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Transcript of Pharmacology
(Posner 2009) Clinical pharmacology is a broad subject. However it is helpful to understand it as having four components:
4. Therapeutics Pharmacodynamics the study of drug action on the body the study of the body's effect on the drug Pharmacokinetics As health professionals we become used to thinking about drugs in terms of:
duration of dosing
benefits and side effects
This is perfectly sensible in terms of everyday practice but makes no attempt to understand drugs' inter-relationships. (Posner 2009) this encompasses the mechanism of action and the end point Cell biology refresher Receptors Agonists Antagonists Absorption Distribution Metabolism Elimination factors affecting distribution: Pharmacogenomics http://www.whocc.no/atc/structure_and_principles/ Pharmacology - under the microscope 'Pharmacology is the science dealing with the interactions between a living system and chemicals introduced from outside the system'
(Jordan 2002) a drug may be defined as any small molecule that, when introduced into the body, alters body function by interactions at molecular level Pharmacology Aims &
learning outcomes Aim:
Improve knowledge and understanding of pharmacology to ensure safe and competent medicines management Pharmaceuticals Therapeutics the study of getting the drug in to the body There are two main issues: 1. compliance 2. drug formulation Compliance Compliance or concordance with medication is the extent to which clients adhere to prescribed regimes and associated professional advice. It is estimated that 40% of patients make major errors in compliance with only 1-5% complying exactly! What could be the issues in midwifery? general compliance issues Women in pregnancy who consider themselves to be healthy
fear of harming the unborn child
taking more than 3 drugs
more than 2 drug admins per day
reduced oesophageal motility e.g. dehydration, age Drug formulation storage requirements for each preparation depend on the formulation. There always check info sheet for each product packing chemicals liquids and solids all medicine sold or administered contain specified active ingredients plus other 'packing' chemicals, which may be there to stabilize the active ingredient or modify its release into the body The 'packing' chemical in a tablet can have clinical effects.
e.g. some preparations contain sodium or potassium ions Practice point: The sodium content of many antacid indigestion remedies may be enough to precipitate fluid retention and pulmonary oedema in pregnancy or in people with mild heart failure The formulation of a drug affects its rate of absorption. what else can impact getting drugs in to the body? 1. policy - how drugs are developed and distributed
2. communication - how we inform families about medications
3. psycho-social factors - family, personal history etc. This will cover: 1. Is the drug getting to the desired site of action?
2. Is the drug getting out of the body?
3. Is there a risk of accumulation and toxicity? Therapeutic range: Every drug has a therapeutic range. This is a desirable range for the concentration of a drug in blood plasma
above the therapeutic range toxic effects may appear
below the therapeutic range the drug does not have the desired effect For some drugs the therapeutic range is very narrow and the therapeutic concentration is very close to the concentration at which adverse effects appear: For some drugs the therapeutic range is very wide in most individuals, and there is a larger safety margin between therapeutic and toxic dose The concentration of any drug in the plasma and tissues depends on the way the drug is treated by the body Sites of administration 1. Oral
5. Intravenous injection or infusion
Eye drops Absorption is the process by which a drug is made available to the body fluids for distribution. The absorption of a drug will depend on:
1. the route of admission
2. the formulation as discussed earlier
3. the way the drug molecules move across cell membranes throughout the body. Oral absorption Most drugs are given orally because of convenience (and cost). All tablets and capsules should be swallowed with a full glass of water, with the recipient in an upright position (remaining so for 30min). remember pain, particularly labour pain, can reduce gut motility, delaying absorption of oral meds pregnancy reduces gut motility (due to increased progesterone and decreased motilin) delays the absorption of certain drugs from GI tract During pregnancy peripheral circulation is dilated which may enhance absorption of drugs given by subcutaneous or IM. practice points: intravenous absorption intramuscular absorption the IV route, using either central or peripheral lines, is used for the infusion of fluids and electrolytes, drug administration and parental nutrition. Drugs commonly given IV include: antimicrobials, oxytocin, tocolytics, anticonvulsants, heparin and anaesthetics practice points: Administration:
IV administration may be by continuous infusion, intermittent infusion or as bolus doses. Formulations are not interchangeable: a woman died when a 60min IV infusion of vancomycin was mistakinly administered as a bolus dose Continuous infusions:
Continuous IVI aims to establish and maintain a steady concentration of drug in the circulation, for example oxytocin. The drug is administered as a dilute solution to reduce irritation of the vein. However, it is important that the drug is compatible with the infusate. E.g. frusemide is incompatible with glucose/dextrose solutions intermittent infusion:
intermittent infusion may cause the concentration of the drug to peak and trough. I.e. fall above or below the therapeutic range. This could occur in women treated with iv antibiotics or heparin. Bolus doses:
An injection can be given directly into a vein or IV line.
Bolus doses must be given slowly most drugs need to be given over 1-3 mins. rapid drug administration can cause:
trauma to vein
a severe hypersensitivity response
serious side effects
pulmonary oedema, or embolisation if large volumes administered IV infusion is the fastest and most certain route of administration. A single bolus will produce a very high concentration of drug in blood plasma.
Quickly achieve therapeutic range
but toxicity a risk
All drug absorbed
doses can be titrated precisely to person's need distribution is the movement of the drug around the body. It is affected by:
1. plasma protein binding
2. the lipid solubility of the drug
3. the biding properties of the drug
4. blood flow to the organs and the state of circulation
5. stage of life cycle, pregnancy, old age, infancy
6. disease state most metabolism takes place in the liver. All drugs given orally must pass through the liver to reach the circulation. This is known as first pass metabolism.
drugs administered by other routes , not utilised by target cells will reach the liver after passing around the general circulation. These metabolites are then rendered soluble in water (conjugation) so they can be excreted by the kidneys liver metabolism depends on liver enzymes. The activity of the liver enzymes is affected by:
genetic make-up/familial tendancies
the liver's environment
liver impairment. This is likely to occur in women with malnutrition, circhrosis of the liver, heatitis, HELLP syndrome or in malnourished babies (neonates, especially preterm infants metabolise and eliminate drugs more slowly than adults). e.g. it can take a neonate 2-3 days to clear pethidine given in labour.
Breastfed infants are less able to metabolise caffiene creating an accumulation - making them irritable and unable to concentrate on feeding. (women should also be made aware that over the counter analgesics contain appreciable amounts of caffeine) Most drugs are dependent on the kidneys for excretion, but some drugs are excreted via the bile (e.g. corticosteroids and oestrogens). the kidney The functioning of the kidneys can be considered as 2 distinct processes:
1. Glomerular filtration rate
2. tubular secretion and re-absorption if GFR levels fall - the elimination of most drugs is impaired.
Causes of low GFR:
renal disorders (e.g. UTI, pre-eclampsia)
shock/ heart failure
NSAIDS practice point: GFR is often estimated from serum creatinine concentrations. In normal pregnancy, the concentration of serum creatinine falls, and any value over 70micromoles/l is indicative of renal compromise.
(this is particularly important to consider for women with pre-eclampsia or UTI)
GFR in neonates is only 30-40% of adults making drug elimination difficult Elimination half-life the elimination half-life for each drug is the time taken for the concentration of the drug in blood or plasma to fall to half its maximum value.
Knowledge of a drug's half-life is essential for planning dose regimens. Drugs are administered approximately every half life. Should drug administration deviate too much from this it could lead to ineffective treatment or toxicity drugs work as a result of physiochemical interactions between drug molecules and recipient's molecules
These chemical reactions may alter the way the cells are functioning which may alter the way tissues are functioning.
drugs modify existing functions, they can not introduce new functions
most drugs act on more than one type of cell and therefore have multiple effects on the body. some facts: Drug molecules work via: protein receptors in cell membranes or within cells
ion channels in cell membranes
enzymes in cells or extracellular fluid
non-specific actions many drugs work by acting on specific receptor proteins. these are components of the cell membrane which normally respond to the body's hormones and neuro-transmitters. Examples: opioid receptor, insulin receptors, dopamine receptors.
Some drugs imitate the bodies own properties. Some drugs are direct replacements. E.g. insulin and adrenalin. An agonist binds to a receptor site and alter it's functioning. agonists usually augment the normal functioning of the receptors. E.g. pethidine stimulates opioid receptors increasing analgesia, sedation and constipation. likewise beta agonists mimic actions of the sympathetic nervous system - increasing heart rate, dilating bronchioles and relaxing the uterus. An antagonist will bind to a receptor and block the receptor to prevent it working. For example naloxone blocks opioid receptors and reverses the actions of pethidine - reducing analgesia and sedation. tolerance:
when a drug is administered over a long time the cells or their receptors may adapt to the drug. the continued presence of a drug may reduce the number of receptors available for it to act. this down regulation of receptors is believed to be responsible for the tolerance seen with continued use of opiates or beta2 agonists Ion channels: Enzymes: Ion channels are similar to receptors in the way that they bind to certain drugs. examples include calcium antagonists (nifedipine) and local anaesthetics such as lignocaine. However, because ion channels are present in a wide variety of cells or tissues, the side effects of these drugs can affect several body systems. E.g. local anaesthetics affect both nerve and muscles. Enzymes are present in all cells, catalysing their vital biochemical reactions. some drugs bind to enzymes and inhibit their actions. examples incluse NSAIDS (non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen). It is likely that these drugs interact with certain enzymes by virtue of their shape and structure - similar to drug-receptor interaction. group work: Law,
medicines and the midwife: Accountability: The Profession:
NMC - medicines management/ rules and standards/code
Midwives have legal binding contracts with their employer. Employers have vicarious liability for any tort committed by an employee.
A mother/child who feels they have been harmed by a midwives actions can seek redress through our civil court system.
We are all accountable to society through criminal law. A midwife who breaks the law is as liable to prosecution as ny other person. The tatutes concernedwith the regulation of medicine, such as theMedicines Act 1968 and the Misuse of Drugs Act 1971 carry criminal penalties if breached.
controlled drugs student midwives: general sales list drugs:
This type of drug may be sold through a variety of outlets without need for registered pharmacist
Can only be purchased under the supervision of a pharmacist e.g. ranitidine, piriton.
This can only be obtained from a registered pharmacist by prescription from a registered doctor, dentist, eligble nurse, midwife or health visitor. Not normally supplied unless prescription issued from an appropriate practitioner. this is regulated by EU directive.
Medicines Act 1968 bestows prescribing authority to registered medicl practitioners, dentists and vets who are able to issue prescriptions from their relevant formularies the law changes in cell physiology Even if the drug is working on cells, there may be no noticeable external response. That is, no measurable response. clinical effects: Clinical response shows considerable individual variation. This is not always predictable. E.g. some women are sensitive to oxytocic drugs and therefore infusions are commenced using very low doses. Clinical effects depend on:
genetic make-up side effects: Side effects are adverse reactions that occur within the normal range of therapeutic doses. most drugs have potential side-effects. These can be grouped under the following headings:
1. related to the drug's main actions
2. unrelated to the drugs main actions:
- related to subsidary actions
- hypersensitivity responses
- cell damage analgesics anaesthetics anti-hypertensive anti-coagulant antibiotic let's explore some common maternity drugs together