Pharmacology Flashcards
Gut absorption is most affected by which property of a drug?
Absorption is proportional to lipid solubility of the drug
Other factors that influence absorption:
Gastric pH
GI transit time
Mucosal permeability
List 3 ways drugs are eliminated from the body
- Elimination in urine**most drugs
- Metabolism (usually by liver)
- Uptake by liver and elimination in bile
What type of elimination kinetics do most drugs exhibit?
First order
Zero order if enzymes are fully saturated (rate of elimination does not change with concentration of drug)
How do you calculate clearance of a drug?
Clearance refers to the ability of the kidney and liver to remove a drug
Clearance=Volume of distrubtion x (0.69/half life)
What is bioavailability?
Proportion of administered drug reaching the systemic circulation
e.g. IV drugs=1000% bioavailiabiity
Affected by first pass metabolism and gut absorption
List 3 reasons for drug metabolism
- To make the drug more hydrophilic to help with excretion in kidney (lipophollic drugs are reabsorbed in renal tubules and would have VERY prolonged action without metabolism)
- Render drug less active
- To render drug active (prodrug)
Explain why cytochrome P450 dependent oxidation results in drug interactions
Liver is the main organ of drug metabolism
Cytochrome P450 oxidizes a bunch of lipophilic drugs (helping to render them more hydrophilic and easily excreted by kidney)
Some drugs INDUCE cytochrome P450:
Increases metabolism of cytochrome P450 dependent drugs
Some drugs INHIBIT cytochrome P450:
Reduces metabolism of cytochrome P450 dependent drugs
List 5 drugs that are substrates for cytochrome P450
Phenobarbital Cisapride Cyclosporine Tacrolimus Macrolides (except azithromycin) Benzodiazepines (diazepam, midazolam) Protease inhibitors Calcium channel blockers (eg, amlodipine) Atorvastatin, simvastatin, lovastatin
What are phase I and phase II reactions?
Describe the steps in drug metabolism in the liver
Phase I
-Most common is oxidation, others are reduction or hydrolysis
Phase II
- Conjugation of drug or Phase I metabolite
- Usually results in less active metabolite that is polar and readily excreted in kidneys
Which drugs induce cytochrome P450?
- Rifampin
- Phenytoin
- Phenobarbital
- Carbamazepine
- Nevirapine, efavirenz
- St. John’s Wort
Which drugs inhibit cytochrome P450?
- Erythromycin, clarithromycin (3A4)
- Ketoconazole, itraconazole (3A4)
- Valproic acid
- HIV protease inhibitors (eg, ritonavir)
- Fluoxetine, paroxetine, codeine (2D6)
- Nefazodone (3A4)
- Grapefruit juice (intestinal CYP 3A4 only)
What is the difference in volume of distribution between infants <6 months and older kids?
Infants <6 months have greater volume of distribution (because 75% total body water!)
How is the activity of many cytochrome P450 enzymes and glucuronsyltransferases different in the first 2 months of life?
Activity of many cytochrome P450 enzymes and glucuronsyltransferase is significantly decreased in the first 2 months of life
List 5 differences between neonates and older kids in pharmacokinetics
- Decreased activity of cytochrome p450
- Greater volume of distribution (more water!)
- Gastric emptying time longer
- Greater mucosal permeability
- Decreased renal clearance function
- Lower protein-binding of drugs
As a result, neonates have LOWER BLOOD CONCENTRATIONS of drugs
List 3 adverse effects of carbamezipine
SJS Agranulocytosis Liver toxicity Tics Hyponatremia Weight gain Dizziness Nausea
List 2 adverse effects of gabapentin
Acute onset of aggression
Hyperactivity
List 3 adverse effects of lamotrigine
SJS
Liver toxicity
CNS effects-headache, ataxia, dizziness, tremor
List 3 adverse effects of levetricetam
Behavioural symptoms Less CNS effects than other AEDs: Somnolence Dizziness Asthenia
List 3 adverse effects of phenobarbitol
SJS Liver toxicity Insomnia Neurotoxicity Hyperactivity Fluctuation in mood
List 3 adverse effects of phenytoin
Concentration dependent: ataxia, nystagmus, dizziness, headache, sedation, visual blurring, diplopia, cognitive impairment
Idiosyncratic:blood dyscrasias, rash(SJS and TEN rare)
Chronic: gingival hyperplasia, folate deficiency, osteomalacia, skin thickening, hirsutism, coarsening of facial features
Rare: DRESS, SLE-like syndrome
List 3 adverse effects of valproic acid in the following categories:
Dose dependent
Idiosyncratic
Chronic
Dose dependent: GI upset Sedation Unsteadiness Tremor Thrombocytopenia
Idiosyncratic:
Acute hepatic failure
Acute pancreatitis
Alopecia
Chronic: Weight gain Hyperammonemia Menstrual irregularities Polycystic-ovary-like syndrome Decreased serum levocarnitine
List 3 adverse effects of topiramate
Precipitation of glaucoma Renal stones Weight loss Cognitive dysfunction Hypohydrosis
Most important adverse effect of vigabatrin
Retinopathy***
Irrerversible visual filed deficits
Hyperactivity
What medications cause acute dystonic reactions?
Antipsychotics, anti-emetics, and antidepressants
What medications cause acute dystonic reactions?
Anti-dopaminergics:
Antipsychotics, anti-emetics, and antidepressants
List 3 clinical features of acute dystonic reaction
- Oculogyric crisis
- Torticollis
- Widely open mouth, tongue protrusion, trismus
- Laryngospasm!!
Treatment of acute dystonic reaction
IV diphenhydramine or benztropine
List 3 adverse effects of inhaled corticosteroids
- Growth deceleration, resulting in 1.2 cm reduction in adult height
- Oral thrush
- Dysphonia
- Rare-adrenal insufficiency, increased IOP
List 10 side effects of systemic steroids
- Striae
- Acne
- Alopecia
- Hirsutism
- Cushingoid appearance
- Elevated IOP
- Increased risk of cataracts
- HTN
- Increased risk of atherosclerosis
- PUD
- Gastritis
- Steatohepatitis
- Osteoporosis
- AVN
- Insomnia
- Behavioural change (euphoria, depression, mania)
- Increased risk of DM2
- Adrenal suppression
- Increased risk of infections
List 5 adverse affects of anabolic steroids
-Suppression of endogenous testicular function ➢ Decreased spermatogenesis and fertility – returns to normal 4mo after stopping ➢ Testicular size may decrease if using for many years -Gynecomastia -Erythrocytosis -Hepatotoxicity -Psychological disorders -Decrease in HDL -Coagulation activation -Premature epiphyseal fusion -Infections -Virilization in women -Risky and violent behavior -?Liver cancer
What is redman syndrome and what drug causes it?
RMS is an idiopathic rate-dependent infusion reaction, not a true allergic reaction
Typically caused by IV vancomycin
Characteristics:
o Flushing/erythema
o Pruritus
o Upper body, neck, and face more than the lower body
o Pains and muscle spasms in the back and chest
o +/- Dyspnea, hypotension
Treatment of redman syndrome
- For mild to moderate reactions (HD stable) → stop infusion → treat with diphenhydramine and ranitidine →restart at ½ original rate
- For severe reactions (e.g. muscle spasm, chest pain, hypotension) → same as previous but may need IV fluids, and run vanco even slower over 4 hours
Name 2 things you can do to prevent redman syndrome
a) Pretreat with diphenhydramine and ranitidine
b) Slow down the infusion rate to half of the original rate
What complication is associated with erythromycin use in infants?
Pyloric stenosis
Which SSRI has most evidence for the treatment of depression in children?
Fluoxetine
What is the minimum trial period for an SSRI?
6 months
List 5 side effects of SSRIs
Common: Sexual dysfunction*** most common Drowsiness***most common GI symptoms: vomiting, diarrhea Headaches
Serious:
Serotonin syndrome
SIADH
Coagulopathy
Others: Insomnia Restlessness Appetite suppression Agitation Suicidality-debatable
Which SSRI is associated with QTc prolongation?
Citalopram
List clinical features suggestive of serotonin syndrome
Mental status changes Myoclonus Ataxia Hyperreflexia Tremors Diaphoresis Fever Autonomic dysregulation
How do you initiate, monitor and titrate an SSRI? (past SAQ)
Start at a low dose, monitor weekly x 4 weeks, then q 2 weeks for 4 weeks, slowly tirate dose up until reach minimally effective dose.
Monitor for symptoms: side effects, suicidality and assess for compliance
List 5 adverse effects of atypical antipsychotics
Have both dopaminergic and serotongergic effects
- Extrapyramidal symptoms (dystonia, rigidity, tremor, and akathisia)
- Weight gain
- Metabolic syndrome and diabetes
- Hyperprolactinemia
- Gynecomastia
- Hematologic adverse effects (e.g., leukopenia or neutropenia)
- Seizures
- Hepatotoxicity
- Neuroleptic malignant syndrome
- Cardiovascular effects: QTc prolongation and sudden death
List 4 side effects of stimulants
- Appetite suppression***most common
- Sleep disturbances***most common
- Irritability
- Headaches
- Stomachaches
- Lethargy and fatigue
- Exacerbate tics (1-2 %)
- Sudden death in children with structural cardiac abnormalities
- Depression (late effect)
Which ADHD medications should be used if there is concern of substance abuse or diversion?
Extended release e.g. Vyvanse Non-stimulant e.g. Atomoxetine (strattera) Non-pill e.g. Methylphenidate patch
Do stimulant meds decrease the risk of the risk of substance abuse?
YES
Describe the principles of homeopathy
- Like cures like
2. Higher dilution=more potent
What conditions has homeopathy been proven to be effective?
Diarrhea
Benefits have been showen in allergy/ADHD, but flawed studies
List 5 drugs that can cause pseudotumour cerebri
- OCP***
- Minocycline***
- Tetracycline***
- Isotretinoin used for acne therapy especially when combined with tetracycline
- Prolonged corticosteroid use
- Nalidixic acid
- Doxycycline
- Sulfonamides
- Nitrofurantoin
- Cytarabine
- Cyclosporine
- Phenytoin
List 5 conditions associated with pseudotumour cerebri
- Metabolic disorders:
- Obesity*
- Hypoparathyroidism*
- Hypervitaminosis A***
- Galactosemia
- Hypophosphatasia
- Refeeding syndrome
- Severe vitamin A deficiency
- Addison disease
- Menarche
- Pregnancy - Infections:
- Roseola
- Sinusitis
- Chronic otitis media
- Mastoiditis
- Guillain-Barré syndrome - Hematologic disorders:
- Polycythemia
- Hemolytic anemia
- Iron-deficiency anemia
List absolute contraindications for OCP (there are 11!)
- Pregnancy
- Breastfeeding <6 weeks post partum (clotting risk)
- Serious cardiovascular disease:
Current DVT, PE, stroke, complicated valvular heart disease - APL-Abs (or lupus and unknown APLA status)
- Uncontrolled hypertension (SBP>160, DBP >100)
- Active liver disease
- Migraine with neurologic symptoms (aura)
- Current breast cancer
- Major surgery with prolonged immobilization
- Undiagnosed uterine bleeding (r/o pregnancy, cancer)
List relative contraindications to OCP
- Hypertension
- Breastfeeding <6 months post partum
- Certain hyperlipidemias
- Past breast cancer, disease free>5 years
- Medications: ritonavir-boosted protease inhibitors, anticonvulsants, rifampin
- Diabetes with vascular disease or >20 years
- Certain liver disease (symptomatic gall bladder disease, acute hepatitis)
List 4 drugs that affect the efficacy of OCPs
Rifampin
Phenobarbital
Phenytoin
Griseofulvin
List 3 chronic adverse effects of marijuana
Cannabis dependence syndrome
Chronic bronchitis
Psychosis and psychotic d/o
Subtle coginitive impairment (in daily users >10 years)
List 5 adverse effects of marijuana use
Short term:
- Conjunctival injection
- Tachycardia***
- Bronchospasm***
- Gynecomastia***
- Decreased libido
Long term:
- Cannabis dependence syndrome
- Chronic bronchitis
- Psychosis and psychotic d/o
- Subtle coginitive impairment
List 3 adverse effects of ketamine
Vomiting Unpleasant hallucinations Apnea Laryngospasm Sialorrhea
List 3 absolute contraindications to ketamine
Absolute:
<3 months of age
Severe adverse reaction in past
Patient with known or suspected psychosis
Relative: <12 months of age Active pulmonary infection Hypertension Angina or heart failure Glaucoma Increased ICP caused by obstructive brain lesions Thyroid disease Porphyria
What sedation drug is the best amnesic?
Midazolam (although may only have antegrade amnesia)
What is the best sedation for a CT scan?
Oral midazolam (shorter duration of action than chloral hydrate)
Which 3 sedatives are associated with the most hemodynamically stability?
Fentanyl
Etomidate
Ketamine
What is the maximum daily dose of tyenol?
Dose should not exceed 75mg/kg/day or 4g/day
How do you assess pain in children in the following age groups? Newborns 3-8 years old 8-11 years Teens
Newborns
- FLACC/PIP scores
- Based on facial expressions, crying, and body movement
3-8 years old
-Visual analog scale with faces
8-11 years
-Visual analog scale with numbers
Teens
-Verbally without visual assistance
Equianalgesic doses of opoids for IV morphine 10 mg:
i) Morphine IV
ii) Morphine po
iii) Fentanyl IV
iv) Hydromorphone IV
v) Hydromorphone po
i) Morphine IV
- 10 mg
ii) Morphine po
- 30 mg
iii) Fentanyl IV
- 0.2 mg
iv) Hydromorphone IV
- 1.5 mg
v) Hydromorphone po
- 7.5 mg
List 5 side effects of morphine
Hypotension (secondary to histamine release***) Constipation Urinary retention N/V Pruritus
Why is there so much variability in the response to codeine in children?
- Codeine is ineffective in a large portion of children due to genetic polymorphisms in CYP2D6 gene that cause poor metabolism of the drug (33% non responders)
- A smaller portion of children may have increased conversion of codeine to morphine (extensive and ultrarapid-metabolizer phenotypes),
How do NSAIDs work?
Cyclooxegenase inhibitor (inhibits prostaglandin synthesis)
List 5 side effects of indomethacin
- Platelet dysfunction and risk of bleeding (IVH)
- GI perforation/gastritis
- Decreased GFR/reduced renal bloodflow
- Hepatic dysfunction
- Reduced cerebral blood flow
What is the most common side effect of cephalosporins?
Diarrhea
What is the recommended dose to limit clavulinic acid when prescribing amox/clav?
10 mg/kg/day
What ratio of amox/clav is recommended for treatment of AOM?
7:1 ratio (4:1 will likely induce diarrhea)
What should you advise a parent regarding cough medicines?
Not effective
Potentially harmful-increased risk of ALTEs, ED visits, death
Pseudoephedrine-agitation, HTN, arrythmias
Should not be used in kids <6 years
Why should parents avoid giving topical nasal decongestants for a prolonged period of time?
Results in rebound nasal congestion
Why is diazepam rarely used in neonates?
Decreased hepatic clearance
Can cause respiratory depression
List 6 clinical signs of Gravol toxicity
Anticholinergic: Anhidrosis Fever Dilated pupils Delirium Urinary Retention Tachycardia Decreased Bowel Sounds Rare: Seizures, arrythmias
List 4 mechanisms of action of insulin
- Inhibition of glycogenolysis and gluconeogenesis
- Increased glucose transport into fat and muscle
- Increased glycolysis in fat and muscle
- Stimulation of glycogen synthesis
- Inhibition of lipolysis
- Decreased proteolysis in muscle
List 4 principles of treatment with opioids in palliative care
- Utilize non-opioid analgesics as adjunct
- Start with short-acting opoids for moderate/severe pain, then switch to long acting with break through
- Avoid codeine
- Administer via the least distressing, most effective route
- Manage side effects-bowel regimen, treat pruritus
- Use adjuvants for opoid sparing-e.g. antidepressants, anticonvulsants
How do you loop diuretics work?
- Inhibits Na-K-2Cl carrier
- Reduces NaCl reabsorption in the thick ascending limb of the loop of Henle
List 4 side effects of lasix
Hypokalemia, Hyponatremia, Hypochloremia
Metabolic Alkaosis
Volume Contraction – elevated Creatinine, Urea
Hypercalciura ->Urolithiasis ->Nephrocalcinosis
Biliary Stones
Pancreatitis
Ototoxicity
What is DRESS?
Drug Rash with Eosinophilia and Systemic Symptoms
- Triad of symptoms: fever, rash, internal organ (e.g., liver, kidney, heart, lung, brain)
- Delayed onset: 6 days to 12 weeks from initial exposure
What drugs typically cause DRESS?
Most commonly AEDs with aromatic ring Phenytoin Phenobarbital Carbamazepine Lamotrigine
Others:
Minocycline
Sulfonamides
Allopurinol
What test needs to be done in patients on ethambutol?
Can cause optic neuritis and impaired colour vision
Eye exam
What 3 drugs are at highest risk of causing C. diff?
Third generation cephalosporins
Clindamycin
Aminopenicillins (e.g. amox-clav)
List 4 manifestations of cocaine use
Increased alertness Euphoria Hallucinations Irritability Tachycardia HTN
Others:
- CNS: increased energy, insomnia, fear, paranoia, aggressive behaviour, psychosis, seizures, stroke
- CVS: MI
- Increased body temperature, sweating
