D441 Medical Dosage Calculations and Pharmacology ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Chapter 2 Pharmacological Principles Exam with ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
accurate detailed solutions ||/|\||| ||/|\|||
Explain the relationship with potassium and digoxin. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Digoxin competes for binding sites with potassium on the sodium-potassium ATPase pump.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Here's how it works: ||/|\||| ||/|\||| ||/|\|||
1. Binding Sites: The sodium-potassium ATPase pump has specific sites where potassium
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
ions usually bind to be transported into the cell.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Competition: Digoxin competes with potassium for these binding sites. When digoxin
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
binds to the pump, it inhibits its function, preventing potassium from entering the cell and
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
sodium from leaving the cell. ||/|\||| ||/|\||| ||/|\||| ||/|\|||
This competition is why low potassium levels (hypokalemia) can increase the effects of
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
digoxin, as there are fewer potassium ions to compete with digoxin for those binding sites.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Conversely, high potassium levels (hyperkalemia) can reduce the effects of digoxin because ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
more potassium ions are available to compete with digoxin for binding to the pump.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
All topical routes of drug administration avoid first-pass effects of the liver, except:
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Rectal administration. Because it is part of the GI tract, some drug will be absorbed into the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
capillaries that feed the portal vein to the liver. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Depot Drugs ||/|\|||
Specifically formulated long-acting IM dosage forms; designed for slow absorption over a ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
period of several days to months. Example: invega ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Blood-brain barrier ||/|\|||
Blood vessels (capillaries) that selectively let certain substances enter the brain tissue and
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
keep other substances out. ||/|\||| ||/|\||| ||/|\|||
How does the lipophilicity of a drug affect its metabolism and excretion? What role does the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
liver play in this process?||/|\||| ||/|\||| ||/|\||| ||/|\|||
, Lipophilicity, or the ability of a drug to dissolve in fats, affects its metabolism and excretion ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
in several ways:
||/|\||| ||/|\|||
1. Absorption and Distribution: Lipid-soluble drugs are readily absorbed through cell
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
membranes, which are composed of lipid bilayers. Once absorbed, these drugs are widely ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
distributed throughout the body, particularly in fatty tissues. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Metabolism: The liver plays a crucial role in metabolizing lipid-soluble drugs. The liver
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
converts these drugs into more water-soluble metabolites through processes like oxidation,
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
reduction, and conjugation. This transformation is essential because it makes the drugs ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
easier to excrete. ||/|\||| ||/|\|||
3. Excretion: Once metabolized, the water-soluble metabolites are excreted through the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
kidneys in urine or through the bile in feces. Because lipid-soluble drugs are stored in fat
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
tissues, they can be released slowly over time, leading to prolonged effects and a longer
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
presence in the system. ||/|\||| ||/|\||| ||/|\|||
Overall, the liver's metabolic processes are vital for transforming lipid-soluble drugs into
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
forms that can be efficiently excreted from the body.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
How does p-glycoprotein affect drug metabolism?
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
P-glycoprotein (P-gp) is a crucial player in drug metabolism and transport. It's a type of ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
efflux transporter protein found in cell membranes, particularly in the intestines, liver,
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
kidneys, and blood-brain barrier. Here's how it affects drug metabolism: ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
1. Drug Absorption: P-gp can pump drugs out of cells lining the intestines, reducing the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
absorption of certain drugs into the bloodstream. This can lower the drug's bioavailability. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Drug Distribution: In the blood-brain barrier, P-gp can limit the entry of drugs into the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
brain, affecting the distribution of drugs that need to act on the central nervous system.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
3. Drug Elimination: In the liver and kidneys, P-gp helps in the excretion of drugs and their
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
metabolites. It pumps drugs into bile in the liver and into urine in the kidneys, facilitating ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
their elimination from the body.
||/|\||| ||/|\||| ||/|\||| ||/|\|||
Overall, P-glycoprotein acts as a protective mechanism to limit drug absorption and enhance
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
drug elimination, which can influence the effectiveness and duration of a drug's action.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Chapter 2 Pharmacological Principles Exam with ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
accurate detailed solutions ||/|\||| ||/|\|||
Explain the relationship with potassium and digoxin. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Digoxin competes for binding sites with potassium on the sodium-potassium ATPase pump.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Here's how it works: ||/|\||| ||/|\||| ||/|\|||
1. Binding Sites: The sodium-potassium ATPase pump has specific sites where potassium
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
ions usually bind to be transported into the cell.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Competition: Digoxin competes with potassium for these binding sites. When digoxin
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
binds to the pump, it inhibits its function, preventing potassium from entering the cell and
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
sodium from leaving the cell. ||/|\||| ||/|\||| ||/|\||| ||/|\|||
This competition is why low potassium levels (hypokalemia) can increase the effects of
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
digoxin, as there are fewer potassium ions to compete with digoxin for those binding sites.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Conversely, high potassium levels (hyperkalemia) can reduce the effects of digoxin because ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
more potassium ions are available to compete with digoxin for binding to the pump.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
All topical routes of drug administration avoid first-pass effects of the liver, except:
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Rectal administration. Because it is part of the GI tract, some drug will be absorbed into the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
capillaries that feed the portal vein to the liver. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Depot Drugs ||/|\|||
Specifically formulated long-acting IM dosage forms; designed for slow absorption over a ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
period of several days to months. Example: invega ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
Blood-brain barrier ||/|\|||
Blood vessels (capillaries) that selectively let certain substances enter the brain tissue and
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
keep other substances out. ||/|\||| ||/|\||| ||/|\|||
How does the lipophilicity of a drug affect its metabolism and excretion? What role does the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
liver play in this process?||/|\||| ||/|\||| ||/|\||| ||/|\|||
, Lipophilicity, or the ability of a drug to dissolve in fats, affects its metabolism and excretion ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
in several ways:
||/|\||| ||/|\|||
1. Absorption and Distribution: Lipid-soluble drugs are readily absorbed through cell
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
membranes, which are composed of lipid bilayers. Once absorbed, these drugs are widely ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
distributed throughout the body, particularly in fatty tissues. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Metabolism: The liver plays a crucial role in metabolizing lipid-soluble drugs. The liver
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
converts these drugs into more water-soluble metabolites through processes like oxidation,
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
reduction, and conjugation. This transformation is essential because it makes the drugs ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
easier to excrete. ||/|\||| ||/|\|||
3. Excretion: Once metabolized, the water-soluble metabolites are excreted through the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
kidneys in urine or through the bile in feces. Because lipid-soluble drugs are stored in fat
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
tissues, they can be released slowly over time, leading to prolonged effects and a longer
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
presence in the system. ||/|\||| ||/|\||| ||/|\|||
Overall, the liver's metabolic processes are vital for transforming lipid-soluble drugs into
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
forms that can be efficiently excreted from the body.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
How does p-glycoprotein affect drug metabolism?
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
P-glycoprotein (P-gp) is a crucial player in drug metabolism and transport. It's a type of ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
efflux transporter protein found in cell membranes, particularly in the intestines, liver,
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
kidneys, and blood-brain barrier. Here's how it affects drug metabolism: ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
1. Drug Absorption: P-gp can pump drugs out of cells lining the intestines, reducing the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
absorption of certain drugs into the bloodstream. This can lower the drug's bioavailability. ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
2. Drug Distribution: In the blood-brain barrier, P-gp can limit the entry of drugs into the
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
brain, affecting the distribution of drugs that need to act on the central nervous system.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
3. Drug Elimination: In the liver and kidneys, P-gp helps in the excretion of drugs and their
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
metabolites. It pumps drugs into bile in the liver and into urine in the kidneys, facilitating ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
their elimination from the body.
||/|\||| ||/|\||| ||/|\||| ||/|\|||
Overall, P-glycoprotein acts as a protective mechanism to limit drug absorption and enhance
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
drug elimination, which can influence the effectiveness and duration of a drug's action.
||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\||| ||/|\|||
