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MBBS - Y1 > Week 7 - pharmacology and patient safety > Flashcards

Week 7 - pharmacology and patient safety Flashcards

1
Q

Explain how hormones are selective in which cells they interact with and affect. (LO1)

A
  • Hormones only affect cells that possess the necessary receptors.
  • Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialised cells.
  • E.g. thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body.
  • Cells also possess receptors for different types of hormones.
  • The sensitivity and response of a cell to a particular hormone is determined by the number of receptors for the hormone.
  • The number of receptors that respond to a hormone can change over time, resulting in a fluctuation of sensitivity.
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2
Q

What is meant by upregulation with regards to hormone sensitivity? (LO1)

A
  • Usually in response to rising hormone levels.
  • The number of receptors to the hormone on the cell surface increases.
  • Cell has increased sensitivity to the hormone.
  • Increased cellular activity.
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3
Q

What is meant by downregulation with regards to hormone sensitivity? (LO1)

A
  • Usually in response to rising hormone levels.
  • The number of receptors to the hormone on the cell surface decreases.
  • Cell has decreased sensitivity to the hormone.
  • Reduced cellular activity.
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4
Q

What are direct-acting hormones? Give some examples. (LO1)

A
  • Lipid-derived (soluble) hormones.

Examples:

  • Steroid hormones.
  • Vitamin D.
  • Thyroxine.
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5
Q

How do direct-acting hormones work? (LO1)

A
  • The hormone diffuses into the cytoplasm and either:
    A) binds to intracellular receptor and the hormone receptor complex relocates to the nucleus (e.g. glucocorticoids).
    B) or, relocates to the nucleus and then binds to the receptor in the nucleus (e.g. oestrogen, androgens, thyroid hormones).
  • The hormone receptor complex binds to hormone response elements on the DNA.
  • The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes.
  • This, in turn, determines the amount of corresponding protein that is synthesised by altering gene expression.
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6
Q

What are indirect-acting hormones? (LO1)

A
  • Non-lipid soluble hormones (amino acid or polypeptide-derived).
  • These cannot directly act upon DNA.
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7
Q

List some classes of receptors that indirect-acting hormones interact with. (LO1)

A
  • G-protein coupled receptors (GPCR).
  • Receptor tyrosine kinases (RTK).
  • Guanylyl cyclase receptors.
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8
Q

Describe the basic structure of a G-protein coupled receptor (GPCR). (LO1)

A
  • Made up of 3 subunits: α, β and γ.
  • When no hormone is bound, the GPCR is inactive and the α-subunit is bound to guanosine diphosphate (GDP).
  • When a hormone binds to the receptor, the receptor conformation changes, allowing guanosine triphosphate (GTP) to bind.
  • After binding, GTP is hydrolysed by the GPCR into GDP and becomes inactive.
  • The α-subunit will then dissociate and bind to another effector protein (cAMP, calcium ion channel or PLC).
  • GPCRs are named according to the alpha subunit: Gₛ, Gᵢ, Gq.
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9
Q

Describe the function of the Gs subtype of GPCR. Give some examples. (LO1)

A
  • Stimulates adenylate cyclase.
  • This increases cAMP.
  • Leads to activation of protein kinase A.

Examples:

  • Beta-1 receptors - adrenaline, noradrenaline.
  • Beta-2 receptors - adrenaline, salbutamol.
  • H2 receptors - histamine.
  • D1 receptors - dopamine.
  • V2 receptors - vasopressin.
  • Receptors for ACTH, LH, FSH, PTH, glucagon, calcitonin and prostaglandins.
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10
Q

Describe the function of the Gi subtype of GPCR. Give some examples. (LO1)

A
  • Inhibites adenylate cyclase.
  • This decreases cAMP.
  • Leads to inhibition of protein kinase A.

Examples:

  • M2 receptors - acetylcholine.
  • Alpha-2 receptors - adrenaline, noradrenaline.
  • D2 receptors - dopamine.
  • GABA-B receptor.
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11
Q

Describe the function of the Gq subtype of GPCR. Give some examples. (LO1)

A
  • Activates phospholipase C.
  • Splits PIP₂ into IP₃ and DAG.
  • Leads to activation of protein kinase C.

Examples:

  • Alpha-1 receptors - adrenaline, noradrenaline.
  • H1 receptors - histamine.
  • V1 receptors - vasopressin.
  • M1, M3 receptors - acetylcholine.
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12
Q

Describe GPCR α-subunit interactions with cAMP. (LO1)

A
  • The α-subunit of the activated G-protein dissociates, binds to and activates a membrane-bound enzyme called adenylyl cyclase.
  • Adenylyl cyclase catalyses the conversion of ATP to cAMP.
  • cAMP activates protein kinases.
  • Protein kinases transfer a phosphate group from ATP to a substrate molecule during phosphorylation.
  • The phosphorylation of a substrate molecule changes its structural orientation, thereby activating it.
  • These activated molecules can mediate changes in cellular processes.
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13
Q

Describe how the effect of a hormone is amplified when a GPCR α-subunit interacts with cAMP. (LO1)

A
  • As the signalling process progresses, the hormone’s effects are amplified.
  • The binding of the hormone at a single receptor causes the activation of MANY GPCRs which activates adenylyl cyclase.
  • Each molecule of adenylyl cyclase then triggers the formation of MANY cAMP molecules.
  • Once activated by cAMP, protein kinases can catalyse MANY reactions.

In this way, a small amount of hormone can trigger the formation of a large amount of cellular product.

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14
Q

Describe the role of phosphodiesterase (PDE). (LO1)

A
  • When a GPCR α-subunit interacts with cAMP due to the presence of a hormone, an amplification process is started.
  • To stop hormone activity, cAMP is deactivated by the cytoplasmic enzyme phosphodiesterase (PDE).
  • PDE is always present in the cell and breaks down cAMP to control hormone activity, preventing overproduction of cellular production - e.g. glucagon.
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15
Q

Describe GPCR α-subunit interactions with phospholipase C (PLC). (LO1)

A
  • The α-subunit binds to PLC.
  • This converts PIP₂ into IP₃ and diacylglycerol (DAG).
  • IP₃ and DAG regulate the activity of enzymes.
  • IP₃ releases calcium ions from the endoplasmic reticulum and opens calcium channels in the plasma membrane.
  • DAG activates protein kinase C which phosphorylates other proteins and activates them - e.g. adrenaline.
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16
Q

Describe the function of IP₃. (LO1)

A

IP₃ releases calcium ions from the endoplasmic reticulum and opens calcium channels in the plasma membrane.

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17
Q

Describe the function of DAG. (LO1)

A

DAG activates protein kinase C which phosphorylates other proteins and activates them - e.g. adrenaline.

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18
Q

Describe GPCR α-subunit interactions with calcium channels. (LO1)

A
  • Here, the calcium channels act as molecular switches inside the cell - e.g. adrenaline.
  • The α-subunit binds to a calcium channel, causing it to open.
  • Calcium ions move into the cell, leading to an increase in intracellular mediators.
  • When the α-subunit hydrolyses the attached GTP to GDP, the α-subunit will dissociate from the calcium channel, closing it so no more calcium ions move into the cell.
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19
Q

Describe the function of receptor tyrose kinases (RTK). (LO1)

A
  • These are enzyme-linked receptors.
  • RTKs phosphorylate tyrosine to allow signal transmission to other parts of the cell.
  • The phosphorylated receptors act as a docking platform for their proteins that contain special types of binding domains.
  • RTKs play an important role in growth factors, signalling molecules that promote cell division and survival - e.g. platelet-derived growth factor (PDGF), nerve growth factor (NGF), insulin, epidermal growth factor.
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20
Q

Describe the function of guanylyl cyclase receptors. (LO1)

A
  • These contain intrinsic enzyme activity.
  • The hormone binds to the receptor linked to guanylyl cyclase (GC), causing a conformational change of the receptor.
  • This leads to the conversion of guanosine triphosphate (GTP) into cytoguanosine monophosphate (cGMP).
  • The cGMP activates protein kinases and these then phosphorylate other proteins to activate them.
  • E.g. atrial natriuretic factor, brain natriuretic factor.
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21
Q

Define what is meant by lipids. (LO2)

A
  • This is collective name for all fats and fat-like substances.
  • These are water-insoluble but dissolve in organic solvents like alcohol.
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22
Q

List the five types of lipids. (LO2)

A
  • Fatty acids.
  • Triglycerides (fats and oils).
  • Glycerophospholipids (membrane lipids).
  • Sphingolipids (membrane lipids).
  • Cholesterol.
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23
Q

Describe fatty acids. (LO2)

A
  • Between 14-24 carbon atoms.
  • Most common have 16-18 carbon atoms.
  • Unsaturated fatty acids contain double bonds.
  • Most unsaturated fatty acids are in cis-configuration.
  • In cis, the functional groups are on the same side.
  • In trans, the functional groups are on opposite sides.
  • Fatty acids are described by the number of carbon atoms and the number of double bonds in them.
  • E.g. Palmitic acid is C16:0 - this means 16 carbon atoms and 0 double bonds.
  • Most fatty acids have an even number of carbon atoms.
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24
Q

Explain how the melting points of fatty acids vary. (LO2)

A
  • Saturated fatty acids have a higher melting point and it increases with the length of the molecule.
  • Unsaturated fatty acids have lower melting points than saturated fatty acids of the same length.
  • For unsaturated fatty acids of the same length, the melting point decreases with the number of double bonds.
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25
Q

What is the difference between saturated and unsaturated fatty acids? (LO2)

A
  • Saturated fatty acids don’t have any double bonds.
  • Unsaturated fatty acids have double bonds.

To make it easier to remember:
When double bonds are introduced, there are fewer hydrogen atoms.
Saturated basically means that the molecule is saturated with hydrogen atoms so it must not have any double bonds.

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26
Q

Why do saturated fatty acids have a higher melting point than unsaturated fatty acids? (LO2)

A

They have a higher melting point because the molecule has the ability to closely pack with other molecules of this nature (due to the lack of double bonds) and forms intermolecular interactions which require a lot of energy to break.

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27
Q

What is linoleic acid? (LO2)

A
  • Vitamin F.
  • An essential fatty acid that the human body cannot synthesise.
  • Must be taken up with food.
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28
Q

What is arachidonic acid? (LO2)

A
  • Can be synthesised from linoleic acid so it’s not an essential fatty acid.
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29
Q

How can omega-6 be obtained from our diet? (LO2)

A

Omega-6 is present in:

  • Vegetable oil.
  • Seeds.
  • Soy bean.
  • Canola oil.
  • Fish oil - fatty fish like salmon and sardines.
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30
Q

What are prostaglandins, thromboxanes and leukotrienes? (LO2)

A
  • These are all inflammatory mediators.
  • Their precursor is fatty acids.
  • Prostaglandins are technically hormones and have a variety of functions in the body.
  • Leukotrienes are powerful constrictor of bronchial and intestinal smooth muscle. They also increase the permeability of capillaries.
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31
Q

How are prostaglandins and leukotrienes produced from fatty acids? (LO2)

A
  • Linoleic acid is converted to eicosatreinoic acid.
  • Eicosatreinoic acid is the precursor for prostaglandins F1 and F1-α (PGF₁ and PGF₁α).
  • Eicosatreinoic acid is further converted to arachidonic acid which is the precursor for leukotrienes and other prostaglandins - e.g. PGE₂α, PGF₂, PGD₂, PGI₂ (prostacyclin), TXA₂.
  • Alternatively, linoleic acid is converted to eicosapentaenoic acid which is the precursor for prostaglandins, PGE₃ and PGF₃α.
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32
Q

Describe the transport and storage of triglycerides. (LO2)

A
  • Triglycerides are not absorbed as whole molecules by adipocytes. They are broken up before they’re taken up.
  • Triglycerides from the liver are transported by very low density lipoproteins (VLDL) to the adipocytes. Lipoprotein lipase splits triglycerides to fatty acids and glycerol.
  • Fatty acids are taken up into the fat cells and activated to form acyl-CoA.
  • The glycerol comes from glucose so glucose is taken up by the fat cells and metabolised to glycerol-3-phosphate.
  • Glycerol-3-phosphate and 3 molecules of acyl-CoA join together to form one molecule of triglyceride.
  • In the event that the body needs energy, stored triglycerides are remobilised. A hormone-sensitive lipase enzyme splits the triglyceride into glycerol and fatty acids.
  • The fatty acids are released into the blood and are transported around the body in the form of fatty acid-albumin complex.
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33
Q

Describe the structure of glycerophospholipids. (LO2)

A
  • In glycerophospholipids, the central glycerol molecule is linked to two fatty acid molecules and via a phosphate group to an alcohol.
  • Main components of cell membranes.
  • They are amphiphilic - have hydrophilic and hydrophobic parts.
  • The fatty acids are the hydrophic parts.
  • The phosphate and alcohol groups are the hydrophilic regions.
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34
Q

Describe the generic chemical structure of glycerophospholipids. (LO2)

A
  • Two hydroxyl groups off the central glycerol are esterified with fatty acids.
  • The third hydroxyl group is esterified by phosphoric acid which is further esterified by an alcohol.
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35
Q

If the alcohol in a glycerophospholipid is ethanolamine, what is the molecule known as? (LO2)

A

Phosphatidylethanolamine.

  • Membranes contain around 13-35% of this.
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36
Q

If the alcohol in a glycerophospholipid is choline, what is the molecule known as? (LO2)

A

Phosphtidylcholine.

  • A.k.a lecithin.
  • Membranes contain around 39-58% of this.
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37
Q

If the alcohol in a glycerophospholipid is the amino acid, serine, what is the molecule known as? (LO2)

A

Phosphatidylserine.

  • Membranes contain around 1-9% of this.
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38
Q

If the alcohol in a glycerophospholipid is the sugar, inositol, what is the molecule known as? (LO2)

A

Phosphatidylinositol.

  • Membranes contain around 5-12% of this.
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39
Q

List the enzymes involved in the cleavage and resorption of glycerophospholipids and their function. (LO2)

A
  1. Phospholipase A₁ - cleaves off the fatty acid at position 1, producing 1-acyl-lisophospholipid.
  2. Phospholipase A₂ - cleaves off the fatty acid at position 2, producing 2-acyl-lisophospholipid.
  3. Phospholipase C - cleaves off the phosphorylated alcohol, producing 1,2-diacylglycerol.
  4. Phospholipase D - cleaves off the alcohol, producing phosphatidic acid.
  5. By the action of all four phospholipases, glycerophospholipases are broken down into glycerol, fatty acids, phosphates and alcohol.
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40
Q

Describe the cleavage and resorption of glycerophospholipids. (LO2)

A
  • Resorption of dietary glycerophospholipids takes place in the digestive tract.
  • Before glycerophospholipids can be resorbed, they need to be cleaved into their building blocks by phospholipases of the pancreas.
  • By the action of all four phospholipases, glycerophospholipids are broken down into glycerol, fatty acids, phosphates and alcohol.
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41
Q

What are sphingolipids? (LO2)

A
  • Components of cell membranes.
  • There are amphiphilic (contain both hydrophobic and hydrophilic parts).
  • There are two main sphingolipids:
    1. Sphingomyelin.
    2. Glycolipids.
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42
Q

Describe the structure of sphingomyelin. (LO2)

A
  • The central long chain amino alcohol, sphingosine, is linked to one fatty acid molecule and two phosphocholine molecules.
  • The fatty acid and part of the sphingosine are hydrophobic parts.
  • Phosphocholine is hydrophilic.
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43
Q

Describe the structure of glycolipids. (LO2)

A
  • The central sphingosine is linked to one fatty acid molecule and two sugars.
  • The fatty acid and part of the sphingosine are hydrophobic parts.
  • The sugars are hydrophilic.
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44
Q

Describe the generic chemical structure of sphingolipids. (LO2)

A
  • The central sphingosine is an 18 carbon amino alcohol with an unsaturated hydrocarbon chain.
  • The amine group is esterified to a fatty acid.
  • The hydrocarbon chain and the fatty acid anchor the sphingosine molecule in lipid membranes.
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45
Q

If the hydroxyl group in a spingolipid is not esterified, what is the sphingolipid then known as? (LO2)

A

Ceramide.

  • Important intermediate in the metabolism of sphingolipids.
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46
Q

If the hydroxyl group in a spingolipid is esterified to phosphorylcholine, what is the sphingolipid then known as? (LO2)

A

Sphingomyelin.

  • They make up approximately 1-20% of membrane lipids.
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47
Q

If the hydroxyl group in a sphingolipid is esterified to a sugar, what is the sphingolipid then known as? (LO2)

A

Cerebroside.

  • The most common cerebrosides are glucocerebrosides and galactocerebrosides.
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48
Q

What are gangliosides? What is their function? (LO2)

A
  • These are the most complex sphingolipids.
  • They contain oligosaccharide groups with one or more sialic acids (Glc-Gla-NANA).
  • Gangliosides have many functions, including cell-cell recognition, as receptors for baterial toxins, e.g. cholera toxin, and as receptors for certain pituitary glycoprotein hormones.
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49
Q

Describe the degradation of sphingolipids. (LO2)

A
  • The degradation of sphingolipids occurs in the lysosomes by exoglycosidase.
  • Deficiency of any of these enzymes leads to an accumulation of substrate in the lysosome.
  • Ganglioside M1 and globoside are both eventually converted into lactosyl ceramide as a final product.
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50
Q

List the enzymes involved in the degradation of sphingolipids and their function. (LO2)

A

Ganglioside degradation:

  1. GM1-β-galactosidase - converts ganglioside GM1 into ganglioside GM2.
  2. Hexosaminidase A - converts ganglioside GM2 into ganglioside GM3.
  3. Ganglioside neuraminidase converts ganglioside GM3 into lactosyl ceramide.

Globoside degradation:

  1. Hexosaminidase A+B - converts globoside into trihexosylceramide.
  2. α-galactosidase A - converts trihexosylceramide into lactosyl ceramide.
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51
Q

What is it known as when there is a defiency of the enzymes involved in the degradation of the sphingolipids? (LO2)

A

Resulting diseases are called lipid-storage diseases or sphingolipidoses. These are genetic.

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52
Q

What disease occurs when GM1-β-galactosidase is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

GM1 gangliodosis.

Features:

  • Mental retardation.
  • Liver enlargement.
  • Skeletal involvement.
  • Death by age 2.
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53
Q

What disease occurs when hexosaminidase A is dysfunctional/deficient? What are the features of this disease?(LO2)

Note: lipid-storage disease.

A

Tay-Sachs disease.

Features:

  • Mental retardation.
  • Blindness.
  • Death by age 3.
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54
Q

What disease occurs when hexosaminidase A and B are both dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Sandhoff’s disease.

Features:

  • Similar to Tay-Sachs but more rapidly progressing.
  • Mental retardation.
  • Blindness.
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55
Q

What disease occurs when α-galactosidase A is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Fabry’s disease.

Features:

  • Skin rash.
  • Kidney failure.
  • Pain in lower extremities.
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56
Q

Why is no disease associated with the dysfunction/deficiency of ganglioside neuraminidase? (LO2)

Note: lipid-storage disease.

A

No genetic disorder is known for the dysfunction of ganglioside neuraminidase because this enzyme is so essential that any foetus with a deficiency of it wouldn’t survive.

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57
Q

List the enzymes involved in the degradation of lactosyl ceramide, sphingomyelin and sulfatide and their function. (LO2)

A

Lactosyl ceramide:

  1. β-galactosidase - converts lactosyl ceramide
  2. Glucocerebrosidase - converts glucocerebroside to ceramide.

Sphingomyelin:
1. Sphingomyelinase - converts sphingomyelin to ceramide.

Sulfatide:

  1. Arylsulfatase A - converts sulfatide to galactocerebroside.
  2. Galactocerebrosidase - converts galactocerebroside to ceramide.

All three products above are converted to ceramide which is further degraded to fatty acids:
1. Ceramidase - converts ceramide to fatty acids.

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58
Q

What disease occurs when glucocerebrosidase is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Gaucher’s disease.

Features:

  • Liver and spleen enlargement.
  • Erosion of long bones.
  • Mental retardation in infantile form only.
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59
Q

What disease occurs when sphingomyelinase is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Neimann-Park disease.

Features:

  • Liver and spleen enlargement.
  • Mental retardation.
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60
Q

What disease occurs when arylsulfatase A is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Sulfatide lipidosis.

Features:

  • Mental retardation.
  • Death in first decade.
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61
Q

What disease occurs when galactocerebrosidase is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Krabbe’s disease.

Features:

  • Loss of myelin.
  • Mental retardation.
  • Death by age 2.
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62
Q

What disease occurs when ceramidase is dysfunctional/deficient? What are the features of this disease? (LO2)

Note: lipid-storage disease.

A

Farber’s lipogranulomatosis.

Features:

  • Painful and progressive deformed joints.
  • Skin nodules.
  • Death within a few years.
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63
Q

Why is no disease associated with the dysfunction/deficiency of β-galactosidase? (LO2)

Note: lipid-storage disease.

A

There is no genetic disorder known for when β-galactosidase is affected because this enzyme seems to be so essential that a foetus with a dysfunction/deficiency of it would not survive.

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64
Q

When these lipid degradation enzymes are dysfunctional, why does the accumulation of substrates cause lipid-storage diseases? (LO2)

A
  • Because the unmetabolised sphingolipids accumulate to toxic levels that affects the function of nerve cells and other cells.
  • The most common disease is Tay-Sachs disease - 1:300.
  • There is no cure for lipid-storage diseases but Gaucher’s and Fabry’s disease can be treated with enzyme replacement therapy.
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65
Q

Describe the structure of cholesterol. (LO2)

A
  • Consists of a condensed 4-ring system, also known as a steroid ring system.
  • Almost the whole cholesterol molecule is hydrophobic.
  • Only the hydroxyl group is the hydrophilic part of the molecule.
  • This makes it weakly amphiphilic.
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66
Q

List the sources of cholesterol. (LO2)

A

Dietary intake:

  • 300mg/day.
  • Can vary with different diets.

Endogenous synthesis:
- 1000mg/day.

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67
Q

Where in the body is cholesterol mainly synthesised? (LO2)

A

All cells are capable of synthesising cholesterol but the main sites are the liver and intestines.

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68
Q

Cholesterol acts as a precursor for other molecules. List some of these. (LO2)

A
  • Bile acids - glycocholate (most common bile salt).
  • Vitamin D3.
  • Glucocorticoids - cortisol, produced from cholesterol by the adrenocortex. Glucorticoids support gluconeogenesis and glycogen production.
  • Mineralocorticoids - aldosterone, produced from cholesterol by the adrenocortex. Mineralocorticoids increase the resorption of sodium chloride and bicarbonate in the kidneys.
  • Androgens - testosterone, by the testis.
  • Progestogens - progesterone, by the yellow body of the corpus luteum.
  • Oestrogens - estrone, by the ovaries.
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69
Q

Describe the metabolism of fatty acids. (LO2)

A
  • Fatty acids can be broken down to acetyl-CoA by a process called β-oxidation.
  • Acetyl-CoA is the building block for synthesis of cholesterol.
  • Glucose can be broken down to acetyl-CoA via glycolysis which can then be used to synthesise fatty acids.
  • Glucose can also be broken down to glycerol which, in combination with fatty acids, can form the triglycerides and glycerophospholipids.
  • The fatty acid, palmitate, is a precursor for sphingosine, which alone with a second fatty acid, can form ceramides and sphingolipids.
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70
Q

What is nicotine? (LO3)

A
  • A naturally occurring plant alkaloid.
  • Found primarily in solanoceous plants - potato, tomato, green pepper, tobacco.
  • Principle source is tobacco and replacement therapies, e.g. nicotine patch, nicotine gum.
  • Structure: 1-methyl-2,3-pyridyl-pyrrolidine.
  • Pure nicotine is a clear liquid with a characteristic odour but it turns brown on exposure to air.
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71
Q

List the sites of absorption for nicotine. (LO3)

A
  • Can be absorbed through:
    1. Oral cavity (absorption is poor).
    2. Skin.
    3. Lung.
    4. Urinary bladder.
    5. GI tract (absorption is poor due to the acidic nature of the stomach).
72
Q

How does pH affect the absorption of nicotine? (LO3)

A
  • Nicotine is a weak base (pKA=8).
  • Absorption through the mucous membranes is pH dependent.
  • Increased absorption in alkaline conditions as the pH increases.
  • Main absorption is through the lungs - alveolar pH is 7.4.
  • At a pH of 7.4, 31% of nicotine from cigarette smoke (pH8.5) is uncharged and easily crosses the alveolar membrane into the blood vessels.
73
Q

Describe the metabolism of nicotine. (LO3)

A
  • Occurs in the liver within 1-2 hours.
  • In most people, 70-80% is metabolised into cotinine, an inactive metabolite.
  • 50% of excreted nicotine is through urine, the rest through faeces, bile, saliva and sweat.
74
Q

List the effects of nicotine at a whole organism level. (LO3)

A
  • Increased heart rate.
  • Increased cardiac contractility.
  • Increased blood pressure.
  • Decreased skin temperature.
  • Mobilisation of blood sugar.
  • Increased free fatty acids (FFA) in blood.
  • Increased catecholamine level in the blood.
  • Arousal or relaxation.
75
Q

List the effects of nicotine at a cellular level. (LO3)

A
  • Increased synthesis and release of hormones.
  • Activation of tyrosine hydroxylase enzyme (rate-limiting enzyme in catecholamine biosynthesis).
  • Activation of several transcription factors.
  • Induction of heat shock proteins.
  • Induction of oxidative stress.
  • Effects of apoptosis.
  • Induction of chromosome aberrations.
  • Induction of sister chromatid exchange.
76
Q

List the effects of nicotine on the nervous system. (LO3)

A
  • Inhibition of the parasympathetic nervous system.

- Activation of the sympathetic nervous system.

77
Q

List the peripheral effects of nicotine. (LO3)

A
  • Sweating.
  • Reduced GI motility.
  • Increased heart rate, cardiac output and arterial pressure.
  • Results from the stimulation of autonomic ganglia and peripheral sensory receptors - mainly in the heart and lungs.
78
Q

What are cholinergic receptors? (LO3)

A
  • There are two types:
    1. Nicotinic (nAchR).
    2. Muscarinic (mAchR).
  • The cholinergic receptor has several subunits (α, β, γ, δ).
  • The α-subunit is a transmembrane domain with 4 transmembrane regions.
79
Q

List the types of nicotinic receptors (nAchR) and state where they are found. (LO3)

A

There are two types:

  1. Nm - receptors found at neuromuscular junctions.
  2. Nn - receptors found in autonomic ganglia, adrenal glands and CNS.
80
Q

Which receptors does nicotine interact with? (LO3)

A

Nicotine acts on Nn receptors:

  • (α4)(β2)3 in the brain (the cortex and hippocampus- plays a role in cognitive function).
  • (α3)2(β4)3 in the autonomic ganglia.
  • (α1)2(β1)(δ)E in the muscles.
81
Q

Describe the pathophysiology of smoking. (LO3)

A
  • Dependence.
  • Increased risk of:
    1. Coronary heart disease - myocardial infarction (MI).
    2. Peripheral vascular disease (hypertension).
    3. Lung cancer (carcinogens, tar and carbon monoxide).
    4. COPD - chronic bronchitis, emphysema.
    5. Abnormal foetal development (low birth weight).
82
Q

Describe ethanol metabolism (LO3)

A
  • Ethanol is first metabolised by alcohol dehydrogenase into acetaldehyde.
  • Acetaldehyde is then metabolised by acetaldehyde dehydrogenase into acetic acid.
  • Rapidly absorbed in the stomach.
  • 90% of ethanol is metabolised, only 5-10% is excreted unchanged in expired air/urine - this is the basis of police breathalyser test/urine alcohol test.
  • Ethanol is metabolised in the liver.
83
Q

List the effects of ethanol on the body. (LO3)

A

Cardiovascular:
- Cutaneous vasodilation. This is a warming feeling but an increase in heat loss due to vasodilation. Could lead to hypothermia.
Endocrine:
- Diuresis. Feeling the need to pee due to inhibition of anti-diuretic hormone (ADH).
Gastrointestinal:
- Increased salivation and gastric secretions.
Liver:
- Most serious long-term complications.
- Increased fat accumulation leads to hepatitis, cirrhosis, and hepatic necrosis + fibrosis.
Lipid metabolism, platelet function, atherosclerosis:
- Esterification of fatty acid into fats which accumulate in the liver.
- Decreased platelet aggregation.
- Risk of atherosclerosis with excessive consumption.
Foetal development:
- Foetal alcohol syndrome (FAS).
- Alcohol-related neurodevelopmental disorder (ARND).

84
Q

Define fibrosis. (LO3)

A

The development of fibrous connective tissue as a reparative response to injury or damage.

85
Q

What is the effect of ethanol on the CNS? (LO3)

A

This effect can be split into two subtypes:

  • Acute intoxication effects.
  • Chronic intoxication effects.
86
Q

List the acute intoxication effects of alcohol on the CNS. (LO3)

A
  • Slurred speech.
  • Motor incoordination.
  • Increased self-confidence.
  • Lack of inhibition (behavioural).
  • Euphoria.
  • Effect on mood can vary: loud and outgoing or morose and withdrawn.
  • Intellectual and motor performance and sensory discrimination all impaired.
87
Q

List the chronic intoxication effects of alcohol on the CNS. (LO3)

A
  • Irreversible neurological damage (dementia, peripheral neuropathy).
  • May be due to ethanol, but also metabolites (acetaldehyde, fatty acid esters).
  • Some effects due to thiamine deficiency.
88
Q

Describe the mechanism of alcohol on the CNS.

A
  • General depressant effects.
  • Enhancement of GABA-mediated inhibition, similar to the action of benzodiazepines (but the effect of alcohol is smaller and less significant).
  • Benzidiazepine antagonists (flumazenil), can reduce the depressive effects of alcohol intoxication.
  • Flumazenil, however, cannot be used in alcohol dependence, since its side effect increases risk of seizures.
  • Alcohol inhibits transmitter release in response to nerve terminal depolarisation by inhibiting the voltage-dependent calcium channels in the neurons (calcium is required for extravasation of neurotransmitter vesicles).
89
Q

Describe the pathophysiology of alcohol. (LO3)

A
  • Dependence.
  • Increased risk of:
    1. CNS atrophy.
    2. Cardiomyopathy.
    3. Peptic ulcers.
    4. Pancreatitis.
    5. Liver damage (cirrhosis and hepatocellular carcinoma/liver cancer).
    6. Varices.
    7. Testicular atrophy.
90
Q

How much alcohol is required to be consumed for mild, severe and fatal intoxication? (LO3)

A
  • Mild intoxication: plasma concentration of 46mg/100mL.
  • Severe intoxication: plasma concentration of 150mg/100mL.
  • Lethal: plasma concentration of 500mg/100mL.

500mg/100mL can cause respiratory failure at this concentration.

91
Q

How do we convert alcohol into units? (LO3)

A

1 unit = 8g ethanol:

  • Half pint.
  • 1 shot of spirits.
  • 1 glass of wine.

Calculation:
units = (strength (ABV) x volume (ml))/1000

  • Alcohol content in drinks varies from 2.5% (weak beer) to 55% (strong spirit).
92
Q

What is the recommended intake for alcohol? How much is classified as binge drinking? (LO3)

A
  • 2-3 units/day or 14 units/week.
  • Binge drinking: >8 units/day.
  • 25% of men exceed the daily recommended limit.
  • 7% of women exceed the daily recommended limit.
  • The average per capita consumption in the UK is 8L/year.
93
Q

Define what is meant by a medical error. (LO4)

A

Any preventable event that may lead to inappropriate medication use or patient harm while the medication is in the control of the health-care professional or the patient.

94
Q

List some system contributions to medical errors (9). (LO4)

A
  • Working hours of prescribers and others.
  • Patient throughput.
  • Professional support and supervision by colleagues.
  • Availability of information (medical records).
  • Design of prescription forms.
  • Distractions.
  • Availability of decision support.
  • Checking routine (e.g. clinical pharmacy).
  • Reporting and reviewing of accidents.
95
Q

List some user contributions to medical errors (12). (LO4)

A

Prescriber knowledge:

  • Clinical pharmacology principles.
  • Drugs in common use.
  • Therapeutic problems commonly encountered.
  • Knowledge of workplace systems.

Skills:

  • Taking a good drug history.
  • Obtaining information to support prescribing.
  • Communicating with patients.
  • Numeracy and calculations.
  • Prescription writing.

Attitude:

  • Coping with risk of uncertainty.
  • Monitoring of prescribing.
  • Checking routines.
96
Q

What is the response to the medical error? (LO4)

A
  1. Protect the patient’s safety.
  2. Clinical review and the taking of any steps that will reduce harm: remedial treatment, monitoring, recording the event in notes, informing colleagues.
  3. Patients should be informed if they have been exposed to potential harms.
  4. For errors that do not reach the patient, it is the prescriber’s duty report them so that others can learn from the experience and take the opportunity to reflect on how a similar incident might be avoided in the future.
97
Q

What is meant by an unintended action with regards to prescribing? (LO4)

A
  • The correct plan is known but not executed.
  • Causes include workload, time pressures, distractions.
  • This could be a slip or a lapse.
98
Q

What is meant by a slip with regards to prescribing? (LO4)

A
  • The prescription is not as intended.
  • The prescriber fails to complete the prescription correctly.
  • Prescriber unaware.
  • E.g. writes the dose in ‘mg’ instead of ‘micrograms’.
99
Q

What is meant by a lapse with regards to prescribing? (LO4)

A
  • Prescription incomplete or forgotten.
  • The prescriber forgets part of the action that important for success.
  • Prescriber may remember.
  • E.g. forgets to prescribe the folic acid with methotrexate.
100
Q

What is meant by an unintended action with regards to prescribing? (LO4)

A
  • The wrong plan is selected.

- Causes include poor training and lack of experience.

101
Q

What is meant by a mistake with regards to prescribing? (LO4)

A
  • The prescription is as intended but written based on the wrong principles or lack of knowledge.
  • Prescriber unaware.
  • E.g. prescribes atenolol for a patient with known severe asthma because of ignorance about the contraindication.
102
Q

What is meant by a violation with regards to prescribing? (LO4)

A
  • Deliberate deviations from standard practice.

- Prescriber aware.

103
Q

How can we prevent medical errors when prescribing? (LO4)

A
  • Appropriate checking routine by the system.

- Focus on training the prescriber.

104
Q

How is steroid production regulated? (LO5)

A

Steroid production is dependent on the hypothalamic, pituitary, adrenal (HPA) axis.

  • The hypothalamus detects stress.
  • Hypothalamus releases corticotrophic releasing hormone (CRH).
  • CRH acts on pituitary gland.
  • Pituitary gland releases adrencorticotrophic hormine (ACTH).
  • ACTH acts on the adrenal cortex.
  • Adrenal cortex produces cortisol.
  • Cortisol decreases immune function and breaks down glycogen, proteins and fat.
105
Q

What are steroids? (LO5)

A

Lipid-soluble hormones made with a base of cholesterol in the adrenal cortex.

106
Q

List the types of steroid hormones (4). (LO5)

A
  • Mineralocorticoids - e.g. aldosterone.
  • Glucocorticoids - e.g. cortisol.
  • Androgens - e.g. testosterone and DHT (dihydrotestosterone).
  • Oestrogens - e.g. oestradiol (E2), estriol (E3) and progesterone.

Note: E2 is the active form of oestrogen.

107
Q

Describe the regulation of cortisol production. (LO5)

A
  • Normally produced with diurnal variation.
  • This means there is a variation based on time.
  • More cortisol is produced during sleep, so the levels remain high through the day.
  • Cortisol has a positive feedback loop with the HPA axis which leads to more CRH/ACTH production.
108
Q

List the effects of cortisol (8). (LO5)

A
  • Catabolises tissues to release amino acids.
  • Has an effect on mood - high cortisol is associated with stress and depression.
  • Reduces bone formation and enhances bone resorption.
  • Increases gluconeogenesis and causes insulin resistance.
  • Breaks down fats into fatty acids and glycerol.
  • Modulates the immune system and causes immunosuppression.
  • Triggers release of catecholamines.
  • Mineralocorticoid effects on blood pressure can weakly mimic aldosterone which increases salt and water reabsorption into blood vessels. This increases blood volume and blood pressure.
109
Q

What is Addison’s disease? (LO5)

A

It’s a primary adrenal insufficiency leading to low levels of cortisol and aldosterone.

110
Q

List the symptoms of Addison’s disease (7). (LO5)

A
  • Low blood pressure.
  • Fatigue.
  • Muscle weakness.
  • Hyperpigmentation - aldosterone regulates the enzyme which synthesises melanin.
  • Hypoglycaemia - since cortisol causes insulin resistance and hyperglycaemia, the inability to produce cortisol leads to the opposite.
  • Hyponatraemia, hyperkalaemia - low sodium and high potassium because of low aldosterone.
  • Nausea and vomiting - associated with electrolyte imbalance.
111
Q

What is an Addisonian crisis? (LO5)

A

It’s a life-threatening situation caused by a lack of hormones produced in the adrenal glands. It is usually triggered by stress. Requires urgent management or can result in death.
E.g. infection, dehydration, trauma, surgery.

112
Q

List the symptoms of an Addisonian crisis (5). (LO5)

A
  • Collapsing.
  • Hypoglycaemia.
  • Hyponatraemia, hyperkalaemia.
  • Hypotension.
  • Abdominal pain, diarrhoea and vomiting.
113
Q

What is the difference between Cushing’s disease and Cushing’s syndrome? (LO5)

A
  • These are two diseases with similar symptoms and presentations but a DIFFERENT UNDERLYING PATHOLOGY.
  • Cushing’s disease is a subtype of Cushing’s syndrome. It constitutes 70% of Cushing’s syndrome cases.
  • Cushing’s disease - increased cortisol due to a pituitary disease. E.g. Pituitary adenoma.
  • Cushing’s syndrome - increased cortisol due to any cause. E.g. pituitary adenoma, overmedication with steroids, adrenal overproduction of cortisol.
114
Q

List the corticosteroids from highest to lowest potency. (LO5)

A
  1. Dexamethasone.
  2. Methylprednisolone.
  3. Prednisolone.
  4. Prednisone.
  5. Hydrocortisone.
  6. Cortisone.
115
Q

List the indications for glucocorticoids (corticosteroid medications) (6). (LO5)

A
  • Respiratory system - e.g. asthma, COPD.
  • Skin + subcutaneous tissue - e.g. eczema, psoriasis.
  • MSK and connective tissue - e.g. joint pain, capsulitis.
  • Nervous system - e.g. brain tumours.
  • GI system - e.g. IBD.
  • Neoplasms - e.g. brain tumours.
116
Q

List the side effects of glucocorticoids (10). (LO5)

A
  • Increased appetite - weight gain.
  • Acne.
  • Easy bruising.
  • Thin skin.
  • Immunosuppression + infection risk (commonly candida infection).
  • Mood changes, depression.
  • Diabetes + insulin resistance.
  • High blood pressure.
  • Osteoporosis.
  • Withdrawal due to adrenal suppression while on the medication. When the medication is stopped, the adrenals do not produce enough steroids.

N.B. risk of side effects increases with dose and time taking medication.

117
Q

Describe the potential side effects of corticosteroids on a patient’s appearance. (LO5)

A

Chronic steroid use can lead to a classic appearance:

  • Truncal obesity.
  • Buffalo hump.
  • Moon face.

13% have this appearance after 2 months. 50% have it after 5 years. The risk can reduced with alternate day use.

118
Q

Describe the potential side effects of corticosteroids on a patient’s metabolism. (LO5)

A
  • Insulin resistance + hyperglycaemia = diabetes.
  • Catabolism of muscle and bone.
  • Sodium retention and potassium loss.
119
Q

List some common infections while on steroids (6). (LO5)

A 
Bacterial:
- Staphylococcus.
- Gram negative.
- Tuberculosis.
- Listeria.
Viral:
- Herpes zoster.
Fungal:
- Candidiasis.
120
Q

Describe the potential side effects of corticosteroids on a patient’s HPA axis. (LO5)

A
  • High dose of steroids triggers a negative feedback loop on the adrenal glands.
  • Due to the high dose of steroid, there is a reduced synthesis of CRH and ACTH.
  • There is less stimulation of the adrenal cortex.
  • Chronic use of steroids and long-term reduction in adrenal cortex action leads to adrenal atrophy and adrenal suppression.
121
Q

List the potential side effects of corticosteroids on the musculoskeletal system (4). (LO5)

A
  • Myopathy.
  • Osteoporosis.
  • Osteonecrosis.
  • Tendon rupture.
122
Q

How can corticosteroid use cause osteoporosis? (LO5)

A
  • Compromised bone strength predisposing patient to increased risk of fracture.
  • Following hip fracture: 20% mortality within 1 year. 50% of survivors have long-term mobility loss. 20% of patients require full-time care.
123
Q

List the consequences of vertebral fractures (6). (LO5)

A
  • 50% symptomatic.
  • 8% need admission.
  • 20% refracture within 1 year.
  • Kyphosis.
  • Decreased lung volune.
  • Reduced height.
124
Q

Describe the potential side effects of corticosteroids on a patient’s GI system. (LO5)

A
  • Like NSAIDs, steroids irritate the stomach lining and can cause peptic ulcers.
  • Pancreatitis.
  • Perforation of the bowel.
  • Steatohepatitis (fatty liver disease).
125
Q

Describe the potential side effects of corticosteroids on a patient’s eyes. (LO5)

A

Glaucoma and cataracts are potential side effects of steroids.

126
Q

Describe the potential side effects of corticosteroids on a patient’s CNS. (LO5)

A
  • Psychosis.
  • Depression.
  • Mood and sleep disturbance.
  • Benign intracranial hypertension.
127
Q

Describe the potential side effects of corticosteroids on a patient’s skin. (LO5)

A
  • Acne.
  • Striae (purple lines).
  • Alopecia (hair loss).
  • Bruising.
  • Skin atrophy.
128
Q

Describe the potential side effects of corticosteroids on a patient’s height. (LO5)

A

Reduces height by suppressing growth hormone release.

129
Q

Describe the potential side effects of corticosteroids on a patient’s cardiovascular system. (LO5)

A
  • Fluid retention.
  • Altered lipid profile (risk of atherosclerosis).
  • Arrythmia (only a risk factor when steroids giving intravenously).
130
Q

Describe the effects of cortisol on the immune system. (LO5)

A
  1. Glucocorticoids are hydrophobic so pass through the lipid membrane and bind to cytoplasmic receptors.
  2. Receptor-steroid complex binds to receptive genes and acts as transcription factor to increase transcription of anti-inflammatory genes.
  3. Synthesis of proteins which block the transcription of inflammatory cytokines and adhesion molecules.
  4. Mainly occurs by suppressing COX-2.
    - COX-2 metabolises arachidonic acid into prostaglandins and leukotrienes needed for inflammatory response and clotting.
  5. Inhibition of COX-2 leads to reduction in both the products and inflammation.
  6. Prostaglandins and leukotrienes are still needed for neutrophil migration and immune signalling so inhibiting this inhibits the immune system.
  7. Cortisol is now widely used as a treatment in inflammatory disorders.
    - Cortisol is increased physiologically in pregnant women due to increased stress load.
131
Q

What is the purpose of patient safety? (LO6)

A
  • The prevention of avoidable harm, whether by an error (doing the wrong thing) or an omission (failure to do the right thing).
  • 1 in 10 hospital patients in the UK suffer harm during care.
  • Often this is due to a system failure leading to a preventable “chain of events” or due to an individual making an error.
132
Q

Give some examples of possible ways patients come to harm. (LO6)

A 
Medication errors:
	- Harm from surgery.
	- Hospital acquired infections.
	- Directly from incorrect medication.
Human factors/training:
	- Systems.
	- Human interactions.
	- Environment.
	- Equipment.
	- Personal factors.

Errors can occur in multiple areas at the same time.

133
Q

Describe the Swiss Cheese Effect. (LO6)

A
  • This is used to describe barriers to prevent hazards due to resulting accidents.
  • These barriers are imperfect and have holes - some due to active failures, some due to latent conditions.
  • When a mistake happens, it’s not an isolated event that leads to that mistake. It’s a series of events which all coincide to result in a mistake.
134
Q

Give some examples of latent factors leading to patient harm. (LO6)

A
  • Organisational processes - workload, handwritten prescriptions.
  • Management decisions - staffing levels, culture of lack of support for interns.
135
Q

Give some examples of error-producing factors leading to patient harm. (LO6)

A
  • Environmental - busy ward, interruptions.
  • Team - lack of supervision.
  • Individual - limited knowledge.
  • Task - repetitive, poor medications chart design.
  • Patient - complex, communication difficulties.
136
Q

Give some examples of active failures leading to patient harm. (LO6)

A
  • Error - slip, lapse.

- Violation of rules.

137
Q

Give some examples of defence-issues leading to patient harm. (LO6)

A
  • Inadequate defences - guidance confusing.

- Missing defences - no pharmacist.

138
Q

List some guidance the NHS picked up from other organisations to prevent mistakes. (LO6)

A
  • Developed organisational frameworks for safer workplaces and safer work cultures.
  • The more complex the organisation, the greater potential for a larger number of system errors.
  • Latent human errors were more significant than technical failures.
  • A system approach will create a safer healthcare culture.
139
Q

Describe what is meant by blame culture. (LO6)

A
  • Singles out individuals directly involved in patient care and holds them accountable.
  • Individuals identified as individuals are also shamed.
  • Focus is still on the individual staff member rather than how the system failed to protect the patient.
  • Often there are bigger mistakes than the staff member, beyond their control.
  • Most people involved do not intend for mistakes to happen.
  • In all cultures, individual HCPs are required to be accountable for their actions, maintaining competency and practicing ethically.
140
Q

How can we protect patients as medical students? (LO6)

A 
Developing relationships with patients:
- Listen to the patient's needs, wants and expectations.
- Ensure that the patient understands that students are not qualified doctors.
- Learn from failures.
Avoid blame culture:
- Support each other.
- Be open and learn from events.
Practice evidence-based medicine:
- Learn how to apply evidence.
- Look for guidelines/protocols in clinical settings and think whether they are best practice or not.
Maintain continuity of care:
- Handover.
- Change of shifts.
- Referral.
Act ethically everyday:
- Opportunity to interview, examine and treat patients is a privilege.
- Stay within competencies.
141
Q

List the 3 checks created by WHO for keeping patients safe in operating theatres. (LO7)

A
  • First check - team brief.
  • Second check - patient checked on the ward by theatre support worker.
  • Third check - sign in and time out.
142
Q

Describe what occurs in the first check. (LO7)

A
  • The first check is the team brief.
  • This is where all the cases in the list are discussed and any issues are highlighted.
  • It’s a meeting in theatres with all nurses, anaesthetists, theatre support workers, surgeons and students.
143
Q

Describe what occurs in the second check. (LO7)

A
  • Check the name tag for: full name, date of birth, hospital number, NHS number.
  • Check consent form for: full name, date of birth, procedure and confirm the signature is the patient’s. Also check this for pregnancy status.
  • Mark the correct limb with a non-washable marker.
  • Consent is taken by the operating surgeon.
  • Any complication which has a >1% risk is documented and the patient signs a form acknowledging the risks.
144
Q

Describe what occurs in the third check. (LO7)

A

Third check is split into three separate checklists: sign in, time out and sign out.

145
Q

What is meant by sign in (third check) and what is checked in this phase? (LO7)

A
  • Is this the correct patient?
  • Has the patient confirmed their identity, the procedure and their consent?
  • Is the site marked?
  • Is the anaesthesia medication check complete?
  • Patient allergies.
  • Airway risks.
  • Bleeding risk (risk of >500ml blood loss).
146
Q

What is meant by time out (third check) and what is checked in this phase? (LO7)

A
  • Have all the team members introduced themselves?
  • Surgeon and anaesthetist confirm patient details and procedure.
  • Anticipated blood loss, samples to be taken/investigations, unexpected steps.
  • Are there any anaesthetic concerns, ASA grade, monitoring equipment check?
  • Scrub nurse to check equipment and do tool counts.
  • Infection bundle, VTE prophylaxis.
  • Essential imaging displayed?
147
Q

What is meant by sign out (third check) and what is checked in this phase? (LO7)

A
  • Has the procedure name been recorded?
  • Confirmed instrument and swab counts are the same as at the start.
  • Have specimens been labelled?
  • Any equipment issues?
  • Recovery concerns.
148
Q

What is meant by ASA (American Society of Anaesthesiologists) grade? (LO7)

A
  • ASA 1 - normal, healthy patient.
  • ASA 2 - patient with mild systemic disease with no functional limitations such as hypertension.
  • ASA 3 - patient with severe systemic disease, functional limitation, no immediate danger of death such as CCF, poorly controlled diabetes, morbid obesity, chronic renal failure.
  • ASA 4 - patient with severe systemic disease that is a constant threat to life such as unstable angina, hepato-renal failure.
  • ASA 5 - moribund, not expected to survive 24 hours, e.g. multi-organ failure.
149
Q

What is included in the infection bundle with regards to surgery? (LO7)

A
  • Antibiotic prophylaxis within the last 60 minutes.
  • Patient warming.
  • Hair removal.
  • Glycaemia control.
150
Q

List the core standards for safe surgery. (LO7)

A
  • The team will operate on the correct patient at the correct site.
  • The team will use methods known to prevent harm from anaesthetic administration, while protecting the patient from pain.
  • The team will recognise and effectively prepare for life-threatening loss of airway or respiratory function.
  • The team will recognise and effectively prepare for risks of high blood loss.
  • The team will avoid inducing any allergic or adverse drug reaction known to be a significant risk for the patient.
  • The team will consistently use methods known to minimise risk of surgical site infection.
  • The team will prevent inadvertent retention of instruments or swabs in surgical wounds.
  • The team will secure and accurately identify all surgical specimens.
  • The team will effectively communicate and exchange critical patient information for the safe conduct of the operation.
  • Hospital and public health systems will establish routine surveillance of surgical capacity, volume and results.
151
Q

What is patient safety? (LO8)

A
  • “Patient safety is a framework of organised activities that creates cultures, processes, procedures, behaviour, technologies and environments in healthcare that consistently and sustainably lower risks, reduce the occurrence of an avoidable harm, make error less likely and reduce its impact when it does occur.” - WHO.
  • A lack of patient safety is a system failure and is most often preventable.
152
Q

What is meant by a never-event? (LO8)

A
  • “A serious, largely preventable patient safety incidence that should not occur if healthcare providers have implemented existing national guidance or safety recommendations.”
  • It is an event that ‘should never be allowed to happen’.
153
Q

Errors in healthcare can be assessed in three steps, what are they? (LO8)

A
  1. Was the action intentional? - Was performing that a conscious or subconscious decision?
  2. Did the action happen as planned?
  3. Was the outcome of the action expected?
154
Q

List some principles of medical errors. (LO8)

A
  • Slips.
  • Lapses.
  • Mistakes.
  • Violations.
  • Adverse-events.
  • Errors.
  • Malpractice.
  • Near-misses.
155
Q

What is meant by slips and lapses and what is the difference between the two? (LO8)

A
  • Slips and lapses are types of errors that occur as a subconscious or automatic action.
  • A slip occurs when the intended action does not go as planned - e.g. surgeon breaks a suture while attempting to tie it.
  • A lapse is when the action itself is accidentally missed, forgotten unintentionally - e.g. doctor forgetting the patient has an allergy when prescribing antibiotics.
156
Q

What is meant by a mistake with regards to patient safety? (LO8)

A
  • A type of error that occurs during conscious problem-solving where someone performs the action they thought was correct based on their knowledge and external rules.
  • E.g. a doctor applying evidence-based guidelines for adult head injuries to the treatment of a paediatric head injury.
157
Q

What is meant by a violation with regards to patient safety? (LO8)

A
  • A violation is when a deliberate, illegal or otherwise unsanctioned action is undertaken.
  • E.g. knowingly skipping a surgical time-out which is required by a hospital or joint commission.
158
Q

Sometimes patient harm is not due to errors in the healthcare treatment. What else could it be due to? (LO8)

A
  • A result of a patient’s underlying condition.

- The result of known side effects of a medication or procedure that the patient is undertaking.

159
Q

How can non-healthcare-related events be avoided? E.g. the side effects of a treatment. (LO8)

A

Medical professionals can work with patients to weigh all the costs and benefits of a particular treatment.

160
Q

What is meant by adverse events with regards to patient safety? (LO8)

A

‘Harm caused by medical treatment’ - whether it is associated with an error or considered preventable.

161
Q

What is meant by error with regards patient safety? (LO8)

A

‘The failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim.’

162
Q

What is meant by malpractice with regards to patient safety? (LO8)

A

To meet the malpractice criteria, there has to have been an occurrence of a negligent adverse event and demonstration that the physician or other healthcare professional had a duty to care and that negligence will have contributed to an injury and that injury will have led to specific damages.

163
Q

What is meant by near-misses with regards to patient safety? (LO8)

A
  • An unplanned event or close call that does not reach the patient or cause an injury/damage to the patient, but it can impact the patient-clinician interaction.
  • A near-miss should be used as a learning opportunity to re-assess/evaluate potential safety risks within the healthcare system.
164
Q

What are the two most common methods for patient safety improvement strategies? (LO8)

A
  • Standardisation.

- Constraint.

165
Q

What is meant by standardisation as a method of patient safety improvement? (LO8)

A
  • A clearly defined expectation of how a process is to be completed.
  • All team members are expected to follow the defined process.
  • Standardisation is beneficial as it has been proven to improve patient outcomes and reduce risk of complications.
  • It also lowers the cost of care.
166
Q

What are the requirements for implementing standardisation as a method of patient safety improvement? (LO8)

A
  • The explanation of processes needs to be simplified for everyone to follow.
  • Processes should use technology/equipment wherever is possible to minimise human error.
  • Those closest to their use should be creating the standards but should be easy for others to understand for training and application purposes.
167
Q

Give some examples of standardisation as a method of patient safety improvement. (LO8)

A
  • Joint commissions “do not use list”.
  • WHO’s surgical safety checklist.
  • Local trust clinical pathways and protocols.
168
Q

What is meant by constraint as a method of patient safety improvement? (LO8)

A
  • A constraint is when there are limitations in a system.
  • These force healthcare professionals to slow down at critical junctures which gives them time to think through necessary steps to avoid error.
  • E.g. a nurse not being able to provide equipment for a procedure until the WHO surgical safety checklist is complete.
169
Q

What is the never-event list? (LO8)

A
  • A list created by the NHS in 2009 to identify these types of events with the aim of eliminating them.
  • The first list in 2009 consisted of a policy framework alongside 8 core never-events.
  • Since the creation of the original list, the never-events list continues to be expanded or narrowed down frequently based on a set of standardised criteria.
  • The never-events continue to occur despite NHS’ best efforts.
  • 226 never-events occurred between 01/04/20 and 30/11/20 - 87 wrong surgery sites, 52 retained objects, 18 misplaced naso/orogastric tubes.
170
Q

List the eight core never-events. (LO8)

A
  • Wrong surgery site.
  • Retained instrument, post-operation.
  • Wrong route administration of chemotherapy.
  • Misplaced naso/orogastric tube not detected prior to use.
  • Inpatient suicide using non-collapsible rails.
  • Escape from within the secure perimeter of medium or high security mental health services by patients who are transferred prisoners.
  • In-hospital maternal death from post-partum haemorrhage after elective caesarean section.
  • Intravenous administration of mis-selected concentrated potassium chloride.
171
Q

List the four ethical principles. (LO9)

A
  • Autonomy - the right to self-govern.
  • Beneficence - do good.
  • Non-maleficence - do no harm.
  • Justice - everyone has a right to fair treatment.
172
Q

Describe what is meant by autonomy. (LO9)

A
  • Relates to consent and confidentiality.
  • This means that a patient with capacity has a right to decide upon their own course of treatment without any outside influence of others.
  • To protect autonomy, doctors must ensure they have all the relevant information.
  • In safeguarding terms, this may mean protecting them from the influence of family and friends.
173
Q

Describe what is meant by beneficence and non-maleficence. (LO9)

A
  • This means you must do what is best for the patient (according to what they think is best) and avoid any harm possible.
  • E.g. if a patient has an open wound and one solution is amputation, you would need to do everything to save the leg.
  • E.g. if you’re aware that a patient cannot afford a new treatment but it’s best for them, would you mention it and potentially make them feel hopeless for not being able to afford it or withhold the information and therefore, withhold treatment?
174
Q

Describe what is meant by justice? (LO9)

A
  • This means that everyone has a right to fair treatment - this doesn’t always mean equal treatment.
  • E.g. if a patient with cancer requires very expensive treatment on the NHS, a patient with a less severe condition with cheaper treatments is not entitled to the same.
175
Q

Discuss the limitations of the four ethical principles. (LO9)

A
  • The biggest limitation is the conflict between autonomy and beneficence/non-maleficence.
  • E.g. if a patient refuses treatment, the beneficence of respecting their wishes comes before doing what you think is best for them.
  • On an individual level, justice causes issues where there are scarce resources - how would you decide which patient deserves a scarce treatment? Is it immoral to choose one patient over another?

MBBS - Y1 (14 decks)

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