VPT 321: Veterinary Neuropharmacology (2+1) copy 1

THERAPEUTIC USES

• Cardiovascular shock – These drugs can be used to overcome compensatory vasoconstriction. They must be used in conjunction with adequate fluid therapy to increase tissue perfusion.
• Pheochromocytoma – Can be used to overcome hypertensive attacks and to counteract effects of manipulation of tumor during surgical removal. (These drugs are used in combination with β blockers).
• Hypertension – Prazosin is used in hypertension.
• Epinephrine reversal (Dale’s vasomotor reversal): Epinephrine acts both on   α  and β  receptors. When given in high doses the vasoconstrictor effect and a rise in blood pressure are observed. But, when the a receptors are blocked using ergot like drugs / alpha 1 blockers and then the same dose of epinephrine is repeated, the a action on blood pressure is blocked and only the β receptors are free to act. Hence a fall in blood pressure is noticed instead of a rise. This is known as epinephrine reversal.

β-adrenergic antagnoists

• Non-selective antagnoists (Interact with β1 and β2 with equal potency)
• Dichloroisoproterenol was the first β -blocker to be synthesized. It is not used clinically, however, because it initially stimulates receptors (partial agonist).
• Propranolol (Inderal) as well as several others including Timolol Alprenolol, Pindolol, Nadolol, Sotalol are non-selective β-receptor antagonists and block β1 and β2 receptors with equal potency.

Pharmacological Actions

• Heart
  • Decrease in heart rate and force of contraction and cardiac output (minimal under resting conditions). Maximum exercise tolerance is reduced, partly because of the limited cardiac response but also because the β mediated vasodilatation in skeletal muscle is reduced. Coronary flow is reduced, but relatively less than myocardial oxygen consumption, so oxygenation of the myocardium is improved. β -Adrenergic receptor blockers can aggravate heart failure.
• Bronchioles
  • Slight increase in airway resistance due to bronchonconstriction and should therefore be avoided in bronchoconstrictor disorders such as asthma and allergic reactions. In these disorders non-selective β antagonists by themselves can cause severe bronchoconstriction, which is unresponsive to b agonists.
• Metabolic Effects
  • Can cause hypoglycemia by inhibiting β -receptor mediated adrenergic responses and should be used with caution in patients prone to hypoglycemia or in diabetes with insulin treatment.

Therapeutic Uses

• Cardiac arrhythmias - Can be used for supraventricular and ventricular arrhythmias, and are especially valuable in anesthetic and digitalis-induced arrhythmias. They have been shown to reduce the incidence of death from ventricular fibrillation during heart attacks.
• Post-myocardial infarction - Prophylactically reduces incidence of recurrent myocardial infarction in individuals with recent history of infarction.
• Glaucoma - Production of aqueous humor is reduced, lowering intraocular pressure. The mechanism of this effect is not clear. The advantage over cholinergic agonists is that accommodation and pupillary reactions are unaffected.
• Pheochromocytoma ( adrenal medullary tumour) - Can be useful for managing tachycardia and arrhythmias and during surgery (in combination with a blockers).
• Hypertension - Usually used in combination with a diuretic. This is a common use in human medicine. Patients with hypertension show a gradual fall in arterial pressure that takes several days to develop fully.
• Angina pectoris - Used prophylactically in human medicine because of improved oxygenation of myocardium.
• Hyperthyroidism - Can be used to control many of the symptoms .