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
See figure. 8
See figure. 8
_______ Routes include intravenous, intraarterial, intramuscular, subcutaneous, intrathecal, Topical, Inhalation.
Parenteral Routes include intravenous, intraarterial, intramuscular, subcutaneous, intrathecal, Topical, Inhalation.
Intravenous
The _______ for the intravenous route for taking a drug are:
Rapid effect
Can watch response and titrate dose
All of dose enters circulation
When oral route not available
For drugs too irritating when given i.m. or s.c.
For drugs given in large volumes of fluid
For infusion and continuous monitoring
Parenteral administration of hypertonic solutions possible
The _______ for the intravenous route for taking a drug are:
Cost
Skill in administration
Danger of infection
Possible anaphylactic reaction
Danger of _______ formation due to air, drug precipitation, RBC agglutination
Danger of adverse cardiovascular effects if administration too rapid
Pain
Intravenous
The advantages for the intravenous route for taking a drug are:
Rapid effect
Can watch response and titrate dose
All of dose enters circulation
When oral route not available
For drugs too irritating when given i.m. or s.c.
For drugs given in large volumes of fluid
For infusion and continuous monitoring
Parenteral administration of hypertonic solutions possible
The disadvantages for the intravenous route for taking a drug are:
Cost
Skill in administration
Danger of infection
Possible anaphylactic reaction
Danger of embolus formation due to air, drug precipitation, RBC agglutination
Danger of adverse cardiovascular effects if administration too rapid
Pain
Intraarterial:
The _______ for the intraarterial route for taking a drug are:
Administration of _______ material for visualization of circulatory tree
High concentration of drug going to local area when desirable
The _______ for the intraarterial route for taking a drug are:
Cost
Skill in administration
Danger of infection
Possible anaphylactic reaction
Danger of _______ formation due to air, drug precipitation, RBC agglutination
Danger of adverse _______ effects if administration too rapid
Pain
Intraarterial:
The advantages for the intraarterial route for taking a drug are:
Administration of radioopaque material for visualization of circulatory tree
High concentration of drug going to local area when desirable
The disadvantages for the intraarterial route for taking a drug are:
Cost
Skill in administration
Danger of infection
Possible anaphylactic reaction
Danger of embolus formation due to air, drug precipitation, RBC agglutination
Danger of adverse cardiovascular effects if administration too rapid
Pain
Intramuscular
The _______ for the intraarterial route for taking a drug are:
When oral route not available
Absorption less variable than with oral route
May be less painful than with s.c. route
Absorption more rapid than with s.c. route
Possibility of slowing absorption to prolong effect
The _______ for the intraarterial route for taking a drug are:
Pain
Sterile technique
Possible local necrosis
Lag period before effect onset
Accidental i.v. injection possible
Not to be used after _______ administration
Intramuscular
The advantages for the intraarterial route for taking a drug are:
When oral route not available
Absorption less variable than with oral route
May be less painful than with s.c. route
Absorption more rapid than with s.c. route
Possibility of slowing absorption to prolong effect
The disadvantages for the intraarterial route for taking a drug are:
Pain
Sterile technique
Possible local necrosis
Lag period before effect onset
Accidental i.v. injection possible
Not to be used after anticoagulant administration
Subcutaneous
The _______ for the Subcutaneous route for taking a drug are:
Absorption usually slower than after i.m.; and effect more prolonged
When oral route not available
Absorption less variable than with oral route
May be less painful than with s.c. route
Absorption more rapid than with s.c. route
Possibility of slowing absorption to prolong effect
The _______ for the Subcutaneous route for taking a drug are:
Pain
Sterile technique
Possible local necrosis
Lag period before effect onset
Accidental i.v. injection possible
Not to be used after _______ administration
Subcutaneous
The advantages for the Subcutaneous route for taking a drug are:
Absorption usually slower than after i.m.; and effect more prolonged
When oral route not available
Absorption less variable than with oral route
May be less painful than with s.c. route
Absorption more rapid than with s.c. route
Possibility of slowing absorption to prolong effect
The disadvantages for the Subcutaneous route for taking a drug are:
Pain
Sterile technique
Possible local necrosis
Lag period before effect onset
Accidental i.v. injection possible
Not to be used after anticoagulant administration
Intrathecal = injection into the spinal fluid.
The _______ for the intrathecal route for taking a drug are:
When local effect on CNS required and other route unsatisfactory
The _______ for the intrathecal route for taking a drug are:
Skill
Danger of spinal cord injury
Intrathecal = injection into the spinal fluid.
The advantages for the intrathecal route for taking a drug are:
When local effect on CNS required and other route unsatisfactory
The disadvantages for the intrathecal route for taking a drug are:
Skill
Danger of spinal cord injury
Topical
The _______ for the Topical route for taking a drug are:
For local action on or under skin
For local action on or under membrane Non-invasive
The _______ for the Topical route for taking a drug are:
Difficulty of absorption through skin
Danger of excessive absorption through membranes and systemic toxicity
Topical
The advantages for the Topical route for taking a drug are:
For local action on or under skin
For local action on or under membrane Non-invasive
The disadvantages for the Topical route for taking a drug are:
Difficulty of absorption through skin
Danger of excessive absorption through membranes and systemic toxicity
Inhalation
The _______ for the inhalation route for taking a drug are:
Rapid absorption for systemic action
High concentration attainable for local effect
Self administration possible
The _______ for the inhalation route for taking a drug are:
Possible excessive absorption and systemic toxicity
Poor regulation of dosage
Irritation of pulmonary
Inhalation
The advantages for the inhalation route for taking a drug are:
Rapid absorption for systemic action
High concentration attainable for local effect
Self administration possible
The disadvantages for the inhalation route for taking a drug are:
Possible excessive absorption and systemic toxicity
Poor regulation of dosage
Irritation of pulmonary
See figure 9.
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_______ is Fraction of dose available for biologic action. Usually pertains to oral drug administration where variable absorption or “first pass” effects will decrease the amount of drug which reaches the circulation. Measured by comparing the AUC (area under the curve) for the oral dose form vs the intravenous dose form. See figure 10.
Bioavailability is Fraction of dose available for biologic action. Usually pertains to oral drug administration where variable absorption or “first pass” effects will decrease the amount of drug which reaches the circulation. Measured by comparing the AUC (area under the curve) for the oral dose form vs the intravenous dose form. See figure 10.
