Pharm block 1.txt

• � As pH increases, a weak base will become more and more unionized, lipid soluble and better absorbed
• � As pH decreases, a weak base will become more and more ionized, lipid insoluble, and will not be absorbed. Also becomes more water soluble and better excreted.
• � As pH increases, a weak acid will become more and more ionized , lipid insoluble and will not be absorbed. Also becomes more water soluble and better excreted .
• � As pH decreases, a weak acid will become more and more unionized , lipid soluble and better absorbed

• � For a weak acid, if pH � pKa is negative it will be more non-ionized and better absorbed
• � For a weak base if pH � pKa value is positive it will be more non-ionized and better absorbed

• Initial large bolus to create a rapid therapeutic dose.
• � Loading dose = Vd x Target Concentration/ bioavailability
• F= 100% if given IV

Dose given after Loading dose to maintain a therapeutic dose.Maintainance dose = clearance x target conc/ bioavailability

• They act by binding directly to cholinoceptors
• � Acetylcholine (not used � lots of Adverse reactions)
• � Bethanechol
• � Pilocarpine (naturally occurring alkaloid)

� It has strong Muscarinic action & no Nicotinic action� Actions� Directly stimulates M receptors causing increased intestinal motility & tone� It stimulates detrusor muscle of the bladder while trigone & sphincters are relaxed causing expulsion of urine� Therapeutic Uses:� Paralytic ileus � Urinary retentions

• Actions-
• When applied locally to cornea Produces rapid moisis & contraction of ciliary muscle, produces spasm and accommodation & vision is fixed at particular distance making it impossible to focus for far situated objects
• Therapeutic Use : In Glaucoma
• It opens trabecular meshwork around schlemm�s canal
• ? causes drainage of aqueous humor
• ? IOP immediately decreases.

� Cholinesterase inhibitors. Can be reversible or irreversible.

• � Ecothiopate
• � Malathion and Parathion (insecticides)
• � Sarin (war gas)

• � Neostigmine (Myasthenia gravis)
• � Physostigmine
• � Edrophonium (Tensilon test)
• � Tacrin (Alzheimer)
• � Danopezil (Alzheimer)

• ? Inhibits cholinesterase enzyme (reversible) --> Higher levels of Ach
• ? Neostigmine Has a strong influence at the neuromuscular junction
• ? Pyridostigmine: Has a longer duration of action than neostigmine
• ? Edrophonium: Diagnostic agent for myasthenia gravis and to diffrentiate myasthenic and cholinergic crisis (Tensilon test )

• � Progressive memory loss
• � ??? Decrease Ach
• � Tacrine
• � Side effect: HepatoToxicity
• � First drug to treat Alzheimer�s dementia
• � Given 4x a day (Q.I.D)
• � Donepezil
• � Has once-a-day dosing advantage (QD)

• � Only Irreversible Cholinesterase inhibitor used in clinical practice is Ecothipate, used in Glaucoma. Very long acting
• � Rest of the drugs are used as pesticides or war gases or poisons: Malathion/Parathion or Sarin

• � The dominant initial signs are those of muscarinic excess: miosis, salivation, sweating, bronchial constriction, vomiting, and diarrhea.
• � Tx: Atropine and Pralidoxime
• � Treatment of OP poisoning
• (1) maintenance of vital signs�respiration in particular may be impaired;
• (2) decontamination to prevent further absorption�this may require removal of all clothing and washing of the skin in cases of exposure to dusts and sprays; and
• (3) Atropine parenterally in large doses, given as often as required to control signs of muscarinic excess stimulation .
• (4)Therapy often also includes treatment with pralidoxime (Acetylcholinesterase reactivator)

• � Irreversible cholinesterate inhibitor.
• � LONG acting
• � Used in Glaucoma (closed angle)
• � Causes miosis of the eye --> increased drainage of aqueous humor

• � Can block Muscuranic Receptors
• � Can block Nicotinic Receptors
• � Uses of Atropine
• � Muscuranic Blocker
• � To produce mydriasis in refraction error testing (short acting preparations of atropine are preferred)
• � To treat Heart block, Bradycardia
• � To treat Cholinesterase inhibitors / Oragnaophosphate (OP)pesticides poisoning
• � Anti-Diarrheal agent

• � Scopolamine: sea sickness
• � Ipatropium: Asthma (M3 blocker)
• � Tropicamide: which acts for 4 hours is preferred to produce mydriasis and cycloplegia in refraction error testing and fundoscopy
• � Benztropine (drug of choice) for treatment of drug-induced Parkinsonism

• � There are 2 subtypes of Niotinic Receptors:
• � Nn and Nm
• � Nn is found in nerves, at the ganglion
• � Nm is found on muscles.
• � Nicotinic receptor blockers
• Ganglionic blocking drugs: Trimethaphen

• :� Nondepolarizing: D-tubocurarine , Atracurium
• � Depolarizing: Succinylcholine
• � Ganglionic blockers� Trimethaphen
• � Nn receptor antagonist. Blocks sympathetic and parasympathetic nervous system
• � Uses: Hypertensive Crsis�
• Side effects: Mixed loss of Sympathetic (hypotension) and
• Parasympathetic Nervous System (tachycardia, constipation, urinary rentention, dry mouth, etc�)
• � Neuromuscular blockers
• * Nm blockers blocks acetylcholine at the Nm receptor. Used in Surgery for skeletal muscle relaxation

• � Long acting: Tubocurarine (ADR: Nn blockage)
• � Intermediate acting: Atracuriun (safe in pts with renal insufficiency)
• � Short acting: Miyacurium

• Succinylcholine (shorting acting)*
• ADR: Succinyl apea* Malignant hyperthermia (tx by dantrolene)

• � Phenylephrine :
• � MOA: Alpha 1 receptor agonist
• � Very low Bioavailability
• � Causes vasoconstriction of vessels.
• � Nasal and ophthalmic preparations.
• � Uses:
• � Nasal Decongestant
• � Mydriasis (doesn�t cause cycloplegia)
• � Side effects/Contraindications: Closed angle Glaucoma. Rebound congestion.

• � At low concentrations: Stimulates D receptors, causes Vasodilation of
• arteries (renal, coronary, GI)� At intermediate doses: Stiumates Beta 1
• receptors --> tachycardia� At high doses: � stimuates alpha 1
• receptors ? Vasoconstriction� Uses: Cardiogenic shock (beta 1
• stimulation), CHF, Hypotension (alpha 1 stimulation)� Adverse effects:
• HTN, Tachycardia, arrythmias

• � Terbutaline � used in
• pre-term labor. Causes smooth muscle relaxation in the uterus.�
• Ritodrine � Also used in preterm labor� Albuterol, Salmeterol � Used in
• asthma. Causes tremers.

• � Alpha antagonists�
• Non-selective (phentalamine, phenoxybenzamine)
• � Alpha 1 selective (-sin,-cin)
• � Alpha 2 selective (Yohimbin)
• � Beta antagonist (-olol)� B1
• selective (ABEAM)
• � Non-selective (the rest)
• � Alpha + beta antagonists
• (labetolol)

� Uses: Pheochromocytoma� Non-competitive inhibitor

• � -Sin, -Cin� --> decrease in BP (not the DOC Of HTN)� --> inrease
• urinary flow (not the DOC of urinary rention)� Used in a patient if
• they have BOTH hypertension and urinary rentention (2ndary to BPH)

• � Cardioselective beta-blockers (ABEAM)
• � Decreases HR � used in treatment of HTN
• � Beta non-selective (Timolol)
• � Used topically for tx of Glaucoma
• � ADR:
• � Mask the sign of hypoglycemia (All beta blockers)
• � --> asthma (Beta non-selective blockers)

• Types of Glaucoma:
• 1. Open Angle Glaucoma � Excessive production of Aqueous Humour
• 2. Closed Angle Glaucoma � Outflow obstruction of Aqueous Humour
• Two Therapy aimed at:
• 1. Reduce (Production, Synthesis or Secretion)
• Acetazolamide, Timolol, and, Mannitol
• 2. Facilitate the drainage(drugs that causes miosis): Pilocarpine, Carbachol, Ecothiopate, and Mannitol

• � Goal is to reduce synthesis of the aqeuous humor
• � Carbonic Anhydrase Inhibitors: Mannitol Is also an osmotic agent that increases drainage
• Acetazolamide (oral), Dorzolamide (topical )
• � Reduces the secretion/synethesis:Timolol topical eye drops Non-selective beta
• blockade and Betaxolol eye drops Selective beta1 blockade

• Pilocarpine, Carbachol, Ecothiopate and Physostigmine :Causes Ciliary muscle contraction, increases Irido-corneal angle and open trabecular meshwork.
• � Mannitol: acts as an osmotic agent, attracting water, and increases drainage of aqueous humor
• � Prostaglandins : Latanoprost : increase the outflow through uveoscleral meshwork

• � Beta Agonists (albuterol, salmeterol)- ADR: Tremors
• � Cholinergic antagonists
• � Steroids (inhaled Beclomethasone or oral prednisone)- Oral Candida or Cushings
• � Xanthine derivatives (Theophylline): ADR: increased urination, cardiac/CNS toxicity
• � LT receptor blockers (Zafirlukast)
• � LT synthesis inhibitor - inhibits LOX enzyme - Zileuton
• � Mast cell stabilizers
• � Sodium cromoglicate