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CP1 > Therapeutics > Flashcards

Therapeutics Flashcards

1
Q

The “5 R’s” of error prevention

A
  1. Right patient
  2. Right time
  3. Right drug
  4. Right dose
  5. Right route
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2
Q

How to take a thorough drug history

A

WIPE

Go through each drug
=> check box if possible
=> check why and how often they take it

Check for any additional drugs
=> e.g. inhalers/creams/sprays/drops – people don’t always consider these!
=> Any HRT and oral contraception?
=> any OTC drugs?
=> any herbal medications?

CHECK FOR ALLERGIES

Ask for consent to access care summary records

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3
Q

Type A drug reaction

A

= augmented response

generally dose-related and usually managed by dose-adjustment

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4
Q

Potential ADRs/side effects of the GI system

A 
Inhibition of saliva
Oesophageal erosion
Ulcerogenic effects
Diarrhoea/infections
Constipation
Hepatotoxicity
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5
Q

Potential ADRs/side effects of the respiratory system

A

Bronchospasm
Fibrosis
Anaphylaxis

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6
Q

Potential ADRs/side effects of the CV system

A 
Cardiac arrythmias (e.g. Q-T prolongation)
Cardiotoxicity
CHF
Postural hypotension
Hypertension
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7
Q

Potential haematological ADRs/side effects

A 
Neutropenia
Thrombocytopenia
Bleeding
Myelosuppression
Aplastic anaemia
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8
Q

Which drug has a risk of causing aplastic anaemia when given orally?

A

Chloramphenicol

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9
Q

Potential renal ADRs/side effects

A

Renotoxicity
Fluid retention
Hypo/hyperkalaemia

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10
Q

Which drugs typically cause hypokalaemia?

A

thiazide / loop diuretics

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11
Q

Which drugs typically cause hyperkalaemia?

A

ACEis

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12
Q

Potential ADRs/side effects on CNS

A 
Sedation
Parkinsonism
Depression
Addiction
Nausea
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13
Q

Potential skin ADRs/side effects

A

Urticaria
Erythematous eruptions
Toxic Epidermal Necrolysis
Stevens-Johnson Syndrome

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14
Q

Stevens-Johnson Syndrome

A

severe skin reaction

fever, rash, blisters – can involve mucous membranes too

can be triggered by drugs - e.g. carbamazepine and phenytoin

Patients can have genetic predisposition towards this condition - involving a HLA allele

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15
Q

Toxic Epidermal Necrolysis

A

severe skin reaction – rare but often fatal

early symptoms are flu-like symptoms. A few days later the skin begins to blister and peel, forming painful raw areas

complications include dehydration, sepsis, pneumonia and multiple organ failure

Risk of TEN with:
•	antibiotics – sulphonamides, beta-lactams
•	NSAIDs/corticosteroids
•	anticonvulsants
•	anti-retroviral drugs
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16
Q

Penicillin Allergy

A

in some patients penicillins couple to proteins, forming immunogens and causing a hypersensitivity reaction

Penicillin allergy is a class effect – allergy to one penicillin is allergy to all penicillins

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17
Q

What is important to consider for a patient taking statins?

A

Any myopathy can rarely progress to rhabdomyolysis, which may result in renal damage.

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18
Q

Mechanisms of drug interaction

A 
Drug absorption
altered pH
CYP inhibition
CYP induction
Renal elimination
Fluid and electrolyte interactions
Pharmacological interactions
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19
Q

What are some important interactions to consider with warfarin?

A

with NSAIDs - increased risk of bleeding

with antibiotics (esp clarithro/erythromycin) - increased risk of bleeding

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20
Q

What are some important interactions to consider with NSAIDs?

A

NSAIDs and warfarin - bleeding

NSAIDs and methotrexate - methotrexate toxicity

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21
Q

What are some important interactions to consider with ACEis?

A

Use with potassium and potassium-sparing diuretics can lead to hyperkalaemia.

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22
Q

What are some important interactions to consider with digoxin?

A

Use with amiodarone/verapamil can lead to digoxin toxicity

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23
Q

What are some important interactions to consider with oral contraceptives?

A

Any inducing agent can cause failure of therapy and unwanted pregnancy

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24
Q

What are important interactions to consider with statins?

A

Macrolides - risk of myopathy

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25
Q

Roughly what percentage of drugs are renally excreted?

What is the significance of this?

A

~25%

Renal impairment may reduce elimination of these drugs, leading to accumulation/toxicity

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26
Q

What are the two measurements of renal function

A 
Creatinine Clearance (CrCl)
estimated GFR (eGFR)
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27
Q

When is eGFR a suitable measurement of renal function?

A

For most adult patients of normal build.

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28
Q

When should CrCl be used to measure renal function?

A

DOACs

Patients taking nephrotoxic drugs (e.g. vancomycin, amphotericin B).

Elderly patients (>75 years)

Patients of extreme muscle mass (BMI <18 or >40)

Patients taking medicines which are largely renally excreted and have a narrow therapeutic window (e.g. digoxin)

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29
Q

Which drugs can cross the placenta?

A

Almost all drugs (except heparin)

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30
Q

Managing epilepsy in pregnancy

A

Continuation of treatment is preferable – need counselling on risks.

Planned discontinuation of treatment.

Use carbamazepine, with high-dose folic acid supplements to reduce changes of NTDs.

Lamotrigine used first-line in generalised tonic-clonic seizures to avoid teratogenic effects

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31
Q

Anti-epileptic drugs in women of child-bearing age

A

Many are teratogenic - e.g. phenytoin, Phenobarbital, Valproate.

Phenytoin, carbamazepine, phenobarbital are enzyme inducers and can cause failure of the OCP.

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32
Q

Anti-coagulation in pregnancy

A

Warfarin is teratogenic - altered bone growth, optic atrophy, mental retardation

Avoid warfarin in trimester 1 (teratogenicity) and 3 (bleeding complications).

Favour LMWHs (e.g. heparin) if anticoagulation required

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33
Q

What should be considered when prescribing in hepatic impairment?

A 
Hepatic clearance
Protein binding
Sodium retention
Effects on coagulation
Gastric effects
CNS effects
Sedation
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34
Q

Dose in 100 % solution

A

1g per ml

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35
Q

Dose in 10 % solution

A

100 mg per ml

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36
Q

Dose in 1 % solution

A

10 mg per ml

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37
Q

Dose in 0.1% solution

A

1 mg per ml

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38
Q

Dose in 1:1000 Adrenaline

A

1 mg/ml

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39
Q

Dose in 1:10,000 Adrenaline

A

100 mcg/ml

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40
Q

Which drugs are prescribed in units?

A

Insulin
Heparin
Streptokinase
Vasopressin

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41
Q

What are the general goals in treatment of hypertension?

A

reduction in blood pressure and when this involves drug treatment, this should be with as few side effects as possible

Aim is to 
•	Reduce cardiovascular damage.
•	Preserve of renal function.
•	Limit or reverse LVH.
•	Prevent IHD.
•	Reduce mortality due to stroke and MIs
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42
Q

What are the NICE treatment targets for treating hypertension?

A

SBP < 140mmHg (<130mmHg in diabetes)

DBP < 90mmHg (<80mmHg in diabetes).

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43
Q

What is the initial step in treating hypertension?

A

Lifestyle changes play a central and primary role:

  • Alcohol consumption should be reduced
  • Weight reduction
  • Reduce excess caffeine
  • Reducing fat and salt intake, increasing fruit and oily fish in the diet (e.g. Mediterranean diet).
  • Increasing exercise
  • Smoking cessation
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44
Q

Why is reducing alcohol consumption important in hypertension?

A

Alcohol increases BP in a significant proportion of patients

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45
Q

How is a diagnosis of hypertension made?

A

After implementing lifestyle changes, 14 ambulatory measurements are required to confirm hypertension

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46
Q

Criteria for “Pre-hypertensive”

A

> 120 / >80

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47
Q

Stage 1 Hypertension

A

> 140 / >90

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48
Q

When is stage 1 hypertension treated?

A 
Treat if <80 years old and one of:
•	End organ damage
•	Diabetes
•	CV disease
•	High CV risk (>20% in 10 years)

If <40 – refer for 2o hypertension referral

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49
Q

Stage 2 hypertension

A

> 160 / >100

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50
Q

When should stage 2 hypertension be treated?

A

All patients

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51
Q

Stage 3 hypertension

A

> 180 / >120

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52
Q

When should stage 3 hypertension be treated?

A

All patients

Medical emergency - same day referral!

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53
Q

When is renin released by the kidney?

A

In response to:

  • Decreased renal perfusion pressure
  • Sympathetic nerve stimulation (via activation of beta1-adrenoceptors).
  • Decreased levels of NaCl
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54
Q

What does renin do?

A

renin acts on angiotensinogen by cleaving it to form a smaller peptide – angiotensin I.

ACE enzyme then converts AI to AII.

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55
Q

What does angiotensin II do?

A

Causes potent vasoconstriction

Potentiates release of aldosterone (sodium + water retention)

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56
Q

How do ACEis reduce BP?

A

prevent the conversion of AI to AII, causing reduced BP via:

Reduced vasoconstriction

Reduced synthesis of aldosterone

Increased levels of bradykinin – a vasodilator

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57
Q

Adverse effects of ACEis

A

Dry cough in ~10% of patients – due to bradykinin.

May cause hyperkalaemia
=> monitor K+ before and during treatment.

Angioedema – swelling of the eyelids/lips; medical emergency.
=> Increased incidence in black patients.

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58
Q

When should ACEis be avoided and why?

A

AVOID in renovascular disease.

=> Reduction in perfusion of the kidneys causes renin-dependent hypertension to maintain perfusion via RAAS.

=> ACEis reducing BP can lead to renal underperfusion (kidney damage) and severe hypotension.

AVOID/lower dose in poor renal function

AVOID in pregnancy

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59
Q

In which patients are an ACEi a good idea?

A

diabetic patients - to prevent diabetic nephropathy

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60
Q

How do AT1 Receptor Antagonists (ATRAs/ARBs) act?

A

block the action of AII at the AT1 receptor.

These agents have similar consequences as ACEIs but do not give rise to a cough due to no effect on levels of bradykinin

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61
Q

How do calcium channel Inhibitors/Blockers (CCBs) act?

How do dihydropyridines and rate-limiting CCBs differ?

A

vasodilators, primarily by inhibiting voltage operated Ca2+ channels on vascular smooth muscle, leading to vasodilatation and thereby a reduction in blood pressure

=> The dihydropyridines (e.g. amlodipine) act mainly on vascular smooth muscle.

=> Rate-limiting CCBs (e.g. verapamil) have greater effects on cardiac tissue (particularly the AV node) and will slow the heart down

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62
Q

When are rate-limiting CCBs a better choice?

A

The body responds to low BP with reflex tachycardia.

RL CCBs will prevent reflex tachycardia

This is a better option in IHD

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63
Q

Which diuretics are typically used in treating hypertension?

A

Thiazide-Like diuretics - 2nd line treatment

Thiazides also but not so much anymore due to diabetogenic nature

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64
Q

How do thiazide-like diuretics act?

A

Inhibit Na+/Cl- transport in distal convoluted tubule

=> Promotes sodium (and water) loss and thereby reduces circulating volume

also cause vasodilatation

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65
Q

What is important to remember with thiazide-like diuretics?

A

They are INEFFECTIVE in moderate renal impairment
=> need to measure eGFR before and during use.

They require secretion in the PCT in order to act in the DCT.

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66
Q

Important side effects of thiazide/thiazide-like diuretics

A

Hypokalaemia

Postural hypotension

Impaired glucose control – can cause T2DM (particularly Bendroflumethiazide).

Do not use in gout – thiazides compete with uric acid for excretion and worsen gout.

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67
Q

Alpha-blockers in treating hypertension

A

Drugs of last choice.

competitive receptor antagonists of alpha1-adrenoceptors

Poorly tolerated - widespread side effects due to “wiping out” the SNS.

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68
Q

How do beta-blockers work to lower BP?

A

Mechanism of action is unclear - thought to be:

=> Reduction in the sympathetic drive to the heart (reducing cardiac output).

=> Reduction in sympathetically-evoked renin release from the kidneys.

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69
Q

When are beta-blockers contraindicated/avoided?

A 
In asthma (caution in COPD)
=> Potential to block bronchial beta2 receptors and cause bronchospasm

In heart block

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70
Q

key adverse effects of CCBs

A

Peripheral oedema

Constipation

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71
Q

key adverse effects of thiazide diuretics

A 
Urination
Diabetogenic
Hypokalaemia
Impotence?
Postural hypotension
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72
Q

A/C/D steps for treating hypertension - Patient <55 years and non-black

A
  1. ACEi/ATRA
  2. add CCB or diuretic
  3. ACEi/ATRA + CCB + Diuretic
  4. Add spironolactone, or beta-blocker, or alpha blocker
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73
Q

A/C/D steps for treating hypertension - Patient >55 years or black

A
  1. CCB
  2. add diuretic or ACEi/ATRA
  3. CCB + diuretic + ACEi/ATRA
  4. Add spironolactone, or beta-blocker, or alpha blocker
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74
Q

A/C/D steps for treating hypertension - patient with hypertension and T2DM

A
  1. ACEi/ATRA
  2. add CCB or diuretic
  3. ACEi/ATRA + CCB + Diuretic
  4. Add spironolactone, or beta-blocker, or alpha blocker
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75
Q

Why is the A/C/D pathway different for black patients?

A

People of Afro-Caribbean ethnicity tend to have hypertension which is less renin-dependent, so a CCB is used first line over an ACEi

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76
Q

Statins in hypertension?

A

Studies show that simvastatin reduces CV risk, even with “normal” cholesterol.

=> statins should be considered for all high risk patients

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77
Q

Hypercholesterolaemia

A

elevated plasma cholesterol, a risk factor for atherosclerosis

= total cholesterol >6.5 mmol/L

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78
Q

Which drugs can adversely affect lipid profile?

A
  • Beta-blockers
  • Thiazides
  • Corticosteroids
  • Retinoids
  • Oral contraceptives
  • Anti-HIV drugs.
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79
Q

Lipoproteins

A

central core of hydrophobic lipid, encased in phospholipid, cholesterol and apolipoproteins

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80
Q

HDL

A

= High density lipoprotein (“good cholesterol”)

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81
Q

LDL

A

= Low density lipoprotein (“bad cholesterol”)

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82
Q

What is the ideal total cholesterol?

A

< 5.0 mmol/L

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83
Q

What is the significant issue with raised cholesterol?

A

High LDL and/or low HDL

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84
Q

What can be a clinical sign of hypercholesterolaemia/dyslipidaemia?

A

Xanthomata and xanthelasma

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85
Q

what is a QRISK score?

How is it calculated?

A

assesses the risk of a patient’s chance of CV event in the next 10 years

uses the patient’s:

  • Age, ethnicity, BMI, smoking status, diabetes
  • Cholesterol:HDL ratio
  • Systolic BP
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86
Q

process of atherogenesis

A
  1. Damage to endothelium – smoking, hypertension, turbulent flow, diabetes.
  2. Inflammation – monocytes/macrophages infiltrate and accumulate, generate reactive oxygen species which can cause oxidative damage.
    => LDL binds to LDL-receptors, oxidised LDL can damage the receptor and prevent cholesterol uptake.
  3. Fatty Streaks form – foam cells beneath the endothelium, rich in cholesterol as it deposits beneath the endothelium (~20/30 years).
  4. Plaque formation – calcified, cholesterol rich plaque beneath the endothelium (~40 years).
    => Begins to cause narrowing of the artery.
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87
Q

How much does a coronary artery need to be narrowed to get symptoms of angina?

A

when the artery is narrowed by >70%

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88
Q

what can happen if an atheromatous plaque becomes unstable and ruptures?

A

Myocardial infarction - in the coronary circulation

Stroke - in the cerebral circulation

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89
Q

Management of dyslipidaemia

A

Modify risk factors:

  • Smoking cessation
  • Treat HTN / DM
  • Exercise
  • Drug-induced?

Low-cholesterol diet (but only ~25-30% of cholesterol comes from the diet).

Cholesterol-lowering drugs.

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90
Q

HMG-coenzyme A reductase

A

enzyme which catalyses the 1st committed step in cholesterol synthesis.

Many steps down the line, cholesterol is formed.

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91
Q

Statins

A

HMG-CoA Reductase inhibitors, hepatoselective

inhibit cholesterol synthesis, thereby reducing plasma cholesterol

Reduction in hepatic cholesterol synthesis leads to an upregulation of hepatic LDL receptors, promoting LDL uptake from the plasma (i.e. a 2nd cholesterol lowering effect)

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92
Q

effects of statins

A

Reduction in LDL cholesterol (increased HDL)

Reduction in mortality

Improve endothelial function

Reduced CV risk in all high-risk CV patients (even with low/normal cholesterols).

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93
Q

NICE Guidance for statins

A

Primary Prevention – patients with >10% risk of CVD, asses via QRISK3.
=> 20mg atorvastatin (low intensity)

Secondary Prevention – patients with CVD
=> 80mg atorvastatin (high intensity)

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94
Q

when should statins be taken?

A

Should be taken at night to offset the nocturnal increase in cholesterol synthesis (except atorvastatin).

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95
Q

adverse effects of statins

A

Muscle pain
=> Very rarely leading to rhabdomyolysis (Simvastatin > atorvastatin)

Increased risk of diabetes but expert view is that this is outweighed by CV benefits.

Nocebo effect

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96
Q

Simvastatin - interactions

A

Contraindicated with macrolides
=> CYP450 inhibitors cause raise in plasma concentration of statin.
=> Increased risk of muscle damage

Interaction with amlodipine, verapamil, diltiazem

Interacts with psoralens (grapefruit juice) which inhibit CYP450

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97
Q

Cholesterol-lowering drugs - Ezetemibe

A

prevents cholesterol absorption from the GI tract.

For use on top of a statin, if the statin isn’t fully controlling cholesterol levels

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98
Q

Cholesterol-lowering drugs - Alirocumab

A

monoclonal antibody inhibiting PCSK9.
=> PCSK9 binds to LDL receptor and leads to its degradation.
=> Alirocumab increases the number of hepatic LDL receptors and lowers LDL.

Used in addition to max. dose statins.

SC administration every 2 weeks

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99
Q

Cholesterol-lowering drugs - fibrates

A

activate PPAR-alpha, alters lipoprotein metabolism

Used with statins when triglycerides and cholesterol are raised.

Reduce IHD but not mortality, so not routinely recommended.

Adverse effects – rhabdomyolysis

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100
Q

What antiplatelet drugs are there?

A

Low-dose aspirin
Dipyridamole
Clopidogrel
Abciximab

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101
Q

How does aspirin have anti-platelet activity?

A

an irreversible inhibitor of cyclo-oxygenase

Prevents production of prostaglandins, thromboxane (TXA2) and prostacyclin (PGI2).

HOWEVER, endothelial cells have a nucleus and can produce more mRNA for COX, and therefore allow the production of PGI2 to occur within a couple of hours.

Platelets lack a nucleus so cannot produce more COX and therefore aspirin will inhibit TXA2 production for the platelet lifespan of 7 days.

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102
Q

Use of low-dose aspirin

A

Used to prevent MI in patients who have previously had an MI
=> Recommended for secondary but not primary prevention.

Reduces incidence of stroke

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103
Q

Dipyridamole

A

Phosphodiesterase inhibitor – prevents the breakdown of cAMP and cGMP.

Raised levels of cAMP and cGMP have inhibitory effects on platelet aggregation. Also inhibits adenosine uptake.

Used to prevent thrombosis.

Used in conjunction with aspirin – evidence of synergy.

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104
Q

Clopidogrel

A

ADP from aggregating platelets leads to expression of glycoprotein IIb/IIIa on the surface of the platelets. GP IIb/IIIa binds fibrinogen (and vWF) which leads to cross-linking of platelets.

Clopidogrel inhibits the ADP-induced expression of glycoproteins.

For patients who cannot take aspirin, clopidogrel is similarly effective/safe.
=> But may be used alongside aspirin for greater antiplatelet effects

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105
Q

Abciximab

A

Monoclonal antibody against GP IIb/IIIa.

Given to patients undergoing angioplasty to prevent thrombosis.

Only use once

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106
Q

Fibrinolysis

A

= A natural endogenous process in the body, activated in parallel with the clotting system.

Plasmin digests the fibrin of the clot (and also some of the clotting factors).

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107
Q

thrombolytics/fibrinolytics/“clot busters”

A

Drugs which interact with fibrinolysis

e.g. alteplase

activate the conversion of plasminogen to plasmin to digest the fibrin of a clot

the earlier these drugs are given and reperfusion is achieved, the more effective they are

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108
Q

what is the primary use of thrombolytic drugs?

A

thromboembolic stroke

can also be used for PE

(was previously the primary treatment for MI, but now angioplasty is the gold-standard)

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109
Q

What are the goals of treatment in chronic heart failure?

A
  • Identify / treat any cause (e.g. valvular disease, IHD)
  • Reduce cardiac workload
  • Increase cardiac output
  • Counteract neurohormonal maladaptation
  • Relieve symptoms
  • Prolong quality life – reduce hospitalisation.
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110
Q

Pharmacological management of CHF

A

Pharmacological management is stage-dependent

All patients with LV systolic dysfunction should receive an ACE inhibitor and a Beta-blocker initially

All patients with oedema should receive a diuretic

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111
Q

ACEIs in chronic heart failure

A

now 1st line as have been shown to prolong life

Reduce arterial and venous vasoconstriction (reduce after- and pre-load)

Reduce salt/water retention, hence reduce circulating volume

Inhibits RAAS, prevents cardiac remodelling?

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112
Q

ATRAs in chronic heart failure

A

if ACEI is not tolerated (cough)

or in addition to ACEI as add on therapy.

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113
Q

beta-blockers in chronic heart failure

A

first line with ACEis for stable, moderate heart failure

Beta1 selective agents only (e.g. bisoprolol)

At a low dose – reduce disease progression, symptoms and mortality

=> Reduce sympathetic stimulation, heart rate and O2 consumption

=> Antiarrhythmic – will control rate in atrial fibrillation

=> Oppose the neurohormonal activation which leads to myocyte dysfunction.

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114
Q

What should you do if a patient is on atenolol but is then diagnosed with CHF?

A

swap atenolol to bisprolol

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115
Q

what is important counselling for prescribing a beta blocker for a patient with CHF

A

Symptoms may get worse at first, before improving in the long-term

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116
Q

Diuretics in chronic heart failure

A

Very important for symptomatic relief.

Usually loop or sometimes thiazide diuretics.

  • Reduce circulating volume.
  • Reduces preload on the heart.
  • Relieve pulmonary and peripheral oedema.
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117
Q

Actions of digoxin

A
  • +ve inotrope (increases the force of contraction)

* Also impairs AV conduction and increases vagal activity - causing heart block and bradycardia

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118
Q

Dose of digoxin

A

Dose is titrated up to reach a HR >60

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119
Q

Digoxin toxicity

A

= major problem due to the narrow therapeutic window.

=> Anorexia, nausea, visual disturbances, diarrhoea

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120
Q

Digoxin in heart failure

A

usually reserved for failure with AF or when ACEI + diuretic fails

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121
Q

What should be monitored in CHF patients?

A

Renal function

Potassium levels

122
Q

IHD - how do nitrates help?

A

e.g. GTN

Main action is to cause venodilatation via release of NO
=> leads to a decrease in preload and a reduction in cardiac work

Can cause coronary vasodilatation to some extent, however, if the artery is narrowed by stenosis then the impact is limited.

Plays an important role for managing acute attack.

123
Q

Tolerance to nitrates

A

Prolonged exposure to nitrates can reduce effectiveness.

Aim is to have a “nitrate free period” (potentially overnight)

124
Q

IHD - beta blockers

A

First choice drugs for prevention.

Negative inotropic and chronotropic effects
=> Reducing cardiac work and preventing symptoms.

Coronary flow only occurs during diastole, then by slowing the heart the diastolic period will be increased, as will the time for coronary blood flow.

Anti-arrhythmic effects and reduce the risk of MI.

125
Q

Why are the anti-arrhythmic effects of beta-blockers useful in IHD?

A

Ischaemic tissue from IHD is prone to generating arrythmias.

126
Q

IHD - CCBs

A

Act by inhibiting voltage operated calcium channels on vascular smooth muscle, reducing contractility.
=> Cause vasodilatation and improve coronary blood flow, thereby preventing symptoms.

Rate-limiting agents are favoured in IHD if the patient has good contractility, as they reduce cardiac work (DHPs tend to cause reflex tachycardia)

127
Q

What are some rate-limiting CCBs?

A

Verapamil, diltiazem

128
Q

What are some non-rate limiting CCBs?

A

The dihydropyridines - amlodipine, nifedipine

129
Q

Drug choice in IHD

A

Stable angina - GTN for relief

For prevention
=> beta blocker +/- nitrate
=> or CCB +/- nitrate (if beta-blocker contraindicated)

If refractory - add:

  • CCB (DHP)
  • beta-blocker
  • Nicorandil
130
Q

what is a combination of drugs to AVOID when prescribing in IHD?

A

a beta-blocker and rate-limiting CCB !!!!

Substantial risk of asystole, potentially fatal.

131
Q

IHD - Nicorandil

A

= a potassium channel activator

Causes vasodilatation of vascular smooth muscle

132
Q

IHD - Ivabradine

A

Inhibits the If channels (pacemaker Na+/K+ currents in the SA node).

Reduces heart rate.

Found to be equally as effective as atenolol, but without the beta-blocker side effects

133
Q

what are the injectable anticoagulants?

A

Unfractionated heparin

Low Molecular Weight Heparins (e.g. enoxaparin, tinzaparin)

134
Q

Why is enoxaparin favoured out of the injectable anticoagulants?

A

actions are very predictable and it can be prescribed as a fixed dose.

135
Q

How do the heparins act?

A

Act by activating antithrombin III (a natural protein in the plasma).

Antithrombin inactivates some clotting factors and thrombin by complexing with the serine proteases of the factors

136
Q

what are the heparins used for?

A
  1. Prevent thrombosis (venous, unstable angina)
  2. Prevent blood clotting on collection
  3. Provide anticoagulation whilst warfarin takes effect (takes about 3 days)

A major use if preventing DVT/PE in hospitalised patients

137
Q

which heparins require anticoagulation monitoring and how?

A

Unfractionated heparins are monitored via APTT – activated partial thromboplastin time

LMWH do not require coagulation monitoring

138
Q

what can occur after >5 days of heparins

A

can cause an immune response that involves the killing of platelets – can lead to thrombocytopaenia.

139
Q

How does warfarin work?

A

Vitamin K is an essential for production of prothrombin and Factors VII, IX and X (Vitamin K important for post-ribosomal carboxylation of glutamic acid residues of these proteins).

Warfarin blocks Vitamin K reductase, needed for Vit K to act as a cofactor (Vitamin K Epoxide Reductase Complex, VKORC).

140
Q

How long does it take for warfarin to take effect and why?

A

Coagulation factors exist in the circulation for ~3 days, so it takes about 3 days for warfarin to take effect.

141
Q

what are the indications for warfarin?

A

to prevent unwanted thrombosis:

  • in patients with replaced heart valves
  • Atrial Fibrillation
  • PE
  • DVT
142
Q

why is warfarin difficult to use?

A
  1. Has a narrow therapeutic window

2. Many drug interactions – activity can be potentiated/reduced.

143
Q

What is Prothrombin Time ?

A

= the time for coagulation following the addition of thromboplastin.

Prolonged by abnormalities of Factors VII, X, V, II, or I

Prolonged by liver disease (as the liver produces coagulation factors)

Prolonged by warfarin

144
Q

International Normalised Ratio (INR)

A

measures normal prothrombin time against the patient’s

normal = ~1

target range varies depending on indication for use
(2.5 for most indications, but 3.5 for mechanical heart valve)

145
Q

what can over-anticoagulation lead to?

A

gastric/cerebral bleeding
haemoptysis
blood in faeces/urine
easy bruising

146
Q

Reversing warfarin

A

Warfarin can be reversed with vitamin K injections if:

  1. Patient is bleeding
  2. Patient has a very high INR (>8)
  3. Warfarin overdose
147
Q

counselling for warfarin

A

Patient must take at the same time every day (6pm)

If they miss a dose, then they should NOT take two doses together and they should inform their doctor at the next blood test

Inform HCPs that they take warfarin - interactions, bleeding, etc.

Females - advised not to become pregnant whilst taking warfarin

Dietary advice

Patients should report any signs of bleeding

148
Q

when is there a need for anticoagulation in pregnancy and how should this be achieved?

A

Pregnancy hormones produce a hypercoagulable state in the mother to prevents post-partum haemorrhage.

=> Risk of thrombosis – thrombophilia, decreased venous return due to the gravid uterus and immobility during labour.

Mothers with artificial heart valves…

  • Warfarin is teratogenic – altered bone growth, optic atrophy, mental retardation.
  • Avoid warfarin in trimester 1 and 3.
  • Favour LMWHs
149
Q

DOACs

A

Dabigatran – an oral thrombin inhibitor

Apixiban and Rivaroxaban: oral inhibitors of activated factor X

Just as effective as warfarin
Less interactions
Do not require INR monitoring
Less reversible

150
Q

what is the recommended alcohol intake?

A

0 – 14 units per week (men and women)

Provided the amount is not drunk in one or two bouts and that there are 2-3 alcohol free days a week

151
Q

what should be done if a drug is causing liver injury as an adverse reaction?

A

stop the drug entirely to prevent further damage

152
Q

what AST:ALT ratio is associated with alcoholic liver disease?

A

AST:ALT of more than 2:1

153
Q

Lifestyle changes in managing dyspepsia

A

Avoidance of causative drugs
Avoidance of causative foods

GORD – propping up bed, removing belts!

154
Q

What are the goals of treatment in dyspepsia?

A

Symptomatic relief
Mucosal protection
Eradication of H. pylori (if indicated)
Prevent development of gastric carcinomas

155
Q

what factors increase acid secretion in a gastric parietal cell?

A

Histamine via H2 receptors
Gastrin
Acetylcholine via mAChRs on parietal cells

156
Q

what factors decrease acid secretion in a gastric parietal cell?

A

Prostaglandins (E2 and I2) via stimulating production of mucous and bicarbonate ions.

157
Q

Antacids

A

Raise the pH of the stomach with an acid-base titration
Widely available (OTC)
Provide rapid relief but not cure

158
Q

what can be an issue with the antacid magnesium hydroxide?

A

can cause diarrhoea

159
Q

Alginates

A

May be combined with antacids, provide rapid relief.

Alginic acid forms a viscous foam when combined with saliva.

The foam floats on the gastric contents forming a raft, which protects the oesophagus during reflux.

160
Q

Histamine H2 antagonists

A

Block the H2 receptor on parietal cells, which are coupled via adenylyl cyclase to increase cAMP which activates the proton pump

Reduce gastric secretion, provide symptomatic relief.

Best given at night, when the histamine system is most active

Low doses are available OTC, High doses are available by prescription

161
Q

PPIs

A

activated by acidic pH due to their pKa

Act via irreversible inhibition of the proton pump (H+/K+-ATPase).
=> Very effective and inhibit H+ secretion by >90%

162
Q

What is there a risk of when taking PPIs?

A

May lead to achlorhydria and increased risk of Campylobacter infection (food poisoning)

163
Q

Rebound acid hypersecretion

A

Following cessation of H2RAs or PPIs

Increase in acid release
=> Potentially due to increased expression of proton pumps??

Causes an increase in dyspepsia symptoms

Avoid prolonged usage of these drugs

164
Q

H. pylori triple therapy

A

Two from:

  • Clarithromycin
  • Amoxicillin – avoided in patients with penicillin allergy
  • Metronidazole – the only antibiotic that you cannot drink alcohol with.

Plus PPI and/or H2 antagonist.

Triple Therapy will be taken for 1 week, and then the PPI alone

165
Q

minimising GI damage when taking NSAIDs/steroids

A

“take with/after food” (probably ineffective but does no harm)

Paracetamol instead?

Prophylaxis with a PPI (H2 antagonists are less or ineffective, except Famotidine)

Give NSAID in combination with misoprostol
=> Stable PGE1 analogue, which acts on prostanoid receptors to inhibit gastric H+ secretion.

166
Q

What is important to remember when prescribing misoprostol?

A

Causes uterine contractions – not used in females of child-bearing age because of the risk of abortion.

167
Q

What is nausea?

A

= an unpleasant sensation that immediately precedes vomiting

A cold sweat, pallor, salivation, self-absorption, loss of gastric tone, duodenal contractions, and reflux of intestinal contents into the stomach

168
Q

what is emesis?

A

= a protective and coordinated involuntary reflex involving powerful sustained contraction of the abdominal, chest wall and diaphragm muscles to increase intra-gastric pressure, and opening of the oesophageal sphincter, glottis and jaws.

169
Q

what can trigger emesis?

A

Toxins – bacterial poisons, alcohol, drugs (especially anticancer agents, opioids, digoxin, SSRIs, levodopa, erythromycin, etc.)

Motion sickness

Smells

Migraine

Pregnancy

170
Q

anti-emetics: H1-receptor Antagonists

A

e.g. cyclizine

Act on vestibular nuclei
Effective in motion sickness
Can also have anti-muscarinic actions

Cyclizine – used in pregnancy.

171
Q

anti-emetics: anti-muscarinic agents

A

e.g. hyoscine.

Effective in motion sickness and irritation of the stomach

Anti-muscarinic side effects – dry mouth, urinary retention, blurred vision, constipation.

172
Q

anti-emetics: Dopamine-receptor Antagonists

A

e.g. metoclopramide.

Acts in Chemoreceptor Trigger Zone

has unwanted CNS effects (e.g. drug-induced parkinsonism)

Effective against anticancer drug-induced emesis

173
Q

anti-emetics: 5-HT3-antagonists

A

e.g. ondansetron

Blocks 5-HT at 5-HT3- receptors in the gut and CNS.

Particularly effective against anti-cancer drugs.
Post-operative N&V.

174
Q

anti-emetics: steroids

A

e.g. dexamethasone

Shown to have some anti-emetic properties

175
Q

What is the main method of managing diarrhoea?

A

= Oral Rehydration Therapy (ORT)

A solution of electrolytes to replace the electrolytes lost in diarrhoea

Must be isotonic to work correctly.

Glucose in the solution allows greater transport of Na+ via a symporter, and water follows the Na+.

176
Q

The role of antibiotics in diarrhoea

A

Most simple infections are viral, and antibiotics are of little value.

If microbiology identifies a causative bacterium, then appropriate antibiotics may be used.

177
Q

Probiotics in diarrhoea

A

May be some benefit in preventing antibiotic-associated diarrhoea and C. diff-associated diarrhoea.

Potentially also infective diarrhoea.

178
Q

Anti-motility agents in diarrhoea

A

If symptomatic relief is required, then anti-motility agents are an option.
=> opioids, anti-muscarinics

However, they do not shorten the length of the infection

179
Q

Antimotility agents: opioids

A

e.g. Loperamide (Imodium)

Loperamide does not penetrate the BBB and has efficient enterohepatic cycling, so is retained largely in the gut

Act by reducing tone and peristaltic movements of GI muscle by inhibiting the pre-synaptic release of acetylcholine - via activation of µ-opioid receptors

Reduced motility leads to increased transit time
=> promotes water absorption
=> symptomatic relief

180
Q

Antimotility agents: anti-muscarinics

A
  • Dicycloverine – antimuscarinic agent.

* Tricyclic antidepressants – also constipating as a side effect through antagonism of muscarinic receptors

181
Q

What is the approach to managing constipation?

A

Best approach to management is a balanced diet, high in fibre.

If dietary treatment fails, laxatives can be used

182
Q

Osmotic Laxatives

A
  • e.g. lactulose – disaccharide of galactose and fructose; enters the colon unchanged and is converted by bacteria to lactic and acetic acid (increases osmolality of stool)
  • e.g. Macrogols (polyethylene glycol)

The increase in osmolality causes water to be retained, which raises the fluid volume.

183
Q

Laxatives - magnesium

A

Has an osmotic effect;

Mg2+ also releases CCK which increases GI motility

184
Q

Laxatives - Bulking Agents

A

e.g. ispaghula, methylcellulose.

Increase the bulk in the lower GI tract

185
Q

stimulant laxatives

A

Senna extracts – enter colon metabolised to anthracene derivatives, which stimulates GI activity.

Dantron – irritant

186
Q

Laxatives - Prucalopride

A

New, highly selective 5-HT4 agonist which increases GI motility

Last choice – used when all other agents have failed

187
Q

IBS - management

A

Lactulose or loperamide for symptoms?

Antispasmodic agents - e.g. mebeverine

Amitriptyline (TCA)
=> Low doses widely used + effective (higher doses used for depression, lower doses for neuropathic pain and IBS).
=> provide some pain relief

188
Q

IBD - 5-Aminosalicylates (5-ASA):

A

e.g. sulphasalazine, mesalazine (both metabolised to yield 5-ASA)

= the mainstay for ulcerative colitis, use is less clear for Crohn’s.

5-ASA acts by inhibiting leukotriene and prostanoid formation, scavenging free radicals, decreasing neutrophil chemotaxis

189
Q

What is there a risk of with mesalazine?

A

Can cause blood disorders by affecting the bone marrow.

Patient should report any sore throats, fevers, easy bruising/bleeding

190
Q

IBD - corticosteroids

A

Used to induce remission in IBD.

• Prednisolone
=> glucocorticoid with anti-inflammatory, immunosuppressive actions
=> lots of side effects

• Budesonide
=> poorly absorbed so far less systemic side effects.
=> Specifically for distal ileal, ileocaecal or right sided colonic disease.

191
Q

IBD - Immunosuppressants

A

azathioprine

methotrexate (Effective in Crohn’s but not UC)

infliximab

192
Q

what is there a risk of when taking azathioprine?

A

Risk of pancreatitis

Risk of myelosuppresion - bruising/bleeding and infections

193
Q

what is a the basis of pharmacological management of T1DM ?

A

replace insulin in an attempt to return blood glucose to normal and preventing diabetic complications.

194
Q

Types of insulin regimens

A

different regimens suit different individuals’ needs

include:

  • Twice daily regimens
  • Multiple dosing regimens
  • Single daily regimens
195
Q

Twice daily insulin regimen

A

= most commonly used

2 daily injections,

one 30 minutes before breakfast and one before the evening meal of short- and longer-acting insulins in combination

two thirds of the insulin given as the morning dose.

196
Q

Multiple dosing insulin regimen

A

= “basal-bolus regimen”

a single dose of medium-acting insulin is given at bedtime and doses of short acting insulin are given 30 minutes before each meal.

allows more flexibility with the timing of meals.

197
Q

Single daily insulin regimen

A

involve 1 daily injection before breakfast or at bedtime of intermediate-acting insulin, with or without a short-acting insulin

rarely used - generally for patients with T2D who are unable to control their blood glucose with antidiabetic drugs

198
Q

when is a patient’s insulin requirement increased?

A 
stress, 
infection, 
accidental or surgical trauma, 
puberty (effects of growth hormone) 
during the latter two trimesters of pregnancy
199
Q

when is a patient’s insulin requirement reduced?

A

coeliac disease,
renal or hepatic impairment
endocrine disorders - e.g. untreated Addison’s disease.

200
Q

Insulin pumps

A

may be used which allow continuous subcutaneous administration.
=> provide a continuous infusion, which may be increased at mealtimes.

particularly useful in difficult to control diabetes.

201
Q

IV insulin

A

reliable route of administration

used in hospital in an acute setting, to hyperglycaemia under control

202
Q

Subcutaneous insulin administration

what is there a risk of developing with this route?

A

= most conventional route

uses a disposable syringe, in which the different insulins may be mixed to achieve the desired combination

at a site of repeated injections, there may be LIPOHYPERTROPHY, leading to unpredictable insulin absorption
=> patients should rotate the sites used

203
Q

T2DM - diet/lifestyle modifications

A

In mild or initial disease: dietary/lifestyle modification

  • reduce the amount of simple carbohydrates in the diet
  • limit the intake of mono and disaccharides,
  • increase non-starch polysaccharides
  • reduce the intake of fat
  • low GI foods
  • weight loss in obese
  • increased exercise
204
Q

when are anti diabetic drugs started in T2DM?

A

after 3 months, if lifestyle changes have been implemented but insufficient

205
Q

anti-diabetic drugs - Sulphonyureas

A

e.g. glibenclamide, gliclazide, tolbutamide

SUs increase insulin secretion by inhibiting ATP-sensitive potassium (KATP) channels

associated with:

  • Weight gain (and increased insulin resistance) so are often avoided in obesity.
  • Hypoglycaemia – especially in the elderly, with long-acting agents, or after missing meals.
206
Q

anti-diabetic drugs - Biguanides

A

= metformin

Its action is less clear – may activate AMP-kinase

It is the drug of choice for obese patients – does not cause weight gain

Does not cause hypoglycaemia

Should not be used in renal impairment.

207
Q

anti-diabetic drugs - Glitazones

A

e.g. Pioglitazone

Activate nuclear PPAR-gamma receptors, which alters gene expression and results in insulin-like effects.

“Insulin sensitisers” which work by enhancing glucose utilization in tissues, and so reduce insulin resistance

Effects include:
=> reduced hepatic glucose output
=> increased glucose transporters (GLUT) in skeletal muscle with increased peripheral glucose utilization
=> Increased fatty acid uptake into adipose cells

208
Q

anti-diabetic drugs - DPP-4 Inhibitors

A

Incretins (e.g. Glucagon-like peptide) regulate the endocrine pancreas

Dipeptidyl peptidase-4 inhibitors (e.g. sitagliptin) inhibit the breakdown of incretins and enhance their activity.

209
Q

Guidelines for T2DM control

A

3 months of diet control

Inadequate control?
Normal renal function => metformin
Renal impaired => SU/ pioglitazone/DDP-4 inhibitor

Poor control => dual, and then triple therapy

(+ HTN control throughout)

210
Q

Depression - SSRIs

A

e.g. citalopram, fluoxetine, paroxetine, sertraline

Selectively inhibit the neuronal reuptake of 5-HT, thus enhancing synaptic concentrations of 5-HT and down-regulating presynaptic 5-HT receptors.

SSRIs are better tolerated than TCAs and are safer in overdose which means that SSRIs are first choice for depression.

Some SSRIs are also licensed for the treatment of anxiety disorders, panic and obsessive-compulsive disorder.

211
Q

Depression - TCAs mechanism of action

A

e.g. amitriptyline, nortriptylline

Inhibit the neuronal uptake of noradrenaline and 5-HT, leading to augmented concentrations in the synaptic cleft.

The increase in catecholamines may lead to down-regulation of presynaptic alpha2¬¬-adrenoceptors and 5-HT receptors and postsynaptic beta-adrenoceptors.

Exhibit binding at a range of receptors including muscarinic receptors, histamine, alpha1-adrenoceptors and 5-HT receptors

212
Q

Problems associated with TCAs

A

sedating
QT interval prolongation
dangerous in overdose

Antimuscarinic side effects limit tolerability of TCAs. These include:

  • dry mouth
  • blurred vision
  • constipation
  • urinary retention
213
Q

why might sedation caused by TCAs be useful?

A

can be useful if the patient is also suffering from sleep disturbances

214
Q

other uses of TCAs, outside of depression

A

amitryptilline (at a low dose) has some uses in:

  1. managing neuropathic pain,
  2. prophylaxis of migraine
  3. irritable bowel syndrome
215
Q

in which patients are TCAs not suitable?

A

Pts with ischaemic heart disease,
Pts aged >70 years
those who are thought to be at high risk of attempting suicide.

216
Q

Depression - NARIs

A

Noradrenaline reuptake inhibitors

e.g Reboxetine

  • Selectively inhibits noradrenaline reuptake .
  • Useful for patients who cannot take TCAs but are resistant to the effects of SSRIs.
217
Q

Depression - SNRIs

A

Serotonin-Noradrenaline Reuptake Inhibitors

e.g. Venlafaxine

• Inhibits serotonin and noradrenaline reuptake but fails to bind to additional receptors

=> fewer side-effects (lack of sedative and antimuscarinic side-effects but does cause gastrointestinal side-effects).

• Associated with causing hypertension

218
Q

Depression - NaSSAs

A

Noradrenergic and Specific Serotonergic Antidepressants

Mirtazapine
• Exhibits alpha2-adrenocepter antagonist activity, inhibiting negative feedback by these presynaptic receptors and thus producing an increase in noradrenaline and 5-HT transmission.

• Sedation in early treatment but antimuscarinic side-effects are limited.

219
Q

Depression - SRMs

A

Serotonin Receptor Modulators

e.g. Nefazodone and trazodone

• Inhibition of serotonin reuptake and the selective inhibition of postsynaptic serotonin receptors.

220
Q

Depression - MAOIs

A

Monoamine Oxidase Inhibitors

  • inhibit the monoamine oxidases, which increases the concentration of these neurotransmitters
  • Most act irreversibly – effects may persist for 2-3 weeks after the cessation of treatment.
  • Can interact with food => “Cheese reaction”
  • Moclobemide, a selective reversible inhibitor of MAO-A (RIMA), reduces interactions with food since tyramine is metabolised by MAO-B.
221
Q

Why are MAOIs rarely used now?

A

MAOIs also prevent the breakdown of the indirectly acting sympathomimetic amine, tyramine (from diet)

=> causes the release of catecholamines and leads to a hypertension.

Tyramine is present in certain foods such as cheese
=> this response is known as the “cheese reaction”.

222
Q

Management of mild depression

A

“watchful waiting” – patient is reassessed after 2 weeks

initial treatment with antidepressants not recommended

223
Q

1st line pharmacological management of depression

A

SSRI (e.g. fluoxetine) = 1st line

BUT a sedating TCA might be preferred if sleep is impaired (unless risk of suicide)

224
Q

How long do anti-depressants usually take to work?

A

~2 weeks

225
Q

management of depression if not managed by SSRI

A

If initial treatment fails, swap to an alternative SSRI or another class of antidepressant

226
Q

how long should antidepressant therapy be continued?

A

Treatment should be continued for at least 6 months after remission

(2 years if 2 recent depressed episodes)

reduce dose gradually to prevent withdrawal.

227
Q

“Manic depression” - 1st line management

A

Lithium remains the first line agent for both acute treatment and prophylaxis of bipolar disorder

Lithium should be avoided in renal impairment.

Narrow therapeutic window – range of interactions and requires therapeutic drug monitoring

228
Q

“Manic depression” - 2nd line management

A

Anticonvulsants - e.g. carbamazepine and valproate
=> prophylactic mood stabilisers in bipolar disorder

Neuroleptics (antipsychotics) - e.g. haloperidol and chlorpromazine
=> control psychotic symptoms (particularly during manic phase)

229
Q

Management of anxiety

A

Beta-blockers reduce physical symptoms

Benzodiazepines reduce anxiety and aggression, and induce sleep

230
Q

Why should the treatment period with benzodiazepines be limited?

A

Issues with tolerance and dependence
=>
Treatment should be limited to 2- 4 weeks

231
Q

what are the two main systems controlling bronchial calibre (and one lesser system)?

A
  1. Parasympathetic ANS
  2. Sympathetic ANS

(3. Sensory local reflex arc)

232
Q

Parasympathetic control of bronchial calibre

A

vagus nerve => release acetylcholine

Acts upon muscarinic M3 ACh receptors in the bronchial smooth muscle

Causes bronchoconstriction and increased mucous secretion.

233
Q

Sympathetic control of bronchial calibre

A

Circulating adrenaline acting on beta2-adrenoceptors on bronchial smooth muscle.

Causes bronchodilation and inhibition of mucous secretion.

Sympathetic nerve fibres releasing noradrenaline will also stimulate adrenoceptors

234
Q

Local reflex arc in the airways

A

sensory nerves sense stimuli => cause a local reflex arc => release transmitters for local effects on the airways

E.g. a cough reflex in response to dust

235
Q

Asthma attack - Spasmogens

A

act rapidly to cause constriction of the airways, leading to bronchospasm = EARLY PHASE

Spasmogens include – histamine, Prostaglandin D2, Leukotrienes (C4 & D4).

236
Q

Asthma attack - Chemotaxins

A

released to attract WBCs (especially eosinophils and mononuclear cells) to the airways, causing an inflammatory LATE PHASE response a few hours later.

Chemotaxins include – leukotriene B4, platelet activating factors (PAFs)

237
Q

How does salbutamol work?

A

Selective agonist for beta2-adrenoceptors on smooth muscle => causes relaxation and in turn an increase in FEV1.

Given by inhalation; localising the action and providing a rapid effect.

238
Q

What might prolonged use of salbutamol lead to?

A

may lead to receptor down-regulation – the beta2-adrenoceptors become less responsive

239
Q

Long-acting beta agonists (LABA)

A

e.g. salmeterol

given for long term prevention and control (e.g. overnight), as it stays bound to the receptors for a lot longer than a SABA

240
Q

Asthma - Xanthines

A

e.g. aminophylline, theophylline

adenosine receptor antagonist/phosphodiesterase inhibitor

cause bronchodilator, but not as good as beta-adrenoceptor agonists (therefore only 2nd line use).

Oral (or IV aminophylline in emergency)

241
Q

Asthma - Muscarinic M-receptor antagonists

A

e.g. ipratropium/tiotropium

Block parasympathetic bronchoconstriction (M3 ACh-receptor)

Given by inhalation to prevent antimuscarinic side effects.

Limited/little value in asthma, however, have a major role in COPD.

242
Q

Asthma - steroids

A

Preventative, they do not reverse an attack.

Takes 2-3 days to have an effect.

Anti-inflammatory by activation of intracellular receptors, leading to altered gene transcription (decrease cytokine production) and production of lipocortin/annexin A1.

Usually given as an inhaler but if the exacerbation is severe, there may be a course of oral steroids.

243
Q

Side effects of inhaled steroids

A

Throat infections, hoarseness (inhalation)

=> counsel patient to wash mouth out after use.

244
Q

Asthma - Leukotriene receptor antagonists (LTRAs)

A

e.g. Montelukast

Increased role as add on therapy.

Has both preventative and bronchodilator uses.

Antagonises the actions of LTs by blocking their receptors

Also useful against symptoms of hayfever and eczema.

245
Q

Stepped management of asthma

A
  1. Short acting beta2-agonist AND Regular inhaled steroid.
  2. Trial of LABA (or LTRA/xanthine if this fails).
  3. Increase dose of inhaled steroid.
  4. Add oral steroid.

If salbutamol is used >2x per week - step up

246
Q

COPD - management

A

Lifestyle advice – STOP SMOKING to reduce further damage to the airways

Pharmacological Management:

=> Bronchodilators – beta2-agonist and tiotropium.

=> Inhaled steroids?
(However only ~15% of patients will benefit)

=> Antibiotics for infectious exacerbations
=> Oxygen therapy

247
Q

Contraindications in asthma

A

NSAIDs

Beta-blockers

248
Q

What is the goal of treatment of cancer pain?

A

symptom management

249
Q

What is the goal of treatment of pain in palliative care?

A

symptom management

250
Q

What is the goal of treatment of pain in post-surgical pain?

A
  • Patient comfort and satisfaction
  • Earlier mobilization
  • Reduce hospital stay
  • Reduce costs
  • Minimise stress response/neuroendocrine effects
  • Minimise adverse effects on respiratory, cardiovascular, GI/urinary and MSK systems
251
Q

WHO Pain ladder - step 1

A

Simple analgesics (e.g. NSAIDs, paracetamol)

252
Q

WHO Pain ladder - step 2

A

Opioids suitable for use in mild-to-moderate pain (e.g. codeine, tramadol) and simple analgesics

253
Q

WHO pain ladder - step 3

A

Opioids suitable for use in severe pain (e.g. morphine) and simple analgesics

254
Q

Adverse effects of NSAIDs

A

GI – erosion and ulceration

Renal – reduce renal blood flow, acute renal failure, sodium/potassium/water retention.

Airway – bronchospasm

Haematological – reduce platelet aggregation (aspirin = irreversible, NSAIDs = reversible).

?CV risk

255
Q

Prescribing NSAIDs

A

The aim is to use the lowest effective dose and for the shortest period of time necessary to control symptoms.

Regular review is required.

Consider co-prescription of a PPI to reduce risk of adverse GI effects

256
Q

what are some weak opioids?

A

Codeine
Dihydrocodeine
Dextropropoxyphene
Tramadol (PO)

257
Q

what are some strong opioids?

A 
Morphine
Diamorphine
Oxycodone
Buprenorphine
Fentanyl
258
Q

Use of weak opioids

A

most effective when used in combination with paracetamol

259
Q

What is important to remember about the metabolism of codeine?

A

Codeine is metabolised to morphine via CYP450 2D6

Pharmacogenetics - some patients are unable to convert it (more common in some ethnicities in particular, e.g. Chinese population)

260
Q

Use of strong opioids

A

Used in acute pain, persistent non-cancer pain and palliative care

261
Q

Adverse effects of opioids

A
  • Nausea & vomiting - manage with anti-emetics
  • Constipation - manage with laxatives
  • Sedation
  • Respiratory depression – overdose
  • Hypotension
  • Urinary retention
262
Q

Initiating morphine

A

Pain assessment, including current analgesia.

Determine opioid requirement
=> Use short acting preparation, regularly, plus PRN doses

Convert total daily dose to modified release formulation
=> Taken every 12 or 24 hours

263
Q

How can you convert to an alternative opioid?

A

Determine 24-hour requirement

Use conversion factor for alternative opiate to determine new 24-hour requirement

Convert to appropriate dosage regimen

Opioid equivalences – found in palliative care section of the BNF

264
Q

Patient Controlled Analgesia (PCA)

A

Morphine IV is the drug of choice
=> 1 mg bolus, 5-minute lock-out = typical settings

Tramadol, oxycodone or fentanyl if morphine allergy

265
Q

Advantages of PCA for pain relief

A 
Rapid analgesia once pain at steady state
Ready prepared
Patient satisfaction
No dose delay
Patient acceptability
No peaks or troughs
266
Q

Disadvantages if PCA for pain relief

A

Expensive
Requires IV access
Training
Monitoring

267
Q

Epidural Opioids

A

especially used in maternity, lower limb, spine or abdominal surgery

Mixture of local anaesthetic and opioid usually (fentanyl commonly)

Adverse effects - hypotension, ‘wrong route’, infection

268
Q

what is a syringe Driver?

what are the indications for its use?

A

Continuous subcutaneous infusion - important use in terminal care

Diamorphine is opioid of choice due to excellent aqueous solubility - can mix in other drugs

Indications:

  • Unable to take medicines by mouth (e.g. N&V, dysphagia)
  • Bowel obstruction
  • Patient does not wish to take regular medication by mouth
269
Q

monitoring of opioid therapy

A
  • Pulse
  • BP
  • Respiration rate – respiratory depression is a sign of opioid toxicity.
  • Oxygen saturation
  • Pain intensity
  • Sedation score
  • Opioid usage
  • Opioid side effects
270
Q

Use of Naloxone

A

= Opioid-receptor Antagonist

  • Used to manage opioid overdose
  • Higher affinity for opioid receptor than agonist – rapid effects
  • Short half-life when given IV – may need repeat doses
  • May induce pain
  • Titrate gradually until effect is achieved
271
Q

Neuropathic pain - clinical presentation

A 
Symptoms:
•	Burning
•	Electric shock
•	Pins and needles
•	Scalding
•	Shooting
•	Stabbing

Signs:
• Continuous vs. evoked
• Hyperalgesia
• Allodynia

272
Q

Pharmacological treatments for neuropathic pain

A

Tricyclic antidepressants

Anticonvulsants - Carbamazepine, Gabapentin, Pregabalin

Opioids
Local anaesthetics
Capsaicin

273
Q

Causes of neuropathic pain

A

Can be:

  1. damage to a peripheral nerve
  2. a change in pain processing, leading to hypersensitivity
274
Q

what is the aim of management in treating hyperthyroidism?

what are the options for achieving this?

A

achieving euthyroidism

  • antithyroid drugs (thionamides)
  • radioactive iodine to irradiate and destroy part of the thyroid gland
  • partial thyroidectomy.
275
Q

What are the anti-thyroid Drugs?

How do they work?

A

Carbimazole and propylthiouracil

Decrease the production of thyroid hormones by inhibiting the iodination of thyroglobulin and this occurs via inhibition of thyroperoxidase

276
Q

Why do anti-thyroid drugs take a few weeks to work?

A

due to the long half-lives of thyroid hormones

277
Q

What can be a side effect of therapy with anti-thyroid drugs?

A

May cause agranulocytosis leading to leucopenia

=> If patients report with sore throats, mouth ulcers, bruising or non-specific illness, a full blood count should be carried out

the drug should be withdrawn if there is leucopenia

278
Q

symptomatic relief in hyperthyroidism

A

beta-blockers reduce the actions of catecholamines at beta-adrenoceptors

Symptomatic relief from Tremor, Anxiety, Palpitations

(diltiazem may control tachycardia in patients who cannot receive a beta-blocker)

279
Q

Regimen options for treating hyperthyroidism

A
  1. High-dose carbamizole for 1-2 months achieve euthyroidism (+beta-blocker), then maintenance dose for ~18 months
  2. BLOCK AND REPLACE: High does carbamizole to suppress all thyroid activity (+ beta blocker), then carbimazole + levothyroxine
280
Q

Treatment of hypothyroidism

A

Restoring thyroid hormone levels is achieved by administration of levothyroxine (thyroxine).

=> The dose required is the one that leads to correct TSH levels

281
Q

Levothyroxine in young patients

A

Starting dose is 50-100 mg per day

May be increased after 6 weeks by 25-50 mg and thereafter until maintenance levels are achieved

282
Q

Levothyroxine in older patients/ patients with IHD

why is this done in patients with IHD?

A

Starting dose used is 25 mg
Increased every 3-4 weeks by 25mg, until normalisation of TSH levels

because thyroxine may lead to the worsening or uncovering of angina

283
Q

What is the goal of management of epilepsy?

A

to control seizures with the lowest possible dose and with the fewest side-effects

mono therapy is preferred, and the treatment is built up slowly

284
Q

what treatment will occur when a patient has a first seizure or isolated seizure?

A

likely go untreated as it may be an isolated event and so it may be preferable to avoid long term medication.

285
Q

What other pathologies can cause seizures and should be ruled out before a diagnosis of epilepsy?

A 
Cerebral tumours	(including metastasis)
Cerebrovascular accident
Alcohol withdrawal
Hyper/hypoglycaemia
Syphilis
Drugs (e.g antidepressants) may reduce seizure threshold
286
Q

treatment of generalised epileptic seizures

A

1st choice: valproate or carbamazepine
(lamotrigine in females of childbearing age)

2nd choice: levetiracetam

287
Q

treatment of absence seizures

A

1st choice: ethosuximde

2nd choice: valproate/lamotrigine

288
Q

AEDs: Valproate

A

Potentiates GABA, causes Na-channel blockade

Side effects include: Sedation, weight gain, tremor

associated with causing birth defects (a reason to avoid in females of childbearing age)

associated with causing liver damage (hence liver function is monitored)

289
Q

AEDs: Carbamazepine

A

Use-dependent blockade of Na-channels

Side effects include: Rashes, Dizziness, Double vision

Induces metabolism of itself and many other drugs

Many interactions: induction leads to accelerated metabolism of interacting drugs

Associated with causing birth defects

290
Q

AEDs: Phenytoin

A

Less commonly used

Many side effects:

  • increased gum growth
  • nystagmus a toxic effect

Associate with causing birth defects

Zero order kinetics => disproportionate increases in plasma concentration on increasing dose

i.e. a small increase in the dose or a drug interaction can quickly shift the plasma concentration above the therapeutic window

291
Q

AEDs: Lamotrigine

A

Use-dependent blockade of Na-channels, reduces release of glutamate

Not particularly sedating

Withdraw if the patient develops a rash/flu-like illness due to the risk of bone marrow toxicity

292
Q

Monitoring AED therapy

A

FBC should be monitored for haematological effects
=> many cause leucopaenia
=> lamotrigine - aplastic anaemia
=> valproate - thrombocytopenia

LFTs/INR should be monitored for liver function

Skin - rashes, severe skin reactions

293
Q

what should be done if an AED is causing severe leucopenia in a patient?

A

withdraw the drug, under the cover of another drug

294
Q

AEDs in pregnancy

A

carbamazepine, valproate and phenytoin are teratogenic
=> Especially causing neural tube defect
=> carbamazepine considered the safest of these

To prevent NTD – 5mg folic acid daily in 1st trimester, with counseling & screening

Neonatal bleeding tendency may occur with carbamazepine, and phenytoin (due to enzyme induction) and so vitamin K1 is given for 3rd trimester

Newer agents (e.g. lamotrigine for generalised seizures) may be considered 1st line in women of childbearing age

295
Q

AEDs - failure of treatment

A

Review drug - use the maximum dose?

Swap with another antiepileptic drug

Further failure – add a second drug

296
Q

what is status epilepticus?

A

= continuous seizure for 30 mins or 2 fits without recovery between them

297
Q

How is status epileptics managed?

A

diazepam/lorazepam/clonazepam or a slow IV of phenytoin

if this fails, a general anaesthetic such as propofol

298
Q

AEDs - interactions

A

ENZYME INDUCTION with phenytoin, carbamazepine and phenobarbitone

This leads to many interactions – e.g. failure of oral contraceptives
=> Patient use additional barrier methods or a high dose pill

299
Q

Epilepsy/AEDs and driving

A

Driving is permitted if seizure free for 1 year
(Or if attacks occur while asleep over a 3-year period)

BUT some drugs may cause drowsiness – avoid driving if affected (see BNF)

300
Q

Withdrawal of AEDs

A

Might be considered if the patient is seizure free for 2-4 years

Withdraw drug gradually, as withdrawal can precipitate epilepsy

Stop driving during withdrawal

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