CSP2 Flashcards
Locus of control
Expectancy that rewards are controlled by external forces or one’s own behaviour (internal vs. external)
Health belief model
action is a function of perceived likelihood of illness, seriousness, costs and benefits of action
Self efficacy
belief in ability to success, task specific
States of change
Pre contemplation (happy with status quo) Contemplation (think about change) Preparation Action Maintenance or Relapse
What extent of obesity is associated with increased all cause mortality?
> 34
Not Grade 1 obesity 30-35
Basal metabolic rate for women
1200-1600 kCal per day
Total energy expenditure for most women
2000-2500
Strategies of behaviour modification
Self monitoring stimulus control goal setting cognitive restructuring incentives
Successful slimming Recommendations
Diet and activity
400 kcal/day activity
Eat 5 times
Weigh 1 a week
Physical activity recommendation
30 minutes moderate activity on 5 or more days a week
Up to an hour/day to prevent obesity
Up to 90 minutes/day to maintain weight reduction
Who can have orlistat Rx (Xenical) - one you prescribe?
- 12 years or older
- BMI >30
- BMI>37 with HTN, diabetes, dyslipidemia
Orlistat Rx (Xenical) dosage
120mg
With fat containing meals
Orlistat OTC (Alli) dosage - over the counter.
18 years
reduced calorie and low fat diet needed as well
60mg with fat containing meals
£12 per week
Orlistat effectiveness
Meta analysis shows weight change at 12 months compared to placebo
Side effects of orlistat
- diarrhea
- steatorrhea
- minimised by maintaining strict low fat diet
- reduce intake of fat soluble vitamins = multivitamins for 2 weeks
Atkins diet
Max 20g of carbs/day
Protein and fat
Appetite Suppressants
Methylcellulose Amphetamine derivatives Sibutramine (SSRI derivative) Rimonabant (cannabis antagonist) GLP1 agonist = liraglutide, daily subcut injection, feel fuller and satisfied, reduces speed of stomach emptying, nausea and vomit, thyroid tumours, pancreatitis
Malabsoprtion inducers
Orlistat
Acarbose
SGLT2 inhibitors
Metabolic stimulants
Thyroxine
Beta-agonists
Gastric surgery
BMI 40 or above or 35 or above with comorbidities
Gastric Bypass = Roux en Y, restrictive and malabsoprtive (changed gut hormones)
LAP BAND = restrictive
Product licence
Marketing Authorisation
Off label
Use/route outside licensed indication
Liability
None to prescriber if
- correct diagnosis
- correct medicine choice
- patient warned of potential adverse effects
MHRA
Medicines and Healthcare Products Regulatory Agency
Classification of Medicinal Products
General Sale List
Pharmacy Only medicines
Prescription Only medicines
Controlled Drugs
Prescription Only Medicines
To anyone except injections
Injections if purpose of saving life
Midwives, chiropodists, opticians, paramedics, practititoners direct
FP10s
GP prescriptions
FP14
Dentist prescriptions
FP10MDA-SS
Addict prescriptions
OM
On-in the morning:at night
PRN
When required
SOS
If neccessary
Black List
Indigestion remedies
Analgesics
Hypnotics & Anxiolytics
(not available on NHS)
Supplementary prescribing
Voluntary prescribing partnership
Between independent prescriber and supplementary prescriber
Agreed patient specific clinical management plan with patient agreement
BAN
British Approved Name
Most commonly implicated medications in adults
Antiplatelets
Diuretics
NSAIDs
Anticoagulants
NPSA
National Patient Safety Agency
Clinical Trial Positives
No confounding
No bias
Gives correlation
Define pharmacodynamics
Relationship between drug level and effect
‘what drug does to body’
Hysteresis
Relationship between drug concentrations and effect is not direct
Counter clockwise hysteresis
Sensitisation of receptors Delay of drug to site of effect Agonist metabolite generation Slow receptor kinetics Time dependent protein binding
Clockwise hysteresis
Tolerance of receptors Feedback regulation Time dependent protein binding Antagonist metabolite generation Disequilibrium between arterial and venous concentration
Drug targets
Enzymes
Ion channels
Ion carriers/transporters
Receptors
Affinity
How avidly drug binds to receptor
Low Kd = high affinity = low conc of ligand to bind half of receptors
- determined by strength of receptor-ligand interaction
Receptor Ligand Interaction
Electrostatic (common)
Hydrophillic
Covalent (least common)
Selectivity
Drugs ability to preferentially binding to certain receptors
Specificity
Number of different mechanisms involved In drug action
Potency
Conc. (EC50) or dose (ED50) of drug required to produce 50% of drugs maximal effect
Median inhibitory concentration
IC50
Concentration of an antagonist that reduces a specified response to 50% of the maximal possible effect
Efficacy
max effect (Emax) of a drug
Full agonist
Maximal response by occupying all or fraction of receptors
Partial agonist
Less than max response even when drug occupies all of receptors
Antagonist
Affinity but no efficacy
Inverse agonists
Agent which binds to same receptor as agonist but induces pharmacological response opposite to that agonist
Competitive antagonist
Reversibily binds to receptors as agonist but without activating receptor so competes for same binding site
Non comp antagonist
Reduces magnitude of max response attained by any amount of agonist
Allosteric modulator
Indirectly influences effects of an agonist
conformational change from binding to distinct site
Positive allosteric modulator
induces amplification of agonist
negative allosteric modulator
Reduces effects of agonist
Other antagonism types
Chemical
Physiologic
Pharmacokinetic
biological therapies
Engineered macromolecule products like protein and nucleic acid based drugs
Antagonists
More specific and high potency/efficacy
Pharmacokinetics
Description and prediction of time course of drugs in the body
Quantitative study of ADME
Bioavailability
Fraction of unchanged drug that is absorbed intact and reaches the site of measurement
Vd
Volume of distribution
= amount in body/conc in plasma
Metabolism
Phase 1 = catabolic, P450 enzymes
Phase 2= anabollic
Cytochrome P450
Haeme co-factor
In mitochondria and ER
activity varies
First pass metabolism
- before reaches site of measurement
- gut wall or liver
Elimination pathways
kidney hepatoiliary lungs saliva tears sweat other secretions
1st order elimination
rate of elimination/metabolism proportionate to drug conc.
0 order elimination
constant rate of drug eliminated/metabolised
Half Life Rules
3.3 half lives to 90% steady state
5 half lives to <5% of initial conc.
Clearance
Total = renal + hepatic + other Links drug conc. to rate of elimination Volume per unit time Clearance of organ = organ blood flow x extraction ratio of organ total = (F x Dose)/AUC
What do pre-contemplators need?
Information
What do those wanting to change need?
Practical advice and guidance
What do those trying and failing need?
Specialist treatment
most to least intensive ways of changing behaviours
Specialist treatments - durg clinics, obesity treatments
Doctor advice
Health promotion
ways of changing behaviours, in order of having largest population impact to smallest
health promotion
doctor advice
specialist treatment
Obesity - strength of drive, effort required, target pop., efficacy of supportive meds
Strong strength
Substantial effort
target - well motivated, varied resources and barriers
Limited supportive meds
Most valuable complication of obesity that by treating obesity would be economically effective?
DIABETES
Define NEAT
non exercise activities - fidgeting
Resting metabolic rate
- increases with muscle mass
- declines with age
- declines during restriction of energy intake (diet)
Approaches to changing behaviour
Behaviour
Diet
Medical
Behaviour Modification Requirements
Goals - specific and realistic
Plan of action
Manageable slow changes
Strategies of obesity behaviour modifications
Self Monitoring
Stimulus Control
Goal Setting - 5% weight loss over 6M, 1lb a week
Cognitive Restructuring
Dietary Interventions
Quack cures
Fad diets
FAT AND SUGAR
About eating less not really about food groups
Problem with fat
High calories but least satiating nutrient unlike protein
Order of calorie content of food groups
Fat
Alcohol
Protein & Carbs
Fibre
Who gets pharmacotherapy obesity treatment?
- if BMI 27-29.9 + co-morbidities
- or higher BMI
Who gets obesity surgery?
- BMI 35-39.9 + co-morbidities
- >40
New obesity drugs
Semaglutide
Lorcaserine
phentermine
Topiramate
What does orlistat do?
- blocks absorption from gut of 1/3 fat which is eaten
- if too much eaten there is oily leakage, flatulence, diarrhoea
- teaches people which foods contain fat = behavioural so then when stop taking tablets stopping eating fats should stay with you
Reasons for initiation and maintenance of smoking?
Initiation = social Maintenance = pharmacological
What is addiction a product of?
Person + drug + circumstances
Peak Seeker
- seeking for peak effect of smoking
vs
Heavy smoker - not very trough and peak life, don’t let it drop as get withdrawal/restless
Only a level of nicotine you can tolerate as it makes you sick
Nicotine
- stimulant
- increases HR
- stops boredom
- immediate reward
- neuroadaptation, dopaminergic, ACH receptor density
- discomfort at low levels and high
- illusion of positive effect as get rid of restlessness when don’t have it
- other chemicals also play a role in smoke
- nicotine hunger when conc deplete in brain or during other stress
- nucleus accumbens
Smoking risk vs benefit
- higher stress until post quit
- social, less bored, enjoy
- weight loss
- increased vigilance but lower performance
How to assess a smoker’s dependence?
- best = time to first cig in the morning (under half hour then dependent, serious if 5 mins)
- CO in expired breaths
- not how many cigs or types
How long is smoking withdrawal?
4 weeks
Help is with these symptoms
IRRITABILITY
worse in heavier smokers
difficulty concentrating <2 weeks
LT urges to smokes but less and less frequent
Rarer = night time waking, constipation, mouth ulcers, RTI, gum bleeding, lower pain threshold, productive cough
Average weight gain post smoking quitting
5-6kg
Signs of smokers post quit
HR drop adrenaline and cortisol drop tremor drop increased skin temp. decreased metabolism of caffeine and other drugs
What effects smoke cessation success?
Heavy smokers
Depression
Urge to smoke
Clinical advice smoking
Drugs for withdrawal
Reassurance and explain
Advise against early dieting regarding weight gain
Adaptive Immunity Features
- vast diversity of cell types
- clonal expansion
- danger of autoimmunity
- B and T lymphocytes
Innate Immunity Features
- no autoimmunity
- no clonal expansion
- neutrophils/monocytes/eosinophils/mast cells
- all cells of one kind
B vs T lymphocytes
mature in bone marrow vs thymus
B have antibody as receptor
T only recognised when presented on cell surface
Clonal deletion of B lymphocytes
- in bone marrow
- If an antigen engages with antibody
- antibody expressed as IgM
- if T dependent, in LN after activation during expansion and mutations
Outer domain of HLA
2 alpha helices on beta pleated sheet
- antigen between helices
HLA function
present peptide antigens to T lymphocytes Endogenous on class 1 to CD8 T lymph Exogenous on class 2 to CD4
MHC define
- cluster of genes which encode molecules in antigen presentation
- HLA region
HLA define
Human Leukocyte Antigen
Genes and the molecules they encode
Class I loci
HLA-A, B, C
Encoded at A, B, C locus
2 of each
Class II loci
HLA-DP, DQ, DR alleles
2 of each
Allele number
Number after locus letter
A*02:01:02:11
First pair = cross reactive group
Second pair = difference in amino acid sequence
Third pair = silent polymoprhisms in exons
Fourth pair = polymorph in introns
What do APCs express
both class I and II
Define haplotype
Team of alleles encoded on short section of 1 chromosome. Inherited from 1 parent and passed on intact if short enough otherwise crossovers
Transplant terms
Auto = given back to same person Iso = between 2 identical twins Allo = between 2 members of same species Hetero/xeno = different species
Kidney transplants
Allografts = antibody/T lymph rejection
AB against = ABO
T lymphocytes = HLA + peptide
Types of rejection in kidney transplants
Hyperacute Rejection = mins to 4 days, complement
Acute = 5 days - 3 months, antibody, T lymphocyte
Chronic rejection = antibody or T lymphocyte, infection
How to avoid rejection
- do not if recipient has AB against donor HLA molecules
- match donor and recipient for HLA alleles
- use antirejection therapy
- perform a cross match between donor cells and recip serum
- screen all patients
- avoid sensitisation = blood transfusion, pregnancy, previous graft
Antirejection therapy
- must be taken except if identical twin
- prednisolone
- azathioprime/mycophenolate
- tacrolimus/ciclosporine
- monoclonal ABs
Bone Marrow Transplant
T lymphocyte mediated all
No need for cross matching of serum screening
Host vs graft disease & graft vs host
How to prevent HvG and GvH
autografts use
in allografts T lymphocyte may be depleted
Antirejection therapy
Type 1 hypersensitivity
IgE mediated
Histamine release from mast cells/basophils
Always allergic
Hayfever, asthma, anaphylactic shock
Type 2 hypersensitivity
IgG & IgM mediated
Complement & phagocytosis
Autoimmune haemolytic anaemia, thrombocytopenia, myasthenia gravis, Goodpastures, pemphigus
Type 3 hypersensitivity
Immune complexes
Autoimmune/allergic/antimicrobial
Extrinsic allergic alveolitis
Vasculitis, glomerulonephritis, arthritis
Type 4 hypersensitivity
Activated T lymphocytes Granulomas = CD4, macrophages Without granuloma = CD8 Antimicrobial = TB, hep B, allergy, nickel sensitivity, coeliac Autoimmune = sarcoid
Type 5 hypersensitivity
ABs
Stimulate rather than destroying target
Graves
HA B27
Ank Spon
RA
Colitic arthritis
Psoriatic Arthritis
Cw6
Psoriasis
DQ2 & DQ8
Coeliac disease
DQ8 & DQ2
T1D
DQ6
MS
DR4
RA
Eaton-Lambert Syndrome
Autoantibody to presynaptic Ca2+ in NMJ = weakness
Small cell lung cancer
Auto-immune haemolytic anaemia
Autoantibodies to red cells
Destruction by complement system and phagocytes
Some AB act in warm and cold
Causes of autoimmune haemolytic anaemia
Infections = syphilis, mycoplasma, EBv, virsus
Neoplasms = CLL, lymphoma
Autoimmune disease = SLE, RA, UC, PSS
Drugs = penicillin, methyl dopa
Autoimmune thrombocytopenia
Idiopathic thrombocytopenic purpura SLE CLL Lymphoma Drugs = AB, co-trimoxazole
Coeliac disease
- inflammatory disease
- steatorrhoea, bloating, malabsorption
- villous atrophy, deepened crypts, ulcers, lamina propria infiltrate, intra-epithelial lymphocytes
Autoantibodies
IgA Antibodies Anti-transglutaminase antibodies Anti endomysial antibodies Anti reticulin antibodies Anti Gliadin antibodies
Gluten Coeliac
Alpha -gliadin - resistant to digestion in lumen of bowel
Transglutaminase
tTG
enzyme
removes side chain amino group from glutamines converting them to glutamate
engaged when alpha gliadin leak into lamina propria and become deamidated
Bind to class II HLA
Activates T lymph which secrete cytokines = changes = villous atrophy, crypt enlargement
HLA in coeliac
DQ2 and DQ8
Role of IgA autoantibodies in coeliac?
Do not activate complement or opsonise for phagocytosis
May contribute by trapping antigen or block tTG action
Coeliac RF
European
Females x 2
Severity varies
Infancy but often later
Other coeliac features
dermatitis herpetiformis
Other coeliac features
dermatitis herpetiformis
IM contraindicated in who?
Haemophillia
Max volume of IM vs subcut
5ml vs 2ml
