2: Basic Principles II Flashcards
Drug Transport Drugs must cross multiple _______ barriers to reach the receptor in the target tissue. The ability of the drug to reach the receptor will influence the effectiveness of the drug. There are single and double cell membranes.
Most drugs that will be dissolved in the gastrointestinal fluid or carried by plasma need to be somewhat _______ soluble and many are highly water soluble. Ultimately, to reach the target receptor the drug will have to cross multiple membrane barriers which are substantially _______.
Drug Transport Drugs must cross multiple membrane barriers to reach the receptor in the target tissue. The ability of the drug to reach the receptor will influence the effectiveness of the drug. There are single and double cell membranes.
Most drugs that will be dissolved in the gastrointestinal fluid or carried by plasma need to be somewhat water soluble and many are highly water soluble. Ultimately, to reach the target receptor the drug will have to cross multiple membrane barriers which are substantially lipid.
Lipid solubility, small size, and facilitated diffusion = ability of drug to get _______ cell.
Lipid solubility, small size, and facilitated diffusion = ability of drug to get into cell.
See figure 3 pg. 2
Passive Processes Follow a concentration gradient or hydrostatic pressure, _______ require metabolic energy.
Simple _______ - most common. For a given drug this will be affected by: lipid solubility (oil/water partition coefficient), size (_______ is better), degree of ionization (_______ is best)
Facilitated Diffusion - uses a carrier _______ - masks drug characteristics that may impede simple diffusion. Selective, can be inhibited, can be saturate.
Filtration - driven by hydrostatic _______ and drug dissolved in the moving fluid is transported through _______ in a membrane or channels between cells. Drug molecule _______ will be limiting.
Passive Processes Follow a concentration gradient or hydrostatic pressure, don’t require metabolic energy.
Simple Diffusion - most common. For a given drug this will be affected by: lipid solubility (oil/water partition coefficient), size (smaller is better), degree of ionization (nonionized is best)
Facilitated Diffusion - uses a carrier protein - masks drug characteristics that may impede simple diffusion. Selective, can be inhibited, can be saturate.
Filtration - driven by hydrostatic pressure and drug dissolved in the moving fluid is transported through pores in a membrane or channels between cells. Drug molecule size will be limiting.
Active Processes use metabolic energy in the form of high energy phosphates such as ATP or electrochemical gradients, transport against a concentration gradient, rapid, selective, can be inhibited, can be saturated.
Active Transport uses carrier _______
In Micropinocytosis the drug is transported in pinched off packets of single layer _______
Active Processes use metabolic energy in the form of high energy phosphates such as ATP or electrochemical gradients, transport against a concentration gradient, rapid, selective, can be inhibited, can be saturated.
Active Transport uses carrier proteins
In Micropinocytosis the drug is transported in pinched off packets of single layer membrane
Capillary membranes have endothelial cells where small molecules can _______ through so even lipid insoluble molecules can make it through the endothelial gaps but _______ the lipid bilayer.
Capillary membranes have endothelial cells where small molecules can leak through so even lipid insoluble molecules can make it through the endothelial gaps but not the lipid bilayer.
See figure 4 on pg. 3
_______ drug forms diffuse best across the cell membrane. Ionized forms do _______ diffuse across lipid membranes.
Neutral drug forms diffuse best across the cell membrane. Ionized forms do not diffuse across lipid membranes.
pka is a physical characteristic that determines ratio of ionized to _______ forms at a particular pH. If the ratio of ionized to nonionized forms can be estimated then the ease of absorption at a particular pH can be predicted
pka is a physical characteristic that determines ratio of ionized to nonionized forms at a particular pH. If the ratio of ionized to nonionized forms can be estimated then the ease of absorption at a particular pH can be predicted
Write the henderson hasselbach equation
pH = pKa + log A-/HA
Write the equation for weak acids and bases.
HA H+ + A- = weak acid
B + H+ BH+ = weak base
We cannot absorb weak base drugs easily in GI tract due to _______ acidity—they need another route. See figures 5 & 6, on pg. 4.
We cannot absorb weak base drugs easily in GI tract due to high acidity—they need another route. See figure 5 & 6, on pg. 4.
Drug administration can be enteral or paraenteral. Enteral uses a portion of the _______ tract: sublingual, oral, rectal administration. Paraenteral administration _______ the GI tract.
Drug administration can be enteral or paraenteral. Enteral uses a portion of the GI tract: sublingual, oral, rectal administration. Paraenteral administration bypasses the GI tract.
The _______ for the oral route for taking a drug are:
Ease
Safety
Self-administration
Cheap
The _______ for the oral route for taking a drug are:
Absorption may be too slow
Absorption often variable and unpredictable
Drug may be too irritating
Drug may be destroyed by gastric acid, enzymes
Drug may be completely metabolized on first pass through liver
Not available for comatose, vomiting patients
The advantages for the oral route for taking a drug are:
Ease
Safety
Self-administration
Cheap
The disadvantages for the oral route for taking a drug are:
Absorption may be too slow
Absorption often variable and unpredictable
Drug may be too irritating
Drug may be destroyed by gastric acid, enzymes
Drug may be completely metabolized on first pass through liver
Not available for comatose, vomiting patients
See figure 7
See figure 7
Rectal route:
The advantages for the _______ route for taking a drug are:
Useful for infants, comatose, vomiting patient.
Useful for foul-smelling, distasteful drugs
Useful for drugs destroyed in upper _______ tract
Avoids immediate _______ in liver
For local action in rectum
The disadvantages for the _______ route for taking a drug are:
Nuisance - poor compliance
Absorption may be erratic, incomplete
Possibility of rectal irritation
Rectal route:
The advantages for the rectal route for taking a drug are:
Useful for infants, comatose, vomiting patient.
Useful for foul-smelling, distasteful drugs
Useful for drugs destroyed in upper gastrointestinal tract
Avoids immediate metabolism in liver
For local action in rectum
The disadvantages for the rectal route for taking a drug are:
Nuisance - poor compliance
Absorption may be erratic, incomplete
Possibility of rectal irritation
Sublingual
The _______ for the sublingual route for taking a drug are:
By-passes liver when first absorbed Rapid absorption
The _______ for the sublingual route for taking a drug are:
Drugs must be soluble in saliva, not too distasteful, have appropriate pKa for rapid absorption
Tablets must be small
Sublingual
The advantages for the sublingual route for taking a drug are:
By-passes liver when first absorbed Rapid absorption
The disadvantages for the sublingual route for taking a drug are:
Drugs must be soluble in saliva, not too distasteful, have appropriate pKa for rapid absorption
Tablets must be small
