NURS 549 MIDTERM 5-8

Another name for Adrenergic Agonists is Sympatholytics.

FALSE Are defined as drugs that have affinity for and have intrinsic activity at receptors that are stimulated by Norepinephrine •These drugs are called adrenergic agonists , and are also referred to as sympathomimetics.

The Beta-2 Receptor Selective agonist activity of Isoproternol ( Isuprel) makes it an ideal choice for Asthma. T/F

FALSE Isoproternol (Isuprel) -Synthetic catecholamine -Direct acting( not dependent on endogenous NE stores) -BETA AGONIST: PURE BETA RECEPTOR AGONIST with NO alpha effects -Unselective for B1 or B2 -Increases HR & FOC ( B1) -Bronchodilation ( B2) -Skeletal muscle arterial smooth muscle relaxation ( B2) - used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma.

Cholinergic Antagonists drugs have: No Affinity and no Inrinsic Activity Affinity and no Intrinsic Activity No Affinity and have Instrinsic Activity Both Affinity and Intrinsic Activity

AFFINITY AND NO INTRINSIC ACTIVITY The cholinergic antagonists ( blockers) bind to cholinergic receptors ( Nicotinic & Muscarinic), but they DO NOT trigger the usual receptor mediated intracellular effects. •Therefore, we have affinity, BUT NO Intrinsic Activity •The most useful of these drugs selectively blocks muscarinic receptors of the parasympathetic nerves. ( at the postganglionic parasympathetic receptor on effector organ )

Match the Adrenergic Agonist to their corresponding physiological responses: 1. EPINEPHRINE 2. NOREPINEPHRINE 3. Isoproterenol a. * Pulse rate increases via action on Beta-1 receptors in the heart * Systolic BP increases via effect on renal Beta-1 receptors in the kidney to release renin which produces angiotensin IIà potent vasoconstrictor * Possesses Alpha-1 receptor activation / vaso-constriction ( at higher does) * PVR & Diastolic BP decrease via Beta-2 receptor activation on skeletal muscles arteries. b. * Systolic BP , Diastolic BP, PVR all increase via intense vasoconstriction from activation of Alpha-1 vascular receptors. * Pulse rate decreases via reflex bradycardia. c. * Pulse rate increases via action on cardiac Beta-1 receptor * PVR & Diastolic BP decrease via skeletal muscle Beta-2 receptor activation on the smooth muscle of arteries in skeletal muscle * Systolic BP may increase ( moderate) because of its cardiac stimulatory action on Beta-1 and renin release from stimulation of renal Beta-1 receptors.

1 A 2 B 3 C

Match the Anti-Cholinergic Drug with it's Associated Anti-Cholinergic Effects. ( an answer can be used more than once) 1. Atropine 2. Scopolamine 3. Ipratropium ( Atrovent ) 4. Nicotine 5. Oxybutinin ( Ditropan ) 6. Tolterodine ( Detrol) 7. Rocuronium ( Zemeron) , Pancuronium ( Pavulon ) and Vercuronium ( Norcuron) 8.succinylcholine 9. Fesoterodine ( Toviaz) A.Depolarizing ( Non-Competitive ) Neuromuscular Blockade B. Blocks Cholinergic transmission in the CNS to the vomiting center and is used for motion sickness c. An Anti-Muscarinic used to relieve urinary and bladder difficulties, including frequent urination ( urge incontinence) by decreasing muscle spasms of the bladder. d. Effects primarily bronchial smooth muscle producing bronchodilation e. ganglionic blocker without therapeutic effect but is used in smoking replacement therapy F. GI Antispasmodic seen in Lomotil and Donnatal, used clinically to blunt parasympathetic influence on heart and increase HR, used for eye exams to dilate eye. g. Non-Depolarizing ( Competitive) Neuromuscular Blockade

1 F. 2. b 3. d 4. e 5 C 6 c 7 g 8a 9 c

Match the Physiological Effect with the Adrenergic Receptor. 1. Alpha-1 Adrenergic Receptor 2. Alpha-2 Adrenergic Receptor 3. Beta-1 Adrenergic Receptor 4. Beta-2 Adrenergic Receptor A. Are located Centrally and peripherally , and when stimulated centrally are associated with inhibiting sympathetic response decreasing peripheral vascular resistance and lowering blood pressure B. When stimulated are associated with increased HR, increased force of contraction of heart , and renin release from the kidneys which leads to Angiotensin II C. When stimulated , are associated with bronchial smooth muscle relaxation, dilation of arteries to skeletal muscle. d. When stimulated, are associated with vascular smooth muscle vasocontriction, pupil dilation

1. D 2. A 3. B 4. C

Match the Adrenergic Agonist with associated receptor activity and physiological effect. 1. Salmeterol ( Serevent) 2. Levalbuterol ( Xopenex) 3. Dopamine 4. Albuterol ( Ventolin) 5.Epinephrine 6.Norepinephrine 7.Isoproternol ( Isuprel) 8. Mirabegron ( Mybetriq) A. Direct Alpha-1 Agonist ; restores blood pressure in emergent acute low BP episodes B. A direct beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. C. A short acting direct Beta-2 specific adrenergic agonist that is an enantiomer of Albuterol, theorized to have less of an effect on Beta-1 receptors D. A short acting beta-2 agonist inhaled for direct bronchodilation. ( most commonly prescribed beta-2 specific agonsist in the treatment of asthma) E. Is an alpha agonist, a beta agonist and also produces renal vasodilation. F. Long acting Direct B2 specific adrenergic agonist ( Inhaled for direct bronchodilation on bronchial smooth muscle ) G. NON-Selective Pure Beta Receptor Agonist with NO alpha effects; increases HR & Force of Contraction ( B1) ; Bronchodilation ( B2) H. Primarily a beta receptor agonist at low doses and an alpha receptor agonists at high doses;mast cell stabalizer for analphylactic reactions

1. F 2. C 3. E 4. D 5. H 6. A 7. G 8. B

Match the CNS Drug to either being used for Parkinson's Disease or Alzheimer's Disease: 1. Donepezil ( Aricept) 2. Carbidopa / Levodpa ( Sinemet 3.Rivastigmine ( Exelon ) 4.Bromocriptine ( Parlodel) a. Alzheimer's Disease b Parkinon's Disease

1. a 2. b 3. a 4. b

Match the Central Neurotransmitter with the 'general' associated physiological CNS effect. 1. dopamine 2. norepinephrine 3. serotonin 4. GABA a. focus,arousal, memory, attention, wakefulness, learning, reward system b. Reward-Motivated Behavior, voluntary movements, fine motor control, motivation, information processing, associated with addiction c. Primary Inhibitory Neurotransmitter in the CNS, regulates CNS excitability, possesses muscle relaxtation properties, regulates the N/V center in the CNS d. Happiness Hormone' , associated with mood, sleep, memory, appetitie, learning

1. b 2. a 3. d 4. c Norepinephrine - Excitatory in the CNS •Arousal, reward system, wakefulness, learning, mood, MEMORY, focus, attention 2. Dopamine - Excitatory in the CNS Review: •synthesized from adrenal medulla and also from CNS neurons. •PNS= affects Alpha + beta + dopamine rec's in kidney •CNS= affects dopamine receptors widely distributed in the brain •Reward-Motivated behavior: Every type of reward that has been studied increases the level of dopamine in the brain. ( addictive drugs act by amplifying the effects of dopamine) •Also: Voluntary movements, motivation, information processing, attention, learning, pleasure, fine motor control •Peripheral Dopamine Does not cross BBB àinto CNS •Precursor to Dopamine ( L-Dopa), however , can cross BBB. 3. Serotonin ( 5HT )- Excitatory in the CNS •'happiness hormone' •Also does not cross BBB & reach CNS when given systemically •Found in CNS ( 10%) , GI tract ( 90%), & platelets •Associated with Mood

Match the Alpha Adrenergic Antagonist to associated indications. ( answer can be used more than once) 1.Doxazocin ( Cardura ) 2. Terazocin ( Hytrin) 3. Prazocin ( Minipress) 4. Tamulosin ( Flomax) a. Alpha-1 selective blocker that is more specific for treating HTN than for BPH b. Alpha-1 selective adrenergic blocker that is more specific for treating BPH than for HTN c. Alpha -1 selective blocker used to treat both HTN and urinary retention associated with BPH.

1. c 2. c 3. a 4. b

Match the Drug Mechanism of Action to the Drug used to treat Parkinsonism: 1. sinemet 2. Bromocriptine ( Parlodel 3. Selegiline ( Eldepryl) 4. Benztropine ( Cogentin ) a. A straight Dopamine Receptor Agonist, but has severe side effects. b.Anticholinergic that plays an "adjunctive' role in lowering cholinergic stimulation and reestablishing a balance with dopamine in the CNS c. A selective Monoamine Oxidase-B ( MAO-B) Inhibitor d. A comination of levodopa ( L-dopa), which crosses the BBB and is coverted to dopamine, and Carbidopa, which dimishes the peripheral metabolsim of L-DOPA by inhibiting dopa-decarboxylase.

1. d 2. a 3. c 4. b

Which of the following physiological effects IS NOT ASSOCIATED with adrenergic stimulation? Vasodilation of Skeletal Muscle Arteries A decrease in glucose levels Pupil Dilation Increase in heart rate and force of contraction Bronchodilation

A DECREASE IN GLUCOSE LEVELS

ONCE NOREPINEPHRINE IS TAKEN UP BY THE PRE-SYNAPTIC NEURON, WHAT HAPPENS TO IT? It can be taken up by a storage vesicle. It can stay in the cytoplasm of presynaptic neuron and persist there. It can be oxidized by MonoAmine Oxidase ( MAO) All of the above are correct

ALL OF THE ABOVE ARE CORRECT ONCE NOREPINEPHRINE IS TAKEN UP BY THE PRE-SYNAPTIC NEURON, IT HAS 3 FATES: a)Can then be taken back up into a cytoplasmic storage vesicle b)Can simply persist in cytoplasm c)Can be oxidized by MAO ( Monoamine Oxidase) -Monoamine Oxidases - a family of enzymes that catalyze the oxidation of monamines. ( Hist, Catecholamines (NE, Dopamine, Epi) Serotonin...)

Cholinergic Antagonism at Autonomic Nervous System ganglia for BOTH the Sympathetic and Parasympathetic Divisions is clinically useful. T/F

FALSE •The most useful of these drugs selectively blocks muscarinic receptors of the parasympathetic nerves. ( at the postganglionic parasympathetic receptor on effector organ ) •Q- Would blocking the nicotinic receptors which exist at both the parasympathetic and sympathetic ganglion be clinically useful? Answer = NO ( ganglionic blockers are not selective enough for clinical benefit) •Remember- DUAL INNERVATION - when parasympathetic influence is antagonized , the sympathetic influence is unopposed àincreased sympathetic influence.

The "First-Dose Phenomenon" is associated with what category of Adrenergic Antagonist? Alpha-1 Adrenergic Antagonist Apha-2 Adrenergic Antagonist Beta-1 Adrenergic Antagonist Beta-2 Adrenergic Antagonist

Alpha-1 Adrenergic Antagonist he first-dose phenomenon is a sudden and severe fall in blood pressure that can occur when changing from a lying to a standing position the first time that an alpha blocker drug is used or when resuming the drug after many months off. •This postural hypotension usually happens shortly after the first dose is absorbed into the blood and can result in syncope (fainting). Syncope occurs in approximately 1% of patients given an initial dose of 2 mg prazosin or greater. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration •The alpha-1 blocker prazosin (Minipress) is most notorious for producing a first dose phenomenon. Other drugs of the same family, doxazosin (Cardura) and terazosin (Hytrin), can also cause this phenomenon, though less frequently.

Alpha-2 Receptor Antagonism is associated with: Vasodilation of blood vessels in the skin, the sphincters of the GI system, kidney and brain. An increase in central symapathetic tone and an increase in blood pressure

An increase in central symapAthetic tone and an increase in blood pressure

All of the following are effects of MUSCARINIC ANTAGONISM EXCEPT Pupil Dilation Decreased Cardiac Heart Rate GI antispasmodic Urinary Retention

Decreased Cardiac Heart Rate Q- Can we think of cholinergic muscarinic antagonism as having the same kind of influence as adrenergic agonists? Answer = Yes, both allow for increased adrenergic influence. Effects of Muscarinic Antagonism: (S.L.U.D.D. all opposed ) •Eyeà dilation •Heartà blocks vagus nerve and INCREASES cardiac heart rate and force of contraction. •GI Systemà antispasmodic to reduce activity of the GI tract •Bladderà reduce hypermotility •Secretionsà antisecretory •S.L.U.D.D. all opposed .....less salivation, lacrimation, urination, defecation, digestion

Norepinephrine in the synaptic cleft, that is NOT terminated by the reuptake back into the presynaptic neuron, is degraded by? Monoamine Oxidase ( MAO) Catechol-Methyltransferase ( COMT ) Acetycholinesterase ( ACHE ) Norepi-terminase ( NET)

Catechol-Methyltransferase ( COMT ) Feedback: 2. COMT - ( Catechol-MethylTransferase) •Secondary mechanism for the removal of NE. This is the NE that has not been taken back up into the presynaptic neuron. ( the NE that persists in synaptic cleft) •Is one of several enzymes that degrades the catecholamines—dopamine, epi, NE • COMT is associated with the post-synaptic membrane in the synaptic space ( much like ACHE for ACH)

Clonidine, Guanfacine and Tizanidine are all classified as: Alpha-1 Adrenergic Agonists Central Alpha-2 Adrenergic Agonists Beta-1 Adrenergic Agonists Beta-2 Adrenergic Agonists

Central Alpha-2 Adrenergic Agonists

A Cholinergic Antagonist that is Surmountable, can be overcome with higer concentrations of Agonistic Drug , and a higher EC50 for the graded Dose Response Curve is observed is categorized as ___________________________, while a Cholinergic Antagonist that is Non-Surmountable, can not be overcome with higer concentrations of Agonistic Drug , a higher EC50 for the graded Dose Response Curve is NOT observed, and a decrease in maximal biological effect is observed is categorized as a_________________________________. Competitive Antagonist, Irreversible Antagonist Irreversible Antagonist, Competitive Antagonist

Competitive Antagonist, Irreversible Antagonist Competitive Antagonists: (surmountable) - compete for the same receptor as Acetylcholine. •They have Affinity , but no intrinsic activity. •Receptor activity determined by affinity of each ( antagonist & agonist at the receptor and relative concentrations •High concentrations of antagonist can be overcome ( surmounted) by higher concentrations of agonist drug. •Q- How does this effect the graded dose response curve? ( A= YES, It pushes curve and EC50 conc to the right) Irreversible Antagonists: •( non-surmountable) - antagonists binds with VERY HIGH affinity to the active site on the receptor, where the agonist can not "out compete" the antagonist, even at higher doses. •Antagonism can not be overcome by increasing the dose of agonist drug( EC50 does not increase) •What happens to the maximal biological effect of the agonist drug? A = decreased maximal biological effect

A drug that lowers Cholinergic Acetylcholine Influence INSTEAD of augmenting Dopaminergic Influence in the treatment of Parkinson's Disease is: Donepezil ( Aricept) Benztropine ( Cogentin ) Bromocriptine ( Parlodel ) Selegiline ( Eldepryl)

Could an Anti muscarinic Drug be useful? A = Yesà lowers ACH influence and 'rebalances" scale with dopamine #6. Benztropine( Cogentin) ( adjunctive role)

Parkinsons Disease is associated with a 80% loss of __________________ fibers & levels in the CNS, while Alzheimers Disease is associated with a reduced synthesis of the neurotransmitter______________? Acetylcholine, Dopamine Dopamine, Serotonin Dopamine, Acetylcholine Serotonin , Acetylcholine

Dopamine, Acetylcholine There is a loss of 80+% of dopaminergic fibers & dopamine levels in the CNS ( Basal Ganglia) Dopamine is involved with voluntary muscle movement, motivation, learning, pleasure, fine motor control. Treatment for Parkinson's Disease only offers temporary relief from the symptoms- does not arrest or reverse nerve degeneration Parkinson's - characterized by tremors, rigidity, postural instability Abnormal movements due to upset of the BALANCE of dopamine and ACH (not enough dopamine and APPARENT over action of ACH) No primary problem with ACH...!!! §The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine.

Low dose Epinephrine is associated mostly with Alpha ( vasoconstrictive ) effects, while high dose Epinephrine is associated beta receptor activity. T/F

FALSE . Epinephrine ( adrenaline): -Natural catecholamine Q- secreted by what? ( Adrenal Medulla) -Shows highest affinity for alpha receptors compared to NE and Isoproterenol. -Direct acting. ( not dependent on endogenous stores of norepinephrine) -ALPHA & BETA AGONIST: For IV infusion, DOSE RELATED AFFINITY for both Alpha and Beta Receptors -Epinephrine is primarily a beta receptor agonist at low doses and an alpha receptor agonist at high doses. -Beta effects are seen throughout -Alpha ( vasoconstriction) effects increase as dose increases..!! -IV Infusion: 1 mg of EPI is mixed with 500 ml of NS or D5W. The infusion should run at 2 - 10 micrograms/min ( titrated to effect) -Bottom line: Potent Inotrope/Chronotrope with variable alpha vasoconstriction effects

An adrenergic agonist that stimulates the release of norepinephrine from storage vesicles, is said to work: DIRECTLY INDIRECTLY

INDIRECTLY Adrenergic Agonists may act directly on the actual receptor, OR indirectly At the nerve ending by releasing NE from storage vesicle, OR they can do both and be mixed acting.

All of the following are true with respect to EpiPen EXCEPT It is injected IM or SQ into the anterolateral aspect of the thigh, through clothing, if necessary. Comes as a single dose auto-injector formulation of Epinephrine It has a low dosage form of 0.15mg that is used for patients less than 15KG ( 33 pounds ) it has a high dosage form of 0.3 mg that is used for patients more than 30KG (66 pounds ) It is indicated in the emergent treatment of allergic reactions ( Type I )

It has a low dosage form of 0.15mg that is used for patients less than 15KG ( 33 pounds )

To allow a released neurotransmitter to be converted VERY QUICKLY into an electrical signal, the receptor type most associated with the CNS is: Ligand Gated Ion Channel Receptor G Protein Coupled Receptor Enzyme Linked Receptor Intracellular Receptor

Ligand Gated Ion Channel Receptor

Neuromuscular Blockers antagonize what cholinergic receptor? NICOTINIC/MUSCARINIC

NICOTINIC These drugs block motor transmission at the Skeletal Muscle nicotinic receptor, not smooth muscle muscarinic receptor. •Clinically useful during surgery for producing complete muscle relaxation without having to employ higher anesthetic doses to achieve comparable muscular relaxation. •Neuromuscular Blockers Are structural analogs of ACH 2 classes of Neuromuscular Antagonists: 1.Non-Depolarizing ( competitive antagonists) 2.Depolarizing ( agonists)

Which Neuromuscular blocking drug class is CAPABLE of being reversed by an Acetylcholinesterase ( ACHE ) Inhibitor ? DEPOLARIZING OR NON-DEPOLARIZING

NONDEPOL Non-Depolarizing ( Competitive) Neuromuscular blockers Interact with nicotinic receptors ( ligand Gated Ion Channel) and prevent binding of ACH at neuromuscular junction giving skeletal muscle relaxation •Q- Since they are competitive, can their action be overcome by increasing the concentration of ACH? •Answer = yes. •Antidote = an ACHE inhibitor that increases endogenous ACH.

A beta receptor blocking drug that is a Beta-1 cardioselective receptor blocker with nitric oxide (NO)-potentiating, vasodilatory effects is: Propanolol ( Inderal) Metoprolol ( Lopressor) Atenolol ( Tenormin ) Nebivolol ( Bystolic)

Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension. ( it releases nitric oxide form endothelial cells and causes vasodilation) • It is highly cardioselective ( beta-1) under certain circumstances, decreasing heart rate, decreasing myocardial contractility, suppression of renin activityà all leading to a decrease in BP.

Muscarinic Receptors are located at which site within the Nervous System. Sympathetic Ganglion in the Autonomic Nervous System Parasympathetic Ganglion in the Autonomic Nervous System Parasympathetic Effector Organ in the Autonomic Nervous System Sympathetic Effector Organ in the Autonomic Nervous System Neuromuscular Junction in the Somatic Nervous System

Parasympathetic Effector Organ in the Autonomic Nervous System

which of the following drugs is a NON-SELECTIVE BETA-BLOCKER , and antagonizes both Beta-1 and Beta-2 Adrenergic receptors? 1.Propanolol ( Inderal) 2.Doxacocin ( Cardura) 3.Metoprolol ( Lopressor 4. Atenolol ( Tenormin ) 5. Nebivolol ( Bystolic)

Propanolol ( Inderal) NON-SELECTIVE ( beta-1 & Beta-2) First successful Beta-Blocker developed HTN, Angina, Tachyarrythmias, Cluster headaches, PTSD

The primary mechanism for termination of the effect Norepinephrine is Oxidation by MonoAmine Oxidase ( MAO) Degradation by Catechol-MethylTransferase ( COMT) Degradation by Acetylcholinesterase ( ACHE ) Reuptake back into the presynaptic neuron

Reuptake back into the presynaptic neuron 1.Reuptake of NE back into presynaptic neuron is the PRIMARY mechanism for termination of NE effect. •ONCE INSIDE THE PRE-SYNAPTIC NEURON, NE HAS 3 FATES: a)Can be taken back up into a storage vesicle b)Can persist in cytoplasm c)Can be oxidized by MAO ( Monoamine Oxidase) -Monoamine Oxidases - a family of enzymes that catalyze the oxidation of monamines. ( Hist, Catecholamines (NE, Dopamine, Epi) Serotonin...)

The Depolarizing Neuromuscular Blocker - Succinylcholine - - has a rapid onset of action and a duration of action that is very short, which is very useful for short procedures. T/F

T

Dopamine is a precursor in the synthesis of Norepinephrine. T/F

TRUE •Norepinephrine is Synthesized by a series of enzymatic steps in the adrenal medulla and postganglionic neurons of the sympathetic nervous system from the amino acid tyrosine: 1.Tyrosine enters the cytoplasm of the neuron and is synthesized into L-DOPA , and then Dopamine. 2.Synthesized Dopamine enters into a protective neurotransmitter storage vesicle and is converted into Norepinephrine 3.A neuron action potential / accompanied by an influx of calcium, causes the storage vesicle to "dock" at cell membrane and release norepinephrine into synaptic space 4.Norepinephrine crosses the synaptic space and then binds to a postsynaptic adrenergic receptor ( alpha or beta) 5.Norepinephrine's effect is terminated primarily by reuptake back into presynaptic neuron, and also by COMT.

Central Alpha-2 receptor agonistic activity is associated with a reduced sympathetic outflow, a reduction in peripheral symapthetic tone and a decrease in blood pressure. T/F

TRUE Activating the central alpha-2 norepinephrine autoreceptors results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone and a decrease in BP.

The abnormal movements associated with Parkinson's Disease are due to the loss of CNS dopamine levels, and an APPARENT over action of __________________. dopamine ach serotonin gaba

ach Abnormal movements due to upset of the BALANCE of dopamine and ACH (not enough dopamine and APPARENT over action of ACH) No primary problem with ACH...!!!

All of the following contributions of Epinephrine in treating Emergent Anaphylactic Reactions are TRUE........ ...EXCEPT. Epinephrine alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its direct blocking action on histaminic receptors, epinephrine inhibits the systemic vasodilation and bronchocontriction associated with histamine release. Through its stabalizing action on mast cells, epinephrine blocks the release of inflammatory mediators mediators from mast cells—including histamine, interleukins, proteoglycans (e.g., heparin), and various enzymes. Through its action on beta-2 Betaadrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm,wheezing and dyspnea that may occur during anaphylaxis.

Through its direct blocking action on histaminic receptors, epinephrine inhibits the systemic vasodilation and bronchocontriction associated with histamine release. Bottom Line for Epinephrine and Allergic reactions: 1. Through its action on alpha adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension 2. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation that helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. 3. Epinephrine blocks the release of inflammatory mediators by mast cells and basophils in response to an antigenic challenge . ( mast cells release histamine, heparin, prostaglandins, leukotrienes ) 4. Epinephrine also alleviates pruritus ( itching) , urticaria ( hives) , and angioedema and may be effective in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder .

The reversal of the Depolarizing ( Non-Competitive) Neuromuscular Blocking Drug Succinylcholine is accomplished via: Answers: An Acetylcholinesterase ( ACHE) Inhibitor that augments ACH levels. Time is the only truly safe reversal agent for succinylcholine

Time is the only truly safe reversal agent for succinylcholine

Which of the following central alpha-2 receptor agonist drugs is utilized more as a muscle relaxant vs. being used as an anti-hypertensive, due to its effects on spinal polysynpatic reflexes vs. the vasomotor center? Tizanidine ( Zanaflex) Guanfacine ( Tenex) Clonidine ( Catapres )

Tizanidine ( Zanaflex)

Alpha-1 receptor Antagonism is associated with: Vasodilation of blood vessels in the skin, the sphincters of the GI system, kidney and brain. An increase in central symapthetic tone and an increase in blood pressure

Vasodilation of blood vessels in the skin, the sphincters of the GI system, kidney and brain Q- what effect will blocking alpha-1 receptors have on BP? ( BP decreases) -Remember - Blood vessels with α1-adrenergic receptors are present in the skin, the sphincters of gastrointestinal system, kidney (renal artery)and brain. •Q- what happens if central alpha-2 receptors are blocked? ( BP increases) -Remember - Stimulation of CENTRAL alpha-2 receptors causes an inhibition of further release of NE from the stimulated adrenergic neuron -BLOCKADE OF CENTRAL ALPHA-2 RECEPTORS WOULD THEN BLOCK THIS INHIBITORY EFFECT OF FURTHER RELEASE OF NE AND CAUSE AN INCREASE IN SYMPATHETIC TONE AND AN INCREASE IN BLOOD PRESSURE.

An Alzheimers Drug categorized as an NMDA Receptor Antagonist is: a. Donepezil ( Aricept) b. Rivastigmine ( Exelon) c. Memantine ( Namenda)

c Meantime, a NMDA (N-methyl-D-aspartate) glutamate receptor antagonist, which works by regulating the activity of glutamate, a chemical messenger involved in learning and memory. •Memantine protects brain cells against excess glutamate, a chemical neurotransmitter released in large amounts by cells damaged by Alzheimer's disease and other neurological disorders. •Attachment of glutamate to cell surface NMDA receptors permits calcium ( with sodium and potassium) to flow freely into the cell. Over time, this leads to chronic overexposure to calcium, which can speed up cell damage. •Memantine prevents this destructive chain of events by partially blocking the NMDA receptors.

An Alzeihmers Drug categorized as Central Acetylcholinesterase ( ACHE ) Inhibitor is? a Donepezil ( Aricept) b. Rivastigmine ( Exelon) c. Memantine ( Namenda) d. both a and b

d. both a and b CENTRAL ACETYLCHOLINESTERASE INHIBITORS: 1.Donepezil ( Aricept) 2.Rivastigmine ( Exelon)

Blockade of ocular beta receptors by Timolol ( Timoptic) will _________________ the production of aqueous humor , lower Intra Ocular Pressure ( IOP) and treat Glaucoma. increase/decrease

decrease Timolol: Non-Selective Beta Blocker (Blocadren)- oral form for HTN (Timoptic)- Opthalmic form used for treating Glaucoma. •MOA for Glaucoma: Blockade of the beta receptors on the ciliary epithelium reduces aqueous humor production, and decreases IOP.

Carbidopa, a dopa-decarboxylase inhibitor that is given with levodopa ( in Sinemet), _________________ the periepheral metabolism of Levodopa. diminishes increases

diminishes what is Carbidopa, and what does it do? Answer = It is a dopa-decarboxylase inhibitor, given with L-dopa, that diminishes the metabolism of L-DOPA in the GI tract and peripheral tissues increasing the availability of L-DOPA to the CNS.

The precursor to Dopamine, Levodopa, which does cross the BBB, by itself, is an effecient and suitable option in the treatment of Parkinson's disease. t/f

false Q-Why is not the L-Dopa precursor ( which does cross the BBB) by itself not a suitable enough option? Answer = very large doses of L-Dopa would be required , because much of the drug is decarboxylated to dopamine in the periphery before it reaches the BBB....and these large doses result in side effects that include N/V, cardiac arrhythmias, and hypotension. Q- What is Carbidopa, and what does it do? Answer = It is a dopa-decarboxylase inhibitor, given with L-dopa, that diminishes the metabolism of L-DOPA in the GI tract and peripheral tissues increasing the availability of L-DOPA to the CNS.

Dopamine given systemically, is capable of crossing the Blood Brain Barrier and treating Parkinson's Disease t/f

false l-dopa is able to cross BBB

Beta-2 SPECIFIC adrenergic Antagonists are clinically useful. t/f

falseBeta-2 antagonism =broncho-constriction

All of the following neurotransmitters are excitatory in the CNS, EXCEPT: GABA ACH NE Dopamine

gaba GABA - ( Gamma- AminoButyric Acid): •Inhibitory Neurotransmitter in the CNS ( mediates Chloride influx into the cell)—Remember for Chapter 9..!! •Chief inhibitory neurotransmitter in the CNS • GABA regulates CNS excitability, regulates the N/V center in the CNS, and has muscle relaxation properties.

When a CNS cell is Hyperpolarized ( via Chloride entry into the cell ) , that CNS cell is_______________________, and when a CNS cell is Partially Depolarized ( via sodium entry into the cell), that CNS cell is _________________________. Less Excitable, More Excitable More excitable , Less excitable

less excitable, more excitable As noted, the majority of CNS receptors are LIGAND GATED ION CHANNEL RECEPTORS •Excitatory Neurotransmitters bind to ligand gated ion channel receptors coupled to Na+ ion channels, allow Na+ to enter cell, and raise RMP ( -70mV) closer to threshold ( -50mV), making the cell more excitable. ( depolarizing effect) •As noted, the majority of CNS receptors are LIGAND GATED ION CHANNEL RECEPTORS •INHIBITORY Neurotransmitters bind to ligand gated ion channel receptors coupled to Chloride ion ( Cl-)channels, allow the anion chloride to enter the cell, and this lowers RMP ( -70mV) further away from threshold ( -50mV), making the cell less excitable. ( hyperpolarizing effect)

The CNS communicates with ______________ neurotransmitters, as compared to the Autonomic Nervous System ( Peripheral Nervous System) . more/less

more Circuitry of the CNS is much more complex than that of the autonomic nervous system and the number of synapses in the CNS is far greater •CNS = 100 billion nerve cells •PNS = 12 cranial nerves + 8 cervical nerves + 12 thoracic + 5 Lumbar + 5 Sacral + 1 Cocycx ( 31 spinal nerves) • 2. CNS contains powerful networks of now....inhibitory neurons that are constantly active in modulating the rate of neuronal transmission. • 3. CNS communicates through the use of as many as 10 different neurotransmitters vs. 2 for the PNS. (perhaps as many as 50) •The autonomic nervous system uses only two primary neurotransmitters, acetylcholine and norepinephrine. 4. CNS receptors are mostly ligand-gated ion receptors vs. G- Protein coupled receptors for the PNS

Alzheimers Disease is associated with the ___________________ of the Central Glutamate NMDA Receptors, which speeds up CNS cell death and reduces the synthesis of the neurotransmitter ACH. overstimulation understimulation

overstimulation Overstimulation of excitatory glutamate receptors is hypothesized to be involved in the etiology of Alzheimer's Disease, and antagonizing this glutamate receptor is utilized in treating Alzheimer's Dx.

What Neuromuscular Blocker is associated with Malignant Hyperthermia? Tubocurarine succinylcholine Rocuronium ( zemeron) Pancuronium ( pavulon) Vercuronium ( Norcuron)

succinylcholine

The Indirect Acting Adrenergic Blocking drugs Reserpine and Guanethidine treat HTN by either blocking the transport of neurotransmitters in the cytoplasm into the storage vesicles or by blocking the release of stored norepinephrine from storage vesicles? t/f

true Reserpine ( rarely used) -Blocks the transport of biogenic amines, NE, Dopamine, Serotonin from the cytoplasm into the storage vesicles in the adrenergic neuron ultimately causing neurotransmitter depletion. -Reserpine is used to treat high blood pressure. - 2. Guanethidine ( Ismelin) -Blocks the release of stored NE in the storage vesicle......as well as displaces NE from storage vesicles leading to a gradual depletion of NE in nerve endings except those in the CNS -Ismelin (guanethidine monosulfate) is indicated for the treatment of moderate and severe hypertension