Skip to main content
Get your brand new Wikispaces Classroom now
and do "back to school" in style.
Pages and Files
Drug action and Adverse Reactions
Opioid Analgesics and Anatagonists
Autacoid and Antihistamines
Respiratory and Gastrointestinal Drugs
A useful website explaining the Autonomic Nervous system, as well as adrenergic and cholinergic receptors:
Mechanism of action of acetylcholinesterase inhibitors
Autonomic nervous system
- aka" visceral", "vegetative"
- involuntary nervous system that regulates the function of involuntary structures such as smooth muscle, heart, secretory glands
- Divided into: Sympathetic and parasympathetic
: Thoracolumbar Outflow
- Activates preganglionic nerves that innervate the adrenal medulla and causes it to release a mixture of catecholamines epinephrine, nor epinephrine
- 1-preganglionic fiber for every 8000 postganglionic fiber
- “Stress”,” fight and flight system”
- Adrenergic and nicotinic receptors
- Oral surgery is considered a stressor that stimulates this system which increase the nor epinephrine level.
Parasympathetic nervous system
: Craniosacral Outflow
- 4- cranial nerves:
- Oclumotor III, facial VII, gloss pharyngeal IX, vagus X
- Only uses Acetylcholine as its receptor
- Main function is protection, restoration, and conservation
- “ rest and digest” response
- One one one ratio of preganlionic and postganglionic fibers which explain the limited response of the parasympathetic system
Chemical mediators that transmit information
Acetycholine (ACH)- Primary neurotransmitter released from pre and post ganglionic nerves in the parasympathetic Nervous System
- Released from majority of postganglionic sympathetic nerves.
Norepinephrine and Epinephrine
- Released after sympathetic stimulation of the adrenal medulla.
- Released from some sites in Autonomic Nervous System
Histamine, Serotonin, Aspartate, ATP, Opiods
- Other molecules that may serve as neurotransmitters.
Adrenergic nerves release norepinephrine as the neurotransmitter for the sympathetic nervous system. The sympathetic system activates and prepares the body for vigorous muscular activity, stress, and emergencies. Adrenergic drugs stimulate the adrenergic nerves directly by mimicking the action of norepinephrine or indirectly by stimulating the release of norepinephrine.
Therapeutically, these drugs are used to combat life-threatening disorders, which include acute attacks of bronchial asthma, shock, cardiac arrest, and allergic reactions. In addition these drugs are used in nasal decongestants and appetite suppressants.
Adrenergic Nerve Transmissions:
Adrenergic nerves release the neurotransmitters: Norepinephrine (noradrenaline, NE), epinephrine, EP, and dopamine DA. The synthesis of the neurotransmitters DA and NE and EP and the hormones NE and EP takes place by a pathway that involves 5 enzymes. Tyrosine is generally considered the starting point to synthesize DOPA (1a), DA (1b), and NE (1c). Norepinephrine is stored at (2).
Norepinephrine is released from the nerve ending in response to a nerve impulse or drug (3). NE interacts with alpha and beta receptor sites at (4). Its receptor action is terminated by recapture and storage in the original nerve ending or inactivated by an enzyme. For example chloropheniramine, an antihistamine, can inhibit the mechanism for uptake and recapture of norepinephrine.
There are at least two adrenergic receptor sites (alpha or beta). Norepinephrine activates primarily alpha receptors and epinephrine activates primarily beta receptors, although it may also activate alpha receptors. Stimulation of alpha receptors is associated with constriction of small blood vessels in the bronchial mucosa and relaxation of smooth muscles of the intestinal
tract. Beta receptor activation relaxes bronchial smooth muscles which cause the bronchi of the lungs to dilate.
In addition beta receptor stimulatory effects cause an increase
in the rate and force of heart contractions. As a result increased amounts of blood leave the heart and is diverted from nonactive organs to areas that actively participate in the body's reaction to stress such as skeletal muscles, brain, and liver.
Adrenergic Receptor Sites:
Alpha Receptor Site:
Important features of the site include in order of importance:
1) An anionic site - which binds the positive ammonium group.
2) One hydrogen bonding area
3) A flat area non-polar area for the aromatic ring.
Beta Receptor Site:
Important features of the site include in order of importance - also see the graphic on the left:
1) An anionic site - shown as Asp anionic negative acid group which binds the positive ammonium group.
2) Two hydrogen bonding areas - shown as two Serine with alcohol (OH) groups hydrogen bonding to the phenol OH groups of the NE.
3) A flat area non-polar area for the aromatic ring.
NE, EP, dobutamine, xamoterol
beta1, beta 3?
Vascular Smooth Muscle
EP, salbutamol, terbutaline, salmeterol
Airway Smooth Muscle
terbutaline, salbutamol, salmeterol and zinterol,
Smooth muscle contraction
NE, EP, phenylephrine, oxymetazoline)
transmitter release Hypotension, anaesthesia, Vasoconstriction
clenbuterol, alpha-methylnoradrenaline, dexmedetomidine, and mivazerol, clonidine, clenbuterol
yohimbine, idazoxan, atipamezole, efaroxan, and rauwolscine
intestinal relaxation (b2)
bladder sphincter contraction
Many adrenergic agonist activate more than one of the adrenergic receptors type.
Aka= sympathomimic because they mimic the effects caused by the sympathetic nervous system
Adrenergic agents= aka= catecholamines
direct acting= binds directly to the adrenergic receptor, requires a hydroxyl group
indirect acting= increase the amount of nor epinephrine available to stimulate the adrenergic receptor., no hydroxyl group, can better penetrate the blood brain barriers and cause a CNS effect.
One type of adrenergic agonist are beta blockers. They are widely used in cardivacular theraputics, they also treat a number of noncardicvascular disease states. Beta blockers can decrease the force and rate of myocardial contraction, they can also inhibt beta-1 receptor mediated responses of the AV node. This results in a decrease in SA nadal firing rate, slowed condution and a decrese in automaticity. The decrease in contractile force occurs largley as a result of beta-1 adrenic receptor blockade associated with ventricular and atrial muscle, these changes result in a decrease in cardiac output. Due to its effectivness in blocking these receptors in the heart, beta blockers are also used to treat hypertension, ischmic heart disease, post myocardial infarction, congestive heart failure and treatment of arrhythmias.
Depends on two factors:
- whether the agonist is direct or indirect acting
- the density of the receptor population in an organ
Epinephrine & nor epinephrine:
Increase contraction of smooth muscle and vasoconstriction of surrounding tissue
Depends on the transmission route and rate, dose given, and presence or absence of drug interaction
Effect on the non vascular smooth muscle
Relaxation of thoracic and abdominal cavity smooth muscle
Alpha= contraction of uterus
Beta= relaxation of uterus
Strengthen the heart contraction
Increase pacemaker cell firing rate
Effect on the salivary gland
Modest secretion with high concentration of protein
Increase in blood pressure
Inhibition of insulin
Little access to CNS because of the hydroxyl group
Uses in Dentistry
1. Prolongs the duration of Local anesthetic
2. Minimizes toxicity by delaying and reducing the peak blood concentration of the anesthetic agent
3. Vasoconstrictors reduce blood loss associated with surgical procedures
4. Can be used to stimulate salivary flow
Treatment of hypotension, shock
Treatment of allergic states
Treatment of hypertension
Mostly dose related- such as tolerance development
Toxic reaction due to too large dose
Accidental IV injection
Impaired uptake of drug
Therapeutic dose given to a patient with preexisting cardiovascular disease
a1 adrenergic receptor blockers
produce less reflex tachycardia resulting in posible syncope from orthostatic hypotension, also side effects such as gastorintestinal upset, palpitation, tinnitus, headache, rash, edema, and urinary incontinenece can also occur.
B-adrenergic receptor antagonists
cause side effects such as nausea, vomiting, anorexia, confusion, dizziness, fatigue, sleep disturbances and depression.
ACh- released from nerve terminals of the preganglionic fibers of the PsNS & SNS, postganglionic fibers of the PsNS & some postganglionic fibers of the SNS, from somatic efferents innervating skeletal muscle
- Cholinergic drugs usually act in one of two ways. Some directly mimic the effect of acetylcholine, while others block the effects of acetylcholinesterase. Agonists produce Ps responses by stimulating muscarinic receptors on tissues innervated by postganglionic of PsNS (referred to as muscarinic) Some produce nonselective stimulation of Ps & S branches of ANS by activating ganglionic nicotinic receptors located on the motor end plate of the neuromuscular junction. Synapses containing nicotinic and muscarinic receptors can be stimulated by agonists that can cross the blood brain barrier.
- directly stimulate muscarinic/nicotinic/both receptors causing pharmacologic response in effector. Choline Esters-include ACh and its synthetic congeners, Alkaloids- including synthetic congeners (muscarine, pilocarpine, cevimeline, nicotine) Most exert prominent Ps effects.
Mechanism of Action
- bind to and stimulating muscarinic and nicotinic receptors located in junctional regions of both the PNS & CNS. Muscarinic responses are produced by low doses of ACh, effects on ganglionic and somatomotor transmission require higher doses. Mediated by the stimulation of several populations of muscarinic receptors.
Choline ester (bethanechol) and alkaloid muscarine
produce relatively selective activation of muscarinic receptors located on the autonomic effector tissues, on cell bodies of unique populations of CNS neurons.
plasma membrane receptor that has 7 helical segments that cover the membrane and are joined by alternating intra and extracellular peptide bridges.
M₁- localized in ganglia, some exocrine glands cells, and enterochmaffin cells of the stomach
M₂- primary subtype in the heart and (along w/ M₄) in lungs
M₃- most prominent in glandular tissues and most widely distributed
M₅- discrete regions of CNS
Stimulation of these receptors causes a cascade that leads to the pharmacologic effects. These receptor subtypes regulate all the activity of G proteins (influencing the 2nd messenger system)
Adrenergic Blocking Drugs:
- These are mostly competitive "antagonists" of either alpha or beta adrenergic receptors "AKA" (adrenoceptors)
These agents block the action of endogenous "neurotransmitters" (epinephrine & norepinephrine) plus, all exogenously administered adrenergic agonists and are called (adrenergic receptor blockers.)
Adrenergic Neuron Blocking Drugs- These drugs act on the "nerve terminals" to produce their sympatholytic affect.
This process uses derivatives of drugs to block "some" but, not all the actions of the agonists.
Beta Blocker- The first clinically useful beta blocker was propranolol, it blocks b1 and b2 adrenergic receptors then, "selective" b1 antagonists were discovered.
9 Adrenergic Receptors-
There are currently nine receptors known ranging as follows, alpha 1A, alpha 1B, alpha 1D, alpha 2A, alpha 2B, alpha 2C, Beta 1, Beta 2, Beta 3
Continuing Development- There are continuing developments being tested of "selective" antagonists to focus on specific receptors and prevent the side effects that non-specific antagonists bring.
Non-Selective Adrenergic Receptor Antagonists- These agents present action of adrenergic transmitters and sympathomimetic agonists at "all" alpha adrenergic receptors. There are two specific to this they are Imidazolines and Haloalkylamines.
directly stimulate cholinergic receptors, muscarinic, nicotinic, or both to cause a pharmacological response in an effector
Cholinomimetric agonist--> Drugs that mimic the actions of endogenous neurotransmitter Acetylcholine
1. Choline esters
2. Natural alkaloids and congeners
peripheral muscarinic effects: the responses mimic parasympathetic nervous system stimulation.
Eye: activate the phincter muscle of the iris ad constrict the pupil, contraction of the ciliary muscle, intraocular pressure is decreased, transient hyperemia of the conjunctiva
Heart: heart rate is decreased, decrease in the force of action
Vascular smooth muscle: prduce a generalized vasodiation that causes a fall in blood pressure
Bronchial smooth muscle: smooth muscle in bronchiales constrict
GI smooth muscle: peristalic contractions, amplitude and tone of contraction is increased and sphincter muscles are relaxed
Secretory glands: salivary, lacrimal, bronchial, sweat, gastric, intestinal, and pancreatic glands and stimulated
Urinary tract: decreased bladder capacity, opening of the urethral orifice in the fundus of the bladder
CNS: both muscarinic and nicotinic receptors are in the CNS.
vary according to the receptors they stimulate, their distribution throughout the body, and their mode of inactviation
Patients with asthma
Patients with increased risk of adverse effects:
Anticholinesterases: drugs that stimulate cholinergic transmission by inhibiting the enzyme acetylcholinesterase
1. Reversible: temporarily inactivate the enzyme by forming noncovalent associations with the enzyme or covalent bonds that are readily hydrolyzed
2. Irreversible: inactivates the enzyme by forming a permanent covalent bond with the enzyme
General Therapeutic uses:
antidote for atropine poisoning
paralytic ileus and bladder atony
senile dementias pf the alzheimer type
Therapeutc uses in dentistry:
1. stimulating salivary flow
Direct acting cholinergic drugs- bind to nicotinic and muscarinic receptors and activate downstream signaling.
Indirect acting cholinergic drugs- inhibit action of acetylcholineesterase (AChE), resulting in ACh-like activation effects.
A) Cholinergic drugs mimic the actions of ACh.
i) Most cholinomimetic agonists produce parasympathetic responses by stimulating muscarinic receptors located on the tissues innervated by the postganglionic fibers of the parasympathetic nervous system.
ii) Most of these drugs are called muscarinic or parasympathomimetic agonists.
B) Cholinomimetic agonists
i) Directly stimulates muscarinic, nicotinic, receptors, or both.
iii) Divided into two classes on basis of origin and chemical composition
a) Choline esters and its synthetic cogeners
b) Naturally occurring alkaloids and there cogeners.
iv) Mechanism of Action
a) Direct-acting cholinomimetic srugs produce their effects by binding to and stimulating mucarinic and nicotinic receptors.
b) Muscarinic responses are produced by low levels of ACh, but effects on ganglionic and somatomotor transmission requires increasingly higher doses.
c) Parasympathomimetic responses to cholinergic drugs are mediated by the stimulation of several populations of muscarinic receptors.
d) A total of 5 muscarinic receptor proteins have been produced from cloned muscarinic receptor genes and it has been established that multiple receptor subtypes can coexist on the same organ or tissue.
e) Systemic administration of high doses of ACh activates nicotinic receptors located on the cell bodies of postganglionic nerve fibers of the autonomic nervous system and nicotinic receptors located in the neuromuscular junction.
v) Pharmacological effects
a) The pharmacological effects produced by direct acting cholinergic drugs vary according to the receptors they stimulate, their distribution throughout the body, and their mode of inactivation.
b) The duration of action of ACh ond its congerners is determined by their susceptibility to hydrolysis by AChE and pseudocholinesterase.
c) The natural alkaloids are not affected by the cholinesterases at all.
d) Peripheral muscarinic effects.
x) Cholinergic agonists that stimulate muscarinic receptors produce end-organ responses that mimic parasympathetic nervous system stimulation.
xi) Muscarinic receptors activate the sphincter muscle of the iris and produce constriction of the pupil. Also there is contraction of the ciliary muscle.
xii) Heart- Direct cardiac effects are similar to those associated with vagal stimulation. Heart rate is decreased. Decrease in force of contraction. Also decreasese myocardial contractility; effect of of muscarinic receptor activation on cardiac currents.
xiii) Vascular Smooth Muscle- Produces a generalized vasodilation; causes fall in blood pressure.
xiv) Bronchial Smooth Muscle- Produces constriction.
xv) GI sm.mus- Motility, peristaltic contractions, amplitude of contractions, and tone are all increased. Sphincter muscles are relaxed.
xvi) Secretory glands- Potentially stimulated
xvii) Urinary tract- Contraction of detruser muscle, which decreases bladder capacity.
e) Peripheral nicotinic effects
x) Nicotinic receptors have varying effects at different nicotinic sites and these effects are related to the structure of the molecule, the dosage of the drug, and the location and type of nicotinic receptor activated.
xii) Two major kinds of perip. nico. recep.: those on ganglia and those in skeletal muscle.
xiii) Stimulation of autonomic ganglia leads to a mixture of parasympathetic and sympathetic effects, which often oppose each other, and means the outcome is difficult to predict.
f) CNS effects
x) Exhibit no direct effect on the CNS.
xi) Behavioral effects is as a result of peripheral influences which can lead to changes in sensory input conducted to the brain by visceral afferent fibers.
vi) Adverse effects
a) Adverse effects to cholinomimetic drugs are predictable consequences of the stimulation of cholinergic receptors.
b) Includes the SLUD effect, bronchospasm, hypotension, and arrhythmias
C) Anticholinesterases inhibit the hydrolysis of ACh by enzyme AChE which produces the cholinomimetic effect indirectly.
i) ACh-esterases prolong the effective life of ACh released at the neuroeffector junctions.
ii) Less selective in effect than direct-acting cholinomimetics.
iii) Can be classified as reversible or irreversible cholinesterase inhibitors. Reversible inhibitors temporarily inactivate the enzyme by
forming noncovalent associations with the enzyme or covalent bonds that are readily hydrolyzed. Irreversible inhibitors inactivate
the enzyme by forming a permanent covalent bond with the enzyme.
vi) Mechanism of Action
a) Prolongs the life of ACh at sites where it is mediator.
b) Actions identical with ACh, but more prolonged and completely dependant on endogenous ACh.
c) Often ineffective in dennervated organ.
v) Pharmacological effects
a) Produce muscarinic effects similar to those elicited by direct-acting cholinergic agonists.
b) Activity is greatest for those organs that receive more or less continuous cholinergic nerve stimulation.
c) Do not cause significant muscarinic receptor mediated vasodilation.
d) Stimulate, and in high doses block, both ganglia and skeletal muscle receptors by indirectly increasing the synaptic concentrations of ACh at ganglionic and neuromuscular sites.
vi) Adverse effects
a) Intoxication usually results from overdosage of drugs used to treat myasthenia gravis and from exposure to insecticides or chemical warfare agents.
b) Signs and symptoms are intense miosis, rhinorrhea, wheezing, laryngospasm, GI effects, fatigability, CNS manifestations.
c) Treatment is to: remove contaminant, administer atropine in large doses, maintain airway and admin artificial respiration, inject a benzodiazepine if atropine fails to stop convulsions, and admin pralidoxime.
D) Therapeutic uses
iii) Myasthenia Gravis
iv) Antidote for Atropine poisoning.
v) Paralytic Ileus and bladder atony
vi) Senile dementias of the Alzeheimers type.
vii) Used in dentistry primarily to treat xerostomia
E) Antimuscarinic Drugs
i) Block responses in muscarinic receptors and are essentially without effect, except at inordinately high doses, at nicotinic receptors
ii) Four Classifications: naturally occurring belladonna deriviatives, semisynthetic derivatives, synthetic quaternary ammonia componds, and synthetic antimuscarinic drugs that are not quat ammon compounds.
iii) Mechanism of Action
a) Antimuscarinic drugs ore competice agonists of ACh at muscarinic receptors. They have an affinity for mauscarinic receptor sites but lack the intrinsic activity.
b) Capable of preventing responses to parasympathetic nervous system stimulation.
c) More effective at blocking the pharmacological effects produced by muscarinic receptor agonists than in blocking physiological responses evoked by parasympathetic nerve stimulation.
x) May be due to the fact that there are subtypes of muscarinic receptors which creates the need for more selective anti muscarinic drugs.
iv) Pharmalogical Effects.
a) Therapeutic doses of the antimuscarinic drugs produce effects attributable to the blockade of peripheral muscarinic receptors, similar receptors in the CNS.
b) PNS- possess both peripheral and CNS actions but the nature and intensity of these vary with the individual drug and the dose administered. Most peripheral effects are caused by an interruption of parasympathetic impulses to a given effector.
The pharmacological effects observed depend in large part on the existing activity of postgangionic cholinergic neurons.
c) Eye- block muscarinic receptors in the sphincter of the iris and the ciliary muscle.
d) Respiratory tract- relaxes of bronchial smooth muscle.
e) Secretory glands- inhibits secretions of glands of the nose, mouth, pharynx, and respiratory tree.
f) Salivary glands- Salivary secretion is abolished in a dose-dependant manner.
g) GI tract- have a marked inhibitory effect on motility throughout the GI tract. Reduces gastric acidity, pepsin secretion, and total gastric secretion.
h) Cardiovascular- Effects differ according to the dose administered and whether the subject is in the erect or recumbent position. At low doses, (0.4-0.6mg), bradycardia results. Above this the heart rate increases. In the standing or upright patient the cardiac output isn’t affected.
i) Genitourinary tract- Ureters and urinary bladder are relaxed. The sphincters and trigone muscles are relaxed.
j) Body temp- Suppress’ sweating, which leads to an increase in body temp.
k) CNS- produced only by antimuscarinic drugs that can cross the BBB.
x) Medulla and higher cerebral centers- Atropine- direct stimulation of the CNS, manifests as mild stimulation of respiratory centers.
Scopolamine- produces effects ranging from decreased psychologic efficiency to drowsiness, sedation, euphoria, and amnesia.
xi) Used for motion sickness.
vii) Therapeutic Uses
a) Difficult to obtain a high degree of selectivity in the organ or organs to be effected because the antimuscarinic drugs tend to affect many muscarinic sites.
c) Respiratory tract
d) Salivary secretion- Used to reduce salivary secretions for oral surgery.
e) GI tract
f) Cardiovascular system
g) Genitourinary tract
h) Preanesthetic medication- To reduce salivary secretions and respiratory suppression
j) Antidote for anticholinesterases.
viii) Adverse Effects
a) Atropine has a large margin of safety in adults.
b) Children are more susceptible to hyperthermia and other toxic effects.
ix) Uses in Dentistry:
a) Used in dentistry to reduce salivary flow. However, dental professionals need to be aware if any antimuscarinic drugs are used by the patient as they would already have a decreased salivary flow and they would need to treat it accordingly.
Ganglionic Blocking Agents
3-Classes of Ganglionic Blockers:
1. Depolarizing Drugs- Drugs such as Nicotine, initially produce stimulation followed by, various degrees of blocking measures. At High doses these agents can stimulate then, block other cholinergic receptors such as the CNS and neuromuscular junction receptors.
2. Competitive Drugs- Drugs for example, Trimethaphan and TEA (tetra-ethyl-ammonium) interfere with the binding of ACh to the nicotinic receptor.
3. Non Competitive Agents- Agents like hexamethonium and mecamylamine, a secondary amine, interfere with ganglionic transmission by blocking the "ION" channels that have been opened by the ACh. The mecamylamine shares components with hexamethonium and the Competitive blocking agents.
Nicotinic receptor antagonist:
inhibit the effects of acetylcholine on nicotinic receptors
Vessels (arteries, veins)
Decrease of tone and motility
Retention of urine
Nicotine: Alkaloid, depolarizing drug that stimulates transmission at autonomic ganglia and at nicotinic synapses in the CNS.
an important feature of nicotinic recptors is that they can become desensitized on continuous exposure
they are highly time and concentration dependent
The only therapeutic use of nicotine is tobacco cessation
Neuromuscular junction blocker: interfere with the ability of ACh to evoke endplate depolarization at the nicotinic receptor
There are 2 types of neuromuscular blocking agents:
Nondepolarizing agents: all these drugs act by occupying the endplate receptor sites of the muscle fiber but do not cause endplate depolarization, blocking access to these sites by ACh causing flaccid paralysis
depolarizing agents: act by binding to the cholinergic receptor at the muscle endplate causing depolarization of the muscle fiber
This is the longest non-depolarization agent used, along with Metocurine and gallamine, these agents are competitive neuromuscular blocking drugs. These are currently infrequently used due to umwanted side effects. These drugs act by occupying the Nicotinic and Muscarinic receptor sites of the muscle fiber blocking the sites to the ACh. This is not directly involved in depolarization, their method is inhibition of the neuromuscular transmission by competively blocking ACh from the binding sites.
Succinylcholine-** This is the most important depolarizing agent that is a bisquaternary compound . This agent unlike the non-depolarizing agents, is a much smaller molecule made up of two ACh molecules with acetyl ends attached. The atypical action of this agent is that it can cause an excitatory response initially then, it can start the depolarization process. This proces starts by binding to the cholinergic receptor at the muscle endplate. The excitation commonly can trigger fasiculation, (twitching of muscles), in its early phase.
An excellent refresher on action potentials in the cell membrane:
Types of drugs
Autonomic nervous system
The release of norepinephrine (noradrenaline) can be evoked or inhibited by the actions of
. Drugs that evoke norepinephrine produce effects resembling those of sympathetic nerve activity and are called sympathomimetic agents. They include
, which act indirectly, mainly by expelling norepinephrine from its storage area in nerve terminals. They cause an increase in the heart rate (sometimes leading to
, or irregular heartbeats) and other sympathetic effects. Ephedrine is occasionally used as a nasal decongestant. Amphetamine-like drugs also have strong effects on the brain, causing feelings of excitement and euphoria as well as reducing appetite, the latter effect leading to their use in treating obesity. Their effects on the brain have led to their recreational use and to their use as agents to enhance athletic performance. These drugs are liable to cause addiction, and overdosage may have dangerous cardiovascular and mental effects. Methylphenidate, an amphetamine-like compound sold under the trade name Ritalin™, has been shown to be useful in the treatment of
Drugs that act as agonists or antagonists to adrenoceptors are listed in the table. Alpha1-adrenoceptor antagonists are important because they block the ability of norepinephrine to constrict the blood vessels (vasoconstriction). Since most blood vessels are subject to the continuous vasoconstrictor influence of sympathetic nerves, blocking these receptors causes a widespread relaxation of the blood vessels (vasodilation). These drugs are sometimes used to treat
high blood pressure
the section [[EBchecked/topic/171942/drug/233953/Cardiovascular-drugs#toc233953|
]]). Alpha1 antagonists can also be used in the treatment of some urinary bladder dysfunction conditions because they block the contraction of the sphincter at the bladder outlet that is mediated by α1-receptors.
Beta-adrenoceptor antagonists are extremely useful in treating various kinds of cardiovascular diseases, particularly hypertension, dysrhythmias, and angina. The effect is usually achieved by blocking the β1-adrenoceptor; however, some drugs also block the β2-adrenoceptor. This gives rise to various unwanted
, such as constriction of the bronchial smooth muscle, which can be dangerous to patients with asthma, and constriction of certain blood vessels, which may cause patients to have cold hands and feet. Beta-adrenoceptor antagonists are also useful in controlling muscle tremors and anxiety that result from overactivity of the sympathetic system.
Alpha2 agonists, such as clonidine, are used to treat hypertension. Clonidine lowers blood pressure by inhibiting the release of norepinephrine from sympathetic nerves, an effect mediated by presynaptic α2-adrenoceptors, and by acting on centres in the brain that are concerned with the control of blood pressure. It is a potent and effective drug, but it has the disadvantage that the blood pressure may rise to a dangerously high level if the drug is stopped or even if the patient misses a dose.
Beta2 agonists relax smooth muscle in many parts of the body (
the section [[EBchecked/topic/171942/drug/10937/Drugs-affecting-muscle#toc10938|
Drugs that affect smooth muscle
]]) and are used mainly to treat asthma. None of the available drugs are completely selective for the β2-adrenoceptor, and they tend to produce unwanted effects on the heart, such as increased heart rate and disturbances of cardiac rhythm, through their action on cardiac β1-adrenoceptors. To reduce these side effects, the β2 agonists are usually given by inhalation.
The action of the released norepinephrine is terminated when it is recaptured by sympathetic nerve terminals, a process that involves a selective transport mechanism in the neuronal membrane. Various drugs block this transport system and thus enhance the effects of sympathetic nerve activity; the most important examples are
. Overdosage with these drugs results in overactivity of the sympathetic system and the occurrence of
. The effects of these drugs on brain function, which are of more clinical importance than their peripheral sympathomimetic effects, may be due to this action of inhibiting the uptake of norepinephrine into adrenergic neurons in the brain.
help on how to format text
Turn off "Getting Started"