Cholinergic Antagonists PDF

Cholinergic Antagonists Atropine Anti muscarinic Derived from Belladona alkaloid Central and peripheral activity Actions Ophthalmic: mydriasis and cycloplegia GI system: antispasmodic Urinary system: enuresis CV: tachycardia Endocrine (secretory): xerostomia, xerophthalmia (dry mouth and eye) Therap...

Cholinergic Antagonists Atropine Anti muscarinic Derived from Belladona alkaloid Central and peripheral activity Actions Ophthalmic: mydriasis and cycloplegia GI system: antispasmodic Urinary system: enuresis CV: tachycardia Endocrine (secretory): xerostomia, xerophthalmia (dry mouth and eye) Therapeutic use Ophthalmic: cycloplegic refraction, uveitis Antispasmodic Antidote: organophosphate intoxication (insecticides) Atropine Therapeutic use - Ophthalmic: cycloplegic refraction, uveitis - Antispasmodic - Antidote: organophosphate intoxication (insecticides) Pharmacokinetics - Readily absorbed, partially metabolize in liver and eliminated in urine - t 1/2 life of 4 hrs Adverse effects dry mouth, blurred vision, tachycardia, constipation, confusion, hallucinations and delirium Scopolamine Belladona alkaloid with similar to atropine but action in CNS is longer Effective anti motion sickness/sedation Cycloplegic refraction, uveitis Ipratropium / Tiotropium Quaternary derivative of atropine used by inhalation for in asthma and COPD (decreases smooth muscle contraction of bronchi) Tropicamide (6hrs) and Cyclopentolate (24hrs) Ophthalmic solutions producing similar effects to atropine Benztropine Centrally acting antimuscarinic agent Employed as adjuvant Tx in Parkinson Disease Also used to minimized dystonia in Tx with anti-psychotic medications Darifenacin /Fesoterodine / Oxybutyin / Solifenacin / Tolterodine Synthetic atropine- like meds employed in Tx for overreactive bladder Increase capacity by lowering intravesical pressure Side effects: Dry mouth Constipation Diminished with regular use Blurred vision Cholinergic antagonists Side effects Blurred vision Confusion Mydriasis Constipation Ganglionic Blockers Act specifically on nicotinic receptors Non- selective for para- or sympathetic ganglia Ineffective as neuromuscular antagonist Block entire output of ANS Rarely used therapeutically Nicotine Depolarize Ganglia ANS and striated muscle Low dose increases BP HR Peristalsis Secretions High dose decrease BP and diminishes muscular activity Neurochemical Effects of Nicotine Ganglionic Blockers Trimethaphan Short acting competitive nicotinic ganglion blocker Use IV in emergency lowering of blood pressure (e.g. pulmonary edema) Mecamylamine Competitive nicotinic ganglion blocker One dose lasts up to 10 hrs Active orally Clinically useful for moderate to severe arterial hypertension Neuromuscular Blocking Drugs Block cholinergic transmission between nerve endings and nicotinic receptors at neuromuscular end-plate Non-depolarizing - compete with acetylcholine for receptors Depolarizing - cause prolonged stimulation and subsequent desensitization of the receptors Clinically useful during surgery producing complete muscle relaxation decreasing anesthetic doses Also used in mechanical ventilation Non-depolarizing (competitive) Blockers Curare (d-Tobocurarine,1st drug) Skeletal neuromuscular junction blocker Low dose - prevents binding of acetylcholine High dose - blocks Na+ ion channels of end plate Non-depolarizing (competitive) Blockers Curare (d-Tobocurarine,1st drug) Actions o Muscle paralysis Small muscles of face an eyes, fingers, limbs, neck and trunk muscles The last one affected is the diaphragm Therapeutic use - adjuvant in anesthesia Pharmacokinetics o used IV o as group do not cross readily blood brain barrier Non-depolarizing (competitive) Blockers Curare (d-Tobocurarine,1st drug) Benefits Decrease concentration of general anesthetic drugs by achieving adequate muscle relaxation ** Vecuronium Rocuronium - others Non-depolarizing (competitive) Blockers Drug interactions Cholinesterase inhibitors (neostigmine, etc.) Overcome depolarizing action at low dose Aminoglycosides (gentamycin or tobramycin) Inhibit acetylcholine release from neuromuscular junction – potentiates the effect of blockers Calcium channel blockers Increase neuromuscular block of tebocurarine and other competitive blockers Depolarizing Blockers Succinylcholine Attaches to nicotinic receptor acting like acetylcholine depolarizing the neuromuscular junction persisting in cleft at [higher] for longer time followed by an altered repolarization 2 phases Twitch/ flaccid paralysis during depolarization Desensitization during repolarization flaccid paralysis Depolarizing Blockers Succinylcholine Actions Paralyzing process similar as non depolarizing agents ending in respiratory muscles Therapeutic use Rapid endotracheal intubation during induction of anesthesia to avoid gastric aspiration Pharmacokinetics rapid onset of short duration (minutes) due to hydrolysis by plasma cholinesterase Administered by IV continuous infusion Depolarizing Blockers Succinylcholine Adverse Effects Hyperthermia In n conjunction with with halothane may cause malignant hyperthermia in genetically susceptible persons Apnea In genetically deficient patients of plasma cholinesterase Miscellaneous Muscle Relaxants Neural acting Benzodiazepines enhance or facilitate the action of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter Diazepam (Valium)* Use for muscle spasms Baclofen Binds to GABAB receptors Upon binding causes an influx of potassium into the neuron, leading to hyperpolarization of the neuronal membrane and decreased calcium influx at presynaptic nerve terminals Others Dantrolene directly inhibits Ca++ release from sarcoplasmic reticulum Orphenadrine Methyl derivative of diphenhydramine (a commonly used antihistamine), but its mechanism of action in causing analgesia and skeletal muscle relaxation