Cholinergic Drugs (direct acting) Part-2

(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 intraoccular pressure in the treatment of glaucoma.

(iii) Adverse effects :

• Few adverse effects occur with opthalmologic use, due to lack of systemic penetration.

• Side effects include accomodation spasm, pupillary constriction, headache, conjuctival hypermia.

(4) PILOCARPINE

• Alkaloid pilocarpine is tertiary amine and is stable to hydrolysis by AChEsterase.

• When campared with ACh and its derivatives, it is far less potent but it is unchanged and can penetrates the CNS at therapeutic doses.

• Pilocarpine exhibit muscarinic activity & is primarily used in opthalmology.

(i) Actions :

• Pilocarpine produce rapid miosis, contraction of ciliary muscle and spasm of accomodation.

• Pilocarpine is most potent stimulators of secerations such as sweat, tears, amd saliva.

(ii) Therapeutic uses:

• Pilocarpine is used for the treatment of glaucoma and is drug of choice for emergency lowering in intraoccular pressure in both open angle and closure angle glaucoma.

• Pilocarpine is extremely effective in opening in Trabecular meshwork around the Schelem canal, cause an immediate drop in intraoccular pressure(IOP) because of increase drainage of aqeous humor. This action occurs wiyhin few minutes and last for 4-8 hours.

• The topical carbonic anhydrase inhibitors, such as : dorzolamide and B-adrenergic blockers are effective in treating glaucoma but are not used for emergency lowering of IOP.

• The miotic action of Pilocarpine is also useful in reversing mydriasis due to atropine.

• This drug is useful in promoting salivation in patients with Xerostomia (Dry mouth resulting from reduced or absence of saliva flow & it also occurs due to irridation of head&Neck).

• Sjögren syndrome, which is characterized by dry mouth and lack of tears, is treated with oral pilocarpine tablets.

(iii) Adverse effects:

• Pilocarpine can cause :

-Blurred Vision

- Night blindness

- Brow Ache (Pain behind or around the eye brow)

• Poisonong with Pilocarpine is characterized by: profuse sweating(diaphoresis) and salivation.

• Parental atropine, at doses that can cross the blood-brain barrier , is administered to counteract the toxicity of pilocarpine.

Comments

Cholinergic neuron & Cholinergic Receptors

•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

Mechanism of absorption of Drugs

Absorption of Drugs • Absorption concerns the process of entry of drug in to systemic circulation from site of administration. •The rate and extent of absorption depend on: -the environment where the drug is absorbed -chemical characteristics of drug -route of administration (which influence bioavailability) • The route of administration other than intravenous may result in partial absorption and lower bioavailability. (A) Mechanism of absorption of drug from GIT • Depending upon their chemical properties , drugs may be absorbed from GI tract by passive diffusion, facilitated diffusion, active transport or endocytosis. (1) Passive diffusion : • In this drug move from area of high concentration to area of lower concentration. - also known as non-ionic diffusion - The driving force for this process is concentration or electrochemical gradient. - P.D does not require carrier, is not saturable, and shows low structural specifity. - The

Autonomic Nervous System Anatomy and Physiology

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

AGONIST & ANTAGONIST with types

AGONIST • Agonist is a chemical(drug) that binds to the receptor and activates the receptor to produce biological response. OR • Agonist is a drug that produce effects on endogenous compounds, when it interacts with it’s receptor. => Agonists are of following types: (1) Full agonists (2) Partial agonists (3) Inverse agonists (1) Full Agonists • If a drug binds to a receptor and produce maximal biological response that mimics the response to endogenous ligand is called full agonist. - All full agonists for a receptor population should produce the same E max. For Example : phenylephrine is a full agonist at alpha1-adrenoceptors, because it produce the same E max as the endogenous ligand, norepinephrine. Upon binding with aplha1-adrenoceptors on vascular smooth muscle, both phenylephrine and norepinephrine stablize the receptor in its active state, thereby increasing the Gq activation. Activation of Gq i

Elimination of the Drug

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

PHARMACODYNAMICS & Drug Receptor Interaction

>Pharmacodynamics deals with the biochemical and physiological effect of drug as well as its mechanism of action. OR We can simply define it as, The action of drug on the body. •Most drug exert effects, both beneficial and harmful, by interacting with specialized target macromollecule called receptor. Receptor : it refers to the drug binding site in the cell or on the surface of cell which mediate the action of drug. • There are some drugs which do not require receptors Example = mannitol , anti-helmintic drugs, etc. NATURE OF DRUG RECEPTOR 1. Regulatory protein which mediates the action of endogenous chemical signals. For example : neurotransmitters , harmones and autocoids. 2. Enzymes. For example : dihydrofolic reductase 3. Transport protein. For example : sodium / potassium ATPase pump. 4. Structural protein. For example : tubulin. RECEPTOR REGULATION •Down Regulation : when receptors becom

Drug clearance & Half Life & Dose

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

Basic Introduction to Pharmacology for beginners

Introduction Pharamcology is the branch of medicine which deals with study of drugs, it’s effect on body(p harmacodynamics ) and action of body on drug ( pharamcokinetics ). OR Pharmacology is the study of substance that interact with living system through chemical process, by binding to regulatory mollecules & activating or inhibiting normal body processes. Branches of Pharamcology 1> Pharmacotherapeutics - Also know as Medical Pharamcology. - It is science of material used to diagnose, prevent amd treatment of disease. - It is divided in to 2 branches : Pharamacodynamics and pharmacokinetics (i) Pharmacokinetics = It deals with the absorption, distribution, bioatranformation and excreation of drugs and it’s metabolities from the body. (ii) Pharmacodynamics = It deals with the biochemical and physiological effect of drug as well as its mechanism of action. 2> Toxicology -It d

Distribution of Drug in simplest way Pharmacology

DRUG DISTRIBUTION • Drug distribution is the process by which the drug reversibly leaves the blood stream and enters the extracellular fluid and tissues. - For drugs administered IV, absorption is not a factor and the initial phase immediately following administration represents distribution phase. - The distribution of the drug from plasma to interstitium depends upon : (i) cardiac output & local blood flow (ii) capillary permeability (iii) degree of binding of drug to plasma & tissue protein (iv) lipophilicity of drug (v) Volume of distribution (1) Blood flow : • The rate of blood flow to the tissue capillaries varies widely. For instance, blood flow to vessel rich organs (like : brain, liver & kidney) is greater than skeletal muscles, adipose tissues, skin which have lower rates of blood flow. -For example: High blood flow together with high lipophilicity of propofol , permits rapid distribution into the CNS and produce

Search This Blog