Week 4: Pain, opioid use disorder, cannabis Flashcards
1
Q
Two examples of painful conditions with episodic flares without baseline pain?
A
migraine attacks
trigeminal neuralgia
2
Q
Nociceptive pain is:
A
somatic r/t bone or muscle involvement
visceral (r/t underlying solid or hollow viscous)
3
Q
What is the goal of buprenorphine for OUD?
A
Bring them from a 3/10 (withdrawal state) to a 5 or 6/10. Feels better but not “high”.
4
Q
What happens if buprenorphine is given to a patient on another opioid? Why?
A
They go from 9/10 (high) to a 5/10 and feel like crap.
That is because buprenorphine is an PARTIAL OPIOID AGONIST. Therefore it has a high affinity to the opioid receptors and kicks other opioids off.
5
Q
How is buprenorphine administered?
A
Sublingual or IV (NOT PO)
No talking or drinking at the same time (this will decrease the effectiveness)
Don’t smoke prior (will dry-out their mouth and decrease absorption).
6
Q
If buprenorphine is not working ask this…
A
How are you taking it?
7
Q
Why naloxone with the buprenorphine?
A
If naloxone is take sublingually with buprenorphine= no effect.
If naloxone is injected = opioid withdrawal.
8
Q
What is delerium tremens? Sx?
A
Delirium tremens (severe, life-threatening manifestation of alcohol withdrawal).
Sx: agitation, aggression, irritability
Confusion
Severe autonomic hyperactivity (trembling, sweating, tachycardia, N + V
Impaired consciousness
Visual, tactile, auditory hallucinations
Tremors, seizures
9
Q
Drug interactions with buprenorphine/ naloxone?
A
Alcohol
Benzos
CNS depressants
10
Q
How many hours to achieve moderate withdrawal from heroin, morphine, hydrocodone?
A
12-16 hours for short acting
11
Q
How many hours to achieve moderate withdrawal from slow release products?
A
17-24 hours
12
Q
Why might someone go into withdrawal upon initiation of buprenorphine/naloxone treatment?
A
They already had opioid in their system “I was nervous so I took something”.
Buprenorphine is a partial opioid receptor agonist, therefore it will overtake opioid receptors being used by other opioid and cause withdrawal from the other drug
13
Q
What is the recommended starting dose for buprenorphine/naloxone therapy?
A
4 mg buprenorphine/1 mg naloxone
14
Q
When would you use a lower dose of buprenorphine/naloxone (such as 2mg buprenorphine/0.5 mg naloxone)?
A
Pt looking well, at a higher risk for withdrawal from other opioid possibly taken
15
Q
When would you use a higher dose of buprenorphine/ naloxone therapy (such as 6mg buprenorphine/ 1.5 mg naloxone)?
A
Pt in moderately severe withdrawal (COW score > 24)
16
Q
COW stands for?
A
Clinical opioid withdrawal scale
17
Q
What do you do on day 1 of buprenorphine/naloxone therapy if sx are controlled after 1-3 hours?
A
Titration for day one is complete
18
Q
What do you do on day 1 of buprenorphine/naloxone therapy if sx are NOT controlled after 1-3 hours?
A
If sx are not controlled = more medication
Increase by 2mg/0.5 or 4mg/1mg increments
19
Q
What is the maximum dose for buprenorphine/naloxone on day one of tx?
A
12mg buprenorphine/ 3 mg naloxone
20
Q
2 parts of the autonomic nervous system?
A
Sympathetic
Parasympathetic
21
Q
Max dose day 1: buprenorphine/naloxone therapy induction?
A
12mg buprenorphine/3 mg naloxone
22
Q
Max day 2 dose buprenorphine/naloxone induction?
A
16mg/ 4mg
23
Q
Why can’t someone resume methadone after 3 days of not having it?
A
The body looses tolerance to methadone quickly. Can lead to a fatal overdose.
24
Q
What is asthenia?
A
Body lacks strength/ looses muscle strength (i.e. wasting disease, anemia, cancer, disease of the adrenal gland).
25
What is the target dose for HOME dosing of buprenorphine/naloxone therapy?
12-16mg buprenorphine/ 3-4mg naloxone daily
| Max dose: 24mg/6mg
26
Other name for suboxone?
buprenorphine/naloxone
27
What is plasma?
55% of overall blood volume
liquid portion of blood, 90% water
Contains:
- fibrinogen
-albumin
-transports antibodies, proteins, nutrients, hormones
-also collects waste from cells and removes it
28
Plasma versus Serum?
Plasma:
-is a liquid.
-Contains fibrinogen.
-Contains albumin
-Obtained BEFORE the clotting of blood.
-Used to treat blood clotting related problems.
Serum:
-is a fluid (less dense than liquid, contains more matter particles).
- obtained AFTER clotting of blood.
- used for blood typing/ diagnostic tests.
29
What do primary afferent C nerve fibres convey?
Dull, perfuse burning pain.
| Unmyelinated.
30
What kind of pain to A beta fibres convey?
Sharp, well localized pain.
| Myelinated. (allows for more precise signal transfer)
31
Hyperalgesia
Pain evoked by a mild noxious stimulus
32
Allodynia
Pain evoked by a non- noxious stimulus
| i.e. feather
33
Opioid
an endogenous or synthetic substance that produces morphine-like effects and can be blocked by antagonists like naloxone.
34
Opiate
Morphine/ codeine like compounds that come from the opium poppy.
35
Narcotic analgesic
Old term for opioid. Use to mean "to induce sleep". Now used to refer to drugs of abuse.
36
Endorphins
endogenous opioid peptides
37
What receptors are responsible for the analgesic effects of opioids and resp depression, constipation, euphoria, sedation, dependence?
U receptors
38
What analgesics suppress cough in subanalgesic doses ?
Codeine
| Pholcodine
39
Opioid antagonists that help with GI side effects? How?
methylnaltrexone bromide
Alvimopan
Naloxegol
- don't cross the blood brain barrier. Therefore, don't stop all analgesic effects (only the peripheral ones)
40
What opioids do not release histamine from mast cells?
Pethidine
| Fentanyl
41
What are some effects of histamine?
urticaria
itching
bronchoconstriction
hypotension
42
What is the relationship between codeine and morphine?
Codeine is slowly converted to morphine via liver metabolism. Usually codeine does not produce euphoria.
43
What is the First line treatment for neuropathic pain? (2)
1. Anti epileptic medications (gabapentin, pregabalin)
| 2. Anti depressants (amitriptyline, nortriptyline, duloxetine, venlafaxine).
44
What is the maximum dose of gabapentin per day?
Gabapentin, also known as Neurontin, has a maximum dose of 1800 mg per day. Bio availability decreases as doses increase.
45
What are the most common adverse events from gabapentin?
Somnolence
Dizziness
Peripheral Edema
(ADE get worse as doses increase. Consider this as the bio availability decreases with increased doses).
46
What is a side effect of gabapentin that can lead to misuse?
Anxiolytic and euphoric affects similar to opioid and benzodiazepines
Gabapentin miss use his higher among patients with concurrent opioid use.
47
What are two conditions that black evidence to support gabapentin usage?
Fibromyalgia
| Neuropathic pain
48
What is the other name for pregabalin?
Lyrica
49
What is the other name for gabapentin?
Neurontin
50
Does gabapentin help with lower back pain?
No
51
What are indications for use for preGabalin?
Fibromyalgia, spinal cord injury, DPN (Diabetic peripheral neuralgia), PHN (post herpetic neuralgia).
52
What are 3 side effects of pregabalin?
Diplopia, blurred vision
Exacerbation of heart failure (similar to Gabapentin).
Cognitive decline (in elderly)
53
What is the other name for a duloxetine?
| What is it indicated to treat in Canada?
```
Cymbalta
Txs:
DPN
Fibromyalgia
Chronic LBP
OA of the knee
```
54
What are contraindications to duloxetine?
Hepatic impairment
CrCl < 30ml/min
Uncontrolled glaucoma
55
What is the starting dose for duloxetine?
| Max dose?
30 mg/day
| Max= 60mg/day
56
What are the most common adverse effects of duloxetine?
Nausea
Dry mouth
Somnolence
Dizziness
57
Tolerance versus physical dependence?
Tolerance: reduced responsiveness to achieve the desired clinical outcome. R/t u receptor desensitization.
Physical dependence: withdrawal from the drug results in adverse physiological effects.
58
Dyskinesia
impairment of voluntary muscle movements = fragmented or jerky movements
59
Ataxia
lack of muscle control or coordination of voluntary movements such as walking or picking up objects
60
Max useful dose of duloxetine/Cymbalta?
60mg /day (delayed release caps)
61
Why is pregabalin/lyrica not recommended in the elderly?
Risk of falls/ other injuries. Benefit doesn't significantly outweigh the risk.
62
What does Cymbalta/Duloxetine treat?
DPN
fibromyalgia
chronic LBP
OA of the knee
63
Side effects of Pregabalin (Lyrica)
Diplopia
blurred vision
dose related abnormal vision
Exacerbation of heart failure (same for Gabapentin and Pregabalin)
64
What is the BEERS criteria
A website listing medications that are not appropriate in older adults (r/t ADEs)
65
What to monitor when initiating or changing amitriptyline or nortriptyline doses?
Na level
It is a anticholenergic
sedating
orthostatic hypotension
66
Clonus
involuntary muscle contractions, = uncontrollable, rhythmic, shaking movements.
67
Myoclonus
quick, involuntary muscle jerk (i.e. hiccups)
68
3 triad signs of serotonin syndrome?
1- neuromuscular excitation (clonus, hyerreflexia, myoclonus, rigidity)
2- autonomic excitation (hyperthermia, tachycardia)
3- altered mental state (agitation, confusion)
69
Mild signs of serotonin syndrome
```
Nervousness
Insomnia
Nausea/diarrha
Tremor
big pupils
```
70
Moderate signs of serotonin syndrome
Hyperreflexia
sweating
agitation/restlessness
inducible clonus (with dorsiflexion of the foot)
side to side eye movements (ocular clonus)
71
Severe serotonin syndrome (5)
```
Fever >38.5
confusion/delirium
sustained clonus/rigidity
rhabdomyolysis (kidney failure from the byproduct of muscle breakdown)
death
```
72
How to prevent serotonin syndrome: (6)
Use lowest effective dose
Ask about ilicit drugs
Check drug monographs for tapering and wash-out periods
Follow up 1-2 days after upper dose or starting new drug
Reassess need for serotonin drug yearly
Teach pt to recognize SS
73
3 guiding principles of pain medication?
1. Measure pain individually
2. expect the drugs to fail (no false expectations)
3. prepare for the next step when failure occurs
74
Odds ratio > 1 =?
Roughly speaking >1 for odds ratio means ur more likely to have the odds of what they're studying.
Higher the OR (odds ratio= higher chance of happening)
75
What are the 5 points of evidence to practice for medications for treating neuropathic pain? (from PAD provincial academic detailing service)
1. Set realistic expectations with clear goals for therapy before trialing medications
2. Aim to evaluate success of trial med by weeks 2-4
3. Discuss discontinuing ineffective medications before trialing another.
4. Consider renal function, med dosage, drug interactions with efficacy and safety.
5. Revisit if ongoing medication is useful or harmful
76
Examples of anticholinergics, antimuscarinics? (7)
- antidepressants
- antihistamines
- antipsychotics
- opioids
- antispasmodics
- bladder drugs
- antimuscarinic inhalers
77
What are LAMAs?
Long acting muscarinic antagonists (i.e. long acting bronchodilators)
78
What do muscarinic antagonists do?
Competitively block cholinergic responses from acetylcholine binding muscarinic receptors.
79
Where do muscarinic antagonists work in the body?
- exocrine glandular cells
- cardiac muscles
- smooth muscles
80
What nerve is stimulated in COPD?
Vagus nerve
81
What does Vagus nerve stimulation in the lungs do?
Increases ACh
= bronchoconstriction of smooth muscles
=inflammation
= mucous
82
What is acetylcholine?
Main neurotransmitter of the parasympathetic nervous system
83
What is the effect of acetylcholine?
```
From the parasympathetic NS:
- slows HR
-bronchoconstriction
-dilated blood vessels
-contracts smooth muscle
(opposite of what you want for people with COPD- hence the use of MA (muscarinic antagonists)
```
84
What does blocking acetylcholine do?
- bronchodilation
- decreases secretions
- increases HR
- constricts blood vessels
85
What is the key point to this whole course?
Use the lowest effective dose for the shortest duration of time.
86
What meds are supported with evidence to treat neuropathic pain?
- Gabapentinoids
| - Tricyclic antidepressants
87
Summary points for treating neuropathic pain? (5)
- set realistic goals with the patient (only 50% will get relief from medication)
- Follow up in 2-4 weeks (onset of effect should occur in a few days but this allows for lifestyle modifications as well).
- Higher dose isn't NOT better
- NO combos
- stop drugs that don't work
88
What is nociceptive pain?
Pain caused by tissue injury. Usually sharp, aching, throbbing.
-examples: stub your toe, sports injury, dental procedure, burn
89
What does the somatosensory NS perceive: (7)
- Touch
- Pressure
- Pain
- Vibration
- Temperature
- Position
- Movement
90
Where are somatosensory nerves located? (4)
- muscles
- facia
- skin
- joints
91
What is neuropathic pain?
Pain caused by lesions or disease to the somatosensory nervous system (includes peripheral nerve fibres and central neurons).
92
What is radiculopathy? (and 3 kinds of sx)
A type of neuropathic pain caused by the pinching of a nerve root in the spinal column (cervical, thoracic, lumbar).
= pain, weakness, tingling
93
What is Syringomyelia (sih-ring-go-my-E-lee-uh) ?
the development of a fluid-filled cyst (syrinx) within your spinal cord. Cause of neuropathic pain,
94
7 P's of pain
```
1-intellectual pain
2-Financial pain
3-emotional pain
4-spiritual pain
5-physcial pain
6-interpersonal pain
7-bureaucratic pain
```
95
Visceral pain is?
pain that arises as a diffuse and poorly defined sensation usually perceived in the midline of the body, at the lower sternum or upper abdomen.
Can radiate from adjacent organ (ie. Left ureter = left lower quadrant, loin).
often associated with marked autonomic phenomena, including: pallor
profuse sweating
nausea
GI disturbances
changes in body temperature, blood pressure and heart rate
-"sharp, cramping, aching"
-"referred pain"
96
2 types of nociceptive pain:
Somatic
| Visceral
97
Somatic nociceptive pain...?
```
- can be localized
Effects the:
- bone
-muscles
-soft tissues
-joints
-"throbbing, aching, boring, deep.."
```
98
What does the OPQRSTUV pain assessment stand for?
```
O-Onset
P-Provoked
Q-quality
R-region/radiation
S-severity
T-treatment
U-understanding
V-values
```
99
Max dose of acetaminophen in elderly?
2600mg/day
100
Dosing of acetaminophen in children and adults? Chronic use dosage maximum?
15mg/kg q4h (children)
Max 4000mg/ day (adults)
Max 3200mg/day for chronic use
Avoid in liver impairment
101
How are NSAIDS anti-inflammatory?
Inhibit prostaglandins (PGE)
102
NSAID categories? (6)
1- salycilates (ASA)
2- proprionic (ibuprofen, ketoprofen, naproxen)
3- Indole (indomethacin, sulindac)
4- Fenamate (mefanamic acid)
5- Other (piroxicam, meloxicam, ketorolac, diclofenac)
6- Cox 2 inhibitors (Celecoxib)
103
What does COX stand for?
Cyclooxygenase
104
What do COX 1 and COX 2 inhibitors block?
Prostacyclins: inhibits platelet aggregation, vasodilation
Prostaglandins: hyperalgesia, vasodilation
105
What do COX-1 (only ) inhibitors do?
Blocks the effect of arachidonic acid on Thromboxane A2 (which would cause vasoconstriction and stimulate platelet aggregation).
106
What do NSAIDS react with?
1- lithium (decreased renal clearance= lithium toxicity)
2- ACE inhibitors/ diuretics = less antihypertensive effects
3- Warfarin= increased risk of bleeding
107
what do non-selective NSAIDs do?
-Decrease prostaglandin and thromboxane A2
| =decreased platelet aggregation
108
What do COX 2 inhibitors do?
Decrease only prostaglandins (potential shift towards thrombosis).
109
Who should avoid NSAIDS and COX 2 inhibitors?
Renal patients
110
The WHO step ladder approach to pain is for?
Palliative/ cancer pain
111
First steps for treating cancer pain? (3)
1- treat underlying disease
(i.e. radiotherapy for bony metastases)
2- psychosocial support
3- consider non-pharmacological thearpy (i.e. massage, relaxation, acupuncture, TENS)
112
Opiate
Any natural compound derived from opium
| • Morphine (principal alkaloid of opium), codeine, papaverine
113
Opioid
All compounds derived from opium (natural or synthetic), and any compound with opioid like actions that are blocked by non-selective opioid antagonists
114
What is the deciphering factor for incident pain?
It is predictable (i.e. dressing changes).
115
What is the breakthrough pain dose?
5-10% of the total daily opioid dose
q 1h po
q 1/2 hour for parenteral.
116
How to calculate adequate pain med dosages in palliative care?
Take the TDD and divide into q 4h *this is your new regular medication plan. (i.e. 45mg / 6 = 7.5mg q4h)
Take 5-10% of the TDD and use that as the BTP dose. (i.e. 45mg TDD= 4 -4.5 mg q 1h po for BTP).
117
What should you consider ALWAYS when doing an opioid conversion dose?
Consider cross tolerance reduction: Give 50% of expected dosage. Easier to go up than to revive after overdose.
118
What genetic variability impairs conversion of codeine to morphine in the liver?
• Low expression of CYP 2D6
119
What is the "wind up" phenomenon?
Glutamine and aspartate = sensitization of the central nervous system
NMDA receptor antagonists
"If pain not controlled it will become chronic"
120
Examples of when to use adjuvant therapy for palliative pain?
- neuropathic pain
- visceral
- somatic
- anxiety related pain
- managing side effects
121
S and S of opioid intoxication:
- Recent use of an opioid
- significant problematic behavioural or psychological changes (e.g., initial euphoria followed by apathy, dysphoria, psychomotor agitation or retardation, impaired judgment) that developed during, or shortly after, opioid use
- Pupillary constriction (or pupillary dilation due to anoxia from severe overdose) AND one (or more) of the following signs or symptoms developing during, or shortly after, opioid use:
- Drowsiness or coma
- Slurred speech
- Impairment in attention or memory
- not attributable to another medical condition, mental disorder, or intoxication with another substance
122
Opioid withdrawal symptom criteria (2)?
| Symptoms of opioid withdrawal? (10)
Presence of either:
1. Cessation of (or reduction in) opioid after heavy and prolonged (i.e., several weeks or longer)
2. Administration of an opioid antagonist after a period of opioid use
3. Three (or more) of the following developing within minutes to several days after Criterion A:
Dysphoric mood
Nausea or vomiting
Muscle aches
Lacrimation or rhinorrhea
Pupillary dilation, piloerection or sweating
Diarrhea
Yawning
Fever
Insomnia
123
What does the COWS scale assess? (2)
the stage or severity of opiate withdrawal
-the level of physical
dependence on opioids
124
When assessing opioid use disorder test for?
- Laboratory tests and/or imaging to assess comorbidities/complications revealed in history and physical
- routine (pregnancy test, CBC, renal/liver function, electrolytes, magnesium, phosphorus)
- as indicated (chest x-ray, CT head, ultrasound).
-Toxicology, including urine testing for drugs of abuse; ethanol and its metabolite, ethyl glucuronide.
125
The most effective treatment for opioid use disorder?
- maintenance therapy with a long-acting agonist like methadone or the partial agonist buprenorphine. *high risk of overdose upon relapse for individuals who have recently undergone detoxification due to loss of tolerance.
* Detoxification in pregnancy should be avoided due to risk of spontaneous abortion.
126
What is clonidine?
- alpha-2 adrenergic agonist
- decreases neuronal output of norepinephrine
- can blunt the noradrenergic sx of withdrawal such as chills, flushing
- N + V, diarrhea, muscle aches, cravings usually persist.
127
Maintenance therapies for treating moderate to severe opioid use disorder? (1,2nd and 3 line tx)
First line tx= buprenorphine/naloxone
2nd line= methadone
3rd (off label)= slow release morphine
128
How buprenorphine works? (receptors?)
Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at other receptors, e.g., kappa
129
Complications of alcohol use disorder?
- Poor nutrition: thiamine def., hypokalemia, low magnesium, low phosphorus
- Liver disease
- bleeding diathesis
- Tremor, ataxia, seizures, Wernicke encephalopathy
- Autonomic dysfunction (hypertension, dehydration, pyrexia)
- neuropathy
- trauma
- increased risk of mouth, throat, liver, colon, breast ca
- infections (aspiration pneumonia, cellulitis)
- concurrent psychiatric disorders (depression, anxiety)
- psychosis (hallucinations, delusions)
- insomnia, sleep apnea
130
Alcohol use disorder has 2 + of these:
1- alcohol in large amounts/longer period of time than intended
2- persistent desire/ unsuccessful attempts to decrease/ control alcohol use
3- A lot of time spent to obtain, use or recover from alcohol
4- Craving, strong desire, or urge for alcohol
5- = failure to fulfill roles at work, school or home
6- continue with alcohol despite its' negative effects on social/ interpersonal life.
7- social, occupational, recreational activities given up because of alcohol
8-recurrent use in physically hazardous situations
9-alcohol used even though it caused/ exacerbated physical or psychological problem
10-Tolerance: more needed to obtain effect
11. withdrawal experience, other meds taken to alleviate withdrawal sx.
131
Alcohol withdrawal sx:
1. autonomic hyperactivity: sweating, HR> 100bpm
2. increased hand tremor
3. Insomnia
4. N + V
5. Transient visual, tactile, auditory hallucinations/ illusions
6. psychomotor agitation (movements without purpose)
7. Anxiety
8. Generalized tonic-cldonic seizures
132
Immunoassay vs. Chromatography urine drug screening
Immunoassay: doesn't differentiate b/w opioids, false positive for poppy seeds, quinolone abx.
Chromatography: no reaction to poppy seeds, differentiates opioids, better at detecting semi and synthetic opioids.
133
Immunoassay detects which drug that chromatography doesn't in a urine drug screen?
Benzodiazepines- 20+ days after regular use.
| -intermediate acting benzos such as clonazepam often not detected.
134
What does an opioid agreement do?
- shows you care
- shows your doing your due-diligence
- shows you may discontinue the medication
135
What are indications that an opioid is not working and should be discontinued?
- 2 to 3 dose increases
| - no benefit after a few weeks
136
Signs of a failed opioid trial?
- no increase in functioning
- signs of misuse, diversion, harm
- no meaningful reduction in pain
- intolerance to opioid
137
What to do if opioid trial fails?
- cautiously trial a different opioid
| - consult pain specialist
138
Morphine is...
- Mu agonist
- Low pharmacokinetic drug interactions (no phase 1 CYP450 metabolism)
- low potential for MAOI interactions (depends on timing)
- many formulations and strengths (PO only for CNCP)
- cheap
- potential for neurotoxicity due to morphine-3-glucuronide
139
Codeine...
- weak Mu agonist
- conflicting evidence: belief is it needs to be converted to morphine via CYP2D6 metabolism to have full effect
- Genetic polymorphism in CYP2D6 can affect safety and efficacy
140
Genetic polymorphism in CYP2D6 can affect safety and efficacy of codeine by: (3)
* poor metabolizer = no effect (doesn't mean they have an opioid tolerance)
* Ultra rapid metabolizers= morphine effect FAST
- risk for morphine toxicity
- 1-10% of Caucasians
* risk for breast feeding (can't predict how much the baby gets via breast milk)
141
What is drug conversion that is a high risk for toxicity?
Codeine to Fentanyl (pt. may be a poor metabolizer, could lead to overdose of fentanyl even though codeine didn't work).
142
Hydromorphone...
- Mu and Delta agonist
- Glucuronidation via UGT2B7
- hydromorphone 3-G-glucuronide (active)
- No significant CYP450 metabolism
- low DDI's (drug drug interactions) with CYP450 metabolism
143
Oxycodone... (5)
- Mu, Delta, Kappa agonist
- Metabolites:
* CYP2D6 (oxymorphone-active)
* CYP3A4 (noroxycodone-active)
- Potential interaction with: CYP2D6, CYP3A4
- SR non-beneficial
- Combos with acetaminophen
144
Oxycontin is ... (3)
"TIN"= long acting
-is now called OxyNeo
-difficult to swallow = jelly when wet
145
Fentanyl...
- steady state after 6 days (2 x 72 hr applications)
- CYP3A4 DDIs (highly clinically relevant)
- renal and hepatic precautions
- only if 60-90 mg morphine x 2 weeks (NOT for opioid naïve patients).
- Serotonin toxicity
- accidental exposure risk (disposal, removal precautions)
- HIGH ALERT MED
- EDUCATE IN PROPRER ADMINISTRATION AND DISPOSAL.
146
Fentanyl conversion NOT established for these 3 drugs:
- tapentadol
- buprenorphine
- tramadol
147
How long after an MAOI is it safe to administer fentanyl?
14 days
148
Precaution of fentanyl when used with:
- renal
- hepatic
- cachectic patients (wasting syndrome)
- elderly
149
Naloxone is not effective in
reversing respiratory
depression due to overdose of:
Buprenorphine
150
Buprenorphine is a ...
- opioid agonist (mu)
| - opioid antagonist (Kappa, delta)
151
Tapentadol
- not commonly used
- exact mechanism unknown (possible DDIs)
- opioid agonist (MU)
- norepinephrine reuptake inhibitor
- weak serotonin reuptake inhibitor
- not reversible by naloxone
- linked to seizures, HTN, serotonin toxicity
- high rates of withdrawal r/t ADE
- no direct conversion to morphine
152
Drugs that interact with opioids to put a patient at risk for serotonin toxicity? (2 neuro drugs, 5 opioids)
```
SSRIs
SNRIs
with
-meperidine
-tramadol
-fentanyl
-pentazocine
-tapentadol
```
153
Symptoms of serotonin syndrome?
```
muscle jerking
muscle rigidity
tremors
sweating
fever
agitation
```
154
CAN pneumonic for serotonin toxicity?
C- conscious state changes
A-autonomic changes
N-neuromuscular changes
155
Conscious state changes in serotonin toxicity? (8)
```
agitation
delirium
restlessness
disorientation
anxiety
lethargy
seizures
hallucinations
```
156
Autonomic changes in serotonin toxicity? (9)
```
diaphoresis
hypertension
hyperthermia
vomiting
tachycardia
dilated pupils
unreactive pupils
diarrhea
abdominal pain
```
157
Neuromuscular changes in serotonin toxicity? (5)
```
myoclonus
tremor
muscle rigidity
hyperreflexia
nystagmus
```
158
How to compensate for incomplete cross-tolerance when switching to a new opioid? (2 options)
≤ 75mg oral morphine (or equivalent) in 24 hours = decrease by 60-70%
> 75mg oral morphine (or equivalent) in 24 hours= decrease by 50%.
OR: Just decrease everyone by 50% . Easier to increase than to reverse! CNCP= non-actue/urgent setting.
159
How to practice good opioid stewardship? 5
1. communicate/collaborate with patient's community pharmacist
2. Write clear and specific Rx
3. Educate pt re: possible adverse events, toxicity, opioid storage and disposal
4. Set realistic goals and expectations
5. avoid interacting medications when possible
160
MME?
Milligrams Morphine Equivalent
161
What is the max MME increase per day? What is the absolute MAX?
Max= 50 MME/day
| ABSOLUTE MAX with good justification of patient benefit and safety= 90 MME/day
162
Opioid associated harms: (serious) 3
```
Serious
• Falls leading to fractures
• Respiratory Depression
– Dosing changes, errors, or
misuse
• Deaths
– Increasing use, inappropriate
intake, rapid dose escalation,
high doses in opioid-naïve
patients, diversion
```
163
Opioid associated harms: (other) 4
```
Other Harms
• Opioid induced androgen
deficiency (OPIAD)
• Opioid induced
hyperalgesia
(experimental settings)
• Potential for misuse and
opioid addiction
• Sedation and cognitive
impairment
```
164
What should you avoid prescribing concurrently?
Opioids + Sedatives (benzos)
165
What are the effects of benzodiazepines? (5)
```
1-anxiolytic
2-hypnotic
3-muscle relaxant
4-anticonvulsant
5-amnesic
```
166
What are the short term benefits to benzodiazepines?
- efficacy
- rapid onset
- low acute toxicity
167
How do benzodiazepines work?
- increases affect of GABA's inhibitory influence on neurons in the brain.
- booster GABA receptor sites= more CL released= more inhibitory
168
What are the brain's excitatory neuro transmitters? (those halted by benzos) 4
```
excitatory neurotransmitters, include:
norepinephrine
serotonin,
acetylcholine
dopamine,
```
169
What do excitatory neurotransmitters control?
```
normal alertness
memory
muscle tone
co-ordination
emotional responses
endocrine gland secretions
heart rate and blood pressure --all of which may be impaired by benzodiazepines.
```
170
Benzo receptors not linked to GABA are located here:
Kidney
Colon
Blood cells
Adrenal cortex
171
4 main types of opioid receptors?
µ (mu), δ (delta), κ (kappa), NOP
172
Where are opioid receptors located?
Dorsal horn of the spinal cord
173
What does activation of the opioid receptor by an agonist result it?
1. Closing of the Ca channels= decreases release of neurotransmitters: glutamate, substance P and calcitonin-gene-related-peptide (CGRP).
2. Opening of K channels
= efflux of K ions
= hyperpolarization= less sensitive to excitatory inputs
174
Examples of synthetic opioids: (7)
```
Fentanyl
Methadone
Meperidine
Oxycodone
Oxymorphone
Hydromorphone
Hydrocodone
```
175
What causes nausea after opioid administration?
Direct stimulation of the chemo receptor in the medulla
176
How does Naloxone work?
pure opioid antagonist with affinity for all 3 classic opioid receptors µ (mu), δ (delta), κ (kappa)
177
4 main opioid receptors?
µ (mu)
δ (delta)
κ (kappa)
NOP
178
Effect of µ (mu) opioid receptor? 6
- most analgesic effects of opioids
- euphoria
- respiratory depression
- constipation
- sedation
- dependence
179
Effect of δ (delta) opioid receptor?
- analgesic
| - can be proconvulsant
180
Effect of κ (kappa) opioid receptor (4)?
- contribute to analgesia at spinal level
- sedation
- dysphoria
- hallucinations
181
Effect of NOP receptors?
-activation results in antiopioid effect (supraspinal), analgesia (spinal), immobility and impairment of learning.
182
Hyperanalgesia:
= pain sensitization or allodynia
=reduced analgesic response to opioid
=NOT the same as tolerance (which is reduced responsiveness a u receptors, occurs with euphoria and respiratory depression).
tx= ketamine, Propofol, decrease analgesic, change analgesic
183
What do opioids do to the GI tract?
```
Increase tone (less easy to move)
Decrease motility
```
184
Tolerance?
- develops within a few days of rapid administration
- mechanism involves u receptor de-sensitization
- Not pharmacological in origin
- overcome through drug rotation
- doesn't decrease constipation or pupillary constriction
185
NSAIDS should be avoided in these pts:
with a history of peptic ulcer disease
renal failure
heart failure
ischemic heart disease
186
What to use on children prior to IV/ IM treatment?
Liposomal lidocaine is as effective as EMLA in decreasing pain associated with venipuncture or IV cannulation. It has minimal vasoactive properties and requires an application time of 30 minutes.
187
What bacteria are becoming resistant to Cipro?
| relating to UTIs
e. Coli
Proteus mirabilis
Klebsiella pneumoniae
188
What bacteria is becoming resistant to TMP/SMX (related to UTIs)?
E, Coli
189
Common pathogens for Pyelonephritis?
```
E. Coli
Enterobacteriaceae (gram negative bacilli):
- Proteus mirabilis
-Klebsiella pneumonia
-Staphylococcus saprophyticus (gram +)
```
190
Treatment of recurrent female cystitis?
< 1 month since tx and different organism= treat same 1st episode (new infection)
< 1 month= Same organism= tx for pyelonephritis
> 1 month = same as tx for 1st episode (this is a new infection)
191
1st line tx for uncomplicated pyelonephritis:
Cefixime 400 mg PO daily x 10 days
192
When should nitrofurantoin be avoided?
Near term (36-42 weeks)
193
1st order
| Kinetics
Concentration dependent drug elimination. A constant percentage of drug is eliminated per unit time.
Half life IS constant
194
Zero Order Kinetics
Drug saturates elimination routes.
NOT eliminated in a concentration dependent manner.
Half life is NOT constant.
195
Antagonist
Reverse the effect of the agonist. Have no biological effect of their own.
196
Agonist
Produces a biological response when bound to a receptor
197
Lethal dose (LD50)
Dose that is lethal to 50% of those taking it.
198
Toxic Dose
Dose that is toxic to 50% of those taking it
199
The higher the therapeutic index =?
Safer drug.
| Higher index = safer than narrow index.
200
Efficacy
Maximum effect a drug can have.
201
Alpha errors?
AAAA! I have a condition!!!! (but you actually don't).
Null hypothesis rejected when it is true!
aka: Say "there is a difference/significant result" when there actually isn't one!
202
Beta errors?
You are told you don't have the condition but you do (BAD).
| Failing to reject the null hypothesis "there is something wrong even though we are saying there isn't"
203
Norepinephrine is released as part of the ?
Sympathetic NS
Alpha 1 & 2
Beta 1,2 & 3
204
Anabolism
Anabolism= growth and building of tissues/cells (parasympathetic)
205
Catabolism
Digestion of food molecules to produce energy (sympathetic NS)
206
All values within a CI are statistically possible in a ?
Superiority Trial
207
Likely pathogens for AECB?
```
Rhinovirus
H. influenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Pseudomonas aeruginosa
```
208
Labs for vanco?
Serum Creatinine (Scr) baseline, then weekly (more if renal fx changing or on other nephrotoxic drugs)
*collect 30 minutes or less prior to next dose
Scr increases by 50% or > = to 40 umol/L = trough level needed to assess dosing
CBC weekly
Peak (post) levels not needed
Trough only if meets guidelines
209
Vancomycin clearance in enhanced in these patients
Morbidly obese
210
GFR levels (3 categories)
A GFR of 60 or higher =normal range.
A GFR below 60 = possible kidney disease.
A GFR of 15 or lower= possible kidney failure
211
< 6mths, immunodeficiencies, craniofacial abnormalities, chronic cardiac or pulmonary conditions, Down syndrome, underlying hearing impairment, history of OM with suppurative complications or chronic perforation
90mg/kg/day (amox) and 6.4mg/kg/day (clavulanate)
TWO prescriptions
- Amoxicillin 45mg/kg/day (div bid-tid) x 10 days
AND
- Amox-clav (7:1) 45mg/kg/day amox (div BID- TID) x 10 d
212
Bacteriocidal are? (2)
Time dependent or
Concentration dependent
MIC = MBC
213
Time dependent Bactericidal Abx?
4 examples
2 things they need?
B lactams
Vanco
Macrolides
Clindamycin
Need: frequent dosing, must stay above the MIC
214
Examples of concentration dependent bactericidal abx?
| 2 aspects of these?
Aminoglycosides
Quinolones
1- less frequent dosing
2-dose to achieve higher peaks
215
What does amoxicillin cover that PCN doesn't? (Hint: It's gram negative)
H. Influenzae
216
Normal Creatinine Clearance? Male and Female
Female 22–75 µmol/L
| Male 49–93 µmol/L
217
Which drug is used off label to tx Raynauds?
Calcium channel blockers
218
Which drug is contraindicated in Raynaud’s ?
Beta blocker
| Can cause cold extremities
219
Which drug should be used with caution in COPD?
Beta blockers
| B2= bronchodilator (blocked= bronchi construction)
220
Example of a calcium channel blocker that causes flushing and edema?
Dihydropyridine
“2 water filled pyramids”
Aka: Nifedipine
221
Side effect of verapamil
Headache
Constipation
*risk of cardiac failure and heart block*
222
Verapamil works on?
The cardiac muscles
| Causes: constipation
223
Dihydropyridine works on?
Smooth muscle. = edema
224
Diltiazem works on ?
Both cardiac and smooth muscle
225
Amlodipine and nifedipine are in this drug grouping?
Dihydropyridines
226
CCB that tx HTN are usually?
Dihydropyridines such as nifedipine or amlodipine.
227
This CCB treats cerebral vascular vaso spasms after sub arachnoid hemorrhage?
Nimodipine
228
These CCB help prevent angina (2)
Dihydropyridines
| Diltiazem
229
This CCB category causes headache, flushing and ankle edema
Dihydropyridines (nifedipine)
230
What is pulse pressure?
Difference between systolic and diastolic pressure.
| Affected with age r/t aortic stiffness
231
ACE does what to bradykinin?
Inactivates it.
Therefore, ACE inhibitors allow an increase in bradykinin (I. E. Ramipril cough).
232
Which pts should not combine ACE and ARBS?
Renal impairment
Diabetic
233
Valvular a fib includes:
rheumatic mitral stenosis
mechanical/ bioprosthetic heart valve
mitral valve repair
234
What is a pro drug?
A drug that needs to be activated before it will work.
