Lectuer 6 Flashcards
what the body does to a drug . This statement refers to ?
Pharmacokinetics
Mention the four pharmacokinetic parameters :
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be bio-transformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
The four pharmacokinetic parameters determine ?
The onset, intensity, and the duration of drug action
Using knowledge of pharmacokinetic parameters, clinicians can design optimal drug regimens including:
✔ The route of administration
✔ The dose
✔ The frequency
✔ The duration of treatment.
The drug is absorbed into the ………
Plasma ( blood🩸)
The drug is distributed from the …….. to the …….
- plasma
- tissues
The metabolism occurs in?
Tissues
Elimination occurs through several ways , mention them :
- Bile
- Breast milk
- Urine
- Sweat
- Feces
- Tears
- Saliva
…………… is the transfer of a drug from the site of administration to the bloodstream.
Absorption
The rate and extent of absorption depend on ?
• The environment where the drug is absorbed
• The chemical characteristics of the drug,
• The route of administration (which influences bioavailabiliy).
Routes of administration may result in partial absorption and lower bioavailability .EXCEPT :
Intravenous
Mention the mechanisms of drug absorption
❑ Passive diffusion
❑ Facilitated diffusion
❑ Active transport
❑ Endocytosis
Give me the features of Passive Diffusion
✔ The driving force is the concentration gradient
✔ Does not involve a carrier, is not saturable, and shows a low structural specificity.
✔ Water-soluble drugs: aqueous channels or pores
✔ Lipid-soluble drugs: biologic membranes due to their solubility in the membrane lipid bilayers
Give me the features of facilitated Diffusion :
• Enter molecules into the interior of cells and moving them from an area of high concentration to an area of low concentration.
• Molecules enter the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules (conformational changes)
• It does not require energy, can be saturated,
•May be inhibited by compounds that compete for the carrier
Give me the features of active transport :
• Moving drugs against a concentration gradient, from a region of low drug concentration to one of higher drug concentration (using ATP)
• Drug entry involves specific carrier proteins that span the membrane
•The process is saturable.
• Active transport systems
are selective .
• May be competitively inhibited by other co-transported substances.
Give me the features of endocytosis :
• Used to transport drugs of exceptionally large size across the cell membrane
• Involves engulfment of a drug by the cell membrane and transport into the cell by pinching off the drug-filled vesicle.
The reverse of endocytosis named as ?
Exocytosis
Many cells use exocytosis to secrete substances out of the cell through a similar process of vesicle formation . (T/F) ?
T
There are many factors influencing absorption , mention them :
- Effect of PH on drug absorption
- Blood flow to the absorption site
- Total surface area available for absorption
- Contact time at the absorption surface
- Expression of P-glycoprotein
We have weak acids such as (HA) which release ………… causing ……….
- proton (H+)
- charged anion (A−)
Weak bases (BH+) can’t release an H+. (T/F) ?
F —> Weak bases (BH+) can also release an H+.
A drug passes through membranes more readily if it is charged , ( yes/no) ?
No , uncharged
Protonated acid HA and un-protonated base B are ( less/ more ) absorbable ?
More
Effective concentration of the permeable form of each drug at its absorption site is determined by ?
The relative concentrations of the charged and uncharged forms .
The ratio between the two forms ( acid / base) is determined by the ?
- pH at the site of absorption
- The strength of the weak acid or base (pKa) .
measure of the strength of the interaction of a compound with a proton is called ?
The ionization constant (pKa)
The higher the pKa of a drug, the less acidic it is .(T/F) ?🌚
True
When pH is less than pk ,
the protonated forms
HA and BH+ predominate . (T/F) ?
True
When pH is greater than pk , the protonated forms
A- and B predominate,
T
The intestines receive less blood flow than the stomach, so absorption from the stomach is favoured over the intestine .
F—> (The intestines receive much more blood flow than the stomach, so absorption from the intestine is favoured over the stomach).💀
Some disease conditions alter blood flow to some organs and subsequently drug absorption . Give me example to explain this statement:
Shock severely reduces blood flow to cutaneous tissues, thereby minimizing absorption from SC (subcutaneous) administration
The intestine has a surface area about 1000-fold that of the stomach because?
The intestine have a surface rich in brush borders which containing microvilli .
💕 صلِّ على سيدنا محمد 💕
💕 لا حول ولا قوة إلا بالله 💕
💕 استغفر الله العظيم واتوب إليه💕
(( والله في عون العبد ما دام العبد في عون أخيه)) 🤍🌿
• If a drug moves through the GI tract very quickly (diarrhea), it is not well absorbed. This statement is an example of
Contact time at the absorption surface
Anything that delays the transport of the drug from the stomach to the intestine delays the rate of absorption of the drug . (T/F) ?
True
Presence of food in the stomach lead to ?
Dilutes the drug and slows gastric emptying.
P-glycoprotein is ?
Transmembrane transporter protein
Where the Transmembrane transporter protein (P-glycoprotein) expressed ?
It is expressed in the liver, kidneys, placenta, intestines, and brain capillaries.
P-glycoprotein involved in transportation of drugs from ?
tissues to blood.
P-glycoprotein “pumps” drugs out of the cells .(T/F) ?
True
In areas of high expression, it (increases / reduces) drug absorption.
Reduces
P-glycoprotein also associated with ……. ?
multidrug resistance.
The rate and extent to which an administered drug reaches the systemic circulation is called ?
Bioavailability
If 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is ?
0.7 or 70%.
The importance of bioavailability is ?
important for calculating drug dosages for non-intravenous routes of administration.
It is determined by ?
comparing plasma levels of a drug after a particular ROA with levels achieved by IV administration.
The area under the curve (AUC) can be measured by ?
By plotting plasma concentrations of the drug versus time .
Bioavailability of a drug given orally is the ratio of ?
The AUC following oral administration to the AUC following IV administration.
AUC (oral) / AUC (IV) .
Mention the factors that influence bioavailability :
• First-pass hepatic metabolism
• Solubility of the drug
• Chemical instability
• Nature of the drug formulation
If the drug is rapidly metabolized in the liver or gut wall during this initial passage, the amount of unchanged drug entering the systemic circulation is decreased. This statement describe?
First-pass hepatic metabolism
Give me example about first-pass hepatic metabolism :
(Nitroglycerin , Levofloxacin)
Give me the absorption power ( poorly , readily , ….. ) of each of the following :
1. Very hydrophilic drugs:
2. Extremely lipophilic drugs:
3. Largely lipophilic , yet have some solubility in aqueous solutions drugs:
- poorly absorbed
- poorly absorbed
- readily absorbed
unstable in the pH of the gastric contents. This statement is an example of ?
Chemical instability
( Penicillin G )
Destroyed in the GI tract by degradative enzymes . This statement is an example of ?
Chemical instability
(Insulin)
Mention the examples that can influence the ease of dissolution and, therefore, alter the rate of absorption :
- Particle size
- salt form
- crystal polymorphism
- enteric coatings
- and the presence of excipients (such as binders and dispersing agents)
Two drug formulations are bioequivalent if ?
They show comparable bioavailability and similar times to achieve peak blood concentrations .
they have the same dosage form, contain the same active ingredient, and use the same route of administration . This statement describe related to ?
pharmaceutically equivalent
Define the therapeutic equivalence .
Drugs should be pharmaceutically equivalent (that is, they have the same dosage form, contain the same active ingredient, and use the same route of administration) with similar clinical and safety profiles .
The clinical effectiveness of therapeutic equivalence is ?
maximum serum drug concentration (Cmax) and the time required (after administration) to reach peak concentration (Tmax).
Two drugs that are bioequivalent may not be therapeutically equivalent.(T/F) ?
True —> very important question
