Pharmacology N225B: Review, Spring 2008Review, Spring 2008

UCLA School of NursingSophie Sokolow, PhD, MPHARM

Factor 6-266

Peripheral Nervous system

Anatomi para simpatis & simpatis

Peripheral nervous system

Somatic motor systemConscious control ofmovement, respiration, postureFunction:

Autonomic nervous systemInvoluntary control of visceral functions. Parasympathetic Sympathetic nervous systemsFunction:

Control Skeletal muscle via neuromuscular junction

Sympathetic nervous systems

3 principal functions:1. Regulate Heart 2. Regulate Secretory glands (salivary, gastric, sweat, bronchial)

3. Regulate Smooth muscles (bronchi, blood vessels, urogenital, GI)

Autonomous Nervous system

Anatomic considerations

Figure 13-3 The basic anatomy of the parasympathetic and sympathetic nervous systems and the somatic motor system.

Locations of cholinergic and adrenergic receptor subtypes

Figure 13-6

Neurotransmitters

Norepinephrine(NA,

adrenergic)

Practically all SNS post-

ganglionic neurons (except sweat

Acetylcholine (Ach,

cholinergic)

All PNS pre-ganglionic

neurons ganglionic neurons (except sweat

glands)

Epinephrine

Released from Adrenal

medulla

neurons

All PNS post-ganglionic

neurons

All SNS pre-ganglionic

neurons

Most SNS post-ganglionic

neurons to sweat glands

All motor neurons to skeletal

muscles

Parasympathetic (PNS)/ Sympathetic nervous (SNS) systems

PNS (Cholinergic)7 functions1. HR 2.gastric secretion

SNS (Adrenergic)3 functions1. Regulating cardiovascular system 2.gastric secretion

3.Emptying of bladder4.Emptying of bowel5.Focusing for near vision6.Constriction pupils (miosis)

7.Bronchoconstriction

system 2. Regulating body temperature3. Implementing fight-or-flight reaction

HR and BPDilate pupils (mydriasis)Dilate bronchiMobilize stored energy

SNS vs. PNS functions

CholinergicAdrenergic

Cholinergic drugs

Direct cholinomimetics

Cholinergic Receptor subtypes

Muscarinic receptors CNS PNS postganglionic endings

Sweat glands

Nicotinic receptors CNS Autonomic ganglia Neuromuscular junction Adrenal medulla Sweat glands Adrenal medulla

Cholinergic Drugs: direct cholinomimetics

MOA: enhance transmission at cholinergic synapsesDrugs:Acetylcholine limited because of short duration ofactionMuscarinic agonistsMuscarinic agonists1.Muscarine: mushroom alkaloid used to discoversubtypes

2.Bethanechol (Urecholine) Treatment of urinary retention Also increases GI motility

3.Pilocarpine Glaucoma

Nicotine

Natural liquid alkaloidMOA: Stimulates nicotinic receptors CNS and CV effectsDrugs:

Varenicline (Chantix):Varenicline (Chantix): Nicotinic partial agonist for smoking cessation

Cholinergic Drugs

Cholinesterases Inhibitors

Anticholinesterase drugs Indirect acting cholinomimetics

MOA: inhibit the enzyme that degrades acetylcholineDrugs and Clinical uses:Reversible agents

Edrophonium (Tensilon)

Myasthenia Gravis

Donepezil (Aricept), Tacrine (Cognex)

Alzheimers disease

Irreversible agentsEchothiophate (phospholine iodide)

GlaucomaMalathion, sarin (nerve gas, no clinical use)

Anti-Cholinergic Drugs

Muscarinic Antagonists

Anti-cholinergic drugs: Muscarinic Antagonists

Agents:Atropine

Clinical uses: Motion sickness

MOA: Block muscarinic receptors

AtropineScopolamine Ipratropium bromidePropantheline Trihexyphenidyl Benztropine...

Motion sicknessAsthmaIncontinence (OAB)AntispasmodicBradyarrhythmiasAnti-parkinsonPreoperativeOpthalmology

Overactive Bladder (OAB) Therapy

Anti-muscarinic agents:Nonselective (block M2 and M3 receptors)Tolterodine (Detrol); older

M3 selective (block M3 receptors, most M3selective)selective)Oxybutynin (Ditropan)Solifenacin (Vesicare)Darifenacin (Enablex)

Anti-Cholinergic Drugs

Neuromuscular blocking agents

Neuromuscular blocking agents

MOA:Block nicotinic receptors at neuromuscular junctionNo CNS effects!Drugs and Clinical uses:Relaxation for surgical procedures, intubationRelaxation for surgical procedures, intubationNon-depolarizing:

Tubocurarine, pancuronium bromide (Pavulon),vecuronium, cisatracurium

Rapid hydrolysis by AChE; NM block lasts 5-10 min

Depolarizing (persistent depolarization makes themuscle fiber resistant to further stimulation byACh)

Succinylcholine (Anectine)

Botulinum toxin

Produced by Clostridium botulinumMOA:Act pre-synaptically inhibit ACh release at the NMJ cause temporary local paralysis of injected muscleEffects last weeks to several monthsEffects last weeks to several monthsClinical Use:FDA Approved for limited disorders (i.e. strabismus, severe primary axillary hyperhidrosis, cervical dystonia)

Worlwide 21 indications are approved for BotoxUnder FDA investigations for several disorders:

Chronic migraineLimb Muscle pain, Back painOAB, etc.

Cosmetic use: treat frown lines between the brows

Adrenergic Agonists

Beta1Heart

Heart rate Force of contraction Velocity of conduction in

Main Functions of Adrenergic Receptor Subtypes

Alpha1Vasoconstriction

Alpha2Located in presynaptic junction Velocity of conduction in

AV nodeKidney

Renin release

Beta2Bronchial dilationRelaxation of uterine muscleVasodilationGlycogenolysis

junctionMinimal clinical significance

DopamineDilates renal blood vessels

Sympathomimetic drugs: catecholamines

1.Epinephrine1 cardiac stimulation2 bronchodilation constriction of arterioles

2.Isoproterenol (-selective)

1 cardiac stimulation

2 bronchodilation

2.DobutaminearteriolesClinical Use: Acute hypersensitivity reactions

Cardiac stimulant

2.Dobutamine1 cardiac stimulation(some 1)

Clinical Use: Increase contractility and cardiacoutput in hypotension and surgery

Sympathomimetic drugs: catecholamines (cont)

4.Norepinephrine(Levophed)

vasoconstriction1 cardiac stimulation

5.Dopamine

MOA:Stimulates dopamine receptors

1 cardiac stimulation

Clinical Use:Hypotension

Stimulates dopamine receptors vasodilation of renal and mesenteric arteries

Clinical Use:Hypotension and shock

Sympathomimetic drugs: Non-Catecholamines

1.1.1.1. 2 selective agonists Terbutaline (Brethine) Albuterol (Proventil, Ventolin)

Ritodrine

2.2.2.2. 1 selective agonists Phenylephrine

3.3.3.3. 2 selective agonists Clonidine (Catapres)

Ritodrine

4.Miscellaneous adrenergic agonists Amphetamine, Methylphenidate Ephedrine Phenylpropanolamine Cocaine

Adrenergic Antagonists

Adrenergic Receptor Antagonists1 selective antagonists

Drugs and Clinical uses:HypertensionPrazosin (Minipres)Doxazosin (Cardura)Terazosin (Hytrin)

Non selective antagonistsDrugs and Clinical uses: Pheochromocytoma

PhenoxybenzamineTerazosin (Hytrin)

Benign Prostatic Hypertrophy (BPH)Tamsulosin (Flomax)selective for prostate smoothmuscle vs. vascular smooth muscle

Other agent used in BPH therapy:Finasteride (Propecia): has different MOA blocks 5- reductase blocks conversion of testosterone to dihydroxytestosterone

PhenoxybenzaminePhentolamine

Adrenergic Receptor -Antagonists: : : : -blockers

Nonselective 1 and 2Propranolol (Inderal)Nadolol (Corgard)

Selective 1(cardioselective)

Partial agonistsBlockers with intrinsic sympathomimetic activity (ISA)PindololAcebutolol: depress heart rate

(cardioselective)Metoprolol (Lopressor) Atenolol (Tenormin)

GlaucomaTimolol (timoptic)Carteolol (occupress) oral or drops

Acebutolol: depress heart rateless than other -blockers

Nonselective -blockade with blockadeLower BP without alterations in heart rate or cardiac outputLabetololCarvedilol

Adrenergic Receptor -Antagonists

3.3.3.3. antagonists (-blockers)

Clinical uses: Hypertension Angina Myocardial Infarction (MI) Myocardial Infarction (MI) Cardiac Heart Failure (CHF) Antiarrhythmics Migraine Pheochromocytoma Glaucoma

Respiratory Pharmacology

Drugs used in the treatment of COPD

1. Bronchodilators short acting (as initial agents):a)Anti-cholinergics (ipratropium bromide), 1st linebronchodilatator alone or in combination with b.

b)2-agonists (albuterol),

2. Bronchodilators long acting (are added to 1.) :a) -agonists (salmoterol, formoterol),a) 2-agonists (salmoterol, formoterol),b)Anti-cholinergics (tiotropium bromide)c) Theophylline

3. Corticosteroids ( of acute COPDexacerbations or chronically in severe patients):a)Oral (prednisone, prednisolone)b)Inhaled (fluticasone, beclomethasone, budesoinde), lessprominent role than in asthma

4. Others (antibiotics, mucolytics, expectorants)