Week 2
Competitive Antagonist
(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)
Epinephrine
* 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.
The abnormal movements associated with Parkinson's Disease are due to the loss of CNS dopamine levels, and an APPARENT over action of __________________.
Acetylcholine 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 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?
True •Some Adrenergic Antagonists act Indirectly on the adrenergic neuron either to interfere with the Neurotransmitter release, or to alter the uptake of the neurotransmitter into the adrenergic neuron. •Due to the advent of newer and more effective drugs, these drugs are seldom used therapeutically. 1.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.
Serotonin
'Happiness Hormone' , associated with mood, sleep, memory, appetitie, learning •Also does not cross BBB & reach CNS when given systemically •Found in CNS ( 10%) , GI tract ( 90%), & platelets •Associated with Mood
Donepezil ( Aricept)
Alzheimer's Disease
Succinylcholine
Depolarizing ( Non-Competitive ) Neuromuscular Blockade
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
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.
Norepinephrine
•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.
Catechol-Methyltransferase ( COMT )
•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)
Central Alpha-2 Adrenergic Agonists
•α2 agonists: inhibit adenylyl cyclase activity. (reduce brainstem vasomotor center-mediated CNS activation; used as antihypertensive, sedatives & treatment of opiate dependence and alcohol withdrawal symptoms)
Isoproterenol
* 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.
Norepinephrine
* Systolic BP , Diastolic BP, PVR all increase via intense vasoconstriction from activation of Alpha-1 vascular receptors. * Pulse rate decreases via reflex bradycardia.
Tizanidine ( Zanaflex)
- is a drug that is used as a muscle relaxant. It is a centrally acting α2 adrenergic agonist. • a potent, central-acting myotonolytic agent that principally affects the spinal polysynaptic reflexes vs. the vasomotor center • Despite its structural and biochemical similarity to clonidine, the cardiovascular properties of tizanidine are mild and transitory in relation to its activity as a muscle relaxant. •It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, ALS, spastic diplegia, back pain, or certain other injuries to the spine or central nervous system.
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
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.
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.
Which of the following drugs is a NON-SELECTIVE BETA-BLOCKER , and antagonizes both Beta-1 and Beta-2 Adrenergic receptors?
1. Propanolol ( Inderal) NON-SELECTIVE ( beta-1 & Beta-2) First successful Beta-Blocker developed HTN, Angina, Tachyarrythmias, Cluster headaches, PTSD
Q- Could an Anti muscarinic Drug be useful?
A = Yesà lowers ACH influence and 'rebalances" scale with dopamine #6. Benztropine( Cogentin) ( adjunctive role) Blockage of cholinergic transmission produces effects similar to augmentation of dopaminergic transmission ( because of imbalance)...!!!
Sinemet
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.
Which of the following physiological effects IS NOT ASSOCIATED with adrenergic stimulation?
A decrease in glucose levels
Mirabegron ( Mybetriq)
A direct beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Selegiline ( Eldepryl)
A selective Monoamine Oxidase-B ( MAO-B) Inhibitor
Albuterol (Ventolin)
A short acting beta-2 agonist inhaled for direct bronchodilation. ( most commonly prescribed beta-2 specific agonsist in the treatment of asthma)
Levalbuterol ( Xopenex)
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
Bromocriptine ( Parlodel)
A straight Dopamine Receptor Agonist, but has severe side effects.
Cholinergic Antagonists drugs have:
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 )
Doxazocin ( Cardura )
Alpha -1 selective blocker used to treat both HTN and urinary retention associated with BPH.
Terazocin ( Hytrin)
Alpha -1 selective blocker used to treat both HTN and urinary retention associated with BPH.
The "First-Dose Phenomenon" is associated with what category of Adrenergic Antagonist?
Alpha-1 Adrenergic Antagonist •The 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.
Tamulosin ( Flomax)
Alpha-1 selective adrenergic blocker that is more specific for treating BPH than for HTN -Tamsulosin is a selective α1 receptor antagonist that has preferential selectivity for the α1A receptor in the prostate versus the α1B receptor in the blood vessels -When alpha 1 receptors in the bladder neck and the prostate are blocked, this causes a relaxation in smooth muscle and therefore less resistance to urinary flow.
Rivastigmine ( Exelon )
Alzheimer's Disease
Fesoterodine ( Toviaz)
An Anti-Muscarinic used to relieve urinary and bladder difficulties, including frequent urination ( urge incontinence) by decreasing muscle spasms of the bladder.
Oxybutinin ( Ditropan )
An Anti-Muscarinic used to relieve urinary and bladder difficulties, including frequent urination ( urge incontinence) by decreasing muscle spasms of the bladder.
Tolterodine ( Detrol)
An Anti-Muscarinic used to relieve urinary and bladder difficulties, including frequent urination ( urge incontinence) by decreasing muscle spasms of the bladder.
Alpha-2 Receptor Antagonism is associated with:
An increase in central symapthetic tone and an increase in blood pressure Answers: Vasodilation of blood vessels in the skin, the sphincters of the GI system, kidney and brain.
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.
Q-Is straight dopamine administration an option?
Answer = NO, it does not cross the BBB.( the precursor to Dopamine..... L-Dopa is given instead( which does cross)and is then converted to Dopamine in the brain.
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.
Benztropine ( Cogentin )
Anticholinergic that plays an "adjunctive' role in lowering cholinergic stimulation and reestablishing a balance with dopamine in the CNS.
Adrenergic Agonists
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.
Alpha-2 Adrenergic Receptor
Are located Centrally and peripherally , and when stimulated centrally are associated with inhibiting sympathetic response decreasing peripheral vascular resistance and lowering blood pressure
Dopamine given systemically, is capable of crossing the Blood Brain Barrier and treating Parkinson's Disease.
False
A drug that lowers Cholinergic Acetylcholine Influence INSTEAD of augmenting Dopaminergic Influence in the treatment of Parkinson's Disease is
Benztropine ( Cogentin )
Scopolamine
Blocks Cholinergic transmission in the CNS to the vomiting center and is used for motion sickness
Low dose Epinephrine is associated mostly with Alpha ( vasoconstrictive ) effects, while high dose Epinephrine is associated beta receptor activity.
False
The Beta-2 Receptor Selective agonist activity of Isoproternol ( Isuprel) makes it an ideal choice for Asthma.
False
An Alzeihmers Drug categorized as Central Acetylcholinesterase ( ACHE ) Inhibitor is?
CENTRAL ACETYLCHOLINESTERASE INHIBITORS: 1.Donepezil ( Aricept) 2.Rivastigmine ( Exelon)
Norepinephrine in the synaptic cleft, that is NOT terminated by the reuptake back into the presynaptic neuron, is degraded by?
Catechol-Methyltransferase ( COMT )
Clonidine, Guanfacine and Tizanidine are all classified as:
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
All of the following are effects of MUSCARINIC ANTAGONISM EXCEPT
Decreased Cardiac Heart Rate
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.
False
Beta-2 SPECIFIC adrenergic Antagonists are clinically useful.
False Beta-2 antagonism =broncho-constriction
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______________?
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.
Ipratropium ( Atrovent )
Effects primarily bronchial smooth muscle producing bronchodilation
Another name for Adrenergic Agonists is Sympatholytics.
False
Cholinergic Antagonism at Autonomic Nervous System ganglia for BOTH the Sympathetic and Parasympathetic Divisions is clinically useful.
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.
Atropine
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.
An adrenergic agonist that stimulates the release of norepinephrine from storage vesicles, is said to work:
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.
Dopamine
Is an alpha agonist, a beta agonist and also produces renal vasodilation.
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 following are true with respect to EpiPen EXCEPT:
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 )
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 •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)
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 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
Salmeterol ( Serevent)
Long acting Direct B2 specific adrenergic agonist ( Inhaled for direct bronchodilation on bronchial smooth muscle )
Bromocriptine ( Parlodel)
Parkinon's Disease
Carbidopa / Levodpa ( Sinemet)
Parkinon's Disease
An Alzheimers Drug categorized as an NMDA Receptor Antagonist is:
Memantine ( Namenda) 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.
Isoproternol ( Isuprel)
NON-Selective Pure Beta Receptor Agonist with NO alpha effects; increases HR & Force of Contraction ( B1) ; Bronchodilation ( B2)
A beta receptor blocking drug that is a Beta-1 cardioselective receptor blocker with nitric oxide (NO)-potentiating, vasodilatory effects is:
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.
Rocuronium ( Zemeron) , Pancuronium ( Pavulon ) and Vercuronium ( Norcuron)
Non-Depolarizing ( Competitive) Neuromuscular Blockade
Non-Depolarizing Neuromuscular Blockers
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
Neuromuscular Blockers antagonize what cholinergic receptor?
Non-Depolarizing Neuromuscular Blockers
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 •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.
Muscarinic Receptors are located at which site within the Nervous System.
Parasympathetic Effector Organ in the Autonomic Nervous System
Epinephrine
Primarily a beta receptor agonist at low doses and an alpha receptor agonists at high doses;mast cell stabalizer for analphylactic reactions
GABA
Primary Inhibitory Neurotransmitter in the CNS, regulates CNS excitability, possesses muscle relaxtation properties, regulates the N/V center in the CNS
The primary mechanism for termination of the effect Norepinephrine is
Reuptake back into the presynaptic neuron
Termination of Norepinephrine
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...)
Dopamine
Reward-Motivated Behavior, voluntary movements, fine motor control, motivation, information processing, associated with addiction •synthesized from adrenal medulla and also from CNS neurons. •PNS= affects Alpha + beta + dopamine receptors in kidney •CNS= affects dopamine receptors widely distributed in the brain •Peripheral Dopamine Does not cross BBB àinto CNS •Precursor to Dopamine ( L-Dopa), however , can cross BBB.
What Neuromuscular Blocker is associated with Malignant Hyperthermia?
Succinylcholine
The reversal of the Depolarizing ( Non-Competitive) Neuromuscular Blocking Drug Succinylcholine is accomplished via:
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)
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
True
Dopamine is a precursor in the synthesis of Norepinephrine.
True
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.
True
Alpha-1 receptor Antagonism is associated with:
Vasodilation of blood vessels in the skin, the sphincters of the GI system, kidney and brain.
Beta-2 Adrenergic Receptor
When stimulated , are associated with bronchial smooth muscle relaxation, dilation of arteries to skeletal muscle.
Beta-1 Adrenergic Receptor
When stimulated are associated with increased HR, increased force of contraction of heart , and renin release from the kidneys which leads to Angiotensin II
Alpha-1 Adrenergic Receptor
When stimulated, are associated with vascular smooth muscle vasocontriction, pupil dilation
Q- Can we think of cholinergic muscarinic antagonism as having the same kind of influence as adrenergic agonists?
Yes, both allow for increased adrenergic influence.
Blockade of ocular beta receptors by Timolol ( Timoptic) will _________________ the production of aqueous humor , lower Intra Ocular Pressure ( IOP) and treat Glaucoma.
decrease (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
Norepinephrine
focus,arousal, memory, attention, wakefulness, learning, reward system
Nicotine
ganglionic blocker without therapeutic effect but is used in smoking replacement therapy
Malignant Hyperthermia
is a rare life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine
The CNS communicates with ______________ neurotransmitters, as compared to the Autonomic Nervous System ( Peripheral Nervous System) .
more 1. 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
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
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.
Depolarizing Drug = Succinylcholine
•Antidote = time..!! (an ACHE inhibitor will not reverse, as succinlycholine it is non-competitive....!!!!) •Therapeutic Use: Succinylcholine has a RAPID onset of action , and a DURATION OF ACTION THAT IS VERY SHORT, therefore Succinylcholine is useful for short procedures and when longer muscle paralysis is not needed and when rapid endotracheal intubation is required during the induction of anesthesia. •( a rapid action is essential if aspiration of gastric contents is to be avoided during intubation)
Adrenergic Stimulation
•Dilation •Increased HR & Force of Contraction •Decreased Motility •Bladder Smooth Detrusor Muscle relaxation ( allows bladder to store urine) •Bronchodilation •Relaxation ( Vasodilation) Glucagon Secreted ( Glucose from glycogen )