Pharm Exam 1 Flashcards
Autonomic Nervous System (ANS)
Functions in homeostasis, stress response, and body tissue repair
Primary Neurotransmitters in ANS
norepinephrine + acetylcholine
Ligands
molecule that binds to another
Affinity
how well a drug can bind to the receptors in the ANS
Agonist
a ligand that alters receptor function and triggers a physiological response
Antagonist
a ligand that binds to a receptor but fails to activate physiological response (or blocks the response)
Signal transduction
cascade of intracellular events that occur when receptors located on target tissues are stimulated by a ligand
SNS Receptors
Adrenergic
Three Adrenergic Neurotransmitters
Norepinephrine, Epinephrine, Dopamine
Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
Metabolize norepinephrine and allows reuptake to occur. Also more slowly metabolizes epinephrine
Tyrosine
Needed in diet to produce Norepinephrine
Anaphylaxis
Narrowing of the airway
Low dose Dopamine
increases renal blood flow to try and wake up the kidneys
High Dose Dopamine
increases blood pressure or the pumping of the heart
Endrogenous
Produced inside the body
Exogenous
Produced by an outside force
Catecholamines
Can be neurotransmitters or neurohormones depending on where they are synthesized
Alpha 1 Receptors
Located in the smooth muscle and in the blood vessels, GI and GU tracts
Stimulation: production of muscle, bladder, and eye contraction
Alpha 2 Receptors
Located in the brain/pancreatic beta cells
stimulation: has an antiandrenergic effect which causes the bladder to relax and inhibits insulin release
Beta 1 Receptors
located in the cardiac cells
Stimulation: increase in HR and force a contraction
Beta 2 Receptor
Located primarily in the smooth muscle of the lungs/skeletal/detrusor and uterine muscles
Stimulation: relaxation of smooth muscles in the lungs to cause bronchodilation
Atenolol
Selective Beta One Blocker: this will be good for an asthmatic who needs a lower BP or HR
Selective
Act on a receptor site which induces the normally occurring action on that receptor site. Has less effects than non-selective
Non-selective
Act on more than one receptor site and has a broader range of effects with more side effects because it is innervating multiple receptors
Phenylephrine
Stimulation of the alpha 1s to constrict secretions. Shrinks the nasal vessels to decrease congestion
Which receptors do Norepi stimulate
A1, A2, B1
Which receptors does Epi stimulate
A1, A2, B1, B2
Midodrine
Alpha Adrenergic Agonist: treats orthostatic hypotension. Increases BP
Albuterol
selective Beta2 adrenergic agonist. Used to open the airway for someone with a high HR or BP
Isoproterenol
non-selective Beta 1 + Beta 2 adrenergic agonist. Not safe for someone with tachycardia or hypertension
Pheochromocytoma
a rare neoplasm that secretes catecholamines and is usually found in the adrenal medulla. This is a contraindication for an adrenergic sympathomimetics
Thyroid disease
This is a contraindication for an adrenergic sympathomimetics because thyroid hormone increase target cell responsiveness to catecholamines
Hypovolemia
Low blood volume. This is a contraindication for an adrenergic sympathomimetics because we don’t want the heart beating faster with little amounts of blood
TCAs
Inhibit the reuptake of norepinephrine. This is a contraindication for an adrenergic sympathomimetics
MAOIs
inhibits liver metabolism of norepinephrine and epinephrine. This is a contraindication for an adrenergic sympathomimetics.
Parasympathetic Nervous System
Cholinergic Receptors
Primary Neurotransmitter of the PNS
Acetylcholine (ACH)
Acetylcholine (ACH)
Formed in cholinergic nerve endings/located in brain, ANS, and neuromuscular junctions
acetylcholinesterase
The enzyme that breaks down ACH
Choline
Taken up by presynaptic neurons to make more ACH
Cholinesterase
The enzyme that breaks down Choline
PNS Receptors
Nicotinic + Muscarinic
Nicotinic
located in the CNS motor nerves and skeletal muscle and adrenal medulla
Activation by ACH causes muscle contraction and releases epinephrine from adrenal medulla
Muscarinic
located in the internal organs and activation by ACH has effects on cardiac, respiratory, GI, and GU
Direct Acting Ligands
bind to and activate receptors themselves to create a cholinergic response in the cholinergic receptors. This has widespread systemic cholinergic effects
Indirect Acting Ligands
inhibit the action of AchE which, in turn, has a cholinergic effect because more ACH is able to activate their synapses. This is used to improve muscle tone and strength
Bethanechol
Direct Acting Cholinergic agonist. Increases detrusor tone which causes contraction and then micturition which will empty the bladder
Carbachol
Direct acting Cholinergic agonist used to treat glaucoma by causing miosis (pupil constriction) which causes constriction which excretes fluid which decreases intraoccular pressure
Donepezil/Aricept
Indirect acting cholinergic medication that is a selective acetylcholinesterase inhibitor used for treatment of confusion for Alzheimer pts. More ACH in the brain may compensate for the loss of functioning cholinergic brain cells
Pyridostigmine
Acetylcholinesterase inhibitor used to treat Myasthenia gravis
Atropine
Parasympatholytic that stimulates HR, reduces salivation and GI spasms
Dicyclomine
Parasympatholytic that is used as a GI antispasmodic to treat IBS
Propantheline
Parasympatholytic used as an antimuscarinic to treat excessive sweating and for cramps/IBS/involuntary urination
Meclizine
Parasympatholytic: Used to treat motion sickness and vertigo
Scopolamine
Parasympatholytic that blocks acetylcholine. Can be given as a patch. Treatment for motion sickness. Has an anticholinergic side effect.
Glycopyrrolate
Parasympatholytic used to decrease oral secretions on oral patients. They are not really breathing so we want to stop salivary secretions to prevent buildup. Also used for cerebral palsy
Ipratropium/Atrovent
Parasympatholitic that blocks muscarinic receptors and opens airways and causes bronchodilation
Tiotropium
Anticholinergic for pts with COPD and works as a bronchodilator
Anticholinergic Contraindications
Glaucoma, GI Conditions, BPH or bladder obstruction, Cardiac Arrhythmias, tachycardia, MI, Renal or hepatic impairment, Pts taking antihistamines, antiparkinsonian drugs, MAOIs and TCAs
Physostigmine
Used to reverse the effects of certain drugs or subranges that interfere with nerve-muscle communication. Tx of severe anticholinergic toxicity.
Ipratropium
Anticholinergic used for Asthma because it dilates the lungs out
Blood brain barrier drugs requirements
must be highly lipid soluble to make it to the brain
Where do direct acting cholinergic medications effect
PNS because they do not readily enter the CNS
Myasthenia Gravis Definition
Chronic autoimmune neuromuscular disease. Weakness and rapid fatigue of muscle under voluntary control. Drug therapy for this disease includes CHOLINERGIC drugs and ACETYLCHOLINESTERASE inhibitors
Myasthenia Gravis Etiology
defect in the transmission of nerve impulses to muscles
Myasthenia Gravis Pathophysiology
Occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction. Or the NMJ.
Clinical Manifestations for Myasthenia Gravis
facial expression (diplopia: double vision). Dysphagia (trouble swallowing). Dysarthria (slurred speech) choking or aspiration risk. weakness of the eye muscles. SOB.
s/sx for Myasthenia Gravis
increase with action and improve with rest
Neostigmine
Acetylcholinesterase Inhibitor used to treat Myasthenia Gravis. Used for long term treatment of myasthenia gravis and as an antidote for nondepolarizing skeletal muscle relaxants used in surgery. Interrupt the enzyme to keep acetylcholine.
Contraindications: cholinergic responses
Does not cross the blood brain barrier
Pharmacokinetics of Neostigmine
Administered slowly intravenously because it is not absorbed well through GI, metabolized in the liver, excreted in the kidneys. Watch out for folks with hepatic issues, kidneys or liver problems.
Action of Neostigmine
Decreases the inactivation of acetylcholine in the synapses by the enzyme acetylcholinesterase because it reduces the enzyme.
Neostigmine
Medication given IV to put electricity through a muscle and see if it contracts
Pyridostigmine
indirectly increasing the concentration of acetylcholine at the neuromuscular junction and promoting increased cholinergic nicotinic receptor activation
SLUDGE
Indicators of a cholinergic overdose: Salivation, lacrimation, urinary incontinence, diarrhea, GI upset, emesis
Atropine
Works on the muscarinic receptors (not the nicotinic) so that you will see changes in the heart, smooth muscles, and glands when this drug is administered to reverse or stop the cholinergic crisis.
BAGPUDDLES
Bronchoconstriction, apnea, grey vision, pupil constriction, increased urination, diaphoresis, defecation, lachrymation, emesis, seizures. Overstimulation of the PNS
Alzheimer’s Disease
memory Loss, loss of other intellectual abilities serious enough to interfere with daily life. Etiology: most common form of dementia
Pathophysiology: Deficiency in cholinergic function in the cortex and basal forebrain
Drug therapy for Alzheimer’s Disease
- cholinesterase inhibitors
- n-mythyl-d-aspertate receptor antagonists
- cholinesterase inhibitor n-methyl-d aspartate receptor antagonist
Donepezil
Cholinesterase Inhibitor that is used to inhibit acetylcholinesterase and increases stimulation of cholinergic receptors in the CNS/PNS.
Crosses the blood brain barrier.
Side effects: increased Parasympathetic response
Pharmacokinetics of Donepezil
absorption with oral administration is good and is unaffected with food (PO). Peak of action is 3-4 hours. Metabolizm is in the liver, excretion is mainly in the urine.
Sick Sinus Syndrome
Sinus node dysfunction. This is not good for pts. taking a cholinesterase inhibitor
memantine/namenda
N-Methyl-D-Aspartate Receptor Antagonist which blocks flow through NMDA receptors which are a breakout of glutamine which is linked to Alzheimers.
memantine/namenda action
likes to glutamate receptor for an antagonist effect; binds to the magnesium site to block the excitatory function by slowing intracellular calcium accumulation
memantine/namenda pharmacokinetics
well absorbed orally, 100% absorption in the GI tract, partially metabolized in the liver
Managing Cholinergic Toxicity
- Hydration
- Activated charcoal
- atropine: antidote
Cholinesterase Inhibitor- N-Methyl-d-aspartate receptor antagonist
Combination therapy of donepezil and memantine used for pt. with severe dementia
Neurogenic Bladder
any condition that impairs afferent and efferent bladder from occurring.
Spastic Neurogenic Bladder
normal or small volume of urine but involuntary contraction happens. Brian or spinal cord damage (above T12) or detrusor sphincter dysregulation.
Flaccid Neurogenic Bladder
Large volume of fluid in the bladder, but there is a decrease in pressure so there is an absence of contraction. Can happen from peripheral nerve damage or damage of s2-s4 in the spinal cord.
Drug Therapy for Urinary Retention
Cholinergic Agonist
Bethanechol chloride
Cholinergic Agonist used to treat urinary retention. This is well absorbed in the GI tract, site of metabolism is unknown, does not cross the BBB, but crosses the placenta
Action of Bethanechol chloride
Parasympathomimetic agent, acts at the cholinergic receptors in the urinary and GI tracts to increase muscle tone and cause micturition
Parkinson’s Disease
chronic, progressive, degenerative disorder of the central nervous system characterized by resting tremor, bradykinesia, rigidity and postural instability. Cause of the nerve cell damage is unknown
Pathophysiology of Parkinson’s Disease
Progressive destruction of or degenerative changes in dopamine producing nerve cells in the substantia nigra in the basal ganglia, decrease in dopamine and increase in acetylcholine
Drug Therapy for Parkinson’s Disease
Dopamine receptor agonists, and COMT inhibitors
Levodopa-Carbidopa (Sinemet)
Dopamine Receptor Agonists used to treat Parkinson’s disease
Levodopa-Carbidopa (Sinemet) Action
Levodopa produces dopamine in the brain and carbidopa prevents the breakdown of levodopa in the blood so that it can get to the brain and we do not have to give as much as an initial dose. It is well absorbed in the small intestine after oral administration, primarily excreted in the urine.
Levodopa-Carbidopa (Sinemet) Cautions
Adverse effects: CNS (headache, anxiety, drowsiness, hallucinations) Cardiovascular (orthostatic HTN), increase in HR and decrease in BP. GI: Anorexia (loss of appetite) and N+V and teeth grinding.
MUST STOP TAKING MAOI
Cannot crush it.
MOA
Mechanisms of Action
Other drugs in the class of Levodopa-Carbidopa (Sinemet)
amantadine, pramipexole, ropinirole, selegiline.
Black Box for Levodopa-Carbidopa
risk for fulminant fatal acute renal failure. Check I+O, BUN, Creatinine, and GFR
GFR
glomerular filtration rate: greater than 60 is normal
Ropinirole
Can be used with restless leg syndrome. Can also be paired with Levo/Carb if LC is decreased. Well absorbed orally (p=1-2h) steady concentration state of 2 days, 40% protein bound, metabolized in the liver, 1/2 life=6 hours
Tolcapone
Catechol-o-Methyltransferase Inhibitors (COMT) Add on therapy with LevoCarb. 2-3 hour half life. Tapered off over 2 weeks. Dont quit suddenly
Tolcapone Pharmakokinetics
absorbed rapidly and is highly protein bound, metabolized in the liver, crosses the placenta, excreted in the feces and urine
COMT
this enzyme breaks down dopamine and levodopa. If we stop the enzyme, we stop the process from happening. Inhibits the metabolism of levodopa in the bloodstream, may also inhibit COMT in the brain and prolong the activity of dopamine at the synapse
Adjudivent
Add on therapy
Other drug in Tolcapone’s class
entacapone
entacapone
Adjudivent for Levo//Carb. COMT and Decarboxylase Inhibitor. Entacapone alters levodopa to increase serum concentration. Contraindication with MAOI
entacapone Adverse Effects
GI (diarrhea, N+V, and drug induced colitis) somnolence (not interactive), dyskinesia (bad or dysrhythmic or unusual movement) bruxism (teeth grinding)
Anticholinergics Overdose s/sx
hyperthermia, mydriasis, delirium, tachycardia, myoclonic movements, seizures, coma, and respiratory arrest. Affects the PNS. Cycloplegia: paralysis of ciliary muscles of the eyes
Atropine Sulfate
is extracted from the belladonna plant or prepared synthetically. It is a salt that is very soluble in water. This medication is also classified as a muscarinic antagonist.
IV peak: 2-4 minutes and lasts 4 hours
Well absorbed in all forms of administration. Metabolized by liver and excreted in the urine
Atropine Sulfate Action
blocks the effects of acetylcholine at muscarinic cholinergic receptors that mediate the effects of parasympathetic postganglionic impulses. Pupils dilate
Atropine Sulfate Use
bradycardia, preoperatively, eye drops, and as an antidote
Centrally Acting Anticholinergics Adverse Effects/Contraindications
CNS (disorientation, confusion), Cardiovascular (HTN, Tachycardia, heaviness of limbs)
glaucoma, GI, myasthenia gravis, cardiovascular
Dicyclomine Hydrochloride Use and Administration
Gastrointestinal Anticholinergic used for peptic ulcer disease. Oral and parenteral administration. Metabolized in the liver, excreted in the kidneys
Dicyclomine Hydrochloride Action
GI smooth muscle relaxant, blocks the effects of acetylcholine at muscarinic cholinergic receptors to help with Irritable bowel syndrome
oxybutynin medication and Pharmacokinetic
Urinary antispasmodic that is metabolized in the liver and excreted in the urine. Used for bladder instability in patients with uninhibited and reflex neurogenic bladder overactive bladder, incontinence, urgency and frequency
oxybutynin action
acts directly on the smooth muscle and inhibits the effects of acetylcholine at muscarinic receptors cause antispasmodic effects to reduce urinary bladder muscle
oxybutynin caution
We cannot give someone who has urinary retention an antispasmodic. Max dose in elders: 2.5mg/PO/bid-tid. Typically given once daily at morning or night.
