Pharmacology Test 4

Front 1

What are preganglionic nerves?

Back 1

-sympathetic and parasympathetic preganglionic fiber that release acetylcholine
-ACh has two receptors: muscarinic and nicotinic
-postgaglionic nerves have nicotinic receptors

Front 2

What is acetylcholine? How is it released?

Back 2

-a small molecule that acts as a chemical messenger to propagate nerve impulses across the neuromuscular junction between a nerve and a muscle
-when the nerve impulse from a motor neuron arrives at the tip of its axon, ACh molecules stored there in vesicles are released into the synaptic gap
-some of these moelcules bind to nicotinic receptors (large proteins embedded into muscle fiber)

Front 3

What are nicotinic receptors?

Back 3

-nicotine can also bind to them lieke acetylcholine
-cholinoreceptors that are activated by alkaloid nicotine
-receptor are localized at the myoneural junctions of somatic nerves and skeletal muscle, autonomic ganglia including the adrenal medulla, and certain areas of the brain

Front 4

What are nicotinic receptors structurally?

Back 4

-consists of 5 protein subunits in skeletal muscle and 2 protein subunit in ganglia that form ligand-gated (ie regulated) ion channel pores in the cell membranes
-causes depolarization

Front 5

What drug is commonly used for nicotinic receptors?

Back 5

-hexamethonium

Front 6

What occurs during binding of acetycholine to nicotinic receptors in skeletal muscle?

Back 6

-1 molecule of ACh per alpha subunit (2 total)
-binding of 2 ACh molecules causes a rapid opening of the channel that permits passage of ions, mostly sodium
-Na+ flows down gradient into cell causing depolarization and an excitatory postsynaptic potential through transverse tubules, resulting in release in calcium from sarcoplasmic reticulum and ultimately muscle contraction

Front 7

What occurs during hydrolysis of acetylcholine in muscle cells?

Back 7

-done by acetylcholine esterase
-results in muscle cell repolarization

Front 8

Where are N1-nicotinic receptors located?

Back 8

-found in both sympathetic and parasympathetic autonomic ganglia and in the adrenal medulla

Front 9

Where are N2-nicotinic receptors located?

Back 9

-found at the neuromuscular junction of skeletal muscle
-similar to N1-nicotinic receptors

Front 10

What do N1-nicotinic receptors do for autonomic ganglia? Adrenal medulla?

Back 10

-automatic firing of postsynaptic connection for both sympathetic and parasympathetic neurons
-secretion of epinephrine

Front 11

What can result due to continued presence of nicotinic agonists at nicotinic receptors?

Back 11

-excessive cholinergic stimulation
-can lead to a "depolarizing blockade" (phase I block) in which normal depolarization is followed by persistant depolarization
-skeletal muscle is unresponsive to either neuronal stimulation or direct stimulation

Front 12

What selective nicotinic receptor antagonists can block the effect of ACh at skeletal muscle and autonomic ganglia respectively?

Back 12

-tubocurarine and trimethaphan

Front 13

What are the five steps of ganglionic neurotransmission? What drugs can block at certain steps?

Back 13

- primary event is rapid depolarization of postsynaptic nicotinic receptors by ACh (duration is milliseconds and blocked by hexamethonium)
-thene development of inhibitory postsynaptic potential also lasting milliseconds (blocked by atropine and alpha adrenergic blockers)
-then devlopement of late excitatory post synaptic potential (which lasts for 30-60 seconds and blocked by atropine due to activation of M1 receptors)
-then late slow EPSP for several minutes
-then secondary events of ganglionic transmission modulate the primary depolarization, by making it more or less likely to occur.
-conventional nicotinic receptor antagonists can inhibit ganglionic transmission completely
-muscarinic antagonists,alpha adrenergic antagonists and peptidergic antagonists can no do so

Front 14

What are the mechanisms of drugs that mimic acetylcholine?

Back 14

-by directly activating cholinoreceptors/ nicotinic receptors
-or inhibiting acetyltransferase, thus blocking the termination of action of endogenous acetylcholine

Front 15

What are direct-acting cholinomimetics?

Back 15

-direect-acting cholinomimetics may have affinity for both muscarinic and nicotinic receptors, or they may be more selective and activate only one of the two.

Front 16

What are indirect-acting cholinomimetics?

Back 16

-amplifiers which act only where acetylcholine is released from endogenous storage
-have little or no effect at innervated cholinoreceptors that are present on endothelium of blood cells

Front 17

What drugs are direct and nicotinic only?

Back 17

-nicotine and succinylcholine

Front 18

What occurs during nicotinic cholinomimetics of autonomic ganglia?

Back 18

-both sympathetic and parasympathetic ganglia have to be activated
-actions on dually innervated organs (pupil, sinoatrial node of heart) are unpredictable

Front 19

What occurs during nicotinic cholinomimetics of skeletal muscle neuromuscular junctions?

Back 19

-opening of the Na/K channels on the end plate results in depolarization and intially contractions of the muscle units

Front 20

What occurs during maintained depolarization caused by a long-lasting nicotinic agonist such as succinylcholine?

Back 20

-results in block of impulse propagation from the end plate to the skeletal membrane and leads to paralysis

Front 21

What is nicotine? mechanism of action?

Back 21

-a constituent of tobacco
-nicotine mimics the action of acetylcholine at the cholinergic nicotinic receptors of ganglia in skeletal muscle and in the CNS
-decreases MAO activity in the brain and other organs resulting in increased levels of dopamine

Front 22

What are pharmacologic properties of nicotine?

Back 22

-volatile liquid alkaloid that is readily absorbed from the respriatory tract, oral membranes, skin and is rapidly distributed
-metabolized primarily in the liver (rapid witha plasma half-life of apporximatly 1 hour), but also in the lung and kidney (rapid excretion of nicotine and its metabolites)
-a strong base and is highly ionized in the stomach and hence poorly absorbed from the stomach
-nicotine is excreted in the milk of lactating mothers who smoke

Front 23

What is the relationship between tobacco smoke and nicotine?

Back 23

-nicotine "rides" on small particles of tar
-when smoke gets to lungs, nicotine is absorbed quickly and reaches the brain in about eight seconds after the smoke is inhaled
-american cigarettes cotnain about 9 mg of nicotine, but because much of the nicotine is burned off, a smoker gets about 1 mg of nicotine in every cigarette
-reaches the central nervous system in about 3-5 minutes when chewed

Front 24

What are the effects of nicotine on the nervous system?

Back 24

-may cause nausea and vomiting in the early stages of smoking
-increases psychomotor activity and cognitive function
-increases release of adrneal catecholamines and antidiuretic hormone (ADH)
-increases blood pressure and heart rate
-increases tone and secretions of the GI tract
-faster respiration
-cnstriction of arteries
-cna be stimulating or relaxing based on dosage and the person's mood
-acts on central and peripheral nervous system

Front 25

What are adverse effects of nicotine?

Back 25

-contributes to cancer (lungs, oral cavity, bladder and pancreas, obstructive lung disease, coronary artery disease and peripheral vascular disease
-poisoning occurs from exposure to insecticides cotnainign nicotine, or in children by accidental ingestion of tobacco products
-death may result within afew minutes from respiratory failure.
-for therapy, vomiting or gastric lavage (followed by activated charcoal)

Front 26

What is the tolerance in nicotine?

Back 26

-developes rapidly
-primarily cellular, some metabolic

Front 27

What is the dependence of nicotine?

Back 27

-produces strong psychologic dependence
-activates the "brain reward system" (increased activity of dopamine in the nucleus accumbens)
-withdrawlal-like symptoms indicative of physical dependence occurs within 24 hrs and persists for weeks or months
-dizziness, tremor, increased blood pressure, drug craving, irritability, anxiety, restlessness, difficulty in concentration, drowsiness, headache, sleep distrubances, increased appetite, GI complaints, nausea, and vomiting may occur

Front 28

What are the various medications and replacement therapies for nicotine dependence? How does overdsose occur?

Back 28

-Nicotine polacrilex
-transdermal patch
-nasal spray
-cna casue overdose if person also smokes cigarettes

Front 29

What is nicotine polacrilex as replacement therapy for nicotine? trasdermal patch? nasal spray? problems with each?

Back 29

-a nicotine resin contained ina chewing gum and has therpeutic value for diminishing withdrawal symptoms with behavioral midification to overcome psychologic dependence
-has objectional tase and may casue stomach discomfort, mouth sores, and dyspepsia
-patch can cause local skin irritation
-nasal spray can casue nasal irritations and irirtatons in nmouth and throat if used as inhaler

Front 30

What is the theory for why long-term exposure to cigarettes cause dependence and addiction?

Back 30

-limbic pathways that use dopamine are affected

Front 31

What are common withdrawal symptoms of nicotine?

Back 31

-anxiety, depression, headaches, and fatigue

Front 32

What is the dopamine reward pathway?

Back 32

-drugs usually increase dopamine so interesty is in the dopaminergic system
-increased levels of dopamine lead to rewarding effects or positive reinforcement of drugs of misuse

Front 33

What are some available pharacologic therapies with some reported success that affects acetylcholine and cholinoergic receptor metabolism?

Back 33

-Clonidine (alpha adrenoreceptor agonist)
-nortripyline (Antidepressant)
-bupropion (antidepressant)
-selegilline (MAO-B inhibitor)
-vareicline (partial nicotine receptor agonists)

Front 34

WHat are nicotinic receptor blockers?

Back 34

-include separate groups of drugs that selectivly block ganglia and the neuromuscular junction in skeletal muscle
-ganglion blockers are rarely used but neuromuscular blockers are very important in modern anesthesiology

Front 35

What are avaiiable ganglionic blockers of nicotinic receptors? How are they administered? Excreted?

Back 35

-trimethaphan and mecamylamine
-competitive antagonists
-trimethaphan has positive charge and is given intraveonously and acts peripherally, excreted by kidney
-mecaamylamine is given orally and does not cross the blood-brain barrier, excreted more slowly by the kidney

Front 36

How do ganglionic blockers of nicotinic receptors work?

Back 36

-have little or no effect at neuromuscular junction
-block both sypathetic and parasympathetic ganglia and therefore have widespread autnomic actions
-work by interfering with the postsynaptic action of acetylcholine

Front 37

What medical uses are ganglionic blockers of nicotinic receptors for?

Back 37

-primary use is for hypertension
-for intial control of blood pressur ein patients with acute dissecting aortic aneurism
-rarly used due to very poorly tolerated autonomic toxicities

Front 38

What are the properties of atropine as a cholinoreceptor blocking agent?

Back 38

-competitive antagonists
-action on muscarinic recptors
-prototype

Front 39

How have cholinoreceptor drugs changed from atropine used as an agent?

Back 39

-agents have become more depolarizing
-actions on more nicotinic receptors
-and act more on neurmuscualr junctions

Front 40

Whata drugs are cholinoreceptor blockign agents?

Back 40

-atropine
-scopolamine
-propantheline
-trimethaphan
-cisatracurium
-succinylcholine

Front 41

WHart are the two groups of drugs that affect skeletal muscle function and where do they primarily act?

Back 41

-neuromuscular blockers: interfere with the transmission at the neuromuscular end plate, lack CNS Activity, peripherally acting
-spasmolytics: centrally acting

Front 42

What are the general properties of tubocuranne as a skeletal muscle relaxant?

Back 42

-long action
-non-depolarizing
-neuromuscular blocker
-skeletal muscle relaxant

Front 43

What are the general properties of mivacurium as a skeletal muscle relaxant?

Back 43

-short acting
-non-depolarizing
-neuromuscualr blocker
-skeletal muscle relaxant

Front 44

What are the general properties of succinylcholine as a skeletal muscle relaxant?

Back 44

-depolarizing
-neuromuscular blocker

Front 45

What are the general properties of baclofen, diazepam, and tizanidine as skeletal muscle blockers?

Back 45

-CNS acting
-chronic use
-spasmolytics

Front 46

What are the general properties of dantrolene as a skeletal muscle blocker'?

Back 46

-muscle action
-chronic use
-spasmolytics

Front 47

What are the general properties of of cyclobenzaprine as a muscle relaxant?

Back 47

-actue use
-spasmolytic

Front 48

What are the prototypes for non-depolarizing neuromuscular blockers?

Back 48

-tubocurarine
-vescuronium
-atracurium

Front 49

What are prototypes for depolarizing neuromuscular blockers?

Back 49

-succinylcholine

Front 50

What are prototypes for spasmolytic neuromusucalr blockers?

Back 50

-diazepam, baclofen, cyclobenzaprine, dantrolene, tizanidine, and botulinum toxin

Front 51

Where do neuromusucular drugs bind?

Back 51

-bind to all nicotinic receptors (at neuromuscualr junction and autonomic ganglia) and some actually bind muscarinic receptors to a small extent.

Front 52

WHat do neuromusucal blockers induce during their mechanism of action?

Back 52

-block skeltal muscle transmission, inducing paralysis

Front 53

WHat is the mode of action of non depolarizing blocking agents of neuromusuclar blockers?

Back 53

-majority of the clinically-relevant neuromuscualar blockers
-act by blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors

Front 54

What is the mode of action of depolarizing blockign agents of neuromuscualar blockers?

Back 54

-agents act by depolarizing the plasma membrane of the skeltal muscle fiber
-persistant depolarization makes the muscle fiber resistant to further stimulation by ACh (succinylcholine)

Front 55

How do neuromusucular blockers work?

Back 55

-act as competitive antagonists against6 acetylcholine at the site of postsynaptic acetylcholine receptors
-depolarizing blocker binds to the receptor and opens the ion channel, resulting in depolarization of the end plate
-non-depoalrizing blocker binds to the receptor but does not open the channel
-effects of these drugs can be reversed by adminstration of a cholinesterase inhibitor

Front 56

What is neuromuscular transmission at the end plate?

Back 56

-arrival of electrical impulse at the motor nerve terminal
-influx of calcium and release of acetylcholine
-acetylcholine diffuses across the synaptic cleft to the nicotinic receptor located on the motor end plate
-casues influx of calcium into muscle cell

Front 57

At what locations can skeletal muscle relaxation and paralysis can occur from interruption of function at several sites along the pathway from the CNS?

Back 57

-myelinaed somatic nerves
-unmyelinated motor nerve terminals
-nicotinic acetylcholine terminals
-motor end plate
-muscle membrane
-intracellular contractile apparatus

Front 58

What are the modes of action of neuromuscular blockers?

Back 58

-competitive pharmcologic antagonism of ACh presynaptically via inhibition of ACh synthesis or release
-and prolonged ACh-like agonist action at the postsynaptically receptor

Front 59

What is the mode of action of tubocurarine as a non-depolarizing neuromuscular blocking agent? Toxicities?

Back 59

-prototype
-competitive antagonism prevents depolarization by ACh at the skeletal muscle and end plate
-respiratory and autonomic effects

Front 60

What is succinylcholine (agonist) as a depolarizing neuromuscular blocking agent? MODe of action? Toxicities?

Back 60

-agonist
-has short action (3-6 min) fiollowing a single dose due to rapid metabolism via plasma cholinesterases
-some patients experiance prolonged duration of action due to enzymatic deficency (genotypic variation)
-end plate is depolarized causing brief defasciculations followed by flaccid paralysis (phase 1), which is not reversed by AChE inhibitors
-muscle end plate repoalrizes (phase II) with continuous infusion but remains blocked
-toxicities include GI distress, emesis, muscle pain, and hyperkalemia

Front 61

What is the role of antagonistic non-depolarizing neuromuscular blockers? toxicities?

Back 61

-prevent normal depoalrization of the end plate
-can be surmounted by increasing acetylcholine concentration in the synapse (Cholinoetserase inhibitors)
-competitive neuromuscular blockign drugs are used to produce skeletal muscle relaxation, which is used for surgical procedures of medium and long duration
-toxicities include hypotension and excessive neuromuscular vlock from requiring prolonged respiratory support

Front 62

WHAT is the major use of succinylcholine clinically? toxicities?

Back 62

-facilitate intubation and other procedures of very shrot duration
-increases abdominal pressure, arrythmias, and postoperative muscle pain

Front 63

What is the difference between non-depolarizing and depolarizing drugs in autonomic effects on neuromuscular junction?

Back 63

-non-depolarizing drugs have no effect on autonomic ganglia, except for tubocurarine (weak blocker)
-depolarizing drugs stimulate autonomic ganglia
-non-depolarizing drugs have from no effect to moderate ability to release histimine
-depolarizing drugs have slight ability to release histimine
-avoid pancuronium with cardiac patients since it's a moderate blocker of muscarinic receptors

Front 64

What are the 2 types of deriviatives of neuromusuclar drugs?

Back 64

-isoquinoline
-steroid

Front 65

What drugs can be used for revrsal of non-depolarizing neuromuscular blockade? How do they work?

Back 65

-neostigmine and pyridostigmine
-increase availabilty of acetylcholine at the motor end plate mainly by inhibition of acetylcholinesterase
-also increase neurotranmitter from the emotor nerve channel
-edorphonium inhibits acetylcholinesterase only

Front 66

What is the main differance between depolarizing and non-depolarizing agents?

Back 66

-non-depolarizing blockers are reversed by acetylcholinestrase inhibitor drugs. Since they are competitive antagonists at the ACh receptor, they cna also be reversed by increasesin ACh
-depolarizing blockers take longer to reverse due to their closly related propeertiees to acetylcholine. patient will experiance fasciculations before paralysis occurs and post-operative pain

Front 67

WHAT is the major use of succinylcholine clinically? toxicities?

Back 67

-facilitate intubation and other procedures of very shrot duration
-increases abdominal pressure, arrythmias, and postoperative muscle pain

Front 68

What is the difference between non-depolarizing and depolarizing drugs in autonomic effects on neuromuscular junction?

Back 68

-non-depolarizing drugs have no effect on autonomic ganglia, except for tubocurarine (weak blocker)
-depolarizing drugs stimulate autonomic ganglia
-non-depolarizing drugs have from no effect to moderate ability to release histimine
-depolarizing drugs have slight ability to release histimine
-avoid pancuronium with cardiac patients since it's a moderate blocker of muscarinic receptors

Front 69

What are the 2 types of deriviatives of neuromusuclar drugs?

Back 69

-isoquinoline
-steroid

Front 70

What drugs can be used for revrsal of non-depolarizing neuromuscular blockade? How do they work?

Back 70

-neostigmine and pyridostigmine
-increase availabilty of acetylcholine at the motor end plate mainly by inhibition of acetylcholinesterase
-also increase neurotranmitter from the emotor nerve channel
-edorphonium inhibits acetylcholinesterase only

Front 71

What is the main differance between depolarizing and non-depolarizing agents?

Back 71

-non-depolarizing blockers are reversed by acetylcholinestrase inhibitor drugs. Since they are competitive antagonists at the ACh receptor, they cna also be reversed by increasesin ACh
-depolarizing blockers take longer to reverse due to their closly related propeertiees to acetylcholine. patient will experiance fasciculations before paralysis occurs and post-operative pain

Front 72

Why are muscular antagonists often administered at the same time as cholinesterase inhibitor?

Back 72

-only want increase in ACh at neuromusucular junction which is nicotinic but cholinesterase inhibitor works everywhere
-it will decrease secretions
-such as atropine and or glycopyrolate

Front 73

What is the mechanism of action diazepam as a neuromusuclar blocker?

Back 73

-benzodiazepine that facilitates GABA mediated presynaptic inhibiton
-action in reducing spasticity is partly mediated in the spinal cord
-produces sedation at doses needed to reduce muscle tone (side effect)
-has an addicitive effect

Front 74

What is the mechanism of action of baclofen as a neuromusuclar blocker? How is it metabolized? Eliminated? Side effects? administration?

Back 74

-P-chlorophnenyl GABA
-was designed to be an orally active GABA-mimetic agent
-activates GABA(beta)-receptors in the spinal cord
-activation of receptors causes hyperpolarization (increasess potassium conductance)
-causes presynaptic inhibiton and reduces calcium influx
-can cross BBB
-acts both pre and postsynaptically to inhibit spinal reflexes
-metabolized by the liver and eliminated by renal excretion
-can cause ssedation, fatigue, dizziness, lowering of the seizure threshold, and cognitive dysfunction
-administered intrathecally or P.O

Front 75

What is the mechanism of action of tizanidine as a neuromuscular blocker? metabolism? elimination? side effects?

Back 75

-cogener of clonidine
-acts through agaonist effects on the alpha-2 adrenergic system at both the spinal and supraspinal levels to reduce spasm
-extensivly metabolized in the liver to inactivee compounds that are excreted by kidneys
-short-acting drug for the management of spasticity
-side effects include sedation, dizziness, hypotension, nausea, and dry mouth

Front 76

What is the mechanism of action of cyclobenzaprine as a neuromusular blocker?

Back 76

-acts centrally to decrease an acute spasm due to muscle injury, but is ineffective in cerebral palsy or spinal cord injury
-closely related to the tricyclic antidepressants (amitriptyline and imipramine)

Front 77

What is the clinical use of dantrolene as a neuromuscular blocker? side effects? mechanism of action?

Back 77

-hydantoin derivative
-site of action is the peripheral muscle rather than the central neurotransmitter systems
-dantrolene is the intial medication of choice for spasticity of cerebral origin because it acts at the level of the pereipheral muscle with minimal untoward central effects
-livere abnormalities can be seen with this agent thus liver enzymes must be monitored
-side effects also include weakness, nausea, diarrhea, and paresthesias
-inhibits release of calcium from sarcoplasmic reticulum durign muscle contraction
-onyl direct acting muscle releaxant
-affects excitation-contraction coupling mechanissm of skeletal muscle by depressing the release of ionic calcium from the sarcoplasmic reticulum to the myoplasma

Front 78

What is botulinum toxin used for as a neuromuscular blocker? How does it work?

Back 78

-used for denervation
-botox and myobloc available as drugs
-toxin exerts its effect by inhibiting the release of acetylcholine into the neuromuscular junction
-cost is major concern in usre, can cost thousands of dollars and is only temporary

Front 79

What are common muscle relaxants used to relax striated muscles? What are they used for clinically?

Back 79

-methocarbamol, carisprodol, chloroxazone, gabapentin, metaxalone, and orphenadrine
-relieef of spasticity in neuromuscular diseases such as multiple sclerosis as well as spinal injury and stroke
-may be also used for pain relief in minor strain injuries and control of the muscle symptomss of tetanus
-used primarily as an adjunct for rest in management of acute muscle spasms associated with sprains, to physical therapy in rehab following stroke, spinal cord injury, or othere musculoskeletal conditions

Front 80

What is malignant hyperthermia? Symptoms? treatment?

Back 80

-an inheritied disease that causes a rapid rise in body temperature (fever) and severe muscle contractions when the affected person receives general anesthesia
-often noted for the first time after patient is given anesthesia during surgical procedure
-rapid rise in temp., muscle rigidity and stiffness, dark brown urine mussclee ache without obvious excercise
-treat with acetaminophen and a cooling blanket, also with dantrolene to reduce death
-fluids given by IV and mouth as well as certain medications are essential for maintaining kidney function durign an acute episode
-succinylcholine sometmes asociated

Front 81

What is histimine?

Back 81

-small molecule produced by decarboxylation of the amino acid histidine
-catalyzed by the enzyme L-histidine decarboxylase ina reaction that requires pyridoxal phosphate

Front 82

Where is histamine synthesized? What are mast cells?

Back 82

-located in many tissues including the brain
-stored and found in highest amounts in mast cells and basophils
-mast cells are found in the respiratory tract, skin (hands and feet), GI tract, and blood vessels
-store histamine ina granule bound in a complex with heparin, adrenosine, ATP and acidic protein

Front 83

How is histimine released?

Back 83

-energy and calcium dependent degranulation reaction
-energy and calcium independent release (displacement)

Front 84

How does energy and calcium dependeent degranulation reaction work in releasing histamine?

Back 84

- induced by immunoglobulin E (IgE) fixation to mast cells (sensitization) and subsequent exposure to a specific antigen
-complement activation (mediated by immunoglobulin G or immunoglobulin M) may also induce deegranulation

Front 85

How does energy and calcium independent release (displacement) work in releasing histamine?

Back 85

-displacement is induced by drugs such as morphine, tubocurarine, guanethidine, and amine antibiotics
-in addition, mast cell damage caused by noxious agents such as veneom or mechanical trauma can release histamine

Front 86

What drugs have a mechanism of action at H1 histamine receptors?

Back 86

-benadryl and loradine

Front 87

What drugs have a mechanism of action at H2 histamine receptors?

Back 87

-ranitidine

Front 88

Where are histamine H1 receptors found? What occurs when activated

Back 88

-found in the brain, heart, bronchi, gastrointestinal tract, vascular smooth muscles, and leukocytes
-membrane bound and couples to G-proteins (Gq-H1)
-activation causs increase in phospholipase A2 and D activity
-increase in diacylglycerol and intracellular calcium and increased cGMP
-increases wakefullness in brain
-causes vasodilation and increae in permeability in blood vessels
-stimulates nonvacular smooth muscles

Front 89

Where are histamine H2 receptors found? What occurs when activated?

Back 89

-membrane bound, found in thee brain,, heart, vascular smooth muscles, leukocytes and parietal cells
-increases cAMP production
-increases gastric acid production in stomach
-causes vasodilation in blood vessels
-relaxes smooth muscles

Front 90

Where are histamine H3 receptors located? What occurs when activated?

Back 90

-found in central nervouss system and peripheral nervous system at presynaptic nerve
-membrane bounc and coupled to G-proteins
-activation increases intracellular calcium and decreases cAMP
-decreases histamine release in nerve cells
-modulates release of dopamine, acetylcholine, serotonin, and norepinephrine
-decreases ACh release from vagus nerve

Front 91

Where are histamine H4 receptors located? What occurs when activated?

Back 91

-H4-receptors are found on hematopoietic cells and in the spleen, thymus, and colon
-increases chemotaxis of mast cells and leukocytes towards sites of inflammation
-inhibit production of cAMP and increasse intracellular calcium

Front 92

What are the histamine agonists?

Back 92

-betazole: 10x act. in H2 receptors that H1
-impromidine: 10000x H2 than H1
-methimepip: H3 agonist

Front 93

What are the uses of histamine agonists? adverse effects?

Back 93

-primarily diagnostic
-used in allergy testing assess histamine sensitivity ad in the test of gastric secretory function
-adverse effects include flushing, burning sensation, hypotension, tachycardia, and bronchoconstriction

Front 94

What are first generation antagonists of histimine H1 receptors?

Back 94

-alkylamins
-ethanolamines
-ethyleenediamines
-piperazines
-phenothiazines
-methylpiperidines

Front 95

What are alkylamines as first generation antagonists of histimine H1 receptors?

Back 95

-include chlorpheniramine and brompheniramine
-produce slight sedation
-antihistamines most frequently used in US

Front 96

What are ethanolamines ass first generation antagonists of histamine H1 receptors?

Back 96

-include diphenhydramine, doxylamine, and clemastine
-dimenhydrinate is a combo of diphendryamine and 8-chlorotheophylline
-producee marked sedation
-doxylamine marketed only as sleeping aid
-act as antiemetics

Front 97

What are ethylenediamines as first generation histamine H1 receptor antagonists?

Back 97

-include pyrilamine and antazoline
produce moderate sedation and can cause gastrointestinal upset

Front 98

What are piperazines as firsst generation histamine H1 receptor antagonists?

Back 98

-include mecliazine and cyclizine
-produce marked adveerse gastrointestinal effects and moderate sedation
-have antiemetic and antivertigo activities

Front 99

What are phenothiazines as first generation histimine H1 receptor antagonists?

Back 99

-include promethazine (nausea) and cyproheptadine (periactin)
-produce marked sedation
-have antiemetic activity
-also weak alpha-adrenoceptor antagonists

Front 100

What are methylpiperidines as first generation histimine H1 receptor antagonists?

Back 100

-include cyproheptadine
-have antihistamine, anticholinergic and antiserotonin activities
-will help increase appetites in pediatric patients

Front 101

What are second generation agents in histamine H1 receptor antagonists?

Back 101

-loratadine/deslortadine
-fexofenadine
-clemastine
-cetirizine

Front 102

What are piperidines of second-generation Histamine H1 antagonists?

Back 102

-includes loratadine and desloratadine (clarinex)and fexofenadinee
-has poor CNS penetration, little or no choliergic activity and greatly reduced sedation
-desloratadine is active metabolite of loratadine and has 15x more affinity for H1 receptor
-fexofenadine (allegra) is structually different but sedative activity is low but dose dependent

Front 103

What are ethanolamines as a second-generation histamine H1 antagonist?

Back 103

-includes clemastine
-much longer duration than dimenhydramine and some antiemetic activity

Front 104

What are alkylamines as a second-generation histamine H1 antagonist?

Back 104

-includes acrivastine and cetrizine (zyrtec)
-not associated with cardiac arrests or abnormalities
-poor penetrating of CNS
-less sedating and ineffective for motion sickness or antiemesis

Front 105

What is the difference between 1st generation and second generation histamine H1 receptor antagonists?

Back 105

-secondaries have marginal to no anticholirgic effect and has little to no sedative effect compared to 1st generation

Front 106

What are the pharmacologic properties of histamine H1 receptor antagonists?

Back 106

-well absorbed after oral administration
-effects seen within 30 minutes with 3-8 hrs with 1st gen. and 3-24 hours for second gen.
-lipid soluble
-1st gen can cross BBB, reduced in 2nd
-metabolized in liveer and induce microsomal enzymes

Front 107

What are pharmacologic actions of histamine H1 receptor antagonists?

Back 107

-ethanolamines, phenothiazines, and ehthylenediamines have muscarinic-cholinergic antagonist activity
-are effective local anesthetics due to blockade of sodium channels ine excitable tissues (dimenhydrinate and promethazine are potent)
-relax histamine-induced contraction of bronchial smooth muscle
-block vasodilator action of histamine
-inhibit histamine-induced increases in capillary permeability
-block mucus secretion and sensory nerve stimulation
-1st gen cause CNS depression but sometimes stimulation in children and some adults

Front 108

What are therapeutic uses of histamine H1 receptor antagonists? Specific drug uses?

Back 108

-treatment of allergic rhinitis and conjunctivitis
-clemastine approved for use with rhinorrhea
-used to treat common cold bases on anti-cholinergic properites
-diphenhydramine also has antitussive effect
-can treat urticaria (rash) and atopic dermatitis (hives)
-doxylamine and diphenhydramine used as sedatives/ sleep-aids
-also prevents motion sickness and suppresses appetite

Front 109

What are adverse effects of histamine H1 receptor antagonists?

Back 109

-produce sedation (synerstic with alcohol and othere depressants), dizziness, and loss of appetite
-can cause GI upset, nausea and constipation or diarrhea
-producee anticholinergic effects (dry mouth, blurred vision, and urine retention)
-astemizole and terfenadine (2nd gen) were taken off markeet due to Q-T prolongation and ventricular tachycardias

Front 110

What are the histamine H2 receptor antagonists?

Back 110

-includes cimetidine, ranitidine, famotidine, and nizatidine
-competitive antagonists at H2 receptor at gastric parietal cell
-used in treatment of gastrointestinal disorderss including heartburn and acid-induced indigestion
-promotee healing of gastric and duodenal ulcers and used to treat hypersecretory states such as zollinger-ellison syndrome

Front 111

What is cimetidine as a histamine h2 receptor antagonist? adverse effecrs?

Back 111

-usually given4 timess daily
-reduces acid secretion by approximatly 70% for 4-5 hours
-associates witha low incidence of mild GI upset, headache, and mental confusion esp. in the elderly
-can cause thrombocytopenia
-acts as a androgen-rceptor antagonist and can inducee dynecomastia adn impotence
-a competitve inhibitor of CYP 450 mixed-function oxidase system and can increase half-life of drugs
-decreasses aborption of ketoconazole
-decrease bioavailbilty by antacids

Front 112

What is ranitidine as a histamine H2 receptor antagonist?

Back 112

-5 to 10 times more potent than cimetidine and requires a less frequent dosing schedule, twice daily
-does not bind to the androgen receptor, it's effects on drug metabolism are less than those of cimetidine
-has low incidence of headache and cutaneous rash

Front 113

What is famotidine as a histamine H2 receptor antagonist?

Back 113

-appoximatly twice as potent as ranitidine and has a longer duration of action, given one daily
-produces adverse effects sismilar to those of ranitidine but does not bind to androgen receptor
-frequently used in its intravenous form for stress-relates gastritis
-mental status changes may occur esp in the elderly

Front 114

Why does benedryl relieve itchy eyes and runny nose?

Back 114

-shifts H1 receptor to inactivated site

Front 115

Why doesn't loratadine cause drowsiness?

Back 115

-ionized at physical pH and doesn't cross BBB

Front 116

Cometidine is a selective H2 receptor antagonists used to inhbit histamine induced gastric acid secretion. What's the potential adverse effect?

Back 116

-altered drug metabolism of CYP 450

Front 117

What are the chromones? What are they used for? Adverse effects?

Back 117

-include cromolyn and nedocromil sodium
-poorly absorbed salts that are administered by inhalation
-inhibit release of histamine and other autocoids from the mast cell
-each are used prophylactically in the treatment of asthma and do not reverse bronchospasm
-adverse effects include sore throat and dry mouth
-nedkcromil sodium appears to be more effective in reducing bronchospasm caused by exercise or cold air

Front 118

How is serotonin synthesized? distribution? Storage?

Back 118

-synthesized from amino acid 1-tryptophan by hydroxylation and decarboxylation
-apporximatly 90% of serotonin is found in the enterochromaffin cells of the gastrointestinal tract
-much of the remaining 10% is found in the platelets
-smaller amounts ar found in the othr tisues, including the brain
-platelets acquire serotonin from the circulation during passage through the intestine by a specific and highly active uptake mechanisms
-stored in granules as a complex with ATP
-major breakdown product is 5-hydroxyindoleacetic acid (5-HIAA)

Front 119

What is the mechanism of action of serotonin type 1 receptors?

Back 119

-coupled to an inhibiton in cAMP, stimulation contracts arterial smooth muscle, especially in carotid and cranial circulation
-at presynaptic sites, neuronal serotonin release is inhibited

Front 120

What is the mechanism of action of serotonin type 2 receptors?

Back 120

-coupled to an increase in phospholipase C activity
-stimulation causes contraction of vascular and intestinal smooth muscle and increases microciculation and vascular permeability
-stimulation of this receptor on platelet membranes causes platelet aggregation
-in the CNS, this receptor mediates hallucinogenic effects

Front 121

What is the mechanism of action of serotonin type 3 receptors?

Back 121

-coupled to a lignad-gated ion channel
-stimulation of this recpetor in the area postrema causes nausea and vomiting
-stimulation on peripheral sensory neurons causes pain

Front 122

What is the mechanis m of action of serontonin type 4 receptors?

Back 122

-increase cAMP
-in gastrointestinal tract, receptors mediate an increase in secretion and peristalsis

Front 123

What is the mechanism of action serotonin type 5 receptors?

Back 123

-expressed in the brain and are coupled to a decrease in cAMP

Front 124

What is the mechanism of action of serotonin type 6 and 7 receptors?

Back 124

-cloned and appear to be coupled to an increase in cAMP biosynthesis
-type 6 receptors appear to be involved in anxiety and cognitive function
-type 7 receptors are involved in thermoregulation, learning memory, and mood

Front 125

What is buspirone as a serotonin agonist?

Back 125

-relativly specific to type 1A receptor agonists
-useful for the management of anxiety disorders

Front 126

What are the triptans as serotonin agonists? mechanism of action? specific drug effects and adverse effects?

Back 126

-includes sumatriptan, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan, and naratriptan
-class of type 1B, 1D, and 1F agonists
-!b agonist activity results in vasoconstriction of dilated cerebral vessels
-1D receptors inhibit vasodilation and inflammation of the meninges and pain transmission and the release of vasodilator substances such as calcitonin gene-related peptide (CGRP) in trigeminal neurons
-major use is the treatment of acute migraine
-about 50%-80% of patients report relief from pain within 2 hours
-may be useful to treat cluster headaches
-sumatriptan has 1B activity in coronary spasms and chest pain is an adverse effect of this
-adverse effects also include flushing, hypertension, nausea, and vomiting
-may also cause irritable bowel syndrome
-all available as oral agents
-sumatriptan and zolmitriptan also available as nasal sprays
-sumatriptan also available for subcutaneous injection

Front 127

What is trazodone as a serontonin agonist?

Back 127

-parent drug is metabolized to m-chlorophenylpiperazine, an activator of serotonin recepto type 1B and type 2 receptors
-also blocks the reuptake of serotonin
-used to treat depression

Front 128

What is tegaserod and cisapride as serotonin agonists?

Back 128

-tegaserod is a specific type 4 agonist used to treat irritable bowel syndrome and constipation
-tegaserod increases the release of acetylcholine in the gut and increase motility (speeds gastric emptying and reduces gastrointestinal sensitivity)
-valube in conditions by inadequate peristalsis
-major toxicity of tegaserod is diarrhea
-cisapride has the same mechansism of action as tegaserod but is available only for compassionate use because of toxicity (torsades de pointe arrythmia)

Front 129

How is cyproheptadine as a serotonin antagonist?

Back 129

-a potent histamine antagonist and also blocks serotonin type 1 and 2 receptors
-used most frequently to limit diarrhea and intestinal spasms produced by serotonin-secreting carcinoid tumors and postgastrectomy dumping syndrome
-produces sedation and anticholinergic actions

Front 130

What is ondasetron, granisetron, dolasetron, and palonosetron as serotonin antagonists?

Back 130

-highly effective in treating the nausea and vomiting associated with chemotherapy and radiation therapy and have become the primary agents used in this circumstance
-administered intravenously or orally
-intravenous administration 20 min prior to anticancer treatment is the most effective

Front 131

What is risperidone as a serotonin antagonist?

Back 131

-antagonist for type 2A-2C and dopamine (D2) receptors
-atypical antischizophrenic agent with reduced extrapyramidal activity

Front 132

What is clozapine as a serotonin antagonist?

Back 132

-mainly blocks dopamine D1 and D4 receptors
-also blocks serotonin type2A and 2C receptors and has mixed muscarinic antagonist/agonist activities
-a atypical antipsychotic with reduced extrapyrimidal effects

Front 133

What is fluoxetine and other SSRI's effects on serotonin receptors?

Back 133

-actions of this class of antidepressants are presumed to be due to decreased serotonin uptake into neurons

Front 134

What is the structure of ergot alkaloids? What are the 2 classes?

Back 134

-include a variety of compounds sahring the tetracyclic ergoline nucleus that are produced by the fungus claviceps pupurea
-these agents have strong structural similarity to the neurotransmitters norepinephrine, dopamine, and serotonin
-includes amine ergot alkaloids
-includes peptide ergot alkaloids

Front 135

What are the amine ergot alkaloids?

Back 135

-include ergonovine, methysergide, lysergic acid and LSD, and methylergonovine

Front 136

What are the peptide ergot alkaloids?

Back 136

-includes ergotamine, dihydroerotamine, ergocristine, ergonovine, bromocriptine, and pergolide

Front 137

What is the mechanism of action of ergot alkaloids?

Back 137

-display varyign degrees of agonist or antagonist activity in three receptor sites:
-alpha-adrenoceptors, dopamine receptors, and serotonin receptors
-pharmacologic application is determined by relative affinity and efficiacy of the individual agents for these receptor systems
-many agents exhibit partial agonist acitivites and thus can cause either stimulatory or inhibitory effects

Front 138

What are the pharmacologic properties of ergot alkaloids?

Back 138

-may be administered parenterally, rectally, sublingually, as inhalents, or orally and vary widely in theri absorption
-amine alkaloids are slowly and relativly poorly abosrbed
-peptide alkaloids are completely absorbed

Front 139

What ergot alkaloids are used therapeutically for postpartem hemorrhage?

Back 139

-ergonovine and methylergonovine
-most uterine-selective agents, cause prolonged and forceful contraction of uterine smooth muscles
-should not be used to induce labor

Front 140

What ergot alakloids are used therapeutically for acute migraines? How does it work?

Back 140

-ergotamine
-for acute migraine attacks
-major effect is cerebral vasoconstricition, reverses rebound vasodilation that is the probable cause of pain
-acts as a central serotonin receptor and alpha-adrenoceptor agonist
-most effective if administered early
-frequently combined with caffeiene which increases absorption
-produces lond-lasting and cumulative effects
-weekly dosage must be strictly limited

Front 141

What ergot alkaloids is used for prophylaxis of migraine? How does it work?

Back 141

-methysergide
-acts as a serotonin-receptor antagonist and it inhibits initial vasoconstriction in the early stages of a migraine
-effective in 60% of aptients for the prophylaxis of migraine
-it is effective after the onset of an attack
-cumulative toxicity of methysergide requires drug-free periods 3-4 weeks every 6 months
-also propanolol and other beta-adrenergic antagonist are also effective aganets for the prophylaxis of migraine

Front 142

What is used therapeutically for hyperprolactinemia? How does it work?

Back 142

-Bromocriptine mesylate and pergolide
-dopaminergic agonists and cause specific inhibition of prolactin secretion (elevated prolactin secretion can induce infertility and amenorrhea in women and galactorrhea in men and women)
-these agents are used to treat prolactin-secreting tumors of the pituitary to counteract central dopaminergic antagonists and to suppress normal lactation
-used as adjunct agents for levodopa in the management of parkinson's disease
-these agents reducre growth hormone secretion

Front 143

WHat drug is used therapuetically for diagnosis of variant angina?

Back 143

-ergonovine produces a diagnostic vasoconstriction of coronary arteries that are prone to vasospasm, as in variant angina
-ergonovine is administered intravenously during angiography

Front 144

What are various drug adverse effects of ergot alkaloids?

Back 144

-most serious adverse effect is prolonged vasospasm which can elad to gangrene and most frequently caused by ergotamine and ergonovine
-most common side effec tis gastrointestinal disturbance (nausea/diarrhea)
-methysergide toxicity includes retroperitoneal fibroplasia and cronoary and endocardial fribrosis, as well as CNS stimulation and hallucinations

Front 145

Which drug should not be given within 24 hrs of an ergot-containing or ergot-type drug b/c of vasospastic reactions?

Back 145

-sumatriptan

Front 146

What is the most useful drug fir reversing severe ergot-induced vasospasms?

Back 146

-nitroprusside

Front 147

What drug do you treat a 54 y/o male tobacco user with cancer in the larynx?

Back 147

-ondansteron

Front 148

Risperidone works primarily through inhibiton of receptors for?

Back 148

-histamine

Front 149

A patient has warfarin toxicity and has started an histimine type 2 blocker. What drug was he taking?

Back 149

-cimetidine

Front 150

What are voltage-gated ion channels?

Back 150

-transmembrane ion channels regulated by changes in membrane potential

Front 151

What are lignad-gated ion channels?

Back 151

-transmembrane ion channels that re regulated by interactions between neurotransmitters and their receptors (also called ionotropic receptors)

Front 152

What are metabotropic receptors?

Back 152

-G protein-couple drecpetors that respond to neurotransmitrters either by a dire actuion of G proteins on ion channels or by G protein enzyme activation that leads to formation of diffusible second messengers

Front 153

What are the receptors for glutamic acid? Drug actions?

Back 153

-excitatory
-antagonized by ketamine, phencyclidine, and newer antiepiletics

Front 154

What are the receptors for GABA? Drug actions?

Back 154

-inhibitory
-sedative-hypnotics and antiepiletic drugs facilitate GABAa receptors
-baclofen activates GABAb receptors

Front 155

What are the eceptors for acetylcholine? Drug actions?

Back 155

-M1: excitatory
-M2:inhibitory
-N: excitatory
-M blockers antagonize both M1 and M2 receptors
-AchE inhibitors facilitate ACh

Front 156

What are receptors of dopamine? drug actions?

Back 156

-inhibitory
-antagonized by older antipsychotics
-activated by anti-parkinsonian drugs, amphetamines, and cocaine

Front 157

How are excitatory postsynaptic potentials initiated?

Back 157

-when excitatory neurotransmitters activates sodium or calcium channels

Front 158

How are inhibitory postsynaptic potentials initiated?

Back 158

-inhibitory neurotransmitter opens chlorine channels and the cell membrane becomes hyperpolarized
-makes it more difficult for neurons to become activated

Front 159

What neurotransmitters exist in the CNS?

Back 159

-5-hydroxytryptamine
-glutamate
-GABA
-dopamine

Front 160

What are associated disorders with dopamine?

Back 160

-parkinson's disease
-psychosis
-drug abuse
-depression
-hyperprolactinemia

Front 161

What disorders are associated with acetylcholine?

Back 161

-parkinson's disease
-alzheimer';s disease
-narcolepsy

Front 162

What disorders are associated with serotonin?

Back 162

-depression/suicide
-psychosis
-obsessive compulsive disorder
-anxiety

Front 163

What disorder is associated with norepeinephrine?

Back 163

-depression
-narcolepsy

Front 164

What disorders are asaociated with GABA?

Back 164

-anxiety

Front 165

What disorders are associated with glutamate?

Back 165

-seizures

Front 166

Activation of metabotropuic receptors located presynaptically causes inhibiton by decreasing the influx of?

Back 166

-calcium

Front 167

What compound is most likely to function as a neurotranmitter in hierarchial systems?

Back 167

-glutamate

Front 168

What are hierarchial neuronal systems?

Back 168

-pathways involved in sensory perception and motot control
-large myelinated fibers conduct action potentials over long distances and release glutamate
-major excitaotry neurotransmitters in these systems are aspartate and glutamate
-local circuit neurons have short axons and release GABA
-these systems also include numerous small inhibitory interneurons, which use GABA and glycine as transmitters
-drugs that affect hierarchial systems have major effects on the overall excitability of the CNS

Front 169

What are diffuse neuronal systems?

Back 169

-contain monoamine and peptide transmitters including amines (dopamine, serotonin, and norepinephrine), opiod peptides or peptides that exert actions on metabotropic receptors
-extensively branched, unmyelinated axons that conduct action potentials slowly and can innervate different regions of the CNS functions such as slep and waking, attntion, appetitee, and emotion

Front 170

What is acetylcholine in the CNS?

Back 170

-5% of brain neurons have receptors for ACh
-most CNS responses to ACh are mediated by G-protein-coupled muscarinic M1 receptors that lead to slow excitation when activated
-the ionic mechanism of slow excitation involves a decrease in memrane permeability to potassium
-of the nicotinic receptors present in the CNS (less common than muscarinic receptors)
, those on the Renshaw cells activated by motor axon collaterals in the spinal cord are best characterozed
-drug affecting the choliergic systems in the brain include the acetylcholine esterase inhibitors and the muscarinic blocking agents used in parkinsonism

Front 171

What is dopamine in the CNS?

Back 171

-exerts a sllow inhibitory action at synapses in specific neuronal systems commonly via G-protein-coupled activation of potassium channels (postsynaptic) or inactivation of calcium channels (presynaptic)
-D2 receptor is the main dopamine subtype in basal ganglia neurons and is widely distributed in the supraspinal level
-dopaminergic pathways include the nigrostriatal, mesolimbic, and tuberofundibular tracts
-drugs that block tyhe activity of dopaminergic pathways include the odler antipsychotics
-drugs that increase the brain dopaminergic activity include CNS stimulants and antiparkinsonism drugs

Front 172

What is norepinephrine in CNS?

Back 172

-noreadrenergic neuron cell bodies are mainly located in the brain stem and the lateral tegemental of the pons. these neurons fan out broadly to provide most regions of the CNS with diffuse noradrenergic input
-excitatory effects are produced by activation of alpha 1 and beta 1 receptors
-inhibitory effects are caused by activation of alpha 2 and beta 2 receptors
-CNS stimulents, monoamine oxidase inhibtors and tricyclic depressants are exampels of drugs that enhance the activity of noradrenergic pathways

Front 173

What is serotonin in CNS?

Back 173

--most serotonin pathways originate from cell bodies in the raphe or midline regions of the pons and the upper brain stem
-these pathway innervate most regions of the CNS
-multipole serotonin receptor subtypes have been identified and with the same potassium channel
-serotonin can cause excitation or inhibition of CNS neurons depending on the receptor subtype activated
-bothe xcitatory and inhibitory actions can occur on the same neutron if apporpriate receptors ar epresent
-most of thre agents used in the treatment of major depressive disorders affect serotonergic pathways
-the actions of some CNS stimulents and newer antipsychotic drugs also appear to be mediated via effects on serotonergic transmission

Front 174

What isglutamic acid in the CNS?

Back 174

-most neurons in the brain are excited by glutamic acid
-high concentrations of glutamic acid in synaptic vesciles arte achieved by the vesicular gklutamate transport (VGLUT)
-both iontropic and metabotropicreceptors have been characterized
-subtypes of glutamate receptors are N-methyl-D-aspartate (NMDA)
-appear to have a role in synaptic plasticity relatedto learnign adn memory
-0excessive activation of NMDA receptor after neuronal injury maybe responsible for cell death
-glutamate metbotropic receptor activation cna result in G protein-coupled activation ofphospholipase C or inhibition of adenylyl cyclase

Front 175

What is GABA and glycine in the CNS?

Back 175

-most neurons in the GABA is the primary neurotransmitter mediating IPSPs in neurons in the brain and is important in the spinal cord
-alpha-GABA receptor activation opens chloride ion channels
-Beta-GABA recpeotrs are coupled to G-proteins that either openj potassium channels orclose calcium channels
-fast IPSPs are blocked by alpha-GABA recpeotr anatagonists and slow IPSPs are blocked by beta-GABA receptor antagonists
-drugs thart influence alpha-GABA receptor systems include sedative/hypnotics and anticonvulsants

Front 176

What are peptide transmitters in the CNS?

Back 176

-best defined peptides are the opiodpeptides (beta-endorphin, met- and leuenkephalin and dynorphin)
-substance P is a mediator of slow EPSPs in neurons involved in nociceptive sensory pathways in the spinal cord and brain stem
-peptide transmitters differ from nonpeptidetransmitters in that:
-peptides are synthesized in the cell bodies and transported to the nerve ending via axonal trasnport
-no reuptake or specific enzyme mechanisms have been identified for terminating their actions

Front 177

What are the different classes of antidepressants?

Back 177

-MAO inhibitors
-tricyclic antidepressants
-heterocyclic antidepressants
-selective serotonin reuptake inhibitors

Front 178

What si the amine hypothesis of mood?

Back 178

-hypothesis that major depressive disorder result from a functionaldeficiency of norepinephrine or serotnon at synpases in the CNS

Front 179

What are tricyclics as antidepressants?

Back 179

-droup of strucurally-related drugs resemblind phenothiazines chemically
-block reuptake of both norepinephrine and serotonin

Front 180

What are MAO inhibitors as antidepressants?

Back 180

-drugs that inhibit monoamine oxidase type A, which metabolizes norepinephrine and serotonin, or monoamine oxidase B, whihc metavbolizes dopamine

Front 181

What are selective serontonin reuptake inhibitors as antidepressants?

Back 181

-a group of drugs that selectvily inhibit serotonin transporters of the nerve-ending membrane

Front 182

Whart are heterocyclics as anti-depressants?

Back 182

-drugs of varied chemical strucutures
-several have actions diferent from those tricyclic antidepressants or selective seotonin reuptake inhibitors

Front 183

Whata re the prototype antidepressants of tricyclic drugs?

Back 183

amitriptyline and imipramine

Front 184

What are tricyclics as antidepressants?

Back 184

-droup of strucurally-related drugs resemblind phenothiazines chemically
-block reuptake of both norepinephrine and serotonin

Front 185

What are MAO inhibitors as antidepressants?

Back 185

-drugs that inhibit monoamine oxidase type A, which metabolizes norepinephrine and serotonin, or monoamine oxidase B, whihc metavbolizes dopamine

Front 186

What are selective serontonin reuptake inhibitors as antidepressants?

Back 186

-a group of drugs that selectvily inhibit serotonin transporters of the nerve-ending membrane

Front 187

Whart are heterocyclics as anti-depressants?

Back 187

-drugs of varied chemical strucutures
-several have actions diferent from those tricyclic antidepressants or selective seotonin reuptake inhibitors

Front 188

Whata re the prototype antidepressants of tricyclic drugs?

Back 188

amitriptyline and imipramine

Front 189

Whata re the prototype antidepressants of heterocyclic (second generation) drugs?

Back 189

-amoxapine
-bupropion
-maprotiline
-trazodone

Front 190

Whata re protoype antidepressantsof heterocyclics (thrid generation) drugs?

Back 190

-duloxetin
-mirtazapine
-nefazodone
-venlafaxine

Front 191

What are prototype antidepressants of selective serotonin reuptake inhibitors?

Back 191

-fluoxetine

Front 192

What are protoype antidepressants of MAO inhibitors?

Back 192

-phenelzine

Front 193

What is the mechanism of action of desiperamine and maprotiline as antidepressants?

Back 193

-inhibiton of neuronealreuptake of norepinephrine and serotonin
-increases the synaptic
-activities of neurotransmitters

Front 194

What is the mechanism of action of MAO inhibitors as antidepressants?

Back 194

-inhibits monamien oxidase and increases the presynaptic stores of both norepinephrine and serotonin
-leads to increases neurotransmitter effects

Front 195

What is the mechanism of action of mirtazapine as antidepressants? fluoxetin and trazadone as antidepressants?

Back 195

-blockade of presynaptic alpha 2 autoreceptors
-prevents feedback inhibiton releaseof norepinephrine

Front 196

What is the mechanism of action od

Back 196

-inhibits the reuptake of serontonin
-increases synaptic acitivies of these neurotransmitters

Front 197

What are tricyclic antidepressants? clinical uses?

Back 197

-chemically related tophenotriazines
-includes imipramine.amitripytiline andclomipramine
-most are long-acting and often converted to acitvie metabolites
-for moderate to severe endogenous depression includign insomnia (amitriptyline) or poor appetite (trazodone)
-for panic disorders (clomitpramine)
-for neuropathic pain
-short term treatment of nocturnal enuresis in older children

Front 198

What are adverse effects of tricyclic antidepressants?

Back 198

-sedatuion
-postural hypotension
-dry mouth
-blurredvision
-constipation
-occasional mania and convulsions
-riskof ventricular dysrhythmias
-overdose can lead toconfusion and mania
-liableto interact with other drugs

Front 199

What are selective serotonin reuptake inhibitors (SSRIs) as antidepressants? Adverse effects?

Back 199

-includes fluoxetine,flucoxamine, paroxetine, sertraline, and citalopram and venlafoxine
-acute toxicity is less than that of MAOI or TCAs
-most commonly prescibed antidepressants
-side effects include nausea, insomnia and sexual dysfunction
-has dangerous serotonin reaction if given with MAOI
-venlafaxine is lisceneced to treat generalized anxiety disorder

Front 200

What are monoamine oxidase inhibitors as antidepressants?

Back 200

-includes phenelzine and tranylcypromine
-unsleective and produce extremely long-lasting inhibition of the enzyme
-noradrenaline-selective (reboxetine) or non-selective (venlafaxime, duloxetine) inhibitors

Front 201

Whata re the differnces in thrid-generation heterocyclics as antidepressants?

Back 201

-duloxetine does NE and serotonin reuptake block
-mirtazapine conducts sedation only
-nefazodone conducts sedation and muscarinic receptor block
-venlafaxine conducts norepinephrine and serotonin reuptake block

Front 202

What are the differences in 2nd-generation heterocyclics as antidepressants?

Back 202

-amoxapine conducts sedation,muscarinic recpetor blokc, NE and serotonin reuptake block
-bupropion ahs no effects
-maprotiline has sedative effects, and muscarinic receptor block with norepinephrine reuptake block
-trazodone coducts sedation and some serotoninj reuptake block

Front 203

What is fluoxetine drug itneractions and effects as an antidepressant?

Back 203

-lithium, tricyclics, and warfarin
-casues increased blood levels of the second drug
-doses may needto be decreased

Front 204

What are the drug interactions with fluvoxamine as an antidepressant?

Back 204

-alprazolam, theophylline, tricyclics, and warfarin
-increased blood levelsof the second drug
-doses may need to be decreased

Front 205

Whata re drug interactions with monoamine oxidase inhibitors as antidepressants?

Back 205

-sympathomimetics, tyramine, and SSRIs
-casues hyeprtensive crisis and serotonin syndrome

Front 206

What are drug interactions with nefazodoneas a antidepressant?

Back 206

-alprazolam and triazolam
-causes increased blood levels of thre second drug
-may needto be decreased

Front 207

What are drug itneractions with paroxetine?

Back 207

-procyclidine, theophylline, tricyclics, and warfarin
-causesincreased vlood levels of the seocnddrug
-doses may need to be decreased

Front 208

Whata re drug interactions of setraline as antifdepressants?

Back 208

-tricyclics and warfarin
-increased effects and doses may need to be decreased

Front 209

What are drug interactuions with tricyclics as antidepressants?

Back 209

- with CNS depressants, causses additive CNS depression
-with clonidine, guanethidine,and methyldopa, causes decreased antihypertensive effects

Front 210

What is the serotonin syndrome?

Back 210

-conditon characterized by dangerously high levels of serotonin in the body
-can occur when you take certain combinations of presciption medications that afect serotonin levels in your body
-occurs if you SSRIs or SNRI's for dperessuion along with triptan medicationsto treat migraine
-can also occur with other drugs or supplements that affect serotonin levels such as st. john's wort
-signs and symptoms range from restlessness and rapid heartbeat to muscle rigidtiy and seizures
-go away quickly with treatment
-may need to disocntinue use of medications

Front 211

How do antidperessants treat major depressive disorder?

Back 211

-elevate mood, increase physical acitivty and mental alertness, increase appetite and sexual drive, improve sleep patterns, and reduce preoccupation with morbid thoughtsd
-drugs are effective in 70% of patients
-SSRI'spreferred over TCA's due tolimitedtoxicity
-MAO's used rarely only if TCA's don;t work or for "atypical"depression

Front 212

How is bipolaraffective disorder treated with antidepressants?

Back 212

-often treated with lithium to control mania

Front 213

How are antidepressants used for anxiety disorders?

Back 213

-treated wtih SSRIs, although unlike benzodiazepines
-full efficacy won;t be seen for weeks

Front 214

How is obsessive-compulsive disorder treatedw tih antidepressants?

Back 214

-treated wtih clomipramine, fluoxetine and other SSRIs

Front 215

How is social anxiety disorder treated with antidepressants?

Back 215

-SSRI's only

Front 216

How is enuresis (bed-wetting) treated with antidepressants?

Back 216

-tricyclic antidepressants,like imi[pramine, are used to suprress enureissi in childre over 6and adults
-exact mechanism is uncertain

Front 217

How is ADD/ADHD treated wtih antidepressants?

Back 217

-tricyclic amines (imipramine and desipramine) are useful in patients unresponsive or intolerant to stimulents
-atomoxetine is also appreoved treatment of ADHD

Front 218

How is chronic pain treated with antidepressants?

Back 218

-tricyclic amines and venlafaxine are often used for chronic pain of unknown oridgin
-SSRI's areineffective
-duloxetine is approved treatment of neuropathic pain associated wtih diabetes
-drugs may work directly on pain pathways, but exact mechanism of action is unknown

Front 219

What is the therapeutic effciacy of antidepresant drugs?

Back 219

-all ahve simialr therapuetic effciacy
-selection based ona dvserse efects
-effciacy occurs several weeks after administration and is associated with adaptive changed overtime such as decrreased AMP accumulation and a reduction of postjunctional beta-adrenoceptors as well as an increase in responsiveness of postjunctional serotonin 1A receptors

Front 220

What is the mechanism of action of tricyclic antidepressants?

Back 220

-block neuronal reuptake of norepinephrine and serotonin increasing their postsynaptic actions
-are generally highly lipid-soluble and have relativelylong half-lives
-are metabolized by ring hydroxylation and glucuronide conjugation or by demethylation
-monodemethylation of the tertiary amines imipramine and amitripytline results in the active secondary amine metabolites despiramine and nostriptyline, respectivly
-plasma levels are used primarily to monitor compliance and toxicity

Front 221

What are central nervous system adverse effects of tricyclic antidepressants?

Back 221

-sedation is common and probably due to antagonist activity at histamine H1 receptors. Confusion and memory dysfunction is a central anticholinergic effect but it is more common in the elderly
-mania occasionally occurs in patients with an underlying bipolar affective disorder
-tremors occur in 10% of patients and is managed with propanolol
-seizures occur occasionally becuaseof lowered seizure threshold
-they aremore common with tertiary amines

Front 222

What is insomnia as an adverse effectof tricycline antidepressants?

Back 222

-movement disorders are occasionally produced by amoxapine
-these effects are due to dopamine-receptor antagonist activity
-overdose of amoxapine causes seizures

Front 223

What adverse effects involve the cardiovascular system wuith tricyclic amine antideperessants?

Back 223

-postural hypotension, which may be severe and may be termporary, is probably due to peripheral alpha-1 adrenoceptor blockade
-may result in reflex tachycardia
-tachycardia, conduction defects, and arrythmia are common with overdose
-risk is highest with imipramine and preexisting heart block or compesated cardiac output

Front 224

What adverse effects are involved in the autonomic nervous system with use of tricyclic amine antidepressants?

Back 224

-reflects the muscarinic cholinoceptor antagonist activity of TCAs. effect are temporary
-use commonly produces dry mouth, blurred vision, difficulty in urination and constipation
-rarely precipitae narrow-angle glaucomaor paralytic ileusor cause urine retention. More common in the elderly

Front 225

What are the rebound/discontinuation effects of tricyclic amines antidepressants?

Back 225

-common effects include dizziness, nausea, hedache, and fatigue
-may persist forup to 2 months
-tapered withdrawal minimizes effects

Front 226

What adverse effects are affected for tricyclic amine depressants?

Back 226

-central nervous system effects
-autonomic nervous system effects
-insomnia
-cardiovascular
-rebound/discontinuation effects
-weight gain
-sexual dysfunction
-rare,but serious hematologic changes, including anemia and agranulocytosis
-infreuently cause allergic reactions and obstructive jaundice
-atomoxetine ,ay increase suicidal thoughts in childrrenm and adolescents

Front 227

What is overdose and toxicity of tricyclic amine antidepressants?

Back 227

-overdoase produces severe anticholinergic and antiadrenergic signs, respiratory depression, arrythmias, shock, seizures, coma, and death
-treatment is supportive and includes sodium bicarbonate for cardiac toxcity, benzodiazepines for seizures and intravenous fluids and norepinephrine for hypotension

Front 228

What are adverse effects of SSRIs?

Back 228

-overall, they produce less efects that tricyclic amines
-headache is temporary
-secula dysfunction up to 40% of allpatients
-gastric irritiation is transient and includes nausea and heartburn
-weight loss initally followed in somepatients by weight gain
-stimulation that is mild and often transient, may beexperianced as dysphoria, and is marked by agitation, anxiety, increased motor activity, insomnia, tremor, and excitement
-apathy (flattened affect) occurs in some patients
-rebound/discontinuation effects like those for TCAs most likly weith paroxetine

Front 229

What occurs when you stop SSRI treatment?

Back 229

-may result in SSRI discontiunation syndrome,with dizziness, vertigo, ataxia, nausea, vomiting, musckle pains, fatigue, tremor and headache
-psychological symoptomssuch as anxiety, crying spells, irritabiklity, feeling sad, memory problems and vivid deams may occur
-common in SSRIs witha shorter half-life such as paroxetine and venlafaxine, and occurs in up to 1/3 of patients on SSRI therapy
-fluoxetine is the least likely to cause this syndrome because of it's long half-life. This symptomis self-limiting.

Front 230

What are the adverse effects of trazodone and nefazodone as heterocyclic antidepressants?

Back 230

-these drugs are highly sedating, cause drowsines and dizziness
-cause insomnia and nausea
-trazodone may cause postural hypotension in the elderly and a rare priapis in men
-trazodone has no significant anticholinergic activity, has fewer autonomic and cardiovascular effects than TCAs and is than TCAs in overdose

Front 231

What are the adverse effects of bupropion as heterocyclic antidepressants?

Back 231

-bupropion has no significant anticholineergic activity or hypotensive activity
-causes little sexual dysfunction
-more likely than TCA's to cause seizure's
-bupropion causes stimulation. insomnia, and weight loss
-makreted as zyban

Front 232

What are the adverse effects venlafaxine of hetereocyclic antidepresants?

Back 232

-causes nausea dizziness, sexual disturbances, anxiety, and insomnia

Front 233

What are the adverse effects of duloxetine as a heterocyclic antidepressant?

Back 233

-causes gastrointestinal disturbances, sexual dissturbances, insomnia, and sedation

Front 234

What are the CNS adversee effects of heterocyclic antidepressants with tricyclic amines?

Back 234

-TCA's and most heterocyclics cause sedation, additive with other CNS depressants
-SSRI's, bupropion and venlafaxine may cause anxiety, insomnia, an d jitteeriness
-most of these drugs caue seizure in overdose

Front 235

What are peripheral nervous system adverse effects of heterocyclic and tricyclic amine antidepressants?

Back 235

--TCA's, amoxapine, maprotiline, and nefazodone cause atropine-like side effcts via muscarinic receptor antagonism
-weight gains occur with TCAs and MAOIs
-weight loss is common with SSRIs

Front 236

What are general drug interactions of tricyclic amine antidepressants?

Back 236

-TCAs potentiate the CNS depressant effcts of alcohol and other drugs with similar activity
-TCAs potentiate the pressor activity of noreepinephrine
-TCAs have additive anticholinergic effects with antiparkinsonian drugs, antipsychotic drugs and otheer drugs with anticholinergic activity
-TCAs block alpha-adrenoceptors and thus reduce the antihypertnsive action of clonidine qand alpha-methyldopa
-interaction with MAOIs can cause excitement, hyperpyrexia, and a hypertensive episode
-serotonin syndrome also may occur with TCAs that are more selectively block serotonin reuptake

Front 237

What are the general drug interractions of SSRI antidepressants?

Back 237

-have a rare and potentially fatal interaction with MAOIs called serotonin syndrome that includes tremor, hyperthermia, muscle rigidity, and cardiovascular collapse

Front 238

What are general drug interactions of MAOI antidepressants?

Back 238

-MAOIs may result in headache, nausea, cardiac arrhythmias, and hyertensive crisis and, rarely, in subarachnoid bleeding adn stroke in the presence of indirectly acting sympathomimetics. These effects are due to the release of increaed stores of catecholamines resulting from inhibition of monoamine oxidase
-these can potenetiate the pressor ffect of high doses of directly acting ssympoathetic amines
-MAOIs may causes a serotonin syndrome in the preence of SSRIs, certain TCAs,, and opiod such as meperidine
-redult in additive sedaton and CNS depresion in the eprsence of barbiturates, alcohol,, and opioids

Front 239

What is bipolar disorder?

Back 239

- a mental illness characterized by mood stability that cna be serious and disabling
-manic behavior is one extreme of this disorder, and depression is the other
-deep mood swings of bipolar disorder may last for weeks or months, causing great distrubances in the lives of those affected, and those of family adn firends, too
-suicide rate is high among those with bipolar disorder

Front 240

What are therapeutic uses oflithium for acute mania or bipolar afective disorder?

Back 240

-lithium normalizes mood in 70% of patients. The onset of the therapeutic effect takes 2-3 weeks
-antipsychotic agents and benzodiapines can be used in the initial stages of the disease to control acute agitation
-the anticonvulsants carbamazepine and vaiproic acid have been used successfully either alone or as adjuncts to lithium therapy
-the dose is similar to that used for epilepsy
-the mechanism of actiion of these drugs are unknown
-lamotrigine may be useful in preventing depression that often follows the manic of bipolar disorders
-prophylaxis of bipolar affective disorder, for which lithium is often administered with a TCA (may precipitate mania)

Front 241

What is the mechanism of action of lithium?

Back 241

-the mehcanism of action for lithium is unclear , although it may be directly related to the inhibition ofphospholipid turnover (lithium inhibits inositolmonophosphatase) and, consequently, decreased activity of the second messengers diacylglycerol (DAG) anmd inositol 1,4,5-triphosphate (IP3)
-lithium also has reported effects on nerve conduction
-on the release, synthesis, and action of biogenic amines
-and on calcium metabolism

Front 242

What are the pharmacologic properties of lithium?

Back 242

-this drug is eliminated almost entirely by the kidney
-80 percent is reabsorbed in the proximal renal tubule
-lithium has a low therapeutic index
-plasma levels must be monitore continuously

Front 243

What are the adverse effects of lithium?

Back 243

-adverse effects are common at therapeutic doses of .5- 1.4 mmol/L or slightly higher
-these effects include nausea, vomiting, diarrhea, fine tremor, polydipsia,edema, and weight gain
-lithium administration produces polyuria, which occurs as the kidney ciollectibng tubule becomes unresponsive to antidiuretic hormone (reversible)
-more rarely, decreased renal function occurs with long-term treatment, similar to nephrogenic diabetes insipidus
-adverse effects of lithium also include benign, reversible thyroid enlargement caused by reducing tyrosine iodination and the synthesis of thyroxine
-lithium more rarely causes hypothyroidism
-lithium is generally contraindicated during the first trimester of opreganacy because of possible risk of fetal congenital abnormalites
-renal clearance of lithium increases during pregnancy
-breast feeding is not recommended because lithium is secreted in breast milk with possible neonate dysfunction

Front 244

What are the drug interactions with lithium?

Back 244

-sodium depletion isincreased by low-salt diets, thiazide diuretics, durosemide, ethacrynic acid, or severe vomiting or diarrhea
-this depeltion results in increased renal reabsortpion oflithium and an increased chance of toxicity
-renal clearance of lithium is decreased and the chance of toxicity is enhanced by some nonsteroidal anti-inflammatory drugs (such as indomethacin and phenylbutazone)

Front 245

What is the toxicity of lithium?

Back 245

-at a toxicity level above 2mmol/L, confusion (first sign of toxicity), drowsiness, vomiting, ataxia, dizziness, and severe tremors develop
-at a toxicity level above 2.5 mmol/L, clonic movements of the limbs, seizures, circulatory collapse, and coma occur
-treatment includes discontinuing lithium administration, hemodialysis, and the use of anticonvulsants

Front 246

How are antipsychotic drugs classified?

Back 246

-either conventional or atypical
-subclassfied by oral milligram potency
-high potency drugs (fluphenazine and haloperidol) are more likely to produce extrapyramidal reactions
-low potency drugs (triflupromazine and thioridazine) are less likely to produce acute extrapyramidal reactions and more likely to produce sedation and postural hypotension
-atypical agents (risperidone and olonzapine) have generally replaced the conventional drugs for intial treatment of first-episode patients. clozapine is reserved for treatment-resistant patients
-other conventional heterocyclic antipsychotic drugs such as loxapine and molindone, with intermediate potency, have no clear advantage over other conventional drugs

Front 247

What is the dopamine hypothesis of schizophrenia? what is the drug of choice for it?

Back 247

-caused by abnormally high activity in brain systems that use dopamine as their primary neurotransmitter
-usually treated with chlorpromazine, a drug that binds to dopamine receptors withotu stimulating them, renderign them unavailable for activation by Dopamine

Front 248

What is the mechanism of action of conventional antipsychotic drugs? Atypical drugs?

Back 248

-antagonist activity at postjunctional dopamine D2-receptors, where dopamine normally inhibits adenylyl cyclase activity
-antagonist activity at both serotonin and dopamine D2 or D4 receptors
-aripiprazole is a partial agonist at dopamine D2 and like ziprasidone, also stimulates with serotonin receptors
-actions are in the mesolimbic and mesocortical areas of the CNS

Front 249

What are the therapeutic uses of antipsychotic drugs on schizophrenia?

Back 249

-produce an immediate quieting action
effects include decreased symptoms of thought disorders, paranoid features, delusions, hostility, hallucinations, and decreased withdrawal, apathy, and blunted affect
-curb acute psychotic attacks and delay subsequent relapses

Front 250

What are other therapeutic uses of antipsychotic drugs other than scizophrenia?

Back 250

-acute mania in bipolar disorder
-atypical psychotic disorders
-depression with psychotic manifestations
-tourette;s syndrome to supress severe tics and vocalization
-severe nausea or vomiting associated witha variety of diseases, radiation treatment, and cancer chemotherapy, as well aspostoperative nausea, and vomiting

Front 251

What are pharmacologic properties of antipsychotic drugs?

Back 251

-most of these drugs show little correlation between plasma levels and therapeutic action
-highly lipophilic and have long half-lives (10-20 hrs)
-metabolized by liver microsomal oxidation and conjugation
-thiroidazine is metabolized to mesoridazine (active metabolite)
-esterification of fluphenazine and haloperidol results in long-lasting depot forms that can be used to manage compliance issues
-plasma esterases convert the parent compound to the active drug when the ester diffuses into the blood-stream

Front 252

Why do anti-psychotic drugs have adverse effects?

Back 252

-due to antagonistic actions at dopamine D2 and histamine H1 receptors (and possibly serotonin receptors) in the CNS and to their antagonist actions at muscarinic cholinoceptors and alpha-adrenoceptors in the periphery.

Front 253

What are adverse effects of anti-psychotic drugs on the CNS?

Back 253

-extrapyramidal syndomes
-tardive dyskinesia
-neuroleptic malignant syndrome
-sedation
-confusional state with memory impairment
-seizures

Front 254

What are the adverse effects of anti-psychotic dryugs on other than the central nervous system?

Back 254

autonomic nervous system:
-alpah-adrenoceptor blockade
-muscarinic cholinoceptor blockade
-endocrine and metabolic distrubances
-withdrowal-like syndrome
-cardiac arrhythmias
-blood dyscrasias
-cholestatic jaundice
-photosensitivity

Front 255

How are extrapyramidal syndromes in the central nervous system from adverse effects of anti-psychotic drugs?

Back 255

-related to dopamine-receptor blockade in basal ganglia that leads to an imbalance in dopamine and acetylcholine actions in the nigrostriatal pathway
-major cause of noncompliance
-most likely to occur with high-potency conventional drugs that have a high afinity for post-junctional dopamine D2 receptors in the basal ganglia
-also unlikly to occur with atypical drugs such as clozapine and olanzapine
-sometimes spontaneously remit

Front 256

What are extrapyrimidal syndromes from anti-psychotic drugs?

Back 256

-acute dystonia
-akathisia
-parkinsonian-like syndrome

Front 257

What is acute dystonia as an extrapyrimidal syndromes from anti-psychotic drugs?

Back 257

-characterized by spastic retrocollis or torticollis
-respiration may be compromised
-may be elicited durign first week of therapy
-can be controlled with more-centrally action antimuscarinic drugs such as benztropine and biperiden with antihistamine diphenhydramine and by reducing antipsychotic drug dose
-this may lead to increase in psychotic symptoms

Front 258

What is akathisia as an extrapyrimidal syndrome from anti-psychotic drugs?

Back 258

-akathisia is the irresistaible compulsion to be in motion
-this condition cna develop as early as the first 2 weeks of treatment or as late as 60 days into therapy
-like acute dystonia, can be controlled by drugs with antimuscarinic activity and by beta-receptor antagonist propranolol

Front 259

How is parkinson like effects a syndrome of extrapyrimidal adverse effects of anti-psychotic drugs in the CNS?

Back 259

-characterized by tremors, bradykinesia rigidity, and othe signs of parkinsonism
-can be controlled with anti-muscarinic drugs or by reducing anti-psychotic drug dose

Front 260

What is tardive dyskinesia as an adverse effects of anti-psychotic drugs in the CNS?

Back 260

-much morelikely with conventional antipsychotic agents than atypical agents
-does not occur with clozapine
-primarily chacterized by disfiguring orofacioligual movements (tics), but it coccasionally includes dystonic movements of the trunk
-these effect may be the result of a developing supersensitivity of the postjunctionaldopamine receptors in the CNS, perhaps in the basal ganglia
-generally occurs after months to years of drug exposure
-it may be exacerbated or precipitated by the discontinuation of therapy
-often irreversible
-has an estimated incidenc eof 10-20%
-more likely to occur with the elderly or in institutionalized patients who receive long-term, high-dose therapy
-only treatment is discontinuation of treatment

Front 261

How is neuroleptic malignant syndrome an adverse effect of antipsychotic drugs in the CNS?

Back 261

-is most likely in patients sensitive to the extrapyramidal effects of the conventional high-potency antipsychotic agents
-characterized by autonomic instability, muscle rigidity, diaphoresis, profound hyperthermia, and myoglobinemia
-condition occurs often explosively in 1% of patients
-associated with 20% mortality rate
-treated by discontinuing drug therapy and intiating supportive measures, including the use of bromocriptine to overcome the dopamine receptor blockade and the use of muscle relaxants such as dantrolene and diazepam to reduce muscle rigidity

Front 262

What is sedation as an adverse effect of anti-psychotic drugs of the central nervous system?

Back 262

-more likely with low-potency drugs with atypical agents
-are due to a central histamine H1-receptor blockade
-these effects may be mile to severe, elderly are particularlyat risk
-may be temporary

Front 263

How is confusional state with memory impairment an adverse effect of anti-psychotic drugs on CNS?

Back 263

-efect is likely with anti-psychotic agents with pronounced antimuscarinic activity

Front 264

How are seizures an adverse effect of anti-psychotic drugs in the CNS?

Back 264

-seizures are common with chlorpromazine and clozapine
-this effect is due to a lowering of the seizure threshold
-antipsychotic drugs may precipitate or unmask epilepsy

Front 265

How is alpha-adrenoceptor blockade an adverse effect of anti-psychotic drugs in the ANS?

Back 265

-more likely to occur with conventional low-potency and atypical agents
-causes orthostatic hypotension, and possibly syncope as a result of peripheral vasodilation
-central depression of the vasomotor center may also contribute
-this effect may be severe and may resulty in reflex tachcardia
-elderly patients and those with heart disease are more at risk
-effect may be temporary

Front 266

How are muscarinic cholinoceptor blockade an adverse effect of anti-psychotic drugs in the ANS?

Back 266

-more common with conventional low-potency agents and atypical agents sucgh as clozapine
-resulting in dry mouth and blurred vision
-blockade may also produe constipation, tachycardia, and difficulty in urination leadign to urine retention
-rarely causes paralytic ileus and severe bladder infections
-elderly patients are more at risk
-effects may be temporary

Front 267

How are endocrine and metabolic distrubances an adverse effect of anti-psychotic drugs?

Back 267

-likely with most conventional agents and atypical agent risperidone
-due to dopamine D2 receptor antagonist activity in the pituitary
-resulting in hyperprolactinemia
-in women these disturbances include induced galactorrhea, loss of libido, and delayed ovulation and menstruation or amenorrhea
-in men, distrubances include gynecomastia and impotence
-weight gain may be due in part to histamine- H1 receptor antagonist activity

Front 268

how is withdrawal-like syndrome an adverse effect of anti-psychotic drugs?

Back 268

-characterized by nausea, vomiting, insomnia, and headache in 30 % of patients, especially with low-potency agents
-symptoms last up to 2 weeks
-minimized with a tapered reduction of drug dosage

Front 269

How are cardiac arrythmias an adverse effect of anti-psychotic drugs?

Back 269

-result froma quinidine-like effect in which ther is local anesthetic activity wtih an increased likelihood of heart block
-more likely with thioridazine and ziprasidone, whcih can prolong the Q-T interval and elad to conduction block adn sudden death

Front 270

How are blood dyscrasias an adverse effect of anti-psychotic drugs?

Back 270

-rare except in the case of clozapine, which may induce agranulocytosis in up to 3% of patients and therefore used only when other drug groups prove ineffective

Front 271

How is cholestatic jaundice an adverse effect of antipsychotic drugs?

Back 271

-caused primarily by chlorpromazine

Front 272

How is photosensitivity an adverse effecy of anti-psychotic drugs?

Back 272

-effect is specific to chlorpromazine
-includes dermatitis, rash, sunburn, and pigmentation, and it may be irreversible
-chlorpormazine and high-dose thioridazine also produce retinitis pigmentosa

Front 273

What is overdose in anti-psychotic drugs?

Back 273

-rarely fatal,. except when caused by thiroidazine or mesoridazine ( and posibly ziprasidone)
-may result in drowsiness, agitation, coma, ventricular arrhythmias, heart block, or sudden death

Front 274

What are possible drug interactions with anti-psychotic drugs?

Back 274

-have potentiated sedative effects in the rpesence of CNS deopressants (sucha s hypotics, opiods, aned antihistamines)
-produce additive anticholinergic effects with tricyclic antidepressants, antiparkinsonian drugs, and other drugs with anticholinergic activity

Front 275

What is sedation?

Back 275

-characterized by decreased anxiety, motor activity, and cognitive acuity

Front 276

What is hypnosis?

Back 276

-characterized by drowiness and an increased tendency to sleep

Front 277

What are general properties of benzodiazepines as sedatives-hypsnotics?

Back 277

-have a great margin of safety over previously available sedatvices-hypnotic agents
-have qualitively similar therapeutic actions
-however, because of quantitative differences in theri relative lipid solubility, biotransformation, and elimination half-life,some benzodiazepines are marketed for specific therapeutic purposes

Front 278

What is the mechanism of action of benzodiazepines as sedative-hypnotics?

Back 278

-facilitate gamma-aminobutyric acid (GAB)-mediated inhibiton of neuronal activity in the CNS
-they bind to a benzodiazepine receptor (2 subtypes available) that is part of, but distinct from the pentameric GABA-rceptor-chloride channel complex that consists of at elast four subuits and their multipleisoforms
-allosterically increase GABA affinity and the frequency of GABA-stimulated chloride channel opening, chloride conductance, and neuronal hypepolarization
-they also inhibit depolarization by excitatory neurotransmitters
-no action in the absence of GABA
-certain B-carboline and other ligands called "inverse agonists", some of which may be endogenous, bind with high affinity to the benzodiazepine receptor and can cause anxiety and induce seizures

Front 279

What are the pharmacologic properties of benzodiazepines as sedative-hypnotics?

Back 279

-generally administered orally to treat anxiety adn sleep disorders, some cna be given parenterally
-onset of benzodiazepine action is relatedto a relative degree tolipid solubility
-benzos that are highly lipid soluble have a rapid onset of action that benzos that are less lipid soluble
-redistribution from the brain to peripheral tissues is considered an important factor in terminating the actions of single, or intermittent nonaccumulating doses of the most highly lipid-soluble benzos
-hepatic metabolism accoutns for the clearnace of all benzos
-active metabolites, particularly desmethyldiazepam, result from acid hydrolysis in the stomach or phase I hepatic microsomal oxidation and extend the half-life of some benzos to as long as 60 hours or more
-biotransformation to ianctive metabolites is the msot imprtant factor for termianted actions fo less-lipid soluble benzos
-excreted by kidney
-clearnace is decreased in the elderly and in patients with liver disease

Front 280

What are the theraputic uses of benzodiazepines as sedative-hypnotics?

Back 280

-effectjve and safe for short-term treatment of anxiety disorders such as generalized sxiety disorder, situational axiety disorders, panic disorders, and social anxiety disorder
-used for insomnia
-used for seizures to elevate threshold, lorazepam (and diazepam) are given by IV, and clonazepam and clorazepate are used as adjuncts for absence, myoclonic, and atonic seizures
-used for preanesthetic and short medical/surgical procedues
-muscle relaxation
-acute mania of bipolar disorder
-can casue physcial dependence from short-acting benzodiazepines, use long-acting

Front 281

What is midazolam as a benzodiazepine?

Back 281

-short acting
-used as a preanesthetic

Front 282

What is triazolam as a benzodaizepine?

Back 282

short acting
-for insomnia and preanesthetic

Front 283

What is alprazolam as a benzodiazepine?

Back 283

-intermediate acting
-for anxiety
-antidepressant for panic disorders

Front 284

What is clonazepam as a benzodiazepine?

Back 284

-itnermediate acting
-for seizures

Front 285

What is estazolam as a benzodiazapine?

Back 285

-intermediate acting
-for insomnia

Front 286

Wgat is lorazepam asa benzodiazepine?>

Back 286

-intermediate acting
-for anxiety, insomnia, and preanesthetic

Front 287

What is oxazepam as a benzodiazepine?

Back 287

-intermediate acting
-for anxiety

Front 288

What is temazepam as a benzodiazepine?

Back 288

-intermediate acting
-for insomnia

Front 289

What is chlordiazepoxide as a benzodiazepine?

Back 289

-long-lasting
-for anxiety
-preanesthetic

Front 290

What is clorazepate as a benzodiazepine?

Back 290

-long-lasting
-for anxiety

Front 291

What is diazepam as a benzodiazepine?

Back 291

-long-lasting
-for anxeity
-preanesthetic
-seizures

Front 292

What is flurazepam as a benzodiazepine?

Back 292

-long-lasting
-insomnia

Front 293

What is prazepm as a benzodiazepine?

Back 293

-long lasting
0for anxiety

Front 294

What is quazepam as a benzodiazepine?

Back 294

-long-lasting
-for insomnia

Front 295

What are flumazenil as a sedative-hypnotic? Adverse effects?

Back 295

-competitive antagonist at benzodiazepine receptors
-used to prevent or reverse the CNS effects from benzodiazepine overdose or to speed recovery from the effects of benzodiazepines used in anesthetic and diagnostic procedures
-it may precipitate withdrawal
-its short duration of action often necessitates multiple dosing

Front 296

What is zolpidem, zaleplon, and eszopiclone as sedative-hypnotic drugs? adverse effects?

Back 296

-zolpidem (and zaleplon, which has a shorter duration of action) is widely used for short-term treatment of insomnia, it also has anxiolytic activity as well
-acts on a specific subtype of the benzodiazepine receptor BZ1 to reduce chloride conductance, has a similar mechanism of action but is structually unrelated to the benzos
-these drugs have only weak muscle-relaxing or anticonvulsant activity, with reduced potential for tolerance, drug abuse, and physical dependence
-their actions are blocked or reversed by flumazenil
-adverse effects of zolpidem and zaleplon include modest daytime sedation, headache, GI upset, and amnesia
-eszopiclone is unreported to alsoproduce dry mouth, headache, some sedation, and an unpleasant taste

Front 297

What is buspirone as a sedative-hypnotic? adverse effects?

Back 297

-nonbenzodiazepine that selectively relieves anxiety without the sedation, hypnosis, general CNS depression, or drug abuse liability of the benzos. Has no other benzo-like activities
-used primarily to treat generalized anxiety disorder, particularly in the elderly, who are more susceptible to the CNS depressant action of the benzos
-buspirone is a partial agonist at serotonin receptors
-a wekk or more of administration may be required to achieve the therapeutic effects of buspirone
-adverse effects include nervousness, restlessness, dysphoria, tachycardia, or GI distress more often than benzos
-causes pupillary constriction

Front 298

What are barbituates as sedative-hypnotics?

Back 298

-includes amobarbital, pentobarbital, secobarbital, and phenobarbital
-weak organic acid
-redistrivbtuion from highly vascular to less vascular tissues is responsible for the short duration of highly lipid-soluble barbituates
-metabolism and excretion are more important determinants for less lipid-soluble babrituates
-25% of a dose of phenobarbitali is excreted unchanged
-alkalinization of the urine enhances excretion and shortens its duration of action

Front 299

What is the mechanism of action of barbituates as sedative-hypnotics?

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-interact witha binding site on the GABA-receptor-chloride channel complex that is separate from the benzo receptor
-at low doses, barbituates allosterically porlong the GABA-induced opening of chloride channels and enhance GABA-inhibitory neurotransmission
-at higher doses, these drugs have GABA-mimetic activity (open chloride channels independently of GABA)
-with long-term use, these drugs, particularly phenobarbital, may induce the synthesis of hepatic microsomal enzymes and increase their own metabolism or the metabolism of numerous other drugs
-increase porphyrin synthesis by the induction of hepatic sigma-aminolevulinic acid synthase, and they can precipitate acute intermittent porphyria
-use as sedative-hypnotic agents is almost obsolete, supplanted by benzos and toehr nonbenzos

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What are the therapeutic uses of barbituates as sedative-hypnotics?

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-mostly obsolete
-phenobarbital is used to some extent
-still widely used as an anticonvulsant
-thiopental is used as an IV general anesthetic
-limited by their strong sedation effects, rapid tolerance, drug interactions, abuse potential, and lethality in overdose
-used to treat physical dependece associated with long-term use of sedative-hypnotic drugs

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What are adverse effects of barbituates?

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-produce dose-related respiratory depression with cerebral hypoxia, possibly leading to coma or death
-this effect results from abuse or suicide attempt
-treatment includes ventilation, gastric lavage, hemodialysis, osmotic diuretics and alkalinization of urine
-depress the medullary vasomotor center , with circulatory collapse
-use of barbituates is contraindicated in patients with pulmonary insuffiency
-hepatic and renal disease may prolong barbiturate action

Front 302

What is the prototype of benzodiazepines as sedative-hypnotic?

Back 302

-diazepam

Front 303

What is the prototype of benzodiazepine antagonist as sedative-hypnotic?

Back 303

-flumazenil

Front 304

What is the prototype of barbituates as sedative-hypnotics?

Back 304

-phenobarbital