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week 18 (Y2) > the patient > Flashcards

the patient Flashcards

1
Q

From the pharmaceutical knowledge that you already have, what might be the issues in delivering person-centred care with children?

A

formulation and availubility and suitability of meds

licencing
off label

communication barrier

Vd

developing immune system

increased risk of ADRs

cognative abilities of child lack understanding

informed decicion making

competency and understanding

dosage forms

calculations

responsibility

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2
Q

what is pill school

A

Tablets are safer and more convenient to use (storage and sugar content)

Children are often reluctant to change and parents lack knowledge about switching tablets

Use a variety of sweets of different sizes

Children as young as 3 can attend pill school (Evelina)

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3
Q

Sources of information - children

A

BNFc

Paediatric Formulary, Guy’s and St Thomas’s, King’s College London and University Hospital Lewisham

Trust guidelines

Summary of Product Characteristics (SPC) for individual formulation
https://www.medicines.org.uk/

Neonatal and Paediatric Pharmacists Group
http://nppg.org.uk

Royal College of Paediatrics and Child Health

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4
Q

What do we need to consider when communicating with children and their parents or carers? (our views)

A

compliance with treatment LT

child friendly language

involve the child

eye contact

remove barriers, crouch to childs level

consent from child / parent esp if examination is involved

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5
Q

what does the green book tell us

A

Provides up to date details of immunisation procedures in the UK
Which immunisations, when, how frequently, indications and contraindication, mechanism of action (briefly)

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6
Q

what is active immunisation

A

The deliberate induction of an immune response

To use the natural immune defence to provide long term protection against infection

Sometimes known as “vaccination”

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7
Q

what is primary infection

A

first interaction with pathogen

response to antigen

antibodies

memory created

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8
Q

what is secondary response to pathogens / infection

A

where there is already a baseline memory

response is more rapid

more abs

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9
Q

describe the course of an infection

A

establishment of infection

induction of adaptive response

adaptive immune response

immunological memory

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10
Q

what is acquired ammunity

A

Acquired immunity, also known as adaptive immunity, refers to the immune response that the body develops over time in response to specific pathogens (such as bacteria, viruses, or parasites) or foreign substances (such as toxins). This type of immunity is characterized by its specificity and memory.

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11
Q

what is vaccination

A

Stimulate our body to develop specific immunity
Protection and memory

When we encounter a pathogen we respond
Rapidly
Effectively
Via secondary immune response

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12
Q

what can a primary response be caused by?

A

vaccination

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13
Q

what is immunoconversion

A

“Immunoconversion” typically refers to a process where a person’s immune status changes from negative to positive due to exposure to an infectious agent or vaccination.

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14
Q

what is herd immunity

A

Herd immunity occurs when a large portion of a population becomes immune to a disease, either through vaccination or previous infection. This indirect protection reduces the spread of the disease, benefiting even those who are not immune. It’s achieved when enough people are immune to disrupt the chain of transmission. Achieving herd immunity through vaccination is safer and more effective than through natural infection.

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15
Q

tell me about immunoconversion with vaccine

A

Not all people respond strongly
No vaccine is 100% effective
No problem
Herd immunity

Chance of an infected person contacting a non-immune person is low

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16
Q

tell me about risk to benefit in vaccination

A

Successful vaccination programmes rely upon engagement/compliance
If people perceive a low disease risk (unlikely to get it; not severe if they do) then they worry about risk
Risk of adverse reaction perceived worse than risk from the disease

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17
Q

what are the features of an effective vaccine

A

safe - should not cause illness or death

protective - protect against illness, resulting in exposure to live pathogen

sustained protection - protection against illness must last several years

includes neutralising antibody - some pathogens like polio infect cells that cannot be replaced. neutralising abs prevent the infection of these non replaceable cells.

induces protective T cells - some pathogens are more effected by cell mediated responses

practical considerations - low cost per dose
biological stability
ease of administration
few side effects

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18
Q

what are the 4 vaccine types

A

Live, attenuated vaccines
Inactivated vaccines
Toxoids
Sub-unit vaccines

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19
Q

what are live attenuated vaccines

A

measles, mumps, polio sabin vaccine, rubella, TB, yellow fever

adv - strong immune response - lifelong immunity with fw doses

dis - refrigerated storage may mutate to virulent form

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20
Q

what are inactivated or killed vaccines

A

cholera, influenza, hep A, plague, polio salk vaccine, rabies

adv - stable, safer, no fridge

dis - weaker immune response, booster usually required

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21
Q

what are toxioid vaccines

A

diphtheria
tetanus

adv - immune system becomes primed and recognises bacterial toxins

dis -

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22
Q

what are subunit vaccines

A

Heb B
pertussis
strep pneumonia

adv - specific antigens lower chance of ADRs

dis - hard to develop

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23
Q

what is attenuation

A

To weaken
Reduce pathogenicity of microbe

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24
Q

Grow organism under abnormal culture conditions meaning

A

Grow virus in non-human cells

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25
Q

tell me about edward jenner

A

Milk maids resistant to small pox
Late 18th Century
Cowpox (Vaccinia virus)
Disease of cows (zoonotic in humans)
Poorly pathogenic in humans
Protects human from small pox

A natural attenuation

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26
Q

1967: WHO Global campaign to eradicate smallpox

A

The Soviet Union first suggested a global effort, and donated >80% of vaccine needed.

A freeze-dried vaccine employed
Storable without refrigeration
(1 month stability).

This was delivered with a bifurcated needle
(low dose and could be sterilized).

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27
Q

attenuation in TB

A

Abnormal culture
BCG strain of M. bovis - doesn’t cause TB but has preserved antigenicity
Variable protection offered (0-80%: Malawi-UK)
Schedule of immunisation is now risk-based

Genetic Modification
More rapid and reliable than above

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28
Q

what are most anti varial vaccines rn

A

live and attenuated

Induce strong immune responses
Promote life-long immunity

29
Q

what mecahnisms can live and attenuated induce

A

Tc

30
Q

in killed virus vaccines, what is not incuced and why

A

no replication → no intracellular proteins
No MHC I presentation → no Tc generation

31
Q

live and attenuated vaccines risk

A

Risk of reversion
Type 3 Sabin vaccine (OPV) differs at 10 of 7429 nt → neurovirulent strain (vaccine-induced disease) (risk 1 in 2.4 x 106)

Can cause disease
Young, old, immuno-suppressed

Vaccinated people can transmit the attenuated vaccine organism

Storage problems

32
Q

tell me about polio sabin vs salk vaccine

A

eradication using sabin was unlikely, so we returned to using the salk vaccine

33
Q

how are toxin vaccines made

A

For diseases caused by exotoxins
Diphtheria (Corynebacterium diphteriae)
Tetanus (Clostridium tetani)

Toxin purified and inactivated
Physical or chemical means
Complete detox needed w/o loss of epitope structure

Toxoid can still seroconvert
Neutralising Abs

34
Q

how are sub unit vaccines made

A

Avoids use of whole pathogens

Immunise with key components of the pathogen
Alone they don’t cause disease
Response to them protects

Streptococcus pneumoniae →Pneumonia
Polysaccharide from capsules inhibit phago
Poor at stimulating
Pneumococcal polysaccharide vaccine (PPV)
Pneumococcal conjugate vaccine (PCV)

35
Q

tell me about peptide vaccines

A

Reductionist

Vaccinate with part of a protein

Problem
Peptides are short and don’t fold
Reduced ability of Abs to bind due to loss of conformation
Poor at humoral stimulation

Provides relatively effective hepatitis B vaccines

Recombinant peptides can be used

36
Q

tell me about DNA vaccination

A

A surprise
Insert cloned DNA for a gene
Animals respond (B&T) to the encoded protein
DC-dependent

37
Q

considerations in vaccines

A

Administration
Route can be crucial
i.m. injection may not protect so well against infection at mucosal surfaces
You must induce protection at the relevant site

Salk vaccine (IPV)
Injectable, killed
Sabin vaccine (OPV)
Oral, live attenuated
Induction of mucosal immunity required
Oral-faecal spread

38
Q

what is an adjuvant

A

An adjuvant is a substance added to vaccines to enhance the body’s immune response to the vaccine antigen, which is the component of the vaccine that triggers the immune system. Adjuvants work by stimulating the immune system, leading to a stronger and more long-lasting immune response to the vaccine.

39
Q

tell me about adjuvant features

A

Non-specifically enhances immune response to Ag with which it is mixed

Used for non-living vaccines

Must be
Safe
Bio-degradable
Stable
Chemically defined
efficient

40
Q

what are the two ways in which adjuvants act

A

Act in two ways
Activate the responding cells of the immune system

Alter the delivery by affecting the rate or route of delivery
e.g. promote DC involvement and delivery to local draining lymph nodes

41
Q

challenges in vaccination

A

Mutating pathogens
Influenza
HIV

New and re-emerging diseases
TB
SARS
New coronavirus
Zika

42
Q

what is Ab

A

antibody

43
Q

what is mAb

A

monoclonal antibody

44
Q

what happened in 1975

A

Kohler & Milstein, Cambridge
Developed MONOCLONAL ANTIBODY TECHNOLOGY

45
Q

what are monoclonal antibodies

A

Monoclonal antibodies (mAbs) are laboratory-produced molecules that are designed to mimic the immune system’s ability to fight off harmful pathogens such as viruses or cancer cells. They are called “monoclonal” because they are made by identical immune cells that are clones of a unique parent cell.

Here’s how they are typically created:

Isolation: Scientists isolate a specific type of immune cell (called a B cell) from an organism that has been exposed to the target antigen, such as a virus or cancer cell.

Fusion: They then fuse the isolated B cell with a cancerous myeloma cell to create a hybrid cell called a hybridoma. This hybridoma has the ability to produce antibodies in large quantities.

Production: The hybridoma cells are cultured in the laboratory, where they multiply and produce large amounts of identical antibodies, known as monoclonal antibodies.

Monoclonal antibodies are highly specific to the target antigen they were designed to recognize

46
Q

what cells procuce abs

A

Antibodies, or immunoglobulins (Ig), are produced by B cells, a type of white blood cell. B cells recognize foreign molecules called antigens and produce antibodies tailored to bind to and neutralize these antigens, helping to eliminate pathogens and provide immunity.

47
Q

How many different Abs does each Ab-producing cell make?

A

Each antibody-producing cell, known as a B cell, produces only one specific type of antibody, determined by its unique genetic arrangement.

48
Q

mAb technology

A

Take a B cell, grow it and harvest the mAb

They die by apoptosis

49
Q

structure and function of Abs

A

heavy inner chain
light outside chain

hinge region attaching two heavy regions

antigen binding region on tips of heavy and light chain

50
Q

what is the fab region of abs

A

tips of heavy and light chains

antigen binding
toxin neutralisation
opsonisation

51
Q

what is opsonisation

A

Opsonization is the process of marking pathogens for destruction by immune cells through the binding of antibodies or opsonins to the pathogen’s surface. This facilitates recognition and engulfment by immune cells, aiding in the pathogen’s destruction.

52
Q

what is the Fc region of an Ab

A

bottom straight halves of the two heavy chains

complement activation
ADCC
phagocytosis

53
Q

what is ADCC Abs

A

ADCC stands for Antibody-Dependent Cellular Cytotoxicity. It’s a process where certain immune cells, such as natural killer (NK) cells, recognize and kill target cells that have been bound by antibodies.

54
Q

what is complement activation

A

Complement activation is a key component of the immune response that involves a group of proteins called the complement system. This system consists of over 30 proteins that work together to help clear pathogens from the body, enhance inflammation, and regulate the immune response. 3 main methods

55
Q

mAb therapy examples

A

Specific
Targeted
Effective
“Magic Bullet”

56
Q

Problems with Ab therapy (monoclonal)

A

Passive therapy
Transfer of immunity to a recipient to give instant protection
No long lasting memory (unlike active immunisation)
Cost of production
Specificity?
HAMA
Human anti-mouse antibodies
mAbs are antigens from mice
They elicit an immune response
“serum sickness”

57
Q

what is Ab engineering

A

Antibody engineering involves modifying or designing antibodies for various purposes, such as therapeutics and diagnostics. Techniques include optimizing antibody properties, creating hybrid antibodies, humanizing antibodies, generating monoclonal antibodies, designing bispecific antibodies, and producing antibody fragments. These approaches have revolutionized antibody-based products and continue to drive advancements in biotechnology and medicine

58
Q

what is CDR grafting

A

CDR grafting is a technique in antibody engineering where the complementarity determining regions (CDRs) from one antibody are transferred to the framework regions of another antibody. This process allows for the creation of antibodies with improved properties, such as enhanced binding affinity or altered antigen specificity.

(CDRs) are regions within the variable domains of antibodies that directly interact with antigens.

59
Q

Ab engineering examples

A

Genetically modified mouse
e.g. Xenomouse (Amgen)
Knock-out of mouse heavy & light chain loci
Graft human Ig loci
Immunise
Mice produce HUMAN mAbs

Phage Abs
Human Ig genes in a library
Ab-like molecules displayed on surface of phage
Grown in bacteria

60
Q

what are antigens, one word

A

bivalent

meaning they have two identical antigen-binding sites.

61
Q

what are bispecific Abs

A

Bispecific Abs
Abs are bivalent
Engineered to recognise two different Ags

62
Q

what is orthoclone OKT3

A

Orthoclone is a brand name for a monoclonal antibody product called muromonab-CD3, which was developed for use in transplantation medicine. Muromonab-CD3 is a mouse-derived monoclonal antibody that targets the CD3 antigen, a protein found on the surface of T cells, a type of white blood cell involved in the immune response.

Muromonab
Fully murine mAb
Mouse anti-human CD3 (a T cell Ag)
Used to treat transplant rejection
Depletes T cells

63
Q

what is a murine mAb

A

A murine monoclonal antibody (mAb) is a type of monoclonal antibody that is derived from mice. Murine monoclonal antibodies are produced by fusing mouse B cells, which produce antibodies, with immortalized myeloma cells, resulting in hybridoma cells that can continuously produce specific antibodies.

64
Q

Remicade, what is it used for

A

Infliximab

lixi

‘-li-’ = immune system target
‘-xi-’ = Chimaeric mAb
Anti-TNF (a cytokine)
Used to treat Rheumatoid arthritis and other inflammatory conditions

65
Q

what is a chimaeric mAb

A

A chimeric monoclonal antibody (mAb) is a type of monoclonal antibody that is engineered by combining genetic elements from different species, typically from mice and humans. Specifically, the variable regions of the antibody, which determine its antigen-binding specificity, are derived from a mouse antibody, while the constant regions, responsible for effector functions and stability, are of human origin.

66
Q

what is rituxan

A

Rituximab
‘-tu-’ = tumour target
‘-xi-’ = Chimaeric mAb
Anti-human CD20 (a B cell Ag)
Used to treat non-Hodgkin’s lymphoma (a B cell tumour)

67
Q

what is herceptin

A

Trastuzumab
‘-tu-’ = tumour target
‘-zu-’ = humanised mAb
Anti-HER2 receptor (a growth factor receptor)
Used to treat SOME breast cancer

68
Q

summary mAbs

A

can be efficient therapeutics

have problems associated with use

strategies developed for avoiding problems

69
Q

mAbs the future of therapeutics?

A

lots of investment
watch and wait
listen to the news for the latest

week 18 (Y2) (3 decks)

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