PHAR101A(7)_DrugActingOnTheANS.pdf

BASIC VETERINARY PHARMACOLOGY LECTURE PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. De La Salle Araneta University NERVOUS SYSTEM PARASYMPATHETIC (Rest & Digest) The nervous system is made up of two parts: Known as crani...

BASIC VETERINARY PHARMACOLOGY LECTURE PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. De La Salle Araneta University NERVOUS SYSTEM PARASYMPATHETIC (Rest & Digest) The nervous system is made up of two parts: Known as craniosacral outflow o Originate from the midbrain, medulla Central Nervous System o Brain oblongata, and sacral spinal cord o Spinal cord Post-ganglionic parasympathetic fibers are usually quite short because the ganglia are Peripheral Nervous System located within innervated organs o Cranial nerve o Spinal nerve Effects specific effector system individually o Somatic Nervous System = voluntary Hormones are Acetylcholine (Ach) o Autonomic Nervous System = involuntary (Nicotinic and muscarinic receptors) SYMPATHETIC & PARASYMPATHETIC NOTES ADRENAL MEDULLA Important component of the sympathetic n.s. VAGUS NERVE (CN X) Most important parasympathetic nerve trunk; arises from medulla oblongata Sends efferent fibers to thoracic and abdominal viscera (from caudal pharyngeal → cranial portions of the large colon) NEURON SYMPATHETIC (Fight or Flight) Known as thoracolumbar outflow Sympathetic postganglionic ganglia are long since most sympathetic ganglia are located close proximity to the spinal cord The functional part of the nervous system; One sympathetic ganglionic neuron may be has 3 parts: innervated by preganglionic fibers Cell body (Cyton) originating from several different nerve body Dendrites Hormones are norepinephrine and Axon epinephrine Synapse – the space between neurons (Alpha and beta receptors) 1 DVM3F 3rd Term  PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. Information is communicated from nerve to 2 BASIC NEUROTRANSMITTERS nerve and from nerve to the effector organ Norepinephrine by a process termed Neurohumoral o Alpha receptor – excitation Transmission, it involves the release from a ▪ α1 (Alpha 1) terminal of a chemical (neurotransmitter Post-synaptic substance), which then reacts with Found in vascular smooth muscle specialized receptor areas in the innervated ▪ α2 (Alpha 2) cell Pre-synaptic Noradrenergic nerves – used to designate Found in brain and periphery neurons that release norepinephrine and o Beta receptor – inhibition epinephrine respectively ▪ β1 (Beta 1) Adrenergic nerves – nerves that release Excitation (stimulates the heart) norepinephrine ▪ β2 (Beta 2) Cholinergic nerves – nerves that release Inhibition (dilation of bronchioles in Ach lungs) Acetylcholine (Ach) o Nicotinic receptor - excitation o Muscarinic receptor ▪ Excitation (heart) ▪ Inhibition (GIT) CLASSIFICATION OF ANS DRUGS 1. Sympathomimetics / Adrenergics / Adrenomimetics 2. Sympatholytics o 2 types: ▪ Receptor-blocking / adrenergic-blocking (inhibits and competes sympathetic nn.) ▪ Neuronal-blocking / adrenolytic (inhibits sympathetic nn. w/o competing) 3. Parasympathomimetics / Cholinergics / NOTES Chlolinomimetics Cholinergic Nerve of the Sympathetic 4. Parasympatholtics Outflow releases Ach in the preganglionic o 2 types: nerve while Adrenergic nerve releases ▪ Receptor-blocking / adrenergic-blocking norepinephrine in the postganglionic nerve (inhibits and competes parasympathetic Cholinergic nerve of the Parasympathetic nn.) Outflow releases Ach in both pre and ▪ Neuronal-blocking / adrenolytic (inhibits postganglionic nerve parasympathetic nn. w/o competing) 2 DVM3F 3rd Term  PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. SYMPATHOMIMETIC / ADRENERGIC II. DOPAMINE DRUGS Tx of Parkinson’s disease in human α-dopamine crosses the blood-brain- I. CATECHOLAMINES barrier and is decarboxylated to dopamine Examples: Selective cardiovascular function on renal o Epinephrine and splanchnic beds o Norepinephrine o Isoproterenol Used for shock and cardiovascular dysfunction, renal failure Causes vasoconstriction in: o Cutaneous b.v. Phenoxybenzamine α – blocks pressor o Mucosal b.v. effect on the heart o Renal b.v. Propranolol β – blocks stimulatory effect on o Mesenteric b.v. the heart Causes vasodilation in: Haloperidol β – blocks depressor effect in o Coronary b.v. the brain Small amount of epinephrine causes vasodilation of skeletal blood vessel; large III. FENOLDOPAM amount cause vasoconstriction Acts on dopamine receptor on vascular bed, Small amount of epinephrine causes causing vasodilation vasodilation of skeletal blood vessel, but Used for hypertension, improve perfusion of large amount cause vasoconstriction GIT, renal protection from vasoconstriction Propranolol – blocks vasodilation effect in the skeletal b.v. IV. DOBUTAMINE o Act as inotropes (increases heart rate) by Agent that selectively increases cardiac changing the automaticity of the contractility without affecting heartbeat, pacemakers cardiac rhythmicity, and blood pressure Halothane & chloroform increases the Tx of low output heart failure sensitivity of the chart to cardiac rhythm irregularities caused by catecholamines V. NON-CATECHOLAMINE Clinical uses: Ephedrine (alkaloid; from a plant named Ma o Adjunct with local anesthetic Huang from a Chinese shrub) affects the o Local hemostatic (stops hemorrhage) CNS ▪ (Epinephrine: Tx of epistaxis in horses) o Undergoes cooking process to become Amphetamine → Methamphetamine o Hypertension (chemical name of Shabu “poor man’s o Cardiac arrest (Isoproterenol: DOC for cocaine”) → Methoxamine → heart block) Metaraminol o Anaphylactic and allergic reaction o Ephedrine also undergoes cooking (Epinephrine: DOC for anaphylaxis) process to become Pseudoephedrine → o Bronchial asthma Phenylephrine (similar to epinephrine except that it lacks the 4-OH group on the benzene ring) → Phenylpropanolamine 3 DVM3F 3rd Term  PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. (used for cough, syrup, decongestant, Ergonovine – oxytocic activity; can treat allergy, topical hemostatic, urinary post-partum hemorrhage incontinence, and heart pressor) Ergotamine – adrenergic blocking; blocks α cells VI. β2 -SELECTIVE BRONCHODILATORS ▪ Causes intense peripheral They only bind with β2 receptor of the vasoconstriction respiratory system ▪ Causes stasis of blood, thrombosis, Dilates the bronchus endarteritis leading to gangrene of Anti-asthma drugs: extremities o Salbutamol ▪ Emesis is due to stimulation of o Terbutaline Chemoreceptor Trigger Zone (CRTZ) o Clenbuterol 2. Synthetic α-blocker o Metaproterenol ▪ Drugs: o Isohaline Phenoxybenzamine Example: Phentolamine o Salbutamol (binds with β2 receptor) Piperoxan → cAMP act as a messenger for activation Azapetine of the receptor Chlorpromazine → lowers phosphodiesterase Dibenamine (intracellular enzyme) that results to Tolazonine bronchodilation Dibozane o If it has high levels of phosphodiesterase, ▪ Clinical uses: it causes breakdown of cAMP Tx of peripheral vasospasm Aminophylline Tx of peripheral hypertension o Treatment of asthma along with the anti- Tx of peripheral pheochromocytoma asthma drug/s Tx of peripheral visceral ischemia o Causes lysis or inhibition of 3. Selective α1 blocker and α2 blocker phosphodiesterase ▪ Selective α1 blocker drug: Prazosin SYMPATHOLYTIC DRUGS ▪ Selective α2 blocker drugs: I. RECEPTOR-BLOCKING SYMPATHOLYTIC Yohimbine DRUG / ADRENERGIC-BLOCKING Rauwolscine (COMPETITIVE) ▪ Used to treat peripheral vasospasm Drugs that compete with norepinephrine for the same receptor β (Beta) blockers 2 types of blockers: α and β blockers 1. Non-selective blocker ▪ Dichloroisoproterenol α (Alpha) blockers ▪ Pronethalol 1. Ergot Alkaloids Produce thymic tumor (in mice) ▪ from fungus Claviceps purpurea ▪ Propranolol ▪ Has 2 types: 4 DVM3F 3rd Term  PHAR101A: DRUG ACTING ON THE AUTONOMIC N.S. Produces an active metabolite These drugs are used for hypertensive and ▪ Action of these drugs are almost the psychiatric disorder; mood same with alpha blocker, such as elevator/antidepressant constriction of blood vessels, action in the respiratory, action in the G.I. Tract but Miscellaneous Agents / Miscellaneous little action in the uterus Sympatholytic Drugs ▪ Action is in the eye/ocular 6-Hydroxydopamine ▪ Clinical uses: o Causes anatomic destruction of nerve Hypertension endings Angina (DOC: Propranolol) α-methyldopa Cardiac dysrhythmia (DOC: o Produces false-transmitter α- Propranolol) methylnorepinephrine Hypertrophic Obstructive α-methyl-para-tyrosine Cardiomyopathy o Inhibits rate-limiting enzyme tyrosine Hyperthyroidism: hydroxydopamine - High T3 and T4 Cocaine / Imipramine / - DOC: Propranolol Desmethylimipramine Anxiety-related tremors (DOC: o Inhibits neuronal amine uptake (tyramine) Propranolol) which take norepinephrine back into the Glaucoma nerve and potentiates its action - Eye problem due to excess fluid o Used as antidepressant inside the eyelid - Constriction of the pupil - As the fluid enters, constriction of the pupil will excrete the fluid Myocardial reinfarction - Infarct – death of tissue 2. Β1-selective blocker ▪ Metoprolol Use for insulin-dependent patient with heart disease without inhibition of lung airways II. NEURONAL-BLOCKING SYMPATHOLYTIC DRUG / ADRENOLYTIC (NON- COMPETITIVE) Causes breakdown of norepinephrine Drugs: o Reserpine o Guantethidine o Bretylium 5 DVM3F 3rd Term