Week 3 Flashcards
1
Q
What percent live births are affected by congential heart disease?
A
1%
2
Q
Heart defects cause problems by what 2 things?
A
- Obstructing flow in heart or vessels near to it
2. Cause blood to take an abnormal route through the heart
3
Q
Name 2 genetic conditions predisposing to congenital heart disease?
A
- Down’s syndrome
2. Turner’s syndrome
4
Q
Name 3 pregnancy factors which may increase the chances of a congenital heart disease?
A
- maternal alcohol misuse
- maternal drug treatment and radiation
- maternal diabetes
5
Q
What is the most common type of congenital lesion?
A
Ventricular septal defect
6
Q
What 3 congential heart defects, with shunts, will present as acyanotic?
A
- Atrial septal defect
- ventricular septal defect
- patent ductus arteriosus
7
Q
What 3 congenital heart defects, without shunts, will present as acyanotic?
A
- Coarctation of the aorta
- Pulmonary stenosis
- Aortic/left heart obstruction
8
Q
What 3 congential heart defects, with shunts, will present as cyanotic?
A
- Fallots tetralogy
- Transposition of great vessels
- All but with PHT (Eisenmenger’s complex)
9
Q
What 3 congenital heart defects, without shunts, will present as cyanotic?
A
- Severe pulmonary stenosis
- Tricuspid/Pulmonary atresia
- Hypoplastic left heart
10
Q
What are possible symptoms of a congenital heart defect?
A
- Difficulty feeding in infancy
- Failure to thrive in infancy
- Shortness of breath
- Syncope
- Squatting in older children
- Symptoms of cardiac failure
11
Q
What are the possible signs of a congenital heart defect?
A
- Murmur
- tachycardia
- tachypneoa
- central cyanosis
- clubbing
12
Q
What are 4 possible complications of a congenital heart disease?
A
- Infective endocarditis
- Paradoxical embolism
- Polycythaemia
- Pulmoary hypertension
13
Q
EIsenmenger’s syndrome?
A
When pulmonary pressure exceeds systemic and so shunt reverses to right to left, resulting in cyanosis
14
Q
What Investigations would you do for congenital heart disease?
A
- History
- Echocardiography: non-invasive, cheap and quick
- Cardiac catheterisation: more serious cases
15
Q
What are the 2 types of atrial spetal defect?
A
- Ostium primum defect- lower in atrial septum, riskier as closer to valves (15% of presentations)
2/ Ostium secundum defect- higher in atrial spetum, less serious (75%)
16
Q
Describe the pathophysiology of an atrial septal defect?
A
Left to right shunt through defect in inter-atrial septum.
Results in dilation of pulmonary artery
Murmur due to increased flow over pulmonary valve
17
Q
What is the presentation of an atrial septal defect?
A
Acyanotic, left to right shunt.
Adult with significant shunt may develop right heart overload/failure.
Parasternal heave/ pulmonary flow murmur
18
Q
What is the clinical management for an atrial spetal defect?
A
- Primum defect: early closure recommended
- Secundum defect: closure for moderate to large defects only
19
Q
Which type of ventricular septal defect is the more severe and why?
A
Membranous as closer to the valves (higher)
20
Q
What is the pathophysiology of a ventricular defect?
A
When left ventrical contracts, some blood enters the aorta whilst some is shunted into the right ventricle to enter the pulmonary circulation. Resulting in pulmonary hypertension- eisenmengers complex for large shunts
21
Q
What is the presentation of ventricular septal defects?
A
Acyanotic left to right shunt.
Large shunts may lead to symptoms of cardiac failure in young children and pulmonary hypertension/eisenmengers
Signs:
Pansystolic murmur (lasts for duration of systole)
22
Q
What is the management for a ventricular septal defect?
A
Larger defects: management of cardiac failure
Surgical intervention may be required.
23
Q
What is patent ductus arteriosus?
A
When the ductus arteriosus fails to close, resulting in a persistent connection from proximal left pulmonary artery to descending aorta
24
Q
Which direction does blood flow in patent ductus arteriosus?
A
From descending aorta (due to higher pressure) down into pulmonary artery
25
What is the pathophysiology of patent ductus arteriosus?
Left to right shunt, acyanotic
Murmur produced by turbulent aortic/ pulmonary artery shunt.
May lead to left heart overload (due to increased pulmonary return), sometimes may cause pulmonary hypertension and eisenmengers
26
What is the presentation of patent ductus arteriosus?
Acyanotic,
with large defect, feeding difficulties in infancy and failure to thrive,
Continous machinery murmur below left clavicle +/- thrill
bounding pulse due to increase left stroke volume
27
What is the management of patent ductus arteriosus?
Prostaglandin synthesis inhibitor, closure of defect
28
What is coarctaion of the aorta?
Locallised constriction in the aortic diameter, usually distal to ductus arteriosus due to abnormalities in tunica media
29
What is the pathophysiology of coarctation of the aorta?
No shunt, severe obstruction of blood, instead aorta is perfused by collateral channels (subclavian, to vertebral arteries, to intercostal anastamosis, to aorta)
30
What are the symptoms of coarctation of the aorta?
May be asymptomatic, or headahces/nosebleeds/intermittent claudication of LL/ cold legs (due to BP difference between Upper and lower body
31
What are the signs of coarctation of the aorta?
Hypertension in the upper limbs,
weak/delayed pulses in the legs,
may have systolic murmur over upper back (due to turbulence through narrowed section)
32
What is the medical management of coarctation of the aorta?
Surgical repair, baloon dilatation and stenting
33
What is fallot's tetralogy?
- Ventricular septal defect
- Pulmonary stenosis
- Hypertrophy of right ventricle
- Overrinding aorta
(although only 3 of them need to be present)
resulting in cyanotic right to left shunt
34
What is transposition of the great arteries?
Cyanotic, usually aorta drains the right ventricle and pulmonary artery drains the left ventricle, resulting in 2 seperate circulations
35
What is peripheral cyanosis?
Blue tinge of the skin. Not as worrying as central cyanosis. Can be due to cardiac failure, shock or pathology.
36
What would you look for on a patients fingers?
- Tar staining (indicating smoking)
- Nail clubbing (abnormality in soft tissue)
- Splinter haemorrhage (due to circulating immune complexes or trauma)
- Osler's Nodes (RARE)
- Janeway lesions (abcesses from septic emboli. RARE)
37
What is central cyanosis?
Blueish colour in lips. Very concerning - needs urgent medical assistance.
38
What is Malar flush?
- Discolouration over patients cheeks, dusky pink and bilateral
- Due to pulmonary hypotension due to mitral stenosis
39
What are Xanthoma(ta)?
- Fatty deposits under the skin, can be over tendons or knees or elbows
- Hallmark of hypercholestoleamia
40
What are Xanthelasma?
- Yellowish plaques around the eyes.
| - Concerning in a young person you need to check cholesterol and blood liver profile
41
What is Corneal Arcus?
- Discolouration around the iris.
- Due to cholesterol crystals.
- May be normal in older patients but could be due to hypercholestaemia
42
What is a normal heartrate?
60-100 bpm
43
How long should you record an irregular pulse?
1 minute
44
What is the character of a pulse?
The rise and fall of a pulse.
45
What might cause a fast and regular pulse?
Exercise, anxiety, pain, fever, medication, hyperthyroidism
46
What might cause a fast and irregular pulse?
Uncontrolled atrial fibrillation, hyperthyroidism (but also predisposes to AF)
47
What might cause a slow and regular pulse?
Athletic training, hypothyroidism, medication
48
What might cause a slow and irregular pulse?
Sick sinus syndrome, second degree heart block, complete heart block
49
What causes low volume?
Hypovolaemia, left ventricular failure
50
What causes increased volume?
Anaemia, fever, thyotoxicosis
51
What changes character?
slow rising pulse - aortic stenosis
| collapsing pulse - aortic regurgitation
52
What is the jugular venous pulse?
- Measured by the right internal jugular vein.
| - Pulsation reflects changes in pressure within the right atrium
53
How do you measure the JVP?
- Position the patient at 45 degrees.
- Ensure neck relaxed/turned to left.
- Measure vertical height from sternal angle to top of jugular venous pulsation.
- Should be less than 4 cm.
- JVP can be obliterated by gently occluding vein.
54
What you can feel on praecodium?
Find apex beat then check its position
Heaves - left sternal edge, right ventricular enlargement (due to right ventricular hypertrophy) as hand is pushed off right chest wall.
Thrills - Palpable murmur as you put your hand on someones chest, and you feel a vibration (apex, upper praecordium, sternal notch)
55
What happens during Ascultation?
Tell patient what you are doing.
Palpate carotid pulse initially and distinguish 1st and 2nd heart sounds. Listen for heart sounds, added sounds and murmurs (turbulent blood flow)
Use bell (higher frequency sounds) and diaphragm (lower frequency sounds)
Manoeuvres to accentuate diastolic murmurs (get patient to lie on left side to bring heart closer to chest wall / make them hold in their breath / make them to lean forwards)
Remember carotids (patient must hold breath)
56
What are the other components of the cardiovascular exam?
- Auscultate lung bases
- Sacral oedema
- Peripheral vascular examination
- BP
- Fundoscopy
- Urinalysis
- Offer abdominal examination
57
What is the first and second heart sound due to?
First heart sound - mitral and tricuspid valves closing
Second heart sound - pulmonary and aortic valves closing
Both listened to with a diaphragm
58
What proportion of people with down's syndrome also have a heart defect?
~50%
59
What are the 4 common heart defects associated with down's syndrome
1. atrial septal defect
2. ventricular septal defect
3. atrioventricular canal defect
4. patent ductus arteriosus
60
Which chromosome is tripicated in down's syndrome?
Trisomy 21
61
How can we establish which genes on chromosome 21 are related to the heart defects associated with down's syndrome in human cases?
Often there is only segments of triplicated 21, or there is a large rearrangement of the tripicated 21 chromosome. See which genes are triplicated most frequently in the individuals with heart defects
62
What technique is used to view the loci of specific genes?
Fluorescent in situ hybridisation (FISH)
63
What are the 2 genes when triplicated that are associated with down's syndrome studied in transgenic mice?
DSCAM (down's syndrome cell adhesion molecule)
| COL6A2 (collagen alpha 2 (VI) chain)
64
What role does the DSCAM gene play in development?
Cell adhesion
65
What role does COL6A2 play in development?
Cell migration
66
What are the 2 other terms used to describe DiGeorge syndnrome?
- 22q11.2 deletion syndrome
| - CATCH-22
67
How can a deletion be shown on a chromosome?
Using FISH
68
What are the 5 phenotypes associated with DiGeorge/22q11.2 deletion syndome?
```
Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypothyroidism
```
69
What are the three cardiac abnomalities associated with DiGeorge syndrome?
1. Interruption of the aortic arch
2. Tetralogy of fallot
3. Ventricular septal defect
70
Why do the deletions arise?
Misalign, resulting in chromosome breakage and rearrangement- the region may be duplicated or deleted.
71
How does a patient aquire the deletion?
Either de novo OR inherited if not detected in the parent
72
How does DiGeorge syndrome arise without deletion?
Instead of being missing, there is a mutation of the gene
73
Which gene, if mutated would result in DiGeorge syndrome?
TBX1 gene
74
What possible mutations could occur in the TBX1 gene?
- Deletion, resulting in a frameshift/nonesense mutation
| - Base pair substitution, resulting in an amino acid change, missense mutation
75
How would you describe a patient with one base at a position on 1 chromosome but another at the same position on another chromosome?
Heterozygous at that position
76
What is TBX1?
- Transcription factor
- Regulated transcription from a particular set of genes on the DNA sequence.
- Located at the 22q11.2 loci
77
What is the effect of the TBX1 gene being increased or decreased?
Abnormal development of 4th pharyngeal arch arteries
78
What is hypertrophic cardiomyopathy?
- Either pathological or due to athlete being highly trained.
- Wells of heart are thickened including the septum, most commonly on the left side
79
What is the phenotype of hypertrophic cardiomyopathy?
- increased muscle thickness,
- disorganised myocytes
- fibrosis
80
In what fashion is the genetic defect for hypertrophic cardiomyopathy passed on?
Autosomal dominant
81
What is the name given to a phenotype that can be caused by a defect in more than one gene?
Locus heterogeneity
82
How is a "long QT" patient defined?
Exceeds the 99th percentile value in a population
83
What causes the long QT signal?
Delay in the repolarisation of the ventricles
84
What causes the delay in repolarisation due to loss of function?
- Channelopathy, loss of function mutation in the K+ ion channel, meaning K+ can't flood out to repolarise myocyte.
- Mutations occur on cytoplasmic side of the channel.
- Inability to repolarise
85
What is the name given to a phenotype that may be produced due to lots of different mutations to the same gene?
Allelic heterogeneity
86
What causes a delay in repolarisation due to a gain in function?
SCN5A sodium channel stays open, due to mutation. This extents depolarisation, making it harder to repolarise.
87
In what fashion are mutations for long QT inherited?
AUTOSOMAL DOMINANT
88
What is penetrance?
The likelyhood that a molecular diagnosis (presence of mutation) will give rise to a clinical diagnosis (phenotype)
89
Will people with c loop, v.s. non-c loop long QT mutations respond well or poorly to beta blockers
C loop mutations responds well to beta-blocker
90
What is familial hypercholesterolaemia?
Inherited predisposition to high concentrations of serum LDL cholesterol (total >7.5mM)
91
What clinical signs may you see with someone with hypercholesteraemia?
Xanthoma, atherosclerosis
92
What possible consequences are there due to the high frequency of familial hypercholesterolaemia?
- Possibility that offspring of two parents with different mutations for hypercholesterolaemia will aquire 2 separate genes contributing to the condition.
- Resulting in a severe phenotype
93
What is the name given to a genotype with two seperate mutations, on from maternal and one from paternal chromosome, contributing to a condition?
COMPOUND HETEROZYGOTE (severe phenotype)
94
What sort of things can happen as a result of mutation in the LDL pathway to cause hypercholesterolaemia?
- receptor not sythesized
- cholesterol not transported properly into the cell membrane
- receptor doesn't bind to LDL well
- Receptor isn't internalised properly
- receptor is not recycled properly
95
What treatment is effective at treating people with familial hypercholesterolamia?
Statins
96
What are the strategies of treatment for treating heart failure?
- Increase cardiac contractility
- Decrease preload and/or afterload to decrease cardiac work demand
- Inhibiting RAAS
- Preventing inappropriate increase in heart rate
97
How would you decrease preload an afterload
Relax vascular smooth muscle (vasodilation) and decrease blood volume
98
What is the acronym for drugs used in heart failure?
DAB (diuretic, ace inhibitor, beta blocker)
99
What are the signs and symptoms of heart failure?
- Shortness of breath
- Swelling of feet and legs
- Chronic lack of energy
- Difficulty sleeping due to breathing problems
- Swollen or tender abdomen with loss of apetite
- Cough with frothy sputum
- Increased urination at night
- Confusion and/or imparied memory
100
What is class 1 New York Heart Association Classification of Heart Failure (NYHA)?
No limitation of physical activity
101
What is class 2 New York Heart Association Classification of Heart Failure (NYHA)?
Slight limitation of physical activity, comfortable at rest
102
What is class 3 New York Heart Association Classification of Heart Failure (NYHA)?
Marked limitation of physical activity
103
What is class 4 New York Heart Association Classification of Heart Failure (NYHA)?
Unable to carry out physical activity without discomfort, pain even during rest.
104
Conditions that increase the chances of developing heart failure?
- Hypertension
- Coronary heart disease
- Cardiomyopathy (genetic, alcohol misuse, infections, medications)
- Atrial fibrillation
- Anaemia
- Overactive thyroid gland
105
What does the body mistake heart failure for which leads it to make the condition worse?
Haemorrhage
106
What does the body release appropriately in haemmorhage that makes the heart failure worse?
Angiotensin II and ADH
107
Why are diuretics used in heart failure
To move/excrete odematous fluid
108
What does heart failure treatments do/dont do?
DOES- Treats symptoms, Prolongs life
| DOESN'T- Treat cause
109
What are the main drugs used in heart failure?
- Loop diuretic
- ACE inhibitor
- ARB
- Beta blockers
- Aldosterone receptor antagonists
110
What is the loop diuretic drug?
Furosemide
111
What are the ACE inhibitors?
Ramipril
| Lisinopril
112
What are the ARBs?
Candesartan
113
What are the beta blockers used?
Bisoprolol
| Carvedilol
114
Aldosterone receptor antagonists?
Spironalactone
115
What are the benefits of using beta blockers?
- Slow heart rate which could decrease cardiac output
- Allows ventricles to fill more completely suring diastole
- May cause vasodilation and decrease afterload
116
What are common side effects of ACE inhibitors?
Persistant dry cough, dizziness, tiredness, headache
117
What are common ARB side effects?
Dizziness, headaches, back/leg pain
118
Aldosterone receptor antagonists side effects?
Hyperkalaemia, hyponataemia, nausea, hypertension
119
What are the loop diuretic side effects?
Acute gout is common in higher doses
120
What are the aims fo treating ACUTE heart failure?
Normalise ventricular filling pressures and restore adequate tissue perfusion
121
What are the treatments of acute heart failure initally?
IV loop diuretics- venodilation and diuresis
IV opiates- reduce anxiety and therefore preload
IV, buccal or sublingual nitrates- reduce preload and afterload
122
What are the second line drug treatments for ACUTE heart failure?
DOPAMINE- increases renal perfusion and increases BP
INOTROPES, ADRENALINE- increase myocardial contractility
123
What is Health promotion?
Process of enabling people to increase control over and to improve their health
124
Common sense model
Primary goal is to explain how a person processes an illness threat (they will take common sense health behaviours).
How to think of an illness and how to act on illness
Target health messages so that they target these perception and then affect behaviour.
1. Health messages
2. Perceptions of treatment (needs and concerns
3. Representation of illness risk
4. Emotional reactions
5. Emotional response to treatment
6. Coping procedures (fear and danger control)
7. Appraisal
125
Health promotion approaches
```
Providing information
Enhancing motivation
Behavioural methods
Health behaviour maintenance
Combined programs
```
126
How does the NHS Provide Information?
Through GP, pamphlets, Tv
| But knowing isnt enough to make you do it as there are other barriers which prevent you changing your behaviour
127
How does NHS Enhance motivation?
Way to make health a priority and help overcome barriers they think exist.
Tailored content
-pt sees info as more relevant so more likely to take into account.
Framing: gain v loss
-health behaviours can be seen as risky.
-eg cervical screening can be painful. Present as loss, if you do it you wont get cancer.
Cognitive behavioural therapy
- get them to think about pros and cons and discuss perceived barriers. Belief that its impossible may not be true.
Motivational interviewing
128
What are the Behavioural methods?
Training
Reminders
Reinforcers
129
Health behaviour maintenance
Lapsing
-helping people deal with a lapse
-reduction in relapse
Lapse is brief, relapse is a much longer return to unhealthy behaviour.
May take these as signs that they cant do it and give up. Have to tell them that this doesnt mean that next time they wont be successful.
130
Combined Health promotion programs
Slimming clubs - weight watchers
Bring together different methods in health promotion
Can help others tell of how they overcame similar barriers.
131
What is Primary Prevention in CVS?
- Aimed at general population to prevent disease occurring.
| - No disease has been detected yet.
132
What is Secondary prevention in CVS?
- Aimed at identifying the risk of or risk factors for illness.
- Helps discover the likelihood that they have the illness.
- Focuses on early identification of individuals or communities experiencing illness.
133
What is Tertiary Prevention in CVS?
- Illness already identified, reduce severity of symptoms of illness or try to prevent recurrence of illness.
- Aims to prevent the long-term consequences of a chronic illness or disability and to support optimal functioning
134
List some examples of CV diseases?
| List the modifiable and non-modifiable risk factors?
```
Hyptertension
Atherosclerosis
Angina
MI
Coronary heart disease
```
```
Non-modifiable:
-education
-social class
-gender
Modifiable:
-smoking
-obesity
-sedentary lifestyle
-personality?
```
135
Give examples of Primary prevention in CVD?
- HEBS walking campaign
- Breaking Addiction barriers
- Breaking Motivation barriers
- Education
- Social support
- Cultural support
136
Describe why the HEBS walking campaign was made?
- High proportion of scotland do very low levels of exercise.
- Targets middle aged people who do very little exercise and were from lower socio-economic statuses.
- Walking not perceived as a good form of exercise but shown to be very effective.
- So ran advert, radio campaign and healthline to try to get specific group to see it as legitimate.
137
Stage model of behavioural change
1. Pre-contemplation
2. Contemplation
3. Preparation
4. Action
5. Maintenance
6. Relapse
138
Awareness of HEBS
69% found to be aware of advertising campaign
Most people it had a +ve change.
Though some still believed you had to sweat and be out of breath to exercise which wasnt the message they tried to conve
139
What is the Healthline?
Focused on those who rang the help line. Followed them up after 10 weeks and then a year.
At baseline majority were contemplating.
By 10 weeks the majority had shifted into action.
People who had biggest shift were those who engaged in the least activitiy at baseline.
140
Give examples of Secondary prevention in CVD?
Check blood pressure and cholesterol
141
Give example of Tertiary prevention in CVS?
```
Cognitive changes
(Type A & B personalities in coronary heart disease)
```
142
What is characteristics of a Type A Personality?
- High competitiveness
- High time urgency
- High hostility
143
What is characteristics of a Type B Personality?
- Low competitiveness
- Low time urgency
- Low hostility
144
How to assess type A behaviour?
- Structured interview
- Questionnaires (self-report)
- Jenkins activity survey
- Framingham type A scale
145
Treatment options for Type A people?
- Stress reduction strategies
- Relaxation techniques
- Anger management
- Type A counselling caused big % reduction in time urgency and free floating hostility
146
What are the five rights of intravenous drug administration?
1. Right patient
2. Right medicine
3. Right route
4. Right dose
5. Right time
147
What would be reasons a drug would be given in IV form?
- Medicine is not available in another form (not stable)
- Cannot tolerate medication by another route
- Constant or high blood level of medicine is needed
- A rapid onset of effect is needed
- Some medications are more effective via IV
- To ensure compliance
148
What are the disadvantages of IV administration?
- Increased cost and time to administer the medicine,
- Req. trained staff to administer in appropriate location,
- Rapid onset of action
- Volume of fluid needed to dilute the medicine (bad for patients with hypervolaemia),
- Causes pain/discomfort to patient,
- Infection and sepsis risk
149
What is a peripheral venous catheter?
- Inserted into locallised region or low capacity, therefore drug is not readily diluted and must be given slowly.
- Inserted into peripheral vein, leading all the way back to the heart.
150
What is a central venous catheter?
Tip inserts into the inferior or superior vena cava, drug enters a high volume of blood going directly to the heart, therefore more drug can be inserted quickly
151
What is the use of arterial catheters?
Measure blood gas and O2 levels, is not used for administration of drugs
152
What is a hickman line?
A catheter which travels a short way under the skin before entering a central vein, this is used to reduce infection risk
153
What are the 3 main methods of administering intravenous medications?
- Continous infusion
- Bolus injection
- Intermittent infusion
154
Describe the type of drugs administered in a continous infusion
- Stable drugs (in IV bag)
- Short half life (in body)
- Time dependent effects
- Needs dedicated IV site
155
Describe the type of drugs given in a bolus injection?
- Rapid response from drug is required,
- Drug has incompatibilities with other drugs given
- Drug is unstable and wont chemically last in solution
156
Describe the type of drugs aministerd by intermittent infusion
- Unstable drugs (in bag)
- Long half life
- Concentration dependent effects
- Less compatibility concerns than drugs administered by bolus.
157
What are complications of IV drug administration?
- fear/phobia/pain
- infection/sepsis
- thrombophlebitis
- extravasion/infiltration
- emboli
- anaphylaxis/hypersensistivity
- Overdose
158
What is extravasion?
When IV administration is incorrect and top of needle is in interstitial space, and toxic substances are administered and are deposited into tissue, causing tissue damage
159
What is infiltration?
When tip of needle is in interstitial space and drug administration causes interstitial swelling
160
What is red man syndrome?
Hypersensitivity reactions due to histamine release:
- erythmatous rash of face, neck and upper torso
- diffuse burning, itching and generalised discomfort
- rare cases: hypotension, angioedema, chest pain and dyspnea
161
What treatment often causes red man syndrome?
IV vancomycin treatment for MRSA
162
How is the incidence of red man syndrome reduced?
Slow infusion rate, more dilute drug solution
163
What factors can affect the stability of medicines in solution?
Light, temperature, concentration and pH
164
What is Bioavailibility?
Fraction of unchanges drug that reaches the systemic circulation.
165
What percent bioavailibility does IV drug injection give?
100%
166
What shaped line would be seen on a graph of plasma conc. over time, if a drug is infused at a constant rate and no drug is removed from the body?
Straight line
167
How is drug eliminated from the body?
Through the liver and kidneys
168
If there is a higher plasma concentration of drug, how will this effect the amount of drug eliminated per unit time?
More drug will be removed per unit time (direct relationship)
169
What is the resulting shape of the graph, as the rate of drug out increases to balance the rate out?
Plateau
170
CL
Clearance
171
What affects clearance?
Function of liver and kidneys
172
What is Clearance (CL)?
Defined as the volume of blood or plasma cleared of drug in a unit- e.g. 10ml/min
173
Does amount of drug eliminated per unit time vary or stay the same?
Vary
174
Does clearance vary or stay the same?
Stays the same
175
What is the equation for working out plasma steady state conc? (Css)
Rate of drug administered (K0)/ Volume of plasma cleared of drug per unit time (CL)
176
What value does time taken to reach Css depend on?
Elimination half life (t1/2)
177
What is the equation for working out the half life of a drug?
t1/2= (ln2 x Vd)/CL
178
What is Css?
Plasma steady state concentration
179
What is Vd?
Volume of distribution
180
What happens to Css if patients CL is higher than expected?
Reached faster, and is lower
181
What happens to the Css if you increase the dose of drug?
Increases, reached faster
182
What are the factors affecting drug distribution?
- Cardiac output and blood flow
- Plasma proteins and binding
- Lipid solubility
- Degree of drug ionisation
- pH of compartments
- Capillary permeability
183
What factor does the initial rate of distribution heavily depend on?
Blood flow
184
how could a reservoir of drug be injected?
Intramuscular or subcutaneously
185
Why does injecting drug into muscle or fat create a reservoir?
What affects the rate of drug dispersal from this?
- Drug held within the fat/muscle compartment, and is released slowly
- Speed of which is related to the blood flow to that area.
186
Which reservoir will give a greater rate of release of drug, fat or muscle?
Muscle, as fat is poorly perfused
187
How will exercise affect the rate of drug dispersal from muscle reserve?
Increase (as increases blood flow)
188
What is the predominant plasma binding protein in blood?
Albumin
189
How do lipid soluble drugs bind to albumin?
Bind non-specifically
190
How do weak acids bind to albumin?
At a specific, saturable site
191
What would competition at the saturable sites do to the free drug levels in the plasma?
Increase free drug levels
192
What dictates the rate of distribution through lipids in hydrophillic drugs?
Diffusion characteristics of the drug ie. if there are transporter proteins, if capillary is permeable etc.
193
What dictates the rate of distribution for lipophillic drugs?
Rate of delivery to tissues. i.e. blood flow
194
What does the ionised:unionised ratio depend on?
pH
195
Which of ionised/unionised drugs will cross cell membranes?
unionised
196
What 3 different types of capillary are there depending on the permeability?
1. Continous
2. Fenestrated
3. Sinusoid/Discontinuous
197
Which things contribute to the intergrity of the BBB?
- Tight junctions between endothelial cells
- Processes of astrocytes
- Basal membane
198
What are the characteristics of drugs which can cross the BBB barrier?
Lipophillic or can hijack transporter proteins
199
Can disease state change the ability of drugs to pass the BBB?
Yes
200
How does meningitis affect how drugs cross the BBB?
Reduces BBB integrity and therefore allows antibiotics to cross over to the brain
201
What sort of drugs can cross the placenta?
Lipid soluble, unionised forms of weak acids and bases
202
What creates the protective integrity to the placenta, seperating blood flows?
Tight endothelial cell junctions
203
What is it about abcesses that makes them difficult to treat?
Avascular necrotic tissue compartment, blood can't reach, therefore drug can't reach
204
What about lung infections makes them difficult to treat?
- Low local PO2 and high PCO2 causes vasoconstriction
| - Diverting blood with drug away from areas of lung that need it
205
What is the units for the Volume of Distribution (Vd)?
Litres (L) or L/kg of body weight
206
Is volume of distribution an accurate measurement of the volume of fluid in body?
No
207
What variables determine the Vd of a patient?
- Height
- Weight
- Age
- Fluid accumulation
- Accumulation of fat
208
Which type of hypertension is most common- Pulmonary or Systemic?
Systemic
209
Which type of BP is difficult to measure?
Pulmonary
210
What are causes of pulmonary hypertension?
- Hypoxia
- Endothelial cell dysfunction
- Reynauds
- Genetics
- Blockage, damage to pulmonary blood vessels
- Side effects of some drugs
211
Hypertension definition?
State of elevated arterial blood pressure
212
What could be causes for secondary hypertension?
- Renal disease
- Phaeochromocytoma
- Diabetes
- Cushings
213
What is the classification for stage 1 hypertension?
- Clinical BP: 140/90mmHg to 160/100mmHg.
| - Subsequent ambulatory/home monitoring: ~ 135/85 or higher
214
What is the classification for stage 2 hypertension?
- Clinical BP: 160/100mmHG or higher
| - ABPM/HBPM: 150/90mmHg or higher
215
What is the classification for severe hypertension?
Clinic systolic BP is 180/110mmHg or higher
216
What are possible causes of primary hypertension (90%)?
- Increase in TPR- increase in sympathetic nerve activity (increases noradrenaline released: pre-synaptic effects on adrenaline and angiotensin II)
- Increased vascular reactivity- Increased extracellular Na+, pathological Na+/K+ATPase inhibition
- Damage to endothelium, decreasing NO production
- Thickened wall, decreasing lumen size
217
What are secondary causes of hypertension (10%)?
- Renal disease: altered blood pressure control
- Diabetes: damaged endothelium
- Endocrine disorders: cushings, chronn's, phaeochromocytoma
- Coarctation of the aorta
- Drugs
- Pregnancy: eclampsia, pre-enclampsia
218
What are some drugs that can cause hypertension?
Contraceptive pill, cocaine, amphetamine, NSAIDs
219
What are non-modifyable risk factors for hypertension?
- Genetic: Abnormal inhibition of Na+/K+ATPase, family history, african/carribbean, male
- Psychogenetic factors: personality
220
What are modifiable risk factors for hypertension?
- Exercise
- Diet
- Obesity
- Smoking
- Alcohol intake
- Stress
221
What is benign hypertension often referred to as?
Essential hypertension
222
Describe benign hypertension and it's effects?
Long standing hypertension, often asymptommatic, causes changes to arterioles and small arteries
223
Describe malignant hypertension and it's effects?
- Cardiac failure with lV hypertension
- Blurred vision (papilloedema, retinal haemmorhage)
- Haematuria and renal failure
- Headache and cerebral haemorrhage
224
What are common deaths from hypertension, heart failure and MI?
Strain on heart due to increased afterload
225
What are the three main effects on the heart from systemic hypertension?
1. Heart failure
2. LV hypertrophy
3. MI
226
Why is heart failure a common effect of hypertension?
Pressure overload from increased TPR, results in left ventricular hypertension, volume overload due to kidney failure, less actin-myosin overlap
227
What things is LV hypertrophy a common risk for?
Heart disease, dysrythmias, sudden death and congestive heart failure
228
What are the 3 common effects on the body vasculature from hypertension?
1. Accelerated atherosclerosis
2. Stroke (narrowing and sclerosis of small cerebral arteries, white matter changes)
3. Retinopathy: Blood vessels damages, arteries narrowed and tortuous, veins occluded and haemorrhage occurs
229
What are the effects of hypertension on the kidneys?
- Autoregulation tries to protect the glomarulus
- Albuminuria
- Continued high pressure (arteriolar walls thicken and narrow)
- Kidney function declines irreversibly (sclerosis due to fibroblast activity)
- Urine formation falls, leading to volume overload, decreased clearance of creatine, urea and waste substances
230
Which speciality has the change to spot hypertension early?
Opthalmology
231
How many millimeters of mercury rise is enough to increase 7% HD chance and 10% stroke chance?
2
232
What lifestyle factor modifications can alleviate heart failure?
- Decrease alcohol intake
- stop smoking
- increase intake of unrefined carbohydrates
- decrease fat intake
- decrease sodium intake
- increase fruit and vegetable intake (K+)
- Increase aerobic exercise
233
What does ACE inhibitor stand for?
Angiotensin Converting Enzyme inhibitor
234
What does ARB 1 stand for?
Angiotensin AT1 Receptor Antagonists
235
If a patient is under the age of 55 with stage 2 hypertension what is the first stage of treatment?
ACE inhibitor or ARB 1
236
If a patient is over the age of 55 or is of african/caribbean origin, what is the first line of treatment?
Calcium channel blocker
237
If either first line treatments do not control blood pressure, what is the second line of drugs?
ACE inhibitor/ARB or calcium channel blocker if not given
238
What is the 3rd line treatment for blood pressure not controlled by the 2nd line measures?
Thiazide-like diuretic
239
What additional therapies are given to resistant hypertension?
Further diuretic, alpha or beta blockers
240
What are the (2) ACE inhibitors used to treat hypertension?
Ramipril
| Lisinopril
241
What are the ARB's (1) used to treat hypertension?
Losartan
242
What Renin inhibitor is used in hypertension?
Aliskiren
243
What calcium channel blockers are used in hypertension?
Amlodipine
| Lercanidipine
244
What (2) diuretics are used to treat hypertension?
Indapamid
| Bendroflumethiazide
245
What (2) beta blockers may be used aditionally to treat hypertension?
Bisoprolol
| Atenolol
246
What alpha-adrenoreceptor blockers can be used to treat hypertension?
Doxazosin
247
What kidney function modifying drug is used to treat resistant hypertension?
Spironolactone
| Potassium sparing diuretic and aldosterone antagonists
248
What are the common side effects of calcium channels blockers?
Flushes, headaches, ankle odema, dizziness
249
What are the common side effects of thiazide-like diuretics?
Can raise potassium and blood sugar levels
250
What are the common side effects of ARB's?
Back/leg pain, dizziness, headaches
