Pharmacology pt. 2 Flashcards
P-glycoprotein is an ____ found on brain capillary endothelial cells (part of the BBB) that inhibits a wide range of substrates/drugs from entering the brain. Inhibition of p-glycoprotein can improve drug delivery to the CNS.
efflux pump
an efflux pump found on brain capillary endothelial cells (part of the BBB) that inhibits a wide range of substrates/drugs from entering the brain.
Inhibition can improve drug delivery to the CNS.
P-glycoprotein
Activation of adrenergic receptors results in arrestin binding and receptor ______.
This effect is responsible for the tolerance effect seen with alpha-adrenergic (eg, decongestants, vasopressors) and beta-adrenergic (eg, bronchodilators) agonists.
internalization
Activation of adrenergic receptors results in ____ binding and receptor internalization.
arrestin
This effect is responsible for the tolerance effect seen with alpha-adrenergic (eg, decongestants, vasopressors) and beta-adrenergic (eg, bronchodilators) agonists.
adrenergic receptor internalization
via arrestin
Antibody-drug conjugates improve drug efficacy and minimize toxicity by allowing conventional chemotherapeutic agents to _______ cancer cells while sparing healthy cells (ie, targeted delivery).
selectively target and kill
*selectively uptaken by cancer cells
Calcineurin inhibitor nephrotoxicity with resultant impairment of renal function is the most significant adverse effect of
cyclosporine
enzyme-replacement therapy is a large molecule that cannot be orally absorbed, the replacement enzyme must be administered ______.
Entry into the cell occurs by endocytosis.
intravenously
*except pancreatic enzymes which function in GI tract
has MAOI activity and therefore can precipitate serotonin syndrome with concomitant use of an SSRI, SNRI, or TCAs
Linezolid
Heart failure leads to reduced liver and kidney blood flow, resulting in reduced drug ____.
clearance
Metformin toxicity causes
lactic acidosis
Decreased activity of hepatic ______ results in a diminished ability to metabolize drugs such as isoniazid and sulfonamides, leading to an increased likelihood of toxicity.
N-acetyltransferase
Overexpression of p-glycoprotein efflux pump in tumor cells has been identified as a cause of
multidrug resistance
Cytochrome P450 polymorphisms occurring in the genes result in various phenotypes that differ in their rates of metabolism; individual differences in phenotype alter treatment ___ and drug toxicity.
efficacy
Prevents hemorrhagic cystitis due to cyclophosphamide or ifosfamide. Mesna binds acrolein, the toxic metabolite formed by these agents.
Mesna
Hemorrhagic cystitis during therapy with cyclophosphamide or ifosfamide is caused by the urinary excretion of the toxic metabolite _____.
acrolein
*treat with Mesna
Drugs that inhibit CYP3A4 like, ____, can cause increased statin drug levels and lead to statin myopathy.
Macrolide antibiotics,
ketoconazole,
NDHP-CCBs (Verapamil)
amiodarone
The changes in the log dose-response curve expected for the effect of a reversible competitive antagonist added to a full agonist are (2)
1) a parallel RIGHT shift (increased ED50)
2) no change in the maximum effect (Emax).
* Noncompetitive = curve height shifts down (decreased Emax) no change (ED50)
Characteristics of a drug resulting in a low Vd (3-5L):
high molecular __,
___ plasma protein binding,
___ charge,
and hydro____
Trap the drug in the plasma compartment resulting in a low Vd
weight
high
high
hydrophilicity
a low Vd is __–__ L
3-5 L
can reverse the toxicity of methotrexate in non-cancerous cells in the gastrointestinal mucosa and bone marrow
Folinic acid (leucovorin)
a serotonin 5-HT3 receptor inhibitor that is used to treat nausea and vomiting following chemotherapy.
Ondansetron
Is used in the treatment of gout and for prevention of tumor lysis syndrome.
Allopurinol
*Rasburicase for tumor lysis syndrome also
When used in combination with 5-fluorouracil (5-FU), _____ potentiates the cytotoxic action of 5-FU (by binding thymidylate synthetase) and is frequently included in colorectal cancer chemotherapy regimens.
leucovorin
The presence of fast and slow ____ within the same population results in a bimodal distribution of the speed of isoniazid metabolism.
acetylators
the higher the Volume of Distribution, the greater the drug distribution into the
tissues
The drug concentration (mg/L)
is equal to drug dose (mg) divided by ___.
Volume of Distribution (L)
Half life is calculated using the ____
drug concentration (mg/L)
First order elimination is ____ DEPENDENT elimination
Flow
*downwards exponentially slope
List 3 drugs eliminated by ZERO order kinetics
Phenytoin
Ethanol
Aspirin (at high concentrations)
a PEA is round like ZERO
In ZERO order kinetics Phenytoin and Ethanol are eliminated in a ______ amount.
Constant amount
Ex:
t1/2 = 2
So elimination would be:
10 – 8 – 6 – 4 – 2 – 0
Zero order elimination is ____ limited
Capacity
*downwards linear slope
Antagonism of Muscarinic Receptors causes what to the pupils and Heart Rate?
Mydriasis
Tachycardia
are nonspecific and act as antagonists muscarinic acetylcholine receptors. This leads to anticholinergic effects (fever, urinary retention, decreased sweating, altered mental status).
First-generation antihistamines
are more specific to the histamine H1 receptor and have less permeability through the blood-brain barrier
second-generation antihistamines (loratadine)
___ adrenoreceptors are located on smooth muscle and neurons.
Alpha-1
Alpha 1 agonist increases smooth muscle tone of the iris dilator causing ____ and blood vessels causing _____
mydriasis
vasoconstriction
are not eliminated by hepatic or renal clearance. Therefore, no dose adjustment is necessary with impaired hepatic/renal function or use of cytochrome P450 inducers or inhibitors.
Monoclonal antibodies (mAbs)
During continuous infusion of a drug metabolized by FIRST-order kinetics, the steady state concentration is reached in ____ half-lives.
4 to 5
To calculate the time to reach 95% steady state concentration you have to multiply the drug’s HALF LIFE by 4 or 5.
Which characteristic should a drug have if hepatic metabolism and clearance is desired?
High lipophilicity (lipid solubility) Good CNS penetration Low first pass metabolism
Drug dosing regimens with ____ dosing have lower peak and average drug levels, which can help reduce drug toxicity.
more frequent
Drugs with a narrow therapeutic window are often dosed _____ to prevent large swings in plasma concentration.
more frequently
Average plasma drug levels are ___ when a fixed amount of drug is given in more divided doses.
lower
Average plasma drug levels are lower when a fixed amount of drug is given in ____ doses.
more divided
*efficacy is the same
_____ is a cholinesterase inhibitor with a tertiary ammonium structure that can reverse both the central and peripheral nervous system symptoms of anticholinergic toxicity (fever, urinary retention, decreased sweating, altered mental status).
Physostigmine
Neostigmine, edrophonium, and pyridostigmine have a quaternary ammonium structure that limits _____ penetration.
central nervous system
Anticholinergic Symptoms
Peripheral (3)
Tachycardia, Flushed skin, Mydriasis
Anticholinergic Symptoms
Central (3)
Delirium, coma, and respiratory failure
The increased drug half-life seen in certain patients is likely due to increased _____, resulting in a higher volume of distribution.
total body weight
A drug’s half life increases with a higher ____
volume of distribution (VD)
Half life = (.7)VD/CL
Metabolites can accumulate in the bloodstream of patients with renal dysfunction and lead to drug ___
toxicity
The most common side effect of aspirin.
Gastrointestinal (GI) mucosal injury & bleeding
Aspirin induced GI injury is due to cyclooxygenase-1 inhibition, which results in impaired _____ dependent
GI mucosal defense and
____ platelet aggregation.
prostaglandin
decreased
The primary adverse effects of ___ include flushing, hyperglycemia, and hepatotoxicity.
niacin
Medication-induced ______ is a common adverse effect of bisphosphonates.
esophagitis
Bisphosphonates are also associated with increased risk of
osteonecrosis of the jaw
atypical femoral fractures
Bisphosphonates decrease ______, thus lowering serum calcium levels. They are sometimes used in the treatment of severe hypercalcemia
bone resorption
Loading dose is affected by _____ and composition.
body weight
Isosorbide dinitrate has a low bioavailability due to extensive _____ prior to release in systemic circulation.
first-pass hepatic metabolism
Sublingual nitroglycerin is absorbed directly from oral mucosa into the venous circulation and has a higher
bioavailability
causes:
Formation of insoluble compounds with polyvalent cations in the gastrointestinal tract
Decreased absorption of drug
Chelation
Tetracyclines, Fluoroquinolones and Levothyroxine are susceptible to ____ thus decreased gut absorption
chelation
*Chelators: Iron, Ca, Mg, Aluminum
Neonates Pharmokinetic parameters:
Blood-brain barrier immaturity ↑ Proportion of \_\_\_ ↓ CYP enzyme activity ↓ Hepatic \_\_\_\_\_\_ ↓ \_\_\_\_ blood flow
body water
glucuronidation
Renal (↓ GFR)
Neonates have ↑ Distribution of WATER SOLUBLE drugs thus may need ____ mg/kg dose
higher
aminoglycosides, vancomycin
*causes lower plasma concentration of drug
Neonates have ↓ Renal blood flow & GFR thus may need ___ doses of renally excreted drugs
lower
have decreased plasma protein concentrations, which can increase free levels of highly protein-bound drugs like phenytoin and penicillin
Neonates
___ administration is capable of partially bypassing first-pass metabolism thus increasing the drug’s bioavailability
Rectal
*decreases drug’s delivery to the liver
In ____ individuals, use of lean body weight or an adjusted body weight may be necessary when dosing hydrophilic drugs (eg, aminoglycosides) that do not distribute into adipose tissue.
obese
In zero-order kinetics, a constant amount of drug is metabolized per unit of time, independent of ___ levels.
serum
*1st order CHANGES with serum levels (aka decreases)
A highly lipophilic drug will be rapidly distributed to organs with high blood flow like the brain, liver, kidneys, & lungs.
The drug is then REDISTRIBUTED to tissues with relatively lower blood flow like ___, fat, bone.
skeletal muscle
Antimuscarinic agents and antihistamines with antimuscarinic action are most effective for ____ prevention.
motion sickness
The presence of Drug A is required for the full effect of Drug B
Permissive
Effect of substance A and B together is equal to the sum of their individual effects
Additive
Drug B with no therapeutic action enhances the therapeutic action of Drug A
Potentiation
Carbidopa + levodopa
Acute decrease in response to a drug after initial/repeated administration
Tachyphylactic
Nitrates, LSD, Fluticortisone
