L16 Beta Blockers

Question 1

What are the condition indications for BB

Answer 1

• Angina: symptom relief
• Hypertension 2/3rd line (metoprolol)
• HF reduced ejection fraction (longterm)
• Arrhythmia (AF, A.flutter,- rate control, SVT- termination)

Symptoms/ related symp drive for
- Thyrotoxicosis, Migraine prophylaxis, Anxiety

Question 2

What effect does BB blockers block from B adrenergic receptors in bv, heart, bronchi and kidney and which B receptor is it and describe the selectivity of BB with examples

Answer 2

heart: B1 tachycardia, increased contractility
bv: B2 dilation, a1 constriction
bronchi: B2 relaxation
kidney: B1 & B2: renin release

There are B1&raquo_space;> B2 eg. Metaprolol
B1 = B2: Propanolol
Mixed antagonists a&B: eg. Carvedilol

Question 3

Describe the mechanism of action/effect of BB cellularly (3)

Answer 3

1. BB antagonise the effect of NE on B receptors on the post synaptic membrane
2. This induces up regulation of post synaptic membrane receptors , increasing their density over time, although they are all still blocked
3. BB can attenuate function reducing intracellular B-adrenoreceptor kinase activity.

Question 4

What is the admin of BB, half life and what is the difference between lipophilic and non lipophilic

Answer 4

• Well absorbed orally, with sustained release preps, for rapid turnaround/arrhythmias: iv.
• half life = 2-5 hours

Lipophlic eg. propranolol, metoprolol - extensive rapid gut absorption, gut wall and liver metabolism, high protein binding and some enter BBB

Hydrophilic eg. atenolol : renal excretion and longer half life

Question 5

What is special about Esmolol in terms of Pk

Answer 5

It has be given constant IV infusion bc of v short half life. Most commonly in ICU the dose is titrated to fine tune hypertension in eg. thoracic aorta dissection

Question 6

How does BB help Angina (chronic - 1st line treatment) specifically and give an eg.

Answer 6

1. Lowering HR –> reduce cardiac work and output
   therefore increase diastole and perfusion time.

• as well as decrease mismatch between stenosed blood supply and increased cardiac work.
  eg. Metoprolol

Question 7

How does BB help initial stages Post MI specifically *5

Answer 7

1. Helps to reduce high Sympathetic drive (centrally)
2. Reduce arrhythmias–> negative chronotropic to decrease SA automaticity, AV node transmission
3. Reduce Ventricular rupture
4. Improve cardiac remodelling
5. Help the ischaemic part get perfusion- lowering cardiac work and increasing diastole duration.

Question 8

How does BB improve prognosis and survival in the long run for HF with Reduced ejection fraction specifically, (7)

Answer 8

Helps

1. Reduces cardiac sympathetic tone:
   - reduce HR , increase diastolic filling, decrease O2 consumption
2. Upregulates B receptors back to normal after heart damage shifts ratio of receptors from B1>B2>a1 to B1 > B2=a1
3. Modulation of post receptor inhibitory proteins (kinases and other mechanisms overtime)
4. Attenuate apoptosis
5. Improve baroreceptor function by resetting: interfere with crosstalk between receptor and resistance vessels
6. Improve LV remodelling
7. Inhibit Renin

Question 9

When should BB be used to treated HF w ref, which drugs and how should treatment be carried out

Answer 9

It is Contraindicated to give it for acute/short term decompensated HF with pulmonary oedema and reduced CO.
This is because symp is needed to improve contractility and HR –> improve CO in that situation.

1) : Sit up, give O2 for hypoxia
2) Diuretics eg. frusemide+/- nitrates, to control fluid overload
3) . When condition is stable, then low dose BB dose titration over wks/months + ACEi+ aldosterone antagonist to start improving ejection fraction.

eg. Carvedilol: mixed B antagonist
eg. Metoprolol: B1 selective.

4) Patients need follow up to make sure no overtreatment and manage any AE - that he was informed of eg. hyperkalaemia

Question 10

Which drug treats Thyrotoxicosis crisis and Migraine, what is the action, how does it help specifically

Answer 10

Propanolol

Thyrotoxicosis

• Blocks T4-T3 conversion
• Improves tachycardia, tremor, agitation: negatively chronotropic SA,AV.

Migraine
- via action on central B1 receptors: mechanism unknown

Question 11

What are the pharmacodynamic effects of BB on Respiratory, eye and metabolic systems

Answer 11

Resp: blocks bronchodilation

Eye: Reduces aqueous humour production so given topically, it can reduce pressure in glaucoma

Metabolic:
Decrease glycogenolysis

Question 12

What are the AE of BB on resp, CVS, metab, CNS and general

Answer 12

Resp:
- contraindicated for childhood asthmatics (not older ppl with smoking damage)

CVS:

• promotes vasospasm - not good for resting limb ischaemia peripheral vascular disease
• Acute CHF exacerbation
• bradycardia and hypotension

Metab
-Masks hypoglycaemia because normally the symp system alerts the diabetic patient

CNS:
-nightmares (BBB crossing)

General

• fatigue, impotence (erectile dysfunction)
• Drug withdrawal: tachycardia, hypertension due to the increased B receptor in PS space so dose needs to be titrated back down over few wks.

Question 13

What drug interactions with BB must you be cautious of

Answer 13

1. Verapamil: contraindicated because marked chronotropic effect is synergistic -> heart block
2. Diltiazem: caution but acceptable as - chronotropic effects can help Ventricular rate in AF
3. Other Bp lowering drugs
4. Anti-diabetics: due to hypoglycaemia awareness.