Pharmacology- Final Exam Study Guide PDF

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Pharmacology- Final Exam Study Guide...

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Pharm Test 2 Study Guide Chapter 12 Informaion to pay atenion to in Neuropharmacology •

Study of drugs that alter processes controlled by the CNS

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Drugs can either excite or depress neuronal acivity

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A neuropharmacologic agent can alter one of two basic neuronal aciviies: •

Axonal conducion •

The process of conducing an acion potenial down the axon of the neuron

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Drugs that afect this process are not very selecive; alters conducion in all the nerves it has access to; therefore, they have limited uses 1. Example: local anestheics non-selecively decrease axonal conducion (look at diagram in book; lidocaine afects every single axon that it comes in contact with; thus, when we give local anestheic, we inject it to keep it localized to a speciic area

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Synapic transmission •

The process by which informaion is carried across the gap between the neuron and the postsynapic cell

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Most neuropharmacologic agents act by altering synapic transmission; therefore, they are more selecive b/c they alter speciic neurotransmiters or receptors.

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Except for local anestheics all neuropharmacologic drugs act by altering the synapic transmission

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Key point: the impact of a drug on a neuronally regulated process is dependent on the ability of that drug to directly or indirectly inluence receptor acivity on target cells.

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In general drugs do 2 things: enhance receptor acivaion or reduce receptor acivaion •

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Acivaion—an efect on receptor funcion equivalent to that produced by the natural neurotransmiter at a paricular synapse

Steps in synapic transmission

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Step 1-Transmiter synthesis; for synapic transmission to take place molecules need to be present in the nerve terminal (igure 12-2)

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Step 2-Transmiter storage-stored in vesicles at nerve terminals unil ime of release

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Step 3-Release of the neurotransmiter into the synapic gap •

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Amphetamines (CNS simulants) represent drug that promote transmiter release, and botulinum toxin inhibits transmiter release

Step 4-Binding of the neurotransmiter to the receptor, causes a physiological change in the body •

Many drugs act directly at receptors by either: 1. Binding to receptors and causing acivaion, e.g. agonists (morphine, epinephrine, and insulin) 2. Bind to receptors and, thereby, blocking acivaion by other agents, e.g. antagonists (naloxone, anihistamines, and propranolol. 3. Binding to receptors components and, thereby, enhancing receptor acivaion by the natural transmiter at the site, e.g. benzodiazepines: diazepam (Valium),

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Step 5-Terminaion of transmiter acion, that is, the degradaion process. •

Transmiter can be removed from the synapic gap by 1. Reuptake, 2. Enzymaic degradaion or 3. Difusion away from the synapic gap.

Chapter 13 Nervous system divided into central nervous system (CNS) and peripheral nervous system.  

CNS=brain and spinal cord Peripheral nervous system= somaic motor system and autonomic nervous system (sympatheic and parasympatheic).

Major neurotransmiters of the peripheral nervous system are: 

acetylcholine (secreted by cholinergic nerve ibers; employed at most juncions of PNS; Acetylcholine is released by 1. Pre ganglionic neurons of PNS 2. All pre ganglionic neurons of the Sympatheic nervous system and 3. ALL POST GANGLIIONIC neurons of the Parasympatheic Nervous system 4. all motor neurons to skeletal muscles, and 5. most post ganglionic neurons of the sympatheic nervous system that go to sweat glands

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norepinephrine (secreted by adrenergic nerve ibers; released by 1. Pracically all postganglionic neurons of Sympatheic nervous systems excepions – post ganglionic sympatheic neurons that go to sweat gland which employ acetylcholine as their transmiter 2. Also some is released by the adrenal medulla epinephrine (secreted by the adrenal medulla) dopamine ( acts as a catecholamine)

Receptor types 

cholinergic receptor are deined as receptors that mediate responses to acetylcholine o three subtypes: nicotinicN, nicotinicM, and muscarinic o a subtype responds to the same neurotransmitter but

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adrenergic receptors are deined as receptors that mediate responses to epinephrine (adrenaline) and norepinephrine (NE) o four adrenergic subtypes: alpha1, alpha2, beta1, and beta2 o another adrenergic type: Dopamine receptors  do not respond to epinephrine or NE, only to dopamine, a neurotransmiter found primarily in the CNS  Dopamine receptors are located in vasculature of the kidney; acivaion dilates renal blood vessels increasing renal perfusion. Can give these neurotransmiters exogenously to control the body pharmacologically

nonetheless is diferent from other subtypes

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Autonomic nervous system 1. 3 primary funcions of the ANS: regulaion of the heart, secretory glands (salivary, gastric, sweat, and bronchial glands), and smooth muscles (muscles of bronchi, blood vessels, urogenital system, and GI tract). 2. A branch of the CNS 3. Regulated by the: hypothalamus, brain stem, and spinal cord 4. Requires no conscious or acion (just happens) 5. Maintains homeostasis by regulaing processes such as body temperature, responds to stress and emergencies 6. Nerve impulses are transmited in the same way as the CNS ANS is divided into Sympatheic Nervous System (SNS) and Parasympatheic Nervous system (PNS) 

The two systems keep each other in balance. The SNS excites and the PNS inhibits. 1. The branch of the ANS that controls organ funcion most of the ime is said to provide the predominant tone to that organ. In most organs, the PNS provide the predominant tone. The vascular system, which is regulated almost exclusively by the SNS, is the principle excepion. 2.

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Parasympatheic funcions: slow heart rate, increase gastric secreion, empty bladder, empty bowel, focus the eye for near vision, constrict the pupil, and contract bronchial smooth muscle Sympatheic funcions (3 main funcions): regulate cardiovascular system (maintain blood low to the brain and other vital organs, redistribute blood low during exercise, vasoconstricion to compensate for blood loss), regulate body temp, and implement the ight or light reacion (increased HR/BP/CO, shuning of blood away from the skin and viscera and into the skeletal muscles, dilaing the bronchi to improve oxygenaion, dilaing pupils to enhance visual acuity, mobilize store energy to provide glucose for the brain and faty acids for muscles).

What you need to know about the ANS: 

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Drugs can act at 2 diferent sites in the PNS and SNS: 1. Synapses between preganglionic neurons and postganglionic neurons  Ganglion-neurons synapse in the ganglion; ganglion is a lump of nerve cell bodies  One excepion is in the SNS where the adrenal medulla is looked on as the equivalent of a postganglionic neuron b/c it inluences the body by releasing epinephrine 2. The juncions between postganglionic neurons and their efector organs. Drugs that afect the somaic motor system have one site of acion: the neuromuscular juncion Fig 13-4: In order to understand PNS pharmacology, you must be able to idenify the transmiters employed at each of the juncions of the peripheral nervous system 1. All preganglionic neurons of the PNS and SNS release acetylcholine as their transmiter 2. All postganglionic neurons of the PNS release acetylcholine as their transmiter 3. Most postganglionic neurons of the SNS release norepinephrine (NE) as their transmiter 4. Postganglionic neurons of the SNS that innervate sweat glands release acetylcholine as their transmiter 5. Epinephrine is the principle transmiter released by the adrenal medulla 6. All motor neurons to skeletal muscles release acetylcholine as their transmiter The process of feedback regulaion is called a relex (arc); main elements of feedback regulaion: 1. Sensor-neuron picks up informaion, which is sent to the brain via the spinal cord 2. CNS: in the brain the informaion is integrated with other relevant info 3. Neurons- signals (instrucions for change) are sent from the CNS along the nerves of the ANS to the efector 4. Efector—the muscle, organ; in response to these instrucions, the efector makes appropriate adjustments in the process.

Adrenergic Agonists-Chapter 17 

Produce efect by acivaing adrenergic receptors- similar to sympatheic nervous system Adrenergic oten referred as sympathomimeics – used for heart failure, asthma, preterm labor.

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Drugs that mimic the efects of adrenergic nerve simulaion (i.e. Mimic norepinephrine or mimic the efects of the adrenal medulla releasing epinephrine)

Adrenergic Agonist Mechanism of Acion: 1. Direct receptor binding: the direct-acing receptor simulants produce their efect by binding to adrenergic receptors and mimicking the acions of natural transmiters (NE, Epinephrine, dopamine); this is the only mechanism that is direct; the next three are indirect 2. Promoion of NE release-act on terminals of sympatheic nerves to cause NE release. Examples: Amphetamines and ephedrine; however, ephedrine can also acivate adrenergic receptors directly 3. Inhibiion of NE reuptake-block causes NE to accumulate within the synapic gap increase receptor acivaion. Examples: cocaine, tricyclic anidepressant (e.g. imipramine); these work to raise NE. 4. Inhibiion of NE inacivaion-increases the amount of NE available for release by inhibits its inacivaion by monoamine oxidase (MAO)- this can enhance receptor acivaion Catecholamines 

CANNOT BE USED ORALLY; can only be given IV o

Acion of MONAMINE oxidase MOA and catechol O methyltransferase and COMT located in liver enzymes destroy catecholamines; therefore, they cannot be given orally b/c of short half life

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Therefore, if we want to turn the infusion of because of HTN, they will be out of the body quickly

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BRIEF DURATION OF ACTION

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CANNOT CROSS BLOOD BRAIN BARRIER because they are polar molecules; posiive charge prevents them from crossing BBB

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Oxidaion cause catecholamines to turn pink or brown over ime; catecholamine soluions should be discarded as soon as discoloraion develops

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Structurally the same ethylamine; contain catechol group and an amine group. Simply a benzene ring that has hydroxyl groups or two adjacent carbons

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Epinephrine, norepinephrine, Isoproterenol, Dopamine and dobutamine have three common properies

Chemically have a catechol and an amine group- DINE o

Dopamine

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Dobutamine

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Isoproterenol

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Norepinephrine (NE)

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Epinephrine

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Important in criical care!!!

Noncatecholamines 

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Have ethylamine do not contain the catechol moiety (a part or funcional group of a molecule) that characterized the catecholamines o Ephedrine, Phenylephrine, terbutaline Because they lack a catechol group, they are not substrates for catechol-O-methyltransferase (COMT) and are metabolized slowly by MAO much longer half-lives and can be given PO Structurally do not have the catechol porion of the molecule- PET o Phenylephrine o Ephedrine o Terbutaline As compared to catecholamines: o Have longer half-lives (not as metabolized in the liver) o Therefore, they can be given orally o Less polar thus cross the B-B barrier (more efects on the CNS)

RECAP: Important Diferences between Noncatecholamines and Catecholamines Catecholamines: Not given orally; Brief duraion of acion; cannot cross blood brain barrier; DINE (Dopamine, Dobutamine, Isoproterenol, Norepinephrine, Epinephrine) Noncatecholamines: Lack catechol group- not substrates for COMT and MAO; Half-lives much longer; Can be given orally; Less polar more able to cross blood brain barrier; PET (Phenylephrine, Ephedrine, Terbutaline).

SNS—Fight or Flight response—Running from the BEAR   

To either deal with stress or run from it Increased BP (increased CO and HR) Increased cardiac output (CO)

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Blood is shunted to the brain, heart, and skeletal muscle Decreased blood low to the visceral organs (skin, kidneys) Increased rate of cellular metabolism Increased blood sugar; increased breakdown of muscle glycogen (to have energy to get away) Increased mental acivity (think beter) Increased coagulaion (don’t want to bleed to death if you fall down) Increased respiratory rate and depth (b/c you’re running as fast as you can) Pupil dilaion (to aid in vision)

The SNS receptors (adrenergic receptors) Alpha 1:  

Located in eyes, blood vessels, male sex organs, prostaic capsule, and bladder (trigone and sphincter) contract muscles; vasoconstricion; rise in BP; GI & bladder sphincter contracion; pupillary dilaion (mydriasis)

Alpha 2:    

Receptors of the peripheral nervous system are located on nerve terminals and not on the organs innervated by the ANS. Referred to as presynapic or prejuncional b/c they’re located on nerve terminals Regulate neurotransmiter releases negaive feedback, if you simulate alpha 2, you inhibit NE; inhibiing NT release, less norepinephrine is released; thus, an aniadrenergic efect: 1) Reducion of sympatheic ouflow to the heart and blood vessels 2) Relief of severe pain

Beta 1:       

receptors located in the heart and kidney acivaion of cardiac receptors increases the rate and force of contracion, and velocity of impulse conducion through the AV node acivaion of the receptors in the kidney causes the release of Renin (precursor in RAS system) into the blood; renin promotes synthesis of angiotensin, a powerful vasoconstrictor that raises BP acivaion- heart failure Shock Atrioventricular heart block-drug used for cardiac arrest-epinephrine Adverse efect of BETA ONE= Altered heart rate or rhythm, angina pectoris (b/c of vasoconstricion)

Beta 2:

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receptors located in the smooth muscles of the uterus, lungs, arterioles of the heart, lungs, and skeletal muscle; also located in the liver Inhibits smooth muscle; causes relaxaion of uterine and bronchial smooth muscle (bronchodilaion); arterioles vasodilate Acivaion in the skeletal muscles and liver promotes glycogenolysis(the breakdown of glycogen into glucose) and gluconeogenesis; it also enhances skeletal muscle contracion Used for asthma, delay of preterm labor Bronchodilaion in asthma (albuterol is a beta 2 agonist) Beta Two adverse efect hyperglycemia and tremor

Dopamine:   

Have receptors located in the peripheral and central nervous system The only peripheral receptors are located in the renal vasculature Acivaion of the receptors in the renal vasculature cause dilaion of blood vessels surrounding the kidney; enhances renal perfusion

Parasympathetic nervous system     

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Rest, reparaive, vegetaive state Aids in digesion, excreion, cardiac deceleraion, anabolism and near vision, balances out SNS 75% of all PNS ibers are in the vagus nerves Body responses of the parasympatheic are basically the opposite of the SNS, not 100% opposite Dilaion of blood vessels, decreased heart rate, increased secreion of digesive enzymes and moility of the GI tract, bronchoconstricion, increased secreions from glands in lung, stomach, intesines and skin, constricted pupils and accommodaion to near vision, contracion of smooth muscle of the bladder No noted efects on blood coagulaion, blood sugar, mental acivity or muscle strength

Regulaion of the PNS:  Acetylcholine regulates the PNS; regulaion PNS results in: o Pupil constricion o Bradycardia o Bronchoconstricion o Vasodilaion o GI acivity o Voiding o Erecion o Generalized sweaing General informaion:  Most drugs simulate muliple receptors but research is on-going to develop those that will work only on speciic receptors thus limiing efects Terms which refer to substances that simulate the SNS:  Sympathomimeic-to simulate the SNS  Alpha and beta adrenergic agonists-simulate the body as the natural body chemicals would

 Adrenergics, adrenomimeics, adrenergic agonists Substances that simulate the PNS: Direct-acing  Parasympathomimeic, cholinomimeic, cholinergics, cholinergic agonists Indirect acing  Cholinesterase inhibitors (anicholinesterase)-increase muscle tone Substances that inhibit the SNS:  Sympatholyic, aniadrenergic, alpha and beta blocking drugs, adrenergic blockers, adrenolyics, adrenergic antagonists Substances that inhibit PNS:  Parasympatholyic, anicholinergic, cholinergic blockers, cholinergic antagonists, or anispasmodics Key points:  Opposite responses on organ issue are caused by sympathomimeics and parasympatheomimeics, and by sympathlyics and parasympatholyics.  Sympathomimeics and parasympatholyics cause similar organ response as do sympatholyics and parasympathomimeics.  Applicaion to pracice: because sympathomimeics and parasympatholyics have similar efects, when a pt. has asystole, alternate between epinephrine and atropine (a parasympatheic depressant)

Adrenergic drugs Produce efects similar to those when the SNS is simulated Therapeuic efects and adverse efects are due to the inluence on blood vessels, lungs and heart  Most body issues have both alpha and beta receptors  Thus efects depend mostly on each drug’s acivaion of paricular receptors and the number of afected receptors in a paricular body issue a. Alpha 1: vasoconstrict, elevate BP and decreases nasal congesion b. Beta 1: cardiac simulaion (rate and force of contracion) c. Beta 2: bronchodilaion, vasodilaion, contracion of urinary and GI sphincters, changes in renin secreion (afects kidneys and luid balance), decreased secreion of insulin (thus higher blood glucose) Some Indicaions for Adrenergic Drugs  Treatment of respiratory, cardiac and allergic emergencies (epinephrine is one of the main drugs we use from this category; allergic rxns)  Decongestants (colds, sinusiis); vasoconstricion of vessels in nose decreases congesion  Pre-term labor (decrease contracions)  Used a lot in crit care seing; when pts get sepic, they become very hypotensive; have to maintain BP, so we use these drugs Adrenergic Contraindicaions  Cardiac arrhythmias (simulaing the rate and force of the heart is not something we want to do).  Angina  HTN  Hyperthyroidism (those pt. are oten tachycardia)  

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Severe anxiety states Psychiatric disorders (due to CNS simulaion)-use caion Elderly (use cauion)

Adrenergics Adrenalin (Epinephrine)     

Simulates both alpha (1 and 2) and beta (1 and 2) receptors (all 4) Mimics endogenous epinephrine At usual doses: beta efects prevail; when we give a dose of epinephrine we usually see more cardiac efects to try to force the heart to respond At higher doses: alpha efects prevail (vasoconstricion); see more vasoconstricion Uses: a. Drug of choice for anaphylacic shock (to relieve bronchospasm and laryngeal edema)high dose b. Used in cardiac arrest as a cardiac simulant and vasoconstrictor c. Acive ingredient in OTC inhalaion asthma products (Primatene Mist, Bronkaid Mist); recommend pt. experiencing anaphylacic atack not use these drugs b/c they will not respond b/c receptors are already occupied; should use albuterol instead

Table 17-2, p. 155 KNOW THIS TABLE Catecholamines Noncatecholamines Drug Receptors acivated Drug Receptors aciv...