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
