Autonomic nervous system

Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Pharmacology of Drugs AffectingPharmacology of Drugs AffectingAutonomic Nervous SystemAutonomic Nervous System


Basic Functions of the Basic Functions of the Nervous SystemNervous System

Recognizing changes inRecognizing changes in Internal environmentInternal environment External environmentExternal environment

Processing and integrating environmental Processing and integrating environmental changeschanges

Reacting to environmental changes by Reacting to environmental changes by producing an action or response producing an action or response


Two Major Divisions of the Two Major Divisions of the Nervous SystemNervous System

Central Nervous System (CNS)Central Nervous System (CNS) Brain and spinal cordBrain and spinal cord

Peripheral Nervous SystemPeripheral Nervous System all nervous tissues outside the CNS, including all nervous tissues outside the CNS, including

sensory and motor neuronssensory and motor neurons


Divisions of human nervous Divisions of human nervous systemsystem


Brain &

Spinal Cord

Nerves enter or leave

CNS

Carry massage from CNS to

peripheral tissues

Carry massage from

peripheral tissues to CNS


Divisions of the Peripheral Divisions of the Peripheral Nervous SystemNervous System

Somatic nervous systemSomatic nervous system Voluntary control over skeletal musclesVoluntary control over skeletal muscles

Autonomic nervous systemAutonomic nervous system Involuntary control over smooth and cardiac Involuntary control over smooth and cardiac

muscle and glandsmuscle and glands


Basic anatomy of ANS

Sympathetic NS Parasympathetic NS Enteric NS

Two main differences- Origin

- Function

-Collection of nerve fibers that innervate GIT, pancrease & gall bladder-Called “brain of gut”-They control motility, exocrine & endocrine secretion, as well asmicrocirculation of gut -Modulated by sympathatic & Parasympathatic systems


Autonomic PharmacologyAutonomic Pharmacology

Autonomic Nervous SystemAutonomic Nervous System This system is divided into two separate This system is divided into two separate

systems.systems. These systems are called the parasympathetic These systems are called the parasympathetic

nervous system and the sympathetic nervous nervous system and the sympathetic nervous system.system.

These systems often produce opposite effects, These systems often produce opposite effects, but bbut branches do not always produce opposite effects.ranches do not always produce opposite effects.

Homeostasis – proper balance of the two Homeostasis – proper balance of the two branches achieved by changing one or both branches achieved by changing one or both branchesbranches

2


Autonomic Nervous System: Sympathetic and Autonomic Nervous System: Sympathetic and Parasympathetic DivisionsParasympathetic Divisions

Drugs in this group are designed to either enhance or Drugs in this group are designed to either enhance or mimic the autonomic nervous system or to block the mimic the autonomic nervous system or to block the effects of the neurotransmitters at their receptor sites.effects of the neurotransmitters at their receptor sites.



Steps of NeurotransmissionSteps of Neurotransmission

Propagation of the nerve impulse in Propagation of the nerve impulse in the preganglionic nerve fiberthe preganglionic nerve fiber

+ + + + + + + + + + +- - - - - - - - - - - - - - --- - - - - - - - - - - - - -+ + + + + + + + + +

PolarizedResting Membrane Potential

+ + + + - - - - + + + - - - - - + + + + - - - - - - - - - + + + + - - - -

+ + + - - - - + +

DepolarizedNerve Action Potential




Synaptic Transmission Synaptic Transmission

Synapse – junction of neuronsSynapse – junction of neurons Connection of two neurons outside CNS – Connection of two neurons outside CNS –

ganglionic synapse.ganglionic synapse.




Efferent neuronsEfferent neurons

Preganglionic neurons: Preganglionic neurons:

Cell body within CNSCell body within CNS Ganglia: aggregation of nerve cell bodies Ganglia: aggregation of nerve cell bodies

located in the peripheral nervous system.located in the peripheral nervous system. Postganglionic neurons: cell body originate in Postganglionic neurons: cell body originate in

the ganglia, terminates on effector organ.the ganglia, terminates on effector organ. Divided into sympathatic and Divided into sympathatic and

parasympathaticparasympathatic


Origin

Symp. NSThoracolumbar

outflow

Parasymp. NS

Function

Craniosacral outflow

Short pre-ganglionic nerveLong post-ganglionic nerve

Long pre-ganglionic nerveShort post-ganglionic nerve


Figure 13.4 Figure 13.4 Receptors in the autonomic nervous system: (a) sympathetic division; (b) parasympathetic divisionReceptors in the autonomic nervous system: (a) sympathetic division; (b) parasympathetic division


Role of CNS in autonomic control Role of CNS in autonomic control functionsfunctions

CNS centers in hypothalamus, CNS centers in hypothalamus, medulla oblongata & spinal medulla oblongata & spinal

cordcord Reflex arcReflex arc EmotionsEmotions



Organs Supplied by ANSOrgans Supplied by ANS

HeartHeart Smooth MusclesSmooth Muscles

- Eye Eye -Bronchi-Bronchi- GIT GIT - Urinary Bladder- Urinary Bladder- Blood VesselsBlood Vessels

GlandsGlands- Exocrine Glands: Lacrymal, Salivary, SweatExocrine Glands: Lacrymal, Salivary, Sweat- Endocrine Glands: Adrenal MedullaEndocrine Glands: Adrenal Medulla

MetabolismMetabolism LiverLiver Adipose TissueAdipose Tissue KidneyKidney


Sympathetic Nervous SystemSympathetic Nervous System

Sympathetic Nervous SystemSympathetic Nervous System This nervous system is designed to This nervous system is designed to

cope with emergency situations. cope with emergency situations. This is commonly known as the “fright or This is commonly known as the “fright or

flight” response.flight” response. Its neurotransmitters are epinephrine Its neurotransmitters are epinephrine

and norepinephrine.and norepinephrine. Its receptors are the Its receptors are the αα and and ββ receptors. receptors.

4


Sympathetic nervous systemSympathetic nervous system

Fight or flight response results in:Fight or flight response results in:

1.1. Increased BPIncreased BP

2.2. Increased blood flow to brain, heart and Increased blood flow to brain, heart and skeletal musclesskeletal muscles

3.3. Increased muscle glycogen breakdown for Increased muscle glycogen breakdown for energyenergy

4.4. Increased rate of coagulationIncreased rate of coagulation

5.5. Pupil dilationPupil dilation

parasympathatic Nervous parasympathatic Nervous SystemSystem

Parasympathetic Nervous SystemParasympathetic Nervous System This system is concerned with the This system is concerned with the

conservation of the body processes.conservation of the body processes. Activated under non stressful conditionsActivated under non stressful conditions Rest-and-digest responseRest-and-digest response Digestive processes promoted, heart rate Digestive processes promoted, heart rate

and blood pressure declineand blood pressure decline Its main neurotransmitter is Its main neurotransmitter is

acetylcholine.acetylcholine. Its receptors are muscarinic, nicotinic.Its receptors are muscarinic, nicotinic.

3


Figure 13.2 Effects of the sympathetic and parasympathetic nervous systems. Figure 13.2 Effects of the sympathetic and parasympathetic nervous systems. Source: Biology Guide to the Natural Source: Biology Guide to the Natural World, 2World, 2ndnd ed (p. 558) by David Krogh, 2002 Upper Saddle River, NJ, Prentice Hall. Reprinted by permission. ed (p. 558) by David Krogh, 2002 Upper Saddle River, NJ, Prentice Hall. Reprinted by permission.


Symp. NS

Parasymp. NS

SingleInnervations

Dilator pupilae muscleAdrenal Medulla

VentriclesBV

Sweat GlandKidney

Constrictor pupillae muscle

Figure 13.1 Functional divisions of the peripheral nervous system. Figure 13.1 Functional divisions of the peripheral nervous system.


Primary Neurotransmitters of Primary Neurotransmitters of Autonomic Nervous SystemAutonomic Nervous System

Norepinephrine (NE)…………..adrenergic Norepinephrine (NE)…………..adrenergic neurotransmission neurotransmission

Acetylcholine (Ach)…………….cholinergic Acetylcholine (Ach)…………….cholinergic neurotransmissionneurotransmission


AcetylcholineAcetylcholine

Released byReleased by

1.1. All preganglionic nerve fibersAll preganglionic nerve fibers

2.2. Preganglionic sympathatic nerves to adrenal Preganglionic sympathatic nerves to adrenal medullamedulla

3.3. All postganglionic parasympathatic nervesAll postganglionic parasympathatic nerves

4.4. Postganglionic sympathatic nerve to sweat Postganglionic sympathatic nerve to sweat glandsglands

5.5. All somatic nerves.All somatic nerves.

6.6. CNS CNS



Cholinergic Transmission (Cont.)Cholinergic Transmission (Cont.)


Rate l imit ing step

ATP & proteoglycan



Cholinergic Receptors

Muscarinic Receptors(Peripheral Cholinergic )

Nicotinic Receptors(Central Cholinergic) R.)

Strong affinity to muscarineWeak affinity to nicotine

Weak affinity to muscarineStrong affinity to nicotine

-Parasympathetic supplying effector organs-Sweat gland- CNS

-Autonomic ganglia (Nn)- Adrenal Medulla (Nn)- Neuromuscular junction (Nm)-CNS (Nn)


Nicotinic receptorsNicotinic receptors Composed of 5-subunits and functions as ligand-gated channelComposed of 5-subunits and functions as ligand-gated channel

Binding of two Ach molecules elicits a conformational change that Binding of two Ach molecules elicits a conformational change that allows the entry of sodium ions, resulting in depolarization of the allows the entry of sodium ions, resulting in depolarization of the

effector celleffector cell

Nm (blocked by tubocurarine) differs from Nn (blocked by Nm (blocked by tubocurarine) differs from Nn (blocked by hexomethonium)hexomethonium)


Muscarinic Receptors

M1 (Neural) M2 (Cardiac) M3 (Glandular)

- CNS- Gastric parietal cells

-CNS Presynaptically- Atria and conducting tissue

-Exocrine glands-Smooth muscles-Vascular endothelium

↑ Phospholipase C

Atropine & Pirenzepine

↓ Adenylate cyclase

Atropine & Gallamine

↑ Phospholipase C

Atropine


Sympathatic neurotransmissionSympathatic neurotransmission

Norepinephrine is released by most Norepinephrine is released by most postganglionic sympathatic nervespostganglionic sympathatic nerves

Dopamine is released by postganglionic Dopamine is released by postganglionic nerves stimulating the kidney.nerves stimulating the kidney.

ACH is released by Postganglionic ACH is released by Postganglionic sympathatic nerve to sweat glandssympathatic nerve to sweat glands

Adrenal medulla acts as ganglia releasing Adrenal medulla acts as ganglia releasing epinephrine and NE.epinephrine and NE.


Adrenergic TransmissionAdrenergic Transmission

Neurotransmitter:Neurotransmitter: Two catecholamines NA Two catecholamines NA & Ad& Ad

Sites of Release:Sites of Release:- Post ganglionic sympathetic nerve ending (80% NA & Post ganglionic sympathetic nerve ending (80% NA &

20% Ad)20% Ad)- Adrenal Medulla (80% Ad & 20% NA)Adrenal Medulla (80% Ad & 20% NA)- CNSCNS





Adrenergic receptorsAdrenergic receptors

αα——αα1 and 1 and αα22 ββ——ββ1, 1, ββ2, 2, ββ33 Dopamine—subsets D1-5Dopamine—subsets D1-5


Adrenergic Receptors

α Subtype β Subtype

↑ Phospholipase C ↓ Adenylate cyclase

α1 α2 β1, β2 & β3

↑ Adenylate cyclase

smooth muscles- Presynaptic adrenergic

nerve terminal-CNS

-β cells of pancreas

β1 (heart)β2 (smooth muscles)β3 (lipocytes)


β Subtype


α Subtype



αα1-adrenergic Receptors1-adrenergic Receptors

In all sympathetic target organs except heartIn all sympathetic target organs except heart ResponseResponse

Constriction of blood vesselsConstriction of blood vessels Dilation of pupilsDilation of pupils Constriction of sphinctersConstriction of sphincters


αα2-adrenergic Receptors2-adrenergic Receptors

At presynaptic adrenergic neuron terminalsAt presynaptic adrenergic neuron terminals Activation inhibits release of norepinephrineActivation inhibits release of norepinephrine Inhibits release of insulinInhibits release of insulin


ββ1-adrenergic Receptors1-adrenergic Receptors

In heart and kidneysIn heart and kidneys ResponseResponse

Activation increases heart rate and force of Activation increases heart rate and force of contraction of heart.contraction of heart.

Increases release of reninIncreases release of renin


ββ2-adrenergic Receptors2-adrenergic Receptors

In all sympathetic target organs except the In all sympathetic target organs except the heartheart

Inhibit smooth muscle (relaxes)Inhibit smooth muscle (relaxes) Stimulates glycogenolysis and Stimulates glycogenolysis and

gluconeogenesisgluconeogenesis




Organ Sympathetic R Parasympathetic R

Heart Stimulant β1 Depressant of atria M2

Smooth Musclesa- BV Constriction

Dilation(BV Sk. M.)

Kidney Vasculature

αβ2

D

No innervation(dilation by EDRF)

M3

b- Bronchi No innervation β2 Constriction↑ Secretion

M3M3

c- GITSmooth muscleSphincterGlands

↓ motilityConstriction

-----

β2α1

↑ motilityDilation

↑ Secretion↑Gastric acid

Enteric system

M3M3M3M1M1

d- Urinary BladderSmooth muscleSphincter

RelaxationConstriction

β2α1

ContractionDilation

M3M3


Organ Sympathetic R Parasympathetic R

e- Eye: * Iris-Radial muscle-Circular muscle *Ciliary Muscle

Contraction

Relaxation (slight)

α1

β2ConstrictionContraction

M3M3

Glands:Salivary GlandsLacrimal GlandsSweat Glands:ThermoregulatoryApocrine (stress)

↑ SecretionNo effect

↑ Secretion↑ Secretion

α1, β2--------

M3α1

↑ Secretion↑ Secretion

M3M3

Metabolic Functions:Liver

Adipose tissueKidney

GluconeogenesisGlycogenolysisLipolysisRenin release

β2β2β3β1



Five Mechanisms by Which Five Mechanisms by Which Drugs Can Affect Synaptic Drugs Can Affect Synaptic

TransmissionTransmission

1.1. Affect the synthesis of the neurotransmitter Affect the synthesis of the neurotransmitter in the presynaptic nerve.in the presynaptic nerve.

2.2. Prevent storage of the neurotransmitter in Prevent storage of the neurotransmitter in vesicles within the presynaptic nerve.vesicles within the presynaptic nerve.

3.3. Influence release of the neurotransmitter Influence release of the neurotransmitter from the presynaptic nerve.from the presynaptic nerve.


Five Mechanisms by Which Drugs Can Five Mechanisms by Which Drugs Can Affect Synaptic Transmission (cont'd)Affect Synaptic Transmission (cont'd)

4.4. Prevent the normal destruction or reuptake Prevent the normal destruction or reuptake of the neurotransmitter.of the neurotransmitter.

5.5. Bind to the receptor site on the postsynaptic Bind to the receptor site on the postsynaptic target tissuetarget tissue


Drugs Not Given to Correct Drugs Not Given to Correct Autonomic Nervous SystemAutonomic Nervous System

System is relatively free of diseaseSystem is relatively free of disease Drugs used to stimulate or inhibit target Drugs used to stimulate or inhibit target

organs of the autonomic nervous systemorgans of the autonomic nervous system


Classification and Naming of Classification and Naming of Autonomic DrugsAutonomic Drugs

Based on four possible actions of Based on four possible actions of sympathetic and parasympathetic nervous sympathetic and parasympathetic nervous systemssystems

1.1. Stimulate sympathetic nervous systemStimulate sympathetic nervous system Adrenergic agents or sympathomimeticsAdrenergic agents or sympathomimetics

1.1. Inhibit sympathetic nervous systemInhibit sympathetic nervous system Adrenergic-blocking agents, adrenergic Adrenergic-blocking agents, adrenergic

antagonists, or sympatholyticsantagonists, or sympatholytics


Classification and Naming of Classification and Naming of Autonomic Drugs (cont'd) Autonomic Drugs (cont'd)

3.3. Stimulate parasympathetic nervous systemStimulate parasympathetic nervous system Cholinergic agents or parasympathomimeticsCholinergic agents or parasympathomimetics

4.4. Inhibit parasympathetic nervous systemInhibit parasympathetic nervous system Cholinergic-blocking agents, anticholinergics, Cholinergic-blocking agents, anticholinergics,

parasympatholytics, or muscarinic blockersparasympatholytics, or muscarinic blockers


Cholinergic AgonistsCholinergic Agonists

They act:They act:

Directly → Receptor (choline receptors)Directly → Receptor (choline receptors)

Indirectly → Drugs that inhibit destruction ofIndirectly → Drugs that inhibit destruction of ACh ACh


Direct-Acting Cholinergic AgonistDirect-Acting Cholinergic Agonist These agents are:These agents are:

Synthetic ester of choline e.g. carbachol & bethanicholSynthetic ester of choline e.g. carbachol & bethanichol Naturally occurring alkaloids e.g. pilocarpine Naturally occurring alkaloids e.g. pilocarpine

They are called “Muscarinic Agonists”They are called “Muscarinic Agonists” ACh has ACh has NONO therapeutic value therapeutic value

The key features of Ach molecule:The key features of Ach molecule: The quaternary ammonium groupThe quaternary ammonium group The ester groupThe ester group



Muscarinic AgonistsMuscarinic Agonists Substitution of acetyl Substitution of acetyl

gp by carbamyl gp → gp by carbamyl gp → CarbacholCarbachol

Addition of methyl gp Addition of methyl gp on on ββ carbon → carbon → MethacholineMethacholine

Combining these two Combining these two modification → modification → BethanicholBethanichol

Pilocarpine: Pilocarpine: Tertiary Tertiary amineamine


Effects of Muscarinic AgonistsEffects of Muscarinic Agonists Cardiovascular effectCardiovascular effect:: Heart:Heart: Slowing the heart Slowing the heart BV:BV: Dilation Dilation BP:BP: ↓↓

Exocrine Glands:Exocrine Glands: SweatingSweating LacrymationLacrymation SalivationSalivation


Effects of Muscarinic Agonists Effects of Muscarinic Agonists

Smooth Muscles:Smooth Muscles: Bronchi:Bronchi: Bronchoconstriction & ↑ secretion Bronchoconstriction & ↑ secretion

GIT:GIT: ↑ motility, sphincter dilation, ↑ gastric secretion ↑ motility, sphincter dilation, ↑ gastric secretion

Urinary Bladder:Urinary Bladder: ↑ motility of detrusor urinae muscle, ↑ motility of detrusor urinae muscle, sphincter dilationsphincter dilation (bladder emptying) (bladder emptying)

Eye:Eye: - Contraction of - Contraction of pupillae sphincter musclespupillae sphincter muscles → miosis and → miosis and widening of filtration angelwidening of filtration angel

- Contraction of - Contraction of ciliary musclesciliary muscles → accommodation → accommodation to near to near vision and vision and opening of opening of canal of schlemmcanal of schlemm


Clinical Uses of Muscarinic AgonistsClinical Uses of Muscarinic Agonists

Glaucoma:Glaucoma: P Pilocarpine ilocarpine (action lasts for 1 day), the most (action lasts for 1 day), the most effective as being a tertiary amine, it can cross the conjunctival effective as being a tertiary amine, it can cross the conjunctival

membrane.membrane.

Bladder emptying in case of neurological disease or Bladder emptying in case of neurological disease or surgery:surgery: Carbachol & Bethanichol Carbachol & Bethanichol

Hair preparation: Hair preparation: Pilocarpine, Pilocarpine, it promotes hair growth by it promotes hair growth by dilation of scalp blood vessels.dilation of scalp blood vessels.

Atropine Poisoning: Atropine Poisoning: Pilocarpine Pilocarpine


Adverse Effects of Muscarinic AgonistsAdverse Effects of Muscarinic Agonists

HypotensionHypotension Sweating & SalivationSweating & Salivation BronchospasmBronchospasm Nausea, abdominal pain & diarrheaNausea, abdominal pain & diarrhea Urinary urgencyUrinary urgency MiosisMiosis


Indirect-actingIndirect-actingcholinergic agonistcholinergic agonist

Inhibition of ChE is Inhibition of ChE is either reversibly or either reversibly or

irreversiblyirreversibly Accumulation of Ach Accumulation of Ach

in the synaptic in the synaptic spaces which can spaces which can

stimulate:stimulate: Both M & N of ANSBoth M & N of ANS

NmNm In brainIn brain


Reversible AnticholinesteraseReversible Anticholinesterase

Quaternary amines:Quaternary amines: NeostigmineNeostigmine PyridostigminePyridostigmine EdrophoniumEdrophonium

Tertiary amines:Tertiary amines: Physostigmine (eserine)Physostigmine (eserine)


Effects of Reversible antiChEEffects of Reversible antiChE

An enhancement of cholinergic transmission at An enhancement of cholinergic transmission at cholinergic autonomic synapses & the cholinergic autonomic synapses & the

neuromuscular junctionneuromuscular junction

Physostigmine → Physostigmine → Eye, GIT, Urinary bladder & CNSEye, GIT, Urinary bladder & CNS Neostigmine → Neostigmine → GIT, Urinary bladder & Sk. M.GIT, Urinary bladder & Sk. M.

Pyridostigmine & Edrophonium → Pyridostigmine & Edrophonium → Sk. M.Sk. M.


Clinical Uses of Reversible antiChEClinical Uses of Reversible antiChE

In In glaucomaglaucoma:: Physostigmine (eye drops)Physostigmine (eye drops)

In intestinal & bladder atonyIn intestinal & bladder atony:: Physostigmine & NeostigminePhysostigmine & Neostigmine

In anesthesia:In anesthesia: Neostigmine (IV), it reverses the action of non-Neostigmine (IV), it reverses the action of non-depolarizing neuromuscular blocking drugs. depolarizing neuromuscular blocking drugs.

In overdose of drugs with anticholinergic actions such as In overdose of drugs with anticholinergic actions such as atropine, phenothiazines & TCAatropine, phenothiazines & TCA

In treatment of Myasthenia gravisIn treatment of Myasthenia gravis


Dental choliergicDental choliergic

1- encourage patients to use good oral 1- encourage patients to use good oral hygiene.hygiene.

2- Raise the patient from the dental chair 2- Raise the patient from the dental chair slowly to avoid hypotension slowly to avoid hypotension


Cholinergic AntagonistsCholinergic Antagonists

They include 3 classes:They include 3 classes:

1.1. Muscarinic Antagonist Muscarinic Antagonist

2.2. Ganglion Blockers (Nn) Ganglion Blockers (Nn)

3.3. Neuromuscular Blockers (Nm) Neuromuscular Blockers (Nm)


1. Muscarinic Antagonists1. Muscarinic Antagonists

They block muscarinic receptors competitively, They block muscarinic receptors competitively, causing inhibition of all muscarinic functionscausing inhibition of all muscarinic functions

They are effective in several clinical situations They are effective in several clinical situations unlike cholinergic agonistsunlike cholinergic agonists


Muscarinic Antagonists (cont.)Muscarinic Antagonists (cont.)

Drugs belong to this groupDrugs belong to this groupa- Atropine & Hyoscine (scopolamine) a- Atropine & Hyoscine (scopolamine) (natural (natural

alkaloids)alkaloids)

b- Homatropine b- Homatropine (synthetic comp.)(synthetic comp.)

c- Atropine methonitrate c- Atropine methonitrate (quaternary comp.)(quaternary comp.)

d- Ipratropium d- Ipratropium (quaternary comp.)(quaternary comp.)e- Pirenzepine e- Pirenzepine (selective M1 antagonist)(selective M1 antagonist)

f- Cyclopentolate and tropicamidef- Cyclopentolate and tropicamide (tertiary amines (tertiary amines developed for ophthalmic use) developed for ophthalmic use)


Effects of Muscarinic AntagonistsEffects of Muscarinic Antagonists

Cardiovascular effect:Cardiovascular effect:• Heart:Heart: (block M2 at SA node, tachycardia 80- (block M2 at SA node, tachycardia 80- 90 beat/min) 90 beat/min)

• BV:BV: No effect No effect • BP:BP: No effect No effect

Exocrine glands:Exocrine glands:• At low dose, it inhibits salivary, lachrymal, bronchial & sweat At low dose, it inhibits salivary, lachrymal, bronchial & sweat

glandsglands• Inhibition of secretions by sweat glands can cause elevated Inhibition of secretions by sweat glands can cause elevated

body tempbody temp• It produces uncomfortable dry mouth & skinIt produces uncomfortable dry mouth & skin

• Gastric secretion is only slightly reducedGastric secretion is only slightly reduced


Effects of Muscarinic Antagonists (cont.)Effects of Muscarinic Antagonists (cont.)

Smooth Muscles:Smooth Muscles:• Eye:Eye:

- Iris: Passive mydriasis & becomes unresponsive to lightIris: Passive mydriasis & becomes unresponsive to light- Ciliary Muscle: Paralysis of accommodation (cycloplegia)Ciliary Muscle: Paralysis of accommodation (cycloplegia)

- In patient with narrow angel glaucoma, IOP may rise dangerously, so In patient with narrow angel glaucoma, IOP may rise dangerously, so short acting antimuscarinic short acting antimuscarinic tropicamidetropicamide or or αα agonist agonist phenylephrinephenylephrine are are

more preferred in ophthalmic examinationmore preferred in ophthalmic examination

CNS:CNS:• Excitatory, at low dose (restlessness) & at high dose (agitation & Excitatory, at low dose (restlessness) & at high dose (agitation &

disorientation)disorientation)• In poisoning, rise in body temp. & hypereactivityIn poisoning, rise in body temp. & hypereactivity


Clinical Uses of Muscarinic AntagonistsClinical Uses of Muscarinic Antagonists

Cardiovascular:Cardiovascular:• Treatment of heart block Treatment of heart block (atropine)(atropine)

Ophthalmic:Ophthalmic:• Mydriatic Mydriatic

Neurological:Neurological:• Prevention of motion sickness Prevention of motion sickness (scopolamine)(scopolamine)

• Reduce involuntary movement & rigidity in case of Reduce involuntary movement & rigidity in case of Parkinsonism Parkinsonism (benztropine)(benztropine)

• Nocturnal enuresis Nocturnal enuresis


Clinical Uses of Muscarinic Antagonists (cont.)Clinical Uses of Muscarinic Antagonists (cont.)

Respiratory:Respiratory:• Treatment of asthma & COPD Treatment of asthma & COPD (ipratropium)(ipratropium)

• To dry secretions & prevent reflex bronchconstriction during To dry secretions & prevent reflex bronchconstriction during anesthesia anesthesia (atropine or hyoscine)(atropine or hyoscine)

GIT: GIT: • Antispasmodic action & suppress gastric acid secretionAntispasmodic action & suppress gastric acid secretion• HyoscineHyoscine is used in case of endoscopy & is used in case of endoscopy & pirenzepinepirenzepine in case of in case of

peptic ulcerpeptic ulcer (H2 antagonists are more preferred)(H2 antagonists are more preferred)


Clinical Uses of Muscarinic Antagonists (cont.)Clinical Uses of Muscarinic Antagonists (cont.)

Antidote for cholinergic agonists:Antidote for cholinergic agonists:• Atropine is used for the treatment of overdoses of Atropine is used for the treatment of overdoses of

cholinesterase inhibitors such as: cholinesterase inhibitors such as: • physostigmine & organophosphate insecticidesphysostigmine & organophosphate insecticides

• Mushrooms (muscarine)Mushrooms (muscarine)• The ability of atropine to enter CNS is of particularly The ability of atropine to enter CNS is of particularly

importanceimportance


Adverse Effects of Muscarinic AntagonistsAdverse Effects of Muscarinic Antagonists

Dry mouth & blurred visionDry mouth & blurred vision

TachycardiaTachycardia

Restlessness, confusion, hallucination & deliriumRestlessness, confusion, hallucination & delirium

Flushing & feverFlushing & fever

In elderly:In elderly: GlaucomaGlaucoma Prostatic enlargementProstatic enlargement


2. Ganglion Blockers (Nn)2. Ganglion Blockers (Nn)

They block nicotinic receptors of autonomic They block nicotinic receptors of autonomic ganglia, therefore they are rarely used ganglia, therefore they are rarely used

therapeutically (experimental tools in therapeutically (experimental tools in pharmacology)pharmacology)


3. Neuromuscular Blockers3. Neuromuscular Blockers

Drugs can block neuromuscular transmission in three Drugs can block neuromuscular transmission in three main ways:main ways:

1.1. By inhibiting Ach synthesisBy inhibiting Ach synthesise.g. hemicholinum & triethylcholinee.g. hemicholinum & triethylcholine

2.2. By inhibiting Ach releaseBy inhibiting Ach releasee.g. botulinum toxins, excess Mg, aminoglycosides e.g. botulinum toxins, excess Mg, aminoglycosides antibioticsantibiotics


3.3. By interfering with the By interfering with the

postsynaptic action of Ach:postsynaptic action of Ach:

a- a- Depolarizing Blocking Agents (DNMB)Depolarizing Blocking Agents (DNMB)• Produce initial stimulation followed by failure of transmissionProduce initial stimulation followed by failure of transmission• e.g. succinylcholine & decamethoniume.g. succinylcholine & decamethonium

b- b- Competitive Blocking Agents (CNMB)Competitive Blocking Agents (CNMB)• They are pure antagonistsThey are pure antagonists

• e.g. curare & gallaminee.g. curare & gallamine


Dental antichloinergicDental antichloinergicThese drugs are used to create a dry, oral These drugs are used to create a dry, oral

fieldfield..

SIDE EFFECTSIDE EFFECT..

xerostomia: xerostomia: 1-you have to direct the patient for meticulous 1-you have to direct the patient for meticulous

oral hygine including floss and brushingoral hygine including floss and brushing 2- plenty of water2- plenty of water 3- instruct the patient to avoid alcohol 3- instruct the patient to avoid alcohol

containing preparations, as well as containing preparations, as well as caffeinated beverages as they increase caffeinated beverages as they increase xerostomiaxerostomia


4-4- instruct the patient not to use fruit juice and instruct the patient not to use fruit juice and soda as they contain sugar and increase risk soda as they contain sugar and increase risk of cariesof caries

5- recommend to chew sugarless candy to 5- recommend to chew sugarless candy to minimize dry mouth.minimize dry mouth.


Adrenergic DrugsAdrenergic Drugs These drugs stimulate These drugs stimulate αα and and ββ receptors receptors

throughout the body.throughout the body.

Adrenergic drugs can be classified as having Adrenergic drugs can be classified as having direct action, indirect action, or mixed action.direct action, indirect action, or mixed action.

1.1. Drugs with direct action (epinephrine, Drugs with direct action (epinephrine, norepinephrine, isoproterenol) produce their norepinephrine, isoproterenol) produce their effect by directly stimulating the receptor site.effect by directly stimulating the receptor site.

2.2. Drugs with indirect actionDrugs with indirect action:: a- Stimulate release of endogenous a- Stimulate release of endogenous

norepinephrine which then stimulates the norepinephrine which then stimulates the receptor; amphetamine.receptor; amphetamine.

20


b- Inhibition of the membrane reuptake of b- Inhibition of the membrane reuptake of catecholamines by drugs such as cocaine catecholamines by drugs such as cocaine and tricyclic antidepressants.and tricyclic antidepressants.c. Inhibition of monoamine oxidase by drugs c. Inhibition of monoamine oxidase by drugs such as Tranylcypromine.such as Tranylcypromine.

3.3. Drugs with mixed action (ephedrine) either Drugs with mixed action (ephedrine) either directly stimulate the receptor or release directly stimulate the receptor or release endogenous norepinephrine.endogenous norepinephrine.




Adrenergic DrugsAdrenergic Drugs

PharmacologyPharmacology Central Nervous System (CNS)Central Nervous System (CNS)

• These drugs produce CNS excitation or These drugs produce CNS excitation or alertness.alertness.

• Higher doses produce anxiety, apprehension, Higher doses produce anxiety, apprehension, restlessness, and tremors.restlessness, and tremors.

EyeEye• These drugs can cause mydriasis.These drugs can cause mydriasis.

Respiratory SystemRespiratory System• These drugs cause a relaxation of bronchiole These drugs cause a relaxation of bronchiole

smooth muscles.smooth muscles.

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Effects of Adrenergic AgonistsEffects of Adrenergic Agonists Cardiovascular:Cardiovascular:

Heart:Heart: ↑HR, contractility ↑HR, contractility »» ↑↑CO + OCO + O22 consumptionconsumption

↑↑Conductivity (atria, AV node & ventricles)Conductivity (atria, AV node & ventricles)↑↑Excitability Excitability »» arrhythmia arrhythmia

BV:BV: VD or VC depending on the selective activity VD or VC depending on the selective activity of drug and the anatomic site of vesselsof drug and the anatomic site of vessels

e.g. Skin, Splanchnic, Sk.M., renal BVe.g. Skin, Splanchnic, Sk.M., renal BV BPBP:: Depends on effect on heart, PR & venous Depends on effect on heart, PR & venous

returnreturn

The effect of The effect of αα-agonist is different from -agonist is different from ββ-agonist-agonist



Metabolic EffectsMetabolic Effects1.1. Hyperglycemia:Hyperglycemia:

Increase liver glycogenolysis Increase liver glycogenolysis ((ββ2)2) Increase glucagon release Increase glucagon release ((ββ2)2) DecreaseDecrease insulininsulin release release ((αα2)2)

1.1. Lipolysis:Lipolysis: Increase hydrolysis of TG into free fatty acids & Increase hydrolysis of TG into free fatty acids &

glycerol glycerol ((ββ3)3) Salivary GlandsSalivary Glands

• These drugs produce vasoconstriction of the These drugs produce vasoconstriction of the salivary glands which leads to decreased salivary salivary glands which leads to decreased salivary flow which results in xerostomia.flow which results in xerostomia.

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Adrenergic Agents (Sympathomimetics) Adrenergic Agents (Sympathomimetics) Primary use:Primary use: depends on receptors activateddepends on receptors activated

Alpha1-receptors:Alpha1-receptors: phenylephrine. nasal phenylephrine. nasal congestion, hypotension, dilation of pupils for congestion, hypotension, dilation of pupils for eye examinationeye examination

Alpha2-receptors:Alpha2-receptors: clonidine. Hypertension clonidine. Hypertension ?? Beta1-receptors:Beta1-receptors: dobutamine and isoprenaline. dobutamine and isoprenaline.

cardiac arrest, heart failure, shockcardiac arrest, heart failure, shock Beta2-receptors: Beta2-receptors: sulbutamol and terbutaline. sulbutamol and terbutaline.

asthma and premature-labor contractions as asthma and premature-labor contractions as they they relax uterine smooth muscle (tocolytics)relax uterine smooth muscle (tocolytics)

Dopaminergic receptors Dopaminergic receptors : dopamine. shock: dopamine. shock


Anaphylactic reactions:Anaphylactic reactions:

Adrenaline is the first line of treatment for Adrenaline is the first line of treatment for bronchoconstriction & CV collapsebronchoconstriction & CV collapse

Haemostatic: Haemostatic: adrenaline and ephedrineadrenaline and ephedrineMydriatic:Mydriatic: EphedrineEphedrineGlaucoma:Glaucoma: Adrenaline dAdrenaline decrease IOP in ecrease IOP in

open angel glaucoma & decrease aqueous open angel glaucoma & decrease aqueous humor production by VC of ciliary body BVhumor production by VC of ciliary body BV

With local anesthetics:With local anesthetics: Ad & NA Ad & NADepression:Depression: Amphetamine Amphetamine





DopamineDopamine

Immediate precursor of NEImmediate precursor of NE Occurs inOccurs in

CNS (act as neurotransmitter)CNS (act as neurotransmitter) Adrenergic nerve ending Adrenergic nerve ending

Adrenal medullaAdrenal medulla

Activates: Activates: αα1(at high doses)1(at high doses)

ββ1 (at small doses)1 (at small doses) D1(occurs in renal vascular bed) D1(occurs in renal vascular bed)

D2 (occurs in presynaptic adrenergic neurons)D2 (occurs in presynaptic adrenergic neurons)


Pharmacological Effects of Pharmacological Effects of DopamineDopamine

CVS:CVS: +ve chronotropic & inotropic effects+ve chronotropic & inotropic effects At high doses: VC of BVAt high doses: VC of BV

Renal & visceral:Renal & visceral: VD of renal and splanchnic arteriolesVD of renal and splanchnic arterioles Effective in treatment of shock (the drug of choice Effective in treatment of shock (the drug of choice

taken by continuous infusion)taken by continuous infusion)


Dental UseDental Use VasoconstrictionVasoconstriction

• These drugs are used in dentistry because of their These drugs are used in dentistry because of their vasoconstrictive actions on blood vessels. They are vasoconstrictive actions on blood vessels. They are added to local anesthetics because they prolong added to local anesthetics because they prolong the action of the local anesthetic, reduce the risk the action of the local anesthetic, reduce the risk for systemic toxicity, and help to create a dry field.for systemic toxicity, and help to create a dry field.

• Act as homeostatic agent aids in control Act as homeostatic agent aids in control bleeding bleeding

• Cocaine has limited use as a local anesthesic Cocaine has limited use as a local anesthesic and vasoconstrictor in surgical procedures and vasoconstrictor in surgical procedures involving oral, laryngeal or nasal cavities.involving oral, laryngeal or nasal cavities.

• But close monitoring regard to cardiac effectsBut close monitoring regard to cardiac effects• These drugs raise blood pressure .These drugs raise blood pressure .

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Cautions Relevant to DentistryCautions Relevant to Dentistry

1)1) Cocaine and amphetamine-like agents (tricyclic Cocaine and amphetamine-like agents (tricyclic antidepressants as well) could potentiate the antidepressants as well) could potentiate the effects of direct acting agonists such as effects of direct acting agonists such as epinephrine. epinephrine.

2)2) epinephrine can be absorbed systemically after epinephrine can be absorbed systemically after intraoral administration. This epinephrine can intraoral administration. This epinephrine can be taken up by nerve terminals and this uptake be taken up by nerve terminals and this uptake contributes to the termination of the actions of contributes to the termination of the actions of epinephrine. Thus, the risk of hypertension and epinephrine. Thus, the risk of hypertension and other problems associated with systemic other problems associated with systemic absorption of epinephrine will be greater in absorption of epinephrine will be greater in patients taking cocaine or amphetamine-like patients taking cocaine or amphetamine-like drugs. drugs.

2)2)



Adverse ReactionsAdverse Reactions The adverse reactions associated with The adverse reactions associated with

these drugs are an extension of the drugs’ these drugs are an extension of the drugs’ pharmacologic effects.pharmacologic effects.

They include:They include:• AnxietyAnxiety• TremorsTremors• TachycardiaTachycardia• Increased blood pressureIncreased blood pressure• ArrhythmiasArrhythmias

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Contraindications to use of Contraindications to use of adrenergicsadrenergics

Cardiac dysrhythmias, angina pectorisCardiac dysrhythmias, angina pectoris HypertensionHypertension HyperthyroidismHyperthyroidism Cerebrovascular diseaseCerebrovascular disease Distal areas with a single blood supply such Distal areas with a single blood supply such

as fingers, toes, nose and earsas fingers, toes, nose and ears Renal impairment use cautionRenal impairment use caution


epinephrineepinephrine

Affects both alpha and beta receptorsAffects both alpha and beta receptors Usual doses, beta adenergic effects on heart Usual doses, beta adenergic effects on heart

and vascular smooth muscle will and vascular smooth muscle will predominate, high doses, alpha adrenergic predominate, high doses, alpha adrenergic effects will predominateeffects will predominate

Drug of choice for bronchospasm and Drug of choice for bronchospasm and laryngeal edema of anaphylaxislaryngeal edema of anaphylaxis


epinephrineepinephrine

Excellent for cardiac stimulant and Excellent for cardiac stimulant and vasoconstrictive effects in cardiac arrestvasoconstrictive effects in cardiac arrest

Added to local anestheticAdded to local anesthetic May be given IV, inhalation, topicallyMay be given IV, inhalation, topically Not PONot PO


ClonidineClonidine ALPHAALPHA22 AGONISTS AGONISTS Actions and Therapeutic UsesActions and Therapeutic Uses

1. This drug stimulates alpha1. This drug stimulates alpha22 receptors in the receptors in the

nucleus tractus solitarius (NTS) to decrease nucleus tractus solitarius (NTS) to decrease sympathetic outflow to the heart and blood sympathetic outflow to the heart and blood vessels.vessels.2. The decrease in sympathetic tone results in a 2. The decrease in sympathetic tone results in a decrease in blood pressure.decrease in blood pressure.

3. Clonidine is used in dental practice in the 3. Clonidine is used in dental practice in the management of chronic pain. It can be given management of chronic pain. It can be given orally or in patch form. orally or in patch form.


Inhibits NE release


Clonidine is a second-line antihypertensive Clonidine is a second-line antihypertensive that has many other uses including opiate that has many other uses including opiate withdrawal, nicotine withdrawal, vascular withdrawal, nicotine withdrawal, vascular headaches, diabetic diarrhea, glaucoma, headaches, diabetic diarrhea, glaucoma, ulcerative colitis.ulcerative colitis.

Side Effects Side Effects

The use of clonidine may result in clinical The use of clonidine may result in clinical symptoms related to dry mouth, such as symptoms related to dry mouth, such as difficulty in swallowing and speech. Chronic difficulty in swallowing and speech. Chronic use of xerostomia-producing drugs is use of xerostomia-producing drugs is associated with a higher incidence of oral associated with a higher incidence of oral candidiasis and dental caries.candidiasis and dental caries.


Monoamine Oxidase InhibitorsMonoamine Oxidase Inhibitors

These drugs inhibit monoamine oxidase and These drugs inhibit monoamine oxidase and are used as antidepressants in psychiatric are used as antidepressants in psychiatric practice. practice.

Can precipitate a hypertensive crisis. Patients Can precipitate a hypertensive crisis. Patients taking MAO inhibitors must not be giventaking MAO inhibitors must not be givendrugs that have indirect sympathomimetic drugs that have indirect sympathomimetic activity or are inactivated by MAO. activity or are inactivated by MAO.


Occasionally, the dentist may find reason to Occasionally, the dentist may find reason to use the vasoconstrictor phenylephrine. use the vasoconstrictor phenylephrine. Because it causes evenBecause it causes evena minor release of norepinephrine from a minor release of norepinephrine from adrenergic nerves and is subject to adrenergic nerves and is subject to metabolism by MAO.metabolism by MAO.

phenylephrine must be avoided in patients phenylephrine must be avoided in patients taking MAO inhibitors. taking MAO inhibitors.

Epinephrine and levonordefrin, which are Epinephrine and levonordefrin, which are most commonly found in local anesthetic most commonly found in local anesthetic solutions, are not contraindicated, since they solutions, are not contraindicated, since they are direct agonists and are largely inactivated are direct agonists and are largely inactivated by catechol-O-methyltransferase. by catechol-O-methyltransferase.


Nonetheless, the avoidance of hemostatic Nonetheless, the avoidance of hemostatic preparations containing high concentrations preparations containing high concentrations of epinephrine isof epinephrine isrecommended.recommended.

Opioids and other CNS depressants should Opioids and other CNS depressants should be used cautiously and usually at lower doses be used cautiously and usually at lower doses ininpatients who are taking MAO inhibitors. patients who are taking MAO inhibitors. Meperidine is absolutely contraindicated.Meperidine is absolutely contraindicated.



Adrenergic Receptor Antagonist Adrenergic Receptor Antagonist αα-Blockers:-Blockers:- Non selective:Non selective: Phenoxybenzamine & Phentolamine Phenoxybenzamine & Phentolamine- αα1-Blocker:1-Blocker: Prazosin, Terazosin, Doxazosin & Prazosin, Terazosin, Doxazosin &

Tamsulosin Tamsulosin - αα2-Blocker:2-Blocker: Yohimbine Yohimbine (Sympatholytic ?)(Sympatholytic ?)

ββ -Blockers:-Blockers:- Non selective:Non selective: Propran Propranolololol , Tim, Timolol olol & Nad& Nadolololol- ββ1-Blocker:1-Blocker: Aten Atenolololol , Metopr, Metoprolol olol & Esm& Esmolololol

αα & & ββ Blocker: Blocker: Labet Labetalolalol & carved & carvediloli lol


Effects of Effects of αα-adrenoceptor -adrenoceptor AntagonistsAntagonists

The most important effect is CVS effectThe most important effect is CVS effect

They block α1 receptors causing decrease in They block α1 receptors causing decrease in peripheral resistance and consequently BPperipheral resistance and consequently BP

The resultant hypotension provokes reflex The resultant hypotension provokes reflex

tachycardiatachycardia pupillary constrictionpupillary constriction

increased motility of GI tractincreased motility of GI tract


Alpha 1 antagonists Alpha 1 antagonists

Used in Benign Prostatic Hyperplasia. Used in Benign Prostatic Hyperplasia. Produces smooth muscle relaxation of Produces smooth muscle relaxation of prostate gland and bladder neck. prostate gland and bladder neck.

Pulmonary hypertension in newborns. Can be Pulmonary hypertension in newborns. Can be given SC , IM or IV.given SC , IM or IV.

May be useful in treating pheochromocytomaMay be useful in treating pheochromocytoma May be used in Raynaud’s disease.May be used in Raynaud’s disease. Side Effect : orthostatic hypotensionSide Effect : orthostatic hypotension


Orthostatic hypotension in Orthostatic hypotension in dentistrydentistry

Orthostatic hypotension is a problem with prazosin Orthostatic hypotension is a problem with prazosin analogs and to a lesser extent tamsulosin. analogs and to a lesser extent tamsulosin. Significantly, orthostatsis is a problem that can be Significantly, orthostatsis is a problem that can be seen with any vasodilator that affects the tone on seen with any vasodilator that affects the tone on venous smooth muscle. venous smooth muscle.

This would include, This would include, organic nitrates, hydralazine, organic nitrates, hydralazine, clonidine, minixodil and the many drugs.clonidine, minixodil and the many drugs.

Orthostatic hypotension or postural hypotension Orthostatic hypotension or postural hypotension occurs when systemic arterial blood pressure falls by occurs when systemic arterial blood pressure falls by more than 20 mmHg upon standing. more than 20 mmHg upon standing.


In this situation, cerebral perfusion falls and In this situation, cerebral perfusion falls and an individual may become light headed, dizzy an individual may become light headed, dizzy or fatality may occur.or fatality may occur.

In changing from the supine to the standing In changing from the supine to the standing position, gravity tends to cause blood to pool position, gravity tends to cause blood to pool in the lower extremities. However, several in the lower extremities. However, several reflexes, including sympathetically mediated reflexes, including sympathetically mediated venoconstriction minimize this pooling and venoconstriction minimize this pooling and maintain cerebral perfusion. If these reflex maintain cerebral perfusion. If these reflex actions do not occur, then orthostatic actions do not occur, then orthostatic hypotension could result.hypotension could result.


By blocking the alphaBy blocking the alpha11-receptors associated -receptors associated

with venous smooth muscle, prazosin-like with venous smooth muscle, prazosin-like drugs, inhibit the sympathetically mediated drugs, inhibit the sympathetically mediated vasoconstriction associated with postural vasoconstriction associated with postural changes. Hence, orthostatic hypotension can changes. Hence, orthostatic hypotension can occur. occur.

Drugs like clonidine cause orthostasis due to Drugs like clonidine cause orthostasis due to its CNS actions that block the sympathetic its CNS actions that block the sympathetic reflexes. reflexes.

Vasodilators such as nitrates, minoxidil, Vasodilators such as nitrates, minoxidil, hydralazine or impotence medications cause hydralazine or impotence medications cause orthostasis because of their actions directly orthostasis because of their actions directly on the vasculature.on the vasculature.


A consideration for patients being treated with A consideration for patients being treated with some sympatholytics is the patient's some sympatholytics is the patient's position position during and after dental proceduresduring and after dental procedures. . Suddenly standing upright after being in a Suddenly standing upright after being in a supine position in the dental chair is very supine position in the dental chair is very probable to cause probable to cause syncopesyncope..


beta blocking drugsbeta blocking drugs Decreased heart rateDecreased heart rate Decreased force of contractionDecreased force of contraction Decreased Cardiac OutputDecreased Cardiac Output Slow cardiac conductionSlow cardiac conduction Decreased automaticity of ectopic pacemakersDecreased automaticity of ectopic pacemakers Decreased renin secretion from kidneysDecreased renin secretion from kidneys Decreased BPDecreased BP BronchoconstrictionBronchoconstriction Less effective metabolism of glucose. May result Less effective metabolism of glucose. May result

in more pronounced hypoglycemia and early s/s of in more pronounced hypoglycemia and early s/s of hypoglycemia may be blocked (tachycardia).hypoglycemia may be blocked (tachycardia).



Uses of Beta blocking Uses of Beta blocking medicationsmedications

Inderal (propranolol) is prototypeInderal (propranolol) is prototype Mainly for cardiovascular disorders (angina, Mainly for cardiovascular disorders (angina,

dysrhythmias, hypertension, Myocardial dysrhythmias, hypertension, Myocardial Infarction and glaucoma.Infarction and glaucoma.

In angina, beta blockers decrease myocardial In angina, beta blockers decrease myocardial oxygen consumption by decreasing rate, BP and oxygen consumption by decreasing rate, BP and contractility. Slow conduction both in SA node contractility. Slow conduction both in SA node and AV node.and AV node.

Useful in pheochromocytoma in conjunction with Useful in pheochromocytoma in conjunction with alpha blockers (counter catecholamine release)alpha blockers (counter catecholamine release)

migrainesmigraines


Combination selectivityCombination selectivity

Labetalol and carvedilol (Coreg) block alpha Labetalol and carvedilol (Coreg) block alpha 1 receptors to cause vasodilation and beta 1 1 receptors to cause vasodilation and beta 1 and beta 2 receptors which affect heart and and beta 2 receptors which affect heart and lungslungs

Both alpha and beta properties contribute to Both alpha and beta properties contribute to antihypertensive effectsantihypertensive effects

May cause less bradycardia but more May cause less bradycardia but more postural hypotensionpostural hypotension

Less reflex tachycardiaLess reflex tachycardia


Application to dentistryApplication to dentistry Because nonselective β-blockers block β2Because nonselective β-blockers block β2--

receptor mediated vasodilationreceptor mediated vasodilation, there is a , there is a risk of a risk of a hypertensive episodehypertensive episode following following administration of local anesthetic agents that administration of local anesthetic agents that contain contain epinephrineepinephrine. .

In this situation, the vasoconstrictor actions of In this situation, the vasoconstrictor actions of epinephrineepinephrine at α1 -receptors are not opposed at α1 -receptors are not opposed by the vasodilatory actions of β2-receptors by the vasodilatory actions of β2-receptors resulting in an exaggerated blood pressure resulting in an exaggerated blood pressure response that could be deleterious in patients response that could be deleterious in patients with hypertension or ischemic heart disease. with hypertension or ischemic heart disease.










2.2. What is implied by «active transport»?What is implied by «active transport»?

a) Transport of drugs through a membrane by a) Transport of drugs through a membrane by means of diffusionmeans of diffusion

b) Transport without energy consumptionb) Transport without energy consumption

c) Engulf of drug by a cell membrane with a c) Engulf of drug by a cell membrane with a new vesicle formationnew vesicle formation

d) Transport against concentration gradientd) Transport against concentration gradient


3-Parenteral administration:3-Parenteral administration:

a) Cannot be used with unconsciousness patientsa) Cannot be used with unconsciousness patients

b) Generally results in a less accurate dosage than b) Generally results in a less accurate dosage than oral administrationoral administration

c) Suitable for drugs not absorbed from the gutc) Suitable for drugs not absorbed from the gut

4. Pharmacodynamics involves the study of 4. Pharmacodynamics involves the study of following?following?

a) Mechanisms of drug actiona) Mechanisms of drug action

b) Biotransformation of drugs in the organismb) Biotransformation of drugs in the organism

c) Distribution of drugs in the organismc) Distribution of drugs in the organism

d) Excretion of drug from the organismd) Excretion of drug from the organism


5- Target proteins which a drug molecule binds are:5- Target proteins which a drug molecule binds are:

a) Only receptors b) Only ion channelsa) Only receptors b) Only ion channels

c) Only transporters d) All of the abovec) Only transporters d) All of the above

6-An agonist is a substance that:6-An agonist is a substance that:

a) Interacts with the receptor without producing any a) Interacts with the receptor without producing any effecteffect

b) Interacts with the receptor and initiates changes in b) Interacts with the receptor and initiates changes in cell function, producing various effectscell function, producing various effects

c) Interacts with plasma proteins and doesn’t produce c) Interacts with plasma proteins and doesn’t produce any effectany effect

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Autonomic nervous system

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