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Test > 3 > Flashcards

3 Flashcards

1
Q

Wound definition

A

Defect or damage in skin caused by chemicals, physical forces, thermal causes or disease

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2
Q

2 broad classifications

A

Wound without tissue loss: eg surgeryWound with tissue loss: eg trauma or burn wounds

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3
Q

Incisions

A

Regular wound Caused by a clean sharp edged object

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4
Q

Laceration

A

Rough and irregular wound Caused by crushing or ripping

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5
Q

Abrasion (graze)

A

Superficial wound where top layers of skin are lost Caused by sliding on a rough surface

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6
Q

Puncture

A

Caused by sharp pointed object punching skinChance of anaerobic bacteria infection

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7
Q

Penetration wounds

A

Caused by entering the body

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8
Q

Avulsion

A

When the integrity of any tissue in the body is compromised Where something is basically torn off

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9
Q

Contusions

A

A bruise Caused by blunt force trauma

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10
Q

Haematoma

A

Caused by damage to blood vessel Blood then accumulates under the skin

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11
Q

3 phases of healing

A

1) Inflammatory 2)Proliferative 3) Remodelling

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12
Q

Inflammatory phase

A

Bleeding first to remove toxins Vasoconstriction begins to stop bleeding Coagulation initiated by platelets forming fibrin network Phagocytes engulf dead cells in the wound

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13
Q

Proliferative phase

A

Granulation tissue builds up in wound space due to fibroblasts and macrophages providing growth factors. (Occurs 2-3 days after wound occurs) This stimulates fibroplasia and angiogenesis (new blood vessels)Fibroplasia causes a bed of collagen to fill defect, pulling wound edges together

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14
Q

Remodelling phase

A

3 weeks after wound occurs Fibroblasts spur on greater collagen formation which forms a helical structure with inter and intra X links The tissue will not regain the properties of uninjured tissue

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15
Q

What pericytes?

A

Pericytes can differentiate into myofibroblasts Vascular pericytes can enter the wound bed and can assume a more contractile and matrix depositing phenotype

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16
Q

Petroleum impregnated dressing

A

For clean, healthy and shallow wounds Use at early stages of wound repair Use non adhering dressings for exuding wounds such as burns

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17
Q

Hydrogel dressings

A

Hydrogel sheets- for shallow wounds Can maintain moisture balance while absorbing exudates Hydrogel gels- for cavities, good for debriding and dislodging They donate moisture Promotes collagenase activity, granulation, epithelisation and contraction

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18
Q

Hypercolloid dressings

A

For early to mid repair wounds Reduces pain and promotes angiogenesis Used where granulation is necessary For minimal to moderate exudation Promotes moist wound healing and granulation

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19
Q

Foam dressings

A

Non adherent Absorbs large amounts of exudates For deep wounds with mild to moderate exudates Best used after granulation to encourage epithelisation and contraction

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20
Q

Alginate dressings

A

Made brown algae Good gel/film forming properties Calcium alginate promotes clotting cascade (10x faster compared to petroleum dressings)For burns, shearing/avulsion, cavity wounds Best for moderate to highly exuding wounds

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21
Q

Film dressings

A

Semi permeable allowing fluid to evaporate whilst still keeping wound moist Comfortable and resistant to wear/tearPrevents bacterial colonisation but does not absorb exudate

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22
Q

Natural polymers

A

Usually protein or polysaccharide in nature Bio-compatible, degradable and hydrophilic Does however vary batch to batch and can degrade way too fast

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23
Q

Collagen dressings

A

The protein is made of three peptide chains with triple helical domains Promotes healing via attachment and migration Dry collagen physically absorbs blood and traps them which adheres them to the wound site giving mechanical strength

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24
Q

Chitosan dressings

A

Made by acetylating chitin Active in slightly acidic media and releases beta 1-4 linked-D-glucosamine (used for hemorrhage control)Promotes fibroblasts, collagen deposition and platelet/RBC mobilisation as well as vasoconstriction Good film forming properties

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25
Q

What is an Aerosol?

A

A relatively stable suspension of solid/liquid particles in a gaseous medium (0.001mcm-100mcm)

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26
Q

Aerosol behaviour is affected by…

A

Interaction with surrounding air molecules and gravityIt’s own size, shape and density

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27
Q

The target site of aerosolised drugs is …

A

Respiratory bronchioles and alveoli

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28
Q

The pattern of deposition in the lungs…

A

The larger the particle the further up the airways it is deposited with any particle >10mcm getting trapped in the back of the throat

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29
Q

Advantages of inhaled drugs (local delivery)

A

-Drugs delivered directly to site of action -The onset of action is rapid -Less drug gets into systemic circulation (For local delivery)-Less of the drug is necessary for a therapeutic effect

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30
Q

Advantages of inhaled drugs (systemic delivery)

A

-Extensive blood supply allows for rapid absorption into systemic circulation -Avoids 1st pass metabolism -Therefore increased availability

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31
Q

Factors controlling deposition

A

Aerosol properties- size and distributionMode of inhalation- volume inhaled, flow rate and breath holding pausePatient factors- anatomy/physiology differences, respiratory disease But primarily affected by size and flow rate

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32
Q

Primary deposition mechanisms in the lung

A

Inertial impact (90%)- kinda just smacks into epithelium because they’re moving in a straight line. Mostly large particlesSedimentation (9%)- the particle moves along slowly, loses energy and plops down. Important for depositing in bronchiDiffusion (1%)- Particle happily floats along an settles down at a dead end, Earns lots of frequent flyer points. Important for deposition in bronchi/alveoliThe smaller the diameter the further along the resp. tract it gets. Small bois fly far. Oropharynx>bronchi>alveoli

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33
Q

Secondary deposition mechanisms

A

Interception- where particles contact walls (especially fibres at airway bifurcations Electrostatic deposition- charged particles can repel each other towards walls

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34
Q

5 essential components of a MDI

A

DrugPropellent Aerosol canister Metering valve Atomising nozzle

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35
Q

Suspension based formulation

A

Suspensions preferred due to chemical stability and is capable of delivering high powder loads Drug must be milled to respirable size <5mcm and must be insoluble Shaking required to redisperse drug to ensure suspension is homogenous

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36
Q

Role of adjuvant

A

To ensure physical stability of suspension Must be capable of dispersing and redispersing the drug Minimise segregation before administration of the drug

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37
Q

Common surfactants

A

SPAN 85, oleic acid and soya lecithins in CFC’sOleic acid, magnesium stearate, PEG/PVP in HFA’s

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38
Q

Solution based formulations

A

Suitable if solubility/stability is adequate Amount of emitted dose is directly related to solubility therefore usually requires a cosolvents as propellants are usually poor solvents Potential for drugs to recrystallise due to changing temperatures

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39
Q

Problems of solution based formulations

A

Polar co solvent can cause corrosion of Al cannister Co solvent lowers internal propellant pressure therefore atomisation less effective Modifying drug to be more soluble is most effective solution

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40
Q

Liquid propellant

A

Good because no loss of pressure after actuations This because the loss in pressure causes vapourisation of the propellant which restores the pressure within the cannister

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41
Q

Advantages of pMDI’s

A

Consistent dose Cheap Resistant to moisture Compact

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42
Q

Disadvantages

A

Patient coordination required Cold freon effect results in inconsistent deliveryTail off at the end of a can High deposition in throatVery little intellectual property protection for pharm R and D

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43
Q

DPI’s (Dry powder inhalers)

A

Driven by patient inspiration Easy to use Patient/environment friendly Long term replacement for pMDI’s

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44
Q

DPI mechanism of action

A

Inspiration creates energy for fluidisation and entrainment of formulation Energy caused by pressure drop (deltaP) that s due to inhalation flow (Q) and internal resistance of device (R)A minimum inhalation flow must be created (Qmin) before dose can be released

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45
Q

Relationship between device and airflow

A

R effects speed/acceleration of airflow through the device Acceleration effects DPI efficacySpeed affects the amount deposited in the lungs

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46
Q

Factors affecting respirable dose

A

R, Q and the powder formulation

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47
Q

Particle interactions are dictated by…

A

Van der waals forces Electrostatic forces Capillary forces Contribution of each of these depends on interacting materials and humidity

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48
Q

Van der waals forces

A

Dominant at short range in low humidity where there is no electrostatic forces

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49
Q

Capillary forces

A

Water condenses between to particles and forms a liquid bridge Force directly related to humidity and hydrophobicity Dominant at ambient conditions

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50
Q

Electrostatic forces

A

Due to friction between different materials Long range force Can be attractive or repulsive and increase at low humidity

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51
Q

3 interactions that must be controlled

A

Drug-drug (Cohesion)Drug-excipient (Adhesion)Drug-device (Segregation)

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52
Q

2 formulation strategies

A

Carrier based- uses adhesion to bind drug to a carrier Agglomerated- uses cohesion to form an agglomerate which is broken up during inspiration

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53
Q

Advantages of carrier based formulations

A

Accurate dosing of small quantities of a potent drug Improved handling and processing Carrier size, shape and morphology can be changed to influence fine particle friction (FPF)

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54
Q

Advantages of agglomerated powder systems

A

More suitable for high dose drugs However efficient deaggregation of agglomerate must occur so that drug is presented as discrete particles in the lung

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55
Q

Advantages of DPI’s

A

Propellant free No or very little excipientsLarge doses can delivered In dry form Breath actuated

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56
Q

Disadvantages of DPI’s

A

Dependant on patients inspiration force Due to higher velocity there is increased chance of inertial impaction Exposure to ambient conditions can reduce stability Less efficient at delivery than a pMDI

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57
Q

Nebulisers

A

A drug contained within a sterile solution Significant variation occurs a lot drug being left within the device, in expiration and many particles are to small or large As little as 10% of the target dose maybe delivered

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58
Q

Pneumatic nebuliser

A

Works by using a high velocity air jet to blow air very quickly causing them to break into small particles A baffle (inertial filter) traps oversized particles

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59
Q

Pneumatic nebuliser pros and cons

A

Cheap and can achieve small particle sizes But: has variable performanceDead (stagnant) volume Lower outputNot very portable

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60
Q

Ultrasonic nebulisers

A

Uses a piezoelectric ceramic disc which oscillates and causes droplet production

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61
Q

Ultrasonic nebuliser pros and cons

A

Consistent Produces small particles High output Small and quiet But: low inertiaparticle size increases at end of life expensive heats solution to 40 degrees celsius Unsuitable for suspensions

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62
Q

Soft mist inhalers (SMI’s) and Liquid dose inhalers (LDI’s)

A

Based on a drug dissolved in non volatile liquid Volumetric dosing Breath actuated Dose emitted as a slow moving cloud

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63
Q

AERx LDI

A

A hand held nebuliser Uses an actuater to extrude drug, held in 50mcl through tiny micron sized holes Microelectronics guide patient for optimum inspiration

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64
Q

Respimat mechanism

A

Drug stored in solution Solution is forced through micro nozzle as patient inhales

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65
Q

Respimat advantages

A

Avoids moisture problems and powder aggregation that can occur with DPI’s Can deliver a metered dose

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66
Q

Advantages of nasal systemic delivery

A

Avoids 1st pass effect and intestinal metabolism Acid sensitive drugs can be used Polar compounds with poor absorption can be used Small lipophilic drugs can be used Easy to use

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67
Q

Functions of the nose

A

Major: AC-temperature -humidity -filtration Minor: Smell

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68
Q

Structural features of nose

A

Volume: 20ml Surface area: 150cm cubed Rich blood supply Lots of turbulence

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69
Q

Nasal epithelium: Ciliated cells

A

200 cilia per cell Movement slightly out of phase with neighbors

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70
Q

Nasal epithelium: Pseudostratified columnar epithelium

A

Has a large surface area due to microvilli Protective mucus layer and cilia for clearance

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71
Q

Mucus consists of…

A

90-95% water 1-2% salts3% lipids 0.5-5% proteins

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72
Q

Functions of mucus

A

Traps particulates Physical barrier between epithelium and outside Can bind to drugs preventing diffuse of drugs Contains enzymes which may degrade drugs

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73
Q

Clearance in the nose

A

If particles are deposited on:Ciliated regions: quick clearance Non ciliated: slower clearance Nasopharyngeal region: gets swallowed and therefore not available Mucus clearance ~ 10-20mins Spray usually better than drops unless v. rapid absorption

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74
Q

How much of the drug delivered nasally is deposited in lungs?

A

None.The major is in nose, pharynx and stomach

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75
Q

Effect of molecular weight on absorption

A

Small MW=well absorbed Absorption >500= much worse MW>1000= 1-3% at most

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76
Q

Nasal formulations

A

Aqueous based so as not to effect clearance of cilia Generally used to treat congesion, allergic rhinitis and infection

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77
Q

Requirements for nasal formulation

A

pH between 5.5 and 6.5Must be isotonicViscosity should be similar to that of mucousMust has preservative as it is multidose Antioxidants for those drugs at risk of degradation

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78
Q

Delivery to brain through nose

A

Olfactory epithelium is one small area (4 cm2) where BBB is not present Drugs can enter via paracellular paths/axonal paths through olfactory nerves

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79
Q

Ways to improve nasal delivery

A

Surfactants/bile salts reduce viscosity of mucus which can increase drug absorption Use mucoadhesives to increase contact time with epithelium Primary purpose is to increase uptake of peptides

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80
Q

ViaNase and Optinose

A

Devices that alter turbulence in nose thereby increasing the dose delivered and minimising lung deposition

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81
Q

Anatomy of ear: external auditory canal

A

Around 23.5 mm in length 4.8-9.3mm wide

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82
Q

Anatomy of ear: Middle ear

A

(Not to be confused with my home, middle earth)Tympanic membrane separates external and middle ear The cavity is small and contains 3 auditory ossicles Infections can spread here

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83
Q

Anatomy of ear: Inner ear (Labyrinth)

A

Contains cochlea (hearing) and vestibular system (balance)Pretty inaccessible, difficult to pop in drugs (also due to blood-cochlea barrier)

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84
Q

Inner ear drug delivery: intra tympanic

A

High amounts of drug must diffuse into scali tympani across round window membrane from middle earRWM permeability is variable so drug accuracy not very good Drug can also be lost into pharynx via eustachian tube

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85
Q

Inner ear drug delivery: intra cochlear

A

Can implant drugs directly into cochlear per-ilymphatic spaces Such drugs have direct access to cells of inner ear Delivered via micro/osmotic pumps

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86
Q

Emulsions and suspensions

A

Liquid or solid phase in external liquid phase Disperse phase=the phase that is split up Continuous phase=the phase in which the disperse phase is split into

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87
Q

Why do emulsions/suspensions require stabilisers?

A

They are inherently unstable systems therefore to give an acceptable shelf life stabilisers are necessary

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88
Q

Emulsions attain equilibrium when…

A

When internal droplet join up to form one micro phase with the smallest possible surface area

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89
Q

3 ways in which particles encounter one another in suspension

A

Brownian movement Creaming/sedimentation Convection

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90
Q

Sedimentation rate (Vsed) is affected by…

A

Particle diameter= increase cause increase in Vsed Particle density= increase causes increase in Vsed Viscousity= increase cause decreases in Vsed

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91
Q

Vtotal=Va+VrExplain this equation

A

Calculates total energy of interaction Va=attractive potential energy Vr=electrostatic repulsive energy

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92
Q

Where do different forces dominate?

A

Primary minimum-At v.short distances attraction dominates causing particles to agglomerate Primary Maximum-At medium distance repulsive forces dominate and particles remain in suspension Secondary minimum-At larger distances repulsive force lessens and particles have weak attraction

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93
Q

Effect of electrolytes on stability

A

Low conc gives a larger primary maximum but no 2ndry minimum Moderate conc gives a 2ndry min allowing flocculation to occur as well as a primary max. preventing coagulation High conc. gives no primary max or min

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94
Q

Flocculation

A

Forms loose aggregates preventing caking Held together with weak interparticulate forces forming a lattice type structure.

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95
Q

How does caking occur?

A

Where particles are deflocculated they aren’t associated and so settle on top of one another The pressure from the particles on top pushes to the bottom particle into the primary minimum This irreversibly binds the particles

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96
Q

Microemulsions

A

Homogenous, transparent and low viscosity Low interfacial tension but v. high interfacial areaLots of surfactant necessary (surfactant+2nd cosurfactant usually)

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97
Q

Semi-solid emulsions

A

Stable o/w cream with:dispersed oil phase crystalline gel phase crystalline hydrate phasebulk phase containing dilute surfactant solution

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98
Q

What is a liposome?

A

Vesicular structure made of a bilayer around a aqueous coreConsidered as a liquid crystal

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99
Q

Functions of liposomes

A

Carries strongly hydrophobic drugs within bilayerCarries strongly hydrophilic drugs in aqueous coreCarries intermediate logP drugs somewhere between

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100
Q

Rigidity and permeability of lipsomes is determined by…

A

Alkyl chain length and unsaturationCholesterol for rigidity

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101
Q

Why use liposomes as carriers?

A

Biocompatible and degradableBiologically inert and low toxicity

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102
Q

Conventional lipsomes are…

A

Neutral -vely charged Passively targets MPS cells in liver spleenThey are rapidly taken up by phagocytes and taken from blood circulationeg. carries amphotericin B, doxorubicin and hep A vaccines

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103
Q

Sterically stabilised liposomes are…

A

Covered in a hydrophilic coating allowing for a prolonged circulation timeThe hydrophilic PEG group creates barrier against interaction with cellular componentsCan cause transient reactions in a subset of patients

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104
Q

Immunoliposomes are…

A

sterically stabilised or convetionalThey have specific antibodies on their surface and are targeted at cancerThe steric PEG chain can interfere with antigen binding

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105
Q

Cationic liposomes are…

A

+vly charged and carry genetic material. Thischarge interacts with -ve DNA condensing it into a more compact structureCan activate complement and cause adverse effects

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106
Q

Three layers of the skin and their thickness

A

Epidermis- 100 micronsStratun Corneum- 10 micronsDermis- 1000 microns

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107
Q

What is the Stratum corneum (SC)?

A

The brick wall layer Made up of corneocytes (brick) and corneodesmosomes (rivets) and mortar (complex lipid mixture)Prevents water loss

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108
Q

Pathways through SC

A

Transcellular- striaght through cells Intercellular- around cells through ‘mortar’Follicular- through hair folliclesEccrine- through glands in the skin

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109
Q

Jmax=(Ksc/v D/h) x CsatvExplain this equation

A

Ficks law of maximum diffusionJmax=max diffusionKsc/v=SC/vehicle partition Coefficient of drugD=diffusivity in membraneh=diffusion path lengthCsatv=saturation concentration of drug in vehicle

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110
Q

Why is the previous equation shortened to Jmax=D/h x CsatSC?

A

Under ideal circumstances Jmax can be independant of vehicle so it is removed from equationThis however assumes vehicle does not alter SC properties or the drug conc in SC

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111
Q

logKp= -2.7+(0.71x logP)-0.00061x MW)What is this equation and why does Guy love it so much?

A

Him and his mate invented itIts predictive of the permeability coefficient

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112
Q

What does introducing a co solvent do?

A

Increases Csatv (solubility in vehicle) but decreases Ksc/v (the partition coefficient)Therefore it is predicted that there will be a decrease in flux when % of cosolvent> the level required to just completely dissolve the drug

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113
Q

Effects of physiochemical properties on bioavailability

A

Increasing lipophilicity gives greater flux (to an extent)Jmax decreases with increasing MW

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114
Q

Rtotal=Rsc +RedExplain this equation

A

This calculates total resistanceRsc= resistance of SCRed= resistance of epidermisRsc»Red therefore Rsc is rate determining factor

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115
Q

Effect of pH on percutaneous drug delivery

A

Skin is acidic so non ionised drugs most easily absorbedReally high/low pH is pretty damaging to skinTherefore pH is usually kept near neutral

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116
Q

Formulation preferred for chronic skin conditions

A

Hydrocarbon based formulations preferred for occlusive properties However not very good for topical drug delivery due to poor drug solubility Solubility can be enhanced with solvents like isopropyl myristate or propylene glycol

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117
Q

4 water free formulations

A

PEG gel- 1 phase, semi solid, polarLipogel- 1 phase, semi solid, polar, based on triglyceridesOleogel- 1 phase, semi solid, polar, triglyceride+ hydrocarbon+ inorganic fillerFatty ointment- 1 phase, semi solid, non polar, hydrocarbon based

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118
Q

Polar gel formulations

A

Water/alcohol based can low lipid or lipid freeCan be made into emulsions (emulsion gel) and suspension gels Not good for occlusive treatments (eczema/psoriasis)

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119
Q

2 types of gel formulations

A

Hydrogel- semi solid, made of large organic mlecules interpenetrated by water Emugel- 2 phase, semi solid similar to the above but with a small fraction of emulsified lipids

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120
Q

Creams (emulsions)

A

Adjustable Requires stabilisers Dispersion is effected by emulsifier films at the oil/water interface

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121
Q

Effect of w/o compared to o/w

A

w/o has higher F as it blends easier with SC lipids but o/w is preferred by patients as it isn’t sticky/greasyAlso provides cooling effect as aqueous continuous phase evaporates but can withdraw moisture from skin due to surfactant like emulsifiers

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122
Q

2 types of w/o creams

A

w/o lotion- hydrohobic, semi liquid, 2 phasew/o cream- hydrophobic, semi solid, 2 phase

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123
Q

Post administration formulation metamorphosis

A

Evaporation of solvent can change drug solubility in residual phase This usually leads to an increase in thermodynamic activity until saturation is reached At this point either supersaturation occurs or a reduction in permeability

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124
Q

Drug delivery to targets below the skin

A

Eg NSAID’s Has lower systemic circulation therefore less side effects

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125
Q

Parts of the eye (that i don’t know)

A

Conjunctiva- fleshy bit under eyeCornea- clear membrane that covers the eye ballChoroid- blood vessels that supplies the back of the eyeSclera- the white of the eye

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126
Q

Advantages of ocular administration

A

Drug delivered straight to target site Higher conc. at target site achieved than with oral forms Lesser side effectsRelatively easy for patient to self administer

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127
Q

Disadvantages of ocular administration

A

Poor drug retention and high clearance from eyeRequires frequent dosing therefore is inconvenient for patient Must be sterile Ointments can cause blurring and other forms can cause local irritation

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128
Q

The problems of ocular administration

A

Blinking eye has vol of 7mcl and unblinking has vol of 30mcl2drops of solution contains 100mcl and the removal of solution from eye is <2 mins Due to these only around 1% of applied dose is absorbed

129
Q

Conjunctiva

A

Made of non keratinised, stratified squamous epithelium, goblet cells and columnar epithelium Good blood supply with relatively large SA of 18cm2 and has greater permeability than cornea. This however means most of the drug is lost to systemic circulation Produces and maintains tear film

130
Q

The three layers of the cornea

A

1) Multilayer, lipid rich epithelium, 50-100 microns2) Aqueous matrix, stroma (has collagen and keratocytes), 0.6-1mm 3) Single layer of cells, lipid rich endothelium, maintains hydration, 5 microns

131
Q

Administering to cornea

A

Must be both oil/water soluble due to differing layers (req. intermediate logP)Low MW drugs have better permeability Is avascular (v. little blood flow) and slightly -vely charged

132
Q

Properties of lacrimal fluid

A

pH=7.4 and buffers pH 3.5-10Isotonic with blood though does not necessarily require isotonic formulations

133
Q

Considerations for ocular formulations

A

Salt to increase solubility to increase conc for absorption (as there is no transporters on cornea, v. reliant on diffusion)Salts can however kinda sting Low MW with intermediate LogP and particle size should be <10microns pH can affect shelf life of drugs

134
Q

Common excipients in ocular formulations

A

Purified water USPHydrophilic polymers control flow from dispenser and increase residence on eyePolyacrylic acid in aq. gels to treat dry eyes Preservatives necessary to maintain sterility of multidose dispenser (eg cationic surfactants, low % parabens)

135
Q

3 ways of manufacturing ocular formulations

A

Produce in clean conditions and autoclaveProduce in clean (or aseptic) conditions and filter Produce under aseptic conditions (essential for suspensions)

136
Q

Ocular ointments

A

Common for infection/inflammationImproved retention therefore less frequent dose Usually paraffin base or PEG/polyacrylic acid for aq. gels

137
Q

Intraocular delivery examples

A

Anti VEGF treatment for age related macular degeneration (AMD)Ganciclovir implant (Vitrasert) to treat cytomegalovirus retinitis Fluocinolone implant (Retisert) to non infectious uveitisDexamethasone implant (Ozurdex) for macular oedema

138
Q

What is the macula?

A

The functional center of the retina and provides the best colour visionHence it is of particular interest to protect

139
Q

Properties of tubercolosis (TB)

A

Slow growing Infects lungs but can become extrapulmonaryAcid fast bacteria, is lipid richV. hydrophobic therefore resistant to drying and weak disinfectant

140
Q

1st stage of TB

A

Just a few needed to be inhaled Settles in alveoli and begins growing Engulfed by phagocytes however not killed in this process Asymptomatic

141
Q

2nd stage of TB

A

TB multiplies in phagocyte Phagocyte bursts and releases TB which are engulfed by other phagocytes This continues for 3-4 weeks Still asymptomatic

142
Q

3rd stage of TB

A

Cell mediated response started Tubercules form (growths of the TB in the lung)Symptoms start appearing

143
Q

Percentage of people that progress infection after 3rd stage?

A

5-10% progress Around 45-50% clear infection while 45-50% just have a latent infection

144
Q

4th stage of TB

A

TB continues multiplying and uncontrolled lysis occurs and the TB spreads around the lungs Enzymes released destroys tissue causing lesions

145
Q

TB symptoms

A

CoughAfternoon fever Weight loss (hence the name ‘consumption)Blood in sputum Night sweats

146
Q

How might you diagnose TB?

A

Chest x-ray will reveal the lesions that have caused scarring Sputum test/cultures will reveal the TB Molecular assays (MTB/RIF assay)

147
Q

How might yo diagnose latent TB?

A

There are no lesions because infection has not progressed past 3rd stage hence chest x ray not usefulTuberculin is given SC and a +ve test gives a lesion on skin >10mm afer 2-3days Molecular assay (IGRA)

148
Q

TB prevention

A

BCG vaccine given to high risk groups

149
Q

How many 1st line drugs for TB are there and how are they used?

A

4 first line drugs and they’re used in combo They include:RifampicinIsoniazidPyrazinamide Ethambutol

150
Q

Rifampicin effect on TB

A

Bactericidal via inhibition of RNA polymerase Absorption reduced by food Can cause liver damagehypersensitivityreduces activity of other drugsbody fluids can turn red/orange

151
Q

Isoniazid effect on TB

A

A prodrug Acts bactericidal if TB growing but bacteriostatic if there is little growth via the inhibition of the synthesis of mycolic acid Metabolised by liver and excreted by kidneys Can cause hypersensitivity, peripheral neuropathy, hepatoxicity and decreases effects of birth control pills

152
Q

Pyrnzinamide effect on TB

A

Prodrug that is bactericidal via inhibition of mycolic acid synthesis and damage of bacterial membrane Metabolised by liver, excreted by kidneys Can cause joint pain, liver damage and hypersensitivity

153
Q

Ethambutol effect on TB

A

Bacteriostatic against growing TB via increasing permeability by affecting cell wall synthesis Half of it excreted unchanged in urineCan cause reversible optic neuritis and joint pain

154
Q

Treating active TB (RIPE)

A

Rifampicin and isoniazid for 6-9months PYrazinamide and ethambutol for the first 2 months

155
Q

Treatment of latent TB

A

Isoniazid for 6 months or Rifampicin and isoniazid for 3 months

156
Q

2nd drugs for TB

A

Streptomycin CapreomycinCycloserine Ciprofloxacin Azithromycin

157
Q

MDR-TB is defined as….

A

Multi-drug resistant TBRes to >2 1st line drugs

158
Q

XDR-TB is defined as…

A

Extra (extreme?) drug resistant TBRes to >2 1st line drugs + 3> of 6 2nd line drugs XXDR-TB and TDR-TB (totally resistant) also exist but not recognised by WHO yet

159
Q

Functions of ANS

A

Contracting/relaxing smooth muscle Regulation of gland secretion Conrtol of heart rateRegulation of metabolism

160
Q

Organs that are controlled by sympathetic only

A

Sweat and blood vessels

161
Q

Organs controlled by parasympathetic only

A

Cilliary muscle of eye

162
Q

Pre ganglionic neuron (PrGN’s)

A

Cell body in CNSSmall and myelinated Releases ACh which acts on nicotinic receptors on post synaptic neuron

163
Q

Post ganglionic neuron (PoGN’s)

A

Cell body in autonomic ganglionSmall diameter and NON myelinated Synapse close to target organReleases noradrenaline

164
Q

The exception to the 2 neuron system

A

Adrenal medullaOnly one neuron straight from CNS to adrenal medullaConsidered a specialised ganglion

165
Q

Properties of nicotinic receptors

A

3 classes- muscle, autonomic neuronal, CNS neuronalAll are ligand gated ion channels, cation channel Na+ in, K+Most ganglia innervated by several PrGN’s and require simultaneous signals to generate action potentialGenerates fast excitatory ppost synaptic potential (fast epsp)

166
Q

Modulating autonomic ganglia transmission -Muscarinic receptors

A

M1- K+ channel closing Slow excitatory PSP (slow epsp)M2- increases K+ conductance induces hyperpolarisation Slow inhibitory PSP (ipsp)

167
Q

Cholinergic signalling in airways

A

ACh released from PoGN activates M3 on smooth muscle causing contraction ACh that is floating about also attaches to M2 receptors on PoGN causing a reduce in the amount of ACh released

168
Q

Sympathetic vs parasympathetic influence on lung smooth muscle

A

Most innervation of lungs is parasympathetic however there is some sparse sympathetic innervation of lungs There is also some sympathetic control via circulating adrenaline

169
Q

How do different receptor subtypes vary their response?

A

They mediate different responses by coupling to different secondary messenger systemsa2, b1, b2, b3 all use cAMP to activate kinase which phosporylates protein inducing cell response a1 uses phospholipase and diacylglycerol to activate kinase and release Ca

170
Q

Adrenoceptor selectivity

A

Unselective for both Adrenaline (A)/Noradrenaline (NA) A slightly more selective for beta2 and alpha2NA slightly more selective for beta1 and alpha1

171
Q

Alpha1 (a1) adrenoceptor function

A

Constrict smooth muscle-except in GI tract where it relaxes

172
Q

Alpha2 (a2) adrenoceptor function

A

presynaptic inhibition of neurotransmitter release

173
Q

Beta1 (b1) adrenoceptor function

A

increases heart rate and force of constriction

174
Q

Beta2 (b2) adrenoceptor function

A

Dilates/relaxes smooth muscle

175
Q

Beta3 (b3) adrenoceptor function

A

Thermogenesis in skeletal muscle

176
Q

2 types of presynaptic modulation

A

Homotropic- nerve inhibits itself Heterotropic- other nerves inhibit them

177
Q

What are NANC transmitters?

A

Non adrenergic non cholinergic transmittersThese include ATP, neuropeptides, NO, prostaglandin, histamines, adenosine and bradykinin They are used for the fine tuning of the autonomic system by changing onset/duration of action or by changing the ratio of transmitters released

178
Q

Co transmission

A

Sometime neurotransmitters released for desired effectATP has very fast onset but shortNA has slower onset but prolonged So both released to achieve both a quick onset and prolonged action

179
Q

Definition of asthma

A

Chronic inflammatory disorder of the airways

180
Q

2 lung function tests

A

PEFR- peak expiratory flow rate FEV1- forced expiratory volume in 1 sec

181
Q

4 mechanisms for increased hyper responsiveness

A

Increased muscle contractility Either bigger muscle cells (hypertrophy) or more muscle cells (hyperplasia)Increased excitatory nerve activity- can be caused by ACh on M3 receptors or NANC molecules on neurokinin receptorsDecreased bronchodilator activity Inflammation

182
Q

How does parasympathetic signalling in the lung work?

A

The para sympathetic nerve release ACh which acts on the M3 receptors on the smooth muscle cells This causes Ca2+ to be released within the muscle cell which initiates a contraction

183
Q

How does Ipratropium work?

A

It is a non selective muscarininc antagonist that blocks both the M1 receptor on the nerve and the M3 receptor on the muscle Only problem is that M2 is not blocked and therefore by negative feedback more ACh is released which can overcome the antagonist effect of ipratropium

184
Q

Why is tiotropium better than ipratropium?

A

Tiptropium blocks only the M3 receptor on the muscle cellThis means that ACh release is not inhibited hence the ACh can still effect the M2 receptor which will inhibit release of ACh

185
Q

Mechanisms of bronchodilation

A

Adrenaline acts on beta adrenceptors in the lungInhibitory NANC transmitters CGRP and VIP- activates adenyl cyclase NO- acts on soluble guanylate cyclase

186
Q

How do beta adrenoceptor agonists work?

A

Activates MLC phosphotase- dephosphorylates myosin chainsG protein is coupled to adenyl cyclase which:ATP converted to cAMP which activates PKA (protein kinase A) which:Opens K+ channels (causes hyperpolarisation)Sequesters Ca2+ (brings it back into stores)Inactivates MLCK

187
Q

Beta2 agonists?

A

In order of lipophilicity:Salbutamol (short acting)FormoterolSalmeterol (long acting)

188
Q

Why are formoterol and salmeterol longer acting beta agonists?

A

Salmeterol interacts with the membrane and slowly diffuses out to the receptorFormoterol forms a depot in the membrane and leaches out to act on receptor but itcan also interact directly with the receptor in the aqueous phase as it maintains an equilibrium between lipid/aq phase.

189
Q

How does theophylline work?

A

It inhibits phosphodiesterase (PDE) an enzyme that inactivates cAMPDue to cAMP still working the dilating effect of the beta2 receptor has is enhanced It does however have a narrow therapeutic window

190
Q

Effect of inflammation on airways

A

Causes epithelial damage Exposes sensory nerves Oedema and secretions lead to decreased airway diameterIn asthmatic patients you also get increased secretion and mucous plugging

191
Q

The difference between extrinsic and intrinsic asthma?

A

Extrinsic is young onset and caused by external allergens Intrinisic is not caused by allergens and occurs later in life. Usually more severe

192
Q

Definition of anaphylaxis

A

Caused by a severe allergic reaction resulting in respiratory collapse

193
Q

How do allergies develop?

A

Genetic with the influence of many genetic lociDriven by Th2 helper cells and the Th2 cytokines it releases Associated with IgE antibodies

194
Q

Th1 and Th2 in allergies

A

Th1 cytokines suppresses Th2 cell production An increased Th2:Th1 ratio is indicative of allergiesTh1 cytokines include IL-12 and interferon gammaTh2 cytokines include IL-4,5,9 and 13

195
Q

How do these cytokines cause allergies?

A

IL-4 and 13 causes B cells to make more IgE antibodiesThe IgE binds to FceR on mast cells and the cross linking causes degranulation Histamines, cytokines, proteases and heparin are released causing the allergic reaction

196
Q

How long can it take for an allergy to develop?

A

The initial sensitisation may take years and are asymptomatic This sensitisation increases over the years until re-exposure triggers mast cell release

197
Q

Antihistamine in allergies

A

Chlorpheneramine, cetirizine and astemizole are effective in relieving allergic rhinitis but not extrinsic asthmaThis is due to the fact that mast cells in the lungs have low levels of histamines hence anti histamines are less effective

198
Q

What are ‘Cromones’?

A

Eg. Disoium cromoglycate, nedocromilKnown as ‘mast cell stabilisers’ as they inhibit mediator release from mast cells in the lungsEffective in half of patients against early and late stage asthmaAlso inhibits the chemotaxis of eosinophils and nerve fibre excitation

199
Q

What is Omalizumab?

A

An anti IgE antibody Binds to the Fc portion of IgE preventing it from binding to mast cells No oral admin and very expensive Hence only approved for severe asthma unresponsive to glucocorticoids

200
Q

Immunotherapy

A

Licensed for allergies but not asthmaGive higher doses of antigen overtime under medical supervision Also very expensive

201
Q

How do glucocorticoids work?

A

Regulates gene transcription -inhibits cytokine transcription-inhibits infammatory leukocyte migration Indirectly inhibits Phospholipase A which stops the production of arachidonic acid which is responsible for prostaglandins and leukotrines (involved in inflammation)

202
Q

Leucotrines in asthma

A

LTC4 and LTD4 constrict airways and cause oedema via increasing vascular permeability LTB4 attracts leukocytes increasing inflammation further

203
Q

How do leukotrine receptor antagonists (LTRA) work?

A

Eg. Montelukast and zafirlukast Blocks the action of LTC4 and LTD4

204
Q

How do leukotrine synthesis inhibitors work?

A

Eg. ZileutonBlocks 5 lipoxygenase which is responsible for the synthesis of leukotrines

205
Q

How do the leukotrine antagonists compare against glucocorticoids?

A

In an RCT glucocorticoid (beta agonist) consistently performed better In labs LTRA’s were equivalent to glucocorticoids Difference in genetics in the population may also account for variation in effect

206
Q

Anticytokines

A

There are high numbers of cytokines in the lungs of asthmatics IL 13,4 and 5 help these eosinophilsAnti-IL-13(4) is only useful in a small amount of people and is not in the UKAnti IL 5 are used in severe steroid resistant asthma

207
Q

Outline the effects of LABA’s

A

Reduced bronchoconstriction Reduced bronchohyperactivity Reduced hyperplasiaReduced inflammatory mediator release Reduced mucousal oedema and tissue remodeling

208
Q

Outline the effects of inhaled steroids

A

Reduced bronchohyperactivity Reduced inflammatory cell conc.Reduced oedemaReduced epithelial damage Reduced tissue remodeling Reduced cell proliferation

209
Q

Why is asthma still such a problem?

A

Under diagnosed and undertreated Misdiagnosed and mistreated Patient compliance with treatment is poor

210
Q

What factors indicate a high probability of asthma?

A

Cough + wheezeCough is worse at night Exercise induced Family history of asthmaEvidence of airway narrowing

211
Q

In the asthma control test, what do the scores mean?

A

Out of 25:25: Perfectly controlled asthma 20-24: Well controlled asthma <20: Further treatment necessary

212
Q

Steps of asthma therapy

A
  1. SABA alone2. SABA + ICS (low) (if need for maintenance is shown)3.SABA + ICS (low)+ LRTA4. SABA+ ICS (low)+ LRTA + LABA (review LRTA effectiveness)5. MART (with low ICS) +/- LRTA 6. MART (with moderate ICS) +/- LRTA7. MART +/- LRTA (Or high ICS on fixed dose therapy)Consider also LAMA and additional advice for step 7
213
Q

What does it mean to have well controlled disease?

A

The patient should suffer from no symptoms during the day and should be able to carry out their regular activities without hindrance

214
Q

What lifestyle messages should you aim to get across to asthma patients?

A

Understand the risks of uncontrolled asthmaEncourage to stay active and lose weight They should know of their lung health and personal health planRecommend taking vaccines Share info with each other about meds and devices

215
Q

BTS/SIGN vs NICE guidance

A

Main difference are the tests done and the order of the drugs given NICE is more cost effective

216
Q

Assessing an acute exacerbation

A

ID the trigger factor ID the type and duration of symptoms ID the treatment started and if its working Assess severity of exacerbation Ask about depression, alcohol misuse, poor compliance, previous exacerbation.Use these as a basis for deciding whether to admit to hospital

217
Q

Assessing the severity of an exacerbation

A

Check for signs of exhaustion: cyanosis, SOBExamine patient chest and record respiratory rate, pulse an BPCheck peak expiratory flow rate:->50-75%=moderate-33-50%=severe-<33%=life threatening Measure O2 sat. if possible

218
Q

How can you manage acute exacerbations?

A

Give high O2 to maintain O2 sat at 94-98%High dose SABA+ICSIV Beta agonists for patient where inhalation not possibleOral steroids in doses suitable for severityIV magnesium sulfate for patients unresponsive to beta agonists

219
Q

The 5 steps of the BTS/SIGN guidelines

A
  1. Low dose ICS2. LABA + ICS (usually as MART)3. -If LABA doesn’t work then stop LABA and increase ICS-If LABA works but inadequate then increase LABA + continue ICS OR continue LABA+ICS and add LRTA 4. Increase to high dose ICS or add 4th drug eg LAMA5. Add in oral steroids at lowest adequate dose
220
Q

What is difficult asthma?

A

Asthma patients suffering from symptoms even on steps 4/5 of BTS/SIGN guidelines and one of:-life threatening exacerbation requiring invasive ventilation in the last 10 years -daily dose of oral steroids >7.5mg daily-2 hospitilisations in last 12 months on high dose ICS-FEV1 <70% of normal

221
Q

Questions you should ask of difficult asthma patients?

A

Do they actually have asthma?Are there conditions that are making the asthma worse?These include:Bronchostasis- abnormal widening of airways causing build up of sputum and causes infection Dysfunctional breathing Severe COPD Vocal chord dysfunction

222
Q

How should asthma be diagnosed in the future?

A

Objective tests such as FeNOand spirometry These are necessary due to over diagnosis based on signs and symptoms This will take time however to build up the infrastructure necessary

223
Q

Alternative treatments for difficult asthma?

A

Anti eosinophils Anti immunoglobulin ESteroid sparing agents: Gold, methtrexate, ciclosporin and Terbutaline (not recommended as can be hard to stop treatment, also monitor heart rate)

224
Q

Anti-IgE (Omalizumab) indications

A

For difficult patient with: FEV1 <80% of normal>2 severe excerabtions+ve prick or RAST test IgE>50 and <700 IU/mlPeople outside of the weight limit and/or serum conc. for IgE should not be given Omalizumab. Usually administered to arm or thigh

225
Q

How does Omalizumab work?

A

Binds to IgE preventing binding to Mast cells Reduces IgE bearing bronchial cells Reduces density of IgE receptors on basophils, mast cells and APC’sReduces conc. of sub mucousal eosinophils

226
Q

T cell profiling

A

Patient with a higher ratio of Th2 to Th1 which is associated with higher levels of interleukins One particular group have higher eosinophil counts and more frequent exacerbations less controlled asthma These patients have eosinophilia promoted by IL-5. Can be treated with anti-IL-5 Mepolizumab

227
Q

Mepolizumab

A

Binds to IL-5 an interleukin which promotes eosinophil growth and activation Reduces clinically significant exacerbations and halves no. of exacerbations requiring hospitilisations

228
Q

Indication for mepolizumab

A

For severe eosinophilicEosinophil count >300 cells/mcl in last 12 months >4 exacerbations requiring oral steroids Maintenance oral steroid dose >5mg prednisolone/dayCompany provides drug at discount for patient access

229
Q

Indications for Resulizumab

A

For severe eosinphilic asthma Eosinophil count >400 cells/mcl in last 12 months>3 exacerbations requiring systemic steroids Company discounts drug for patient access

230
Q

Steroid sparing agents

A

Usually immunosuppressant Reduces the need for steroids but have significant side effects Should be done by specialist Only given after other treatments have proven unsuccessful

231
Q

Terbutaline Infusion

A

2.5mg/day via PICC (Peripherally inserted central catheter)

232
Q

Consequences of long term oral steroid use

A

Endocrine: Cushings syndrome, adrenal suppression Eye: cataracts, glaucoma and papilloedema (optic disk swelling)GI: Ulceration, pancreatitis and candidiasis Immune: Increased chance of infection Musculoskeletal: Myopathy, osteoporosis, fractures, growth suppression Neurological: Makes epilepsy worse Psychiatric: Psychosis, behavioural and cognitive disorders

233
Q

What is COPD?

A

Chronic obstructive airway disease -progressive airflow limitation that isn’t completely reversible -associated with inflammation due to noxious gases

234
Q

What is Chronic bronchitis?

A

Chronic bronchitis is a productive cough present over years and associated with excessive mucous production Symptoms present as:-overweight -cyanosis-increased haemoglobin -peripheral oedema -rhonchi and wheezing

235
Q

What is emphysema?

A

Emphysema is associated with alveolar wall destruction resulting in a reduction in the surface areas of the lungSymptoms present as:-in older men-skinny -SOB-Quiet chest -Hyperinflation -Flattened diaphragm

236
Q

Risk factors that cause COPD?

A

Smoking Urban pollution Textile dust Industrial pollution Biomass

237
Q

COPD vs Asthma

A

COPD has neutrophil rich sputum as opposed to eosinophil rich sputumThere is little variation in air flow There is limited hyper-responsivenessThe t cells involved are Th1 and Tc1 cells (no Th2)

238
Q

How are the airways obstructed in COPD?

A

Airways blocked by mucus Airway walls are thickened due to:-cell infiltrate -thickened smooth muscle -peribronchial fibrosis Loss of elasticity due to emphysema

239
Q

What is the cause of the mucus hypersecretion?

A

Mucous glands are enlarged Goblet cell hyperplasia (lots of them) and metaplasia Mucus production is controlled by neuronal impulses and inflammatory mediators There is increased production but reduced clearance

240
Q

Regulation of mucus production

A

Inhaled irritants stimulate sensory nerve Signal sent to CNS via vagus nerve and signal sent back through cholinergic nerveACh released by nerve and acts on M3 receptor on mucus releasing cellLocal nerves release neuropeptides which act on NK1 receptors Adrenaline suppresses mucus production

241
Q

Inflammation in COPD

A

Leukocytes (macrophages and CD8+ cytotoxic cells) are sent in to clear up irritants Elevated CD8+ counts indicate both this mechanism and also increased susceptibility to infection due to extra mucusNeutrophils will release proteases that damage cells as well as IL-8 and LTB4 which attracts more leukocytes

242
Q

Consequences of inflammation in COPD

A

Epithelium damaged:cilia damaged: less mucus clearance muscle hyperplasiaincreased bronchial permeability Increased stimulation of sensory nerves:neurogenic inflammation stimulates cough

243
Q

What causes a cough?

A

A motor reflex initiated by irritants, chemicals and excessive mucus in the airwayNerves are sensitised by inflammatory mediators

244
Q

Treatments for a cough

A

High dose opioids effective -OTC opioids are pretty ineffective, it does however cause the release of endogenous opioids which can suppress cough The sugar in products can increase salivation which can also soothing coughPlacebo effect is pretty significant in cough suppression: can still be suppressed by opioid antagonists (naloxone)

245
Q

Emphysema

A

Destruction of alveolar walls Smoking can cause imbalance of protease/antiprotease where protease becomes higher alpha1 anti-trypsin deficiency can exacerbate effects of COPD

246
Q

What is elastase?

A

Protease most common in alveolar wall destruction Comes neutrophils/macrophages Degrades elastin, basement membrane and connective tissue in the airways Levels of elastase increase after smoking

247
Q

What are metallo proteinases?

A

Proteinases released by neutrophils and monocytes (collagenase is one example)Inhibited by TIMP TIMP decreased in emphysema and metallo proteinases are increased

248
Q

Cytokines in COPD

A

TNF and IL-8 are increased in COPDTNF increases mucin secretion and elastase production

249
Q

Bronchodilators in COPD treatment

A

Since bronchoconstriction is not the biggest cause of constriction in COPD it’s effect is limited

250
Q

How do muscarinic antagonists help?

A

Reduces parasympathetic stimulation of mucus secretion of mucusMucus associated with reduction in FEV and hospitilisations eg. Ipratropium, Tiotropium and Aclidinium

251
Q

Corticosteriods in COPD

A

I.V corticosteroids help in acute exacerbations Steroids in maintenence have limited effect (but still help a little) on neutrophil counts, cytokine levels or proteases

252
Q

PDE inhibitors

A

PDE 3/4 inhibition leads to bronchodilation PDE 4 inhibition leads to reduced chemotaxis, granule release, respiratory release and TNFalpha release Roflumilast is a PDE 4 selective inhibitor

253
Q

Acute exacerbations of COPD

A

Usually involve infection of some sort Bacerial; H. Influenza, S. Pneumoniae, Viral: Rhinovirus, influenza, parainfluenza and coronavirus

254
Q

What are Serpins?

A

Serine protease inhibitors They are inactivated by oxidative stress

255
Q

Protease inhibitors and antioxidants

A

alpha1 antitrypsin augmentation therapy can be used in patients who have a deficiency Elastase inhibitors have not been great in trials Anti oxidants have limited evidence for efficacy-includes: Vit C/E, Omega 3 etc

256
Q

Alondroate: How can it be used in COPD?

A

A bisphosphonate that acts by killing osteoclasts which are similar to macrophages Could be used as an inhaled powder to kill macrophages in the airways Shown to reduce symptoms of emphysema: alveolar enlargement, TNF production, macrophage production

257
Q

Alternative treatments for COPD

A

High % O2Physiotherapy Mucolytics; N-acetyl cysteine breaks disulphide bonds in mucin DNAse Not useful in COPD but effective in CF

258
Q

Why don’t ICS work in COPD?

A

Oxidative stress results in reduced steroid sensitivity Steroids inhibit neutrophil apoptosis which are causative of COPD Smoking reduces binding of glucocorticoids to the glucocorticoid receptor

259
Q

What is histone acetylation?

A

Histone acetyltransferase (HAT) unpacks chromatin and allows RNA polymerase to bind to DNAAllows for increased binding of transcription factors This enhances inflammatory gene expression Histone deacetylase (HDAC) does the exact opposite-it wraps the DNA tightly on the nucleosome surface -steroids inactivate HAT hence increasing amounts of HAT reduce sensitivity to steroids

260
Q

How does smoking/irritants effect histone acetylation?

A

Infammatory stimulation increases HATOxidative stress reduces HDACMechanism for this might be inactivation via peroxynitrate made by reaction of NO with cigarette smoke and superoxide anions (O2-)The peroxynitrate nitrates the tyrosine residue on HDAC2 blocking enzyme activity and marking it for destruction via protease Combined effect of these increases inflammation

261
Q

Pink puffer (Pp) and blue bloater (Bb)

A

Pp’s suffer mostly from emphysemaBb’s suffer mostly from chronic bronchitis

262
Q

How can COPD be diagnosed?

A

Confirm using post-bronchodilator spirometry (FEV1/FVC <0.7)Rule out alternatives using chest x ray, ecg and blood tests Patients should be >35yrs have one of the following symptoms:-SOB on exertion-chronic cough-regular sputum production-frequent chest infections-wheeze

263
Q

The GOLD standard for post-bronchodilator spirometry

A

1) Mild-FEV1>80%2)Moderate- FEV1= 50-80%3)severe- FEV1= 30-50%4)Very severe- FEV1<30%

264
Q

What are the aims of COPD treatment?

A

Reduce breathlessnessReduce exacerbation frequency Reduce hospitalisation The damage caused by COPD is irreversible hence most treatment is aimed at slowing down the progress of the disease

265
Q

What is the mMRC?

A

The modified Medical Research Council A scale used to measure shortness of breath

266
Q

What is CAT?

A

The COPD assessment test

267
Q

How does the GOLD 2017 ABCD assessment tool work?

A

C and D= A= mMRC=0-1, CAT<10, 0-1 exacerbations (not leading to hospitalisation)B= mMRC>2, CAT>10, 0-1 exacerbations (not leading to hospitalisation)C= mMRC=0-1, CAT<10, >2 exacerbations or 1 exacerbation leading to hospitalisation D= mMRC>2, CAT>10, >2 exacerbations or 1 exacerbation leading to hospitalisation

268
Q

NICE guidance

A

If FEV>50% then offer LABA or LAMAIf FEV<50% then offer LABA+ICS/LAMAIf COPD stable, have FEV1>50% are on a LABA and still are SOB and/or have frequent exacerbations then consider LABA+ICS combo inhaler or LABA+LAMA if ICS not tolerated Give LAMA+LABA+ICS if still SOB despite LABA/ICS treatment NICE recommends Roflumilast (PDE4 inhibitor) if symptoms do not improve despite triple therapy and FEV1<50%

269
Q

Other things to consider with patients on multiple therapy

A

ICS is associated with increased risk of pneumoniaLAMA/LABA is preferred to LABA/ICS in the most recent global guidelines for COPD as they tend to have a greater clinical effect Patient on two inhaled drugs may benefit from a combo inhaler as they are more convenient

270
Q

Trimbow triple therapy inhaler

A

Delivers 100mcg beclometasone, 6mcg formeterol and 9mcg glycopyrrolateHas extra fine particles (on avg. 1.1microns) as it gives a more potent effect for beclometasone (100mcg extra fine=250mcg non-extrafine)

271
Q

What is an acute excerbations?

A

Worsening of patient condition from stable state that is acute in onset and may warrant additional treatmentResults in SOB, worsening cough, increased sputum, change in sputum colour

272
Q

How can exacerbations be reduced?

A

Improved inhaler technique Take flu vaccines, pneumococcal jabEducate on signs and symptoms Emergency antibiotics/steroids to be kept at home

273
Q

Oxygen treatment for COPD

A

Possible lengthening of life seen in severe COPDVery little clinical effect seen in mild-moderate COPDPatients who have type 2 respiratory failure should carry 24-28% Venturi mask and an oxygen alert card detailing oxygen to be given and target O2 sat

274
Q

What is respiratory failure?

A

Where Pa02<8kPa (hypoxia) or PaCO2>6.7kPa (hypercapnia)Hypoxia is known as type 1 resp. failureHypercapnia is type 2 resp. failureCOPD patients require controlled oxygen treatment as they may retain CO2 which could contribute to hypercapnia

275
Q

The 4 steps in the role of a pharmacist in COPD

A

1) Education on signs and symptoms 2) Early diagnosis 3) Management and support during disease 4) Follow up sessions and meds optimisation

276
Q

What is eczema?

A

A reduction in the lipid layer of the skin leading to a loss in moisture No single known cause and is likely a mix of genetic and environmental factorsCan be exacerbated by stress/hormones

277
Q

Complications associated with eczema

A

Infection (usually S. Aureus)Psychosocial- distress caused due to self image Erythroderma- generalised redness of skin can result in dehydration, heart failure, infection and deathEye abnormalities- conjunctiva may be irritated

278
Q

Diagnosing eczema

A

Assess severity:clear, mild, moderate, severe, infected Assess effect on quality of life (impact on sleep, activites and well being)

279
Q

IDing triggers

A

Ask about symptoms after eating certain foods. Perhaps keep a food diary for 4-6weeks Ask about change sin skin care products especially if eczema was well controlled before Ask about symptoms around pets/pollen esp. if eczema is seasonal OTC allergy testing not really recommended

280
Q

Treatment for mild eczema

A

Generous amounts of emollient Mild corticosteroid for flare ups Advise to stay away from irritants and to not scratch eczema affected skin

281
Q

Treatment for moderate eczema

A

Advise to stay away from irritants and to not scratch eczema affected skinGenerous amounts of emollient Moderate potency steroid for flares Mild potency steroids for face/flexuresAntihistamine for itching Topical antibiotics or oral flucoxacillin if infected

282
Q

Treatment for severe eczema

A

Advise to stay away from irritants and to not scratch eczema affected skinGenerous amounts of emollient Moderate potency steroid for face/flexures ~5 daysShort course of oral steroids if eczema is very severe Sedating antihistamines if itching affects sleepOcclusive dressings may help

283
Q

Two approaches to steroid use

A

Step down: Use lowest possible amount to control symptoms Intermittant: Weekend therapy-use on two consecutive days or twice weekly

284
Q

2nd line treatments for moderate/severe eczema

A

Calcineurin inhibitors such as tacrolimus and pimecrolimus-act as immuonmodulating drugs -Calcineurin is responsible for inflammation in the skin via activation of t lymphocytes Should only be prescribed by specialists

285
Q

Tacrolimus

A

Calcineurin inhibitorfor >2yrs Used where appropriate max strength steroids have been used but are ineffective and there risk of further side effects from further use of steroids

286
Q

Pimecrolimus

A

Same indications tacrolimus but for face and neck

287
Q

Alitretinoin

A

For severe hand eczema that has not responded to steroid treatmentstop if:-adequate response achieved -no response at 12 weeks-adequate response not achieved in 24 weeks Part of the retinoid family- related to vit A

288
Q

What is psoriasis?

A

Chronic inflammatory multisystem disease Presents as scaly, itchy skin lesions in the form of patches, papules or plaques Inflammatory cells accumulate in stratum corneum If enough neutrophils build up it is known as pustular psoriasis

289
Q

What can trigger psoriasis?

A

Strep throat infection (esp. guttate psoriasis)Drugs-lithium, NSAIDS, beta blockersSunlight trauma stresssmoking climate changes

290
Q

Treatment for plaque psoriasis

A

Potent steroid OD + Vit D analogue Phototherapy/systemic therapy (specialist only)

291
Q

Treatment for scalp psoriasis

A

Potent steroid ODCoal tar shampoo (but not on its own for severe psoriasis)Where topical steroids cannot be used in mild/moderate cases, Vit D preparations can be usedPhototherapy/systemic therapy (specialist only)

292
Q

Treatment for face/flexure/genital psoriasis

A

Emollient + mild/moderate topical steroid~ 2 weeksPhototherapy/systemic therapy (specialist only)

293
Q

Treatment for gutatte psoriasis

A

If greater than 10% of body surface then referUsually self limiting in~3months so no treatment is an option However if necessary, treat as with limb/trunk psoriasis

294
Q

Pustular psoriasis

A

Generalised pustular psoriasis is a medical emergency that requires immediate specialist treatmentLocalised psoriasis requires dermatologist intervention and usually systemic treatment

295
Q

Erythrodermic psoriasis

A

Requires immediate specialist treatment as it can be life threatening

296
Q

Nail psoriasis

A

Keeps nails short to avoid detachment of nailsAvoid prosthetic nails and manicuresIf mild give no treatment, if severe refer to dermatology

297
Q

How do the eyes constrict?

A

Parasympathetic nerves innervate the sphinteric musclePupils are generally rather small hence there is a high basal level of activity Muscarinic agonists will therefore constrict the eye (miosis) and antagonists will dilate the eye

298
Q

How might the eyes dilate?

A

Radial muscles in the iris are innervated by sympathetic nervesTheir contraction will dilate the eyes (mydriasis)Agonists will dilate and antagonists will constrict the eyes

299
Q

What do the ciliary muscles do and how do they work?

A

They have parasympathetic innervation When they contract, the ligaments attached to the lens go slack and allows for focus on near objectsWhen they are relaxed, the ligaments go taut and stretch the lens out allowing for focus on far objectsVery little adrenergic innervation

300
Q

What does the ciliary body epithelium do?

A

Produces aqueous humour which:Maintains intraocular pressure Provides nutrient to eyeReleased into posterior chamber

301
Q

How can we control the formation of aqueous humour?

A

alpha1 agonists: constrict blood flow thereby by reducing blood supply and pressure to ciliary body alpha2 agonists: reduces cAMP which reduces the vol of AH produced beta1 agonists: increases the amount of AH produced Hence to limit the amount of AH produced we use alpha agonists (clonidine) or beta blockers (timolol)

302
Q

Dipiveferin

A

Pro-drug of adrenalineConsists of adrenaline ester bonded to lipd molecule Esterase breaks the ester bond allowing adrenaline to interact with receptors Not very selective hence not licensed in UK

303
Q

Acetazolamide- How does it work?

A

Production of AH is dependent on the active transport of HCO3- hence if you can inhibit the production of HCO3- you can reduce production of AHAcetazolamide inhibits carbonic anhydrase reducing production of HCO3-Brinzolamide is same mechanism but has long half life

304
Q

How can we improve the drainage of AH?

A

Muscarinic agonists constrict the ciliary muscle as when it is relaxed the extra bulk can block the drainageUveosclereal flow can be improved via use of prostoglandin analogues (Latanoprost)

305
Q

What abnormality causes closed angle glaucoma?

A

The iris deforms and blocks the trabecular network and uveosclereal canalWhile open angle glaucoma is slow onset and progressive, closed angle is rapid onset and can cause irreversible damageMore common amoungst asians and inuits

306
Q

Treatment for closed angle glaucoma

A

Osmotic drugs to remove water from aqueous humour reducing its vol. thereby reducing intraocular pressure however it is only a temporary fixThe only permanent treatment is surgery

307
Q

The 2 types of age related macular degeneration (AMD)

A

Macula necessary for sharp vision Dry AMD- slow onset, caused by degeneration of one area, no treatmentWet AMD- rapid onset, can be treated by reducing leakage of local vasculature

308
Q

Wet AMD

A

Caused by growth of leaky blood vessels under retinaTreatment with photodynamic therapy-verteporforin photoactivated by red low energy laserCauses occlusion of vasculature meaning that they don’t leak anymoreVascular endothelial growth factor (VEGF) causes such leakge so can be used as a target for inhibition (anti-VEGF)

309
Q

Screening for glaucoma

A

If 35-50yrs then eye check every 4 yrsIf>50yrs the eye check every 2yrsAlso consider at risk groups:afro/carribeanfamily historyshort sightednessdiabetes

310
Q

First line treatment for chronic open angle glaucoma (COAP)

A

Generic PGA (eg. Latanoprost) if there is risk of COAP in their lifetime Offer additional topical treatment if not sufficiently controlled with monotherapy If not controlled with double therapy then refer to specialist Do not offer treatment to those with intraoculaar pressure less than 24mmHg

311
Q

Pharmacological augmentation in surgery

A

Mitomycin C to prevent scar tissue from blocking drainage tubes

312
Q

Common side effect of PGA eye drops

A

Conjunctival hyperaemia- eye becomes pink/redThis is due to more blood in the conjunctiva as a result of the dilation of the supplying arteries

313
Q

Can patients apply two eye drops at once?

A

Not recommended as it would cause overflow hence most of the drug would be lost leave at least 5 mins between the application of each Always check patients eye drop technique as they could be rubbish at it so their condition doesn’t improve

314
Q

How can patients absorb systemic absorption of their drugs?

A

Keep eyes closed for 2 mins after administration Keep pressure on lacrimal punctum (press on the tiny knobbly bit of the eyelid)

315
Q

Can the patient use contact lenses with eye drops?

A

Unless medically indicated remove contacts before application Contra indicated for ointments/oily formulationsFor long term therapy unpreserved drops can be used

316
Q

Cautions for PGA’s (Latanoprost)

A

Care need in patients with COPD, asthma or compromised respiratory function

317
Q

Cations for beta blockers (Timolol)

A

Contraindicated in patients with bradycardia, heart block or heart failure Do not use in patients with respiratory conditions

318
Q

Cautions for carbonic anhydrase inhibitors (Dorzolamide, brinzolamide)

A

Stop if sulfonimide like reaction occurs Can enhance effect of ACE inhibitors and other anti hypertensives

319
Q

Cautions of alpha2 agonists (clonidine, brimonidine)

A

Cautioned against use where there is CVD cerebral deficiency, raynauds syndrome, hypotension, depression

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