenothiazines
– Decreased drowsiness and hypotension tends to be produced by chlorpromazine
– Look for signs of inadequate response.

Propranolol
– In smokers who have angina, the therapeutic effect of propranolol is inhibited, as they are liable to have lower serum concentrations
– Look for signs of inadequate response.

Theophylline
– Theophylline is metabolised more rapidly, so a higher dose may therefore be required
– Look for signs of inadequate response.

Indirect interactions arising from smoking

Allergy
It can be more difficult to treat smokers for allergic conditions as tobacco smoke itself may produce allergic symptoms.

Angina pectoris
Smoking and tobacco smoke can exacerbate angina.

Diabetes mellitus
The chances of developing arteriosclerosis obliterans may be increased.

Hypertension
Smoking increases the risk of coronary heart disease and may produce an additive risk together with hypertension.

Pulmonary disease
A variety of pulmonary diseases are caused or aggravated by smoking.

Peptic ulcer disease
There is an increased chance of developing a peptic ulcer as well as increased mortality and morbidity. Ulcers may heal more rapidly in those who have stopped smoking.

Vascular diseases
Smoking increases the risk of premature death in those who have a family history of vascular disease.

Herb-drug interactions

A final interaction to be considered is herb-drug interactions. The use of herbs alongside drugs may alter the pharmacological or toxicological effects of either or, where a herb and a drug are being used for the same symptoms, there may be a compound effect, resulting in complications. There is a high likelihood that herb-drug interactions are under-reported, which means that we do not currently know about all potential interactions. If you suspect a herb-drug interaction in a patient, you are encouraged to report it through the Yellow Card scheme.

Link to another Unit

You will find more information about this in Unit 4. Prescribing Partnerships and in Unit 5. Prescribing in Practice.

Below is a table of common herb-drug interactions for you to print out and keep for future reference.

Herb

Drug

Interaction

Devil's claw

Warfarin

Purpura

Eleuthero (Siberian ginseng)

Digoxin

Raised digoxin concentrations

Garlic

Warfarin

Increased International Normalised Ratio (INR)

Ginkgo

Aspirin

Spontaneous hyphema

Paracetamol and ergotamine/caffeine

Bilateral subdural haematoma

Warfarin

Intracerebral haemorrhage

Thiazide

Diuretic hypertension

Ginseng

Warfarin

Decreased International Normalised Ratio (INR)

Phenelzine

Headache and tremor, mania

Alcohol

Increased alcohol clearance

Guar gum

Metformin, Phenoxymethylpenicillin, Glibenclamide

Slows absorption of digoxin, paracetamol and bumetanide; decreases absorption of metformin, phenoxymethylpenicillin and some formulations of glibenclamide

St John's wort

Paroxetine

Lethargy/incoherence

 

Trazodone

Mild serotonin syndrome

 

Sertraline

Mild serotonin syndrome

 

Nefazodone

Mild serotonin syndrome

 

Theophylline

Decreased theophylline concentration

 

Digoxin

Decreased peak and trough concentrations

 

Cyclosporin

Decreased concentrations in serum

 

Combined oral contraceptive

Breakthrough bleeding

(Fugh-Berman, 2000)

If you are unfamiliar with the term 'mild serotonin syndrome', click on the following link for more information:
http://www.uspharmacist.com/oldformat.asp?url=newlook/files/feat/acf2fa6.htm

Reading

Reading

Greenstein, B. (2004) Trounce's Clinical Pharmacology for Nurses (17th Edition). Edinburgh: Churchill Livingstone.
Chapter 32, Adverse reactions to drugs, testing of drugs and pharmocovigilance, Types of Adverse Reactions, 407-410.

Further Reading

Further reading

Drug and Therapeutics Bulletin (1996) Drugs and alcohol: harmful cocktails? Drug and Therapeutics Bulletin 34: 5, 36-38.

Drugs and Therapy Perspectives (1996) Be alert for interactions between prescription and OTC drugs. Drug and Therapeutics Bulletin 7: 5, 12-14.

Mason, P. (2002) Drug food interactions. (1) Food and medicines. Pharmaceutical Journal 269: 571-573.
www.pharmj.com/pdf/cpd/pj_20021019_drugfood.pdf

Mason, P. (2002) Drug food interactions. (2) Nutritional supplements and drugs. Pharmaceutical Journal 269: 609-611.
www.pharmj.com/pdf/cpd/pj_20021026_drugfood2.pdf


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