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Clinical Pharmacology, Therapeutics & Principles of Prescribing > Session 4 > Flashcards

Session 4 Flashcards

1
Q
  1. Revision of basic renal physiology
  2. Pharmacology of agents acting on the renal tubules (affect salt and water balance)
  3. Brief outline of major indications for diuretic therapy
  4. Drugs causing renal complications
  5. Treating hyperkalaemia
A
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2
Q

Revision of basic renal physiology LO

what is the Renal Physiology Mnemonic?​

A
  • Regulatory
  • Excretory
  • Endocrine
  • Metabolism
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3
Q

What do we mean by Regulatory

A

– Fluid balance
– Acid-base balance
– Electrolyte Balance

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4
Q

What do we mean by Excretory

A

– Waste products
– Drug elimination
– Glomerular Filtration
– Tubular Secretion

​

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5
Q

What do we mean by Endocrine

A

– Renin
– Erythropoietin
– Prostaglandins
– 1-alpha calcidol

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6
Q

What do we mean by Metabolism

A

– Vitamin D

in the proximal tubule 25- hydroxyvitamin D3 -> calcitriol

allows uptake of Ca2+ from the proximal tubule and from the gut

– Polypeptides
• Insulin

– Drugs
• Morphine
• paracetamol

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7
Q

Pharmacology of agents acting on the renal tubules (affect salt and water balance) LO

  1. Drugs Acting on the Renal Tubules (7)
  2. Diuresis –

Natriuresis –

A
  1. • Carbonic anhydrase inhibitors
  • Osmotic Diuretics
  • Loop Diuretics
  • Thiazides
  • Potassium sparing diuretics
  • Aldosterone antagonists
  • ADH Antagonists

CATAPOL(T)

  1. Diuresis – loss of water;

Natriuresis – loss of sodium

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8
Q

Effect of aldosterone on the kidney

A
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9
Q

Include lithium / demeclocycline

•Reduces concentrating ability of urine in collecting ducts

Filtered at Glomerulus Increase osmotic gradient throughout nephron Excessive water loss Hypernatraemia

A
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10
Q

How does aldosterone affect he collecting duct

A

Aldosterone increases expression of ENaC and Na/K/ATPase in principal cells of the collecting duct

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11
Q

Other substances with diuretic action (lifestyle substances)

A
  • Alcohol – inhibits ADH release
  • Caffeine - ↑GFR and ↓ tubular Na+ reabsorption
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12
Q

Give e.g. of ADH antagonists

A
  • Lithium – diuretic but not natriuretic. Inhibits action of ADH
  • Tolvaptan – ADH antagonist. Diuretic but not natriuretic. Used to treat hyponatraemia (& prevent cyst enlargement in APCKD)

​

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13
Q

Diuretics: Generic Adverse Drug Reactions (4)

A

• Anaphylaxis / photosensivity rash etc

• Hypovolaemia & hypotension
– Activates RAAS
– Can lead to acute kidney injury

  • Electrolyte Disturbance (Na+, K+, Mg2+, Ca2+)
  • Metabolic Abnormalities (depends on individual drug)
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14
Q

Diuretics: Common Specific ADRs

  1. Thiazides
  2. Spironolactone
  3. Frusemide
  4. Bumetanide
A
  1. • Gout
    • Hyperglycaemia
    • Erectile dysfunction
    • ↑LDL ↑TG
    • Hypercalcaemia
  2. • Hyperkalaemia
    • impotence
    • Painful gynaecomastia
  3. • Ototoxicity
    • Alkalosis
    • ↑LDL ↑TG
    • Gout
  4. • Myalgia
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15
Q
A
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16
Q

Uses for Diuretics

A

Hypertension

Heart Failure

Decompensated Liver Disease

Nephrotic syndrome

Chronic Kidney Disease

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17
Q

What diuretics can be used for Hypertension

A

• Thiazide diuretics (vasodilatation as well as diuresis)

e.g. Chlortalidone

PO 25 mg daily (morning), then increased if necessary to 50 mg

e.g. indapamide

PO immediate-release: 2.5 mg daily (morning)

PO modified-release: 1.5 mg daily (morning)

• Spironolactone adjunt (resistant hypertension)

PO: 25 mg once daily

  • (Loop diuretics)
  • ACE inhibitors / Ang II antagonists
  • b-blockers​
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18
Q

What diuretics can be used for Heart Failure

A

• Loop diuretics

https://bnf.nice.org.uk/drug/furosemide.html

• (Spironolactone – non-diuretic benefits)

Oedema in CHF

PO: Initially 100 mg daily, alternatively initially 25–200 mg daily, dose may be taken as a single dose or divided doses, maintenance dose adjusted according to response.

Moderate to severe HF (adjunct)

PO: Initially 25 mg once daily, then adjusted according to response to 50 mg once daily.

  • ACE Inhibitors / Ang II antagonists
  • b -blockers
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19
Q

What diuretics can be used for Decompensated Liver Disease​

A
  • Spironolactone
  • Loop diuretics
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20
Q

What diuretics can be used for Nephrotic syndrome

A
  • Loop diuretic (often big doses needed)
  • +/- thiazides
  • +/- potassium-sparing diuretic / potassium supplements

*Role of secondary hyperaldersteronism

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21
Q

What diuretics can be used for Chronic Kidney Disease

A
  • ↓GFR leads to salt and water retention
  • Loop diuretics
  • (+/- thiazide-like)
  • Alkalosis & kalliuretic effects potentially beneficial
  • Generally avoid K+-sparing diuretics
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22
Q

Diuretic resistance
All these patients are taking oral furosemide 80 mg daily

All are gaining weight & becoming more oedematous

How is furosemide delivered to the kidney tubule?

A
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23
Q

What should you do if your patient is in refractory oedema?

A
  • Check salt intake (24 hour sodium excretion if necessary)
  • Give furosemide iv if gut oedema likely
  • Find minimum effective dose
  • Give repeated bolus or infusion (short t1/2)
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24
Q

Thiazide, loop diuretics, sodium & potassium
• Two 75 year old patients are taking diuretics

Why is patient 1 hyponatraemic and hypokalaemic while patient 2 has normal electrolytes?

A
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25
Q
A
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26
Q

Drugs causing renal complications LO

  1. • Drugs may reduce kidney function by ?
  2. • Drugs may accumulate to toxic levels if ?
A
  1. direct or indirect toxicity
  2. they are excreted through the kidneys & renal function is impaired
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27
Q

Give examples of Potentially Nephrotoxic Drugs (​4)

A
  • Aminoglycosides: e.g: gentamicin
  • Vancomycin (intravenous only)
  • Aciclovir
  • NSAIDs

• ++ more
Double Whammy if renal function is impaired Can cause irreversible renal damage

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28
Q

Drugs that can cause problems with renal dysfunction (4)

A
  • ACE-Inhibitors
  • Diuretics
  • NSAIDs
  • Metformin
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29
Q

State how Renal artery stenosis, hypovolaemia would affect this? (Image)

A
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30
Q

How ACE-Inhibitors and NSAIDs affect renal perfusion

A
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31
Q

Prescribing in Patients with Chronic Kidney Disease
1. Avoid?

  1. If ? required, dose very carefully in consultation with pharmacist.
  2. Check with pharmacist – whether any of existing drugs need dose altering
    – Allopurinol

– Digoxin

– Cyclosporin / Tacrolimus

– Low molecular weight heparins

  1. • Side effects of some common drugs are increased with renal disease(accumulation of metabolites) e.g.
A
  1. nephrotoxins
  2. gentamicin / vancomycin

3.

4.
– Morphine & other opiates
– Nitrofurantoin
– Statins

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32
Q

Hyperkalaemia LO

  1. Causes of hyperkalaemia (4)
A

• Excess intake (virtually never the only cause)

• Movement out of cells
– Acidosis
– Hypertonicity
– Tissue (especially muscle) damage

• Reduced urine loss
– Reduced GFR
– Reduced distal delivery of Na+ (oliguric AKI, obstruction)
– Reduced secretion in collecting duct

• Drugs
– RAAS Inhibitors (ACE-Inhibitors, spironolactone), NSAIDs, ENaC blockers (trimethoprim, amiloride)

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33
Q

Major risks of Hyperkalaemia (2)

A
  • Increased catabolism / tissue damage
  • Reduced urine production
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34
Q

What are the changes on the ECG for hyperkalaemia

A
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35
Q

What is this ECG showing?

A

Hyperkalaemia – initial ECG changes
Tall T waves

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36
Q
A
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37
Q
A

Severe Hyperkalaemic changes - Sine waves

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38
Q

Management of Hyperkalaemia

A

• Identify cause! • ECG • Treatment:

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39
Q

Treatment is composed of?

A
40
Q

Diuretics don’t work if taken with?

A

salt

41
Q

• Know the key physiological targets for drugs that are used in treating patients with hypertension and heart failure.
• Understand that decisions about drug therapy are informed by both blood pressure level and total cardiovascular risk
• Be aware of non-pharmacological management of hypertension
• Describe the main classes of antihypertensive drugs, sites of action and main
side effects
• Appreciate how drug choices are made with the use of combination therapy and the key clinical trial evidence / NICE guidance supporting drug choice
• Appreciate the multidisciplinary, multi-factorial nature of treating heart failure
• Summarise the major principles underlying drug therapy in heart failure
• Appreciate the important side effects of commonly prescribed drugs in heart failure
• To be aware of current clinical guidelines for the treatment of heart failure
• Apply your knowledge of heart failure therapy to case studies in heart failure

A
42
Q

What are the physiological controls of bp?

A

Physiological Control
• Autonomic Nervous System

• Renin-Angiotensin System

(have not included - prostaglandins & ADH)

• Others:
– Bradykinin
– Endothelin
– Nitric Oxide
– Atrial Natriuretic Peptide

43
Q

Describe what happens when a drop & rise in bp occurs

A
44
Q

Describe RAAS

A
45
Q

How does a high bp lead result in morbidity

A
46
Q

What does this graph show?

A

Reduction in Mortality and Morbidity

Significant drop on bp after 5 yrs

47
Q
  1. Define hypertension
  2. Lowering diastolic BP by 10mmHg is associated with reductions in ?
  3. Causes of Hypertension​
A
  1. 140/90mmHg, 40% of the adult population of England are hypertensive although the proportion increases with age
    • stroke of 58%
      - coronary heart disease of 37%
  3. Primary (Essential) hypertension

High BP without any single evident cause

90% hypertensive population

Genes and lifestyle?

Secondary hypertension

High BP with a discrete, identifiable underlying cause

10% hypertensive population

Conns renal artery stenosiS Cushings

48
Q

Classification of Hypertension – BHS Thresholds for treatment

A
49
Q

• Be aware of non-pharmacological management of hypertension LO

Give e.g. of Lifestyle Therapy

A
  • Patient education
  • Maintain normal body weight (BMI 20-25 kg/m2)
  • Reduce salt intake to <6g/day
  • Limit alcohol consumption to <3units/day for men, <2 units/day for women
  • Engage in regular aerobic physical exercise for >30 minutes/day
  • Consume >5 portions of fresh fruit/vegetables daily
  • Reduce intake of total and saturated fat
  • (Smoking cessation) reduce CVS no effect on hypertension
  • (Relaxation therapies)
50
Q

• Describe the main classes of antihypertensive drugs, sites of action and main side effects LO

1st Line UK Pharmacological Therapy:

A
  • Angiotensin Converting Enzyme (ACE) inhibitors/ Angiotensin Receptor Blockers
  • Calcium channel blockers
  • [Diuretics]

(ARB)

51
Q
  1. How do ACE inhibitors lower BP?
  2. What is there substrate and product?
  3. Give examples
  4. Side effects?
A

ACE breaks down bradykinin when you inhibit it you increase bradykinin

  1. Reduction in formation of angiotensin II

Mainly arteriolar vasodilators

Some venodilation

Circulating aldosterone is reduced

  1. • Inhibit Angiotensin Converting Enzyme activity • Prevents generation of Angiotensin II
  2. E.g. lisinopril, ramipril
  3. Main side effect – dry cough (10-15%) -> Potentiates the action of bradykinin (prevents breakdown) -> build up in lungs-> local vasodilation
  • Important side effects
  • Angio-oedema (rare, but more common in black pop.)
  • Renal failure (incl. renal artery stenosis)
  • Hyperkalaemia
52
Q

Angiotensin Receptor Blockers

  1. Give examples
  2. Which receptor does it bind to?
  3. Function i.e. wha physiological processes does it initiate to lower bp
  4. Swipe effects
A
  1. Eg. Losartan, Candesartan
  2. angiotensin AT1 receptor
  3. Inhibit vasoconstriction and aldosterone stimulationcaused by angiotensin II
  4. Well tolerated few side effects

Important side effects:

  • Renal failure
  • Hyperkalaemia
53
Q

Calcium Channel Blockers

  1. What is its substrate? Effect it has?
  2. Three main groups:
  3. Physiological effect?
A
  1. Bind to specific alpha subunit of L-type calcium channel, reducing cellular calcium entry.
    • Dihydropyridines (Nifedipine, Amlodipine) -> Anti hypertensive
      - Benzothiazepines (Diltiazem) -> anti anginal
      - Phenylalkylamines (Verapamil) -> rhythm disturbance
  3. • Vasodilates peripheral, coronary and pulmonary arteries
  • No significant effect on veins
  • Short acting dihydropyridines -> baroreflex mediated tachycardia
  • Verapamil depresses SA node and slows A-V conduction
54
Q
  1. Calcium Channel Blockers Dihydropyridines e.g.
  2. Properties:
  3. Adverse effects:
A
  1. amlodipine
  2. • Good oral absorption
  • Protein bound > 90%
  • Metabolised by the liver
  • Few have active metabolite
  1. • Sympathetic nervous system activation – tachycardia and palpitations
  • Flushing, sweating, throbbing headache
  • Oedema -> ankle swelling
  • Gingival hyperplasia (rare)
55
Q
  1. Calcium Channel Blockers Phenylalkylamines - e.g.
  2. Properties:
  3. Adverse effects:
A
  1. Verapamil
  2. • Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
  • Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period
  • Peripheral vasodilatation and a reduction in cardiac preload and myocardial contractility
  1. • Constipation
  • Risk of bradycardia -> not a good drug to use with bradycardia
  • Reduce myocardial contractility (negative inotrope) – can worsen heart failure
56
Q
  1. Calcium Channel Blockers Benzothiazepines - e.g.
  2. Properties:
  3. Adverse effects:
A
  1. Diltiazem
  2. • Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
  • Prolongs the action potential/effective refractory period
  • Peripheral vasodilatation and a reduction in cardiac preload and myocardial contractility
  1. • Risk of bradycardia

• Less negative inotropic effect than verapamil – can worsen heart failure

57
Q
  1. Thiazide/Thiazide Like Diuretics e.g.
  2. Effect on the nephron? Results in?
  3. Dose-blood pressure response curve:
  4. Thiazide class: Adverse Effects:
A
  1. (Bendroflumethiazide / Indapamide )
  2. • Reduce distal tubular sodium reabsorption
  • Sustained action
  • Blood pressure reduction – complex
  • Several mechanisms
  • Initial blood volume decrease
  • Later - total peripheral resistance falls
  1. flat
  2. • Hypokalaemia
  • Increased urea and uric acid levels
  • Impaired glucose tolerance (especially with beta-blockers)
  • Cholesterol and triglyceride levels increased
  • Actives renin angiotensin system
58
Q

• Appreciate how drug choices are made with the use of combination therapy and the key clinical trial evidence / NICE guidance supporting drug choice LO

What does this graph show?

A

Compared three drug classes
Any other additional drug to reach the target blood pressure
Followed up individuals
Did not matter what treatment regimen was used
Outcome is measure by blood pressure control not what type of drug you use

59
Q

• Appreciate how drug choices are made with the use of combination therapy and the key clinical trial evidence / NICE guidance supporting drug choice LO

  1. Complete the flow diagram treatment for hypertension advised by NICE Guidance: Aug 2011
A
60
Q

What is this graph showing?

A

NICE Economic Modelling

Cost of intervention- drug and outcome
Cost of non treatment and there outcome
Include factors
Higher number good effect
B blockers not that effective or well tolerated
The other three much the same benefit and cost

61
Q
  • *Other Anti-hypertensive Drugs**
  • *1. Other ‘diuretics’:**

2. • Alpha-adrenoceptor blockers (e.g. ?)

• Beta-adrenoreceptor blockers (e.g. ?)

  1. • Direct Renin Inhibitor: ?
  • Centrally acting agents (e.g. ?)
  • Vasodilators (e.g. ?)
A
  1. • Spironolactone (ARB) blocks ENAC & Na+/K+ atpase

• Amiloride (K+ sparing) blocks ENAC

  1. doxazosin

bisoprolol

  1. Aliskiren

Methyl Dopa / Moxonidine

Hydralazine / Sodium nitroprusside

62
Q

Alpha Blockers (Doxazosin)

  1. Properties:
  2. Adverse effects:
A
  1. • Selective antagonism at post-synaptic α-1 adrenoceptors and antagonise the contractile effects of noradrenaline on vascular smooth muscle
  • Reduce peripheral vascular resistance
  • More effect in upright position
  • Benign effect on plasma lipids / glucose
  • Safe in renal disease
  1. • Postural hypotension………Dizziness
  • Headache and fatigue
  • Oedema (especially if combined with dihydropyridines)
63
Q

Beta Blockers

  1. Give examples
  2. Use? Physiological effect?
  3. Not thought to be as effective in terms of CVS outcome compared to others plus not well tolerate
  4. β-Blockers Adverse Effects
A
  1. Atenolol, bisoprolol, nebivolol
  2. Developed for angina but found to lower blood pressure, should be given in initial treatment of MI
  • Reduce heart rate and cardiac output
  • Inhibit renin release
  • Initially TPR increases later falls to normal
  1. • Lethargy, impaired concentration
  • Reduced exercise tolerance
  • Bradycardia

‘• Cold hands – Raynaud’s

  • Impaired glucose tolerance
  • Contraindication - asthma
64
Q

What is Aliskiren?

thus what is its substrate?

A
65
Q

Draw a diagram showing how aliskiren reduces BP.

How much percentage activity of renin does it reduce?

A

Aliskiren reduces plasma renin activity by 50-80%

Vasodilatory properties leading to BP reduction

66
Q
  1. Give e.g. of Centrally acting Agents & their effect (Less commonly used in hypertension)
  2. General effective
  3. Side effects restrict use:
A
  1. • Methydopa: converted to α-methyl-noradrenaline - a potent α2-adrenoceptor agonist
  • Clonidine: direct pre-synaptic α2-adrenoceptor agonist
  • Moxonidine: imidazoline I1 receptor agonist and ​some α2 agonist effect
  1. Reduce sympathetic outflow
  2. – Tiredness/lethargy

– Depression

*α-Methyldopa can be used to treat hypertension in pregnancy

67
Q
A
68
Q
  1. Give an example of ComboRx e.g. ?
A
  1. Thiazide - Amiloride
  • Hydrochlorthiazide: thiazide diuretic
  • Lowers BP (~14 mmHg)
  • Can raise glucose / lower K+
  • Amiloride: K+-sparing diuretic
  • Lowers BP (~14 mmHg)
  • Has no effect on glucose
  • Combo at half normal dose:
  • Lowers BP (~17 mmHg)
  • No effect on K+ nor glucose

Combine the two drugs but half the dose
Better bp dec
Negate each other’s effect on K nor no effects of glycaemic control

69
Q

Aetiology of heart failure (4)

A

• Ischaemic Heart Disease (most common)

• Hypertension (2nd most common)

• Cardiomyopathies
(e.g. alcohol / idiopathic / chemotherapy /iron overload, etc)

  • Valve disease
  • Others
70
Q

What is this ECG showing

A

MI

71
Q

What happens to the heart after an MI

A

Scar
Remodelling of the heart to protect scar area- then dilating

72
Q

Explain why people with heart failure have a high bp/ describe the vicious cycle of HF

A
73
Q

Appreciate the multidisciplinary, multi-factorial nature of treating heart failure LO

Management of Heart Failure - Principles

  • Correct underlying cause
  • Non-pharmacological measures
  • Pharmacological therapy
  1. Symptomatic improvement
  2. Delay progression of heart failure
  3. Reduce mortality

• Treat complications / associated conditions / cardiovascular risk factors e.g. arrhythmias

A
74
Q

What does it mean by correct underlying cause?

A

Intervention
– Treat underlying cause: + Valve surgery + Revascularisation

– Heart Transplantation

– Mechanical assist devices

Aetiology of heart failure:

  • Ischaemic Heart Disease -> i.e. PCI (i.e. Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing (stenosis) of the coronary arteries of the heart found in coronary artery disease. After accessing the blood stream through the femoral or radial artery, the procedure uses coronary catheterization to visualise the blood vessels on X-ray imaging. After this, an interventional cardiologist can perform a coronary angioplasty, using a balloon catheter in which a deflated balloon is advanced into the obstructed artery and inflated to relieve the narrowing; certain devices such as stents can be deployed to keep the blood vessel open. Various other procedures can also be performed.)
  • Hypertension -> Angiotensin Converting Enzyme (ACE) inhibitors/ Angiotensin Receptor Blockers (ARB), Calcium channel blockers, [Diuretics]
  • Cardiomyopathies

(e.g. alcohol / idiopathic / chemotherapy / iron overload, etc)

  • Valve disease -> replace valve i.e mechanical
  • Others
75
Q

State the Non-pharmacological measures for management of HF

A

Lifestyle Modification
– Reduce salt
– ↓ Alcohol
– ↑ Aerobic exercise
– ↓ BP

76
Q

• Summarise the major principles underlying drug therapy in heart failure LO

State Pharmacological therapy which allows for

  1. Symptomatic improvement
  2. Delay progression of heart failure
  3. Reduce mortality

for HF

A

Pharmacological
– Diuretics
– ACE (-)/ARB
– β-blocker

– Spironolactone

– Ivabradine -> bradycardia via specific inhibition of the funny channel
– Sacubitril -> inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure-lowering peptides that work mainly by reducing blood volume.

– Hydralazine/Nitrate -> Blacks
– (Digoxin) -> AF
– (Inotropes – Acute setting)
– (Phosphodiesterase Inhibitors – Acute setting)

– Antiarrhythmics

77
Q

Explain how we Treat complications / associatedconditions / cardiovascular risk factors e.g. arrhythmias

A

Implantable Pacemakers: + Biventricular Pacing

Implantable Defibrillators

78
Q

What is a pacemaker?

A
79
Q

What is a defibrillator?

A
80
Q

What is ramipril

A

ACE Inhibitors e.g. ramipril

81
Q

What is an ARB? Give an e.g.

Which is better an ACE or ARB?

A

3.5 yr follow up
After a handful of months separation of two curves
Early on effects

82
Q

In physiology, aldosterone escape is a term that has been used to refer to two distinct phenomena involving aldosterone that are exactly opposite each other:

A
  • Escape from the sodium-retaining effects of excess aldosterone (or other mineralocorticoids) in primary hyperaldosteronism, manifested by volume and/or pressure natriuresis.
  • The inability of ACE inhibitor therapy to reliably suppress aldosterone release, for example, in patients with heart failure or diabetes, usually manifested by increased salt and water retention. This latter sense may rather be termed refractory hyperaldosteronism.
83
Q

What are the levels of aldosterone when given an ACE or ARB, why?

A
  • In spite of ACE inhibitor / ARB therapy, aldosterone concentration returns to normal
  • Aldosterone “escape”
84
Q

How does aldosterone lead to sudden cardiac death?

A
85
Q
A

Individuals more likely to survive with spironolactone (in those with sever HF)

86
Q

β-blockers: Physiological effects (Heart Failure): (4)

A
  1. Reduce heart rate (cardiac beta receptor)
  2. Reduce BP (Reduced Cardiac Output)

1+2 ⇒ Reduced myocardial oxygen demand

(Reduce work of the heart)

  1. Reduce mobilisation of glycogen
  2. Negate unwanted effects of catecholamines

Not good in hypertension but good in heart failure (but what if hyper was the cause of Hf’
Reduce morbidity and mortality because of below

Reduce work of the heart

87
Q
A
88
Q

β-blockers in heart failure
How do we take care when using B-blockers?

A
  • Failing myocardium dependent on heart rate
  • Initiate at low dose
  • Titrate slowly
  • May have to alter concomitant medication (e.g. diuretic)
89
Q

• Appreciate the multidisciplinary, multi-factorial nature of treating heart failure LO

What are the different ways of HF

A
90
Q

Secondary causes of hypertension:

A
91
Q
  • *Phaeochromoctyoma**
    1. What is it?
  1. Give examples of catecholamine
  2. Describe the symptoms
  3. How is it diagnosed:
  4. 10% Rule (bilateral / non-adrenal / malignant etc)
  5. How would you treat? General
  6. Give examples of drugs
A
  1. Adrenal catecholamine-secreting tumour
  2. Adrenaline / Noradrenaline / (dopamine)
  3. Paroxysmal (sudden recurrence or intensification of symptoms) symptoms v. sustained high BP
  4. urinary catecholamines / Imaging

5.

  1. Non-selective alpha blockers: Direct effect on α-1 and α-2 adrenoceptors preventing the action of released noradrenaline
  2. Phenoxybenzamine – oral non competitive

Phentolamine – IV competitive for use in hypertensive crisis

β-blockers are given AFTER α-blockade

92
Q

Primary Hyperaldosteronism

  1. Results in what major sign/symptom?
  2. Causes:
  3. Physiology
  4. Treatment?
A
  1. hypertension
  2. o Conn’s syndrome
    o Bilateral adrenal hyperplasia
  3. • Excess secretion of aldosterone

• Plasma renin suppressed

  1. Aldosterone receptor antagonists:
  • Spironolactone
  • Eplerenone
  • Alternative: high dose amiloride
93
Q

Hypertensive Emergencies

  1. Very high BP (often over ?)
  2. Associated with acute complications e.g.
  3. Need to reduce BP by ?
  4. How?
A
  1. 220/120 mmHg
  2. pulmonary oedema, renal failure, aortic dissection etc
  3. ~20% or to 100 mmHg diastolic within 1-2 hours
  4. Sodium Nitroprusside: Mimics the action of endogenous nitric oxide on vascular smooth muscle, acting as a potent vasodilator

Intravenous use with powerful rapid onset and offset

Breakdown to cyanide – caution in liver disease, but renal excretion. Avoid prolonged use (>72 hours).

94
Q

• Apply your knowledge of heart failure therapy to case studies in heart failure LO

Case History A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure. PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.

  1. What factors might be contributing to his hypertension?
  2. Would you consider antihypertensive treatment at this level of blood pressure?
A
  1. Naproxen - retention of salt and water
    Age over 55
    Diabetes glycated basement membranes less complaint
    Arthritis - activities
    (Primary hypertension)
  2. Grade 3 hypertension
    So yes
    GP notebook for blood pressure targets varies for age, comorbities (diabetes 135)
    Also non pharmacological
95
Q
  1. What might he gain from effective control of his blood pressure?
  2. What drug might be most suitable for first line treatment?
  3. What target blood pressure would you aim for on treatment?
A
  1. Reduction in CV risk factors strokes, IHD, DEMTIA
  2. ACE inhibitors
    Thiazides diuretics
    Calcium channel blockers

As he is over 55 give calcium channel blockers first BUT
Problem is not straight forward patient may have HF or diabetes ACE I helps stops remodelling of heart do not get fibrotic tissue reduced TPR and effect of kidneys and blocks aldosterone
HF and diabetes ace inhibitor better than a calcium channel blocker

5.

96
Q

Your first line treatment achieves a blood pressure of around 160/100.

  1. What action would you take?
A

CCB

Go down the pathway
Check adherence
Titratable does up fully maximal dose
Before starting something else
Blood tests 7days after make sure have not pushed them into AKI - if drugs affect kidneys

97
Q

Case History - Heart Failure A 50-year-old man is admitted to hospital complaining of central, crushing chest pain. An acute anterior myocardial infarction is diagnosed. He receives treatment with aspirin, oxygen and primary PCI etc. He makes an uncomplicated recovery. His only identifiable risk factor for coronary heart disease is smoking (20 cigarette-pack-year history) and his only significant previous medical history is of “asthma” for which he uses a salbutamol inhaler. 48 hours after admission he is asymptomatic, BP 110/78 mmHg, heart rate 102 beats per minute, respiratory and cardiovascular examinations are otherwise normal.
1. What drug treatments would you consider at this stage?

An echocardiogram confirms significant left ventricular dysfunction in spite of normal examination. You decide to initiate ACE inhibitor therapy.
2. What mechanisms underlie the beneficial therapeutic effect of ACE
inhibitors in this clinical situation?
3. What are the possible adverse effects of ACE inhibitors and how
would you monitor the patient for these?

  1. What other pharmacological & non-pharmacological factors would
    you consider in the clinical treatment of this man?
A

1.Aware they have asthma but can give B blocker
Statin - reduce CV risk factors
ACE inhibitor after MI
B blocker reduce sympathetic s overdrive so prevent risk of HF after an MI
anticoagulants

2.• Inhibit angiotensin 2 reduce BP
• REDUCE PRELOAD
• prevents remodelling
• Less aldosterone
• Increase bradykinin which vasodilates- why u get a cough accumulates in the lungs
• Less Na and water resorption reduce blood volume less stress on the heart
• Vasodilation
• Venodilation
more blood in the circulatory system
Aldosterone causes damage to the heart leading to fibrosis

  1. Hyperkalaemia - blood test
    Dry cough
    Low Bp- must titratable carefully
    Angioedema affects the deeper layers, including the dermis, subcutaneous tissue, the mucosa, and submucosal tissues

4.Statins
Lifestyle changes
Diabetics furosemide to offload fluids

Clinical Pharmacology, Therapeutics & Principles of Prescribing (19 decks)

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