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1
Q

major consequences of Beta receptor blockade

A

• negative chronotropic and inotropic actions on the
heart (β1)
• decreased blood pressure (in part due to the inhibition of renin release - β1)
• bronchoconstriction (β2)
• local vasoconstriction – end-arteries, and diseased peripheral vessels (β2)
• decreased aqueous humor production in the eye
• impaired recovery from hypoglycemia (β2)
• increased plasma concentrations of VLDL and
decreased concentrations of HDL

2
Q

Potential indications of β blockers

A

• hypertension
• angina pectoris (exc.: vasospastic)
• tachyarrhythmias (supraventricular)
• congestive heart failure (long-term use prolongs
survival – acutely they may worsen heart failure!)
• after myocardial infarction (secondary prophylaxis)
• hypertrophic obstructive cardiomyopathy
• hyperthyreoidism, pheochromocytom
• portal hypertension, esophagus varices (reduce risk of bleeding)
• glaucoma (eye drop)
• somatic manifestations of anxiety (performance anxiety)
• migraine headache (prevention: propranolol, pindolol – as 5-HT2-antagonists?)
• essential tremor, proliferating hemangiomas in newborns (propranolol)

3
Q

Adverse effects of β blockers

A

Adverse effects of β blockers
• bronchoconstriction (worsening of bronchial asthma)
• cardiac decompensation - if cardiac output is critically dependent on
increased sympathetic drive (interaction with other negative inotropic drugs is
dangerous, combination is contraindicated)
• bradycardia, decreased AV-conduction
• cold extremities, worsening of peripheral vascular diseases
• uterus contractions in pregnancy
• hypoglycaemia
• hyperlipidemia
• contribution to increased potassium level
• sleep disturbances (nightmares), mental depression

• abrupt discontinuation of therapy after chronic use –
increased risk of ischemic heart disease- MOST IMPORTANT!!!

4
Q

Major differences among the

β blockers

A

similar: all clinical available beta blockers are competitive antagonists.
divided into 2 major groups: non selective and cardioselective (block beta 1 receptors).

differ:
• selectivity
• intrinsic avtivity (partial agonistic activity - ISA)
• lipid solubility
• additional actions on ion channels
• additional vasodilatory action
• half-life
5
Q

advantage of beta 1 receptor blockers

A

less bronchoconstriction, hypoglycemia and peripheral circulatory problems.
All beta blockers will lower BP but will not cause postrual hypotension because the alpha adrenoreceptors remain functional.

6
Q

mention all selective Beta 1 antagonists!

A
β1 selective (cardioselective)
blockers (2nd generation)
1. atenolol
2. metoprolol
3. bisoprolol 
4. esmolol 
5. celiprolol 
6. betaxolol 
7. nebivolol (+ NO) 
8. acebutolol
nmemonic for 5: AMEBA+ CBN
β1 selective blockers cause less
bronchoconstriction, hypoglycaemia
and peripheral circulatory problems.
CAUTION: β1 selectivity is never absolute!
7
Q

non selective-

A
Nonselective β blockers
• propranolol- important
• pindolol - important
• oxprenolol 
• alprenolol 
• nadolol 
• carteolol 
• levobunolol 
• penbutolol 
• timolol - important
• sotalol (+K-ch-bl.) - important
• carvedilol (+α1 -bl.) - important
• labetalol (+α1 -bl.)- important

pro-car-lab- so timpin

8
Q

which are not beta blockers?

A

labetalol, sotalol, carvedilol

9
Q
Partial agonistic (ISA) activity of the
β blockers
β blockers with ISA (intrinsic sympathomimetic activity)
A
the beta blockers exert partial agonism at the adrenergic receptors while simultaneously blocking the endogenous catecholamines from binding to the receptor; meaning they are less potent than other beta agonists or the endogenous catecholamines- baiscly partial agonist.
• pindolol
• acebutolol
• oxprenolol
• alprenolol
• celiprolol

so in effect this causes:
Less bradycardia (B1).
Slight vasodialation or bronchodialation (B2)
Minimal change in plasma lipids.

10
Q

Lipid solubility of the β blockers

A
β blockers with the highest lipid solubility
• propranolol
• nebivolol
lowest lipid solubility
• atenolol
• sotalol
• acebutolol
• Pharmacokinetics

lipophilic drugs – must be metabolized in the liver
hydrophilic drugs – can be excreted unchaged
(importance of kidney/liver diseases in elimination)
• Only lipid soluble β blockers can be used for CNS
indications (e.g. tremor)
• Drugs with low lipid solubility cause less CNS adverse
effects (e.g. nightmares, mental depression)

11
Q

Action of the β blockers on ion channels

A
• Some β blockers possess weak local anesthetic
(Na+ channel blocking) effect
• propranolol 
  metoprolol
• acebutolol
• pindolol

It is unlikely that this effect is important in case of systemic use.

Eye drops mustn’t possess this action - timolol doesn’t block
Na channels - that is one reason why it is used for glaucoma.

• Sotalol blocks K+ channels – a class II + III. antiarrhythmic drug

12
Q

β blockers with additional vasodilatory action (3rd generation)

A

β blockers with additional vasodilatory action (3rd generation)

• additional blockade of α1 receptors
• labetalol, carvedilol
• racemic mixtures: one isomer is a selective α1 blocker,
another isomer is a β blocker

  • indications: hypertension, congestive heart failure, stable angina
  • synergistic antihypertensive actions without tachycardia

• less (no) changes in lipid profile
• NO-mediated vasodilation
• nebivolol • antihypertensive indication
• racemic mixture: one isomer is a selective β1 blocker,
another isomer induces NO release

13
Q

Half-life of the β blockers

A

Half-life of the β blockers
• Ultrashort-acting
• esmolol
• β1 selective blocker, 10 min. half-life
• It is much safer in critically ill patients who require β
blocker therapy (e.g. supraventricular arrhythmias,
perioperative hypertension)

  • β blockers with long half-life (more than 10 hours)
  • nadolol (16-20 h)
  • betaxolol (14-20 h)
  • bisoprolol (10-12 h)
  • nebivolol (~10 h)
14
Q

propanolol

A

non-selective beta blocker.

action:
1. Diminishes CO and reduce workload on the heart (oxygen consumption decreases).
2. Peripheral vasoconstriction: nonselective beta2 blockade- vasodialation- reduction of diaastolic blood pressure.
3. Bronchoconstriction- contraindicated in COPD and asthmatics.
4. Hypoglycemia may ensue after insulin treatment in diabetics (beta blockade reduces glucose production and insulin release).

Theraputic use:

  1. Hypertension- decreased cardiac output and inhibition of renin release and decrease of TPR with long term use.
  2. Angina pectoris- decrease of oxygen requirement.
  3. prophylatic MI-> reduction of MI size and hastens recovery.
  4. Migraine- reduced migrane episodes and also lipophilic so it can enter brain.
  5. Hyperthyroidism- lifesaving in protection against arrhythmias which may be induced by thyroid hormone storm.

pharmacokinetics- oral administration, almost completely absored.
25% bioavailability (subject to first pass effect).
volume of distribution is quite large- 4L per Kg.
excreted in urine.

Adverse effects:
Bronchoconstriction- contra-indicated in asthmatics and COPD.
arrhythmias- should never be stopped abruptly and can worsen angina.
Sexual impairment.
Metabolic disturbances- glycogenolsysis and glucagon secretion decreased.
Fasting hypoglycemia.
increase of LDL and reduced HDL.
CNS effects- depression, dizziness, lethargy, fatigue and weakness, and more.
d

15
Q

what is the advantage of b1 selectve drugs

A
β1 selective blockers cause less
bronchoconstriction, 
hypoglycaemia
peripheral circulatory problems.
CAUTION: β1 selectivity is never absolute!
16
Q

contraindications of B blockers

A
  1. cardiac (bradycarida AV block, prinzmental.
  2. Pulmonary (Serve asthma).
  3. Diabetes mellitus.
  4. Peripheral vacsular disease.
  5. Central disordrs.
  6. Hyperlipidemia.
  7. Pregnancy.