Pharm 1: Block 1 Flashcards
Define Prescription
Prescriber’s order for a specific patient
Define “Sig”
Signetur
“let it be labeled”
What are the two safety categories of prescriptions
Legend- federal requires Rx for drug prescription
OTC- considered safe for self-administration
FDA determines if a drug should be a legend or OTC based on what?
Safety Consideration
Who controls and monitors drugs considered to have abusive potentials?
DEA
Who approves what indications a drugs is used for?
FDA
Define Labeled Use
FDA approved a New Drug Authorization saying drug is safe/effective for an indication
Define Unlabeled Use
Use of a medication for an indication that has not been approved by the FDA
What is the generic name for Neurontin?
Gabapentin
PAs may be privileged to write Rxs for medication that have been approved and recommended by whom?
Pharmacy and Therapeutics Committee
What is the military’s Rx form number?
DD 1289
Rxs for children 12 y/o and younger need to include what other two pieces of info?
Age
Weight
What are the 4 drug name/classifications?
Chemical Name
Drug Name- Trade/Brand, Generic
Pharmacotherapeutic Class
Target Physiologic System
What drug name is used by the FDA and which one is used by a company/manufacturer?
Trademark= trade/brand Generic= FDA
DoD allows a __ day supply for a maintenance medication
90 days
How many refills are allowed for Schedules 2-5?
2: None
3-5: 5 x in 6mon, what ever happens first
What additional info is added to a hand written prescription for controlled substances?
Quantity of meds is written/spelled out in numeric and letters
What are 4 factors that encourage PT noncompliance?
Asymptomatic
Inc frequency
Direction difficulty
Side effects
Define ASA
Define ATC
Aspirin
Around the clock
Define HA
Define HTN
Define HOTN
Headache
Hypertension
Hypotension
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Abbreviations
What is the difference between adverse drug reaction and medication error?
ADR: unexpected/unintended response to a med
ME: event leading to inappropriate medication use
Define Allergic Reaction
Immunologic hypersensitivity that occurs after medication use where the drug acts as an Ag in the body
Define Idiosyncratic Reaction
Abnormal susceptibility to a medication that is peculiar to an individual
Antihistamine causing excitement instead of sedation
Who classifies/categorizes controlled substances?
DoJ
DEA- Office of Diversion Control, Title 21 USC CSA
What are the limitations/regulations on filling a Schedule II Rx?
No Federal limit on quantity, limited by State/local law
90 day limit for matinenance
No federal time limit to fill
No refills
What happens if a pharmacist fills a Schedule II drug in an emergency situation?
May dispense quantity to adequately treat PT during emergency period
Prescribing practitioner must provide written/signed Rx w/in 7 days
What are 3 exception for when a faxed prescription can serve as an original Rx and no further verification is required?
Compounded for direct administration
Long term care facilities
Hospice
During what period of instruction is a human embryo’s growth disrupted?
Organogenesis- 3-8wks
Teratogenic agents
What does maternal alcohol abuse do to a developing fetus?
Microcephaly
What does maternal ACE inhibitor use cause to a developing fetus?
Renal function
What does maternal warfin use do to a developing fetus?
Cartilage defects
Define Category A Drug
Safe for human and baby
Define Category B Drug
No risk to fetus
Define Category C Drug
Adverse to fetus
Define Category D Drug
Evidence supporting adverse effect to fetus
Define Category X Drug
Do not give to pregnant woman
FDA required the use of what 3 subsection labeling?
Pregnancy
Lactation
Reproductive risk potential
What makes up Tiers 1 and 2 of DoD Formulary?
BCF- 1 & 2, must be carried by all MTFs
ECF- 1&2, must be carried if medical service is offered
UF Drugs- 1&2
Define Tier 3 Drugs
Non formulary drugs
Define Tier 4 Drugs
Medication is not covered, copayment reduction for required need
What is the Uniform Formulary?
Pharmaceuticals listed by therapeutic classes determined by DoD P&T committee
Define Non-Formulary Unit
Agents not selected for UF
Define Basic Core Formulary
List of pharmaceuticals required to be on local formulary
Define Extended Core Formulary
Medicatoins used to support specialized scopes of practice than the BCF
What happens if an MTF chooses to have an ECF on its formulary?
Must have all ECF medications in that class on the formulary
Define Non-Formulary
Medication that can be provided at formulary cost share if the provider supplies information showing there is a medical need/necessity
What are the phases of drug development?
Pre-clinical Phase 1-4 Pre- animal pharm/tox 1- Healthy volunteers 2- PTs w/ disease/condition 3- Large scale multi-center 4- Post-marketing surveillance
Define Pharmacokinetics
Define Pharmacodynamics
What body does to drug
What drug does to body
What do the 4 phases of pharmacokinetics encompass?
ADE
Administration
Systemic circulation
Site of action concentration
What are the 4 phases od pharmacokinetics?
ADME
What are the pharmacokinetics taken into consideration when determining dosage regimen
Bioavailability Volume of distribution Drug accumulation Clearance Elimination
What are some factors that determine drug’s access to a molecules site of action?
Route Absorption Distribution Binding Metabolism Clearance
What happens when a weak acid is placed into an acid medium?
Shift to left, suppresses ionization
What happens when a weak acid is placed in an alkaline medium?
Ionization increases
What happens when a weak base is placed into an acid medium?
Shift to left, increased ionization
What happens when a weak base is placed into an alkaline medium?
Shift to right, suppresses ionization
A drugs ability to move from an aqueous to lipid environment depends on what?
Charge
pH of solution
Define Hydrophilic
Hydro: Charged, Polar
Lipo: Uncharged
Define the Henderson-Hasselbalch equation
Relationship between ratio of acid to base
Define pKa
negative base log of the acid dissociation constant of a solution
Low= acidic
High= basic
Ph of a biologic fluid that dissolves a drug affects what two results?
Degree of ionization
Rate of transport
What happens if/when the pKa of a drug equals the pH of the surroundings?
50% ionization occurs
Define Weak Acid
H: concentration of protonated/unionized form
A: concentration of ionized/unprotonated form
Define Weak Base
BH: concentration of protonated form of base
B: unprotonated concentration
How will sodium bicarbonate effect the renal excretion of weak acids?
Increases elimination by increasing urine’s pH, turns the weak acid into unprotonated/ionized
Alkalinizing urine will have what effect on elimination?
Acidification of urine will do?
Alk: increases elimination of acidic
Acid: increases basic drug elimination
Define Bioavailability
Fraction of unchanged drug reaching the systemic circulation after oral administration
What determines/how is bioavailability determined?
Extent of absorption
First pass metabolism
What is an example of a drug that is close to 100% bioavailable?
IV drugs
What factors affect passage of drugs across biologic membranes?
Lipid-aqueous partition coefficient (ionization/non-ionized coefficient)
Specific transport
Plasma binding
Perfusion rate
____ is the primary site of drug metabolism and _____ is reduced
Liver
Bioavailability
First Pass Metabolism primarily applies to what type of drug but may limit efficacy if ?
Oral administerred
Efficacy limited if clearance by liver is large
What systemic circulation by influence overall first pass metabolism?
Enterohepatic
What are 3 ways to obtain better systemic absorption of a drug that has high first-pass effects?
Increased dose
Alternate admin route
Delayed release drug product
What are the two drug transport proteins?
Albumin
A1-acid glycoprotein
Drugs bound to ___ proteins are not active and only ____ drugs are active
Plasma
Free
Free drug is available to undergo what two processes?
Bind w/ receptor
Metabolize/eliminated
When/why is plasma protein binding important?
High plasma protein bound drugs- ibuprofen
Drugs w/ narrow therapeutic index- phenytoin
Define Drug Modeling
Describes drug distribution behavior in body by using compartmental models
What are 4 characteristics of compartmental models?
Simplification
Non-representative of single tissue
1 / 2 / 3 compartment model
Highly perfused compartments = 1 compartment
Define One Compartment Model
Simplest
Comprises all body tissues
Assumes instant distribution through body
Define Two Compartment Model
Distribution is not instant
Fist compartment- blood, and highly perfused tissue
Second- less accessible tissues
Define Volume of Distribution
Volume that drug distributes and evaluates extensive/limited distribution
“Where the drug goes in body”
What is the volume of distribution equation and parts?
Vd=Fdose/Co
F- bioavail
Dose- weight of drug given
C- concentration of drug in blood/plasma
What unit of measurement is Volume Distribution (Vd) reflected in?
L
L/kg
Define Small and Large Volume Distribution
Minimal drug distribution
Extensive drug distribution
How does plasma proteins affect volume of distribution?
Drug w/ affinity for protein in plasma will have reduced Vd, decreased plasma proteins will increase Vd
What is the major plasma protein involved in drug protein binding?
Albumin
What two structures make the BBB?
Capillaries covered in astrocytes
Endothelial cells making tight junctions
How does the placenta affect drug passage?
Lipid solubility facilitates entry
Placenta is porous, allows large hydrophilic molecules to cross which allows fetal blood levels to increase slowly
Metabolic pathways of drugs normally alter drugs in what ways?
Deactivate
Detox
Less active
What are the two major type of drug metabolism reactions?
Phase I: Non-synthetic, Cytochrome P450
Phase 2: Synthetic, Glucuronidation
Phase 1 -> Phase 2= conjugation
What are examples of Phase 1, Non-Synthetic reactions?
Oxidation
Reduction
Hydroxylations
How does Phase 1, Non-Synthetic reactions work?
Introduce function groups to molecules
Converts parent drug to polar metabolite
Causes loss of pharmacologic activity
How do Phase 2, Synthetic metabolism reactions work?
Conjugation reactions
Covalent linkage w/ functional group on parent compound
Highly polar conjugates= rapid drug elimination from body
Define Inactive Metabolite
Active compound becomes inactivated/detoxed
Metabolites that retain similar activities are retaining what part of their molecular structure?
Retain activity of parent compound
What does a metabolite with altered activity mean?
Develops different activity from parent drug
Define Bioactive Metabolites
Prodrug- inactive substance that must be converted by metabolism to become biologically active
Prodrug= inactive form
Define Cytochrome P450 Enzymes
Mixed function oxidases responsible for majority of drug metabolism
Define Cytochrome P450 System Substrate
Substance on which enzyme acts
Define Cytochrome P450 System Induction
Accelerated metabolism resulting in decreased action of inducing/co-administered drugs
Define Cytochrome P450 System Inhibition?
Reduced metabolism of substrates/co-administered drugs metabolized by specific enzyme causing increased action of co-administered drug/substrates
What system is behind most clinically important drug/drug interactions?
Cytochrome P450 System
Define Chirality
Sereoisomerism
Geometric property of molecules/ions
What are characteristics of chiral molecules?
Non-superposable on mirror image
Rectus- right
Sinister- left
Define a Racemic Mixture
Equal mixture of enantiomers
What are chiral molecules role in pharmacology?
Seperate an active enantiomer from a pair to create new drug, reduce side effects, extend presence in PTs
Define Zero-Order Kinetics
Metabolic rate is dependent on time and not drug concentration
Linear kinetics
No true half-life
Define First-Order Kinetics
Metabolic rate is proportional to drug concentration
Non-linear kinetics
Drug disappears w/ time
Half life is constant
What are 4 characteristics of nonlinear kinetics?
Area under curve, not proportional to dose
Amount excreted in urine, not proportional to dose
Half life increases w/ high doses
Metabolite ratio changes w/ increased dose
What are 4 variables that cause alterations in drug metabolism?
Genetic variability
Age
Nutrition
Concurrent Disease
Define Child-Pugh Classes A, B, and C
A/B- mild/moderate impairment, no dosage adjustment needed
C- extended release tablets, not recommended
A drugs ability to be reabsorbed from glomerular filtrate is determined by what?
Their lipid solubility
Charged compounds are poorly re-absorbed
Define Clearance
Measure of removal of drug from plasma
Systemic= renal + hepatic + other
What two factors determine a drug’s half-life?
What is it related to?
Clearance
Volume of distribution
Related to duration of action
How is drug clearance of an organ determined?
Blood flow
Extraction ratio of organ
Define Creatinine Clearance
Estimated renal function from 24hr UA to estimate GFR by using Serum Creatinine
Define the Cockcroft-Gault equation
CrCl= ((140 - age) x kg)) / (Scr x 72)
Add (0.85) after kg for female PT
Define Steady State and it’s General Rule
Drug intake is equal to elimination
5 half live to reach steady state AND for washout
Changes in a drugs concentration do not have an effect on it’s ______
Half-life
How does No Interval/Short Interval drug administration effect the concentration?
Less fluctuation
Same dosing rate but as an infusion
Cmax and Cmin changes will be minimal
How does Longer Interval drug administration change concentration?
More fluctuation
Longer interval, same rate
Cmax and Cmin changes will be higher toward Cmax
Regardless of No Interval / Short Interval / Long Interval drug administration, what remains the same?
Average plasma concentration
Dosing doesn’t change time to steady state as long as _____
Half life remains constant
If a fluctuation in plasma concentration occurs, what controls the magnitude of fluctuations?
Controlling dosing interval
Shorter= decreased fluctuation
Longer= increased fluctuation
Define Maintenance Dose
Does req’d to replace amount of drug lost from body to maintain plasma concentration
What are two benefits of changing a dose interval?
Achieve similar steady-state concentrations
Limited dosage forms (oral)
What is an advantage of changing a dose?
When goal is to maintain steady therapeutic concentrations
What are two benefits of changing a dose and interval?
For substantial dose adjustment w/ limited dose forms
Narrow therapeutic index drugs w/ target concentrations
If a drug is given more than once daily then adjust ______
but if it’s given daily or less adjust the _____
Interval
Dose
Define Loading Dose
Higher dose of a drug to raise concentration to desired level or steady state concentration followed by a maintenance dose
When is a loading dose used?
When therapeutic concentrations of drug in plasma is needed rapidly/initially
Time to reach a steady state concentration depends on ?
Elimination half life
What pharmacokinetic variables influence dosage regimens?
Absorption
Volume distribution
Clearance
Define Potency
Amount needed to cause a response, determined by half life
Define Efficacy
Drugs ability to produce desired result, determined by height of log-dose response curve
More important than potency
Define Effectiveness
Degree of success in producing desired effect
Graded response takes into account what three variables?
BP
Enzyme activity
Muscle tension
Define Quantal Response
Number of subjects showing an all or nothing response
Pain
Death
Number anesthetized
The higher a drugs therapeutic index means what?
Safe the drug is and less monitoring is required
What is the lab monitoring rule for therapeutic indexes?
Small index requires plasma concentration monitoring
Define Agonist
Drugs that activate a receptor
Define Partial Agonist
Drug can act as an agonist or antagonist
Define Antagonist
Drug reduces/prevents responses
Define Inverse Agonist
Binds to same receptor as agonist but induces response opposite of an agonist
Define Competitive Antagonist
Binds to same receptor as agonist but reduces potency and efficacy of agonist
Define Irreversible Antagonist
Permanently antagonizes agonist through covalent bonds and prevents agonist binding and reduces efficacy
Define Indirect Agonist
Inhibits termination of an action of endogenous agonist
Define Allosteric Agonist
Binds to different receptor sight and indirectly blocks agonist
Define Drug Specificity
Drug has one effect and only one effect
Define Drug Selectivity
Greater selectivity for a receptor means fewer adverse reactions caused
General rule is that if a drug dose goes up then ____?
Selectivity goes down
Define Down Regulation
Decrease in number of receptors due to continuous prolonged exposure
Define Desensitization
Result of down-regulation
Requires an increase drug concentration to cause desired effect
Define Up-Regulation
Increase in number of receptors
3rd trimester pregnancy increase of uterine oxytocin receptors
Define Supersensitivity/Hypersensitivity
Enhanced response from long term exposure and abrupt cessation of drug
Give 4 examples of drugs who do not act at receptors?
Osmotic diuretics
Detergents
Antacids
Chelating agents
Define a Chemical Agonist and give an example
Inactivates an agonist by not allowing agonist able to bind to activating receptor
Protamine Sulfate
Define Physiologic Antagonist and give an example
Drugs that compete for interacting with opposing regulatory pathways
Epi and Ach
Preganglionic neurons originate with ____
Postganglionic nuerons originate at _____ and terminate at ____
CNS
Ganglion, effector organ
What are the two types of receptors?
Nicotinic neural Nicotinic muscluar (Muscarinic, A, B D)
What are the neurotransmitters?
Ach
NE
Epi
D
Parasympathetic preganglionic nerves originate from _____ and leave via ____
CNS
Cranial and sacral regions
Parasympathetic reganglionic neurons are _____ than postganglion
Longer
Sympathetic preganglionic nerves leave the CNS via ____
Thoracic
Lumbar
Sympathetic preganglionic nerves are ____ than postganglion nerves
Shorter
Parasympathetic postganglionic nerves result in a ___ response while sympathetic postganglions result in a ___ response
Discrete
Diffuse
3 examples of chemical signaling
Neurotransmitters
Hormones
Local mediators
What effects do acetycholinesterase inhibitors have on the body?
Prolong Ach action at muscarinic sites as an indirect agonist
Difference between endocrine gland and exocrine gland
Endo- ductless secretion into bloodstream
Exo- duct secretion to environment
M1 muscarinic receptors
Nerves
Salivary/stomach secretions
CNS
M2 muscarinic receptors
Cardiac cells
Bladder
Smooth muscle
M3 muscarinic receptors
Bladder
Exocrine glands
Smooth muscle
Cholinergic agents modulate Ach effects in what 3 ways?
Agonist
Antagonist
Indirect agonist
Drugs that mimic or prolong actions of Ach are called ?
Parasympathomimetics
Cholinomimetics
Drugs that antagonize or block actions of Ach are called ?
Anticholinergics
Cholinergic agonists cause what effects on the body?
DUMBBELLS Defecation Urination Miosis Bradycardia Bronchospasm Emesis Lacrimation Lethargy Salivation
Sweat and salivary glands increase secretions from what types of stimulation?
Cholinergic and Sympathetic
What are the major therapeutic uses for cholinomimetics?
Anti-cholinergic OD Glaucoma Xerostomia Reduced GI/GU motility Alzeihmers Myasthenia Gravis Reversal of Curare-induced neuromuscular paralysis
Don’t give cholinergic agonists to PTs with what diseases/illnesses?
Bradycardia/hypotension Asthma Peptic ulcers GI obstruction GU obstruction Parkinson's Disease
What are the cholinergic agonist effects on eye muscles and pupils?
Radial Iris- a1 SNS conraction, mydriasis
Circular Iris- m3 PNS contraction miosis
Ciliary- B2 SNS relaxation/M3 PNS contraction accomodation
How does the eye accomodate for close vision?
Tightens cilliary muscles allowing lens to become more rounded
What is the cholinergistic effect on eyes?
Muscarinic receptors contract circular muscles (pinpoint)
Produces a spasm of accommodation
Lens bulges for near vision
What is the cholinergistic use for clinic?
Refractive measurements
Ophthalmoscopic exam of retina
What is an example of a cholinergistic drug used in clinic for eyes?
Pilocarpine- cholinergic agonist
How do cholinomimetics exert their effect?
Increases resistance to degradation by cholinesterases
Increases selectivity for muscarinic receptors relative to nicotinic receptors
Why is acetylcholine not used in clinic often?
Poor bioavailability, rapidly hydrolyzed by GI tract and inactivated by acetylcholinesterase
Acetylcholine is nonspecific for what receptors?
Nicotinic and muscarinic
Although not used often, what is a use for acetycholine such as Miochol-E?
Induces miosis for eye procedures
What effect does pilocarpine have on the eye?
What effect does it cause on the rest of the body?
Increases aqueous humor outflow by contracting the ciliary muscle
Stims lacrimal/salivary secretions
What is a clinical indication for using Pilocarpine?
Reduce intraocular pressure in glaucoma PTs (angle-closure and open-angle)
What medication is prescribed to prevent post-operative intraocular pressure associated with laser surgery?
Pilocarpine
What medication is given to PTs w/ Xerostomia?
Pilocarpine
Post radiation therapy for head/neck tumor
Sjogren’s Syndrome (autoimmune disease destroys salivary/lacrimal glands)
What are the adverse effects of Pilocarpine use?
Miosis
Decreased far vision
What is the normal flow of aqueous humor through the eye? How is this inhibited?
Ciliary body to trabecular mesh work
Angle-closure: increased IOP from posterior chamber pushes iris against mesh work and closes ocular angle
What is the mechanism of action for Bethanechol?
Cholinergic agonist increases bladder muscle tone causing detrusor muscle contractions and trigone sphincter relaxation increasing urination
What is the clinical indication for Bethanechol?
Acute postoperative/postpartum non-obstructive urinary retention
Neurogenic atony of bladder w/ retention/ileus
What are the contraindications for Bethanechol use?
Physical obstruction of GI/GU Bladder strength is questionable Asthma Peptic ulcer disease Bradycardia
What is the indirect action of acetylcholinesterase inhibitors?
Inhibit actetylcholinesterase from metabolizing Ach causing a prolonged effect
What is the mechanism of action of Edrophonium?
Plant-derived reversible competitive Achesterase inhibitor that increases Ach potency by inhibiting the molecules destruction but is short lasting, 30sec-10m
What is the clinical indication for using Endrophonium?
Tensilon Test for Myasthenia Gravis and adjunct for treatment
Evaluates emergency Myasthenia crisis
Used as curare antagonist to reverse non-depolarizing neuromuscular blocking agents
What is an example of a medication that Edrophonium would not be useful using to treat?
Depolarizing neuromuscular agents
Succinylcholine chloride
What is the contraindications for using Edrophonium?
GI/GU obstruction
Bladder wall strength is questionable
What is the MOA for Physostigmine Salicylate
Plant derive competitive Achesterase inhibitor that potentiates its action by preventing destruction
What is the clinical indication for Physostigmine Salicylate?
Reverse CNS effects of Achergics
Routine use is not recommended due to adverse effects
What are the possible adverse effects of using Physostigmine Salicylate for routine use?
Delirium/agitation
Hallucinations
Hyperthermia
Supraventricular tachycardia
What type of monitoring should be used for Physostigmine Salicylate?
ECG
Vitals
Seizures since it can cross BBB
What are the contraindications for using Physostigmine Salicylate?
GI/GU obstruction
Bladder wall integrity is questioned
Respiratory distress/seizures
What is the MOA for Neostigmine?
Synthetic competitive inhibitor that prolongs effect by preventing destruction
What is the clinical indication for using Neostigmine?
Symptomatic treatment for Myasthenia Gracis
Reverses nondepolarizing neuromuscular agents
What are the two formulations for Neostigmine?
N. Bromide- tablet
N. Methyl Sulfate- IV
Why would the use of Neostigmine be preferred over Physostigmine?
More polar, does not cross CNS, no seizures
PTs with what conditions should be warned before using Neostigmine?
Asthma
Peptic Ulcer
Bradycardia
What are the contraindications for Neostigmine?
GI/GU obstruction
Bladder wall integrity is questioned
What is the MOA for Pyridostigmine Bromide
Synthetic
Pyridostigmine is preferred over neostigmine because?
Longer duration
Fewer GI symptoms
Allows for better transmission of impulses across neuromuscular junction
What is the clinical indication for Pyridostigmine Bromide?
Myasthenia Gravis treatment
Reverses nondepolarizing neuromuscular blocking agents
Nerve agent pretreatment pyridostigmine
Pyridostigmine Bromide has historically served as _______
Nerve Agent Pyridostigmine Pretreatment (NAPP)
What are the cautions for using Pyridostigmine?
Peptic Ulcer
Bradycardia
Asthma
What are the contraindications for Pyridostigmine Bromide?
GI/GU obstruction
Bladder wall integrity is questioned
Most noncompetitive (irreversible) Ach inhibitors find their uses as what two things?
Insecticides
Nerve agents
Increased Ach at the nicotinic receptors can lead to what issues?
Seizure
Coma
Cardiac arrhythmia
Respiratory arrest
What are examples of Irreversible Acetylcholinesterase Inhibitors?
Ecothipoate- eye drops for glaucoma, target postganglionic ParaSymp junction
Sarin- mimics insecticides
Parathion- insecticide
What is the MOA of Echothiophate Iodide?
ONLY noncompetitive Achesterase inhibitor used on a regular basis
What is the effect of Echothiophate Iodide on the eye?
Contracts ciliary muscles to increase aqueous humor flow
What are the adverse effects of using Echothiophate Iodide for glaucoma?
Miosis Decreased accommodation (far vision)
What is the MOA of Pralidoxime?
Reactive cholinesterase (mainly outside of CNS) that were inactivated by phosphorylation from organophosphate pesticides
What is the most critical part of Pralidoxime’s MOA?
Slows aging process of phosphorylated cholinesterase to non-reactive form
Reverses paralysis of respiratory muscles
The use of Pralidoxime relieves what symptoms?
Salivation
Bronchospasm
What is the form of Pralidoxime for chemical warfare?
ATNAA- reactive cholinesterase
What are the clinical indications for using Pralidoxime?
Treat pesticide poisoning (nerve agents of organophosphate class)
OD of anticholinesterase drugs from treating myasthenia gravis
What are the adverse effects of using Pralidoxime?
Anticholinergic effects: anticholinergic drug symptoms
How do acetylcholine and acetycholinesterase interact?
Pos charge of acetylcholine attracted to ionic site of acetylcholinesterase
Hydrolysis catalyzed to form choline and acetic acid
How do cholinesterase inhibitors and acetylcholinesterases react with each other?
Partial pos phosphorus attracted to partial neg serine
Nerve agent binds to serine hydroxyl group on achesterase
Prevent Ach from interacting with cholinesterase enzyme and being broken down
How do Pralidoxime and Achesterase react with each other?
Pralidoximes N attracted to Ach neg charge
Pralidoxime removes Ach inhibitor
Achesterase regenerated
_____ is the major neurotransmitter of the PNS
What other three areas is it seen in?
Ach
CNS, Symp/ParaSymp NS, Somatic NS
How can the degeneration effects of Alzheimers be slows?
With drugs that increase Ach concentrations in CNS by inhibiting central Achesterase
What are 4 drugs that could be used to increase Ach levels in Alzheimer’s PTs?
Tacrine- multiple doses/day, hepatotoxic
Donepezil- daily dose preferred
Galantamine- metabolized by CYP2D6/3A4
Rivastigmine- Patch form better tolerated
Nicotine is an example of what type of stimulant?
Ganglionic
What effects does Nicotine have at low doses? What effects a high dose?
Low- Depolarizes autonomic ganglia causing euphoria/arousal
High- blocks autonomic ganglia causing decreased BP and possible respiratory paralysis
Where does a greater amount of nicotine absorption take place?
75% smoke held in mouth
95% smoke held in lungs
Anticholinergic agents block Ach interaction with what type of receptors?
Muscarinic
Nicotinic
Define M Receptor Antagonist
Antimuscarinic
Define Nn receptor agonist?
Why is this not usually used?
Ganglionic blocker
Blocks both Symp/ParaSymp transmission
Defein Nm receptor Agonist
Neuromuscluar/skeltal muscle blocking agent
Anticholinergic agent effects are the opposite of ? stimulation
Cholinergic
What is the saying for remembering the S/Sx of anticholinergic agents?
Blind as a bat, Mad as a hatter, Red as a beet, Hot as a hare, Dry as a bone,, Bowel/bladder lose their tone,
Heart runs alone
What are the major therapeutic uses of Anti-Muscarinic agents?
Reduce glandular/bronchiolar secretions before anesthesis Induce sedation Alleviate motion sickness Reduces vagal stimulation Ophthalmic mydriasis/cycloplegia Reduce GI smooth muscle spasms Treat bronchospasms Control cholinergic agonist intoxication Parkinson's Disease
What are the contraindications for Anticholinergic Agent use?
Narrow angle glaucoma Angina Alzheimers Asthma Diarhhea Increased heat injuries Myasthenia gravis
What is the prototype anticholinergic?
Atropine
What are the Anticholinergics for the eye?
Cyclopentolate
Tropicamide
What are the Anticholinergics for GI?
Dicyclomine
Belladonna Alkaloids
What are the Anticholinergics for the lungs?
Ipratropium
Tiotropium
What are the Anticholinergics for GU?
Oxybutynin Darifenacin Solifenacin Tolterodine Fesoterodine Trospium
What are the Anticholinergics for Parkinsons?
Benztropine
Trihexyphenidyl
What is the MOA of dopamine?
Inhibits muscarinic actions of Ach on post-gang cholinergic nerves
Atropine is a ____ and _____ anticholinergic
Central
Peripheral
What are the pharmacodynamic effects of atropine?
Reduces oral secretions
Relieves broncho constrictions/spasms
Stops vagal cardiac slowing/bradycardia
Asystole
What are the clinical indications of atropine?
Mydriatic/cyclopegic diagnostic agent
Bradycardia
Relaxes upper GI
Cholinergic OD
What has to be monitored during atropine administration?
HR
BP
Mental status
What are the clinical uses for anticholinergics for the eye?
Diagnostic procedures requiring mydriasis and cyclopegia
Refractive measurement
Ophthalmoscopic exam of retina
What is the MOA of anticholinergics for the eye?
Produces cycloplegia by paralyzing ciliary muscles
Loss of accommodation
Mydriasis by blocking parasympathetic tone
What is the MOA of anticholinergics for GU use?
Dec bladder muscle tone causing detrusor muscle relaxation and sphincter constriction causing urinary retention
What is the clinical indication for using anticholiinergics for GI use?
Overactive bladder w/ incontinence, urgency and frequency
What are the adverse effects of using anticholinergics for GI use?
Dry mouth
Constipation
Site reaction/itching of patch
Stopped on
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