PMY2204 - Clinical Pharmacology and therapeutics Flashcards
(312 cards)
1
Q
outline cellular mediators of inflammation.
A
- cytokines
- Produced by immune cells but also fibroblasts and endothelial cells etc…
- Integral part of inflammatory signaling
- Includes chemokines, interferons, interleukins, tumour necrosis factors
- Cytokines bind to cell surface receptors to trigger intracellular signaling pathways
2
Q
outline plasma derived mediators of inflammation.
A
- produced mainly in the liver eg bradykinin
- most mediate vasodilation and endothelial permeability
3
Q
outline rolling in leukocyte recruitment and activation
A
- Adhesion receptors on surface of circulating leukocytes bind to adhesion proteins expressed on endothelial cells
- P-selectin and E-selectin expressed on surface of endothelium
- Integrins and glycoproteins expressed on leukocytes
- Leukocytes roll slowly along surface of blood vessel wall
- Low affinity interactions
- Blood flow promotes rolling
4
Q
outline stable adhesion in leukocyte recruitment and activation.
A
- Chemokines secreted from macrophages activate the rolling leukocytes
- Integrins bind with higher affinity
- Leukocytes immobilized on blood vessel surface (stable adhesion)
- Endothelium express integrin ligands (ICAM-1)
- Adhesion of leukocyte to endothelium is a key hallmark of inflammation
5
Q
outline the vascular stage of acute inflammation.
A
- Arterioles and venules near the site of injury constrict briefly, then dilate causing cell congestion
- Increased capillary permeability results in fluid moving into affected tissue
- Fluid leaves capillaries
- Blood in the circulation becomes more viscous flowing slowly and allowing clotting to occur
6
Q
what are some causes of chronic inflammation?
A
Persistent injury or infection
7
Q
A
8
Q
Prolonged exposure to a toxic agent
A
9
Q
A
10
Q
Autoimmune disease
A
11
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A
12
Q
what are the 2 main types of inflammation?
A
- Acute inflammation
- Rapid onset
- Short duration
- Initial response of the body to harmful stimuli (ceases when stimuli is removed) - Chronic inflammation
- Prolonged inflammation
- Slow onset
- Longer lasting
13
Q
what are the 2 overlapping stages of acute inflammation?
A
Vascular and cellular
14
Q
what are the 4 stages of leukocyte recruitment and activation?
A
1- chemoattraction
2- rolling
3- stable adhesion
4- transmigration
15
Q
what are the 4 stages of phagocytosis?
A
- engulfment of target
- phagosome formation
- phagosome formation with lysosome
- ## degradation of target
16
Q
what are the 5 signs of inflammation? PRISH
A
• Pain: chemicals released at nerve endings
• Redness: increased blood flow
• Immobility: fluid accumulation
• Swelling: fluid accumulation
• Heat: increased blood flow
17
Q
what can mediate inflammation?
A
- cellular mediators eg histamine / serotonin / prostaglandins / thromboexanes / cytokines
- Eicosanoids eg arachidonic acid / prostaglandins / thromboexanes
- plasma derived radiators eg bradykinin (produced mainly in the liver)
18
Q
what is chemosttrcation ion leukocyte recruitment and activation?
A
- Macrophages in affected tissue release pro-inflammatory cytokines
- Cytokines recruit leukocytes
- Triggers endothelial cells to express cellular adhesion molecules known as selectins
- P-selectin first to be expressed on endothelial cells during acute nflammation then E-selectin
- Selectins have carbohydrate recognition motifs enabling binding to glycans on leukocyte
19
Q
what is chronic inflammation?
A
- Develops when the causative agent in acute inflammation is not resolved
20
Q
A
21
Q
- Prolonged duration (weeks or months) Characterized by simultaneous destruction and repair of the tissue
A
22
Q
A
23
Q
- Inflammation should cease when repair is complete
A
24
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A
25
what is inflammation?
- Complex biological reaction that occurs in vascularized tissues in response to harmful stimulus
- Brings cells and molecules from circulation to site of damage/injury
- Aim is to eliminate the ‘threat
26
what is the cellular stage of acute inflammation?
- Initiated by leukocyte recruitment to area - mostly neutrophils
- Leukocytes adhere to vessel wall and then pass through into site of inflamed tissue (emigration/extravasation)
- Leukocytes move through tissue, guided by chemical signals (chemotaxis)
- eukocytes engulf and degrade bacteria/cellular debris (phagocytosis)
- Leukocyte recruitment and activation are crucial steps in cellular stage of acute inflammation.
27
what is transmigration in leukocyte recruitment and activation?
- Also referred to as diapedesis, emigration and extravasation
- Leukocytes extend pseudopodia through gaps between endothelial cells
- Migration occurs via PECAM expressed on leukocytes and endothelial cells which interact, pulling leukocyte across
endothelium wall
- Leukocytes cross basement membrane (proteolytic degradation)
- Leukocytes move to site of injury via chemotaxis
28
how do sterioids work as anti inflammatory simply?
they reduce the production of inflammatory mediators (cytokines)
29
how does dexamethasone work?
Anti-inflammatory mechanism of action
- Reduces vasodilation and permeability of vessels
- regulates gene expression
- Dampens activation of immune cells
30
Outline the mechanism of action of steroids.
- Directly affect cells of the immune system to suppress pro-inflammatory responses
- Inhibit production of pro-inflammatory cytokines such as IL-2, TNF, IL-1β
- Promote production of anti-inflammatory cytokines such as IL-10
- Promote the apoptosis of T-cells, macrophages and dendritic
cells leading to a reduced immune response
+ Reduce NK cell cytotoxicity
+ Reduce B cell antibody production
+ Reduce expression of cell surface molecules important for T-cell activation
- Collective anti-inflammatory effect
31
what are steriods?
- Natural and synthetic compounds
- Important physiological role in the body
- Cell membranes and cell signaling
- Function as anti-inflammatory agents
32
whats an example of endogenous steroid and what role do they play?
eg Cholesterol
- Highly important biological role
- Present in lipid membranes
- Facilitates membrane fluidity (temperature dependent)
- Controls membrane permeability
- Reduces passage of molecules across the membrane by
increasing packing density of phospholipids
33
whenever steroid - receptor complex get into the nucleus what two things happen?
1. Cause transcription/translation of proteins such as IkB by binding to DNA and functioning as a transcription factor
2. Directly interact with NFkB (p50:p65) to suppress cytokine synthesis
34
give 2 examples of short acting and long active B2 adrenergic agonists.
Short acting (4hrs)
- salbutamol / terbutaline
Long acting (8-12hrs)
- salmeterol / formoterol
35
how do b2 adrenergic receptors work?
- they are G protein coupled receptors
- G protein associates with adenylate cyclase and activates it
- enhances conversion of ATP to cAMP
- activates PKA and downstream signals
36
how do leukotrienes work? Are they preventers?
they bind to and activate receptors (GPCRs)
In asthma leukotriene release and receptor activation
results in Bronchoconstriction as well as contributing to
inflammation
- they are used as preventer drugs
= Causes bronchodilation
= Dampen inflammation
= Relieve symptoms
EG montelukast
37
how do methylxanthines work?
- act as a bronchodilator
- act as anti inflammatory
only administered in Hospital as requires monitoring, not given as an inhaler but instead orally
38
how do muscarinic antagonists work? are they short acting / long acting or both?
they block the action of acetylcholine on M3 muscarnic receptors (these cause the constriction therefore we are blocking this from happening)
- they are competitive antagonist
- cause relaxation of smooth muscle in bronchioles
these are SHORT acting
39
whar are bronchodilators used to treat and what do they do?
they are used to treat asthma and COPD and they open up the airway which relieves the difficulty in breathing
40
what do b2 adrenergic agonists work?
- stimulate B2 receptors preferentially
- cause relaxation of smooth muscle in bronchioles
used in both relievers and controllers
41
what is the difference between relievers and controller bronchodilators?
How do they both work (what do they act on) = both the same
Relievers
- short acting beta-2 agonist
- muscarinic antagonist
Controllers
- long acting beta-2 agonist
- leukotriene receptor agonist
both act on the autonomic nervous system
- causes relaxation of muscle in the airways making them open up.
42
do males of females get it more often?
prevalance of wheeze and diagnosed asthma is higher in boys than girls, but rate of decline is higher in boys than girls
43
outline 4 diagnosis points of acute severe asthma.
Any one of;
Respiratory rate ≥ 25/min
Heart rate ≥ 110 beats/min
PEF 33-50% best or predicted
Inability to complete sentences in one breath
44
outline some stimuli that would trigger an asthmatic attack.
- allergens
- infection
- pollutants
- occupational
- drugs (NSAID)
- exercise
45
outline the early phase of asthma response
- allergens interact with mast cells causes release of histamine, cysteine-leukotrienes and prostaglandin D
- these cause spasm of the bronchiole smooth muscle
46
outline the late phase of asthma response
- a progressive inflammatory reaction, initiated during early phase
- activated cytokine-releasing T helper lymphocytes infiltrate and release further leukotrienes, cytokines, chemokines and toxic protein
- toxic proteins cause damage and loss of epithelium
- growth factors released from inflammatory cells cause hyperplasia and hypertophy
47
what are the 3 classifications of asthma?
Episodic/seasonal asthma – occurs at intervals throughout the year e.g. when fungal spores are released
Chronic asthma – persistent disease state, with acute exacerbations periodically
Exercise induced asthma – airways sensitive to colder, drier air from ‘mouth breathing’
48
what is the definition of asthma?
chronic inflammatory disorder of the airways.
49
how do antimuscarinics work?
inhibit acetylcholine-mediated bronchospasm
Block muscarinic receptors causing ↓ smooth muscle tone and a resultant bronchodilation. Can be short or long-acting
50
how do b2 adrenoceptor agonists work?
Stimulation of 2 receptors increases intracellular cAMP – leading to airway relaxation
51
how do corticosteroids?
- preventer
Anti-inflammatory agents which reduce local hypersensitivity reactions, bronchial oedema and mucus secretion
52
how do methylxanthines work?
Inhibit phosphodiesterase, hence ↑ cAMP and causing airways to relax
53
outline Leukotriene receptor antagonists eg montelukast
- Leukotrienes show increased potency and more protracted effect in producing bronchospasm, compared to histamine
- Particularly useful in exercise-induced asthma or asthma with concurrent rhinitis
- Not to be used for acute attacks
- Less effective than inhaled steroids, but appear to have additive effect
54
what are the main bronchodilators (relievers)?
B2 adrenoceptor agonists - can be short / long acting
55
outline the effets of smoking cessation in COPD.
- 40% of those with COPD are current smokers
- About 25% quit rates with effective cessation programmes
- Nicotine replacement therapy (NRT), varenicline or bupropion combined with a support programme
56
outline the main aspects of the pathophysiology of COPD
- airflow obstruction and gas trapping occours
- gas exchange abnormalities
- pulmonary hypertension
- exacerbations
- multimorbidity
57
what causes COPD?
- gene - environment interactions
Eg smoking, pollution, AAT deficiency etc
58
what is copd?
Heterogeneous lung condition characterised by chronic respiratory symptoms due to abnormalities of the airways
59
what is FEV1?
the volume exhaled in the first second of a FVC measurement
Remember this is always done as a % of the expected value when we are clinically interpreting the result.
60
what is FVC?
Forced Vital Capacity: the volume of air you can forcibly exhale from the point where you have inhaled fully
61
62
what is the definition of FVC forced vital capacity?
The volume of air you can forcibly exhale from the point where you have inhaled fully
63
what is the first treatment for COPD. What then happens if symptoms are still lowering the quality of life?
1. First use short acting bronchodilators
- SABAs* (beta-2) and SAMAs (muscarinic) – agonists and antagonists
2. If symptoms still limiting quality of life or has exacerbations
- Move to long-acting bronchodilators (LABA plus LAMA)
- If asthma features present (e.g. atopy, high eosinophils, variability) consider LABA plus ICS (inhaled corticosteroid)
64
outline cholesterol sources?
• Majority is produced endogenously by the liver
• Dietary cholesterol comes almost entirely from animal
sources
65
outline how high density lipoproteins work?
- Removes excess cholesterol from membranes and other lipoprotein particles and convert it into cholesteryl ester (a more hydrophobic form of cholesterol)
66
outline how low density lipoproteins work?
- Major carrier of cholesterol in humans, about 70% of total plasma cholesterol is in LDL
- LDL arise from further degradation of IDL.
- LDL deliver cholesterol to tissues for the synthesis and repair of cell membranes. There are two mechanisms by which cholesterol is transferred from LDL to cells: passive endocytosis and receptor- mediated uptake
67
outline tricglycerides and fatty acids.
- most abundant lipid + most concentrated energy source
- consist of (1) glycerol and (3) fatty acid; joined together via condensation reactions
68
what 3 lipoproteins transport cholesterol?
1. Chylomicrons
Largest; lowest in density;
Transport dietary lipids to adipose, cardiac, and skeletal tissue
2. VLDL (Very low-density lipoproteins)
Transport of lipids synthesised in the body begins with their incorporation into VLDL
3. IDL (Intermediate-density lipoproteins)
The remnants of VLDL metabolism are called IDL
69
what are essential fatty acids?
group of fatty acids which the body needs to survive
- the human body cannot manufacture these; need to be derived from our diet.
70
what are phospholipids?
Similar to triglycerides but one of the fatty acids
bound to the glycerol molecule is replaced by
another type of chemical structure containing
phosphorous and nitrogen
- phosphorous group is polar and therefore water soluble
71
what are prostaglandins?
- Tissue hormones
- Lipids comprising a 20 carbon unsaturated fatty acid that contains a five carbon ring
- They are formed and released by cell membranes based on different stimuli
- Typically exert a local effect and then deactivated
72
what are sterioids?
- A large and important class of lipids
- All have as their main feature a steroid ring system - shown in yellow in this figure
- Four carbon ring structure
73
what are the 4 classifications of lipids?
- triglycerides, phospholipids, steroids and prostaglandins
74
what are the general roles of lipids?
energy, structure, vitamins, protection, insulation, regulation are some functions of lipids
75
what are the two types of statins?
1. Type I eg simvastatin
• All derived from fungal metabolites
• All share similar structure
2. Type II eg atorvastatin
• Synthetic
• Larger structures, easier synthesis
• Fluorophenyl group instead of butyryl group
• Form more robust interactions with HMG-CoA reductase
• Longer lasting inhibition
76
what is atherosclerosis?
- Formation of atheroma is a uniquely human disease
• Affects large and medium-sized arteries
• Atheromatous plaques occur in most people and progress silently over many years
• Leads to luminal narrowing or precipitates thrombi (clots) which obstruct blood flow
• Heart - coronary artery disease
• Brain - ischemic stroke
77
what is the difference between saturated and unsaturated?
double bonds = unsaturated
no double bonds = saturated
78
when does cholesterol becoming a problem?
• The body makes too much low density lipoprotein (LDL)
• Cholesterol intake from food exceeds the body’s ability to dispose of it
79
outline some co-morbidities of CVD.
- hypertension
- diabetes
- chronic kidney disease
- dyslipidaemia
- AF
and more
80
outline some risk factors for CVD.
- age
- family history
- ethnicity
- smoking
- lifestyle
- weight
and more
81
outline the stages of atherosclerosis.
• Fatty material (atheroma) typically begins to build up in the
lining of the artery walls in early adulthood (fatty streak)
• Over time, the body tries to deal with this by creating a seal
over the atheroma, encasing it in fibrous connective tissue
(fibrous plaque)
• Over time (can be years), this plaque can enlarge, leading
to advanced atheroma
• Eventually, the artery can become so narrow that it doesn’t
let enough blood through, or atheroma plaques can
rupture.
• When a plaque ruptures, a blood clot forms to try and
repair the damage to the artery wall, but can lead to
complete blockage, starving the affected part of the body
of blood
82
what is cardiovascular disease?
CVD is an umbrella term to describe diseases which affect the heart and blood vessels
83
what is dyslipidsemia? and what are two types?
• Dyslipidaemia refers to unhealthy levels of one or more lipids in your blood
• Typically, it means elevated LDL or TG levels and low levels of HDL
1. Primary dyslipidaemia- genetic factors interacting with environmental factors
2. Secondary dyslipidaemia is an acquired condition- i.e. caused by other things such as diabetes or obesity or certain medications
Total cholesterol is a powerful predictor of CVD events
HDL-C levels are inversely relate to CVD risk
84
what should you do if patients QRISK score is >10%.
offer lifestyle advice however this needs checked to see if they actually do make the changes.
Offer a statin treatment
85
how do angiotensin receptor blockers (ARBs) work?
• They block the action of Angiotensin II on the Angiotensin type I receptor
• Blockade of binding, reduces peripheral vascular resistance (afterload)
• Dilates the efferent glomerular arteriole which ↓ intraglomerular pressure and slows the progression of CKD
• ↓ aldosterone reduces NA+ and water retention- this can reduce venous return (pre-load)
used when persistent cough with ACE inhibitor
86
how do thiazide-like diuretics work?
• Inhibits the Na+/Cl- co-transporter in the distal convoluted tubules of the nephron
• Prevents re-absorption of Na+ and therefore water by osmosis
• Results in diuresis causing an initial fall in extracellular fluid volume
eg indapamide
87
how do you calculate blood pressure?
blood pressure = cardiac output x peripheral resistance
88
Outline how calcium channel blockers work (dihydropyridine class)
• Mechanism of action:
• Decrease Ca2+ entry into vascular and to a lesser extent cardiac cells
• Reducing intracellular Ca2+ concentration
• Causing relaxation and vasodilation of the arterial smooth muscle
• Lowering blood pressure
eg amlodipine
89
what is a side effect of calcium channel blockers?
flushing on the face or chest area
If they have swelling around ankles they will need to be changed to a different class
90
what is beta blocker’s mechanism of action?
• Reduce force of contraction and speed of conduction in the heart
• Prolong the refractory period at the AV node
• Reduce renin secretion from the kidneys
91
what is daily circadian variation?
In non-hypertensive patients, BP will naturally decrease by 10-
20mmHg overnight and increase upon waking for the first few hours of the day.
• Statistically, more strokes/MI are noted at this time
92
what is spironolactone mechanism of action? (Potassium sparing diuretics)
• Blocks the action of aldosterone, increasing sodium and water excretion and potassium retention. Therefore, reducing blood pressure
• Also known as potassium-sparing diuretics
• Patient must have a potassium level of <4.5mmol/l and resistant hypertension
93
what is the main side effect of ACE inhibitor and what do you need to do?
persistent cough - needs swapped to a different class
94
what is the mechanism of action for angiotensin converting enzyme (ACE) inhibitors?
- block the action of ACE which prevents the conversion of Angiotensin I to Angiotensin II
- angiotensin II stimulates release of aldosterone which increases blood pressure (hence why we block it)
95
what is the normal range of blood pressure?
90/60 to 120/80
the top number is when heart pump bloods out
bottom number is when the blood is going back to heart
96
whst is alpha blockers mechanism of action? (Eg doxazasin0
• Blockade of alpha1 adrenoreceptors found in the smooth muscle of blood vessels. Causes vasodilation and a fall in BP.
97
outline the metabolism of morphine.
1. Glucuronidation is the principal route for metabolism of morphine
2. Conjugates are mostly excreted in the urine (90% within 72 h) – glucuronic acid conjugate
3. 3-conjugate is made in more abundance than the 6-conjugate
4. Drugs that inhibit/induce UGT (i.e. glucuronidation) may influence effect of morphine
5. Oxidative metabolism (e.g., by CYP3A4 to normorphine) is a minor contributor
98
outline the metabolsim of codeine.
1. Codeine is relatively inactive
2. Codeine is a prodrug – because it requires metabolism to promote analgesic effect
3. Active metabolite? Morphine or C6G? – How can poor metabolisers still experience analgesia
4. C6G is the principal metabolite
5. Morphine and norcodeine both glucuronidated
99
outline the site of action of opioids.
1. Ascending pain pathways:
All three opioid receptors are expressed in the dorsal horn of the spinal cord inhibit dorsal horn pain transmission &
release of excitatory transmitters from the primary afferents
Opioids activate the descending inhibitory pathways, reduce the transmission of pain signals in the spinal cord
100
what is the mechanism of action of opioids ?
1. Main cellular actions are:
- Close voltage gated ion channels on presynaptic nerve terminals
- Decrease release of glutamate, the main excitatory amino acid released from nociceptive nerve terminals
- Also inhibit release of substance P release
- Hyperpolarise and thus inhibit postsynaptic neurones by opening K+ channels.
101
what is the principal effects of morpine (opium)
- analgesia
- reduce GI motility (hence constipation side effect)
- nausea / vomiting
- dependence / tolerance
102
what is used to treat morphine overdose?
• Naloxone – used to overcome respiratory depression post
surgery
– Rapid onset (1-2 min post i.v administration)
– Complete antagonist of morphine (no analgesia/respiratory
depression)
– Specifically used to treat morphine/diacetylmorphine overdose
103
outline how paracetamol works
- weak inihibotor of COX activity
- inhibits COX pathway in the central nervous system (CNS) but not in peripheral tissues
• Analgesic and anti-pyretic activity is comparable to other anti-inflammatory drugs
• Lacks any significant peripheral anti-inflammatory activity (might be inactivated by the high
levels of ROS in the inflammatory environment
• Thought to predominantly act on CNS – PGs are important in pain perception
104
outline NAPQI and how it gets broken down?
NAPQI is produced via the N-hydroxylation metabolic pathway.
It is liver toxic
It gets detoxified by conjugation to glutathione.
105
outline what inhibition of COX 1 and COX 2 bring about?
Inhibition of COX-2 accounts for the therapeutic benefits
and inhibition of COX-1 for the side-effects of NSAIDs
COX 2 is only expressed when there is a pathology going on eg pain
106
what does homodimer refer to?
that there is two COX enzymes that work together (they come in pairs) - homo refers to that they are both the same type eg you wouldnt get a COX 1 bound with a COX 2. It would be the same type eg two COX 1’s
107
what is COX? What does it do?
What is COX?
Cyclooxygenase (COX) is an enzyme responsible for converting arachidonic acid into prostaglandins (PGs) and thromboxanes (TXs), which play key roles in pain, inflammation, fever, and clotting. There are two main isoforms of COX:
COX-1 ("Housekeeping Enzyme")
Produces prostaglandins that protect the stomach lining, maintain kidney function, and support platelet aggregation (clotting).
Found in most tissues and involved in normal physiological processes.
COX-2 ("Inducible Enzyme")
Expressed during inflammation, injury, and fever.
Produces prostaglandins that cause pain, swelling, and fever.
108
what is the metabolic pathways of paracetamol?
• Glucuronidation (40-65%)
• Sulphation (20-40%)
• N-hydroxylation and GSH conjugation (<15%)
• N-hydroxylation and GSH conjugation (<15%)
= NAPQI!!!!! toxic to the liver
109
where is COX-1 found?
COX-1 is constitutively (always) expressed in most tissues, and appears to act in a homeostatic or cytoprotective manner
110
where is COX-2 mainly found?
COX-2 is an inducible enzyme which means it becomes upregulated in response to a stimuli
111
what is naloxone used for and why?
to reverse respiratory depression (antagonist)
- mainly used post surgery, where the patient has a lot of opioids due to pain. Side effect of opioid is respiratory depression hence why we use this to reverse it
112
what is the difference between endogenous opioids and exogenous opioids?
• Endogenous opioids
– peptides produced by the body which have morphine-like properties (the body produces its own opioids in reponse to pain)
• Exogenous opioids
– administered drugs eg. Morphine
– bind to opioid receptors to produce analgesia and other effects
113
Where are high concentrations of opioid receptors located?
Found in high concentrations in
– Brain
– Spinal cord
– Periphery eg. Gut, lungs
114
outline the role of the hypothalamus and pituatary gland in control of the thyroid gland.
🔹 1. Hypothalamus
Role: Acts as the control center.
Releases Thyrotropin-Releasing Hormone (TRH).
TRH travels to the anterior pituitary gland.
🔹 2. Pituitary Gland (specifically the anterior pituitary)
Role: Receives TRH and responds by releasing Thyroid-Stimulating Hormone (TSH).
TSH travels via the bloodstream to the thyroid gland.
🔹 3. Thyroid Gland
Role: Stimulated by TSH to produce and release:
Thyroxine (T₄) – mostly inactive form
Triiodothyronine (T₃) – the active form
115
What are signs and symptoms of hypothyroidism?
• Fatigue
• Weight gain
• Being sensitive to cold
• Constipation
• Depression
• Muscle ache and weakness
• Muscle cramps
116
what are some signs and symptoms of hyperthyroidism?
• Nervousness, anxiety and irritability
• Mood swings
• Difficulty sleeping
• Persistent tiredness and weakness
• Sensitivity to heat/ increased sweating
• Swelling in your neck from an enlarged
thyroid gland (goitre)
• Irregular and/or unusually fast heart rate
(palpitations)
117
what does T4 and T3 do?
• Stimulate metabolism
– Lipid metabolism
– Carbohydrate metabolism
• Influence growth and development
both are produced by the thyroid gland - controlled by the hypothalamus and anterior pituitary
118
what is hyperthyroidism?
• Production and secretion of excessive amounts of thyroid hormone
• Characterised by Increased metabolism of all body
systems
119
what is hypothyroidism?
• Decreased production of thyroid hormones
• Characterised bye the Slowing down of body processes
• Disease onset is Usually 30-60 years
120
what is the classification of hypothyroidism?
1. Primary hypothyroidism
– Autoimmune hypothyroidism
– Antithyroid drugs
– Postoperative hypothyroidism
2. Secondary hypothyroidism
– Hypopituitarism
– Hypothalamic disease
121
what is the treatment for hyperthyroidism?
• Antithyroid drugs (carbimazole), initially
supplemented by ß-blockers
• Radioactive iodine
• Surgery (partial thyroidectomy)
122
what is used to treat hypothyroidism?
levothyroxine
123
outline some risk factors of type 2 diabetes.
Over 40 years of age
• Asian and African-Caribbean background
(over 25 years old)
• History of gestational diabetes
• High blood pressure, heart disease and
stroke (CAD)
• Family history of Type 2 Diabetes
• Overweight (BMI>30)
• Waist circumference (M>94cm, F>80cm)
• Sedentary lifestyle (little or no exercise)
124
what are sine symptoms of type 1 diabetes?
• Onset relatively quick
• Consequence of high blood glucose levels
– Excessive urination (polyuria)
– Thirst (polydipsia)
– Visual disturbances
– Fungal infections
125
what are some common initial presentations of type 2 diabetes?
• Thrush
• Blurred vision
• Slow healing of cuts/wounds
• Chest pain
• Erectile dysfunction
126
what are the 3 main actions of insulin?
– Rapid
• Active transport of glucose & amino
acids from blood
– Intermediate
• Promotes action of enzymes
– Long-term
• Promotion of growth
127
what does insulin do in short?
it reduces circulating blood glucose.
128
what is causes symptoms of type 2 diabetes?
Cause
– Absolute insulin deficiency
– Relative insulin deficiency
– Insensitivity to insulin
• Rises in prevalence with age
129
what is diabetes?
Diabetes is a condition where the amount of glucose in the blood is too high
130
what is type 1 diabetes?
– Body cannot produce insulin
– Acute onset
– Normally presents before age 40
– Accounts for about 8-10% of all people with diabetes
131
what is type 2 diabetes?
– Cannot make enough insulin or insulin does
not work properly (insulin resistance)
– Often present for years before diagnosis
132
what is type 3,4 and 5 diabetes?
• Type 3 diabetes
– Diabetes associated with other diseases e.g. Pancreatic disease
• Type 4 diabetes
– Gestational
– Occurs in 2-12% of pregnancies
– More common in minority ethnic groups
– Higher risk of developing diabetes later in life
• Type 5 diabetes
– Malnutrition
133
what other tests do you need to carry out to diagnose someone with type 2 diabetes?
Symptoms PLUS one of following
• RANDOM PLASMA GLUCOSE > 11.1mmol/l
• FASTING PLASMA GLUCOSE > 7.0mmol
• ORAL GLUCOSE TOLERANCE TEST > 11.1mmol
Testing on a second day ESSENTIAL if symptoms absent
134
why do you need to take basal levels of insulin?
because it causes an increase in protein synthesis and a decreasd breakdown in protein
135
is insulin normally used for type 1 or type 2?
type 1 it is essential but may be used in type 2 to help control blood glucose.
136
outline biphasic insulin.
• Contain combinations of insulins (eg.
short acting and intermediate acting)
• Profile has two phases
– Immediate part to cover meal which follows
injection e.g. breakfast or evening meal
– Longer acting part to cover lunch or overnight
• Reduces number of injections required
137
outline intermediate acting insulin.
• Absorbed slowly after injection
– Onset of action (1-2 hours)
• Peak action 3-12 hours
• Duration of action 11-24 hours
138
outline prolonged action analogues.
• Insulin released at a steady state from injection site
• Peakless plateau ~ 90mins following injection
139
outline rapid-acting insulin analogues?
• Provide more physiological insulin profile
• Quick onset (~15 min) and short duration (2-5 hours)
• Peak effect after one hour
140
outline soluble insulin.
• Slow onset of action (30-60 minutes) compared to analogues
• Peak action 1-4 hours after injection
• Duration up to 9 hours
141
outline some common injection sites for insulin.
– Abdomen (fastest absorption)
– Upper Arm
– Buttocks
– Thighs (slowest absorption)
142
what is the aim of treatment with insulin?
– Sufficient meal-time insulin to avoid high post-prandial blood glucose
– Sufficient basal insulin to prevent hyperglycaemia and hypoglycaemia
143
outline some advantages and disadvantages of metformin.
1. Advantages
• Enhances weight loss
• Drug of choice in overweight (BMI>25kg/m2)
• Improves lipid profile
2. Disadvantages
• Gastric intolerance
• Contra-indicated in impaired renal function
• Lactic acidosis
144
outline some non-drug treatment of type 2 diabetes.
• Non-drug treatment
– Healthy eating
– Regular exercise
– Weight loss
– Smoking cessation
– Safe and sensible alcohol intake
145
Outline the effects of thiazolidinediones.
• Enhance the effects of insulin in adipose tissue & skeletal muscle
• Inhibits hepatic gluconeogenesis
146
outline the mechanism of action of sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors)
Eg dapagliflozin
- Block re-absorption of glucose in the kidneys
- Promote excretion of excess glucose in the urine
- Once daily dosing
- Urine will test positive for glucose
- Effectiveness dependent on kidney function
- Increased incidence of genital & urinary tract infections
- they also promote weight loss
147
outline the mechanism of action of the classes of oral antidiabeteics.
• Sensitize body to insulin and/or decrease
glucose production
• Block glucose reabsorption in kidneys
• Stimulate insulin production
• Target incretin system
• Slow absorption of starch
148
what are incretins and what are there effect?
- gastrointestinal hormones released in response to meals to increase insulin secretion
• Two gut peptides
– GLP-1 (Glucagon like peptide 1)
– GIP (Glucose dependent insulinotropic
peptide)
• Rapidly degraded in the circulation by the
enzyme dipeptidyl peptidase-4 (DPP4)
149
what is the mechanism of action of metformin (Biguianides)
acts on the:
- intestine (increase glucose metabolism)
- liver (decrease hepatic glucose production)
- skeletal muscle (increases glucose uptake)
all leads to hyperglycaemia
150
outline some clinical presentations of chronic kidney disease?
• Lethargy
• Itch
• Breathlessness
• Cramps (can be worse at night)
• Poor sleep
• Weight loss and loss of appetite
• Increased nocturia and increased urine output
151
outline the pathophysiology of CKD.
1. Hyperfiltration at the glomeruli occurs- this increases glomerular permeability and contributes to patients developing proteinuria (protein in urine)
2. The renin-angiotensin-aldosterone system is activated, increasing blood pressure and further increasing hyperfiltration at the glomerulus
3. Cytokines and growth factors are also released
4. Increased capillary pressure in the glomerulus and the presence of inflammatory mediators causes chronic inflammation- the filtering ability of the glomerulus is reduced, and therefore, the eGFR is reduced. This can lead to systemic complications
152
problems that can arise from CD?
A WET BED
| Letter | Function lost | Resulting Complication |
| ------ | -------------------- | ----------------------------------------- |
| A | Acid-base balance | Metabolic acidosis |
| W | Water removal | Pulmonary oedema |
| E | Erythropoiesis | Anaemia |
| T | Toxin removal | Encephalopathy |
| B | Blood pressure | Hypertension, CVD |
| E | Electrolyte balance | Hyperkalaemia |
| D | Vitamin D activation | Bone mineral disease, hyperparathyroidism |
153
what are some general management strategies for CKD?
- achieving good control of bp
- eating a healthy balanced diet
- smoking cessation
154
what is chronic kidney disease?
CKD is defined as abnormalities in kidney function or
structure or both present for more than three months with
associated health implications
155
what is CKD hyperphosphatemia?
- Caused by reduced phosphate excretion
- Noted by elevated phosphate levels in blood tests
- Treated using low phosphate diet and phosphate binders
156
what is proteinuria?
• Proteinuria- the presence of protein in your urine
• Indicates a degree of kidney damage
• Measured via a urine sample
• Reported as the albumin: creatinine ratio (ACR)
157
what is the main thing when when treating CKD?
you need to treat the problem that is being caused due to CKD, eg iron deficiency.
158
what test results would indicate that the patient has chronic kidney disease?
A diagnosis of CKD is made if any of the following are present
for a minimum of three months:
• Signs of kidney damage such as:
• ACR >3mg/mmol
• Presence of active urinary sediment or ongoing haematuria
• Abnormalities noted following biopsy (histological changes)
• Structural changes noted following ultrasound
• An eGFR <60ml/min/1.73m2
159
outline OTC treatment and advice for acute bronchitis.
- expectorant = guaifenesin
- suppressant = dextromethorphan
- demulcent = simple linctus
- adequate fluid intake and rest
160
outline the interpretation of CRB65 test?
o0: Suitable for home treatment (low severity)
o1: Consider hospital assessment (intermediate severity)
o2: Strongly consider hospital assessment (intermediate severity)
o3 or 4: Urgent hospital assessment (high severity)
161
what are some defence mechanisms of the lower respiratory tract?
• Mucociliary transport
• Swallowing, coughing and sneezing
• Alveolar macrophages
• Immunoglobulin A
• Normal bacterial flora
162
what are some red flags for acute bronchitis?
- duration > 3wks
- short of breath/wheezing
- chest pain
- persistent nocturnal cough in children (can be sign of asthma)
- nature and colour of mucus (if red) (if frothy can be a sign of heart failure)
163
what are some symptoms / clinical features of acute bronchitis?
• Increased mucus production
• Oedema (build up of fluids) in the bronchus
• Patients may have wheeze
• Patients may have a temperature
• Infection may clear in several days (self-limiting infection, but repair of the bronchial wall may take several weeks - hence the cough for up to 3 weeks)
164
what are some symptoms of community acquired pneumonia?
• Cough
• Shortness of breath
• Sputum production
• Pleural pain
• Sweating
• Fevers
• Rigors
• Aches and pains
165
what causes community acquired pneumonia?
it can be viral or bacterial
- often the exact microbe does not get identified
- it is a very common cause of death
166
what does the CURB-65 severity test test for?
o Confusion: new disorientation in person/place or time or abbreviated mental test score of 8 or less
o Blood Urea Nitrogen level >7 mmol/mol
o Raised Respiratory Rate: ≥30 breaths per minute (normal between 12-18)
o Low Blood pressure: diastolic ≤60 mmHg or systolic <90 mmHg
o Age, 65 years or older
167
what is acute bronchitis?
• Acute inflammation of the bronchial tree producing mucus which gets evacuated via a cough
• Acute cough can last up to 3 weeks
• Absence of pneumonia
• Usually self-limiting (usually is viral)
168
what is back up (delayed) prescribing?
• When there is clinical uncertainty about whether a condition is
self‑limiting or is likely to deteriorate, back‑up prescribing (also
known as delayed prescribing) is an alternative to immediate
antimicrobial prescribing
• Encourages the patient to try self-management in the first instance
• However, it also allows a person to access antimicrobials without another appointment if their condition gets worse
169
what is the CRB 65 test?
it is a severity test for community acquired pneumonia.
o Confusion: new disorientation in person/place or time or abbreviated
mental test score of 8 or less
o Raised Respiratory Rate: ≥30 breaths per minute (normal between 12-18)
o Low Blood pressure: diastolic ≤60 mmHg or systolic <90 mmHg
o Age, 65 years or older
170
what is the interpretation of the CURB-65 test score?
score:
0-1 = low risk
2 = intermediate risk
3-5 = high risk
171
How can you distinguish between hospital acquired pneumonia (HAP) and community acquired pneumonia (CAP)
- if a pt develops pneumonia 1-2 days after admission then this is classified as CAP
- if a pt develops pneumonia 48 hrs or more after admission this is classifieds as HAP ( cause by bacteria that are related tp hospitals, tend to have higher rates of resistance)
172
outline councelling points for CAP after they have been prescribed antibiotic.
• Rest
• Pain management
• Maintain fluids and nutritional support in prolonged illness
• Preservation of the cough reflex (huff cough technique – see Canvas)
• Stop smoking if applicable
• Adherence to treatment i.e., completing the course of antibiotics even if they improve
• Seek re-assessment if managed in the community and symptoms worsen/do not
improve within 3 days or they become systemically very unwell
• Antibiotic side effects
• Provision of written information on condition (to refer to when go home)
8
173
what antibiotic do you give for a pt with CAP bit has intermediate risk severity?
- amoxicillin capsules 500mg tid
If atypical pathogen suspected then use dual therapy with:
- clarithromycin tablets 500mg bd for 5 days
or in pregnancy
- erythromycin tablets 500mg aid for 5 days
174
what antibiotic is used to treat CAP in a pt with penicillin allergy who has an intermediate risk severity?
- doxycycline capsules 200mg on the first day, then 100mg once a day for 4 days
Or
- calrithromycin 500mg tablets bd for 5 days
175
what is 1st line treatment for HAP for non severe?
Co-amoxiclav: 500/125 mg three times a day orally for 5 days then review
176
what is bronchiolitis?
• A respiratory condition which typically affects infants less than 12 months of age
• Caused by a viral infection
• In conjunction with mucus leads to variable obstruction of the small airways - complete obstruction in some and partial obstruction in others
• Leads to impaired gas exchange
177
what is the choices of antibiotics for community acquired pneumonia? Think if the are allergic the first line and pregnant.
1st line (pt with low risk)
= amoxicillin 500mg tid for 5 days
Allergic to amoxicillin (pt with low risk)
= doxycycline capsules 200mg on first day then 100mg od for 4 days
or
= clarithromycin tablets 500mg bd for 5 days
in pregnancy
= erythromycin 500mg qid for 5 days
178
what is the options of an antibiotic for a pt with high severity CAP?
- co-amoxiclav 500/125 mg TDS orally or 1.2g TDS intravenously for 5 days
Plus one of the following if atypical pathogen is suspected.
= clarithromycin 500mg bd orally / intrvenously
or
pregnancy : erythromycin QDS orally for 5 days
or
penicillin allergy : levofloxacin 500mg bd orally / intravenously for 5 days
179
Inhaler technique need to know:
- how to use MDI and PDI, what are councelling points??
- when and how to breathe in? how this differs between devices??
- where does the drug go?
- when should spacers be used? how to clean them??
180
outline causes of asthma’s
- genetic component
- environmental factors - lots of triggers
- exposure to triggers makes asthma uncontrolled
181
outline lifestyle advise for COPD?
- smoking - quitting is the single best intervention (remember fletcher-peto!!!!!!)
- rehabilitation / exercise / mental health counselling etc…. usually managed by the respiratory team
- normally 6-8 week programme - leads to great improvements
reviews
- annually if GOLD is 1-3
- biannually if GOLD 4
182
rightbreathe website is very good for respiratory drugs
183
things to know for test..
Definitions:
- FEV1
- FVC
- how are these performed
Diagnosis:
- COPD = postbronchodilator FEV1:FVC ratio of < 0.7
- Asthma = expect significant increase post bronchodilator vs pre bronchodilator (10-12% increase)
Results:
- Obstructive lung disease (COPD and Asthma) = FEV1 and FVC reduced
- restrictive lung disease (fibrosis) = FEV1 reduced, but ratio doesn’t change
184
what advise to give to someone with asthma?
- avoid triggers
- the use of inhalers
- recognition of symptoms of uncontrolled asthma and what to do
- lifestyle advice eg loosing weight and exercise
- regularly review adherence to medicine
185
what are causes of COPD?
- smoking
- pollution
- genetic
- lung development issues eg born prematurely
SMOKING IS THE MAIN ONE
186
what are the assessments of COPD?
- spirometric measures eg FEV1 and FVC
- GOLD grading of COPD - 1 to 4 scale from mild to severe based on predicted FEV1
- mMRC scale for breathlessness - graded from 0 to 4
- COPD assessment test (CAT)
187
What are the causes of exacerbation of COPD, and treatment?
- commonly caused by respiratory tract infections
- main treatment is SABA initially // systemic corticosteroids
- long term oxygen therapy - need at least 15hrs a day
188
what are the main problem with inhaled drugs?
- most drugs don’t make it to the lungs
- issues with steroids can cause adverse effects, such as hoarseness
189
what are the treatments for COPD
- mainly bronchodilators - SABA/SAMA as needed and LABAs and LAMAs regularly (combo device preferred)
- inhaled corticosteroids only when asthma symptoms are also present (must be removed if no improvements)
190
what drugs are used to treat asthma?
1. relievers
- short acting / long acting
2. Preventers
- steroid (inhaled)
- leukotriene receptor agonists (tablet)
- AIR therapy - Anti Inflammatory Reliever therapy includes formoterol and corticosteroid on an ‘as needed' basis
- when AIR is used on a prescribed basis, it becomes MART = maintenance and reliever therapy
191
What is the main symptom of COPD?
chronic breathlessness
- this is due to the airflow being obstructed
192
outline some people who are at risk of sepsis.
Babies <1yr Recent surgery in past 6 weeks
Cut or breach to the skin Indwelling catheter or central line
People who misuse drugs intravenously
Adults >75yrs
Frail adults
Pregnant women or women who have recently given
birth
People with a weakened immune system
193
what are some more unique signs of sepsis?
- reduced urine output
- dehydration
- feeling card / shivers
- rapid breathing / heart rate
- blue colour on skin, lips or toungue
- non-blanching rash
194
what are the most common sites of infection?
• Respiratory (most common)
• Gastrointestinal
• Renal and genitourinary tracts
• Blood
• Skin or soft tissue
50% of patients will never have the causative pathogen identified.
it can be caused by any pathogen - not a unique one that causes sepsis
195
What are the signs / symptoms of sepsis?
• Signs or symptoms suggesting an infection causing significant illness or deterioration
• They have one or more risk factors for sepsis and look unwell
• There is concern expressed by a relative or carer about how the person looks or is behaving (care to be undertaken here when English is not a person’s first language or in patients with communication challenges)
but there is no one single test to diagnose - people do not always have an elevated core temperature
196
what is septic shock?
A subset of sepsis in which particularly circulatory, cellular, and
metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.
197
What is the name of the care plan for people with sepsis and what is the aim of it?
Sepsis 6
- reduces the death risk if used within 1 hour of presentation by 46.6%
- aim is to find the source of infection, measure and restore circulation and give supplemental oxygen. By finding the source we can use an appropriate antibiotic to treat. Chance of mortality increases if we do not find the source
198
what is the normal heart rate in a healthy person?
60-90 bpm
199
what os sepsis?
Sepsis is a syndrome defined as life-threatening organ dysfunction due to a dysregulated host response to infection
200
what other treatments should you give as treatment aside from antibiotic.
1. IV fluid if >16yr and with high risk of severe illness or death and either lactate >2mmol/litre or systolic blood pressure <90mmHg
2. Supplemental oxygen - if they have reduces SpO2 and be aware if someone has COPD as they will have lower targets
3. Serial lactate measurements - raised lactate is used to gauge severity of illness and predictor of risk of mortality
4. urine output - important indicator of patients circulation (directly proportional) and blood flow to kidneys
201
outline some host defence mechanisms for UTI
- neutrophils
- urine osmolity and pH
- commensal organisms
- urine flow
- blood group antigens (some people do secrete these, depending where they were born eg Asia) - this is what puts people more at risk
202
outline some host risk factors of UTI/
- sex
- pregnancy
- elderly
- diabetes
203
outline some virulence factors for E. Coli.
- Flagellae (for motility)
204
- Aerobactin (for Fe acquisition in Fe-poor urinary tract)
205
- Haemolysin (to form pores in target cells)
206
- Presence of adhesins on bacterial fimbriae (pili) and cell surface
207
what all locations fall under the term urinary tract infections?
- kidney
- bladder
- prostate
- urethra
208
what are the key symptoms of UTI in women aged under 65?
- you need 1 or more of these key symptoms to be diagnosed:
1. Dysuria (burning, stinging, pain on urination)
2. New nocturia
3. Cloudy urine (not catheterised)
209
what are the two types of E. Coli (fimbriae)
Those with Type I fimbriae (FimH adhesin) -> cystitis
210
Those with Type P fimbriae (PapG adhesin)-> pyelonephritis
211
212
what defines recurrent UTI?
- Defined as ≥ 2 episodes in last 6 months or ≥3 in the last year
- Re-infection - isolation of a new pathogenic strain after ≥14 days
213
what does the dipstick diagnosis test test for?
- many urinary pathogens catalyse reduction of nitrate to nitrite
- urine needs to be in the bladder for >4 hours
- test for leukocyte esterase (LE) – esterases released by leucocytes when significant pyuria is present. Other conditions can cause pyuria test for the presence of blood – could be microscopic haematuria
214
what is some prophalyxia and self care of UTI.
- 2.5L of fluid a day (of which at least 1.5L is water) – 6 to 8 mugs a day
- Void at 2-3 hour intervals – x2 if reflux present
- Void at bedtime and after sexual intercourse
- Avoid spermicidal jelly, bubble baths and other chemicals in bath
- Avoid constipation (can impair bladder emptying)
215
what is the first line treatment of UTI
nitrofurantoin
216
what is virulence?
- The ability to adhere to epithelial cells determines the degree of virulence of the organism.
217
218
when would you use the dipstick vs culture?
dispstick = to like double confirm diagnosis ( you don’t diagnose off these )
Culture = used when you arent sure, this can be used as the sole diagnosis
219
how do prostaglandin analogues eg litanoprost work?
- PGAs reduce the IOP by increasing the outflow aqueous humour via the uveoscleral pathway.
- They reduce IOP without significantly affecting the production of aqueous humour
- Used in ocular hypertension or glaucoma
220
outine how carbonic anhydrase inhibitors work?
• Inhibit the enzyme carbonic anhydrase
• Carbonic anhydrase catalyses the conversion of carbon dioxide and water to carbonic acid.
• Carbonic acid dissociates into bicarbonate and hydrogen
• Bicarbonate is needed by the cells of the ciliary body and therefore reduces aqueous secretion and therefore reduces the IOP
221
outline risk factors for primary open angle glaucoma.
• Raised IOP
• Age
• Family history and genetic history (10% of patients will have a first-degree relative with COAG)
• Ethnicity- increased prevalence in black ethnicity
• Corticosteroid use- oral, inhaled or high-potency topical corticosteroids
• Myopia (near-sightedness)
• Type 2 diabetes
• Hypertension and cardiovascular disease
• Secondary causes include; deposition of materials in the trabecular meshwork, formation of new blood vessels blocking flow through trabecular meshwork
222
outline risk factors of Primary angle closure glaucoma.
• Females are affected more commonly than males (4:1)
• Can be due to the natural anatomy of a patient’s eye
• Family history and genetics
• Advanced age
• Ethnicity: It is more common among the SE Asian population,
Chinese. Prevalence worldwide is highest in China
223
outline some drugs that can cause eye problems as side effects
- amiodarone
- antimuscarinics
- antiepileptics
- corticosteroids
- digoxin
- ethambutol
- alpha blockers
224
outline sympathomimetics mode of action?
- Agonism of α2- adrenoreceptors
- Decrease production of aqueous humour by action on ciliary epithelium
- Increase uveoscleral outflow of aqueous humour
- Reduce IOP
225
outline the prognisis of primary open angle glaucoma.
Prognosis = the likely cause of a medical condition
• Slowly progresses over the years
• Patients are typically asymptomatic until late in the disease
• Visual field loss typically presents first
• Central vision is affected later- this affects reading
• Most don’t go blind- blindness occurs in 5-10% of patients
• Loss of vision cannot be corrected- requires prompt and early
treatment
226
what are beta blocker mode of action?
- Block β2 receptors on the ciliary body and on ciliary blood vessels.
- Induces vasoconstriction and reduced aqueous
production
systemic absorption may occur therefore be aware of side effects eg asthma patients (same as Beta blockers for bp)
227
what are the 5 stages of primary angle closure glaucoma?
What are some symptoms of this?
• Latent
• Subacute
• Acute
• Chronic
• Absolute
• History- Pain- severe and rapidly progressive
• Blurred vision
• Coloured haloes around lights
228
what are the two types of glaucoma?
1. open angle
- the angle between the cornea and iris is normal
• Primary open angle glaucoma (POAG) is the most common type
• Affects people typically over 40yrs
• Insidious onset
• Affects both eyes, usually
• Typically, the patient has raised IOP
2. closed angle
- the angel between the cornea and iris is at least partially closed
• Primary angle closure glaucoma (PACG) most common type of angle closure glaucoma
• Occurs in patients with anatomically predisposed eyes- iris pushes forwards onto the trabecular network
• Acute angle closure is an ocular emergency with symptoms developing suddenly
229
what changes happen to the eye during glaucoma?
- build up of aqueous humour fluid (increased intraocular pressure)
- can lead to damage to the optic nerve
230
what is the first line therapy for glaucoma ?
Prostaglandin analogue
Eg - latanoprost 50mcg/ml eye drops or bimatoprost
231
what is the normal intraocular pressure? When does this become raised?
1. Normal Intraocular pressure (IOP)
• 10-15mmHg
2. Raised IOP >21mmHg
• Pressure in the eye leads to retinal damage and visual field loss
232
what is the steps in order or primary open angle glaucoma’s impact on vision?
1. Progressive deterioration of visual field
2. loss of colour sensitivity
3. Loss of spatial resolution
4. Loss of motion detection
5. Loss of contract sensitivity
233
give example of ototoxic drugs.
Aminoglycosides
Macrolide antibiotics
Loop diuretics eg furosemide
NSAIDs, aspirin
etc
234
what are common causes of subjectuve tinnitus?
- ear infection
- hearing loss
- impacted wax
- really any problems with the ear can cause tinnitus as a symptom
235
what are red flag symptoms of vertigo?
• Symptoms suggestive of stroke or TIA (FAST)
• Central cause of vertigo suspected
• Severe nausea and vomiting and unable to tolerate fluids or
symptomatic drug treatment
• New onset unilateral deafness
• Severe ataxia
• Very sudden onset of symptoms (seconds)
236
what are symptoms of nasal polyps?
• Blocked nose
• Runny nose /sneezing (50%)
• Poor olfactory abilities
• Hyposmia, anosmia
• Altered sense of taste
• Catarrh / post-nasal drip
• Feeling of fullness or pressure in the face
• Large polyps
• Headaches, snoring, sleep apnea
237
what are the 2 categories of causes for vertigo?
1. Peripheral- caused by an inner ear problem affecting labyrinth or vestibular nerve. Most common type.
2. Central- caused by a pathology in the brain, brainstem or
cerebellum. These are uncommon
238
what is a class of medication we give for vertigo, what does this class of drug end in. What is the advantage of this drugs being administered in many different routes?
Antihistamine
- all end in -zine eg: cyclizine, promethazine
- available buccal, oral and IM which means if someone is vomitting due to vertigo then oral is not appropriate as it will be thrown up.
239
what is an ototoxic drug?
Drugs that cause damage to the hearing or balance functions of the ear
240
what is benign paroxysmal positional vertigo (BPPV)
• Caused by loose calcium carbonate in the semi-circular canals of the inner ear.
• When the head moves these move in the semi-circular canals, cause motion in the fluid of the inner ear and therefore symptoms of vertigo
• Does not tend to respond to pharmacological management
241
what is Ménière’s Disease
• Disorder of the inner ear characterised by episodes of vertigo,
fluctuating hearing loss, tinnitus and a feeling of fullness in the
affected ear
• Usually unilateral but can present in both ears (2-73% of people)
242
what is nasal polyposis?
• Pale bags of benign oedematous tissue, like small grapes
• Bilateral (unilateral is more sinister)
243
what is objective tinnitus? What are some causes?
- a sound that the person and examiner can both hear (very rare, must be referred)
1. Commonly associated with venous or arterial abnormalities examples include:
• Aortic stenosis and mitral regurgitation
• Carotid or vertebral artery stenosis
• Vascular tumours
2. Other causes can include:
• Acoustic neuromas
• Anaemia or high CO states
• Benign intracranial hypertension
• Middle ear infection
244
what is tinnitus?
It is the perceived sound that can only be heard by the individual eg ringing / buzzing etc
It is a symptom, not a disease
245
what is vertigo? What is the difference between dizziness and vertigo?
• Symptom not a diagnosis
• False sense of movement (spinning or rotation) of the person or their surroundings without physical movement
• Distinct from dizziness. Dizziness is disturbed or impaired
spatial orientation without the false sense of motion
246
How does asthma epidemiology differ by gender and age?
More common in boys during childhood, shifts to being more common in females with age.
247
How is asthma diagnosed?
Clinical history plus spirometry (FEV1/FVC), peak flow variability, bronchodilator reversibility, FeNO.
248
Question?
Answer
249
What are common asthma triggers?
Dust, pollen, pollution, cold air, exercise, infections, stress, smoking.
250
What are common side effects of β2 agonists?
Tremor, tachycardia, hypokalaemia.
251
What are key points for MDI use?
Requires synchronisation; spacers reduce deposition and improve delivery.
252
What are leukotriene receptor antagonists (LTRAs) used for?
Exercise-induced or allergic asthma, not useful in acute attacks.
253
What are the main symptoms of asthma?
Wheeze, shortness of breath, chest tightness, cough; variable and worse at night or early morning.
254
What are the two main drug types for asthma?
Relievers (e.g., β2 agonists) and preventers (e.g., corticosteroids).
255
What are the types of inhaler devices for asthma?
MDIs, breath-actuated MDIs, DPIs, and spacers.
256
What are the underlying causes of asthma?
Genetic predisposition and non-genetic factors such as infections, smoking, and pollution.
257
What characterises acute severe asthma?
RR≥25, HR≥110, PEF 33-50%, inability to complete sentences, possible cyanosis.
258
What counselling should be given on asthma medications?
Explain reliever vs preventer, proper inhaler technique, adherence, monitoring.
259
What is the aim of a Medicines Use Review for asthma?
Improve technique, reduce waste, identify side effects, and enhance outcomes.
260
What is the Asthma Action Plan?
A personalised plan for recognising and managing worsening symptoms.
261
What is the key pathological feature of asthma?
Inflammation of the bronchial tree leading to hyper-reactivity and airway narrowing.
262
What is the purpose of the new NICE/SIGN/BTS asthma guidelines?
To unify and standardise asthma management in the UK.
263
What is the role of corticosteroids in asthma?
Reduce inflammation, used regularly; ICS preferred for fewer side effects.
264
What non-pharmacological strategies help manage asthma?
Avoiding triggers, smoking cessation, allergen control, immunotherapy.
265
When should LABAs be used in asthma?
Only when the patient is already on corticosteroids.
266
Why is inhaler technique so important?
Correct use is critical for drug delivery; issues are common with MDIs.
267
How can you reduce side effects of MDIs?
Use a spacer, clean properly, rinse mouth after use.
268
Main treatments for COPD exacerbation?
SABA ± SAMA, short course corticosteroids, antibiotics if needed.
269
Name a good online inhaler resource.?
Rightbreathe website.
270
Name two spirometric features of COPD.?
Reduced FEV1 and FEV1/FVC ratio < 0.7.
271
Name two types of beta-2 agonists used in asthma treatment.?
Short-acting (e.g., salbutamol) and long-acting (e.g., formoterol).
272
Question?
Answer
273
What advice should be given to asthma patients?
Avoid triggers, use inhalers correctly, recognise uncontrolled symptoms, follow action plan.
274
What are common side effects of inhaled corticosteroids?
Hoarseness, oral candidiasis.
275
What are the first-line drugs for COPD without asthmatic features?
SABA/SAMA as needed, then LABA + LAMA.
276
What defines uncontrolled asthma under new guidelines?
Needing oral corticosteroids or frequent reliever use (3+ days/week) or night-time symptoms (1+ nights/week).
277
What does the GOLD grading system measure?
COPD severity based on predicted FEV1.
278
What is a serious MHRA alert associated with montelukast?
Changes in mood, sleep or behaviour, including nightmares and aggression.
279
What is AIR therapy?
Anti-Inflammatory Reliever therapy using formoterol and corticosteroid as needed.
280
What is one of the major changes in the new asthma guidelines?
No SABA monotherapy for patients over 12; use combined inhalers only.
281
What is recommended for asthma diagnosis under new guidelines?
FeNO, eosinophils, and bronchodilator reversibility testing.
282
What is the main cause of COPD in high-income countries?
Smoking.
283
What is the primary cause of asthma?
A combination of genetic predisposition and environmental triggers.
284
What is the role of pulmonary rehabilitation in COPD?
Improves dyspnoea, exercise tolerance, quality of life.
285
What should you know about inhaler technique?
Correct inhalation method, device-specific use, when to use spacers.
286
What two spirometric values are key in diagnosing obstructive lung disease?
FEV1 and FEV1/FVC.
287
When should ICS be used in COPD?
Only if asthmatic features are present or benefit is seen.
288
Describe the general mechanism of steroid action.?
Steroid binds intracellular receptor, forms complex, enters nucleus, and regulates gene expression.
289
How do steroids affect arachidonic acid metabolism?
Increase lipocortins that inhibit phospholipase A2 and COX enzymes, reducing prostaglandin and leukotriene production.
290
How do steroids interact with NFkB?
They inhibit NFkB by inducing IkB and directly binding to it to suppress pro-inflammatory gene expression.
291
How do steroids reduce inflammation?
By decreasing cytokine production and immune cell activation.
292
How does Dexamethasone help in severe COVID-19 cases?
Suppresses excessive immune response and cytokine storm, reducing mortality in ventilated patients.
293
How is Budesonide metabolized?
Undergoes high first-pass metabolism in the liver.
294
How is Prednisolone administered and excreted?
Orally administered, excreted in urine.
295
List some diseases treated with steroids.?
Asthma, COPD, eczema, lupus, Crohn’s disease, COVID-19.
296
Name common anti-inflammatory steroid drugs.?
Dexamethasone, prednisolone, fluticasone, beclometasone.
297
Question?
Answer
298
What are corticosteroids?
Steroids from the adrenal cortex that regulate immune function and metabolism.
299
What are sex steroids?
Steroids like testosterone and estrogen involved in reproduction and secondary sex characteristics.
300
What does the steroid-receptor complex do in the nucleus?
Acts as a transcription factor to upregulate or downregulate gene expression.
301
What enzymes are involved in steroidogenesis?
Cytochrome P450 monooxygenases.
302
What immune cells are suppressed by steroids?
T-cells, macrophages, dendritic cells, NK cells, B cells.
303
What is a steroid?
A lipid molecule with a four-ring structure involved in physiological processes and drug treatments.
304
What is the biological role of cholesterol?
Maintains membrane fluidity and acts as a precursor to other steroids.
305
What is the characteristic structure of steroids?
Three cyclohexane rings and one cyclopentane ring.
306
What is the half-life of Fluticasone?
7.8 hours.
307
What is the main route of excretion for Hydrocortisone?
By the kidneys after liver metabolism.
308
What is the mechanism by which Dexamethasone reduces ACE2 expression?
Blocks stress-induced upregulation of ACE2, potentially limiting viral entry.
309
What is the prodrug of Beclometasone?
Beclometasone dipropionate.
310
What is the role of HSP90 in steroid function?
Chaperone protein that facilitates proper receptor folding and function.
311
Which cytokine is promoted by steroids?
IL-10.
312
Which cytokines are suppressed by steroids?
IL-2, TNF, IL-1β.
