MHD - Exam 1 > Pharm- # 4 > Flashcards

Pharm- # 4 Flashcards

(24 cards)

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1
Q

What are the 3 drugs most common to have adverse drug effects?

A
  1. Pain medications
  2. Anticoagulant/antiplatelet agents
  3. Oncology (anti-neoplastic)
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2
Q

What provides the basis for the “usual” dose?

A

Population Pharmocokinetics (PK)

-PK:
picking a group of people, giving medication and seeing how much absorbed, distributed, metabolic pathway, elimination half life
 average this info

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3
Q

____: how the drug gets into the body from the site of administration.

_______: the fraction of administered drug that reaches systemic circulation unchanged.

A
  1. Absorption

2. Bioavailability

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4
Q

Which has 100% bioavailability? (parenteral or enteral)

Which type of non-enteral routes (3 specific) have less than 100% bioavailability?

What other factors impact bioavailability of NON-ENTERAL routes?

A

Parenteral

Non- enteral:

  1. Topical
  2. Transdermal
  3. Subcutaneous
  4. thick vs. thin skin
  5. Intact vs. impaired
  6. Lipophilic vs. hydrophilic
  7. Skin temp
    Fentanyl transdermal patches increase absorption with warm skin
     warmth dilates blood vessels
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5
Q

What are some Vd distribution basics? (3)

Medications with decreased protein binding cross ____ easier

A
  1. Will the medication reach its target?
    - area of body
    - perfusion
  2. Properties of the medication
    - lipophilic, hydrophillic (glycoside, antibiotic)
    - penetration into difficult areas
  3. Physiologic barriers
    - protein binding
    (low binding = higher Vd)
    - BBB
    - bone
    - eye
  4. BBB!
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6
Q

Reported _____ levels measure amount bound to albumin.

Decreased albumin can result in falsely ____ level

What can occur if the albumin level is not interpreted correctly?

A
  1. calcium
  2. LOW calcium level
    - calcium is 80% bound to albumin
  3. hypercalcemia
    - Calcium level 7.9 (low) serum albumin 1.9 (low)

Corrected calcium level for albumin: 9.58 (normal)
Corrected calcium = measured calcium + 0.8(4 – albumin

**Ionized calcium measures ‘non bound’ calcium

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7
Q

What is the primary site of METABOLISM of a drug?

What occurs here?

Which is conjugation, phase I or II?

A
  1. LIVER

a) Phase I
Reduction, oxidation, hydrolysis with CypP450 systems
Cyp 1A2, Cyp 2C9, Cyp 2C19, Cyp 2D6, Cyp 3A4

b) Phase II (Conjugation)
Glucuronidation, Acetylation, Sulfation (GAS)

Alterations in metabolism
Disease state(s)
Medication competition

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8
Q

Most drugs undergo _____ elimination.

Creatinine Clearance (CrCl ml/min) estimates function of what?

What is normal CrCl?

Elimination affects what?

A

RENAL!!!!! (test)
**Fecal / biliary less common – no adjustment
ex: ceftriaxone = biliary
linezolid = fecal

Renal function!

  1. “normal” = 70-100ml/min
    Cockroft and Gault formula is the ‘standard’ for adults
    CrCl will be different for healthy 30yo and 80yo
  2. Affects HALF LIFE

Useful equations

(a) t1⁄2=0.693/K(hr-1)(b) Cl (L/hr) = K(hr-1) x Vd (L)

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9
Q

What are 4 factors affecting elimination?

A
  1. Age
    - renal fx. decreases with age
    - Cr also comes from muscle and may overestimate renal fx. if using actual Cr level if
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10
Q

Phenytoin protein binding ___ (varies in pediatrics)

How does Vd change with:

  1. Dehydration
  2. Neonates
  3. Chronic Liver disease
  4. Renal failure
  5. Sulfadiazine co-administration
A

.9%

  1. Dehydration Vd decreases
  2. Neonates Vd increases
  3. Chronic Liver disease - Vd increases since protein binding decreases
  4. Renal failure
    Vd increases, Clearance decreases
  5. Sulfadiazine co-administration
    - Vd increases since protein binding decreases

**clearance increases for all but Renal failure

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11
Q

How does Loading dose (due to Vd) change for the following?

  1. Cystic Fibrosis
  2. CHF
  3. Gross obesity (for water soluble drug)
A
  1. CF = Vd INCREASES so loading dose Increases
  2. Vd increases = Ld increases for CHF
  3. Gross obesity Vd for WATER soluble drug decreases since ECF decreases
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12
Q

Who’s info is lacking in PK?

A
  1. neonates

2. Elderly patients

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13
Q

Because neonates have immature skin, their hydration _____ and absorption therefore _____ (increase or decrease).

A

Increase for both

  • increase ECF = increase Vd for water soluble drugs (aminoglycosides)

Metabolic pathways mature at different times

GFR, tubular secretion & reabsorption immature at birth

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14
Q

Elderly:

Skin thinning therefore absorption ____ (increase/decrease)

More or less adipose tissue? How does this affect Vd of fat soluble drugs?

ECF increase or decrease? How is Vd for water soluble drugs affected?

How is renal function affected?

A
  1. Skin thinning = increase absorption of topical products
  2. MORE adipose tissue = increase Vd of fat soluble drugs
    (neonates for water soluble)
  3. extracellular fluid DECREASES = decrease Vd of H2O soluble drugs*****
  4. Age related changes in renal function = decrease GFR
    * * 87 year old has low GFR —>must check dose
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15
Q
  1. What is TDM?
  2. Starting doses are designed based on ____.
  3. _________ may be given to help achieve an immediate therapeutic response.
A
  1. Therapeutic Drug monitoring

Medications for which drug levels are checked.

2.Starting doses are designed based on population pharmacokinetics.

Adjustments are made utilizing patient specific PK parameters calculated from patient specific drug levels.

  1. Loading Dose (LD) may be given to help achieve an immediate therapeutic response.
    Levels approximate those seen at steady state (SS)
    SS NOT reached faster —3 -5 half-lives still needed. !!!!!!
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16
Q

For TDM, dose adjustments are best made when the patient is at what?

SS is dependent only on ____.

What must remain stable for accurate dosing?

What are 3 reasons being at steady state is important?

Study These Flashcards
A

STEADY STATE

  1. HALF LIFE
  2. PK parameters!
  3. a) Minimizes potential for over/under dose adjustment
    b) Ensures maximum and stable distribution
    c) Safe and potentially cost effective dose adjustments
17
Q

Define the following:

A ‘peak’ drawn 12 hours after a dose is no longer a peak

(A reported ‘toxic’ level drawn from an IV line through which the drug was infusion may be falsely elevated)

A ‘trough’ drawn one hour after the dose is not a trough (too long after)

Study These Flashcards
A

Need to assess the test drawn in relation to when it was drawn to administered dose and from WHERE it was drawn

18
Q

What are some medication (drug) interactions that can affect the following:

  1. Absorption
  2. Distribution
  3. Metabolism
  4. Elimination
Study These Flashcards
A
  1. Absorption
    - Drug A effects Drug B
    - Chelation (2 drugs bind together & not absorbed)
    - pH changes
  2. Distribution
    - binding site comp. (albumin)
    - disease state alteration in proteins, fluid status, adipose
  3. Metabolism
    - hepatic
    - Cyp450 enzymes (induction/inhibition)
  4. Elimination
    - competition for pathways
    - primarily RENAL!!!
19
Q

What do the following drugs have in common:

  1. Sucralfate & levothyroxine (thyroid)
    - Ciprofloxacin and Calcium Carbonate
    - Itraconazole PO & Pantoprazole
  2. Aspirin & warfarin
    - Itraconazole & warfarin
Study These Flashcards
A
  1. DECREASED ABSORPTION
    - ciproflazacin & calcium carbonate are chelating agents

-Itraconazole (Sporonax®) (azole antifungal) + pantoprazole (Protonix®) (proton pump inhibitor)
Pantoprazole increases stomach pH
Decreases absorption of itrazonazole- possible clinical failure
Choose alternative acid reducing agent if possible

  1. Decreased PROTEIN BINDING
    - aspirin competes for protein binding sites of warfarin= increased free warfarin & more active drug
20
Q

What do the following have in common:

  1. Carbamazepime and oral contraceptives (OCP)
    - Rifampin and cyclosporine
  2. Voriconazole and tacrolimus
    - Disulfiram & a Cosmopolitan martini (alcohol)
    - Simvastatin (dose >20mg) and amiodarone
  3. Probenecid & Amoxicillin - decreased elimination
    Tobramycin & Cyclosporine
Study These Flashcards
A
  1. a) DECREASED levels
    Carbamazepime is a CyP450 inducer
    Increased OCP metabolism
    Decreased OCP concentrations = clinical failure
    *(b) Increased metabolism – decreased effect

b) Rifampin is a CyP450 inducer
Decreased cyclosporine concentrations may lead to clinical failure if
monitoring does not occur and if dose adjustments are not made

  1. Increased levels

a)Voriconazole is a CyP450 inhibitor
Increased tacrolimus concentrations = supratherapeutic effect
Black Box warning but in clinical practice, levels are monitored with
adjustments as needed
b)Disulfiram (Antabuse ®) + Pinot Grigio (wine)
Disulfiram inhibits aldehyde and alcohol dehydrogenase leading to
increased alcohol concentrations = SICK

  1. Probenecid & Amoxicillin - decreased elimination
    a)Probenecid blocks tubular secretion of amoxicilllin
    Increased amoxicillin concentrations = increased effect
    Intentional

Tobramycin & Cyclosporine – increased risk of toxicity
b)Tobramycin(aminoglycosideantibiotic)+Cyclosporine(Neoral®,
Sandimmune®) (immunosuppressant)
Both agents are renally eliminated and known to be nephrotoxic
Augmentation of adverse effects – increased risk of renal toxicity

21
Q

What does ciprofloxacin do to nutrient supplement shakes?

How do warfarin and vitamin K interact?

Study These Flashcards
A

Cause chelation
- decreased absorption of ciprofloxacin resulting in sub therapeutic levels

  1. (a) Warfarin affects vitamin K dependent clotting factors to prolong bleeding time
    (b) Consumption of vitamin K negates this effect leading to decreased warfarin efficacy (decreased PT/INR)
    (c) Patients CAN eat vitamin K containing products, but must be consistent with vitamin K content ingestion (not necessarily consistent with source types)
22
Q

What two drugs prolong QT interval?

Study These Flashcards
A

Heloperidol & Methadone

- predispose to arrhythmia

23
Q

What drug is 90% bound to albumin?

How does this change during significant burns?

How does Vitamin A supplement affect this undergoing hemodialysis?

How are codeine & CYP2D6 linked?

Study These Flashcards
A

Phenytoin

  • decreased albumin during burns & decreased bound phenytoin
  • measured total level may appear low so possible increased effect if dose increase is made
  • need to correct for albumin level
  1. Vitamin A is lipid soluble not removed by hemodialysis
    - may result in toxicity
  2. Codein is metabolized by CYP2D6 to morphine which elicits pain relief
24
Q

How are amoxicillin & probenecid linked?

Ritonavir & lopinavir?

Study These Flashcards
A

probenecid decreases the elimination of amoxicillin

  • ritonavir decreases metabolism of lopinavir
MHD - Exam 1
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