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Pharmacology Exam 1-
| Question | Answer |
|---|---|
| Drugs alter nervous system functions primarily by affecting ___ or their ____. | Neurotransmitters; receptors |
| The nervous system consists of the ____ and ____ nervous systems. | Central; Peripheral |
| The CNS includes the __ and __ (organs) | brain; spinal cord |
| The PNS includes the ___ nervous system and the ___ nervous system | Autonomic (ANS); Somatic |
| The 2 divisions of the PNS are: | Efferent and Afferent Divisions |
| The efferent division of the PNS can further be divided into the: | Autonomic Nervous System (ANS) and Somatic Nervous System |
| The ANS can be divided into these three divisions: | Parasympathetic, Sympathetic, and Enteric |
| The ____ dvision of the ANS receives inputs from both the parasympathetic and sympathetic nervous system, but it can also function on its own. | Enteric |
| The Somatic NS has how many nerve fibers? | 1 neuron that goes all the way to the muscle |
| The Somatic NS is activated by ___, which originate in the ___, and by ____ reflexes | corticospinal tracts; motor cortex; spinal |
| The Somatic Nervous system is ___ and activates what type of muscles? | voluntary; skeletal |
| The ANS is ___ and regulates the activity of ___. | involuntary; internal organs (Cardiac and smooth muscle, etc) |
| The ANS is regulated by ___ in the CNS and consists of how many neurons? | brain stem; 2 neurons |
| In the Sympathetic NS, nerves arise from the __ and ___ part of the spinal cord | Thoracic and Lumbar (Dr. Petkov refers to this as thoracolumbar) |
| The Sympathetic NS has a ___ preganglionic fiber and a ___ postganglionic fiber. | short; long |
| The Parasympathetic NS has ___ nerves | craniosacral |
| The Sympathetic nervous system is adrenergic or cholinergic? | Adrenergic |
| The Parasympathetic NS is adrenergic or cholinergic? | Cholinergic |
| The SNS tends to be excitatory or inhibitory? | Excitatory, with the exception of the urinary bladder which is inhibitory |
| The PNS tends to be excitatory or inhibitory? | Inhibitory |
| What did Cannon call the Sympathetic system? | "Flight or Fight" |
| What is the PNS called? | "Rest or Digest" |
| What is the major NTs of the SNS? | norepinephrine (noradrenaline), but also ATP and neuropeptide-Y as co-transmitters |
| What is the major NTs of the PNS | Acetylcholine but also vasoactive intestinal peptide (VIP) as co-transmitter |
| What are the receptor types of the SNS? | alpha and beta |
| What are the receptor types of the PNS? | nicotinic and muscarinic |
| Acetylcholine is the primary NT at what type(s) of neuroeffector junctions? | Parasympathetic and Somatic |
| Norepinephrine is the primary NT at what type(s) of neuroeffector junctions? | Postganglionic Sympathetic neurons |
| What are Neurotransmitters (NTs)? | Chemicals that are used to relay, amplify, and modulate the electrical signals between a neuron and another effector cell |
| Acetylcholine is the NT for: (4 things) | 1) postganglionic parasympathetic neurons 2) all autonomic ganglia 3) the adrenal medulla 4) the somatic system |
| What is the definition of receptor? | A protein structure located on the cell membrane that binds to a specific molecule (a ligand), and initiates the cellular response to that ligand. |
| What are the 2 classifications of the cholinergic receptors? | Muscarinic (M) and (N) |
| Muscarinic receptors are ___ receptors and have this many types. | G-protein coupled receptors; 5 types--> M1-M5 |
| Nicotinic receptors are ____ ion channel receptors | Nonselective |
| Name the 2 types of alpha-adrenergic receptors, and how is each type further divided? | alpha1: a1A, a1B, a1D alpha2: a2A, a2B, a2C |
| What are the 4 types of beta-adrenergic receptors? | Beta1, Beta2, Beta3, Beta4; the existence of B4 is not confirmed, it is considered to be an isoform of B1. |
| How does the SNS tend to function? | It tends to discharge as a unit, affecting the entire system or body (diffuse) |
| How does the PNS tend to function? | It can discretely activate specific target tissues (discrete); it can activate one organ, but not affect others at the same time. |
| What are the major effects of activating the SNS? (5 things) | a) increased heart rate b) blood vessel constriction; increased arterial pressure c) Inhibition of GI tract d) Dilation of pupils e) Increased glycogensis & release of glucose in blood |
| What are the major effects of activating the PNS? (5 things) | a) pupil constriction b) Bronchoconstriction c) Simulation of GI tract and bladder d) Slow heart rate e) Promotes digestion, defecation, and micturition |
| What type of receptor is in the heart? | Beta1 |
| What type of receptors are in the skeletal muscles? | Alpha1 and Beta2 |
| What type of receptor is in the skin mucosa? | Alpha1 |
| What type of receptor is in the bronchial muscles? | Beta2 |
| What type of receptors are in the Detrusor muscle of the bladder? | Beta2 and Beta3 |
| What type of receptor is in the Trigone and Sphincter of the Bladder? | Alpha1 |
| What type of receptor is in the Iris? | Alpha1 |
| What type of receptor is in the ciliary muscle of the eye? | Beta2 |
| What types of receptors are in the uterus? | Alpha1 and Beta2 |
| What type of receptor is in the Kidney? | Beta1 |
| What type of receptor is in adrenergic neurons? | Alpha2 |
| The sympathetic nervous system effect on the heart is: | increase in contractility |
| Tetrodotoxin (TTX) is: | Na-channel inhibitor |
| Which are the 2 most important ion channels responsible for the neuronal action potential? | Na-channel and K-channel |
| Tetraethylammonium (TEA) is: | a K-channel inhibitor |
| The action of which enzyme is considered the rate-limiting step in the biosynethesis of endogenous catecholamines? | tyrosine hydroxylase |
| In the presence of MAO inhibitors, you would expect to see a decrease in: | urinary VMA |
| Norepinephrine released at the neuroeffector junction is inactivated primarily by: | the reuptake in the nerve ending |
| Drug A is an alpha agonist; you would therefore expect it to cause contraction of: | blood vessels to skeletal muscles, blood vessels to skin, and radial muscle of iris |
| Alpha1 receptors | Blood vessels to skeletal muscles & Skin, the trigone/sphincter of bladder, the radial muscle and iris of eye, and the uterus |
| Alpha2 receptors | Only the adrenergic receptors |
| Beta1 receptors | Heart and Kidney |
| Beta2 receptors | Blood vessels to skeletal muscle, bronchial muscle, detrusor muscle of bladder, ciliary muscle of eye, and the uterus |
| Drug B is a beta agonist; you would therefore expect it to cause constriction of: | atria and ventricles of heart |
| Acetylcholine released at neuroeffector junctions is inactivated primarily by: | degradation by acetylcholinesterase |
| Which of the following is NOT an effect of acetylcholine? miosis, increased heart rate, constricted bronchi, and increased peristalsis | increased heart rate |
| Use of acetylcholine in clinical therapeutics is: | minimal due to its chemical instability and lack of selectivity |
| Characteristics of atropine include: | produces cycloplegia |
| Atropine blocks the effects of acetylcholine by: | competing at receptor sites |
| Which of the following agents enhances cholinergic activity by forming an irreversible bond with acetylcholinesterase? | diisopropylfluorophosphate |
| The agent most useful for protection against the muscarinic manifestations of anticholinesterase poisoning is: | atropine |
| Which of the following agents act by promoting reactivation of phosphorylated acetylcholinesterase? | Pralidoxime |
| Which of the following agents block neuromuscular transmission by depolarizing the muscle end plate? | succinylcholine |
| Neostigmine is an effective antidote for? | d-Tubocurarine |
| Hypotension caused by the release of histamine and ganglionic blockade is most often associated with the use of? | d-Tubocurarine |
| Which agent is most like acetylcholine in molecular structure? | succinylcholine |
| Which one of the following drugs is classified as a cardioselective beta antagonist? | metoprolol |
| The cardiovascular responses to tyramine following pretreatment with reserpine are: | decreased |
| Phenylephrine is similar to epinephrine in its: | vasoconstriction |
| The drug of choice in treating severe anaphylactic shock is: | epinephrine |
| A drug used in treatment of cardiogenic shock b/c of its cardiac stimulant and renal vasodilator properties is: | dopamine |
| Which of the following therapeutic uses of epinephrine is related to beta receptor stimulation? | treatment of severe bronchial asthma attack |
| Which one of the following is most effective in treating bronchial asthma when administered by oral route? | albuterol |
| In general, local anesthetic agents lacking a hydrophilic group are: | used only topically |
| The effect of local anesthetics on nerve conduction is to prevent the generation of an action potential by: | blocking the transient increase in membrane permeability to Na |
| At which of the following pH values would the greatest concentration of lidocaine be required to produce nerve block? | 7.8 |
| Lidocaine is metabolized primarily by: | Liver |
| The duration and depth of local anesthetic action would be increased in the presence of: | epinephrine |
| What are the 2 basic classes of cell membrane transporters? | Carriers and Ion Channels |
| What is a carrier? | They bind to specific cargo molecules and transfer them across the membrane. |
| What can carrier-mediated transport be further divided into? | Passive transport and Active transport |
| Describe passive transport | 1) does not require energy 2) moves ions down their electrochemical gradient |
| Describe Active transport | 1) uses energy (ATP hydrolysis) 2) moves ions against their gradient 3) most important active transport based carrier are ion pumps (aka ion ATPases) |
| What are ion channels? | They form pores in the membrane and facilitate the flow of ions down their gradient. Ions include Na, K, Ca, and Cl. |
| How are ion channels different from carriers? | 1) carriers have limited flux capacity; ion channels can permit 1-100 million ions per second across membrane |
| All cells maintain a ___ resting membrane potential in the range of __ to ___. | Negative; -90mV to -30mV |
| Definition of membrane potential | The voltage difference across the membrane. |
| Define action potential | The rapid and transient change in the resting membrane potential |
| What are the two most essential ion channel properties? | Ion selectivity and Gating |
| What is ion selectivity? | The property of a channel to discriminate among different ions, allowing some to pass through the pore, while hindering others |
| What is gating? | The process by which the ion channel is physically opened or closed to permit the movement of ions |
| What are the two types of ion channels? | Voltage-gated and Ligand-gated |
| What are the two factors of electrochemical gradient that form the ionic current? | 1) the conc of ions in the intracellular and extracellular space 2) the potential difference across the cell membrane |
| Na is in high concentration ____ the cell membrane, whereas K is in high concentration ___ the cell. | Outside; inside |
| What two ion channels are inward currents? | Na and Ca |
| What ion channel is an outward current? | K |
| What is the equilibrium potential? | Also known as the Reversal Potential; The cell membrane's potential at which there is net flow of ions through the membrane |
| Why does the cell maintain a negative resting potential? | Because, overall, there is more K channels (outward) open than Na or Ca channels (inward). |
| What is a ligand? | Any molecule that interacts with an ion channel and regulates channel opening and closing by producing a conformational change. |
| What happens in the Action Potential (AP) depolarization phase? | Opening of the Na-channel (think of this as inward current, which will increase the number) |
| What happens in the AP repolarization phase? | Opening of the K-channel (think of this as outward current, decreasing the voltage) |
| What is tetrodotoxin (TTX)? | a) a paralytic toxin extracted from pufferfish, etc b) TTX is highly specific and potent Nav channel inhibitor |
| What is saxitoxin (STX)? | a) a toxin isolated from dinoflagellate plankton, which also inbits the Nav channel, in the same way as TTX |
| What is tetraethylammonium (TEA)? | TEA was shown to block the voltage-dependent K current, which inhbits the Kv channel |
| What are the two mechanisms of ion channel inhibition? | Pore plugging and Allosteric Binding |
| In general, how does pore plugging work? | Pore plugging inhibitors enter the channel pore, bind somewhere in the pore region, and physically obstruct the ion transport in the pore. |
| Is pore plugging a reversible or irreversible process? | Reversible; washing out the inhibitor restores normal funciton to the channel |
| How does TTX and STX work? | TTX and STX work through pore plugging. They bind and plug the Nav channel from the extracellular side of the channel. |
| Where does most pore plugging take place (which side of the membrane)? | Intracellularly; this means the inhibitor must first pass through the ion channel, and then plug the pore. |
| How does TEA work? | TEA works as a pore-plugger to inhibit the Kv channel. It moves through the ion channel and binds intracellularly. It also has a second binding site that binds extracellularly providing additional inhibition of the K channel |
| What is "use-dependent" inhibition? | Under repeated depolarizations of the membrane, the amount of inhibition will be cumulative. This is seen in local anesthetics. |
| How does allosteric binding inhibit the ion channel? | This mechanism requires a specific binding site, which is usually found extracellularly. The allosteric inhibitor will bind to the channel and cause a conformational change, that prevents ions from passing through the channel |
| What are some examples of allosteric binding inhibitors? | 1) Dihydropyridines (DHPs) 2) L-type Ca channel inhibitors 3) most natural toxins |
| Where is a common binding site for voltage-gated channels? | the Voltage-Sensor domain (S4); it is partially exposed to the extracellular space |
| What are common characteristics of animal toxins from venom? | usually small peptides, from 1-70 amino acids long. Some advantages of these toxins are that they have high ion channel specificity, high activity and relative insensitivity to proteases. They also usually use allosteric binding. |
| Name 3 examples of Openers/Activators of Voltage-gated Na-Channels | Veratridine, Aconitine, and Batrachotoxin |
| Highly poisonous plant alkaloids, whic open sodium channels | Veratridine and Aconitine |
| A highly lethal sodium channel opener, found in poisonous dart frogs | Batrachotoxin |
| Why is Bactrachotoxin extremely lethal? | It opens all members of the Na-channel family, so can cause extensive nerve and cardiac muscle effects. Can cause neurotoxicity, arrhythmias, ventricular fibrilation, and cardiac arrest. Very small amounts of this toxin can be lethal. |
| What is the mechanism of action for local anesthetics? | They block voltage-dependent Na-channels by directly binding to a high affinity site on the inside of the cell. The Na-channel must be open for it to bind--> Use-Dependent Block |
| Based on electrochemical gradients, say which way the 4 common ions move. | Na and Ca move in to cells K moves out Cl can move in and out of the cell |
| Activation of Na and Ca-channels ___ excitability, and activation of K-channels ___ excitability. | Increase; decrease |
| Nicotinic receptors is a ___ cation channel; it conducts ___ and ____. | nonselective; Na and Ca |
| What does the initial step of junctional transmission involve? | The opening of voltage-gated Ca channels located in the presynaptic membrane. |
| What does the entry of Ca into the neuron do? | It initiates the release of NTs |
| What is a neuromuscular junction? | A synapse between a motor neuron and a muscle cell |
| What are the 2 primary NTs found in the ANS and Somatic NS? | Acetylcholine and Norepinephrine |
| Where is Norepinephrine the primary NT? | At most Sympathetic Postganglionic neuroeffector junctions |
| Description of Epinephrine | 1) role as a hormone 2) Is the principal catecholamine released from the adrenal medulla |
| What are nonadrenergic-noncholinergic neurons (NANC)? | 1) Primarily found in the Enteric NS, genitourinary tract, and certain blood vessels. 2) NTs released include neuropeptide Y, Vasoactive Intestinal Polypeptides (VIP), enkephalin, substance P, serotonin, ATP, and Nitric oxide (NO) |
| Similarities between Adrenergic and Cholinergic Neurotransmission | 1) NT is synthesized in nerve terminals 2) NT is stored in vesicles 3) NT is released into synapse in response to nerve stimulation. 4) NT is terminated by metabolism or reuptake |
| What does Hemicholinium do? | It blocks choline transport into neuron and thereby inhibits the syntheis of acetylcholine. (Cholinergic) Has no medical use |
| What does Vesamicol block? | Blocks Acetylcholine storage in vesicles. Has no medical use |
| What does the Botulinum toxin do? | Blocks the release of Acetylcholine |
| What does reserpine do? | Blocks the storage of dopamine and norepinephrine in the vesicles |
| What does Bretylium do? | Blocks the release of Norepinephrine |
| What does Cocaine do? | Can block the process of norepinephrine reuptake |
| What do amphetamines do? | Indirectly increases the release of Norepinephrine into the synapse |
| How is Acetylcholine synthesized? | Synthesized from Choline and acetate. |
| What ion mediates the release of acetylcholine?What is this process called? | Calcium; exocytosis |
| What is alpha-latrotoxin, and what does it do? | black widow spider venom; stimulates release of acetylcholine, which produces excess activation of cholinergic receptors in abdominal muscles, etc. |
| What are 2 direct-acting cholinergic receptor agonists? | Bethanechol and Pilocarpine |
| What do cholinesterase inhibitors do? | Prevent the breakdown of Acetylcholine, increasing the concentration of acetylcholine in the synapse (increases activation of cholinergic receptors) |
| What is the precursor for endogenous catecholamines, dopamine, norepinephrine, and epinephrine | Tyrosine |
| What is the rate-limiting step of the synthesis of catecholamines | Tyrosine reacts with tyrosine hydroxylase to form dopa |
| Steps of the synthesis of catecholamines (Dopamine, NE, and epinephrine) | 1) Tyrosine is taken into symp neurons. 2) Tyr reacts w Tyrosine Hydroxylase to Dopa 3) Dopa is decarboxylated to dopamine 4) Dopa reacts w/ dopamine beta hydroxylase to form NE 5) NE reacts w/ phenylethanolamine N-methyl transferase to form epinephri |
| What is the major urinary metabolite of epinephrine and norepinephrine? | VMA (Vanillyl Mandelic Acid) |
| What is the major urinary metabolite of dopamine? | HVA (homovanillic acid) |
| How is NE stored? | NE is stored in association with ATP in synaptic vesicles; Dopamine beta hydroxylase is also present |
| How is NE released? | Released through exocytosis; ATP and dopamine beta hydroxylase also released |
| How is NE inactivated? | MAO (in mitochondria) and COMT (in cytoplasm of effector cells, and in liver/kidney) have a MINOR role in inactivation. The MAJOR role is the reuptake of NE by active transport. |
| Alpha receptors are generally ___ (exception is GI smooth muscle) whereas beta receptors are generally ____ (exception is the heart) | Alpha=excitatory Beta=inhibitory |
| What is purinergic neurotransmission? | Release of extracellular purines and pyrimidines |
| Where is nitric oxide stored? | Trick question. It is NOT stored, but is synthesized as needed by NO synthase (NOS) from its precursor L-arginine. |
| How does NO get to the synapse? | It diffuses from the terminal, rather than through exocytosis. It does NOT react with receptors. |
| How does inactivation of NO occur? | NO is inactivated by it diffusing away from the synapse. |
| What does the activation of muscarinic and alpha-adrengeric receptors do? | Produce smooth muscle contraction |
| What does activation of beta-adrenergic receptors do? | Produce smooth muscle relaxation and heart stimulation |
| What are indirect-acting drugs? | Drugs that effect neurotransmitter synthesis, storage, release or metabolism. |
| Name 2 cholinergic agents | Pilocarpine, bethanechol |
| Name 2 antimuscarinic agents | atropine, scopolamine |
| Name 3 anticholinesterase agents | Neostigmine, physostigmine, diisopropyl fluorophosphate (DFP) |
| Name 1 cholinesterase reactivator | pralidoxime |
| What blocks muscarinic effects? | atropine--most common antagonist |
| What blocks nicotinic effects? | Hexamethonium and d-tubocurare. |
| Muscarinic receptors have a __ affinity for muscarine, a __ affinity for nicotine, and a ___ affinity for acetylcholine. | high, low, same |
| Nicotinic receptors have a __ affinity for muscarine, a __ affinity for nicotine, and a __ affinity for acetylcholine | low, high, same |
| Properties of M1 receptors | 1) found in CNS, brain, autonomic ganglia 2) mechanism of transduction: increased IP3 and DAG 3) Effects: modulation of neurotransmission 4) "neural" |
| Properties of M2/M4 receptors | 1) "cardiac" 2) found in cardiac tissue 3) Mechanism of transdution: increased K efflux or decreased cAMP 4) slows hear rate and conduction |
| Properties of M3/M5 receptors | 1) "glandular" 2) smooth muscles and glands 3) Increased IP3 and DAG 4) Contraction of smooth muscles and stimulations of gland secretions |
| Properties of Nm receptors | 1) found in somatic neuromuscular junctions 2) Increased sodium influx 3) Contraction of muscles |
| Properties of Nn receptors | 1) Autonomic ganglia 2) Increased sodium influx 3) Excitation of postganglionic neurons |
| Three types of Direct-acting cholinergic receptor agonists | Choline Esters, Plant alkaloids, other drugs (cevimeline) |
| 3 Choline Esters | Acetylcholine, bethanachol, carbachol |
| 3 Plant alkaloids | Nicotine, muscarine, pilocarpine (pilocarpine is the only one that is used therapeutically) |
| Reversible Cholinesterase inhibitors | Donepezil, edrophonium, neostigmine, physostigmine, pyridostigmine |
| Irreversible Cholinesterase inhibitors | Echothiophate, Isoflurophate, Malathion |
| Drugs that augment acetylcholine | silendafil, tadalafil, vardenafil (these are all ED drugs) |
| Choline ester properties | 1) designed to be more selective and prolonged action 2) none penetrate the BBB 3) Carbachol and bethanechol are resistant to cholinesterase |
| Therapeutic uses of direct-acting cholinergic agonists | 1) uses are limited 2) Bethanachol: gastic atony and urinary retention 3) Opthalmology: Ach, carbachol, pilocarpine, cevimeline 4) Xerostomia: pilocarpine, cevimeline |
| Contraindications for direct-acting cholinergic agonists | 1) Bronchial asthma, coronary insufficiency, peptic ulcers, hyperthyroidism |
| What are cholinergic agonists side effects? | diarrhea, sweating (diaphoresis), miosis, nausea, urinary urgency |
| Properties of Edrophonium | 1) Combines electrostatically at the anionic site and by H-bonding to imidazole nitrogen 2) inhibition is reversible 3) very brief duration of action |
| Properties of Neostigmine | 1)carbamylated enzyme reacts w/ water at less than a millionth the rate of acetylated enzyme 2) combines with the enzyme in the same manner as acetylcholine |
| Irreversible Anticholinesterase agent (Diisopropyl Fluorophosphate (DHP)) | 1) Reacts only at the esteratic site 2) Phosphorylated enzyme is extremely stable 3) are organophosphates--> highly toxic |
| Structure of Reversible Anticholinesterase agents (Physostigmine, Pyridostigmine, Neostigmine) | 1) lacks a carbamyl group--> decreases duration of action 2) Presence of quaternary amine imparts agonist activity |
| Main therapeutic effects of Reversible anticholinesterase agents | 1) Eye: produce miosis 2) GI: stimulates secretions 3) Urinary tract: contract detrusor, relax sphincter 4) Skeletal muscle: stimulate muscle |
| Structure/Properties of Irreversible anticholinesterase agents | 1) contains some of the most toxic synthetic agents known 2) used as insecticides (malathion, parathion) 3) generally highly lipid soluble, rapidly absorbed by all routes including skin 4) long duration of action |
| What is used to treat anticholinesterase poisioning? | 1)atropine; large doses at short intervals; has no effect at skel neuromuscular junction 2) Pralidoxime (PAM): promotes reactivation of AchE. Must admin soon after poison to work. Is a cholinesterase reactivator. effect is at skel neuromuscular junc. |
| Therapeutic Uses of Anticholinesterase agents | 1) Glaucoma 2) atony of bladder 3) Myasthenia gravis 4) atropine poisoining 5) reversal of paralysis produced by d-tubocurare |
| What does Sildenafil (and other ED drugs) do | inhibit the degradation of cGMP by 5-PDE, which causes vasodilation action of AcH in the penis |
| The 5-PDE inhibitors should not be used by men who take nitroglycerin (or other organic nitrates) b/c... | Nitrates also increase cGMP formation |
| 3 Examples of Muscarinic Receptor Antagonists | Atropine, Hyosyamine, Scopolamine (all are examples of Belladonna alkaloids) |
| Examples of Semisynthetic and Synthetic Muscarinic Receptor Antagonists (7) | 1) Dicyclomine 2) Glycopyrrolate 3) Ipratropium 4) Oxybutynin 5) Sulifenacin 6) Tolterodine 7) Tropicamide |
| 1 Nicotinic Receptor Antagonists and also a ganglionic blocking agent | Trimethaphan |
| 2 Classes of Neuromuscular BLocking agents | Non-depolarizing and Depolarizing |
| 3 Examples of Non-depolarizing neuromuscular blocking agents | Mivacurium, pancuronium, tubocurarine |
| 1 Example of depolarizing neuromuscular blocking agents | succinylcholine |
| What is the major action of antimuscarinic drugs? | To competitively antagonize the muscarinic action of acetylcholine at postganglionic parasympathetic neuroeffector junctions |
| Different parasympathetic neuroeffector junctions are not equally susceptible to antimuscarinics. The order of susceptibility (in decreasing order) is: | 1) Salivary, bronchial and sweat glands--> decreased 2) Eye: mydriasis, cycloplegia, tachycardia 3) Bladder: inhibition of bladder control, decreased tone of gut 4) GI (M3 receptor): decreased gastric secretions |
| What are common side effects of antimuscarinic drugs? | dry mouth, blurred vision, tachycardia, difficult micturition, constipation |
| Therapeutic Uses of Antimuscarinic Drugs: | 1) CNS: parkinsonism, motion sick (scopolamine) 2) General anesthesia: decrease secretions and produce sedation; atropine and neostigmine to reverse curarization 3) Opthalmology 4) GI: PUD, relieve increased tone and motility 5)Bladder: failure to st |
| Overactive bladder is associated with increased or decreased smooth muscle contractions? | increased |
| What drugs are used to treat overactive bladder? | **Antimuscarinic Drugs!!** Atropine, Hyoscamine, Propantheline, Emepronium, Trospium, Darifenacin, Oxybutynin, Tolterodine |
| What side effects are associated with overactive bladder drugs? | Dry mouth, tachycardia, constipation, change in mental status in long term use....These drugs are largely ineffective and have major undesirable side effects! |
| How does Trimethaphan work? | It is a ganglionic nicotinic receptor blocker. It selectively blocks Nn (neuronal) receptors at sympathetic and parasympathetic ganglia. |
| What does blockade of sympathetic ganglias cause? | Hypotension |
| What does blockade of parasympathetic ganglias cause? | Dry mouth, blurred vision, urinary retention |
| What is the rise of threshold called? | Accommodation |
| What are some common structures in neuromuscular blocking agents? | 1) All have at least 2 quaternary nitrogens 2) Competitive blockers are large and bulky; depolarizing agents are slender, flexible, and long (like Ach) |
| Competitive Blocking Agents have: (4 things) | 1) no direct effect on resting membrane potential 2) Compete with Ach for postjunctional receptors 3) Large margin of safety for neuromusc transmission ( 75% need to be blocked to have effect) 4) Readily antagonized/reversed by anticholinesterase agent |
| Competitive=Non-depolarizing agents | this is just a note!! |
| Major therapeutic uses of neuromuscular blocking agents | 1) General Anesthesia: muscle relaxation for surgery (competitive for long surgery) 2) Electroshock therapy: Succinylcholine to prevent fractures |
| Succinylcholine is the only depolarizing agent we are studying! Can it be reversed by cholinesterase inhibitors? | No it can't be reversed, but non-depolarizing agents can be reversed! |
| What are sympathiomimetic drugs? | They are adrenergic agonists; drugs that mimic the effects of norepinephrine and the hormone, epinephrine |
| What are sympatholytic drugs? | adrenergic antagonists; drugs that decrease sympathetic neuronal activity. They oppose the physiological effects caused by stimulation of the sympathetic nervous system |
| Examples of Sympathiomimetic Drugs (7) | Isoproterenol, Epinephrine, Norepinephrine, Phenylephrine, Albuterol, Dobutamine, Dopamine |
| Receptors of the adrenergic agonist, Epinephrine | alpha 1, alpha 2, beta 1, beta 2 |
| Receptors of Norepinephrine | alpha1, alpha2, beta1 |
| Receptor of Phenylephrine | alpha1 |
| Receptors of isoproterenol | beta1, beta2 |
| Receptor of Albuterol | beta2 |
| What kind of receptors are adrenergic, and how many transmembranes does it have? | G-protein coupled; 7 |
| Facts about Beta1 receptors | 1) found primarily in heart 2) Stimulation leads to activation of Gs, which culminates in the activation of adenylate cyclase and production of cAMP 3) cAMP activates PK-A, which enhances Ca release, to enhance myocardial contraction 4) Dobutamine=agon |
| Facts about Beta2 receptors | 1) found in peripheral tissue 2) Stimulation produces cAMP and activation of protein kinase A like described for B1. 3) cAMP-dependent PK-A decreases availability of Ca, resultin in smooth muscle relaxation 4) Selective agonists: terbutaline, albuterol |
| Facts about Alpha1 receptors | 1)Located postsynap on effector tissues 2) mediates response to NorE 3) stimulation leads to activation of phospholipase-C which hydrolyzes PIP2 to IP3 and DAG 4) IP3 interacts w ER to release Ca into cytoplasm. Ca acts w calmodulin for response. |
| Facts about alpha2 receptors | 1) located pre- and post-synap at periph & central sites 2) activation of presynap A2 receptors on peripheral sympath nerve terminals is a feedback inhibition of NorE 3)Stimulate A2 causes cAMP production by activating Gi protein 4) opens K channels |
| Routes of Admin for Epinephrine | Can not be dosed Orally! SubQ, IM, IV, inhalation, local instillation okay |
| Routes of Admin for Norepinephrine | IV only |
| Therapeutic Use of Epinephrine | 1) prolongs duration and decreases toxicity when used w local anesthetics 2) wide angle glaucoma 3) anaphylactic shock 4) cardiac arrest 5) Bronchial asthma 6) Cardiac stimulant |
| Therapeutic Use of Norepinephrine | 1) Shock |
| Therapeutic Use of Isoproterenol | 1) Bronchial asthma and COPD 2) Heart block 3) Acute cardiac depression |
| Therapeutic Use of Albuterol | 1) Bronchial asthma 2) Uterine relaxation |
| Therapeutic Use of Dobutamine | 1) Cardiovascular effects |
| Therapeutic use of Phenylephrine | 1) Decongestant |
| What are direct and indirect acting drugs? | These drugs derive part of their pharmacological actions by displacing Norepinephrine from nerve endings (Dopamine, Ephedrine, Pseudoephedrine, Mephentermine, Metaraminol, Amphetamines) |
| What does activating alpha1 adrenergic receptors do? | 1) smooth muscle contraction 2) vasoconstriction 3) dilation of pupils 4) contraction of bladder sphincter |
| What does activating alpha2 receptors do? | 1) inhibits release of Norepinephrine 2) decreases tears 3) decreases secretion of insulin |
| What does activating beta1 do? | 1) cardiac stimulation 2) increases secretion of renin |
| What does activating beta2 do? | 1) mediates smooth muscle relaxation |
| Catecholamines | Norepinephrine, Epinephrine, Isoproterenol, dopamine, and dobutamine; They are rapidly metabolized, dosed IV, and used to treat cardiac disorders and shock |
| Noncatecholamines | Phenylephrine and Albuterol; resistant to degradation by COMT; can be given orally, have a longer duration of action than catecholamines, and have a wide range of uses |
| 3 Examples of Alpha Adrenergic Antagonists | Prazosin, Phentolamine, Phenoxybenzamine |
| 3 Examples of Beta Adrenergic Antagonists | Metoprolol, Atenolol, Propranolol |
| 2 Examples of Adrenergic Neuronal Blocking Drugs | Reserpine, Guanethidine |
| Mechanism of action for Phenoxybenzamine | alpha1, alpha2; Binds covalently to receptor forming a non-competitive, non-reversible block |
| Pharmacological action of Phenoxybenzamine | 1) reduces blood pressure 2) increases heart rate and contractile force 3) increases release and blocks the reuptake of NorE, which prolongs cardiac stimulation |
| MofA of Phentolamine | alpha1, alpha2; competitive blockade of alpha receptors; short duration |
| MofA of Prazosin | alpha1; competitive blockade of alpha receptors |
| Name 2 nonselective beta antagonists | Propanolol, timolol |
| Therapeutic Use of Propanolol | 1) arrhythmias 2) angina pectoris 3) hypertension 4) decreases moralility after heart attack 5) stagefright |
| Therapeutic Use of Timolol | Glaucoma |
| Cardioselective B1 Antagonists | Metoprolol, atenolol, esmolol, acebutolol |
| Therapeutic Use of Metoprolol | antihypertensive, antiarrhythmic, angina pectoris |
| What is the proposed advantage of metoprolol over propanolol? | It is cardioselective, so it won't cause asthma attack in patient |
| MofA of Reserpine (Adrenergic Neuron Blocker) | 1) Diffuses across terminal membrane and binds irreversibly to amine pump, blocking the uptake and storage of biogenic amines 2) Causes depletion of NT stores 3) Depletion in CNS caus sedation and depression; also is very lipid soluble |
| Therapeutic Use of Reserpine | Was once used for hypertension, but is being replaced by better drugs |
| MofA of Guanethidine (Adren. Neuron blocker) | 1) is a substrate for amine pump in neuron terminal, so transported into nerve terminal 2) Is also taken up into storage granules, with an initial increase in NE release--> increase in bp 3) after initial NE release, blocks NE; not well understood |
| Definition of Analgesic | Reduced sensibility to pain w/o loss of consciousness and with sense of touch |
| Definitino of Anesthesia | Reduced or abolished sensation |
| Definition of Local Anesthetics | Drugs that produce transient and reversible loss of sensation or feeling in a circumscribed area of the body w/o loss of consciousness |
| Prototype Drugs of Local Anesthetics | Esters: Procaine Amides: Lidocaine Natural Alkaloid: Cocaine |
| The 3 components of the fundamental struction of Local Anesthetics | 1)Aromatic part: responsible for lipophilic 2) Amine part: usually a 2 or 3 amine, assoc w/ water solubility of drug; not necessary to be LA, but LAs w/o amine are insoluble in water; must use topical 3) Intermediate Link: ester or amide; Metab/allergy |
| What other 2 classes of drugs are structurally similar to Local anesthetics? | Beta blockers and antihistamines |
| Examples of a LA that has esters | Procaine, Cocaine, Benzocaine |
| Examples of LA that has an amide | Lidocaine |
| MofA of LA | Interfere with the generation and conduction of nerve impulses |
| LA are weak ___ and at physiological pH they exist as ___. | bases; nonionized base and cationic form. |
| What form must the Local Anesthetics be in to penetrate the nerve sheath? | nonionized form |
| Concentration of local anesthetic increases as pH ___. | decreases |
| Why is pH important clinically in regards to LA? | Inflammation decreases pH, therefore decreasing effectiveness of local anesthetics. |
| What effect does fiber size have on sensitivity to LA? | small fibers will be anesthetized first, then larger ones |
| What effect does myelin have on sensitivity to LA? | unmyelinated fibers will be anesthetized first, then myelinated |
| What is the order of the loss of senses (most sensitive to least sensitive)? | Pain >temperature >touch >Pressure >Skeletal muscle movement |
| What are the CNS Side Effects when LA are absorbed systemically? | Primarily involves the CNS, and 2ndary the CV system. Mild CNS: talkative, sensory distrubances, drowsy, lightheaded, restless, tremor, excitation. Progressive symptoms: seizure, lethargy, no movement in extemeties, drop in bp |
| What are the CV side effects when LA are absorbed systemically? | )Vasodilation (except cocaine produces vasoconstriction), which is bad bc dilation speeds up the removal of drug. 2) Heart: antiarrhythmic effects; can be used to treat cardiac arrhythmias |
| What are common allergic reactions to LA? | 1) more common with ester LA; no cross sensitivity to amide type 2)contact dermititis, bronchospasm, hives 3) rare cases: angiodema w/ swelling that reduces airways 4) allergy to amides-type is rare 5)if pt allergic to all LA, diphenhydramine can be u |
| How does the LA, prilocaine, affect blood? | It can cause methemoglobinemia, bc its metabolite, o-toluidine, can convert hemoglobin to met-Hb. If significant, pt appears cyanotic and blood chocolate-colored. Can be treated w/ methylene blue (reducing agent) |
| Why do we combine LA with vasoconstrictors? | 1) increases duration of action b/c increases time drug spends with tissues 2)Reduces rate of systemic absorption 3) Increases depth of penetration into tissue 4) Most common vasoconstrictor used: Epinephrine |
| Factors that influence absorption | 1) site of injection 2) vasodilator properties of drugs 3) presence of vasoconstrictor |
| How is ester-type LA metabolized? | hydrolyzed in plasma by pseudocholinesterase |
| How is amide-type LA metabolized? | Metabolized by liver |
| What is the major excretion route of LA? | Kidney |
| What are clincial uses of LA? | 1) topical or surface anesthesia 2)Infiltration anesthesia 3)Regional Nerve Block anesthesia 4) Spinal Anesthesia 5) Epidural |
| LA that are Ester Parental Administration | Chloroprocaine, tetracaine, procaine |
| LA that are Amide Parental Admin | bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine, ropivacaine |
| LA that are topical Esters | Benzocaine, Butacaine, Butamben |
| LA that are topical Amides | Chlorobutanol, dyclonine, hexylcaine, pramoxine |
| Majority of LA CV toxicity is caused by potent, highly lipid soluble, highly protein bound LA, such as: | bupivacaine and etidocaine |
Created by:
brookshiree2