(3) CARBACHOL (Carbamylcholine )   • Carbachol is is an ester of carbamic acid and poor substrate for AChEsterase. It is biotransformed by other esters at very slow rate.    • Carbachol has both Muscarinic and Nicotinic actions. Functions   (i) Actions :    • Carbachol has profound effects on both Cardiovascular system and GI system.    • It has ganglion stimulating activity and it may first stimulate and then depress these systems.    • It can cause release of epinephrine from adrenal medulla by its nicotinic functions.   On Eye :     • It cause miosis    • It cause spasm of accomodatiom in which the ciliary muscle of the eye remains in a constant state of contraction.    • Carbachol is also used to stimulate micturation by contraction of detrusor muscle. (ii) Therapeutic uses :     • Carbachol has high potency, receptor non-selectivity and relatively long duration of action.     • Carbachol is rarely used.     • Carbachol administered ocularly to induce miosis to reduce the intr

Cholinergic Agonists (direct acting)  • Cholinergic agonists mimic the effect of acetylcholine by binding directly to cholinoceptors (muscarinic & nicotinic).   • These agents are classified into 2 groups;     (1) Choline esters : it includes endogenous ACh and synthetic esters of choline. Such as Carbachol & Bethanechol .     (2) Naturally occuring Alkaloids : Nicotine & Pilocarpine .    • All direct-actings Cholinergic drugs have longer duration of action than Acetylcholine.    (1) ACETYLCHOLINE   • ACh is the quaternary ammonium compound that cannot penetrates membranes.    • It is nuerotransmitter of parasympathetic, somatic nerves & autonomic ganglia.    • It lacks the therapeutics importance b/c of multiple actions and its rapid inactivation by the cholinesterases.    • ACh has both muscarinic and nicotinic activity.    Functions :     (a) Decrease in heart rate and cardiac output :      • ACh mimics the effects of vagal stimulation on the heart.      • If in

 •Drugs affecting the autonomic nervous system(ANS) are divided into two groups according to the type of neuron involved in mechanism of action.    •The cholinergic drugs, which act on receptors activated by acetylcholine(Ach), Where as adrenergic drugs act on receptors stimulated by epinephrine or norepinephrine.    •The cholinergic drugs act by either stimulating or blocking the receptors of the ANS.  The cholinergic neuron   • The preganglionic fibres terminating in adrenal medulla.    • The postganglionic fibres of parasympathetic division use ACh as a neurotransmitter.  The postganglionic sumpayhetic division of sweat glands also uses ACh.    • Ina ddition, cholinergicneurons innervate the muscles of somatic system and play an important role in CNS.  NEUROTRANSMISSION @ CHOLINERGIC NEURON :   • Neurotransmission at cholinergic neurons involves 6 sequential steps :   (1) Synthesis of ACh   (2) Storage of ACh    (3) Release of ACh   (4) Binding of ACh to the receptor   (5) Degradati

           The Autonomic       Nervous System   • The Autonomic Nervous System(ANS) along with endocrine system coordinates  the regulation amd integeration of body functions.    •The ANS largerly independent (autonomous) in that its activities are not under direct conscious control. It is concenred primarily with visceral functions such as cardiac output, blood flow to various organs and digestions, which is necessary for life.    • Drugs that produce their primary therpeutic effect by mimicking or altering the functions of ANS are called autonomic drugs.    - The autonomic agents act either by stimulating portion of ANS or by blocking the action of autonomic nerves .    Nervous System overview :    • The N.S is divided into 2 anatomical divisions : The Central Nervous System which is composed of brain & spinal cord and the Peripheral Nervous System .    • Peripheral nervous system includes neurons which located outside the brain and spinal cord.    • The peripheral nervous syste

Drug Clearance It refers to the ratio of rate of drug elimination to the concentration of drug in biological fluid(C).                       CL = rate of elimination / C Rate of elimination   • For most of the drugs, elimination is not saturable & rate of drug elimination is directly proportional to concentration.                     Rate of elimination = CL x C ==> The difference between drug clearance and drug elimination is that :     • Clearance is Volume of blood cleared of drug per unit time and Elimination is amount of drug cleared from blood per unit time.  Total Body Clearance   • The total body systemic clearance , CLtotal is the sum of all clearances from drug metabolising and drug eliminating organs.                                         OR   • Dividing the rate of elimination at each organ by concentration of drug presented to it yeilds respective clearance at that organ and sum of these is total body clearance.                CLx = rate of elimination x / C      

          Drug Elimination   • Drugs must be sufficiently polar to be eliminated from the body.  • Removal of drugs from body occur via number of routes; the most important is elimination through kidney in to urine.  Renal Elimination of Drug • A drug passes through several process in the kidney before elimination, Glomerular filtration, tubular seceration , and passive tubular reabsorption.     (1) Glomerular filteration :   • Drugs enter the kidney through renal artries, which divide to form a glomerular capillary plexus. Free drug (not bound to albumin) flows through the capillary bed into bowman’s space as a part of glomerular filterate.    > Glomerular filteration rate is normally about 120mL/min. But may decrease sugnificantly in renal disease.       > pH and lipid solubility do not influence the passage of drugs into glomerular filterate.      > Variation in GFR and protein binding to drugs donot affect this process.    > water and polar compounds easily enter in gl

   Q1: Pharmacokinetics include which of the following?           (a) Drug biotranformation in the organism           (b) Influence of drugs of genes           (c) Complications of drug therapy           (d) Influence of drug on metabolism procss    Answer ~ A Q2: Pharmacokinetics include :            (a) Interaction of substances           (b) Localization of drug action           (c) Mechanism of drug action           (d) Excreation of substances     Answer ~ D Q3: Pharmacokinetics include :             (a) Unwanted effects of drugs           (b) Pharmacological effects of drugs           (c) Distribution of the drug in the organisms           (d) Chemical structure of medical agent    Answer ~ C Q4: Which kind of substances can not cross membrane by passive diffusion ?           (a) Hydrophobic substances           (b) Hydrophilic substances           (c) Non-ionized substances           (d) Lipid soluble     Answer ~ B Q5: Pharamcokinetics parameter that reflects the effects of var