Propranolol depression with

The beta blocker propranolol (Inderal) has been studied in the treatment of impulsivity and appears to provide a slight benefit to some patients. It can be started at a dose of 10 mg taken three times per day and increased gradually to a maximum of 200mg/day. Side effects of propranolol include depression, fatigue, lowered blood pressure, impotence, and a worsening of symptoms in patients with asthma. 

Adverse effects of the TCAs on the brain include confusion, impaired memory and cognition and occasionally delirium some of these effects have been reported to occur in up to 30% of patients over the age of 50. These effects may occasionally be confused with a recurrence of the s)nnptoms of depression and are probably due to the central antimuscarinic activity of these drugs. Tremor also occurs frequently, particularly in the elderly, and may be controlled by the concurrent administration of propranolol. Neuroleptics are normally not recommended to be used in combination with TCAs as they are liable to accentuate the side effects of the latter drugs. The risk of seizures, and the switch from depression to mania in bipolar patients, has also been reported following TCA administration. 

The toxicity associated with propranolol is for the most part related to its primary pharmacological action, inhibition of the cardiac (3-adrenoceptors. This topic is discussed in detail in Chapter 11. In addition, propranolol exerts direct cardiac depressant effects that become manifest when the drug is administered rapidly by the IV route. Glucagon immediately reverses all cardiac depressant effects of propranolol, and its use is associated with a minimum of side effects. The inotropic agents amrinone (Inocor) and milrinone (Primacor) provide alternative means of augmenting cardiac contractile function in the presence of -adrenoceptor blockade (see Chapter 15). Propranolol may also stimulate bron-chospasm in patients with asthma. 

Since propranolol crosses the placenta and enters the fetal circulation, fetal cardiac responses to the stresses of labor and delivery will be blocked. Additionally, propranolol crosses the blood-brain barrier and is associated with mood changes and depression. School difficulties are commonly associated with its use in children. Propranolol may also cause hypoglycemia in infants. 

Propranolol is contraindicated for patients with depressed myocardial function and may be contraindicated... 

The prominent depressant action of verapamil and diltiazem at the SA and A-V nodes finds use in specific arrhythmias. They are of proven efficacy in acute control and long-term management of paroxysmal supraventricular tachycardia (see Chapter 16).Their ability to inhibit conduction at the A-V node is employed in protecting ventricles from atrial tachyarrhythmias, often in combination with digitalis or propranolol. 

Tremor and akathisia are less common and can be managed with dose reduction or the addition of a P-blocker such as propranolol (10-40 mg). There are isolated case reports of SSRl-related dystonia and increasing reports of SSRl-related exacerbation of Parkinson s disease (Di Rocco et al. 1998 Linazasoro 2000). The advisability of SSRl use in depressed patients with Parkinson s disease remains to be determined. Bupropion and electroconvulsive therapy (ECT) may be reasonable alternatives for these patients. 

Jitteriness, tachycardia, and tremor can occur early in the course of treatment, particularly in patients with co-morbid panic attacks. TCAs may cause a persistent, fine, rapid tremor, particularly in the upper extremities. Desipramine and protriptyline may be the most common offenders. Propranolol (60 mg per day) may help and is unlikely to worsen depression. Alternatively, switching to a drug with less NE activity may also help. 

Propranolol inhibits the stimulation of renin production by catecholamines (mediated by receptors). It is likely that propranolol s effect is due in part to depression of the renin-angiotensin-aldosterone system. Although most effective in patients with high plasma renin activity, propranolol also reduces blood pressure in hypertensive patients with normal or even low renin activity. Beta blockers might also act on peripheral presynaptic adrenoceptors to reduce sympathetic vasoconstrictor nerve activity. 

Propranolol Nonselective competitive antagonist at adrenoceptors Decreased heart rate, cardiac output, and blood pressure decreases myocardial oxygen demand Prophylaxis of angina for other applications, see Chapters 10, 11, and 13 Oral and parenteral, 4-6 h duration of action Toxicity Asthma, atrioventricular block, acute heart failure, sedation Interactions Additive with all cardiac depressants... 

Propranolol 13- Adrenoceptor blockade Direct membrane effects (sodium channel block) and prolongation of action potential duration slows SA node automaticity and AV nodal conduction velocity Atrial arrhythmias and prevention of recurrent infarction and sudden death Oral, parenteral duration 4-6 h Toxicity Asthma, AV blockade, acute heart failure Interactions With other cardiac depressants and hypotensive drugs... 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

Baldassano et al. (1996) described a depressed 18-year-old student who was started on paroxetine 20 mg/day and clonazepam 0.5 mg at night who developed worsening insomnia, a need to move about, restlessness, physical tiredness, and anxiety. The akathisia resolved on propranolol. The authors reviewed their charts and found 3 cases of akathisia among 67 patients (4%) treated with paroxetine. They concluded,... 

In the treatment of the acute attack it would seem rational to use any safe means of depressing the formation of ALA-synthase. Indeed, haem arginate (human haematin) infusion, by replenishing haem and so removing the stimulus to ALA-synthase, appears to be effective if given early, and may prevent chronic neuropathy. Additionally, attention to nutrition, particularly the supply of carbohydrate, relief of pain (with opioid), and of hypertension and tachycardia (with propranolol) are important. 

Since the introduction of propranolol, it has been recognized that patients with bronchial asthma treated with beta-adrenoceptor antagonists can develop severe airways obstruction (84), which can be fatal (85) or near fatal (86,87) this has even followed the use of eye-drops containing timolol (88). Beta-blockers upset the balance of bronchial smooth muscle tone by blocking the bronchial beta2-adrenoceptors responsible for bronchodilata-tion. They also promote degranulation of mast cells and depress central responsiveness to carbon dioxide (89,90). 

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