THE FIRST MIDTERM Flashcards
What is another name for cell body?
Perikaryon
What is the definition of a direct action of neurotransmitters?
The neurotransmitter binds to and opens ion channels, which promotes rapid responses by altering the membrane potential.
What is the definition of an indirect action of neurotransmitters?
The neurotransmitter acts through intracellular second messengers, usually G-protein pathways, which ends up having broader and longer-lasting effects.
How does a voltage-gated channel work?
A channel that opens and closes in response to voltage changes across the membrane, or changes in the membrane potential in the cell. An example is a voltage -gated sodium channel, lidocaine.
How does a ligand-gated ion channel work? And what is another name for these types of channels?
A hormone, drug, or transmitter binds to the protein and the channel opens up. Action is immediate and brief, some are excitatory and open channels for small cations, some are inhibitory and allow Cl- influx or K+ efflux to cause hyperpolarization. Examples include glutamate (AMPA) and nicotinic ACh receptors and GABA-A. They are also called Ionotropic.
How do Metabotropic receptors work?
These are seven-transmembrane G protein-coupled receptors. The binding of neurotransmitter to this type of receptor does not result in the direct gating of a channel. Rather, binding to the receptor engages a G protein, which results in the production of second messengers that modulate voltage-gated channels and change the excitability of the neuron, thus they are not directly linked to ion channels. Metabotropic receptors initiate biochemical processes that mediate more long-term effects (tens of seconds to minutes) and modify the responsiveness of the neuron.
What are the two types of Metabotropic receptors?
Membrane-delimited and Diffusible second messengers
With which type of Metabotropic receptor does the G-protein subunit interact direct with the voltage-gated ion channel?
Membrane-delimited
Which two types of voltage-gated ion channels are the targets of Membrane-delimited signaling?
Calcium channels and potassium channels
With membrane-delimited receptors, what happens when G-proteins interact with calcium channels?
They inhibit channel function. This mechanism accounts for the presynaptic inhibition that occurs when presynaptic metabotropic receptors are activated.
With membrane-delimited receptors, what happens when G-proteins interact with potassium channels?
They activate channel function and with potassium, they will be postsynaptic, resulting in a slow postsynaptic inhibition.
How does a diffusible second messenger metabotropic receptor work?
A classic example of this type of action is provided by the β adrenoceptor, which generates cAMP via the activation of adenylyl cyclase. Whereas membrane-delimited actions occur within microdomains in the membrane, second messenger-mediated effects can occur over considerable distances.
What is the definition of an autoreceptor?
It is a receptor on an axon terminal through which the neuron’s own neurotransmitter can influence the function of the terminal, and this is almost always inhibitory. The D2 receptor is an example.
What is the definition of a heteroreceptor?
It is a receptor on an axon terminal through which neurotransmitters from other neuronal types can influence the function of the terminal, and they are almost always inhibitory.
What are the three main catecholamines?
Dopamine, Norepinephrine, and Epinephrine
What is name of the neurotransmitter that looks very similar to catecholamines, but isn’t?
Amphetamine. A lot of times the way drugs exert their effect is by mimicking the neurotransmitter, and if the structure is similar, it is easier.
What is the precursor amino acid for catecholamines?
Tyrosine
What are the four main monoamine neurotransmitters?
Dopamine, Epinephrine, Norepinephrine, and Serotonin. Histamine is also a monoamine. But remember, serotonin is not a catecholamine like the first three are.
What are the two main classes of fibers/receptors of the autonomic nervous system?
Cholinergic (Muscarinic and Nicotinic) and Adrenergic
What is the process of Dopamine entering at the adrenergic junction?
Tyrosine is transported into the noradrenergic ending or varicosity by a sodium-dependent carrier. Tyrosine is converted to DOPA (Dihydroxyphenylalanine) by tyrosine hydroxylase, and dopa is converted to dopamine by aromatic amino acid decarboxylase, and transported into the vesicle by the vesicular monoamine transporter (VMAT). Physiologic release of transmitter occurs when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium. Fusion of vesicles with the surface membrane results in expulsion and dopamine can enter the synaptic cleft and do one of the following three things: 1) Bind to a post-synaptic receptor (there are 5, D1-D5), 2) Bind to the D2 autoreceptor (which would shut down tyrosine hydroxylase, so dopamine cannot be made nor released, and 3) Re-enter the neuron through a dopamine transporter. Once it does so, dopamine can be metabolized by MAO, Monoamine Oxidase, which converts dopamine into DOPAC.
What is the process of NE entering the synaptic cleft of an adrenergic junction and when does it happen?
For this to happen, it all starts with Tyrosine again, which is converted to Dopamine and Dopamine’s same process takes place but once it enters the synaptic vesicle via VMAT, Dopamine is then converted to NE by Dopamine Beta Hydroxylase, DBH. NE can then enter the synaptic cleft and have the same three options as Dopamine does. However, instead of binding to D1-D5 post-synaptic receptors, NE binds to alpha and beta receptors. And there is no D2 pre-synaptic receptor, it is an alpha-2 receptor.
Where is Epinephrine usually found? And what converts NE to Epinephrine?
It is mainly found in adrenal medullary cells, although it is also found in some CNS neurons. It is converted from NE by PNMT, phenylethanolamine-N-methyltransferase.
What is another name for Serotonin?
5-HT, 5-hydroxytryptamine. It is associated with sleep, depression, and migraines.
What is the amino acid precursor for Serotonin?
Tryptophan
What is the process of Serotonin entering at the synaptic cleft?
Tryptophan enters the neuron, is then converted by Tryptophan Hydroxylase to 5-HTP, and 5-HTP is then converted by AAD to 5-HT (Serotonin). 5-HT then enters the synaptic vesicle via VMAT, and eventually makes its way to the synaptic cleft where it can do the usual 3 things, bind to post-synaptic receptor, bind to autoreceptor (5-HT 1A and 1B), or re-enter through a Serotonin Transporter. And because Serotonin is a monoamine, it can also be metabolized by MAO.
What is the process of choline at the cholinergic junction?
Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). In the cytoplasm, acetylcholine is synthesized from choline and acetyl-CoA (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicular acetycholine transporter (VAT). Release of ACh occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft. Acetylcholine’s action is terminated by metabolism by the enzyme acetylcholinesterase, which breaks it down into choline, which can then re-enter the presynaptic nerve terminal, but it doesn’t do so through a acetylcholine transporter, but through a choline transporter, and the lack of this transporter is what makes this process a little different. ACh can also bind to post-synaptic nicotinic or muscarinic receptors, or it can bind to an autoreceptor, which is usually a Muscarinic Receptor (It shuts down the synthesis of ACh and shuts down its release, like an auto receptor does).
What are the two main neurotransmitters that are amino acids?
GABA (inhibitory) and Glutamate (excitatory)
What is the process of glutamate at the glutamatergic junction?
Alpha-ketoglutarate is the precursor to glutamate. It enters and is converted by amino transferase to Glutamate. It then enters a storage vesicle through a vesicular glutamate transporter. When it enters the synaptic cleft, glutamate can do 1 of 4 things. 1)It can re-enter the neuron through a glutamate transporter, however MAO does not metabolize it here because glutamate is not a monoamine. 2) It can bind to a post-synaptic receptor like AMPA, or NMDA. 3) It can bind to an autoreceptor. 4) It can enter an astrocyte, be converted to glutamine by glutamine synthetase, and by converting to glutamine, it serves as a storage buffer to be taken back up and be converted back to glutamate.
What is the process of GABA at the gabaergic junction?
Glutamate is the precursor, it enters and is converted to GABA by glutamate decarboxylase. It then enters a storage vesicle through the vesicular GABA transporter. When GABA enters the synaptic cleft, it can do 1 of 4 things. 1)It can re-enter the neuron through a GABA transporter, however MAO does not metabolize it here because GABA is not a monoamine. 2) It can bind to a post-synaptic receptor like GABA-A or GABA-B, usually just one or the other. 3) It can bind to a GABA-B autoreceptor. 4) It can enter an astrocyte and can be degraded by GABA-transaminase.
What are the five “other” neurotransmitters mentioned in class?
- Histamine 2. Endorphins 3. Neuropeptides 4. Endocannabinoids 5. Nitric Oxide
How many main histamine receptors are there, and what does H3 do?
There are 3, H1-H3, and H3 functions as an inhibitory heteroreceptor. So activation of brain H3 receptors decreases the release of ACh, dopamine, NE, serotonin, and certain peptides.
What type of receptors do endorphins act on?
u opioid receptors
How do opioid receptors modulate the release of neurotransmitters?
If endorphins bind to opioid receptors, it decreases the release of GABA (because opioid receptors are found on GABA neurons), which in turn will increase release of dopamine, because the dopamine neuron relies on a GABA receptor with GABA occupied in it in order to slow down release of dopamine.
What are some of the neuropeptides that we need to know
Neurotensin, somatostatin, cholecystokinin, substance P, neuropeptide Y.
What does neurotensin do and where is it found?
It regulates dopaminergic systems, inhibitory feedback, and it is found in the G.I. tract and inhibits G.I. motility and causes vasodilation.
What is the main endocannabinoid neurotransmitter and to what receptor does it bind?
Anandamide, and it binds to CB1 cannabinoid receptors, and by doing so, causes dopamine release. Endocannabinoids are main ingredient in marijuana.
What is nitric oxide and what does it do?
It is a gaseous signaling molecule that relaxes vascular smooth muscle.
What are Kainate receptors?
They are a receptor subtype for Glutamate, permeable to Na+ and K+, and are expressed in brain and spinal cord.
What does glutamate decarboxylase do?
It is an enzyme that catalyzes the decarboxylation of Glutamate to GABA and CO2.
What is the definition of a ganglion?
A collection of cell bodies
What two nervous systems is the Peripheral Nervous System made up of?
Somatic and Autonomic Nervous Systems
Most organs are innervated by either the parasympathetic or the sympathetic nervous system, but not both. True or False?
False. Most are dually innervated, each having separate effects.
Where are the cell bodies of the parasympathetic nervous system?
Craniosacral regions
What is the pre-ganglionic neurotransmitter for both parasympathetic and sympathetic and what type of receptor is found where the pre meets the post-ganglionic?
Acetylcholine (ACh)…….Nicotinic (which is a type of cholinergic receptor)
What is the post-ganglionic neurotransmitter, receptor, and target site of the parasympathetic nervous system?
ACh, Muscarinic receptor, and cardiac and smooth muscle, gland cells, and nerve terminals.
What is the post-ganglionic neurotransmitter and receptor for the sympathetic pathway innervating sweat glands?
ACh, Muscarinic receptor
What is the post-ganglionic neurotransmitter and receptor for the sympathetic pathway innervating cardiac and smooth muscle, gland cells, and nerve terminals?
NE, and alpha and beta receptors
What is the post-ganglionic neurotransmitter and receptor for the sympathetic pathway innervating renal vascular smooth muscle?
Dopamine, D1 receptor
Where are the cell bodies of the sympathetic nervous system?
Thoracolumbar region
How does innervation of the adrenal medulla work, and is it parasympathetic or sympathetic?
It is sympathetic, and the pre-ganglionic goes all the way to the adrenal medulla, and at the junction is ACh with a nicotinic receptor, and the adrenal medulla then release NE and epinephrine into the bloodstream.
What type of neurotransmitter and receptor are found at the junction of somatic motor nerves?
ACh and nicotinic receptors. These innervate skeletal muscle. The movement is voluntary.
Are sympathetic pre-ganglionic axons short or long?
They are short, they extend to para- and pre-vertebral ganglia. The post-ganglionic extend to effector organ and are longer. These are all coming out of the thoracolumbar region.
Are parasympathetic pre-ganglionic axons short or long?
They are long, they extend to ganglia near effector organs, so the post-ganglionic are short. These are all coming out of the craniosacaral region.
If a drug inhibits the release of ACh, will it effect the parasympathetic or sympathetic pathway?
It will affect both.
What type of receptor does ACh released from pre-ganglionic neurons act on, and where are these receptors found?
It acts on nicotinic receptors found on post-ganglionic fibers.
On which type of receptor do motor neurons innervating skeletal muscle act?
Nicotinic receptors
What are the three different neurotransmitters that post-ganglionic sympathetic fibers release?
Dopamine, NE, and Epinephrine. Most use NE.
What are the main two types of adrenergic receptors that NE and epinephrine act on?
Alpha and Beta
What are the three types of receptors that dopamine activates?
D1, alpha, and beta
What neurotransmitter does post-ganglionic parasypathetic fibers release?
ACh
What type of receptor does ACh act on for post-ganglionic parasympathetic fibers?
Acts on muscarinic receptors in most effector tissues.
What percent of epilepsy patients are therapy-resistant?
25-40%
What is the definition of a seizure?
A finite clinical manifestation of abnormal & excessive excitation of a population of cortical neurons.
What is the definition of epilepsy?
A syndrome characterized by chronic, recurrent seizures unprovoked by systemic or neurologic insults.
How do you get a diagnosis of epilepsy from seizures?
You have to have three or more non-provoked seizure events to be considered Epilepsy.
What is the definition of epileptogenesis?
A sequence of events that converts a normal neuronal network into a hyperexcitable network.
What is the lifetime prevalence of seizures for a person?
9-10%
What is the prevalence of epilepsy in world population vs US?
1% and 1 in 26
In terms of the etiology of epilepsy, what is the biggest factor, and is it inherited or acquired?
Ion channels, and they are inherited.
What are the main nine precipitants (causes) of seizures
• Metabolic and/or Electrolyte Imbalance (People’s blood glucose too high or too low, too low sodium, calcium, magnesium, potassium too high) • Stimulant or other pro-convulsant intoxication • Sedative or ethanol withdrawal • Sleep deprivation • Reduction or inadequate ASD treatment • Hormonal variations • Stress • Fever or systemic infection (HSV can be linked) • Concussion and/or closed head injury
At what ages is epilepsy most prevalent?
Very young and very old
What are the main causative factors for epilepsy at a young age?
Genes, status epilepticus (a continuous seizure activity lasting more than 3 minutes), CNS infection, trauma
What are the main causative factors for epilepsy at a middle age?
Trauma, status epilepticus
What are the main causative factors for epilepsy at an older age?
Cancer, CVA, neurodegenerative disorders, trauma, status epilepticus
What are the three types of partial seizures?
- Simple partial (single focus that doesn’t spread) 2. Complex partial 3. Initial onset of secondarily generalized
What are the five types of generalized (affecting the whole brain) seizures?
- Tonic-clonic (grand mal) 2. Absence (petit mal) 3. Atonic 4. Myoclonic 5. Tonic
What are the three things you need to maintain the characteristic of a simple partial?
- Normal awareness 2. Memory 3. Consciousness (All throughout entire seizure)
How long do simple partial seizures usually last?
60-90 seconds
What are the four classes of symptoms that classify simple partial seizures based on cortical involvement?
- Motor 2. Somatosensory 3. Autonomic 4. Psychic (“aura”)
What are the characteristics of a complex partial seizure and how long do they usually last?
Localized onset, spreads bilaterally usually, either awareness, memory, or consciousness is lost during seizures, and they usually last 15 sec to 3 minutes.
What are the characteristics of secondary generalized seizures?
They begin as simple or complex partial seizures, and when it continues to spread, it becomes generalized. Has tonic (stiffening) and clonic (jerking) phases once it becomes generalized. And all of this is finishes with a postictal phase.
What is a postictal phase?
It is a confusion, somnolence ,with or without transient focal deficit that can lasts minutes-hours. Happens with tonic-clonic activity.
What do all generalized seizures include?
Loss of responsiveness or lack of awareness.
What is probably the cause of absence seizures and how long do they usually last?
Probably represent abnormal interactions between cortical and thalamic transmissions. 2-15 seconds.
What is the main difference between tonic-clonic actions happening with secondary generalized seizures and generalized tonic-clonic seizures? And how long does tonic-clonic usually last?
The two are synchronized with generalized tonic-glonic seizures. Lasts 1-2 minutes.
What are some properties of the “ideal” Anti-Seizure Drug (ASD)?
Effective for the specific seizure type Wide therapeutic index No toxicity No drug-drug interactions Long half-life No protein binding (if binds, not active) Water soluble No active metabolites
What ratio of patients with epilepsy remain refractory to all pharmacological treatments for seizure symptoms?
1/3 of patients
How many generations of ASD’s are there?
3
What are the main reasons why the newer ASD’s are safer than the old ones?
The newer drugs are safer because they have fewer reactions with liver enzymes and fewer drug-to-drug interactions.
What is the issue with having to give more than one ASD to a patient?
If you’re lucky, the patient will be controlled with a single drug, but if you are not getting good control, you will have to give another drug, which will be an inhibitor or an inducer of the other drug. If the second drug is an inducer of that enzyme, then the first drug will get chewed up and its levels will go down, and same applies the other way. If drug has a broad therapuetic index, you don’t need to worry as much about their interactions.
What are the main three mechanisms of ASD’s?
- Enhancement of GABA-mediated inhibition 2. Reduction of excitatory (usually Glutamatergic) transmission 3. Modification of ionic conductances, and modifying these channels with either accomplish #1 or #2.
Carbamezepine
Used for all Partial seizures as well as Tonic-Clonic seizures. Although rare, Steven-Johnsons Syndrome is a side effect. This drug may also activate spike-wave seizures. It is also associated with toxic levels when patients drink grapefruit juice. It is a great drug for epilepsy but the potential for a drug-to-drug interaction is high. It’s MOA is it blocks Na+ channels to inhibit repetitive firing from neurons.
What is Steven-Johnsons syndrome? Who are most at risk? And with which drug is it a side effect?
It is a milder form of toxic epidermal necrolysis. You get fever, sore throat, painful red lesions all over body. The most at-risk patients are those that are slow acetylators, immunocompromised, and patients on combination ASD’s. Carbamezepine.
Which drug is associated with toxic levels if taken with grapefruit juice?
Carbamezepine. Grapefruit juice inhibits CYP3A4 enzyme in liver, so when patients take drug, the liver doesn’t metabolize the drug as it normally does and you can get toxic levels of the drug.
Ethosuximide
Used for uncomplicated absence seizures. Has a very narrow clinical spectrum. It’s MOA is reduces T-type Ca+ channel currents in thalamic pacemaker neurons to quiet rhythmic discharges.
What do barbiturates do?
They increase the duration of opening time of GABA channels.
Phenobarbital
Used for all Partial seizures as well as Tonic-Clonic seizures. Has long-term cognitive memory and behavioral side effects. This drug is also the BIG TIME INDUCER, interact with almost every drug out there. Can precipitate spike-wave seizures in patients with absence seizures. Used mainly because of low cost and broad spectrum but not great option because of side effects.
Phenytoin
Used for all Partial seizures as well as Tonic-Clonic seizures. It masculinizes (hirsuitism) and causes severe gingival hyperplasia, osteopenia, anemia, acne. This drug is special because it has zero-order kinetics at high doses. Most drugs have first-order kinetics. So with this, as you give Phenytoin to patients, it overcomes the metabolize enzymes in the liver, so with even the smallest increase in dose, you get an upshoot increase and can become highly toxic. You have to constantly monitor the levels in your patient. It’s MOA is that it blocks sustained high frequency of action potentials by blocking Na+ channels during repetitive firing.
Topiramate
Used for all Partial seizures as well as Tonic-Clonic and Lennox-Gastaut syndrome seizures. This drug is unique because it is the only one that causes weight loss. Decreases word-finding ability as well. One of its side effects is that it metabolizes estrogen which will lower the efficacy of birth control. It’s MOA is that it blocks repetitive firing of Na+ channels, inhibits Ca+ channels, inhibits AMPA/Kainate receptors, and potentiates GABA currents. Know that this drug is broad spectrum and causes weight loss.
Valproic Acid
Used for all Partial seizures as well as uncomplicated absence seizures, atypical absence seizures, primary tonic-clonic seizures, and myoclonic epilepsy. Very broad spectrum similar to Topiramate. Associated with weight gain however. As well as Reye-like syndrome and hepatic failure. It is strictly contraindicated with people who have liver problems. It also has an increased risk of spina bifida, category D pregnancy risk. It’s MOA is it blocks Na+ channels, reduces NMDA currents, and increases GABA at high doses.
What are the common dose-related ASD adverse effects?
Dizziness, fatigue, ataxia, diplopia, irritability, word-finding difficulty, weight loss, weight gain.
Is it better to use fixed or removable prostheses for patients with epilepsy?
Fixed
What are some recommendations if a patient has a seizure in the dental chair?
Do not restrain patient and do not put anything in mouth. Place patient on their side and give them oxygen and call 911 if patient is cyanotic or seizure lasts for more than 3 minutes. Administer 10mg diazepem.
What is the neurotransmitter, agonists, and antagonists that act on Muscarinic receptors?
Ach Agonists: Bethanechol and Pilocarpine Antagonists: Atropine and Scopalamine
What are some of the tissue effects that agonists have on Muscarinic receptors?
Increase stomach acid secretion Decrease heart rate via SA node Decrease contractions via ventricles, atrium, and AV node Increase GI smooth muscle contractions (except sphincters) Increase secretory gland secretions
What are the two types of Nicotinic receptors, and what tissues do they act on?
N-m (Neuromsucular - neuromuscular junctions) and N-n (Neuronal - ganglia, adrenal medulla, CNS)
What are the two main antagonistic drugs of Nm receptors?
Succinylcholine and d-tubocurarine
How does Succinylcholine work as a neuromuscular blocker?
It is depolarizing and non-competitive, it depolarizes/desensitizes the neuromuscular endplate; it opens the NIC channels and keeps these “open” such that the neuron is depolarized and unresponsive to another ACh challenge
How does d-tubocurarine work as a neuromuscular blocker?
It is non-depolarizing and competitive. It competes with ACh at nicotinic receptors.
What is Sarin and what does it do to the body?
Sarin is nerve gas, an acetylcholinesterase inhibitor, so it allows ACh to accumulate at the cleft and interact with cholinergic receptors to cause too much stimulation. You get a very slow heart rate, diarrhea, cramping, gland secretions, twitching, suffocation, blurred vision, sweating. Soldiers carry around Atropine as a nerve gas antidote, which will block muscarinic receptors to stop all these side effects. Atropine was originally derived from this plant on the left. And blocking these receptors would cause pupils to dilate I think.
What are the three main cholinesterase inhibitors and how do they work?
- Sarin - irreversible; long duration of action, nerve gas 2. Phsyostigmine - short duration of action, used for glaucoma, antidote for atropine 3. Donepezil - extended duration of action, used to treat Alzheimer’s
What does botulinum toxin do?
It prevents the release of ACh. It relaxes intraocular muscles, treats muscle dystonia (spasms), removes wrinkles.
What are the two main drugs to treat xerostomia and how do they work?
- Cevimeline (Evoxac) - used for Sjogren’s syndrome 2. Pilocarpine (Sialagen) - used for radiotherapy
Which neurotransmitter has a greater affinity for alpha1, alpha2, beta1, and beta2 receptors, Epinephrine or NE?
Epinephrine does. Except for Beta1 receptors, they have the same affinity here.
How does phenylephrine work?
It serves as an agonist to alpha1 receptors and it causes vasoconstriction to sinus vessels in order to act as a decongestant. Also causes a decreased heart rate from baroreceptor reflex essentially.
Which tissues do alpha1 agonists act on and what do they do?
Radial muscle of iris - constriction (dilation) Genitourinary and GI sphincters - constrict Vasculature - constrict
What does Prazosin and Terazosin do?
They are alpha1 blocker/antagonisst so they help treat hypertension.
Which tissues do alpha2 agonists act on and what do they do?
Vasculature - constriction NE terminals - decrease NE release Brainstem - decrease NE release
What happens to blood pressure when you act on alpha2 autoreceptors?
You can lower blood pressure by acting on these, because it will decrease the release of NE and you will get less vasoconstriction.
What does Clonidine act on and what is it used for?
Alpha2 receptor agonist, helps treat hypertension and ADHD
What does Guanfacine act on and what is it used for?
Alpha2 receptor agonist, helps treat hypertension and ADHD
What does it mean if a drug ends in the letters -OL?
They are most likely a beta blocker.
Which tissues do beta1 agonists act on and what do they do?
Increase heart rate via SA node Increase conduction velocity via atrium, AV node, purkinje system, and ventricles
Which tissues do beta2 agonists act on and what do they do?
Act on ciliary muscle to relax them for far vision They relax vasculature, especially skeletal muscle for vasodilation They relax lungs, specifically brachial smooth muscle They relax urinary bladder and uterine wall
How do beta blockers work to treat hypertension?
By slowing down the heart rate. They are used by athletes and banned by most sports.
What does Isoproterenol act on?
Beta1 and Beta2 receptor agonist
What does Propranolol act on?
Beta1 and Beta2 receptor antagonist (beta blocker)
What does Albuterol act on?
Beta2 agonist (for asthma)
What does Terbutaline act on?
Beta2 agonist
Where are Beta3 receptors found and do they have a greater affinity for NE or epinephrine?
NE (only one with NE being greater)
What are the pathway effects and receptors on iris circular muscle?
Parasympathetic pathway contracts via M receptors
What are the pathway effects and receptors on iris radial muscle?
Sympathetic pathway contracts via alpha1 receptors
What are the pathway effects and receptors on heart conduction and contractility?
Sympathetic pathway accelerates and increases via beta receptors, and parasympathetic pathway decelerates and decreases via M receptors
What are the pathway effects and receptors on skin splanchnic vessels?
Sympathetic pathway contracts via alpha receptors
What are the pathway effects and receptors on skeletal muscle vessels?
Sympathetic pathway relaxes via beta2 receptors
What are the pathway effects and receptors on bronchial smooth muscle?
Sympathetic pathway relaxes via beta2 receptors and parasympathetic contracts via M receptors
What are the pathway effects and receptors on walls of GI tract?
Sympathetic pathway relaxes via alpha2 and beta2 receptors and parasympathetic contracts via M receptors
What are the pathway effects and receptors on GI and GU sphincters?
Sympathetic pathway contracts via alpha1 receptors and parasympathetic pathway relaxes via M receptors
What are the pathway effects and receptors on GI secretion?
Parsympathetic pathway increases via M receptors
What are the pathway effects and receptors on bladder wall?
Sympathetic pathway relaxes via beta2 receptors and parasympathetic pathway contracts via M receptors
What are the pathway effects and receptors on the pregnant uterus?
Sympathetic pathway relaxes via beta2 receptors and constricts via alpha receptors while the parasympathetic pathway contracts via M receptors
What are the pathway effects and receptors on the penis?
Sympathetic pathway ejaculates via alpha receptors and parasympathetic pathway helps form erection via M receptors
What are the pathway effects and receptors on eccrine glands?
Sympathetic pathway increases via M receptors?
What are the pathway effects and receptors on Apocrine glands?
Sympathetic pathway increases via alpha receptors
What are the pathway effects and receptors on the liver?
Sympathetic pathway increases gluconeogenesis and glycogenolysis via alpha and beta2 receptors
What are the pathway effects and receptors on fat cells?
Sympathetic pathway increases lipolysis via beta3 receptors
What are the pathway effects and receptors on the kidney?
Sympathetic pathway increases renin release via beta1 receptors
From what type of terminals is dopamine released in the kidney?
From sympathetic nerve terminals
Which tissue types and what effect does Dopamine have on D1 receptors?
Increases renal blood flow, GFR, and sodium secretion in Kidney Vasodilation in renal, cerebral, and cardiac vasculature CNS effect
What are the two agonists to D1 receptors?
Dopamine and Fenoldapam
Which tissue types and what effect does Dopamine have on D2 receptors?
It decreases neurotransmitter release in post-ganglionic sympathetic nerve terminals It causes nausea and vomiting in the chemoreceptor trigger zone CNS effect
Will Baroreceptor charge, Sympathetic pathway, and Parasympathetic pathway each increase or decrease if you get a drop in mean arterial pressure?
Decrease baroreceptor charge Increase sympathetic pathway, increase in vasoconstriction and total peripheral resistance Decrease parasympathetic pathway, heart rate goes up and cardiac output goes up
Does NE favor alpha or beta receptors more in general?
Beta
What is the difference with injection epinephrine systemically at low doses compared to high doses?
At a low dose, you may see decrease TPR and diastolic pressure. At higher doses, you may see increased TPR and blood pressure. But you are increasing systolic with both (ventricle contraction with epinephrine). So in the end, at low doses, you don’t have a huge change in mean arterial pressure if you do this slow because systolic and diastolic are counteracting each other. Whereas with high, you have an increased systolic and a flat diastolic so an overall increase in blood pressure and peripheral resistance.
What is the definition of the pupils dilating?
Mydriasis
What does epinephrine do to the aqueous humor of the eye and what does this help treat?
It increases outflow of aqueous humor and is important for treating glaucoma.
What are the five main therapeutic uses of epinephrine?
- Bronchospasm 2. Anaphylaxis 3. Restore function in cardiac arrest 4. Treat glaucome 5. Prolong action of local anesthetics because it is a vasoconstrictor
What are the three main side effects of epinephrine?
- Cardiac – increased heart rate, palpitaKons, arrhythmias, anginal pain 2. Vascular – increased TPR leading to pallor and increased BP 3. Respiratory – increased TRP can lead to pulmonary edema
What is the definition of sympatholytic?
A drug that will block the action of the sympathetic nervous system.
Why administer epinephrine with caution if a patient is taking a beta blocker or has heart disease?
Epinephrine still has effects on alpha receptor which would vasocontstrict, increases pressure, which would decrease HR
Why administer epinephrine with caution if a patient is taking tricyclic antidepressants?
–Tricyclics work with either 5-HT or NE nerve terminals, which are released, taken back up through their transporters, but these drugs block their re-uptake -So you would have synergistic effects and frankly too much adrenaline going around
Why administer epinephrine with caution if a patient is pregnant?
-You would vasoconstrict and would worry about blood flow to the placenta
Why administer epinephrine with caution if a patient is diabetic?
It can alter sugar balance in these individuals and it would increase gluconeogenesis and glycogenolysis via alpha and beta 2 receptors
Why administer epinephrine with caution if a patient is hyperthyroid?
Has nothing to do with autonomics directly, but if you have too much thyroid hormone in general, you will have increased HR already and putting epinephrine into the mix, you can exacerbate it.
How does Pilocarpine work for glaucoma (it also works for xerostomia)?
It acts on muscarinic receptors on iris sphincter muscle, causing the muscle to contract - resulting in pupil contraction (miosis). Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension. This action facilitates aqueous humor leaving the eye to decrease intraocular pressure.
To which receptor does NE have the least affinity?
Beta2
What is the double-edged sword aspect of NE?
-Because NE doesn’t have much effect on Beta-2, we don’t get much dilation to compensate and we are already getting vasoconstriction so it is a double-edged sword, and when blood pressure increases, the baroreceptors will kick in and the heart rate will slow down to compensate.
What is the main therapeutic use of administering NE?
Shock
What are the main side effects of administering NE?
Slow heartbeat if BP increased (baroreceptors); forceful beat (β1); vasoconstrict (decreased blood flow to vital organs; α1)
What is the administering of Dopamine used for?
Used to treat shock and heart failure (at high doses, increased BP and TPR (α1); increased HR (β1); increased organ perfusion (D1))
What does ephedrine do? And what is it used for?
It releases NE, also some direct action on α and β receptors. Used for decongestion and dietary supplements. Side effects: increase HR, vasoconstriction, dilate airways, stimulant (if penetrates CNS)
What does amphetamine do?
It helps dopamine be released
What does cocaine do?
It blocks the reuptake of dopamine
What does methylphenidate do?
It blocks the reuptake of dopamine
What does an NRI do?
Blocks reuptake of NE
What do TCA’s (Tri-Cyclic Anti-depressants) do?
They increase dopamine levels
What is Tyramine’s role with the sympathetic nervous system?
Tyramine is a naturally occurring monoamine compound that serves as a catecholamine releasing agent, in other words, it helps activate the sympathetic pathways. It can displace NE once Tyramine finds its way into nerve terminals. However, tyramine is found in high amounts in certain foods like cheddar cheese and pistachios and if you are taking Monoamine oxidase inhibitors, because MAO is needed in order to break this down and metabolize it.
What are the main two non-selective alpha receptor antagonist drugs?
Phenoxybenzamine and Phentolamine. Uses of non-selective α antagonists include treatment of pheochromocytoma (catecholamine secreting tumor), hypertensive emergencies. Effects: - Decreased TPR (α1) and thus decreased BP - Increased HR (baroreceptor response to decreased BP)
What are the two main side effects of Phenoxybenzamine and Phentolamine, non-selective alpha receptor antagonists?
- Orthostatic hypertension (Getting up in a hurry, you don’t have the baroreceptor working appropriately and people can fall down) 2. Nasal stuffiness
What are the two main alpha1 antagonists and what do they do?
Prazosin and Terazosin, they help block vasoconstriction so essentially cause vasodilation and are used to treat hypertension as well as benign prostatic hypertrophy (Tamsulosin - flomax). The side effects here are also Orthostatic hypertension and nasal stuffiness.
What are the two selective beta1 receptor blockers? And what do they do?
Atenolol and Metoprolol. Uses of β blockers include treatment of hypertension, angina, open- angle glaucoma.
What effect do beta blockers have on the heart?
decreased HR and contractility (impair exercise tolerance)
What effect do beta blockers have on vasculature?
Increased TPR (blockade of β2 in skeletal muscle) (??Which doesn’t make sense to me?)
What effect do beta blockers have on the kidney?
Decreased renin (which would raise BP) release
What effect do beta blockers have on the lungs?
Bronchial constriction
What effect do beta blockers have on metabolism and the liver?
Decreased glycogenolysis in response to hypoglycemia
What things are cholinergic agonists used to treat?
Uses include treatment of myasthenia gravis, glaucoma, Alzheimer’s disease, smoking cessation
What are the two main antimuscarinic drugs and what are they used for?
Atropine and Scopolamine. Used for Parkinson’s disease (adjunctive therapy), motion sickness, COPD, urinary urgency……
What are the five side effects that should scream anti-cholinergic?
- Dry mouth 2. Constipation 3. Blurred vision 4. Sedation 5. Urinary retention
What are the eight main mechanisms involved with CNS degenerative diseases?
- Hypoxia 2. Excitatory Amino Acids 3. Ion Fluxes 4. Free Radicals 5. Immune Responses 6. Infections 7. Apoptosis 8. Protein Aggregation
What is the mechanism behind hypoxia triggering CNS degenerative diseases?
-These will be cardiovascular in nature, and when you deprive the brain of oxygen you end up with strokes.
What is the mechanism behind excitatory amino acids triggering CNS degenerative diseases?
-Glutamate….NMDA/non-NMDA receptors. These are Ionotropic receptors -Too much Ca2+ in cell messes up everything and can kill cells.
What is the mechanism behind ion fluxes triggering CNS degenerative diseases?
-Ca2+/Mg2+ can kill neurons and result in degenerative disorders
What is the mechanism behind free radicals triggering CNS degenerative diseases?
-Free radicals are usually not good things and the body like to keep these things controlled. -They are reactive electrons that cause a cascade of protein damage and interfere with gene expression -The two places most likely to do this are the catecholamines, especially dopamine, and the other source of free radicals is glutamate, which generates nitric oxide -e.g., catecholamines [quinones] and glutamate [NO
What is the mechanism behind immune responses triggering CNS degenerative diseases?
-Autoimmune disorders
What is the mechanism behind infections triggering CNS degenerative diseases?
-Viral/bacterial trigger immune systems -Infections can trigger autoimmune responses -Viruses are more common with brain infections because bacteria have a harder time getting across blood-brain barrier
What is the mechanism behind apoptosis triggering CNS degenerative diseases?
-Programmed cell death, is part of natural development, healthy when done within certain framework, and uncontrolled cell death is bad. You have more glutamate neurons when you are young than when you are old. Once the area of our brain is developed we don’t need that stimulation anymore so a lot of glutamate goes under apoptosis.
What is the mechanism behind protein aggregation triggering CNS degenerative diseases?
-Proteins by nature are very sticky because of negative and positive charged sides. -They are also abnormally sticky because of a protein alteration because of genetics, trauma. -These can elicit an inflammatory response, which can then compromise function, and this is all associated with Beta-amyloid (which is known with Alzheimers)
What are lewy bodies?
They are abnormal aggregates of protein that develop inside nerve cells in Parkinson’s disease (PD), Lewy body dementia, and some other disorders. The primary structural component of which is alpha-synuclein. These are associated with Genetics.
What are the five main clinical manifestations of Parkinson’s Disease?
- Tremor/rigidity/bradykinesia 2. Postural abnormalities (-Stooped, they shuffle feet) 3. Autonomic and neuroendocrine (-Increased salivation, can give an anticholinergic like Atropine to help -Speech is slurred as it progresses, they get frustrated -Dysphagia - they can’t swallow very well -They also get altered taste, and that can be an early indication that Parkinson’s is starting) 4. Late symptoms (-Depression, about 60-70% of patients get significant depression, new studies are showing that depression throughout life can make you 4X more likely to get Parkinson’s. ADHD is also linked and Ritalin) 5. Oral status (-They usually come in with a lot of root canals because it is hard for them to take care of their mouths-They salivate more but the saliva isn’t normal, it is very thick and ropy and doesn’t clean and they get cervical caries)
What are the characteristics of Stage I of Parkinson’s Disease?
Mild/Early Disease - Only one side of the body is affected, so tremor in just one limb for example, and usually with minimal or no functional impairment
What are the characteristics of Stage II of Parkinson’s Disease?
Both sides of the body are affected but posture and balance remain normal
What are the characteristics of Stage III of Parkinson’s Disease?
Moderate Disease - Both sides of the body are affected, and there is mild imbalance when standing or walking; however, the person remains independent
What are the characteristics of Stage IV of Parkinson’s Disease?
Advanced Disease - Both sides of the body are affected, and there is disabling instability while standing or walking; the person in this stage requires substantial help and cannot live alone
What are the characteristics of Stage V of Parkinson’s Disease?
Severe, fully developed disease is present; the person often is cachectic, restricted to bed or wheelchair unless aided
What percentage of the general population has Parkinson’s?
0.3%
If you are older than 85, what percent chance do you have of getting Parkinson’s?
50%
If you are older than 60, what percent chance do you have of getting Parkinson’s?
1%
What is the pathophysiology of Parkinson’s Disease?
It is associated with the Nigro striatal Dopamine pathway. It is only the dopamine neurons that get damaged. It is progressive, nothing you can do to stop and halt the disease. When the dopamine neurons get damaged and we lose dopamine and D2 (which is usually inhibitory), GABA and ACh become overactive, so we try and increase dopamine or block ACh, but we would never block GABA. You can also try and activate D2 receptors to help out.
What are some common environmental factors that might induce Parkinson’s Disease?
Mg and Hg, Pesticides (farmers are more likely), Trauma (quinones)
What are the six main drugs used to treat Parkinson’s Disease?
- L-dopa + Carbidopa 2. Benztropine 3. Trihexyphenidyl 4. Selegiline 5. Entacapone 6. Pramipexole
L-dopa + Carbidopa
Used for Parkinson’s Disease. L-dopa gets across blood-brain barrier much better than dopamine, and Carbidopa blocks the metabolism of L-dopa and dopamine so it can last longer. Some drugs are used in combination with carbidopa-levodopa to either inhibit dopamine breakdown by the body or to improve the effectiveness of carbidopa-levodopa. Azilect inhibits dopamine breakdown while Entacapone improves the effect of Carbidopa-levodopa by inhibiting COMT, Catecholamine Methyl Transferase, which metabolizes neurotransmitters like MAO does.
Benztropine
Used for Parkinson’s Disease. This is an anticholinergic medication that helps with tremors, and is effective because it counteracts the cholinergic sensitivity that arises in response to dopamine depletion. It helps dry sialorrhea from PD patients as well. It can give you confusion, blurred vision, urinary retention.
Trihexyphenidyl
Used for Parkinson’s Disease. Anticholinergic medication. Everything almost identical to Benztropine.
Seligiline
This is used for Parkinson’s Disease. This is an MAO inhibitor, blocking monoamine oxidase B from metabolizing dopamine in the brain, so prolonging the effects of levodopa. Side effects include cardiac dysrhythmias.
Entacapone
Used for Parkinson’s Disease. It inhibits COMT, Catecholamine methyl transferase, which metabolizes like MAO does. So works similar to Seligiline, in the sense that they are both inhibiting metabolizing agents.
Pramipexole
This is a dopamine agonist, a D2 agonist, which bypasses the depleted neurons int he substantia nigra and provides long-lasting direct stimulation of dopamine receptors. Side effects include orthostatic hypertension, nausea, vomiting, confusion.
How does administration of local anesthetic change with Parkinson’s Disease patients?
For patients receiving levodopa and/or entacapone, limit administration to three cartridges of 2 percent lido with 1:100,000 epi per 30 minute period to avoid hypertension and tachycardia. For patients on selegiline, do not administer agents containing epinephrine because of result of severe hypertension.
For initiation of treatment on PD patients, how long after PD meds should treatment start?
Should begin 90 minutes after PD meds, and appointments should be shorter than 45 minutes.
What are seven tips for maintaining and improving dental health with PD?
- Use an electric toothbrush 2. Try one handed strategies 3. Apply stannous fluoride gel 4. Visit dentist in the morning 5. Take levodopa 60-90 minutes before visit 6. Try non-alcohol based mouthwash 7. Plan several shorter dentist visits
What are the main two clinical manifestations of Huntington’s Disease?
- Abnormal moves (These moves are eruptive, unpredicted, twisting, turning, grimmacing, facial contortions. We have excess dopamine activity going on here) 2. Progressive intellectual dysfunction (Early on with this disease, they have poor judgment, withdraw from people, get severely depressed. Later on, they become psychotic (Schiz), they get paranoid, compulsive about doing things certain ways)
How many have Huntington’s Disease? How long do you live once you’ve been diagnosed on average? What is the name of the gene involved?
0.01% 5-10 years once diagnosed Hunting gene, if you have it, you will get Huntington’s Disease
What is the pathophysiology of Huntington’s Disease?
Increase in dopamine and a decrease in GABA because the cell bodies in GABA die. Patients have lost most of the cell bodies because the caudate has been lost, which sits right next to the ventricles on the outside. The hunting gene seems to alter NMDA/AMPA receptors for Glutamate, and you end up killing these receptors from over-excitation of the glutamate system. The hunting gene is found in the GABA neurons.
How do you treat Huntington’s Disease?
Do genetic screening. And you use a dopamine antagonist (antipsychotics), usually a D2 antagonist, and Dopamine depletion for choreiform movement, and antidepressants. The D2s are going to be on GABA, but we have lost GABA, then we don’t have a lot of it and we need whatever we can get so we shut down the inhibitory D2 so we can salvage as much GABA as we can to fight the excess dopamine.
What are the clinical manifestations, stages, and brain regions affected in Alzheimer’s disease?
-Most common, anywhere from 3-4 million people have it at any given time -Once diagnosed, 10-20 years usually they live -It is broken down into three stages, and all of this relates to eliminating extra capacity of the brain -The brain determines what kind of capacity it will have later on when we are children and adolescents. Brain regions involved are frontal cortex, which is intelligence, judgement, and behavior, memory in the temporal lobe, and language right behind it in the parietal lobe. -Early stage is annoying stage, they have memory lapses and forget names, don’t like change -Moderate stage is when they have problems functioning, normal routine is disrupted -Late stage the motor system gets disrupted, they get less mobile, no judgment, immobile and stop eating.
If you are above 85, what is the percentage of you getting Alzheimer’s?
40-50% chance
What is the pathophysiology of Alzheimer’s Disease?
Has a lot to do with old age and genetics. It affects the hippocampus, cortex, and nucleus basalis, and is associated with degeneration of cholinergic systems, ACh neurons.
What are the histological components of Alzheimer’s?
-Senile plaques (they are inside of the neuron), associated with the B-amyloid plaques -Neurofibrillary tangles, associated with a tau protein -Protein aggregates precipitate and cause inflammation and kills cells. Diminish capacity of brain, not able to do multiple tasks concurrently.
What are the main genetic components of Alzheimer’s?
Certain apolipoprotein that has relevance, as well as abnormal APP (amyloid precursor protein) to beta amyloid
How do we go about treating Alzheimer’s? What about treating symptoms of Alzheimer’s?
-We try and increase ACh activity -We largely use Cholinesterase inhibitors -The main drug to know is Donepezil -Anti-inflammatories also help -For treating symptoms of Alzheimer’s, antipsychotics/antidepressants and other drugs. -They say you can help prevent it with exercise.
What is the main drug in treating Alzheimer’s Disease and what does it do?
Donepezil, it is a cholinesterase inhibitor, targeting the cognitive and functional decline symptoms.
What are four tips for managing dental needs in Alzheimer’s Disease?
- Provide short simple instructions. 2. Use a “watch me” technique 3. Monitor daily oral care 4. Keep up with regular dental visits as long as possible
What are the clinical manifestations of Multiple Sclerosis?
Symptoms are highly diverse because they correspond to where the damage is happening in the brain. You can have optic, hearing, sensory, autonomic, cognition, mood, fatigue, muscle weakness and heat tends to worsen everything.
What is the incidence of multiple sclerosis?
Less than, 1,000,000
What is the group of people must susceptible to multiple sclerosis? More males or females?
Scandinavians have a high incidence, Japan has low. 2:1 ratio from male to female.
What is the pathophysiology of Multiple Sclerosis?
It all comes down to oligodendrocytes getting damaged and the myelin is then lost, which results in abnormal or missing conduction. They believe that a virus might trigger it causing acute inflammation and an auto-immune response.
What are the four classifications of Multiple Sclerosis?
- Benign 2. Relapsing remission (symptoms are more severe and you are likely to be diagnosed, episodes typically don’t worsen) 3. Relapsing progressive (cycle, and symptoms worsen) 4. Chronic progression (there is no relapse, and the symptoms progressively get worse, most likely to be fatal, and represents about 10% of all types)
How is Multiple Sclerosis best diagnosed?
There are no definitive tests but MRI’s are used often to get a way to feel good about diagnosis. -MRI measures blood perfusion, and these white spots show that there is tissue damage, inflammation, cell death, and could indicate MS, you need 2 or more of these lesions to have a definitive diagnosis that it is multiple sclerosis -These white areas could also be a tumor, stroke scar, cancer -And you combine all this with increased symptoms
What are the main treatment options for Multiple Sclerosis?
Prednisone is most common, it is a steroid used for anti-inflammation. Interferons are more extreme, as well as methyltrexate, which are both anti-cancer treatments.
What are the main side effects to Prednisone for Multiple Sclerosis?
Bladder dysfunctions, bowel dysfunction, depression, fatigue, pain, tremors.
How much does “pain” cost the US each year?
Around $635 billion
What is a definition of pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
What are the three components of pain?
- Sensory-discriminative 2. Cognitive 3. Emotional/affective
What is the definition of nociception?
The physiological process by which information on actual/potential tissue damage is conveyed to the CNS
What is the definition of nociceptors?
Specialized ion channels on sensory nerve endings that respond to noxious stimuli. There are 4 or 5 different nociceptors that we will be talking about
What is the definition of nociceptive pain?
Pain resulting from activation of nociceptors as a result of actual or potential tissue damage and processing by the CNS (Somatic/visceral/inflammatory)
What is the definition of neuropathic/neurogenic pain?
A pathophysiological process resulting from abnormal sensory processing, which does not signal actual or potential tissue damage, does not promote healing or repair, and may be considered a disease. Fibromyalgia is an example of neuropathic pain.
What is the definition of somatic pain?
Pain associated with musculo-skeletal system and skin - it is well defined. We will see mostly somatic pain in the dental office.
What is the definition of visceral pain?
Pain associated with internal organs and associated tissues - it is dull, burning, poorly defined.
What is the difference between analgesia and anesthesia?
Analgesia is a selective reduction of pain perception. Anesthesia is the absence of any sensation due to suppression of CNS function.
What are the four basic physiologic processes in nociception? And where do they take place?
Transduction, transmission, modulation, and perception. Transduction happens in primary afferent nociceptor, then transmission happens when action potential passes through dorsal root ganglia to actual spinal cord, where modulation takes place, crosses the midline, and goes up spinothalamic tract to the thalamus, and then into the cortex where pain perception takes place.
What does TRP stand for and what is it?
TRP stands for transient receptor potential. They are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. They are indirect mediators of pain, making things more or less sensitive. They are involved with transduction.
What are the four different subtypes of specific ion channels on free nerve endings that respond to actual or potential tissue damage?
- Mechanical 2. Chemical 3. Thermal 4. Polymodal
What is Capsaicin used for and which nociceptor does it activate primarily?
It is used as a topical pain reliever that activates the TRPV1 directly and indirectly to make them less sensitive.
How does secondary activation of nociceptor nerves work?
Chemical messengers released from activated nociceptor nerve endings act locally to release messengers that further activate the nociceptors. This is positive feedback. Action potentials propagate toward the cell body in the dorsal root ganglia and then enter the spinal cord.
What is sensitization when it comes to pain?
It is increased sensitivity and response to stimuli in and near the injured area. It is produced by chemical messengers that do not directly activate nociceptors but which sensitize them, making them more excitable and more likely to be activated by stimuli and produce enhanced discharge frequencies.
What is hyperalgesia?
It is an increased perception of pain in response to painful stimuli. On same line as allodynia.
What is allodynia?
It is pain evoked by normally non-painful stimuli. On same line as hyperalgesia.
Why is pain sensitization so important?
It is important for protection of damaged area, and because it promotes healing.
What are the two major candidates for pain sensitization?
Substance P (SP) from nerve endings and Prostaglandins from damaged cells
What happens when prostaglandin receptors are stimulated?
It results in activation of specific Na+ channels, making the nociceptive nerve ending more excitable, so it is increasing pain sensitization of nociceptors. If you block PG’s or don’t let them form, it doesn’t end up letting sodium come in, which doesn’t activate the TRPV1 nociceptor, and we don’t feel as much pain.
Are COX-1 and COX-2 constitutive or induced?
COX-1 is constitutive, meaning it is always there under normal conditions in many tissues. COX-2 is induced by hormones, growth factors, and inflammatory mediators, and isn’t always present.
What does COX-1 normally help out with?
GI protection, platelet aggregation, renal activities.
What does COX-2 normally help out with?
Cardiovascular protection, renal activities, pain, fever, inflammation. The pain, fever, and inflammation are the inducible activities of COX-2, while the others are constitutive.
What is the primary function of NSAIDS?
They inhibit synthesis of prostaglandins that are involved in sensitizing the nociceptor nerve ending.
What kind of stimulation usually takes place with nociceptors in the viscera?
Mechanical stimulation, like distention, contractions, and may even be “referred” to somatic sites (like a brain freeze)
What are the main two types of sensory nerve fibers than transmit pain?
A delta and C fibers. They carry nociceptive transmission to the spinal cord.
What is the difference between A delta and C fibers.
A delta fibers are small, myelinated, fast conducting, associated with mechanical, thermal nociceptors, and they transmit “first” or “fast” pain, diameter of 1-6 mm, sharp localized pain when dentin is first exposed, and more associated with a reflex than C fibers. C fibers are small, unmyelinated, slow conduting, associated with polymodal nociceptors, and they transmit “slow” or “second” pain, diameter of 2 mm, associated with conduction of dull, difuse pain.
What is the name of the plexus of nerves in the pulp called? And what two groups of fibers does it consist of?
The Plexus of Raschkow, or Sub-Odontoblastic Plexus. It consists of sensory afferents of the trigeminal nerve and sympathetic branches from the superior cervical ganglion.
What do nociceptive fibers synapse with in the dorsal horn?
With “projection” neurons, because they are projecting up, and this is called modulation.
What are the two important pain neurotransmitters that are released from A delta and C fibers in order to excite the projection neurons to go up into the thalamus from the dorsal horn?
Glutamate and Substance P
What is the pathway of pain transmission starting at the injury?
Starts at injury, the noxious stimuli activate the sensitive peripheral ending of the primary afferent nociceptor by the process of transduction. The message is then transmitted over the peripheral nerve to the spinal cord, projection neurons send axons across the midline, where it synapses with cells of origin of the major ascending pain pathway, the spinothalamic tract. The message is relayed in the thalamus to the somatosensory cortex 1 and 2.
What is the name of the nucleus that inputs the information to the thalamus?
Trigeminal nucleus
What kind of modulation takes place at the dorsal horn, facilitatory or inhibitory?
Nociceptive input is heavily modulated at the dorsal horn by both facilitatory and inhibitory influences, there are transmitters at all of the levels that will do either one of these.
What is central sensitization?
It is when dorsal horn projection neurons become sensitized and hyper-responsive to nociceptive input, which contributes to hyperalgesia, and to touch input, which contributes to allodynia. Prostaglandins released from neurons and/or glia in the dorsal horn in response to neural input and inflammatory mediators are probably involved in central sensitization as well. And NSAIDS can inhibit the synthesis of prostaglandins in the dorsal horn that participate in central sensitization, this is considered a second mechanism for the anti-nociceptive action of NSAIDS.
The dorsal horn is also a major site of action for what?
The action for analgesic drugs, including opioids.
What is the “gate control” theory of pain? What fibers converge for this?
The gate control theory of pain asserts that non-painful input closes the “gates” to painful input, which prevents pain sensation from traveling to the central nervous system. Therefore, stimulation by non-noxious input is able to suppress pain. So an example is putting pressure on palate to attempt to inhibit nociception from the injection. Gate control is inhibition of pain by touch. There is a convergence of inputs from A-beta and A-delta fibers, competing for same train tracks.
What happens during “referred pain?”
Visceral afferent nociceptors converge on the same pain-projection neurons as the afferents from the somatic structures in which the pain is perceived, and the brain cannot distinguish the origin. An example is sinusitis and dental pain.
Why is nociceptive pain important to feel and how is it usually terminated?
It is important in signaling actual or potential tissue damage, and is normally terminated by the healing and repair process. However, too much pain can also be maladaptive.
What is the periacqueductal gray?
It is the primary control center for descending pain modulation. It has enkephalin-producing cells that suppress pain. The ascending pain and temperature fibers of the spinothalamic tract send information to the PAG via the spinomesencephalic tract (so-named because the fibers originate in the spine and terminate in the PAG, in the mesencephalon or midbrain).
What is the key locus in the endogenous pain suppressant neural system? And what are the primary opioid mediators of these pain modulation systems?
Periacqueductal gray, although there are multiple stations in which modulation of pain can occur. Enkephalins.
What is another name for the endogenous opioid peptides? And what do they do?
The Endorphins. They play a key role in inhibitory feedback and other physiological processes. They activate various opioid receptors, which are also receptors for opioid analgesic drugs (Mu, delta, and kappa)
What are the three main classes of opioid receptors and what are the three endogenous opioid peptides that interact with them?
Mu, Delta, and Kappa. Enkephalin, Beta-Endorphin, and Dynorphin.
What are the characteristics of enkephalins?
Act on Delta and Mu receptors. 5 amino acids long. Made up of Methionine and Leucine.
What are the characteristics of beta-endrophins?
Act on Delta and Mu receptors. 91 amino acids long. -You can’t give a Beta-endorphin therapeutically, it would be proteased too quickly, but we have drugs that have opioid agonist properties that have a number of naturally occurring narcotics that have selective activities that act on mu or delta receptors.
What are the characteristics of dynorphins?
Act on Kappa receptors. 17 amino acids long. There are A and B Dynorphins, they are inhibitory, they tend to block a lot of the typical reward functions. The kappa receptors are antagonistic to mew and delta, but they still have analgesic properties.
What kind of effects do drugs that enhance the action of NE and 5HT in the CNS have?
Antinociceptive effects. They don’t give you much of a sensation other than the pain goes away.
In what two areas do opioid analgesics primarily act on?
The Periacqueductal Gray (PAG) and the Dorsal Horn.
Why would combining an opioid agonist (something that mimics enkephalin) with a substance P antagonist?
You would get synergism and additivity, and it would enhance the drug, and you wouldn’t have to use as much opioid agonist so you could reduce the side effects caused by opioids.
How can you get analgesic effects in the dorsal horn of the spinal cord?
Any influence that reduces the release of glutamate and substance P from the primary afferent are analgesic.
What is the definition of neuropathic pain?
Pain sensations that may be continuous or periodic, but occur without activation of nociceptors by actual or potential tissue damage. Hyperalgesia and allodynia are common and dramatic here. May result form abnormal activity in nociceptive fibers that have been damaged, but after injury has healed, or from abnormal activity in central pain pathways. There is no protective function and it does not terminate with healing. Triggers can initiate. Involves continuous deep burning, aching, or periodic shock, and is characterized by 1 or more peripheral nerves caused by damage to the nerve.
What are five common examples of neuropathic pain?
- Phantom Limb 2. Shingles 3. Fibromyalgia (9 common points of pain) 4. Diabetes Neuropathies 5. Trigeminal Neuralgia (tic douloureux)
Does neuropathic pain respond to NSAIDS, opioids, or antidepressants, anticonvulsants, corticosteroids?
Never to NSAIDS, inconsistently to opioids, and some responses to antidepressants, anticonvulsants, and corticosteroids.
What is the name of the antidepressant used for neuropathic pain?
Cymbalta
What is the name of the two anticonvulsants used for neuropathic pain?
Lyrica and Gabapentin
What are the four main possible mechanisms for neuropathic pain?
- The peripheral sensitization process may persist rather than subside 2. Damaged nociceptive nerves may fire spontaneously (without activation of nociceptors by usual stimuli) 3. Prolonged input from hyperexcitable nociceptive fibers 4. Decreased activity of endogenous pain-suppressant neural system
What is the role of placebos and pain?
They may have an endogenous analgesia effect, most likely caused by release of endorphins, and there might be a connection with acupuncture.
What are the three different types of pain that will factor in to which analgesic we choose?
- Musculoskeletal 2. Inflammatory 3. Visceral Pain
What three groups of pain medications work at the Brain level?
- Opioid narcotics 2. Glutamate, GABA (Tramadol) 3. Antidepressants (5HT/NE) (Maybe 10% of dentists prescribe antidepressants for pain, usually when the person can’t use the common drugs like NSAIDS because of ulcers and GI side effects and stuff)
What two groups of pain medications work at the Descending Modulation level?
- Serotonin drugs 2. Neuropeptides
What three groups of pain medications work at the Dorsal Horn (modulation sites) level?
- Local Anesthetic 2. Opioids 3. NSAIDS
What four groups of pain medications work at the Peripheral Nociceptor (transduction site) level?
- Local Anesthetic 2. NSAIDS, COX-2 inhibitors 3. Acetaminophen 4. Capsaicin (works on TRPV and also releases substance P)
What two compounds does COX-1 produce, and what are their four roles in the body?
- Prostaglandins E2 2. Thromboxane A2 1. Gastric mucosal barrier 2. Renal function 3. Platelet aggregation 4. Vasoconstriction
What two compounds does COX-2 produce, and what are their three roles in the body?
- Prostaglandins 2. Prostacyclin 1. Pain, inflammation, fever 2. Renal function 3. Vasodilation
Which COX inhibitor (1 or 2) is more associated with cardiovascular issues?
COX-2 inhibitors are more inclined to cause cardiovascular issues, because you are getting a block of vasodilation and getting vasoconstriction and have a coronary issue than you could have a stroke or myocardial infarction.
Which COX inhibitor (1 or 2) is more associated with GI issues and bleeeding?
COX-1 inhibitors. Wouldn’t want to use Cox-1 inhibitor on a bleeding ulcer because it is an anticoagulant and causes GI problems.
Which drug is notorious to avoid for anyone with liver damage/alcohol dependencies?
Acetaminophen
What are the “anti-“ properties of COX-1 and COX-2 inhibitors?
They are both analgesic, anti-pyretic, and anti-inflammatory.
What is acetaminophen’s mechanism?
It is a Non-NSAID, Non-COX 1 or 2 inhibitor—perhaps blocks a COX 3 and/or works on 5HT. It is non-anti-inflammatory, has good anti-pyretic and some good analgesia. So does not help with inflammation, but can help with pain caused by inflammation.
What should you avoid if you have kidney disease?
COX-1 and COX-2 inhibitors
What are salicylates?
They are non-selective COX-1 and COX-2 inhibitors, ibuprofen-like, so they are NSAIDS.
What is Celebrex?
It is a COX-2 inhibitor
In general, does it usually take a higher dose to relieve pain or inflammation?
Inflammation
What three compounds is Excedrin made up of?
Aspirin, Acetaminophen, and Caffeine
What are the dose requirements and characteristics of Salicylates?
COX-1 and COX-2 inhibitor. Analgesia is 600 mg Anti-inflammation is 1 gm Antipyretic is 300-600 mg Duration is 4h -Causes GI irriation, anti-clotting (-You are permanently damaging the platelet when you take these, and you have to regrow platelets, and this anti-clotting can happen with less than 100 mg of salicylates. Don’t prescribe salicylates when you are doing surgery on patients. -When the acetyl group breaks off, this turns into an acid. It has direct and indirect effects on this.), ringing in ears, and Reyes Syndrome in children (With Reyes- You can have permanent damage done to the brain, that is why aspirin-containing products are forbidden in children)
What are the dose requirements and characteristics of Ibuprofen-type NSAIDs?
COX-1 and COX-2 inhibitor Analgesia is 400 mg Anti-inflammation is 800 mg Antipyretic is 400 mg Duration is 4 hours Often a little better pain relief than aspirin -Causes GI ulcers, anti-clotting (-Only indirectly affects platelets unlike salicylic acid, but indirectly through prostaglandins), cardiovascular effects.
What are the names of the two Ibuprofen-like NSAIDS?
Ketoprofen and Naproxen. Ketoprofen is same properties, but more potent; 50 mg is recommended analgesic dose. Naproxen is longer-lasting and slower-acting (Aleve)
What is the main COX-2 selective antagonist?
Celecoxib (Celebrex). • Prescription only • Same analgesia as ibuprofen • Lacks GI and anti-clotting action • Warning about cardiovascular side effects
What are the three “other” NSAID agents that are all prescription only?
- Indomethacin - potent non-selective NSAID/ due to side effects not a common analgesic 2. Meloxicam - preferentially inhibits Cox-2 over Cox-1/ means less GI problems 3. Diflunisal - Related to salicylates- supposed to be good for bone pain
What are the analgesic uses of NSAIDS?
Dental pain, headaches, muscle/joint/bone pain, earaches. All NSAIDS have a plateau at the mild to moderate pain reliever level
What are the main NSAID contraindications?
- Coumadin 2. Joint replacement 3. Heart attack/stroke 4. Major surgery 5. Atrial fibrillation 6. Frequent Upset stomach 7. Bleeding in stools 8. Takes antacids 9. Takes H2 blockers (Tagamet) 10. Hemophiliac 11. Already taking high doses (ex. arthritis) 12. Child or adolescent 13. History of allergies
What are the main three therapeutic uses for opioid narcotics?
- Analgesia (somatic and visceral) 2. Antitussive 3. Antidiarrheal
What is the most potent opioid narcotic and what is it’s equipotent IM dose?
Fentanyl at 0.1 mg
What is the order of equipotent IM doses of opioid narcotics?
Fentanyl at 0.1 mg Oxymorphone at 1 mg Hydromorphone at 1.5 mg Morphine at 10 mg Oxycodone at 20 mg Hydrocodone at 30 mg Codeine at 200 mg
What are the four “other” opioid narcotics?
- Meperidine (for moderate pain, demerol) 2. Pentazocine (It is unique because of its interaction with the kappa receptor, so makes it less likely that people will abuse this, it has a mixed agonist/antagonist effect) 3. Methadone (If an opioid addict is going to methadone clinics, then chart that and know that you don’t need to give them more pain coverage, also used to treat opioid addiction) 4. Buprenorphine (As they go to higher doses it turns into an antagonist, shuts everything off, and kicks them into withdrawals, so harder to get addicted to, similar to two above)
What are the four major opioid agonist side effects, and on which receptor do they primarily take place?
- Respiratory depression/decreased pulmonary reflex 2. Constipation/slow bowel movement 3. Sedation/additive or synergistic with other CNS depressants (e.g., alcohol, antianxiety, sleep aids and natural sleep 4. Euphoria/dependence, addiciton -Mostly Mu opioid receptor mediated
How are opioid narcotic overdoses treated?
Inject the Mu antagonist - naloxone (Narcan). Although it may precipitate withdrawals, and it will block the endorphins (endogenous opioid systems), and if you take these alone, you will get anxiety, stress, or hypersensitivity to pain
What are the four main contraindications to opioid narcotics?
- History of substance abuse (alcohol, opioids, etc) 2. Severe constipation and upset stomach 3. Respiratory problems (emphysema or asthma) 4. Use of other CNS depressants (sedative/sleep aids/muscle relaxants)
What are the two main suggestions for use of analgesics with dental pain>
- Use prior to dental procedure, may reduce post-operative pain and inflammation 2. Start with NSAIDS- if not sufficient, start opioid drugs at low dose and go slow (prescribe only a few at a time)
What is the first-line drug treatment (3 of them, and they are all FDA approved) to manage neuropathic pain like Trigeminal neuralgia?
- Gabapentin (antiseizure 2. Duloxetine (antidepressant) 3. Nortriptyline (antidepressant)
What is the “next-line” of drug treatment for neuropathic pain like Trigeminal neuralgia?
Tramadol (Ultram). It is a schedule 4 drug. Low drug abuse potential, but some minor opioid action.
What is the definition of drug use?
Prescribed and clinically appropriate
What is the definition of drug misuse?
Either not prescribed or clinically inappropriate
What is the definition of drug dependence?
Persistent use resulting in adaptations typically accompanied by accommodation or tolerance (causing compensatory escalation) and withdrawal (e.g., aches, diarrhea, depression and cravings)
What is the definition of drug addiction?
Compulsive drug use that consists of repetition to satisfy intense urges, despite severely negative consequences
What drug schedule are most opioid drugs?
Schedule II. Schedule I is strongest.
What is the six-step addiction cycle for prescription drugs?
- Relieve medical condition 2. Causes reinforcing effects (increased dopamine in brain) 3. Induces physical dependence 4. Often there is a tolerance and withdrawal issue 5. Patients often have substance abuse risk before treatment (mental risk/pre-existing problem) 6. Patient uses various strategies to maintain drug supply
How many million Americans use prescription drugs at least once a year for “non-medical” reasons?
9 million
Where do abused prescription drugs come from primarily?
Friend or Relative (66%) Buy the drugs (21%) Doctor’s prescription (19%) Took/stole the drugs (12% Dealer (8%)
How many hours of CE credit on drug abuse issues in Utah do you have to take a year if you want to maintain your license?
2 hours of CE credit
What is SBIRT?
It stands for Screening, Brief interview, Intervention, Referral, & Treatment. It is how we assess and monitor drug prescriptions and abuse.
What is DOPL?
It stands for Division of Occupational and Professional Licensing. It monitors and regulates the prescriptions of drug prescribers, like Dentists. It also establishes qualifications and requires training for licensing and certifications.
How can you best manage high-risk patients for drug prescription abuse?
Medication management agreements, tight control on prescription drug numbers and routine accountability, and drug screens with associated consequences.
What does DSM-5 stand for? And what does it do?
Diagnostic and Statistics Manual of Mental Disorders. It organizes each psychiatric diagnosis into five dimensions (axes) relating to different aspects of disorder or disability.
What does Axis I through V cover?
Axis I - All psychological diagnostic categories except mental retardation and personality disorder Axis II - Personality disorders and mental retardation Axis III - General medical condition; acute medical conditions and physical disorders (Meningitis, which means I have inflammation, a fever, cause symptoms that look like psychiatric disorders) Axis IV - Psychosocial and environmental factors contributing to the disorder (e.g. stress) Axis V - Global Assessment of Functioning or Childrens Global Assessment Scale for children and teens under the age of 18
What are some disorders found in Axis I?
Depression, anxiety disorders, bipolar disorder, ADHD, autism spectrum disorders, anorexia nervosa, bulimia nervosa, schizophrenia and drug dependence (usually).
What are some disorders found in Axis II?
Personality disorders: paranoid personality disorder, schizoid personality disorder, antisocial personality disorder, narcissistic personality disorder, dependent personality disorder, obsessive-compulsive personality disorder; and intellectual disabilities.
What are some disorders found in Axis III?
Brain injuries and other medical/physical disorders which may aggravate existing diseases or present symptoms similar to other disorders, (sometimes drug abuse?). (-So if you get schizophrenia from a brain injury from a car crash, it is axis III, If you have schizophrenia coming from drug abuse, it is also axis III)
What is MSE and how is it collected?
Mental Status Examination. The data are collected through a combination of direct and indirect means: unstructured observation while obtaining the biographical and social information, focused questions about current symptoms, and formalized psychological tests.
In regards to the MSE, what is mood?
Types and extreme
In regards to the MSE, what is affect?
Appearances, how do you carry yourself, communicate
In regards to the MSE, what is thought, and its three categories?
Thought process (organization, able to organize a reasonable answer to a question, needs to be consistent and sequential Thought content (relevant, insightful) Thought perception (understanding, interpretation of what is happening in the environment)
In regards to the MSE, what is appearance?
-Relevant attire in certain situations -Hygiene is important -Aware of the environment -Motivation to take things seriously and dress appropriately
In regards to the MSE, what is cognitive function, and what are the means of assessing?
It is information processes, decision-making, planning and implementing. The assessment takes place with orientation (-Relate to environment, do you know who you are, question after concussion), concentration (-Can they focus -Can they stay on task), memory (-Short, intermediate, long-term memory? The first one to dissapear for Alzheimer’s is short), fund of knowledge (-Do you have a wealth of knowledge, well-informed, read the newspaper), abstraction (-Going obvious to subtle -Taking basic instruction, extrapolate to real-life case), judgment (-Appropriate reactions to situations like someone telling you your zipper is down), and insight (-Subtle-Intuitive-Schizophrenics are horrible at reading facial expressions)
Besides the Mental Status Examination (MSE), what are the two other tests used?
Electroencephalogram and Brain imaging. Electroencephalograms measure the surface electrical activity of the brain. They don’t diagnose this from that but they can indicate reliable diagnostic patterns. Brain imaging involves a CT, MRI, and PET.
How would an MRI help with mental status examination?
It measures the amount of oxygen in blood in brain, BOLD - Blood Oxygen Level Dependancy.
How would a PET help with mental status examination?
It will tell us where our metabolism of a certain sugar occurred. For a depressed patients, it won’t light up in many places.
What is psychosis? What is schizophrenia? And what are the demographics?
Psychosis -They are not able to perceive what is real, they have an impaired sense of reality -They have an altered cognition and emotion -This is a symptom, like hypertension Schizophrenia -is most commonly recognized -This is referred to as the cancer of mental illness -This costs us about $40 billion a year in the US -1% of people in the United States are schizophrenics -Poor urban U.S, because that’s where they end up
What are the symptoms of schizophrenia?
-There are many types -There are remissions -They will do better than have a relapse, it is a cycle -They have withdrawn -Their thinking and speech is abnormal -Usually anhedonic, they don’t get pleasure out of life, not rewarding -Often thinking about and occasionally implement suicide -Personal appearance is abnormal -Tends to be worse in men -For men, late teen to 20’s, more aggressive and faster in mens -For women, late 20s to 30s -Their thinking has loose connections -They are dillusional (your sensory input is ok, but the way you interpret that input doesn’t relate to reality) -They have hallucinations (sensory input has been corrupted) -Emotions - flat affect -Difficulty in filtering sensory input, get distracted easy -Lack of pre-pulse inhibition (they get a heightened startle reflex and their brain cannot tone it down)
What is the DSM-5 criteria for schizophrenia?
-They need to persist for longer than 6 months -You have deteriorating functions, can’t take care of family or self -Active psychosis, not relating to reality -A differential diagnosis is that there are no drugs or trauma
What are the four subtypes of schizophrenia and their features?
- Disorganized type - -Blunted affect, nothing to read about facial expressions -They are incoherent, don’t make sense -Not particularly dellusional -Bizarre mannerisms 2. Catatonic type - -Nonresponsive, but aware of what is going on -Rigid/bizarre posture 3. Paranoid type - -Positive symptoms, so they are ofen delusional, halllucinations -Aggressive and uncooperative -You would actually want this type if you were a doctor giving medications because of the positive symptoms, most likely to respond 4. Residual type - -Negative symptoms, so no delusions, socially withdrawn -Flat affect -Later stages is when these all get worse -This type is most difficult to treat
What is the prognosis of schizophrenia?
- Chronic equals poor 2. Residual = poor prognosis 3. Institutionalized a lot, that is indication of severity, not a good sign 4. Life expectancy is shortened = 10% suicide, not taking care of selves 5. Best prognosis = temporary, cause-related, principally positive symptoms, If onset is later than 30 years, if person is female, and if there is no family history
What is the biology such as the neurochemical basis and genetic elements of schizophrenia?
-No organic measure -But there are hints, Increase in ventricular size suggests that brain damage has occurred, and because only one of the identical twins had brain damage, this says that environmental factors play a role. You get a decrease in corpus callosum, which is the pathway between the cortex, there is a decrease in frontal cortex blood (MRI), these folks don’t yawn, altered startle and accomodation -Dopamine mechanism, D2 receptor in excess, and early anti-psychotics are D2 antagonists -But the more we study, 5HT may also contribute as well as glutamate, especially to the negative symptoms, and dopamine is more associated with the positive symptoms. -There is also a genetic predisposition
What is the mechanisms of drugs treating schizophrenia?
-All of them block D2 (-Both pre and post synaptic receptors, you can’t have selective D2 blockers) receptors, but also have other effects that likely contribute. (e.g., atypical antipsychotics also block 5HT2 (-Also an autoreceptor, and sits on dopamine neurons) receptors)-correlates with antipsychotic actions. -A side effect is excessive D1 activity because everything else is blocked
What are the two extrapyramidal side effects that drugs that target D2 and 5HT2 receptors have?
- Tardive dyskinesias - -These tend to be D1 mediated, because dopamine isn’t acting on D2 with the D2 blockers, it is going to D1, and causing these problems, and this is a bizarre motor behavior, and this can become permanent if you leave them on these drugs for too long. 2. Parkinson’s like-tremors - Same thing, because of anti-dopamine activity. And people don’t want these medications because of side effects so there is a problem with compliance, and they end up on the streets.
What causes the sleepiness side effect in anti-psychotic drugs?
It is due to the anticholinergic actions in the drugs, which are added in order to reduce excess ACh activity that is taking place because we are blocking all the dopamine, which would normally regulate the amount of ACh. These anti-psychotics can also cause restlessness, dysrupt endocrine, and pseudodepression and some weight gain.
What are the two main classes of anti-psychotic drugs?
- Phenothiazines - Least expensive, older, more sedation and weight gain, less extrapyramidal side effects, antiemetic action. Anticholinergics mask the effects of tardive dyskinesias but the damage is still being done. Anticholinergics are also used to treat Parkinson’s Disease. 2. Butyrophenones - High extrapyramidal side effects, lacks anticholinergic action
What are the two main Phenothiazines (anti-psychotic drugs)?
Chlorpromazine and Thioridizine
What is the main Butyrophenone drug?
Haloperidol
What are the characteristics of atypical anti-psychotic drugs?
They are newer, and along with D2 antagonism, these are also good 5HT2A antagonists. They have little extrapyramidal side effects, and are most effective against the “negative” symptoms of schizophrenia.
What are the main three atypical anti-psychotic drugs?
- Clozapine (Can cause serious agranulocytosis, wiping out WBC’s) 2. Quetiapine 3. Olanzepine
What are the two “other” schizophrenia types?
- Acute psychotic disorder (-Stress-related/maybe delusions, and maybe halucinations. There is a fast recovery, and once you can resolve the stress, the psychosis goes away) 2. Schizoaffective (-Poorly defined, You have severe depression and bouts of schizophrenia, Looks a lot like bipolar)
What are the two minor affective disorders (which are mood disorders)?
- Depression-dysthymia (-Dysthymia is minor depression, DSM5 qualification requires: longer than two years, lowered mood/anhedonia, incidence is about 6% at any one time females are more likely) 2. Cyclothymia (-Cycles of dysthymia to minor state of mania-minor bipolar-longer than two years-no gender bias -No drugs for these usually, some of our most brilliant people like Einstein entered this manic part of cyclothymia and was productive
What are the two subtypes of major mood depression?
- Post-partum (1-4 weeks, usually second or third child) 2. SADS (Seasonal affective disorder, prolonged darkness, no light)
What are the common features to anti-depressants?
Delayed onset, 4-8 weeks sometimes before they kick in, about 70% effective, side effect profile differ
What are the three main categories of anti-depressants?
- Monoamine Oxidase Inhibitors (MAOI) 2. Tricyclic Anti-depressants 3. Monoamine uptake blockers
What are the characteristics of Monoamine Oxidase Inhibitors?
They block the metabolizing enzyme for monoamines (serotonin, dopamine, epinephrine, NE), so they increase these neurotransmitters. Side effects include altered autonomic system activity, orthostatic hypertension, weight gain, may interact with foods that have tyra mine, people have died from eating these foods and taking an MAOI inhibitor, remember these will enhance the nervous system, so when we provide local anesthetic with epinephrine, it could cause cardiovascular problems
What are the two main drugs that are Monoamine Oxidase Inhibitors?
- Phenelzine (MAO A/MAO B inhibitor) 2. Selegiline (MAO B inhibitor)
What are the characteristics of Tricyclic Anti-depressants?
Have long half-life, single daily lose, they block the uptake of NE and varying affinity for 5HT transporters. They give dry mouth pretty bad, H1 blockade (H1 blockers are decongestants, used for reactions to allergies, look like traditional anti-histamine drugs, H2 blockers are used to treat GI problems, diminishing gastric secretions), some orthostatic hypertension, withdrawal with abrupt discontinuation and subsequent diarrhea because you are taking away anticholinergic effect.
What are the three main drugs that are Tricyclic Anti-Depressants?
- Amytriptyline 2. Desipramine 3. Doxepin
What are the characteristics of Monoamine Uptake Blockers?
They block 5HT, NE, doppamine receptors. They have minimal withdrawal because of less or no anti-cholinergic activity, so less xerostomia, constipation, etc. There are two main kinds: Selective Serotonin Reuptake Blockers (SSRI’s) and NE or Mixed transport blockers.
What are the two main SSRI’s?
- Fluoxetine 2. Sertraline -They are popular but can give GI upset, sexual dysfunction, and depression in adolescents. They have no anti-cholinergic activity, so you don’t get dry mouth.
What are the two main NE or mixed transport blocker drugs?
- Venlafaxine 2. Duloxetine -They have no anti-cholinergic properties, so no dry mouth, unlike Tri-cyclics, have more CVS side effects due to increased NE/sympathetic activity, and are moderately a CNS stimulant (insomnia, anxiety)
What are the main two types of Bipolar?
- Cyclothymia (minor bipolar, not treated with meds) 2. Major Manic/Depressive (-When they are manic, they have episodes of grandiosity that might not be realistic -During manic episodes they can’t sleep, they are unrealistic, divorce is common-They get lost for days -They look schizophrenic)
What are the two main classes of drugs to treat Bipolar Disorder?
- Lithium Carbonate 2. Anti-epileptic agents
What are the characteristics of Lithium Carbonate for treating Bipolar Disorder?
Slow onset, likely works by altering 2nd messenger systems such as those involving adenylyl cyclase and G proteins, often combined with anti-depressants, still among the most potent mood stabilizers, has many side effects, requires monitoring blood levels (narrow therapeutic window), tremors are common, kidney damage, weight gain, edema, high rate of compliance problems.
What are the characteristics of Anti-epileptic agents for treating Bipolar Disorder?
These have fewer side effects, better compliance, more expensive, usually for maintenance after lithium starts, GABA/Glutamate pathways might be responsible for some of the bipolar cycling, depression and manic staging, and that is why antiepileptic agents work.
What are the three main anti-epileptic drugs used for Bipolar Disorder?
- Valproic Acid 2. Carbamazepine 3. Lamotrigene
What are the biological theories of mood disorders?
The catecholamine theory. Somehow this on the right (neural junction) has been disrupted at some level and they are not functioning at a smooth well coordinated way, and you end up with the bottom line below, or a combination of all of those. And the bottom line is an imbalance of dopamine, NE, or 5HT activity.
What is the background to, and the different types of Anxiety disorders?
It is a natural response but in excess. Involves adrenaline and the sympathetic nervous system 1. Chronic, mild anxiety - -Constant frequent times of irritation, you don’t have patience, you can’t focus -Linked to environment, there is a cause, you can say this happened and then I got anxiety. Usually don’t need drugs, just relax, take a trip 2. Chronic, moderately severe –Anxiety feelings persist for longer than 6 months, and while they may be coming and going, it is there, and it is genetic, and there is no obvious stressor. Anxiolytics, sedatives, psychotherapy, relaxation, exercise.
What are the three main classes of sedative/hypnotic drugs used for anxiety disorders?
- Benzodiazepines 2. Barbiturates 3. Bupropion
What are the characteristics of Benzodiazepines?
They are agonists on BDZ receptors (allosteric modulators of GABA A receptors). BDZ doesn’t directly activate the GABA receptor, isn’t an agonist, but it indirectly regulates the sensitivity of the receptor so making it more or less receptive to GABA. These have little effect on respiration, most popular CNS depressants, anxiolytic, helps with alcohol withdrawal, treats insomnia (is short-acting, so they don’t sleep the whole day). Tolerance is common with long-term use, interacts synergistically with other depressants, drowsiness, motor impairment, kids can have paradoxical reaction, don’t use with people with intellectual disability to avoid suicide.
What are the two “sedative” benzodiazepine drugs used to treat anxiety disorder?
- Diazepam 2. Alprazolam -Sedative are longer-lasting (8-12 hours), while hypnotic are shorter lasting (2-4 hours).
What are the characteristics of Barbiturates?
They enhance GABA, has short-acting for anesthesia induction, and long-term for seizures. This one is a major depressor of respiration and tolerance (careful with the airway). Not frequently used, narrow margin of safety, major interactions with liver.
What are the two main barbiturates for treating anxiety disorders?
- Pentobarbital (short-acting, helps with anesthesia induction) 2. Phenobarbital (longer-acting, for seizures)
What does Bupropion treat, and what are its characteristics?
It is used to treat anxiety disorders, and it is a non-sedating sedative, not a depressant, but still has anxiolytic activity. We use it for everyday stress and anxiety. Usually for short-term use. Not very addicting, can interact with MAO inhibitors or anti-seizure medicines.
What is a severe acute anxiety-panic attack?
It is a dramatic acute outburst, peak in 10 minutes-Self-limiting-Autonomic outburst-Sense of dread and impending doom, confusion-Sometimes associated with depression
How do you treat a severe acute anxiety-panic attack?
Treat them with an SSRI, like Paxil or anti-depressants that have mixed effects, like Venlafaxin.
What are phobic disorders and how do we usually treat them?
They are irrational fears, we know what the cause is unlike anxiety sometimes, but it’s not rational. Symptoms are not always precipitated (meaning all of the sudden it overcomes you, it can happen that way), and they are illogical. We treat them with SSRI’s like Sertraline.
What are the two “hypnotic” benzodiazepine drugs used to treat anxiety disorder?
- Lorazepam 2. Triazolam -Sedative are longer-lasting (8-12 hours), while hypnotic are shorter lasting (2-4 hours).
What are the main three characteristics associated with Autism?
- Problem with social interactions
- Verbal or non-verbal communication problems
- Problems with repetivie behavior
What is the main cause for autism?
Genetics and environment. It tends to associate with certain medical conditions, like Fragile X syndrome, congenital rubella syndrome, PKU. They are also more vulnerable to toxins because they can’t metabolize them as well.
Who is autism most prevalent in?
White boys. 1 in 42 boys, and 1 in 189 girls.
What are the drugs that might help with autism psychotic, aggressive or repetitive behaviors, but don’t help with the progression of the disease?
Atypical antipsychotics or SSRI’s
What are some symptoms of Anorexia Nervosa?
Restriction of eating, osteoporosis, dry yellow skin, muscle wasting, damage to heart, infertility
What are some symptoms of Bulimia?
Frequent binging and purging, usually normal weight, damage to esophagus. Tooth damage, acid reflux, dehydration.
What are the main drugs used to treat bulimia or anorexia?
Fluoxetine and other antidepressants. The compulsiveness is more involved with Bulimia than with Anorexia, at least the treatment shows more improvement with Bulimia
What is the definition of drug abuse?
The use of a drug in a manner not medically or socially approved.
What is the definition of drug dependence?
Persistent use resulting in adaptations typically accompanied by accommodation or tolerance causing compensatory escalation and withdrawal (e.g. depression and cravings)
What is SUD and what does it stand for?
Substance Use Disorder, it is the correct jargon for drug dependence
What is the definition of drug addiction?
A disorder of pathologic decision making, expression of compulsive destructive behavior despite extreme negative consequences.
What do most abused substances do to the brain?
They enhance dopamine activity in the nucleus accumbens (particularly reltaed to pleasure, motor, and cognitive function). Glutamate and GABA are other pathways also involved.
What is the nucleus accumbens?
It is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. Each cerebral hemisphere has its own nucleus accumbens. The nucleus accumbens, being one part of the reward system, plays an important role in processing rewarding stimuli, reinforcing stimuli (e.g., food and water), and those which are both rewarding and reinforcing (addictive drugs, sex, and exercise). The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.
What are the main functions of the dopamine pathway? And where in the brain does it go?
Reward, pleasure, motor function, compulsion, perserveration, decision-making. It starts in the Substantia nigra, gets dropped off in the nucleus accumbens, the hippocampus, the striatum, and the frontal cortex.
What is the function of serotonin in the brain and what is its pathway?
Mood, memory processing, sleep cognition, and it starts in the dorsal raphe in the brainstem and gets dropped off in the nucleus accumbens, frontal cortex, hippocampus, and striatum, just like the dopamine pathway.
All drugs of addiction increase release of dopamine where in the brain?
The Nucleus Accumbens
How do opioid narcotics cause dopamine release?
They activate opioid receptors
How dooes nicotine cause dopamine release?
It activates nicotinic receptors
How does marijuana cause dopamine release?
It activates cannabinoid receptors
How does caffeine cause dopamine release?
It activates adenosine receptors
How does alcohol and sedative/hypnotics cause dopamine release?
They activate GABA receptors; an inhibitory transmitter
How does Cocaine and ritalin work in regards to dopamine?
They sit on the dopamine transporter so dopamine cannot be picked up back into the neuron, so they are reuptake blockers.
Is the D1 or D2 receptor more involved with pleasure?
-D2 receptor is more involved with the pleasure than D1, and if you activate these too much, it could start to look like Schizophrenia (to treat Schizophrenia you use a D2 antagonist)
What are the four amphetamine-related drugs?
- Methamphetamine
- MDMA (Ecstasy
- Ephedrine
- “bath salts”
How does amphetamines work in regards to dopamine release?
They release dopamine from vesicles and then they pump them in reverse out of the dopamine transporter so they can be in the synaptic cleft and activate dopamine receptors.
Which drug causes the highest activity of dopamine release in the nucleus accumbens?
Amphetamines, by far, so it causes the greatest amount of neurotixicity. 1000 for meth and 350 for cocaine.
Which part of the brain integrates CNS information to make complex decisions and select appropriate behaviors, GO-NO Go system?
-Prefrontal cortex,
Which part of the brain is involved with being the impulsivity center, rapidly selects behaviors based on dominance, rewards, and pereceived immediate emotional needs?
Amygdala/nucleus accumbens.
Which part of the brain establishes priorities and motivation to assist Pre-frontal cortex in decision making?
Orbitofrontal cortex
What happens to the pre-frontal cortex, orbitofrrontal cortex, and amygdala/nucleus accumbens during drug addiction?
- You damage the prefrontal cortex
- You foul up saliency
- And you lose control of impulsivity and reward systems
What does amphetamines do th dendrites and synaptic connections?
They alter dendrites and increase synaptic connections and the influence of an axon is dependent on how many connections are made from one cell to another so Meth makes reward become a more potent driver with these increased synaptic connections.
What does meth do to the expression of the dopamine transporter?
It suppresses its expression. You are very more likely to get Parkinson’s disease with substance use disorders or addictions.
What happens to post-synaptic D2 receptors after long-time drug addictions?
The ability to experience rewards is damage, the receptors are not as receptive or plentiful because the body is trying to get rid of them because of the increased synapses that have been taking place bcause of the drug addiction. If their D2 receptors are not receptive, they are not getting the same high from something that we might be getting high from.
What is the percentage chance that someone has of inheriting genes that might affect their chance of abusing drugs?
40-60%. The process if polygenic and complex. And there might be genes that express variant receptors that are development sensitive or age sensitive, and that is why crap starts in the teens. This was shown using nicotine receptors as an example, 5X more likely if smoking began before 17 years of age, and recent studies have shown alpha 5 subunits linked to reward of nicotine.
What percentage of smokers want and try to quit? What percentage of long-term smokers began before 18 years old?
75% and 92%
Most people entering drug treatment have additional mental health problems. What type of mental disorders are YOUTH more likely to have, in comparison with OLDER ADULTS?
Youth are more likely to have conduct disorders while older adults are more likely to be depressed or have anxiety.
What is SSRT and what does it mean?
It stands for stop-signal reaction time, and it relates to the ability for this pathway, the slower the connector is from the amygdala, the poorer the reaction time, and the more likely that the person will have problems controlling impulsiviity.
What part of the brain do cognitive therapies help out with?
Frontal Cortex
What part of the brain do motivational enhancement therapies help out with?
The Orbital Frontal Cortex, where your saliency or your priority list is kept
What part of the brain do contingency management therapies help out with?
The cortial-amygdala region, this is saying, if you stay drug-free, I am going to give you a reward.
Methylphenidate
Indirect adrenergic agent, similar to amphetamine, cocaine, SNRI’s and TCA’s. This drug blocks DA reuptake. It is Ritalin, is used for ADHD, it is a stimulant.
Phenobarbital
Used for all Partial seizures as well as Tonic-Clonic seizures. Has long-term cognitive memory and behavioral side effects. This drug is also the BIG TIME INDUCER, interact with almost every drug out there. Can precipitate spike-wave seizures in patients with absence seizures. Used mainly because of low cost and broad spectrum but not great option because of side effects.
Ethosuximide
Used for uncomplicated absence seizures. Has a very narrow clinical spectrum. It’s MOA is it reduces T-type Ca+ channel currents in thalamic pacemaker neurons to quiet rhythmic discharges.
Phenoxybenzamine
Non-selective alpha antagonist. Treatment of pheochromocytoma, hypertensive emergencies. Helps you get decreased TPR through blocking alpha-1 and thus decreased BP, and an increased HR through baroreceptor response to decreased BP. Major side effects are orthostatic hypertension and nasal stuffiness.
Phentolamine
Non-selective alpha antagonist. Treatment of pheochromocytoma, hypertensive emergencies. Helps you get decreased TPR through blocking alpha-1 and thus decreased BP, and an increased HR through baroreceptor response to decreased BP. Major side effects are orthostatic hypertension and nasal stuffiness.
Botulinum toxin
It prevents the release of ACh. It relaxes intraocular muscles, treats muscle dystonia (spasms), removes wrinkles.
Bethanechol
It is a muscarinic receptor agonist. Specifically, is a cholinesterase inhibitor.
Pilocarpine
Muscarinic receptor agonist. Used for radiation therapy xerostomia, glaucoma, myasthenia gravis. It acts on muscarinic receptors on iris sphincter muscle, causing the muscle to contract - resulting in pupil contraction (miosis). Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension. This action facilitates aqueous humor leaving the eye to decrease intraocular pressure.
Atropine
Muscarinic receptor antagonist. Sarin is nerve gas, an acetylcholinesterase inhibitor, so it allows ACh to accumulate at the cleft and interact with cholinergic receptors to cause too much stimulation. You get a very slow heart rate, diarrhea, cramping, gland secretions, twitching, suffocation, blurred vision, sweating. Soldiers carry around Atropine as a nerve gas antidote, which will block muscarinic receptors to stop all these side effects. Atropine was originally derived from this plant on the left. And blocking these receptors would cause pupils to dilate I think. Also helps with Parkinson’s disease, motion sickness, COPD. But causes dry mouth, constipation, blurred vision, sedation, urinary retention.
Scopalamine
Muscarinic Receptor Antagonist. Along with Atropine, Also helps with Parkinson’s disease, motion sickness, COPD. But causes dry mouth, constipation, blurred vision, sedation, urinary retention.
Clonidine
Alpha-2 receptor agonist, helps treat hypertension and ADHD.
Carbamezepine
Used for all Partial seizures as well as Tonic-Clonic seizures. Although rare, Steven-Johnsons Syndrome is a side effect. This drug may also activate spike-wave seizures. It is also associated with toxic levels when patients drink grapefruit juice. It is a great drug for epilepsy but the potential for a drug-to-drug interaction is high. It’s MOA is it blocks Na+ channels to inhibit repetitive firing from neurons. Also used for Bipolar Disorder.
Atenolol
Selective beta-1 blocker. Uses of β blockers include treatment of hypertension, angina, open- angle glaucoma.
Metoprolol
Selective beta-1 blocker. Uses of β blockers include treatment of hypertension, angina, open- angle glaucoma.
Isoproterenol
Beta-1 and Beta-2 receptor agonist
Propranolol
Beta-1 and Beta-2 receptor antagonist (beta blocker)
Physostigmine
Cholinesterase inhibitor. Short duration of action, used for glaucoma, antidote for atropine
Sarin
Cholinesterase inhibitor. Irreversible; long duration of action, nerve gas
Donepezil
Cholinesterase inhibitor. Used to treat Alzheimer’s.
Cocaine
Blocks the reuptake of dopamine
Cevimeline
Cholinergic agonist used to treat xerostomia in Sjogren’s Syndrome
Terbutaline
Beta-2 agonist
Topiramate
Used for all Partial seizures as well as Tonic-Clonic and Lennox-Gastaut syndrome seizures. This drug is unique because it is the only one that causes weight loss. Decreases word-finding ability as well. One of its side effects is that it metabolizes estrogen which will lower the efficacy of birth control. It’s MOA is that it blocks repetitive firing of Na+ channels, inhibits Ca+ channels, inhibits AMPA/Kainate receptors, and potentiates GABA currents. Know that this drug is broad spectrum and causes weight loss.
Endocannabinoids
Anandamide is the main endocannabinoid neurotransmitter, and it binds to CB1 cannabinoid receptors, and by doing so, causes dopamine release. Endocannabinoids are main ingredient in marijuana.
Phenytoin
Used for all Partial seizures as well as Tonic-Clonic seizures. It masculinizes (hirsuitism) and causes severe gingival hyperplasia, osteopenia, anemia, acne. This drug is special because it has zero-order kinetics at high doses. Most drugs have first-order kinetics. So with this, as you give Phenytoin to patients, it overcomes the metabolize enzymes in the liver, so with even the smallest increase in dose, you get an upshoot increase and can become highly toxic. You have to constantly monitor the levels in your patient. It’s MOA is that it blocks sustained high frequency of action potentials by blocking Na+ channels during repetitive firing.
Dopamine
The adminestering of Dopamine itself is used to treat shock and heart failure (at high doses, increased BP and TPR (α1); increased HR (β1); increased organ perfusion (D1))
Prazosin
Alpha-1 antagonist, used to treat hypertension. It helps block vasoconstriction so essentially cause vasodilation and are used to treat hypertension as well as benign prostatic hypertrophy (Tamsulosin - flomax). The side effects here are also Orthostatic hypertension and nasal stuffiness.
Terazosin
Alpha-1 antagonist, used to treat hypertension. It helps block vasoconstriction so essentially cause vasodilation and are used to treat hypertension as well as benign prostatic hypertrophy (Tamsulosin - flomax). The side effects here are also orthostatic hypertension and nasal stuffiness.
Guanfacine
Alpha-2 receptor agonist, helps treat hypertension and ADHD
D-tubocurarine
Nicotinic (muscle) antagonist. It is non-depolarizing and competitive. It competes with ACh at nicotinic receptors.
Albuterol
Beta-2 agonist
Amphetamine
Helps dopamine be released. Adderall is an example, used to treat ADHD. It is a stimulant.
Phenylephrine
Alpha-1 receptor agonist and it causes vasoconstriction to sinus vessels in order to act as a decongestant, helps with mydriasis for eye exams. Also causes a decreased heart rate from baroreceptor reflex essentially.
Fenoldapam
D1 receptor agonist, along with dopamine
Ephedrine
It releases NE, also some direct action on α and β receptors. Used for decongestion and dietary supplements. Side effects: increase HR, vasoconstriction, dilate airways, stimulant (if penetrates CNS)
Succinylcholine
It is a Nicotinic (muscular) antagonist. It is depolarizing and non-competitive, it depolarizes/desensitizes the neuromuscular endplate; it opens the NIC channels and keeps these “open” such that the neuron is depolarized and unresponsive to another ACh challenge.
Valproic Acid
Used for all Partial seizures as well as uncomplicated absence seizures, atypical absence seizures, primary tonic-clonic seizures, and myoclonic epilepsy. Very broad spectrum similar to Topiramate. Associated with weight gain however. As well as Reye-like syndrome and hepatic failure. It is strictly contraindicated with people who have liver problems. It also has an increased risk of spina bifida, category D pregnancy risk. It’s MOA is it blocks Na+ channels, reduces NMDA currents, and increases GABA at high doses. Also used for Bipolar Disorder.
Selegiline
This is used for Parkinson’s Disease. This is an MAO inhibitor, blocking monoamine oxidase B from metabolizing dopamine in the brain, so prolonging the effects of levodopa. Side effects include cardiac dysrhythmias. They block the metabolizing enzyme for monoamines (serotonin, dopamine, epinephrine, NE), so they increase these neurotransmitters. Side effects include altered autonomic system activity, orthostatic hypertension, weight gain, may interact with foods that have tyra mine, people have died from eating these foods and taking an MAOI inhibitor, remember these will enhance the nervous system, so when we provide local anesthetic with epinephrine, it could cause cardiovascular problems
Enkephalins
Act on Delta and Mu receptors. 5 amino acids long. Made up of Methionine and Leucine.
Barbiturates
They enhance GABA, has short-acting for anesthesia induction (Pentobarbital), and long-term for seizures (Phenobarbital). This one is a major depressor of respiration and tolerance (careful with the airway). Not frequently used, narrow margin of safety, major interactions with liver.
Pramipexole
This is a dopamine agonist, a D2 agonist, which bypasses the depleted neurons int he substantia nigra and provides long-lasting direct stimulation of dopamine receptors. Side effects include orthostatic hypertension, nausea, vomiting, confusion. Used to treat Parkinson’s Disease.
Clozapine
Atypical anti-psychotic drug. Can cause serious agranulocytosis. Besides D2 antagonism, these typically are also good 5HT2A antagonists. Little extrapyramidal side effects. Most effective against the negative symptoms in some forms of schizophrenia.
Quetiapine
Atypical anti-psychotic drug. Besides D2 antagonism, these typically are also good 5HT2A antagonists. Little extrapyramidal side effects. Most effective against the negative symptoms in some forms of schizophrenia.
Olanzepine
Atypical anti-psychotic drug. Besides D2 antagonism, these typically are also good 5HT2A antagonists. Little extrapyramidal side effects. Most effective against the negative symptoms in some forms of schizophrenia.
Celecoxib
Celebrex. Cox-2 selective antagonist. • Prescription only • Same analgesia as ibuprofen • Lacks GI and anti-clotting action • Warning about cardiovascular side effects
Trihexyphenidyl
Used for Parkinson’s Disease. Anticholinergic medication. Everything almost identical to Benztropine.
Acetaminophen
Tylenol. It is a Non-NSAID, Non-COX 1 or 2 inhibitor—perhaps blocks a COX 3 and/or works on 5HT. It is non-anti-inflammatory, has good anti-pyretic and some good analgesia. So does not help with inflammation, but can help with pain caused by inflammation.
Lyrica
Anticonvulsant used for neuropathic pain
Gabapentin
Anticonvulsant used for neuropathic pain
Capsaicin
It is used as a topical pain reliever that activates the TRPV1 directly and indirectly to make them less sensitive.
Lorazepam
Hypnotic benzodiazepine drug used to treat anxiety disorder
Triazolam
Hypnotic benzodiazepine drug used to treat anxiety disorder
Tramadol
(Ultram). It is a schedule 4 drug. Low drug abuse potential, but some minor opioid action. Works at brain level. Is the “next-line” of drug treatment for neuropathic pain like Trigeminal neuralgia.
Lamotrigene
Anti-epileptic drugs used for Bipolar Disorder
Amytryptiline
Tri-cyclic anti-depressant. Have long half-life, single daily lose, they block the uptake of NE and varying affinity for 5HT transporters. They give dry mouth pretty bad, H1 blockade (H1 blockers are decongestants, used for reactions to allergies, look like traditional anti-histamine drugs, H2 blockers are used to treat GI problems, diminishing gastric secretions), some orthostatic hypertension, withdrawal with abrupt discontinuation and subsequent diarrhea because you are taking away anticholinergic effect.
Desipramine
Tri-cyclic anti-depressant. Have long half-life, single daily lose, they block the uptake of NE and varying affinity for 5HT transporters. They give dry mouth pretty bad, H1 blockade (H1 blockers are decongestants, used for reactions to allergies, look like traditional anti-histamine drugs, H2 blockers are used to treat GI problems, diminishing gastric secretions), some orthostatic hypertension, withdrawal with abrupt discontinuation and subsequent diarrhea because you are taking away anticholinergic effect.
Doxepin
Tri-cyclic anti-depressant. Have long half-life, single daily lose, they block the uptake of NE and varying affinity for 5HT transporters. They give dry mouth pretty bad, H1 blockade (H1 blockers are decongestants, used for reactions to allergies, look like traditional anti-histamine drugs, H2 blockers are used to treat GI problems, diminishing gastric secretions), some orthostatic hypertension, withdrawal with abrupt discontinuation and subsequent diarrhea because you are taking away anticholinergic effect.
L-dopa + Carbidopa
Used for Parkinson’s Disease. L-dopa gets across blood-brain barrier much better than dopamine, and Carbidopa blocks the metabolism of L-dopa and dopamine so it can last longer. Some drugs are used in combination with carbidopa-levodopa to either inhibit dopamine breakdown by the body or to improve the effectiveness of carbidopa-levodopa. Azilect inhibits dopamine breakdown while Entacapone improves the effect of Carbidopa-levodopa by inhibiting COMT, Catecholamine Methyl Transferase, which metabolizes neurotransmitters like MAO does.
Dynorphins
Endogenous peptides. Act on Kappa receptors. 17 amino acids long. There are A and B Dynorphins, they are inhibitory, they tend to block a lot of the typical reward functions. The kappa receptors are antagonistic to mew and delta, but they still have analgesic properties.
Benztropine
Used for Parkinson’s Disease. This is an anticholinergic medication that helps with tremors, and is effective because it counteracts the cholinergic sensitivity that arises in response to dopamine depletion. It helps dry sialorrhea from PD patients as well. It can give you confusion, blurred vision, urinary retention.
Beta-endorphins
Endogenous peptides. Act on Delta and Mu receptors. 91 amino acids long. -You can’t give a Beta-endorphin therapeutically, it would be proteased too quickly, but we have drugs that have opioid agonist properties that have a number of naturally occurring narcotics that have selective activities that act on mu or delta receptors.
Phenelzine
MAO A/MAO B inhibitor. They block the metabolizing enzyme for monoamines (serotonin, dopamine, epinephrine, NE), so they increase these neurotransmitters. Side effects include altered autonomic system activity, orthostatic hypertension, weight gain, may interact with foods that have tyramine, people have died from eating these foods and taking an MAOI inhibitor, remember these will enhance the nervous system, so when we provide local anesthetic with epinephrine, it could cause cardiovascular problems
Entacapone
Used for Parkinson’s Disease. It inhibits COMT, Catecholamine methyl transferase, which metabolizes like MAO does. So works similar to Selegiline, in the sense that they are both inhibiting metabolizing agents.
Venlaxafine
NE or mixed transport blocker drug. They have no anti-cholinergic properties, so no dry mouth, unlike Tri-cyclics, have more CVS side effects due to increased NE/sympathetic activity, and are moderately a CNS stimulant (insomnia, anxiety).
Duloxetine
NE or mixed transport blocker drug. They have no anti-cholinergic properties, so no dry mouth, unlike Tri-cyclics, have more CVS side effects due to increased NE/sympathetic activity, and are moderately a CNS stimulant (insomnia, anxiety).
Prednisone
Drug that treats Multiple Sclerosis. Bladder dysfunctions, bowel dysfunction, depression, fatigue, pain, tremors.
Naloxone
Mu antagonist, used to treat opioid narcotic overdoses - naloxone (Narcan). Although it may precipitate withdrawals, and it will block the endorphins (endogenous opioid systems), and if you take these alone, you will get anxiety, stress, or hypersensitivity to pain
Meperidine
“Other” opioid narcotics, for moderate pain.
Pentazocine
“Other” opioid narcotic. It is unique because of its interaction with the kappa receptor, so makes it less likely that people will abuse this, it has a mixed agonist/antagonist effect.
Methadone
“Other” opioid narcotic. (If an opioid addict is going to methadone clinics, then chart that and know that you don’t need to give them more pain coverage, also used to treat opioid addiction)
Buprenorphine
“Other opioid narcotic.” (As they go to higher doses it turns into an antagonist, shuts everything off, and kicks them into withdrawals, so harder to get addicted to, similar to two above)
Lithium Carbonate
Used for Bipolar Disorder. Slow onset, likely works by altering 2nd messenger systems such as those involving adenylyl cyclase and G proteins, often combined with anti-depressants, still among the most potent mood stabilizers, has many side effects, requires monitoring blood levels (narrow therapeutic window), tremors are common, kidney damage, weight gain, edema, high rate of compliance problems.
Salicylates
They are non-selective COX-1 and COX-2 inhibitors, ibuprofen-like, so they are NSAIDS.
Ketoprofen
Ibuprofen-like. Ketoprofen is same properties, but more potent. Remember that NSAIDS negate the effects of anti-hypertension medications.
Naproxen
Ibuprofen-like. Naproxen is longer-lasting and slower-acting (Aleve).
Chlorpromazine
Phenothiazine, anti-psychotic drug. Least expensive, older, more sedation and weight gain, less extrapyramidal side effects, antiemetic action. Anticholinergics mask the effects of tardive dyskinesias but the damage is still being done. Anticholinergics are also used to treat Parkinson’s Disease
Thioridizine
Phenothiazine, anti-psychotic drug. Least expensive, older, more sedation and weight gain, less extrapyramidal side effects, antiemetic action. Anticholinergics mask the effects of tardive dyskinesias but the damage is still being done. Anticholinergics are also used to treat Parkinson’s Disease
Fluoxetine
SSRI. They are popular but can give GI upset, sexual dysfunction, and depression in adolescents. They have no anti-cholinergic activity, so you don’t get dry mouth.
Sertraline
SSRI. They are popular but can give GI upset, sexual dysfunction, and depression in adolescents. They have no anti-cholinergic activity, so you don’t get dry mouth.
Haloperidol
It is a butyrophenone that is used to treat Psychotic disorders. High extrapyramidal side effects, lacks anticholinergic action
Indomethacin
“Other” NSAID agent. Indomethacin - potent non-selective NSAID/ due to side effects not a common analgesic
Meloxicam
“Other NSAID agent.” Meloxicam - preferentially inhibits Cox-2 over Cox-1/ means less GI problems
Diflusinal
“Other NSAID agent.” Diflunisal - Related to salicylates- supposed to be good for bone pain
Diazepam
Sedative benzodiazipene drug used to treat anxiety disorder.
Alprazolam
Sedative benzodiazipene drug used to treat anxiety disorder.
Bupropion
It is used to treat anxiety disorders, and it is a non-sedating sedative, not a depressant, but still has anxiolytic activity. We use it for everyday stress and anxiety. Usually for short-term use. Not very addicting, can interact with MAO inhibitors or anti-seizure medicines.
Nortryptiline
First-line drug treatment (3 of them, along with Gabapentin, Duloxetine, and they are all FDA approved) to manage neuropathic pain like Trigeminal neuralgia.
Modafinil
It is a minor stimulant, or non-stimulant, to treat ADHD, called the “smart drug.” Has few side effects, biggest complaint is that it alters sleep patterns, and it is also used for narcolepsy.
Mecamylaline
Nicotinic (neuronal) antagonist
