PPP Quiz III Flashcards
Describe the pain pathway
Action potential travels along the 1st neuron, meets the synapse, and transacted to the second order neuron, and then to the brain.
Where does the Spinothalamic tract go to?
PAIN to the higher centers
MOA of NSAIDS
Inhibit COX to decrease synthesis of prostaglandins
Describe the physiology of Eicosanoids
PG sensitive AFFERENT nerves to pain; Increase of prostaglandins lead to increase sensitivity to pain fibers by altering the phosphorylation status of the neuron
Where do NSAIDS block?
COX; Conversion of Arachidonic acid to prostaglandins
What does Ibuprofen block?
COX1 & COX2
What does aspirin block (81mg)?
COX1
Name the housekeeping functions of PG: Stomach
COX1 to PGE2: Decrease of gastric acid secretion; Increase of mucus and bicarbonate secretion
Name the housekeeping functions of PG: Renal
COX2 to PGE2, PGI2: Increase renal blood flow; Increase glomerular filtration rate
Name the housekeeping functions of PG: Platelet
COX1 to TXA2; Increase of platelet aggregation
Name the housekeeping functions of PG: Endothelial Cells
COX2 to PGI2: Decrease platelet aggregation
AE of NSAIDS
Abdominal pain, ulcers, GI bleeding, Decrease renal blood flow, decrease glomerular filtration rate
AE of Aspirin
COX1: Increase risk of bleeding; ANTITHROMBOTIC effect; Used for CV benefits
AE of Celecoxib
COX2: Increase risk of MI and Stroke
AE of Acetaminophen
Liver toxicity (4g/day)
MOA of Opioids in Midbrain
Block release of GABA; Increase activation of noradrenergic descending pain modulation systems; At spinal level, NE and 5HT2 acting through a2 adrenergic and serotonergic receptors, inhibit spinal pain input.
MOA of Opioids in Dorsal Horn
Presynaptic action: Decrease release of neurotransmitter (substance P); Postsynaptic: Hyperpolarization of postsynap. neuron
Describe Opioid AE: Reward
Opioid action leads to sensation of reward (endorphins): Increase substance use disorder
Describe Opioid AE: Drowsiness
Decrease wakefulness and drowsiness (inhibition of excitatory drive from ascending reticular activating system)
Describe Opioid AE: Respiratory depression
Chemosensitive area in brainstem: Block rise of CO2; dependent on fall in O2 (periphery)
Describe Opioid AE:GI
Increase segmental (nonpropulsive) contractions –> constipation; Decrease peristaltic (propulsive) contraction (contraction below, relaxation above)
Describe Opioid AE: N/V
Nausea and emesis: stimulate u-R in CTZ (chemoreceptor trigger zone)
Describe Opioid AE:Urinary retention
Inhibit voiding reflex (opioid naive pt only)
Describe Opioid AE: CV
Bradycardia –> Increase parasympathetic
Hypotension –> Morphine can release histamine from mast cells –> decrease SVR –> Decrease BP
Describe opioid MOA
Opioids stimulate u receptor –> Less GABA, more ACh –> Parasympathetic
Describe Opioid AE: Pruritus (itching)
Morphine can release histamine from mast cells
Describe Opioid AE:Miosis
Results from inhibition of inhibitory GABA interneurons –> Increase para –> miosis
Important sign of opioid intoxication
Describe Opioid AE: Cough suppression
Morphine suppresses cough reflex: Not well understood ?
Clinical uses of Morphine (Full u agonist)
Chronic pain (cancer): PO (1st pass metabolism), intrathecal, epidural
Postoperative Pain: IV, inthrathecal,epidural)
Works in 15-30 min
Morphine AE
Releases histamine from mast cell –> vasodilation, allergic symptoms (pruritus)
Clinical uses of Methadone (Full u agonist)
Chronic Pain
Maintenance drug for opioid-dependent pt (heroin)
Long 1/2 life
Clinical uses of Fentanyl (Full u agonist)
Induction agent of anesthesiology
Chronic pain (transmuscosal, transdermal)
Transmucosal lozenge –> quick onset
Clinical uses of Codeine (Full u agonist)
Mild to moderate pain (ceiling effect)
Dependent on conversion of codeine to morphine by CYP2D6 (liver)
10% population have polymorphism in CYP2D6 –> makes codeine ineffective as analgesic
Clinical uses of Buprenorphine (Partial u agonist)
Post-Op pain
Maintenance drug for opioid-dependent patients
Long 1/2 life
Acts as an agonist in presence of antagonist
MOA of Naloxone (u Antagonists)
Blocks all opioid receptors
Used for opioid overdose
IM, IV, auto-injector
Short 1/2 life
Naloxone auto-injector
Narcan
Evzio –> approved for emergency treatment of OD
MOA of Naltrexone (u Antagonists)
Blocks all opioid receptors
Used for opioid dependence (alcohol dependence)
Administer by PO
CANNOT GIVE FOR AN OVERDOSE!!
MOA of Tramadol
Weakly stimulate u opioid receptors
Weakly inhibit NET and SERT
DONT GIVE WHILE ON AN SSRI
Used for mild to moderate pain (PO)
AE of Tramadol
Risk of causing seizures
CAUTION WITH PT PREEXISTING SEIZURE DISORDERS
DONT GIVE WHILE ON AN SSRI (serotonin syndrome)
Opioid interactions/Tolerance
CYP interactions = Codeine
CNS depressants = BZD, etc.
Tolerance –> Need more of drug to see same effect
Cross tolerance
Degree of tolerance
Clinical uses of Clonidine (a2 agonist)
Used as analgesic and neuropathic pain
Postop and neuropathic pain
MOA: Gi couple (less cAMP, less phos. Ca channel, less exocytosis of SP, less transported to 2nd neuron)
AE of Clonidine
Hypotension
Sedation
Dry mouth (a2 receptors on parasympathetic postgang nerve terminals)
Decrease Ach
Clinical uses of Gabapentin
MOA: Uncertain
Neuropathic pain
Seizures (adjunct therapy)
What drugs prolong the inactivated state of Na and what are the clinical uses?
Carbamazepine, Phenytoin, topiramate
Seizures
Neuropathic pain
Which antidepressants can you use for neuropathic pain? What is the MOA?
Amitriptyline, duloxetine (SNRI)
Inhibit NET –> More NE, binds to a2 –> Less SP –> Less signal transduction
How does Lidocaine treat neuropathic pain?
Blocks VG Na channels
Anesthetic
Neuropathic pain (But lower dose)
What is a seizure?
Excessive and hyper-synchronous neural activity
Name the events that a seizure could alter
Consciousness, motor, sensory , psychic
What is epilepsy?
Chronic disorder that requires the occurrence of two or more seizures that are NOT provoked by other illness (Eg. pt has seizure but then finds a brain tumor, not seizure)
Describe the focal onset seizure
One hemisphere
-Normal awareness –> consciousness NOT impaired, clonus on right side of face and in right arm
-Impaired awareness –> consciousness impaired, lip smacking, repeating words
MAY SPREAD TO BECOME BILATERAL TONIC-CLONIC SEIZURE (focal onset –> generalized)
Describe the generalized onset seizure
Both hemispheres
-Tonic (stiffen) clonic (jerky movement) described as (“grand mal”) –> motor movement
-Body rigid, limbs extended, head back, grimace
-Other motor–> Tonic OR Clonic
-Absence –> Primarily in children, brief loss of consciousness, NO MOTOR symptoms
Levels of neurotransmitters during a seizure
Excitation: Glutamate is too HIGH
Inhibition GABA is too LOW
Name the 4 ways to treat a seizure.
1) Prolong inactivated Na
2) Inhibit excitatory
3) Enhance inhibitory
4) Ca-Channel blockade (T-Type)
Describe the stages of prolonging the inactivated Na state
1) Resting
2) Activated
3) Inactivated (PROLONG HERE)
Recycles from 3–>1
Which drugs prolong inactivated state?
VG-Na Channel blockade
Phenytoin
Carbamazepine
Lamotrigine
Topiramate
Valproic Acid
“Please call Larry to Vaccinate”
Which drugs block excitatory glutamatergic synapse?
Blocks SV2A proteins –> Less glutamate released
Levetiracetam (Keppra)
What drugs block straight glutamate receptor?
BLOCK AMPA
Topiramate
Perampanel
What drug blocks the release of Glutamate
Lamotrigine
Which drugs enhance inhibitory GABA?
Tiagabine
Doesn’t let in the GABA (targets GAT-1)
Which drug block the breakdown of GABA?
Valproic Acid (GABA-T)
Which drugs act at GABA(A) receptor?
Barbiturates
BZD
Topiramate
Which drugs block T-type Ca Channel?
USED IN ABSENCE SEIZURES
Valproic acid
Ethosuximide
Lamotrigine
Which drugs are involved in Glutamate transmission?
Lamotrigine
Topiramate
Gabapentin?
Levetiracetam
Perampanel
“Larry took ‘good’ lab precaution”
Which drugs are involved in GABA transmission?
Valproic acid
Topiramate
Gabapentin
Tiagabine
Levetiracetam
Phenobarbital
Diazepam
“Larry took ‘good’ peaceful talented violinists dancing”
What drugs are used for absence seizures?
Blocking Ca T Type channels
Lamotrigine
Valproic Acid
Ethosuximide
“Larry eats vegetables”
What seizure drugs cover the most?
Valproic Acid
Ethosuximide
“Eats vegetables”
Name 5 considerations of seizure treatment
Social
Drivers license
Career
Avoid triggers (light, sleep, noise)
Long term treatment (counseling side effects)
What’s the MOA/PK/AE of Phenytoin?
Prolong inactivated state of Na
-Used for ANY seizure except for absence
-Particularly effective against focal onset and generalized tonic clonic
-High protein binding
-Induces CYP3A4 (metabolism of oral contraceptives, other anti seizure drugs eg. carbamazepine)
-Teratogenicity (when prego its fine): cleft lip and palate
-Nonlinear –> Constant amount is eliminated, so it could be hella toxic
-Iv form: fosphenytoin
AE
-CNS: Nystagumus (“dancing eye”), ataxia (can’t walk a straight line when drunk), diplopia (double vision), sedation (can limit dose)
-Endocrine: Osteomalacia (soft bones) with hypocalcemia (altered metabolism of vitamin D and inhibition of Ca absorption)
-Hematologic: megaloblastic anemia (due to folate deficiency; blocks folate absorption)
-Gingival hyperplasia (too much connective tissue)
-Facial coarsening (large lips n tongue)
-Hirsutism (when girls look like dudes)
What’s the MOA/Clinical Use/AE of Carbamazepine?
Similar to phenytoin!
-Any seizure except for absence seizures
-Effective for foal onset with or without spread to bilateral tonic-clonic seizure
-Trigeminal neuralgia(specific neuropathic pain) –> DRUG OF CHOICE
Bipolar disorders
-Induction of CYP3A4,CYP2CP (induces its own metabolism–> auto inducer)
-might have to adjust dose
-CNS: Diplopia, ataxia, drowsiness
-Hypersensitivity (BBW): Rash, steven johnson, NO ASIANS)
-Hematologic effects (BBW): Leukopenia (reversible), aplastic anemia (rare)
-Endocrine: Stimulates ADH secretion (control water and salt in body–> dilution hyponatremia)
What’s the MOA/Clinical Use/AE of Ethosuximide?
-Block T-type Ca channels in thalamic neurons
-Absence seizures (DOC)
-Hepatic metabolism
AE
-GI tract: anorexia, N/V, used in kids
-CNS: Sedation, dizziness, ataxia
What’s the MOA/Clinical Use/AE of Valproic acid?
-Prolongs inactivated state of Na
-Inhibition of GABA –> increase GABA
-Blockage of T-type Ca Channels
-Used for any seizures except absence)
-Migraine prophalaxais
-Bipolar
PK: High protein binding, hepatic metabolism
Inhibition of CYP2C9 (decrease metabolism of phenytoin and phenobarbital)
-caution pt with liver disease
-caution in children –> increase risk of fatal hepatotoxicity
-Teratogenicity: spina bifida (BBW PREGO USE PROTECTION REQUIREMENT)
-TAKE PREGO OFF OF DRUG!!!!
AE
Weight gain, hepatotoxicity
Tremor, dizziness, sedation, alopecia
What’s the MOA/Clinical Use/AE of Lamotrigine?
Prolongs inactivated state of Na channels
CNS: diplopia, headache, ataxia
Hypersensitivity: steven johnson (BBW)
What’s the MOA/Clinical Use/AE of Topiramate?
Prolong inactivated state of Na channels
-Enhances GABA
-Blocks AMPA
Any seizure except absence
-Good for primary and secondary generalized tonic-clonic seizures, focal seizures
Hepatic metabolism
CNS: memory, speech, language, headache, fatigue, dizzy, weight loss (phentermine together Qsymia)
-Induces CYP3A and Inhibits CYP2C19
-Precaution teratogenicity: cleft lip/palate
What’s the MOA/Clinical Use/AE of Gabapentin?
Enhances GABA effects/block Ca channels?
-Focal onset seizures and focal onset that spends to bilateral tonic clonic (adjunct)
-neuropathic pain
-Absorbs via :L-amino acid transporter –> saturable –> decrease F with dose
-RENAL EXCRETION
AE
Sedation, dizziness, ataxia, weight gain
What’s the MOA/Clinical Use/AE of BZD?
Diazepam
Lorazepam
GABA A receptor
-used for status epileptics (greater than 5 min!)
What’s the MOA/Clinical Use/AE of Barbiturates?
Phenobarbital
GABA A receptor
-used for status epileptics (greater than 5 min!)
Sedation, cognitive issues, ataxia
can be used for kids
What is status epilepticus?
Prolonged/repeated seizures without recovery of consciouness
Treatment
-IV Lorazrpam
-Wait 1 min, if no response, lorazepam again
-Even if seizure stops, administer non BZD (fosphenytoin)
What’s the MOA/Clinical Use/AE of Levetiracetam?
MOA: Binds to SV2A modified release of glu and gaba
-Used for any seizures (adjunct)
-Renal elimination
AE
-Minor CVS effects (sedation, psych)
What’s the MOA/Clinical Use/AE of Perampanel?
Blocks AMPA receptor
-Used for any seizures (primary or adjunct)
AE: CNS, Neuropsych (BBW)
Which drug cannot be given to a pregnant woman?
Valporic acid
What drug causes gingival hyperplasia?
Phenotoyin
What drug causes hirsutism?
Phenotoyin
What drug causes Osteomalacia?
Phenotoyin -vit D activation
What drug causes weight gain?
Valporic acid/ Gabapentin
What drug causes weight loss?
Topiramate(Weight loss drug approved)
What drug causes alopecia?
Vaporic acid
What drug causes rash?
Lamotrigine (BBW-Life threat)
Carbamazepine
What drug causes anemia?
Phenotoyin and carbamazepine
What drug causes cognitive changes?
topiramate
What drug is approved for neuropathic pain?
Gabapentin, Phenyotonin
What drug is approved for trigemninal neuralgia?
Carbamazepine
Which drugs are approved for bipolar?
Carbamazepine, valproic acid, and lamotrigine
Which drugs are approved for migraine?
Valporic acid
Phenytoin AE
P450 Inducer
Hinutism
Enlarged gums
Nystagmus (dancing eye)
Teratogenic
Osteomalacia (softening of bone)
Interferes with folate
Neural
Carbamazepine AE
Cyp Inducer (own metabolism)
ADH Increase (Hyponatremia)
Rash
Blood dysgraias –> aplastic anemia dis. bone ma
Amazepine
Valproic acid
V weight gain
Alopecia
Liver toc
Procic acid
Lamotrigine AE
Rash
Topiramate AE
Cognitive impairment, weight loss
What is sleep onset insomnia?
Difficulty falling asleep
What is sleep maintenance insomnia?
difficulty staying asleep
Name the MOA/Clinical Use/AE of a BZD.
Bind to “ALLOSTERIC MODULATOR” site off GABA(A)–> the BZD specific binding site
-Phase I reaction –> CYPS (Liver)
Phase II reaction –> Glucuronidation –> elimited by kidney
Consider AGE and HEPATIC function
Name the drugs that skip phase I CYP activation
Lorazepam
Oxazepam
Temazepam
” a LOT of drugs skip phase I”
What do you use to treat a BZD overdose?
Flumazenil
Name the MOA/Clinical Use/AE of Z-Compounds
Zolpidem
Same as BZD –> Bind to allosteric modulated
-Sleep onset and maintenance insomnia
fewer ae of BZD
Name the MOA/Clinical Use/AE of RaMELteon
Agonist at MT1 and MT2
-Sleep onset insomnia
-ONLY SEDATIVE HYPNOTIC DRUG APPROVED
Name the MOA/Clinical Use/AE of Suvorexant
Antagonist at OX1 and OX2 orexin receptors
-Sleep onset and sleep maintenance
Sedation, impaired driving, SUD
Name the MOA/Clinical Use/AE of Barbiturates
ALLOSTERIC MODULATORS (different binding site )
Insomnia, seizures
Tolerance, physical dependence, high addition potential, LTI
Name the MOA/Clinical Use/AE of Antihistimines
Antagonist at H1
insomnia
Anticholinerigc effects, daytime sedation
Amphetamine AE
Increase NE –> Increase Bp, arrhythmias, insomnia
-Increase dopamine –> growth inhibition
5HT–> anorexia
Ritalin MOA
Blocks NET and DAT to increase
-ADHD/sleepiness
Modafanil Indirect sympathomimetics
Block NET and DAT to increase
-excessive sleepiness
less AE
