Advanced Pharmacology Flashcards
Cytochrome P450: CYP2C9
WARFARIN, glypizide, phenytoin
Cytochrome P450: CYP2C19
PPIs (OMEPRAZOLE), Anti-depressants.
Omeprazole - poor metabolizers of 2C19 had 5x higher serum concentrations - higher “cure” rate of GERD
Cytochrome P450: 2D6
CODEINE
Tramadol
oxycodone
hydrocodone
Deficient in 2D6 or taking an inhibitor: LESS ANALGESIA
Rapid metabolizers/inducers: EXCESSIVE side effects - respiratory depression
*Reason why we don’t give children codeine: rapid metabolizers will have excessive morphine production and resp depression
Malignant Hyperthermia: Genetics/diagnosis
Autosomal Dominant with variable penetrance
Incidence 1:100,000
Ryanodine (RYR1) - chromosome 19q
Other genes:
- severe phenotype from point mutation: Arg614Cys
- protein regulating excitation-contraction coupling: alpha1DHPR & FKBP12
Diagnosis:
Halothane-caffeine contracture test
- 100% sensitivity, 78% specificity
Malignant Hyperthermia: Ddx/Treatment
DDx:
- Sepsis (most often confused for MH)
- Pheochromocytoma
- Hypoxic encephalopathy
- Mitochondrial myopathies
- Periodic Paralysis (HypoK, hyperK)
Treatment:
- d/c triggering agents
- hyperventilation with 100% O2
- Dantrolene 2.5mg/kg, PRN within 36hr
- Foley (dantrolene has mannitol)
- Cool
- Treat hyperK, titrate resus (bicarb) to vitals
- ICU admission
- Cool
- NO Calcium channel blockers (use lidocaine)
Pseudocholinesterase Def (Butyrylcholinesterase): Factors affecting BuCHE levels
Decrease:
- Liver disease
- Advanced age
- Malnutrition
- Pregnancy (75% normal)
- Burns
- OCPs
Increase:
- EtOHism
- Obesity (increase dose of Sux)
*remember - only 10% of sux enters NMJ
Pseudocholinesterase Def: Dibucaine Number
Normal: 70-80
Heterozygous: 50-60, incidence 1/480. Sux dose effect lengthened 50-100%
Homozygous atypical: 20-30, incidence 1/3200. Sux dose prolonged 4-8hr
Prolonged QT Syndrome: QT prolonging drugs
Anti-arrhythmics: Amio, sotalol, quinidine, procainamide
Abx: cipro, levo, moxifloxacin, erythromycin, ketoconazole
Anti-depressants: amitriptyline, imipramine, desipramine, fluoxetine, sertraline
Antipsychotics: droperidol, haloperidol, thioridazine
Other: dolasterol, ondandsetron, methadone, volatile anesthetics
Prolonged QT Syndrome: Congenital Long QT
Deafness: Jervell and Lange-Nielsen syndrome
No deafness: Romano-Ward syndrome
Effects:
- Lightheadedness
- Syncope
- Torsades
- Cardiac Arrest
Triggers:
- Adrenergic Stimulation
- Auditory Stimulation
Three Ion Channel Abnormalities:
- LQT1
- LQT2 (K+)
- LQT3 (Na+)
Sudden Death:
- Female gender
- Males with QT3
- Deafness
- QT >500
- Widened T waves
Treatment:
- Acute: Mg++, replace K+, Ca++
- Chronic: BETA BLOCKADE, +/- pacing
Prolonged QT Syndrome: Acquired Long QT
Ddx:
- Pharmacologic (see drugs)
- Metabolic
- HypoK
- HypoMg
- HypoCa
*EKG is more notable for unusual T waves
Tx:
- IV Mg++
- Correct K+, Ca++
- AVOID AMIO
- Beta blockade
Prolonged QT Syndrome: Methadone
Black box warning
- Sudden death in doses as low as 20mg/day
- Etiology: inhibitor of gene hERG which encodes IKR-delayed rectifier inward K channel
Pre-treatment EKG required, f/u @ 30 days, then annually.
More frequent f/u required for:
-Daily dose >100mg
-QTc >450
Addiction Terms
Physical dependence: withdrawal symptoms occur with cessation
Tolerance: initial dose of substance loses its effect
Addiction: psychological/behavioral response that develops with use.
Behavior syndrome:
- craving (psych dependence)
- uncontrolled/compulsive use despite harmful s/e’s
- drug related aberrant behavior
Aberrant behaviors
- altering Rx’s
- manipulating health care providers
- unsanctioned drug escalation
- prevalence: opioid addiction as high as 50% in pts with chronic non-malignant pain.
- co-existing with psych d/o’s
Cocaine: abuse incidence, MOA, kinetics
1.5 million users
ER - 2nd most common cause of acute related visits - Chest pain is most common complaint
most common cause of drug-related deaths, MC drug in those seeking rehab
high lipid solubility, rapid aborsption with IV & inhaled use.
Kinetics: peak effect 1-60min, T_1/2: 30-90 min.
Can be detected in urine 15-60min after use
MOA: Slow Na ch blocker
-Inhibits re-uptake of norepi, dopamine, serotonin
Cocaine: systemic effects
Neuro:
- Initial euphoria (5-30min)
- Anxiety & restlessness
- Movement d/o’s
- Seizures
- Dopaminergic
- Benzos, barbs, phenytoin for tx
- Precedex may paradoxically lower sz threshold
Cardiac ACUTE: -HTN -Tachycardia -Arrhythmias -Coronary vasoconstriction -Aortic/coronary dissection CHRONIC: - cardiomyopathy - myocardial hyperthrophy - accelerated atherosclerosis - sudden death
Pulmonary ACUTE: - bronchospasm, - pulm hemorrhage, - ptx Chronic: - pulm nodular amyloidosis - pulm HTN - pulm edema - "Crack lung" - ARDS picture
Renal
-Ischemia, failure
Cocaine: Anesthetic implications
Airway: edema, bronchospasm may lead to diff ventilation. Lower airway disease
-Prolonged action of sux (cocaine metabolism competes)
- cardiac: at risk for arr’s, HTN, tachycardia/ischemia
- NTG & benzo’s for induction/premed adrenergic stim
- HTN: NO BETA BLOCKADE! - unopposed alpha
- Hydralazine: reflex tachy may worsen myocardial O2 demand
- use regional when possible
- no ephedrine, no ketamine
Cocaine: OB anesthesia implications
If cocaine use in pregnancy, likely other drug use
rapid transplacental diffusion, high fetal blood tissue levels detected
vasoconstriction incr risk of uteroplacental insuff acidosis, hypoxia, fetal distress
incr risk of placental abruption, uterine rupture, preterm delivery, and IUFD
neuraxial best technique, GA may cause tremendous hemodynamic shifts
