Fundamentals of Midwifery: A Textbook for Students (140 page)

Another aspect to consider is barriers within the body. If you wish the medicine to work within the central nervous system, then it must pass the blood–brain barrier (BBB). The BBB will only allow lipid soluble medicines through (unless there is a specific carrier/transport system). Some medicines will not routinely pass the BBB unless the barrier is inflamed such as in meningitis.

Another ‘barrier’ to consider is the placenta. When any medicine is administered to a pregnant woman, consideration must be given as to whether this will cross the placenta and the implications of this. For example, the medicine may not be known to be harmful, or the benefit outweighs the risk, or it should not be used in pregnancy or a particular point in the pregnancy.

Metabolism is often described as how the body gets rid of the medicine which has been admin- istered. Metabolism is actually where the chemical structure of a medicine is changed, usually

from fat soluble to more water soluble. Medicines which are excreted from the kidney must be water soluble. Metabolism usually occurs in the liver, but not exclusively and not all medicines undergo metabolism.‌

Metabolism in the liver is an enzymatic process utilising the liver enzymes known as cyto- chrome P450 (CYP450). Metabolism of fat soluble compounds is often a two-stage process. Phase I involves a chemical change using involving oxidation, reduction or hydrolysis. Phase II involves conjugation with another compound, this results in a water-soluble compound which can be excreted via the kidney.

Cytochrome P450 is the main enzyme system involved in metabolism. There are many differ- ent types (isoenzymes) which are all very similar to each other. Common types involved in the metabolism of medicinal compounds include (although there are many others) are CYP 3A4 and CYP 2D6. These enzymes can be influenced by: other medication, smoking, genetic variation.

This simplistically is the removal or excretion out of the body. This usually happens via the kidneys, but excretion can occur via the lungs (in the case of anaesthetics and gases) or via the liver and bilary tract (into bile) for large molecular weights. Although the following routes are not routinely used to remove medicines from the body, metabolites can be found in the tears, saliva and breastmilk. Medication within breastmilk is a key consideration for midwives; consid- eration must include whether the medicine is presented in breastmilk, in what concentrations and whether it is known to be harmful. For example, often medicines will be present in breast- milk, but are not known to be harmful to such a degree that the mother should not breastfeed. This is when it is important to refer to specific literature (Hale 2012) and liaise with your local lactation consultant for guidance, rather than just referring to the BNF; otherwise women may be given inaccurate advice about whether or not they can continue to breastfeed when using medication.

Another aspect to consider is whether the prescribed medication actually affects breastmilk production in terms of volume. For example, knowing the pharmacodynamics of the medicine (what the medicine is doing to the body) will help this. An example is cabergoline; dostinex tablets will work on the D

receptor and suppress milk lactation. It is licensed for the inhibition of physiological lactation soon after delivery (eMC 2013); an example of this would be following the birth of a stillborn baby.

There are some terms to review in this section and again more detail will be available in a dedi- cated pharmacology text.

This is a medicine (hormone; ligand) which binds to a receptor and produces a specific response. For example, when Salbutamol binds to the beta

receptors in the lungs, this produces bronchodilation and helps open up the airways, this is used for acute relief during an asthma attack.

This is a medicine which when bound to a receptor does not produce a response; its action is to block. Antagonists can be competitive or non-competitive, with competitive antagonists

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making easily reversible bonds. For example, ranitidine is an H

receptor antagonist; this means it blocks the H

receptor which is involved in stomach acid secretion and acid secretion is reduced.

The half life of a medicine is the time taken for plasma concentration to reduce by a half of its original value. It is normally taken that when a medicine is stopped it needs five half lives to be eliminated from the body. For examples, if a medicine has a half live of 24 hours and the patient stops taking it, in 5 days time it will not detected in the body. Conversely, to reach steady state,

i.e. a constant level of medication in the body, it takes five half lives to reach steady state with regular administration. Some medications have a very short half life (e.g. adrenaline) and others have a very long half life (e.g. amiodarone).

When a medication is taken orally, it is absorbed and reaches the liver via the hepatic portal vein. When the medicine passes through the liver it will undergo some degree of metabolism,

i.e. first pass through the liver. For some medication the degree of metabolism is extensive and the metabolite has little biological activity and therefore is rendered biological inactive. If a medicine undergoes extensive first pass metabolism then usually another route other than oral is used. An excellent clinical example is GTN; this is not given orally due to extensive first pass metabolism and is given sublingually (usually), which means it reaches the blood stream first and has a biological effect before been rendered inactive via the liver. First pass metabolism can account for the dose differences between the same medications but different routes of admin- istration – please see the section on bioavailability.

This is the proportion of an administered dose which will reach the circulation unaltered, and therefore will be able to have an effect. The IV route ensures 100% bioavailability, but the oral route can be reduced by: Gastrointestinal contents and gastric retention time; pH: First pass effect. This will often mean that the dosages given for same medication is different if given IV or oral but the manufactures have already calculated this.

Morphine 10 mg IV = 30 mg oral

We will also explore other terms encountered when administrating medicines such as adverse drug reactions and drug interactions. An adverse drug reaction has been defined by the World Health Organization (2008) as ‘harmful and unintended reaction to a medicine’. Adverse drug reactions are always harmful.

Any medicines can cause a side effect. Some can be unintended such as drowsiness with codeine, but some side effects can be intended and in fact be beneficial. For example sedating antihistamines cause drowsiness as a side effect, but this can be used to aid sleep; another example is amitriptyline has the side effect of urinary retention but this can be used for noctur- nal enuresis.

The following sections are summary monographs for the commonly encountered medicines you may administer. All the following information should be reviewed with the latest edition of the British National Formulary and a copy of the Summary of Product Characteristics, these explain how medicines work. The monographs have also been constructed with the latest edition of

(2012).

Penicillin – Co-amoxiclav, Penicillin, Fluxcloxicillin

Licensed indication

Prescription only medicine (POM).

You should refer to the latest edition of the British National Formulary.

Pharmacodynamic

Penicillins are bactericidal (kill). They affect the bacterial cell wall synthesis.

Co-amoxiclav inhibit the synthesis of bacterial peptidoglycan; this weakens the cell wall; which is followed by death of the cell.

Pharmacokinetics

Generally are well absorbed when given orally. Penicillins cross the placenta and into breastmilk. There are trace amounts in breastmilk.

There are excreted in the urine (kidneys).

Contraindications

Penicillin hypersensitivity.

Rashes and anaphylaxis – which can be fatal.

Full details will be given in the summary of product characteristics (the data sheet) for each individual medicine.

The latest edition of the British National Formulary will also have a section on this. Co-amoxiclav is contraindicated with patients with jaundice or hepatic problems.

Fluxcloxicillin – should not be used in patients with hepatic dysfunction, caution with hepatic impairment.

Side effects

Include: nausea, diarrhoea, vomiting.

Broad spectrum penicillins can cause antibiotic-associated colitis.

Consideration for practice

Allergy status.

With or after food administration.

The prescribing of antibacterial medicines should follow your Trust antibacterial guidelines/ Public Health England.

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Macrolides, e.g. erythromycin

Licensed indication

Prescription only medicine (POM).

You should refer to the latest edition of the British National Formulary.

Pharmacodynamic

Macrolides inhibit bacterial protein synthesis. They bind to the 50s ribosomal subunits of susceptible organisms. Action can be bactericidal or bacteriostatic.

Pharmacokinetics

Usually given orally, clarithromycin and erythromycin can be given by intravenous infusion. Diffuse readily in to most tissue, but not across the blood brain barrier.

Care must be taken when these are prescribed in patients with hepatic or renal impairment. Azithromycin and clarithromycin – not suitable in pregnancy. Manufacturers advise only if no other alternatives; is present in breastmilk, use only if no other alternatives.

Erythromycin not known to be harmful in pregnancy and small amounts present in breastmilk.

Contraindications

Hypersensitivity.

Macrolides should be used in caution with patients with QT interval prolongation.

There are several important and potentially clinically significant interactions with macrolides including:

Antihistamines

Calcium channel blockers Lipid-regulating drugs and several more.

Side effects

Include: