WEEK 3 Flashcards
(124 cards)
1
Q
What is congenital heart disease defined as?
A
Heart disease that pt is born with
2
Q
What are the 6 causes of congenital heart disease?
A
- Genetic defects
- Chromosome abnormalities (Downs, turners etc.)
- Intrauterine infection (Rubella)
- Drugs (thalidomide)
- Maternal alcohol (FAS, especially septal defects)
- Maternal diabetes
3
Q
What is the mneumonic for the 4th arch derivative?
A
FOUR rhymes with aOR
Remember “fouRS”
- Arch of Aorta
- Right Subclavian Artery
4
Q
What are 5 things that can go wrong & as a result lead to congenital heart disease?
A
- Failure of septation
- VSD, ASD - Failure of development
- obstruction: tricuspid/pulmonary atresia, pulmonary stenosis, coarctation of the aorta
- hypoplasia: hypoplastic left heart (no formation of L heart) - Failure of or incorrect rotation
- TGA & congenitally corrected transposition of the great vessels, dextrocardia - Abnormalities of the great vessels
- wrong connections: transposition of the great vessels
- wrong embryology: trucus - Failure of closure
- PDA
5
Q
What is the incidence of congenital heart disease in live births? What is the most common & least common type of congenital heart diseases?
A
About 1% of live births
Most common = VSD
Least common = aortic stenosis & Fallot’s Tetralogy
6
Q
What are the issues & presentation of congenital heart disease? (HINT: there’s 4 points)
A
- INCIDENTAL
- murmur, echo finding - HEART FAILURE
- Qp(pulmonary flow)>Qs (systemic flow) (shunt ratio) - CENTRAL CYANOSIS
- >5g/dl deoxyhaemoglobin resulting from venous mixing with systemic blood - PULMONARY HYPERTENSION = >30mmHg systolic resulting from increased Qp
7
Q
What are the 6 presenting problems if congenital heart disease?
A
- Heart failure
- difficulty feeding
- failure to thrive (don’t pass milestones)
- tachypnoea (rapid breathing)
- cyanosis - Cyanosis
- Clubbing
- Murmur
- Squatting (Fallot’s)
- Syncope
8
Q
How is congenital heart disease prevented?
A
Foetal echocardiography
9
Q
How is congenital heart disease managed palliatively? (relieving pain w/out dealing with the cause of the condition)
A
- To allow growth for definitive treatment:
- Maintain arterial duct (prostaglandins)
- PA banding
- Atrial septostomy (Rashkind) - As long-term treatment
- Creation of systemic to pulmonary shunt (Subclavian to PA (Blaylock) OR Central PA to Aorta (Waterstone)) - Definitive treatment:
- Radical correction of TGA, Fallots
- Percutanous closure devices - PDA, ASD, VSD - Transplantation
- Heart
- Heart-lung for conditions complicated by PHT
10
Q
What are the 7 complications associated with congenital heart disease?
A
- Failure to thrive
- Paradoxical embolus (venous to arterial)
- Endocarditis
- Pulmonary hypertension
- Polycythaemia
- Haemoptysis
- Arrythmias - flutter, VT/VF
11
Q
What is an atrial septal defect?
A
Blood flows between the atria. Normally, the atria are separated by the interatrial septum. If this septum is defective/absent, then oxygen-rich blood can flow directly from the left side of the heart to mix with deoxygenated blood in the R side of the heart, or vice versa. This can lead to lower-than-normal oxygen levels in the arterial blood that supplies the brain, organs, & tissues. NOTE: an ASD may not produce noticeable signs or symptoms, especially if the defect is small
12
Q
What 2 ways is an atrial septal defect (ASD) managed? How is it decided which route to go down?
A
- Nothing
- Percutaneous closure
- it depends on the size of the shunt
13
Q
What is the most common ventricular septal defect?
A
Perimembraneous
14
Q
If a patent ductus arteriosus is larger what can happen? What does it cause if it is small?
A
It will present as heart failure with continuous murmur & wide pulse pressure
Can cause PAH (pulmonary arterial hypertension) but this will only show lower body cyanosis.
If small it causes a “continuous murmur” normal pulse pressure
15
Q
What is coarctation of the aorta? Who is it common in? What can it cause? What 2 things can it be associated with?
A
A large range of narrowing from complete interruption to small low gradient stenosis
More common in males (if in females, think of Turners)
Causes systemic hypertension in adults
Associated with intercranial aneurysms & bicuspid aortic valve
16
Q
What is TGA (transposition of the great arteries)?
A
When the 2 main arteries going out of the heart—the PA and the Ao—are switched in position, or “transposed”.
17
Q
How is TGA palliated? (means to relieve or lessen without curing) (HINT: there’s 4 things)
A
Pharmacologic maintenance of arterial duct
Atrial septostomy
Radical switch procedure
(Palliative surgery – Mustard procedure)
18
Q
How does oxygenated blood from the umbilical vein bypass the lungs? Why does it bypass the lungs?
A
- Crossing the oval fossa (inter-atrial septum)
- Passing from PA to Ao through arterial duct (ductus arteriosus)
The lungs are not inflating, as resistance is very high so blood cannot get through
19
Q
What diseases (i) with shunts (ii) without shunts will the pt present as cyanotic?
A
(i) All but with PHT (eisenmenger’s complex)
TGV
Fallot’s tetralogy
(ii) Hypoplastic left heart
V. severe pulmonary stenosis
Pulmonary/tricuspid atresia with OR without intact septum
20
Q
What diseases (i) with shunts (ii) without shunts will the pt present as acyanotic?
A
(i) ASD, VSD, PDA
(ii) pulmonary stenosis
coarctation of the Ao
Aortic/L.heart obstruction
21
Q
What is Eisenmenger’s complex/syndrome?
A
defined as the process in which a long-standing left-to-right cardiac shunt caused by a congenital heart defect causes pulmonary hypertension & eventual reversal of the shunt into a cyanotic right-to-left shunt.
22
Q
What are the investigations done for congenital heart diseases?
A
- Echocardiography & doppler measurement
- Cardiac catheterisation
- used much less but still needed sometimes to measure PA pressure - Genetic
23
Q
What is the difference in the primum & secundum ASD?
A
Primum = is often complicated by other lesions e.g. mitral valve clefts, anomalous venous drainage
Secundum usually uncomplicated.
24
Q
Describe (i) Small VSDs (ii) Large VSDs.
A
(i) Safe, never cause PAH but have a loud murmur. No treatment necessary
(ii) have high Qp:Qs, present in early infancy. Palliated until definitive treatment. Have a loud holosystolic murmur
25
What are the 2 types of treatment for coarctation of the aorta?
Balloon dilatation
| Sometimes surgery
26
What are the signs for coarctation of the Ao?
Absent/delayed femoral pulse
Lower BP in legs
Scapula collaterals
Rib notching on chest Xray
27
What is Tetralogy of Fallot?
involve four anatomical abnormalities of the heart (although only three of them are always present).
1. Pulmonary stenosis
2. VSD
3. Over-riding aorta
4. Right ventricular hypertrophy
28
Why is the Tetralogy of Fallot of particular interest? (There's 2 reasons)
It is a definitive cause of cyanosis but one which is reversible as they never had PAH
Squatting is a common characteristic to raise systemic resistance (often after exercise)
29
How is the severity of Tetralogy of Fallot determined?
By degree of RV outflow obstruction
30
What are the fundamentals of a cardiovascular examination?
INTRO - hygiene of hands & stethoscope, introduce, name, DoB, discomfort, explain, permission, position at 45degrees with chest adequately exposed
INSPECTION
PALPATION
(PERCUSSION)
AUSCULATION
OTHER AREAS
CONCLUSION (thanks, wash hands, summarise & present findings orally)
31
What does the inspection of a CV examination consist of?
```
At end of bed:
- look around pt (oxygen, cigarettes), look at pt (breathless, discomfort, pain),
Inspect hands (warmth, capillary refill)
- peripheral cyanosis
- nail clubbing
- tar staining
- splinter haemorrhage
- koilonchyia
- oslers nodes
- janeway lesions,
Look at face eyes & mouth (pallor, sweating)
- central cyanosis
- malar flush
- conjunctivae
- xanthelasma
- corneal arcus
```
32
What pulses are taken in a CV examination? (HINT: there's 3)
RADIAL PULSES:
- palpate both
- rate
- rhythm (if irregular take pulse for one min)
- collapsing pulse (aortic regurgitation)
CAROTID PULSE:
- one at a time
- volume
- character
BLOOD PRESSURE:
can be done now with other two or at end of examination
33
What are the types of abnormal rate/rhythm of pulses that can be heard & what do they suggest?
1. Fast & regular
e. g. exercise, anxiety, pain, fever, medication, hyperthyroidism
2. Regularly irregular
e. g. ectopic beat
3. Irregularly irregular
e. g. atrial fibrillation (fast if uncontrolled) - risk factor for stroke
4. Slow & regular (bradycardia)
e. g. athletic training, hypothyroidism, medication (beta blockers)
5. Slow & irregular
e. g. Sick sinus syndrome, second degree heart block, complete heart block
34
What are the types of abnormal volume/character of pulses that can be heard & what do they suggest? (In the carotid pulse)
1. Low volume
e. g. hypovolaemia, left ventricular failure
2. Increased volume
e. g. anaemia, fever, thyrotoxicosis
3. Character
- Slow rising pulse = aortic stenosis
- Collapsing pulse = aortic regurgitation
35
Ausculation is one of the steps in a CV exam, describe the stages of this step.
1. Palpate the carotid pulse initially
- distinguish the 1st & 2nd heart sounds
2. Listen for:
- heart sounds
- added sounds
- murmurs (turbulent blood flow)
3. Use bell & diaphragm & listen in all 4 key areas (aortic, pulmonary, tricuspid, mitral)
- Manoeuvres to accentuate murmurs & remember carotids
36
What are the 4 movements done to accentuate murmurs?
1. At apex in left lateral position
- Bell at apex
- In expiration
- Accentuation of mitral stenosis
2. At left axilla
- With diaphragm
- Radiation of systolic murmur of mitral regurgitation
3. At lower left sternal edge with patient sat forwards
- With diaphragm
- In expiration
- Accentuation of atrial regurgitation
4. Over carotids
- With diaphragm
- In held inspiration
- For aortic radiation/carotid bruits
37
What is the JVP? Where is it located? What is it measured as? What tests are done to ensure it is the JVP you are palpating & not the carotid
Jugular venous pulse
Between clavicular & sternal heads of sternoceidomastoid
- measured as the vertical height of the highest point of pulsation above the sternal angle (should be less than 4cm)
Tests: Double wave form of venous pulsation, it can be obliterated by gently occluding vein, abdominojugular reflex
38
What steps are done when looking at the praecordium?
1. LOOK
- shape, RR, scars, visible apex beat, pacemaker
2. APEX BEAT
- find it first then check its position ("normal" = 5th IC space mid-clavicular line)
3. HEAVES
- left sternal edge, RV enlargement
4. THRILLS
- palpable murmur (apex, upper praecordium, sternal notch)
39
What are the 4 sites for auscultation?
5th IC space mid clavicular line = mitral
4th IC space L sternal edge = tricuspid
2nd IC space L sternal edge = pulmonary
2nd IC space R sternal edge = aortic
40
How are murmurs graded?
```
1/6 = very quiet ABSENT
2/6 = Quiet ABSENT
3/6 = Easily audible ABSENT
4/6 = Loud PRESENT
5/6 = V.loud PRESENT
6/6 = Audible w/out stethoscope PRESENT
```
41
What is a "thrill"?
A palpable murmur that you can hear with your hands
42
What other areas are needed to be examined to complete a CV examination?
1. Ausculate lung bases
2. Sacral oedema
3. Offfer abdominal examination
4. Peripheral vascular examination (femoral, popliteal, dorsalis pedis & post tibial, oedema)
5. Ankle oedema
6. BP
7. Fundoscopy
8. Urinalysis
9. Observation chart
43
What is the difference between between locus heterogeneity and allelic heterogeneity?
LOCUS HETEROGENEITY = defects in more than one gene can cause the same phenotype
ALLELIC HETEROGENEITY = different mutations in the same gene can cause the same disease
44
What is genetic penetrance?
The proportion of individuals carrying a particular variant of a gene (allele or genotype) that also expresses an associated trait (phenotype).
In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms
45
What are 4 common CV defects in down syndrome?
Atrial septal defect
Ventricular septal defect
AV septal defect
Patent ductus arteriosus
46
If someone has 22q11.2 deletion syndrome (DiGeorge Syndrome) their signs/symptoms are remembered by CATCH-22, what does this stand for?
```
Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypothyroidism
```
47
What are the cardiac abnormalities involved in 22q11.2 deletion syndrome (DiGeorge Syndrome)?
1. Interruption of aortic arch
2. Tetralogy of Fallot
3. Ventricular septal defect
48
DiGeorge Syndrome can arise without deletion, explain how this is the case.
Mutation(s) in TBX 1
49
What happens if you lose 1 copy of the TBX1 gene?
Loss of 4th pharyngeal arch arteries
50
What happens to transcription when there is (i) too little (ii) too much of the TBX1 dosage?
(i)
| (ii) it will dimerise to itself & become inactive & blocks active sites for the heterodimer
51
What is the phenotype of hypertrophic cardiomyopathy? In what manner is it inherited? What is different in their ECG?
Increased muscle thickness (particuarly of septum)
Disorganised myocytes
Fibrosis
- Autosomal dominant manner
- They have a long QT interval that exceeds 99th percentile values due to a delay in repolarisation
52
Why is it important to identify mutation?
Because knowing what mutation it is is a factor for choosing the correct medication for treatment
53
What is familial hypercholesterolaemia associated with? What criteria is used to determine familial hypercholesterolaemia? In what manner is it inherited?
Early aged mortality
Xanthoma
Atherosclerosis
- Simon Broome criteria
- Autosomal dominant manner
54
What is cascade testing?
the identification of close relatives of an individual with a disorder to determine whether the relatives are also affected or are carriers of the same disorder. It is intended as a form of medical screening.
55
Define the term angina pectoris & understand the pathological processes that cause it.
It is chest pain due to an inadequate supply of oxygen to the heart, it is typically severe & crushing & experience a feeling of pressure & suffocation behind the breastbone
Pain begins in chest then travels to arm, neck & jaw respectively. It is brought on by exertion, cold or excitement
It is thought chemical factors that cause pain in skeletal muscle (i.e. K+, H+ & adenosine) are responsible
56
What are the 3 different types of angina? Explain them.
STABLE ANGINA(fixed stenosis):
- predictable chest pain on exertion
- caused by a fixed narrowing of the coronary arteries
- treated by decreasing the workload of the heart & therefore decreasing oxygen requirement
- also use drugs to prolong survival (e.g. aspirins, statins, ACE inhibitors)
UNSTABLE ANGINA(thrombus):
- occurs at rest & with less exertion than stable
- associated with a thrombus around a ruptured atheromatous plaque but without complete occlusion of the vessel (similar to MI)
VARIANT (Prinzmetal) ANGINA(vasospasm):
- uncommon. Is caused by coronary artery spasm
- it's not completely understood but is sometimes associated with atherosclerosis
57
What are the classes of drugs used to treat angina? (HINT: there's 2 different classes)
Mainly work by decreasing the metabolic demand of muscle
1. Organic nitrates, nicorandil & calcium antagonists are vasodilators - they decrease preload or afterload
2. Beta blockers & ivabradine slow down the heart, decreasing the metabolic demand of muscle
58
For beta blockers, explain their MoA, link this to their therapeutic outcomes & explain any unwanted side effects they have. Give 2 named examples of beta blockers
First line treatment in the prophylaxis & treatment of both stable & unstable angina
- They decrease cardiac oxygen consumption by slowing the heart
- also have an antidysrhythmic action, reducing death after MI
E.g. bisoprolol, atenolol
59
For calcium antagonists, explain their MoA & explain what the 2 main types of this drug are.
They prevent the opening of V-gated L-type Ca2+ channels, therefore blocking calcium entry. This mainly affects the heart & smooth muscle to inhibit calcium entry upon muscle depolarisation
There are 2 main types; Dihydropyridine derivatives e.g. amlodipine & lercanidipine OR rate limiting e.g. verapamil & diltiazem (can reduce & impair AV conduction & myocardial contractility)
Has a vasodilator effect mainly on resistance vessels, therefore reducing afterload & dilating coronary vessels (important in variant angina)
60
What is the clinical uses of calcium antagonists in angina? & What do unwanted side effects include? Give 2 other clinical uses that calcium antagonists are used for.
The choice of type depends on comorbidity & drug interactions:
- amlodipine or lercanidipine are safe in pts with heart failure, they are used instead of a beta-blocker in Prinzmetal angina or alongside beta blockers in most angina
- Diltiazem or verapamil are used but contradicted in heart failure, bradycardia, AV block or in the presence of a beta blocker.
SIDE EFFECTS = headache, constipation, ankle oedema
1. ANTIDYSRHYTHMICS - verapamil
2. HYPERTENSION - amlodipine or lercanidipine
61
What are the 2 types of organic nitrates? What is their MoA?
Glyceryl trinitrate & isorbide mononitrate
- powerful vasodilators that work by being metabolised to NO & relax smooth muscle (particular vascular smooth muscle)
- they act on veins to decrease cardiac preload, but higher concentrations can affect arteries therefore decreasing afterload
- decreasing cardiac workload is helped by dilation of collateral coronary vessels, improving distribution of coronary blood flow towards ischaemic areas. Dilation of constricted coronary vessels is particularly beneficial in variant angina
62
What are the 2 clinical uses of organic nitrates in angina? What are the side effects that are associated?
1. STABLE = prevention by sublingual GTN shortly before exertion or isosorbide mononitrate long before
2. UNSTABLE = IV GTN
SIDE EFFECTS = headache & postural hypertension
NOTE: side effects are common
63
What are 2 other clinical uses of organic nitrates other than angina?
1. Acute heart failure (in specific circumstances)
- intravenous GTN
2. Chronic Heart Failure (CHF)
- isosorbide mononitrate with hydralazine in pts of African American origin especially (or pt cannot tolerate more commonly used CHF drugs)
64
What is the MoA of Nicorandil? What side effects can it have? What type of pts is it used for?
Is a potassium channel activators
- it combines the activation of potassium K+ATP channels with nitrovasodilator actions causing hyperpolarisation of vascular smooth muscle
- is both an arterial & venous dilator
SIDE EFFECTS = headaches, flushing & dizziness
Used in pts who remain symptomatic despite optimal management with other
65
What is the MoA of (i) ivabradine (ii) ranolazine?
(i) Inhibits funny "f"-type channels in heart which reduces cardiac pacemaker activity, therefore inhibiting HR
(ii) Unique anti-anginal used as a last resort
66
What is health promotion?
The process of enabling people to increase control over, and improve, their health
67
What are the methods of health promotion?
1. Providing info
2. Enhancing motivation
- tailored content, cognitive behavioural therapy, gain vs loss, motivational interviewing
3. Behavioural methods
- training, reminders, reinforcers
4. Health behaviour maintenance
- helping people deal with a lapse OR reduction of a relapse
5. Combined programmes
- e.g. slimming clubs
68
Describe health promotion programmes in the context of CVD
Primary prevention example = HEBS walking campaign
Secondary prevention
- BP, cholesterol checks
E.g. ppl with one or more modifiable CV risk factors
- behavioural conselling vs nurses normal methods (of info + exhortation), 2 or 3 sessions
Tertiary prevention
- people who already have the illness, looking to relieve symptoms
69
How can personality impact on coronary heart disease & treatment options?
TYPE A & TYPE B personalities
Type A = high competitiveness, high time urgency, high hostility
Type B = low competitiveness, low time urgency, low hostility
70
How do you assess Type A behaviour?
Structured interview
Questionnaires (self-report)
- Jenkins activity survey
- Framingham type A scale
71
How are type A behavioural characteristics reduced?
1. Stress reduction strategies
2. Relaxation techniques
3. Anger management
72
What are the disadvantages of IV administration?
1. Increased cost & time to administer the medicine
2. Requires staff to administer (plus location)
3. Rapid onset of action
4. Volume of fluid needed to dilute the medicine
5. Can cause discomfort/pain to the pt
6. Health risks (e.g. infection)
73
What are the 5 rights of medicine administration?
RIGHT:
- patient
- medicine
- route
- dose
- time
74
What are the different types of intravascular devices (IVDs)?
1. Peripheral venous catheters
2. Central venous catheters (CVCs)
- peripherally inserted or skin-tunneled (e.g. Hickman & broviac lines)
3. Arterial catheters
75
What is red man syndrome?
A hypersensitivity reaction due to histamine release
- erythematous rash of the face, neck & upper torso
- diffuse burning, itching & generalised discomfort
- in rare cases experience hypertension, angioedema, chest pain, dyspnea
76
What 4 things is the stability of medicines in solution dependent upon?
1. Light (e.g. total parental nutrition [TPN])
2. Temperature (e.g. insulin, TPN)
3. Concentration (e.g. amiodarone)
4. pH (e.g. midazolam)
77
What 4 things is the stability of medicines in solution dependent upon?
1. Light (e.g. total parental nutrition [TPN])
2. Temperature (e.g. insulin, TPN)
3. Concentration (e.g. amiodarone)
4. pH (e.g. midazolam)
78
When would the graph of plasma concentration against time be a straight line? Why is never the case in practice?
If the drug is infused at a constant rate & no drug is removed from the body
BUT drug is being eliminated from the body as soon as it is in the circulation (e.g. via the kidneys)
79
What 3 things shrink the window for coronary flow?
1. Shortening diastole e.g. increased HR
2. Increased ventricular end diastolic pressure e.g. aortic valve stenosis
3. Reduced diastolic arterial pressure e.g. mitral/aortic valve incompetence, heart failure
80
For most drugs, the amount of drug eliminated per unit time is related to what? Explain this relationship with regards to both higher & lower concentrations of drug. What will the graph therefore look like?
the concentration of drug in the plasma (first-order kinetics)
- Higher concentrations, more drug is removed per unit of time
- Lower concentrations, less drug is removed per unit of time
The graph of plasma concentration against time for most infusions will bend towards a plateau when the rate in of drug equals the rate out.
81
What is Clearance? (CL)
The volume of blood/plasma cleared of drug in a unit - e.g. 10ml/min
it is a constant
82
What are the reasons for iV administration? (HINT: there's 6 reasons)
1. Not available in another form
2. Cant tolerate medication by another route
3. Constant or high blood level of medicine is needed
4. Rapid onset of effect us needed
5. Some medications are more effective via IV
6. Rarely, to ensure compliance
83
The plasma steady state constant is written as Css. What does the Css value reached depend upon?
the rate of drug administered (K0) / volume of plasma cleared per unit time (CL)
84
The time taken to reach Css depends on what? How is t1/2 calculated?
depends on the elimination half-life (t1/2)
t1/2 directly depends on the volume distribution (Vd) & inversely on the clearance (CL) of drug from the body
t1/2 = (ln2 x Vd) / CL
85
What are the 3 methods of administering IV medications?
1. CONTINUOUS INFUSION
- stable drugs, short half-life, time dependent effects, needs a dedicated IV site
2. BOLUS INJECTION
- rapid response required
- incompatibilities
- unstable drugs
3. INTERMITTENT INFUSION
- unstable drugs, long half-life, concentration dependent effects, less compatibility concerns
86
What are the 3 complications of IV drug administration that is due to the chemical composition of said drug?
1. Insufficient mixing
2. Stability of medicines in solution
3. Interaction of medicines with the syringe/bag
87
What are the 6 factors that affect drug distribution?
1. Cardiac output & blood flow
2. Plasma protein binding
3. Lipid solubility
4. Degree of drug ionisation
5. pH of compartments
6. Capillary permeability
88
What does the initial rate of distribution of drugs depend on?
On blood flow
89
How do (i) lipid soluble drugs (ii) weak acids bind to albumin?
(i) Non-specifically
| (ii) Bind to specific, saturable site
90
For hydrophilic drugs, (i) what are they soluble in? (ii) what is their rate of distribution dependent on?
(i) aqueous, polar media
(ii) On diffusion characteristics of the drug
Don't get across membrane easily
91
For lipophilic drugs, (i) what are they soluble in? (ii) what is their rate of distribution dependent on?
(i) fats & non-polar solutions
| ii) rate of delivery to tissues (e.g. blood flow
92
What does the ionised:unionised ratio depend on?
pH
93
What is the blood brain barrier?
Prevents the easy & ready exchange of things into the brain
Is both a physical & functional barrier
94
What are other specialised barriers/compartments within the body? (HINT: there's 3)
1. PLACENTA
- tight endothelial cel junctions in maternal & fetal capillaries
- is partially protective, except with lipid soluble drugs or unionised forms of weak acids & bases
2. CHRONIC ABSCESSES
- avascular tissue compartments
3. LUNG INFECTION
- local low PO2 & high PCO2 cause vasoconstriction
95
How many litres of fluid are in the (i) extracellular fluid (ii) intracellular fluid?
(i) 15
| (ii) 27
96
What is the apparent volume of distribution of a drug (Vd)?
The theoretical volume required to account for the amount of drug in the body
UNITS = litres or sometimes L/kg of body weight
= total amount of drug in the body / blood plasma conc of drug
97
What 2 things does the single compartment mode of distribution assume?
1. rapid mixing of drug in plasma
| 2. drug in plasma is in rapid equilibrium with drug in extravascular tissues
98
What is Vd used to determine? What does it vary with?
To determine a loading dose to achieve a desired plasma conc of drug
Varies with:
- height
- weight
- age
- fluid accumulation (ascites, oedema, pleural effusion)
- accumulation of fat
99
What is a key factor for determining a drug's half life?
The volume of distribution
100
What is the difference between systemic & pulmonary hypertension? (HINT: there's 4 points)
systemic is much more common than pulmonary
Pulmonary artery pressure is hard to measure
Pulmonary hypertension may be idiopathic or associated with other diseases
It is usually only diagnosed when severe & symptomatic
101
What are the 6 main causes of pulmonary hypertension?
```
Hypoxia
Endothelial dysfunction
(Raynaud's)
Genetics
Blockage/damage to pulmonary BVs (PE; sickle cell etc)
Side-effects of some drugs
```
102
Define (i) hypertension (ii) primary hypertension (iii) secondary hypertension.
(i) a state of elevated arterial BP
(ii) aka idiopathic. >90%cases
(iii) known cause; <10% cases
e. g. renal disease, diabetes, cushing's, phaeochromocytoma, some drugs
103
How is (i) stage 1 hypertension (ii) stage 2 hypertension (iii) severe hypertension classified?
(i) Clinic BP is 140/90mmHg or higher & subsequent ambulatory or home BP monitoring (ABPM or HBPM) daytime average is 135/85mmHg or higher
(ii) Clinic BP is 160/100mmHg or higher & subsequent ABPM or HPBM daytime average is 150/95mmHg or higher
(iii) Clinic systolic BP is 180mmHg or higher or clinic diastolic is 110mmHg or higher
104
What are the possible causes of primary hypertension?
1. INCREASE IN TOTAL PERIPHERAL RESISTANCE
- balance between contraction/relaxation changes
- increased sympathetic nerve activity (increased firing rate or increase in NA released)
2. INCREASED VASCULAR REACTIVITY
- increase in [Na+]ECF
- Pathological Na/K-ATPase inhibition
- Damage to endothelium, decreasing NO production
- altered BV wall morphology, increasing the wall thickness to lumen ratio
105
What are the causes of secondary hypertension? (HINT: there's 6)
1. Renal disease
- altered BP control
2. Diabetes
- damaged endothelium
3. Endocrine disorders
- Cushing's, Conn's, phaeochromocytoma etc
4. Coarctation (narrowing) of the aorta
5. Some drugs
- e.g. contraceptive pill, cocaine, amphetamine, NSAIDs, some herbal remedies
6. Pregnancy
- eclampsia; pre-eclampsia
106
What are the risk factors for hypertension?
```
Age (the older you are, the higher the risk)
Modifiable factors:
- exercise
- diet (high salt; high fat)
- obesity (especially central obesity)
- smoking
- alcohol intake
- stress
Genetic Factors
- abnormal inhibition of the Na/K-ATPase
- family history
- being of African or Caribbean origin
- Male
Psychogenic factors:
- personality type
```
107
What effects does hypertension have on the body with relation to the heart?
Heart failure
- pressure overload from increased TPR; LV hypertrophy
- volume overload due to kidney failure; decreasing actin-myosin overlap
LV hypertrophy is a major risk factor for coronary heart disease, dysrhythmias, sudden death & congestive heart failure
MI
108
With regards to vasculature, what are the effects of hypertension on the body?
Accelerated atherosclerosis
- smaller arteries & arterioles
Stroke
- narrowing & sclerosis of small cerebral arteries; white matter changes
Retinopathy
- retinal BVs damaged by high pressure
- arteries become narrowed & tortuous
- subsequently veins are occluded & oedema haemorrhage occurs
109
With regards to renal failure, what are the effects of hypertension on the body?
Autoregulation tries to protect the glomerulus
Albuminuria
Continued high pressure
- arteriolar walls thicken & narrow
- kidney function declines irreversibly (sclerosis due to fibroblast activity)
Urine formation falls
- volume overload
- decreased clearance of creatinine, urea & waste products
110
For a 35 year old male, explain the effect hypertension has on life expectancy.
BP - Life Expectancy
120/80 - 38-40 years
140/100 - 15-20 years
150/120 - 8-10 years
111
What life style changes can reduce BP without the need for drugs?
```
Reducing alcohol intake
Stop smoking
Increase intake of unrefined carbs
Decrease fat intake (especially saturated)
Decrease Na intake
Increase fruit & veg intake (k+)
Increase aerobic exercise
```
112
What are the common side effects of antihypertensive drug treatment?
1. Renin-Angiotensin system inhibitors
– Angiotensin converting enzyme inhibitors
= Persistent dry cough, dizziness, tiredness, headaches
– Angiotensin AT1 receptor antagonists (ARBs)
= Dizziness, headaches, back/leg pain
2. Calcium channel blockers
= Flushes, headaches, ankle oedema, dizziness
3. Diuretics
– Thiazide-like diuretics
= Can raise potassium & blood sugar levels
113
What are the major drug classes used to treat hypertension?
1. Renin-Angiotensin system inhibitors
- angiotensin converting enzyme inhibitors E.g. ramipril, lisinopril
- angiotensin AT1 receptor antagonists (ARBs) e.g. losartan
- renin inhibitors e.g. aliskiren
2. Calcium channel blockers e.g. amlodipine, lercanidipine
3. Diuretics
- thiazide-like diuretics e.g. indapamide, bendroflumethiazide
114
What are the additional treatments that are used to treat resistant hypertension?
1. SYMPATHETIC NERVOUS SYSTEM ANTAGONISTS
- beta blockers e.g. bisoprolol, atenolol
- alpha-adrenoreceptor blocker e.g. doxazosin
2. KIDNEY FUNCTION MODIFIERS
- potassium sparing diuretics & aldosterone antagonists e.g. spironolactone
115
What are the 3 types of Renin Angiotensin System Inhibitors?
1. Angiotensin converting enzyme inhibitors
e. g. ramipril, lisinopril
2. Angiotensin AT1 receptor antagonists (ARBs)
- losartan
3. Renin inhibitors
- aliskiren
116
What are the 2 examples of calcium channel blockers that are dihydropyridine-like?
Amlodipine & lercanidipine
117
What are the 2 types of drugs which modify kidney function? Explain them.
1. THIAZIDE-LIKE DIURETICS
- indapamide
- bendroflumethiazide
2. ALDOSTERONE ANTAGONISTS
- spironolactone
118
In kidney modifying drugs in hypertension, where do the different drugs act on the tubule?
Thiazide-like diuretics: Distal tubule Na/Cl channel inhibitor
Aldosterone antagonists: Collecting tubule Na/Cl channel inhibitor
119
What is the difference between preload and afterload?
```
Preload= Dictates how much blood that is returned to heart
Afterload= Pressure that the heart is pumping against
```
120
What are the five domains of failure, outlined by Noble & Donaldson, which they believe have been present in the area of intrathecal vincristine administration error?
Failure to learn from adverse events
Failure of international translation
Failure of solutions
Failure to achieve compliance with safety guidance
Failure of investigations & enquiries
121
What are the three possible solutions, outlined by Noble & Donaldson, to prevent wrong route delivery medication errors?
1. Drug alerts that warn healthcare institutions, medical
practitioners and other relevant personnel about new risks.
2. Development of consensus and evidence-based protocols & guidelines to create a standard operating procedure that
prevents against error.
3. Physical redesign of delivery systems such that it is impossible
to deliver drugs by the wrong route.
122
What are the reasons for inserting a central line? (HINT: there's 5 reasons)
1. Measurement of CVP
2. Administration of drugs or products that would damage smaller caliber veins such as chemotherapy or parental nutrition
3. Need to obtain venous access in a pt whose peripheral veins are shut down e.g. a pt with shock
4. Administration of high flow fluids
5. Ease of administration of products in a pt likely to need IV access for several days e.g. post major abdominal surgery
123
What are the 2 most common sites for central line insertion? Where are the other 2 places it can also be done?
Internal jugular & subclavian vein
| Femoral & external jugular vein can also be used but less commonly
124
What are the complications that can arise when inserting a central line? (HINT: there's 7 complications)
1. Puncturing the apex of the lung = pneumothorax
2. Puncturing a major vessel as well as the lung = haemothorax
3. Accidentally cannulating a large artery
4. Damage to the thoracic duct if placing a line on the left
5. Introducing air into circulation when entering the line = air embolism
6. If inserted in un-sterile conditions then introducing an infection to a major blood vessel & into the bloodstream
7. Risk of damage to anomalous venous valves which may result in thrombus formation of thrombus
