Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college
Unit V: Introduction and classification of the drugs acting on: a. Central nervous system
CNS Stimulants (Analeptics)
Doxapram
It is used most frequently in veterinary medicine as a CNS stimulant.
Mechanism of action: Doxapram stimulates respiration, which is a result of direct stimulation of the medullary respiratory centers and probably via activation of carotid and aortic chemoreceptors.
Therapeutic uses:
a) Doxapram is used to arouse animals from inhalant and parenteral anesthesia or anesthetic overdose. The depth of anesthesia is reduced, but the effect could be transient.
b) Doxapram is not effective in reviving a severely depressed neonate and is not a good substitute for endotracheal intubation and ventilation.
Adverse effects:
High doses of doxapram may induce seizures.
Hypertension, arrhythmias, seizures, and hyperventilation leading to respiratory alkalosis can happen.
Tranquilizers, Ataractics, Neuroleptics, And Sedatives
These terms are used interchangeably in veterinary medicine to refer the drugs that calm the animal and promote sleep but do not necessarily induce sleep, even at high doses. Ataractic means “undisturbed”; neuroleptic means “to take hold of nerves.” Tranquilized. Animals are usually calm and easy to handle, but they may be aroused by and respond to stimuli in a normal fashion (e.g., biting, scratching, kicking). When used as pre-anesthetic medications, these drugs enable the use of less general anesthetic.
Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college
Phenothiazine derivatives
Phenothiazine derivatives include acepromazine, promethazine, chlorpromazine, fluphenazine, prochlorperazine, and trimeprazine.
Mechanism of action: Phenothiazine derivatives affect the CNS at the basal ganglia, hypothalamus, limbic system, brain stem, and reticular activating system. They block dopamine, α1-adrenergic and serotonergic receptors Pharmacologic effects:
a) CNS effects: (1) The tranquilizing effects( depression of the brain stem via blockade of dopamine and 5-HT receptors. (2) All phenothiazines decrease spontaneous motor activity.
b) Cardiovascular effects: 1. Hypotension (α1-adrenergic receptor blockade and a decrease in the sympathetic tone) 2. Reflex sinus 3. Antiarrhythmic effects 4. Inotropic effect.
c) Respiratory effects: Respiratory depression
d) GI effects: 1. Motility is inhibited 2. Emesis is suppressed e) Effects on blood: Packed cell volume decreases
f) Metabolic effects: 1. Hypothermia/hyperthermia 2. Hyperglycemia 3.
Hyperprolactinemia.
Therapeutic uses:
a) tranquilization.
b) antiemetics.
c) prior to use of inhalant anesthetics can reduce the incidence of arrhythmias sensitization to catecholamines.
d) Promethazine and trimeprazine are used to control allergy, because they
Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college
Adverse effects: There is no reversal agent for this class of drugs.
a) Accidental intracarotid administration in horses results in the immediate onset of seizure activity and, sometimes, death.
b) They inhibit cholinesterase (ChE) and may worsen the clinical signs of anti- ChE poisoning. They should not be given to animals within 1 month of treatment with an organophosphate compound.
c) The H1-antagonistic effect makes phenothiazines an undesirable drug for sedation of animals prior to allergy testing.
d) Paraphimosis may occur in stallions, which is due to relaxation of retractive penis muscles via α1-receptor blockade. Thus, phenothiazines should be used cautiously or avoided altogether in breeding stallions.
Contraindications:
a) Anti-ChE poisoning or suspected treatment with anti-ChE antiparasitic drugs.
b) History of blood loss and hypotension.
c) Avoid in animals with moderate to severe liver dysfunction or portacaval shunt.
α2-Adrenergic agonists
These drugs activate α2- adrenergic receptors in the CNS, thereby causing analgesia, sedation, and skeletal muscle relaxation.
Mechanism of action: α2-Agonists activate α2- receptors that are Gi/o- coupled receptors; Gi/o mediates many inhibitory effects on the nervous systems and endocrine glands. High doses of xylazine, detomidine, and romifidine also activate α1-receptors.
Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college
Pharmacological effects:
Analgesia:
(1) α2-Receptors are located on the dorsal horn neurons of the spinal cord, they can inhibit the release of nociceptive neurotransmitters, substance P and calcitonin gene-related peptide (CGRP).
(2) α2-Adrenergic mechanisms do not work through opioidergic mechanisms, because cross- tolerance is not usually present. α2-Agonist- mediated analgesia is not reversed by opioid antagonists.
Sedation:
1. Ruminants are most sensitive to α2-agonists, followed by cats, dogs, and horses. Pigs are least sensitive to α2-agonists in domestic animals.
2. High doses of α2-agonists may induce CNS excitation, which is attributable to activation of α1-receptors
Skeletal muscle relaxation: α2-Agonists produce skeletal muscle relaxation by inhibiting intraneuronal transmission of impulses in the CNS.
Emesis: It is induced in carnivores and omnivores, and is commonly seen in the cat, and less frequently in the dog.
Cardiovascular effects:
3. Bradycardia,
4. hypertension is due to activation of the postsynaptic α2-receptors of vascular smooth muscle.
5. hypotension is caused by reduced norepinephrine release by the sympathetic nerve at the vascular smooth muscle
6. Bradycardia (with or without sinus arrhythmia) is due to decreased
Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college
Respiratory effects: α2-Agonists cause hypoxemia.
Neuroendocrine effects: α2-Agonists inhibit sympathoadrenal outflow and decrease the release of norepinephrine and epinephrine.
(3) α2-Agonists inhibit insulin release; this effect is very pronounced in ruminants, which results in a moderate to severe hyperglycemia lasting up to 24 hours.
(4) α2-Agonists increase growth hormone release by inhibiting somatostatin release from the hypothalamus and stimulating growth hormone—
stimulating hormone release from the median eminence. The α2-agonist- induced growth hormone release is not sustained; consecutive daily drug administration can only maintain increased secretion for <1 week.
Therapeutic uses: α2-Agonists are used as a sedative, analgesic, and immobilizing agent. - They are also used to induce epidural analgesia, - as a preanesthetic, and as a part of the anesthetic combination. - xylazine- ketamine is a commonly used, but not very safe, parenteral anesthetic combination
