Pharmacology Flashcards
What is the definition of anticholinergic burden?
The cumulative effect of medications that have anticholinergic properties
What pharmacokinetic changes occur with aging?
Absorption - slowed gastric emptying, inc gastric pH, dec small bowel surface area
Distribution - body fat increases (longer half life lipophilic), total body water decreases (inc plasma conc of hydrophilic)
Metabolism - hepatic first pass metabolism decreased
Elimination - renal decreased
How do pharmacokinetic changes affect morphine in an older patients?
Absorption - no change
Distribution - morphine is hydrophilic, higher conc
Metabolism - dec first pass metabolism
Elimination - renal decreased
What are the mechanisms of action of donepezil, rivastigmine and galantamine?
Donepezil - reversibly inhibits acetylcholinesterase
Rivastigmine - reversibly (pseudo) inhibits both acetylcholinestase and butylcholinesterase
Galantamine - reversibly inhibits acetylcholinesterase, binds to presynaptic Ach nicotinic receptor and inc AcH release
List 6 evidence based benefits of cholinesterase inhibitors
- Improved cognition (MMSE, ADAS-Cog)
- Improved behaviours (NPI, SIB)
- Improved function
- Improved global clinical state
- No evidence for QOL
What are 2 pharmacokinetic differences between intrajejunal levodopa gel and oral?
Intrajejunal bypasses impact of gastric emptying which can affect rate of absorption of oral = variable blood concentration
IJ more stable concentration, oral has short half life and more rapid wearing off
What is the main motor symptom that IJ Sinemet helps with?
Off symptoms (motor fluctuations)
What antidepressant would you not prescribe in a patient with hx of seizures?
Bupropion - lowers seizure threshold
What 6 categories of interventions to improve medication adherence?
- Clinical pharmacist consultation
- Patient education
- Incentives to promote
- CBT
- Medication regimen management
- Medication taking reminders
What are absolute contraindications to cholinesterase inhibitors?
- Hypersensitivity (drug monograph)
Off drug monograph - High grade cardiac condition block (second or third degree in unpaced, except RBBB)
- Bradycardia <50 bpm
- QT prolongation
What are precautions when using cholinesterase inhibitors?
- Not recommended if cardiac conduction abnormalities
- PUD, NSAID, high dose ASA - monitor
- Bladder outflow obstruction
- COPD/asthma
- May lower seizure threshold
- Rare rhabdo
- Rare NMS
What are 2 drug categories associated with C diff infections?
- PPIs
- Systemic antibiotics
Why should someone on DOAC not take clarithromycin?
Clarithromycin (also ketoconazole and itroconazole) is a CYP3A4 and P-gp inhibitor
Apixaban, rivaroxaban and dabigatran are P-gp substrates
Clarithromycin therefore decreases clearance of DOACs leading to inc levels and bleeding
What is the drug interaction between paroxetine and tramadol?
Paroxetine = CYP2D6 inhibitor
Tramadol = substrate of CYP2D6
This leads to inc tramadol = serotonin reuptake inhibition
In combination with SSRI leads to serotonin syndrome
Compare cholinesterase inhibitors with regards to their distribution
Donepezil - 96% plasma protein bound (esp albumin)
Rivastigmine - 40% plasma protein bound
Galantamine - 18% plasma protein bound
Compare cholinesterase inhibitors with regards to their metabolism
Donepezil - slow extensive liver metabolism by CYP3A4/2D6, glucoronidation. Half life 58-90 hrs.
Rivastigmine - extensive rapid first pass metabolism, doesn’t use P450
Galantamine - metabolized by liver, using CYP3A4/2D6, glucuronidaiton
What medications can cause B12 deficiency?
- PPI
- H2 blockers
- Metformin
- Colchicine
- Phenytoin
What pharmacokinetic reason can cause phenytoin toxicity?
Phenytoin is 90% bound to plasma proteins (albumin) and in unbound form is active
If you have malnutrition = low albumin = inc unbound phenytoin = phenytoin toxicity
What are 4 adverse outcomes of benzodiazepines use in the elderly?
- Memory impairment
- Inc risk falls/fractures
- Inc mortality risk
- Psychomotor retardation
- Inc accidents
- Respiratory issues in COPD
What is the mechanism of action of trazodone?
Serotonin reuptake inhibitor
What are 3 adverse effects of trazodone that can increase risk of falls?
Dizziness, drowisness, blurred vision
1. Sedation
2. Confusion
3. Blurred vision
4. Dizziness
5. HOTN
Comparing trazodone to atypical antipsychotics what are the risks for falls, OP fracture, hip fracture and 90 day mortality?
Falls = similar
OP fracture = similar
Hip fracture = similar
90 day all cause mortality = lower
What are 5 common adverse effects of donepezil?
- N/V/D
- Poor appetite/weight loss
- Vivid dreams/nightmares
- Bradycardia/syncope
- Worsening urinary frequency
What are two potential drug interactions with donepezil?
- Negated with use of anticholinergic drugs
- Inc levels with erythromycin, ketoconazole, paroxetine
- Dec levels with carbamazepine, dexamethasone, phenytoin
How does warfarin interact with the following drugs: ginseng, amiodarone, allopurinol, phenytoin, carbamazepine, trazodone, sulphonamide, citalopram
Increase effect = inc INR = inc bleeding risk
1. Amiodarone
2. Sulphonamide
3. Allopurinol
Decrease effect
1. Ginseng
2. Carbamazepine
3. Trazodone
Unpredictable
1. Phenytoin
Inc risk bleeding but not necessarily due to INR
1. Citalopram
What are donepezil cyt P450 enzymes?
CYP3A4
CYP2D6
What are 3 drugs that are inducers and 3 inhibitors of the cytochromes that metabolize donepezil?
Inducers
CYP3A4 - carbamazepine, phenytoin
CYP2D6 - dexamethasone
Inhibitors
CYP3A4 - ketoconazole, erythromycin,diltiazem, amiodarone???
CYP2D6 - bupropion, fluoxetine, paroxetine
What is a target Li concentration in older adults?
0.4-0.8 mmol/L
8-12 hours post dose
Why are elderly more prone to lithium toxicity?
Lower GFR
Reduced volume of distribution (lower body water)
Dehydration
What two drug classes worsen the renal toxicity of lithium?
Medications the impair renal filtration
1. ACEi
2. Thiazide diuretics
What are 6 neurologic effects of acute lithium toxicity?
- Seizure
- Encephalopathy
- Tremor
- Fasciculations
- Myoclonic jerks
- Confusion
- Ataxia
What are 4 categories of pharmacokinetic changes with aging that are associated with processing pain meds and how it affects drug handling?
Absorption - not affected
Distribution -
Hydrophilic = reduced distribution = inc serum concentration
Albumin bound = more unbound active
Elimination - inc conc with renal impairment
What is the mechanism of action behind 4 side effects of cholinesterase inhibitors?
- Bradycardia - Ach binds to M2 muscarinic R = dec HR
- Nausea/weight loss = Ach receptor in chemoreceptor trigger zone = vomiting
- Bronchospasm = Ach constricts smooth muscle
- Urinary frequency = Ach stimulates contraction of bladder wall
What are 4 possible reasons that the flu vaccine is ineffective?
- Different strain of flu
- Getting flu before immunity
- Decreased sensitivity to vaccinations overall with aging
- Coexisting lung disease
- Other illness causing flu like symptoms
- Antibody titers wane faster in OA
What are 4 potential significant benefits of flu vaccine?
- Less influenza like illness
- Prevent hospitalization in older adults
- Decreased mortality
- Decreased LOS
What effect does flu vaccine in HCW in nursing homes have?
Little or no effect on lab proven influenza
No change to number of admission to hospital for respiratory illness
What is the efficacy of live attenuated VZV vaccination in patients over 70?
Live attenuated = Zostavax which is 61% efficacious
Shingrix - 96.6-97.9% for all age groups
Efficacy similar throughout age groups
What are three common trazodone side effects?
- Drowsiness
- Dizziness
- Headache
- Nervous/anxiety
- Dry mouth
Name 5 side effects of dopaminergic agents
- Excessive daytime sleepiness
- Orthostatic HOTN
- Hallucinations
- Impulse control disorder
- Dyskinesia
- Ankle edema
- N/V
What are 3 side effects of gabapentin?
- Dizziness
- Drowsiness
- Ataxia
- Fatigue
What are 4 messages to use regarding not using sedatives for sleep?
- Not better quality of sleep
- Not feeling more refreshed
- Increased daytime somnolence
- Risk of falls, fractures, cognitive decline
List 6 drugs that interact with antiretrovirals and what is the interaction
Ritonavir, Indinavir, Saquinovir –> substrate and inhibitor of CYP3A4
Clindamycin - inc conc ARVs
Diltiazem - inc conc ARVs
Carbamazepine - dec conc ARVs
Rifampin - dec conc ARVs
Phenytoin - dec conc SRVs
Atorvastatin - inc conc statin
What is a pharmacokinetic and pharmacodynamic interaction between glyburide and Septra?
PK
Septra is a CYP2C9 inhibitor
Glyburide is metabolized by CYP2C9
Therefore less glyburide metabolized = inc insulin secretion = hypoglycemia
PD
Septra can independently increase insulin by stimulating pancreatic beta cells = hypoglycemia
What are some drug interactions with warfarin?
Quinolones = may enhance anticoagulant effect
Amiodarone = inc warfarin effect
Plavix = inc bleeding risk
What are the components of the hAS-BLED score?
HTN (SBP>160)
Abnormal liver or renal function - Cr 200+ or dialysis, AST/ALT >3x ULN
Stroke
Bleeding
Labile INR
Elderly >65
Drugs (associated with risk of bleeding) or Alcohol
What are four potential AEs of topical beta blockers?
Bradycardia/heart block
Worsen CHF
Mask hypoglycemia symptoms
Depression
Bronchospasm
What is the mechanism of action of memantine?
NMDA receptor antagonist
Prevents glutamatergic over stimulation and resulting neurotoxicity
Therefore has neuroprotective effects
What are the benefits of the rivastigmine patch?
Similar efficacy with oral
Improved tolerability - less GI symptoms
Caregivers preferred patch over pill
Easy of use
