Central Nervous System Drugs Flashcards
Cerebrum
Thinking portion: Perception, Speech, Conscious motor movement, Skeletal muscle movement, memory, smell
Higher brain functioning
Thalamus
All nerve endings come here
Relay center: Sounds, sights, pain, touch, temperature.
Sends out motor response - needs to go back to the had to tell it to take it off the burning iron
Controls mood and motivation
- Associated with bipolar, anxiety, panic disorder, OCD
Hypothalamus
Ventral to Thalamus
Controls homeostasis
Major visceral control center: Hunger, thirst, water balance, body temp
Part of limbic (emotional balance)
Connection with brainstem (HR, RR, BP, Pupil size)
Plays a big part in the autonomic system
Cerebellum
Little brain at base of brain
Controls: Muscle movement, balance, posture, tone
Recieves info on vision, position, equilibrium, touch, and calculates strength
Injury results in uncontrolled jerkiness
A lot of Parkinson drugs work here
Brain Stem
Connects spinal cord to brain
Medulla oblongata (A lot of vital signs are regulated here), pons and midbrain here
Major relay center
Major reflex and control center: Breathing, Heart rate, swallowing, coughing, vomiting, vision
Spinal cord
Transmits to and from brain
Disruption: Paralysis, Paresthesia
Afferent nerves - to the brain
Efferent nerves - away from brain
Limbic system
Group or series of brain pathways
Responsible for emotion and mood
Some pain meds designed to effect Limbic system due to the emotional factor or pain
Reticular Activating System
Responsible for heightened alertness
Sleep meds designed to slow down RAS
Some motor units involved
Basal Ganglia
Responsible for Posture and movement
Cognitive function.
Blood brain barrier
Protects brain from pathogens and toxins
Supplies Oxygen, glucose, and nutrients
CNS drugs must penetrate
Neuron parts
Dendrites come before cell body
Carry message to the cell body
Cell body interprets message and pushes info down the axon.
Transfers to another nerve through the synapse
Monoamines
Dopamine. Epinephrine, Norepinephrine, Serotonin.
Amino Acids
Asperate, Aminobutyric acid (GABA), Glutamate, Glycine.
Gamma Aminobutyric acid (GABA)
Inhibits over excitation of brain
Slows things down
Used for seizure medication and sleep disorders
Opiod peptides
Dynorphins, Endorphins, Enkephalins
They are endogenous; therefore the body makes it’s own opium.
Nonopioid peptides
Neurotensin, Oxytocin, Somatostatin, Substance P, Vasopressin
Substance P
Pain control
Acts as a neurotransmitter
Has a role in interpreting pain
Has a role in regulating self produced endogenous analgesic response.
Big reason why we have different pain tolerance levels.
Actions of drugs
Blocking the reuptake of neurotransmitters
Blocking the enzymes that break down the neurotransmitters
Stimulating specific receptor sites when neurotransmitter is unavailable
Stimulating presynaptic nerve to release greater amounts of neurotransmitter
Pain definition
Whatever the experiencing person says it is and wherever he says it does.
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Four phases of pain
Transduction
Transmission
Perception
Modulation
Transduction
Stimulation of first nerve; at the site of injury
Injured tissue release chemicals that propagate pain messages such as prostoglandins or kinnins or histamines (become neurotransmitters)
Neurotransmitters stimulate or sit on nociceptors (nerve ending) located on skin, connective tissue, muscle, circlulatory system, thoracic, abdominal, and pelvic areas.
Stimulated by trauma, injury or chemical mediators.
Stimulates first nerve
Transmission
Nerve 1 to the spinal cord then to the brain
Pain stimuli enters spinal cord in the dorsal horn
Substance P is released in response to pain (a peptide in the dorsal horn) (Acts as neurotransmitter)
Glutamate and ATP also act as neurotransmitters
Differences here may be why we have different pain tolerances.
Afferent Neurons
Carry signals TO CNS
Pain begins in nociceptors in afferent neurons and gets carried to CNS
Perception of pain
Pain impulse reaches brain
Brain now has a conscious awareness of pain sensation
LIMBIC SYSTEM ACCOUNTS FOR EMOTIONAL RESPONSE
Higher cortical structures will identify as “pain”
Modulation
Brain interprets and decides what to do with the information
Pain message is inhibited through this phase
Descending from brain to spinal cord, we produce another set of neurotransmitters that will impeded pain impulse
Neurotransmitters include serotonin, norepinephrine, neurotensin, GABA, our own endogenous opioids
Modulation of pain
Within spinal cord are opioid receptors called kappa and mu.
Endogenous opioids can block kappa and mu
Exogenous opioids or opioid medications kick off the endogenous opioids because they are stronger and block kappa and mu
If kappa and mu are not blocked then move to thalamus in brain
Opioid Receptors
Mu and Kappa
(And Delta… red headed step child no one cares about)
Mu most important from a pharmacological stand point
Responses of an activated Mu receptor
Analgesic, Respiratory depression, sedation, euphoria, Physical dependence, Decreased GI motility
Responses of and activated Kappa receptor
Analgesic, Sedation, Decreased GI motility, Miosis
Miosis
Pinpoint pupils
Endorphins
endogenous opioids, enkephalins, and dynorphins are made in own body
Released in synapse and bind with opioid receptors on (mu and kappa recepters) dorsal horn to prevent further transmission of painful stimuli.
Nociceptive pain
Pain caused by damage to the body.
Somatic and Visceral
Somatic Pain
Pain to skin, muscle. More superficial. Injury to tissues.
Visceral pain
Dull, throbbing, poorly localized. Deep tissue; organs.
Neuropathic pain
Pain in the nerve pathway. Hardest to treat. Tingling, burning, stabbing, radiates. Usually long term.
Vascular pain
Caused by spasms which cause inflammation which causes pain. Migraines an example
Psychogenic pain
No cause; in patients head
Phantom Pain
Nerve endings still raw from amputation. Brain is interpreting the pain wrong. (Egg.. I mean Leg pain when there is no leg). Will go away within 6 mo-1 year.
Acute pain
Organic cause: Common
Environmental contributions and family involvement: small
Insomnia: Unusual
Treatment goal: Cure
Usually has a physical cause that can be treated
Chronic pain:
Harder to treat than acute. Can be life changing.
Dependence and tolerance to medication is common.
Psychological component: Often a major problem
Organic cause: Often not present
Environmental contributions and family involvement: Significant
Insomnia: Common
Treatment goal: Functionality
Pain lasting longer than 3 mo or longer than medically expected.
Signs of acute pain
Hypoxia
Hypercapnia (Hanging on to CO2 from holding breath)
Hypertension
Tachycardia
Emotional difficulties
If left untreated can lead to chronic pain
Chronic pain - 4 subtypes
- Pain that persists past the normal healing time for an acute injury
- Pain related to chronic disease (arthritis)
- Pain without identifiable organic cause
- Pain that involves both the chronic and acute pain associated with cancer (not worried about them about becoming addicted. We treat differently)
Consequences of unrelieved pain
- Stress hormone response
- Impaired muscle movement
- Quality of life changes (Decreased social relationships, decreased sleep, depression, anger, hopelessness)
Barriers to pain management: The professional
- Lack of knowledge about pain medication
- Misconceptions
- Inadequate assessment
- Concerns about opioids (addiction, respiratory depression, side effects)
Barriers to pain pain management: The patient and family
Stoicism (Lack of reporting pain, pain is weakness)
(Supposedly men complain of pain less then women… apparently they needed to include our husbands in this study)
Concerns about medication (Addiction, just say no, side effects)
Medication administration (confusion about dose, times, etc)
True or false: Pain is a natural consequence of getting old.
False
True or false: Older patients don’t feel pain as acutely as younger
False: Transmission of pain may be altered by chronic disease, but they will still feel it.
True or false: Older patients can’t reliably report pain
False: Make sure hearing aids are in and glasses on if using a pain scale.
What is the first step in pain management??
Assessment!
What do we need to know about the patient’s pain?
Location Severity Type Duration Effect of daily life
What are some non-pharmacological treatments?
Heat for muscle, Cold for acute injury, Accupuncture, Massage, Biofeedback, Guided imagery, Relaxation, Exercise, Trancutaneous Electrical Nerve Stimulation (TENS)
Opioid agonist
Occurs when opioid “Turns on” the opioid receptors. They kick our endogenous opioids off and are able sit on the receptors longer, thus causing better and longer pain relief.
Opioid Agonist Effects
Analgesia, sedation, mental clouding, Euphoria, Respiratory depression, Miosis, Decreased GI movement, Depression of cough reflex, Orthostatic hypotension, Stimulate vomiting reflex.
Opioid Kinetics
Absorption: Good oral (Thats what she said) and Large first pass effect
Metabolism: Hepatic
Elimination: Renal, Feces (With morphine when given PO)
Onset: 15-30 minutes
Duration: 3-7 hours
Opioid Cautions
Contraindicated for patients with a TBI, respiratory depression, pts receiving other CNS depressants, head injury.
Dose reduction may be necessary in elderly due to altered pharmacokinetic properties.
Drug addicts assess case my case. Monitor how much. May give a lower dose.
Opioid Adverse effects
CNS: mood changes, lethargy, delerium, euphoria, pupillary constriction
Respiratory: Decreased RR, Resp Arrest, apnea
Cardiovascular: Hypotension, bradycardia, Cardiac arrest, shock, coma
GI: N/V, constipation
GU: Urinary retention (Watch with elderly men with BPH)
Histamine release: Pruritis and uticaria (May need to give benedryl)
Why would we give someone having a Heart Attack opioids?
Opioids cause bradycardia and lower BP
Opioid drug interactions
Possible with any other hepatically cleared drug (Will increase opioid level or other drug level)
Potentiation of sedation and respiratory depression
Caution with other CNS depressant drugs including alcohol
Opioid Patient Education
Correct any fears or misconceptions about pain meds
Reassure that you will listen and act on their reports of pain
If patient is going home with a prescription, avoid operating heavy machinery, driving, alcohol or other CNS depressants, Storage of drugs (away from children)
Educate on High Fiber diet
Treatment of an opioid overdose??
Narcan
Nursing interventions
Assess pain prior to and during therapy Use pain assessment tool Assess vital signs, esp resp Keep pulse ox on pt Administer stool softeners/laxatives prn Assist patient when getting out of bed
Strong Narcotic Agonists are ordered when pain level is a ___________ out of 10 and higher
7
Morphine is ordered in ______
mg
Morphine is prototype
fentanyl is ordered in __________
mcg
Fenanyl is ______ times more potent than morphine
100
Meperidine (Demerol)
Synthetic; less resp depression than morphine. Less likely to have constipation.
Methadone
Half life 36 hours so we can help patients with withdrawls
Oxycodone (Percodan, Percocet (Oxycodon + Tylenol))
Prescribed for moderate to strong pain
Often mixed with tylenol
Oycodone has more of an effect on the brain
Tylenol effects more peripheral
Wont need as much of narcotic if mixed with tylenol
Morphine mechanism of action
- Occupies mu and kappa in brain and dorsal horn or spinal cord which…
- Reduces the release of neurotransmitters in the presynaptic space which…
- Produces hyperpolarization of postsynaptic dorsal horn neurons
- These actions prevent transmission of nociceptor pain
- Decreases release of substance P which modulates pain perception.
Morphine has high first pass effect.
Hydrocodone (Vicodin)
Considered a Mild Narcotic Agonist
Codeine
#1 drug abused
Schedule 2 drug
Codeine is ____________ the potency of morphine
1/6
Codeine mechanism of action
Similar to morphine
Acts on opioid receptors in the CNS to produce analgesia (less than morphine), euphoria, and sedation
Acts on medullary cough relfex center to depress the cough reflex.
Has drying effect on mucous membranes
Codeine adverse effects as cough suppressant
Dry mouth, drowsiness, sedation.
When dosed as an analgesic similar adverse effects as morphine
Less physical dependence than with morphine
Less sedation, euphoria
Caution use of codeine with…
need their cough reflex. Patients with a chest tube, Patients who have had abdominal surgery, Stroke patients, patients with an aspiration risk.
Opioid Agonist-Antagonist
Have mixed opioid effects
Agonist as some receptor and antagonist at other receptor
Blocks opioid effect on one receptor while producing opioid effects on a second receptor.
May be good with addicts
Narcotic Agonist-Antagonist
pentazocine (Talwin) buprenophine (Buprenex) butorphanol (Stadol) nalbuphine (Nubain) Dont have to worry about resp depression. Prescribed for mild to moderate pain Often ordered for addicts
Drugs that end in -erase
break down neurotransmitters are destroy
Opioid Antagonist
High affinity for opioid receptor but cause no effect
Opioid antedote: Narcan
Tolerance
Body has become accustomed to the effects of the substance and that the patient must use more of it to achieve the desired effect
Develops to analgesia, resp effects, and euphoria
Dependence
Body physically dependent on drug.
Characterized by withdrawal symptoms when drug is discontinued
Physiological effects… not psychological
May need to taper medication when possible
Addiction
Psychological syndrome
Compulsive use of drug for secondary gain, not for pain control
Genetic, psychosocial and environmental factors influence the development of addiction.
Addiction to opioids rare for med reasons
Opioid Withdrawl symptoms
Sweating, runny nose, irritability, Increased BP, tremor, anorexia, N/V, diarrhea, cramps, muscle spasms, pupils dialated, seizure risk
Narcan (naloxone)
Adverse effects: hypotention/HTN
Given IV
Only stays in the system one hour
Have to monitor closely
Principles of pain management with opioids
Start with low dose and titrate up
Around the clock is better than PRN
Equianalgesia
Producing the same degree of analgesia
Equianalgesic dose charts show the dose of an analgesic required to produce the same effect as 10 mg of morphine. (Standard measure of pain relief)
ALWAYS COMPARING TO 10 mg OF MORPHINE
Inflammation Signs
Heat, Redness, Swelling, Pain, Loss of Function
We treat with corticosteroids
Inflammation process
Vascular resoponse (vasoconstriction and vasodilation) Cellular response (neutrophils)
Pathophysiology of inflammation - Vascular response
Occurs immediately after injury
Vasocostriction happens in the surrounding tissues first (10-15 min)
Then, vasodilation occurs (increased blood flow to the area)
Capillary permeability increases (Fluid accumulates in tissues so WBC can get into the tissue leaking fluid/swelling. Chemical mediators are released causing pain and impaired function
Pathophysiology of inflammation - Cellular response
WBC’s prepare for emigration by moving to periphery of blood vessels
WBC’s pass through cappilary walls into tissue spaces
Cellular debris or bacteria become attracted to WBC’s
Neutrophils and monocytes engulf the cellular debris
Pathophysiology of inflammation - Chemical response
Mast cells rupture and release biochemical mediators such as histamine, prostaglandins, and leukotrines. All which contribute to inflam.
Prostaglandins
Help regulate some parts of inflammation, body temp, pain transmission, platelet aggregation
Derived from an acid which is released from the cell membrane in response to stimuli
Acid is converted to prostaglandin by cyclooxygenase (COX) enzyme)
Prostaglandins effects
Increase uterine or other smooth muscle contraction
Decrease BP
Decrease gastric acid secretion and increase mucous production
Increase body temp
Increase platelet aggregation - clotting
Increase renal vasodilation
Increase inflammation and capillary permeability
Effect blood vessels and bronchials
COX 1
Synthesizes prostaglandins that are involved in regulating normal cells activity
Found in blood vessels, stomach, kidney
Leads to prostaglandin formation that protects gastric mucosa and helps maintain normal renal function and temperature
COX 2
Produces prostaglandins at sites of inflammation
Found in brain and kidney
Leads to prostaglandin formation that causes inflammation
Do not have any antiplatelet activity
Prostaglandins again
acid + cyclooxygenase (COX 1 or 2)
COX 1 again
Good! Normal cell activity Protects GI mucosa - Decrease HCl acid Blood vessels = Vasodilation = decreased BP Lungs and Bronchials = dilation Help renal function Promote platelet aggreagtion
COX 2 again
BAD Sensitive to pain Increase fever Increase inflammation Increase cap permeability
NSAIDS block ___________
Prostaglandins
NSAIDS are COX ____________
Blockers
Some may only inhibit 1 and some only 2
COX 1 on NSAIDS
Increase HCl acid (Therefore GI Ulcers and GI bleeds)
Increase risk for bleeding
Impaired renal function
Bronchoconstriction (Caution NSAIDS with Asthma and COPD)
COX 2 on NSAIDS
Decrease risk of colorectal cancer (fun fact)
Cause renal impairement
Decrease vasodilation; therefore increase vasoconstriction therefore risk of MI or Stroke
NSAIDS - Mechanism of action
Inhibit COX
Decrease production of prostaglandings
NSAIDS - Indications
Arthritis (both osteo and rheumatoid)
Mild to moderate pain
Fever
Inflammation
NSAIDS - Absorption
Oral
First pass effect variable between agents
NSAID - distribution
Highly protein bound
Onset: 30 min (inflammation response takes days to weeks)
Half life: range from 1.5 to 50 hours
NSAID metabolizes in the ____________
Liver
NSAIDS get excreted through the _________
Kidney
NSAID Adverse effects
GI distress, ulcers, bleeding Sedation, confusion Rash, fever Tachycardia Acute bronchospasm Renal: sodium and water retention; impairement Head ache, dizziness Tinnitus
NSAIDS cautions
Elderly may be more sensitive to adverse effects Asthmatics Ulcers or history of GI bleeds Renal disease Hepatic disease (Tylenol Bad) Pregnant women should no use Pts on anticoag therapy Gout Children with varicella or flu like symptoms
NSAIDS drug interactions
Increase effects of anticoags and antiplatelets
Intereferes with metabolism of these drugs: digoxin, phenytoin, cyclosporine, fluconazole
Aspirin Absorption
Occurs with 30 min depending on form gastric pH, presence of food
Mostly absorbed in small intestine
Suppositories are slower and have more variable absorption than oral forms.
Can give as a suppository
Aspirin - Antipyretic effect
Works on hypothalamus which is the body’s temp regulator
Aspirin - Anti-inflammatory effect
Inhibits prostaglandin synthesis
Aspirin - Analgesic effect
Pain is mediated by prostaglandins that synthesize pain receptors
ASA inhibits COX 2 which decreases prostaglandins
Aspirin - Anti-platelet effect
Has irreversible inhibition of throboxane A2
Which is a prostaglandin that indiced platelet aggregation
ASA cautions
Contraindicated for peptic ulcer patients or other bleeding disorders
Do not give alcoholics
Do not give with anticoag therapy
Do not give to gout patients, renal (depends on how bad kidneys are functioning), or liver
Do not give to children with fever or flu like symptoms
Use in caution with smokers
ASA causes sodium retention; therefore harder on the kidneys.
Nicotine is considered ____________; therefore do not give ASA’s
Ulceragenic
ASA - Pregnancy Category
First and Second trimester: Category C
Third Trimester: Category D
Salicylism is _______
Mild aspirin toxicity
Occurs with long term or high dose therapy
Signs and Symptoms: Headache, tinnitus, GI distress, resp stimulation, drowsiness or confused.
Treat by reducing the drug or stop therapy still together
Absorption rate effected with suppositories
Due to diarrhea, constipation, fever
We never know how much gets absorbed
Salicylate poisoning
Life threatening
No antidote
Signs and Symptoms are the same but more pronounced, occurs quickly.
Treat by gastric emptying and life support if needed. Charcoal
Prostaglandin synthesase inhibitors
Ibuprophen (Motrin, Advil)
Ibuprofen
Propoinic acids: fenoprofen, naproxen (ALEVE), fetoprofen
Acetic acids: indomethacin (Indocin), ketorolac (Toradol)
Ibuprofen Absorption
Mostly GI system
Slower if taken with food
Analgesic and antipyretic effects take 2-4 hours
Inflammatory response takes a few days to weeks (Usually need higher doses)
Highly protein bound (Stays longer in the system)
Ibuprofen Cautions
Ulcer, bleeding disorders
Contraindicated in heart patients
There may be a black box warning (May increase serious and potentially fatal cardiovascular thrombotic events, Serious GI events also listed)
Caution in renal patients (inhibition of renal prostaglandins can decrease renal blood flow)
Can increase BP
Can cause blurred vision and corneal deposits
Selective COX 2 inhibitors
celecoxib (Celebrex)
Cant use with patients with sulfa allgery
Someone with history of GI bleed this would be the best drug to put them on
Celebrex - Mechanism of action
Selectively inhibits the enztme COX 2
Inhibits prostaglandin synthesis
Celebrex - Indications
Arthritis ad relieve dysmenorrhea
Category D in third trimester
Doesn’t effect kidneys
Increase INR
Papa-aminophenol derivatives
Acetaminophen - ASA or APAP
Acetaminophen mechanism of action
Fever - direct action on the hypothalamic heat regulating center
Inhibits the action of chemical that causes vasodilation and sweating
Pain - not completely clear how it works
No peripheral prostaglandin synthetase inhibition which means no anti-inflammatory effect or platelet aggretation inhibition
Acetaminophen indications
Fever
Mild to moderate pain
Drug of choice for infants and children with flu or flu like symptoms and analgesic choice during pregnancy and lactation
APAP Absorption
Rapid and completely absorbed orally
APAP distribution
onset 30 min
peak 1-2 hours
Duration 4 hours
APAP is metabolized in the ________
Liver
APAP is excreted through the _______
Kidneys
APAP adverse effects
Rare
Rash, uticaria, nausea, fever, neutropenia, throbocytopenia, Jaundice (Liver problems)
APAP interactions
Use in caution with hepatic disease
Increased hepatoctoxicity with other drugs that cause liver damage
Major contraindication: hepatic disease, viral hepatitis, alcoholism
May exacerbate anemias
APAP overdose
Can be fatal
It is partially metabolized into a toxic metaboliite that your body converts to a nontoxic form with the help of glutathione
In an overdose, glutathione is quickly depleted
Accumulation of toxic metabolite occurs, resulting in liver damage
Mucomyst Acetylcysteine
Tylenol anecdote
APAP symptoms of toxicity
Anorexia, N/V, Pallor, Abdominal discomfort (RUQ pain in the first few days), Jaundice (Later stage) #1 poisoning in children
