Lecture 7.2 Flashcards
The influence of ionization on drug absorption is important only in circumstances in which biologic
pHs vary dramatically, such as those in the stomach (varying from 1.5 to 7.0) and the urine (varying from 4.5 to 7.5).
True or false.
True
Both ionized and nonionized drugs are absorbed from subcutaneous and intramuscular sites of injection,
ionization does not appear to play an important role in the passage of drugs across the capillary wall.
True or false
True
Although drugs such as acetylsalicylic acid are best absorbed from an acidic medium such as that in stomach, most of the aspirin is absorbed in the upper small intestine. Why?
small intestine has a considerably greater absorptive surface
Compare the total absorptive area of small intestine and the stomach.
small intestine and its microvilli:
200 m2
stomach:
1 m2
–>most drugs, whether nonionized or ionized and whether acidic, basic, or neutral, are absorbed mostly from the small intestine.
Most drugs, whether nonionized or ionized and whether acidic, basic, or neutral, are absorbed mostly from the small intestine.
True or false.
True
What is meant by perfusion rate in the context of drug absorption?
rate at which blood flows through the tissues surrounding the injection site
–> determines how quickly drug molecules can be carried away from injection site into the bloodstream
State a scenario in which the perfusion rate has to be considered.
Morphine sulfate
–> morphine may not be absorbed in circulatory collapse and shock in which the peripheral circulation is impaired
–>for patient suffereing from injuries in accident, requires more morphine to induce analgeisc effect, lead to death when stabilised
For drug that is administered through intramuscular and subcutaneous sites, how could the rate of absorption be increased and retarded?
increase: massaging the site of administration
decrease: place ice pack
Name a method of deliberately retarding the absorption of drugs by reducing the peripheral absorption.
Local anesthetics combined with a vasoconstricting substance such
as epinephrine (adrenaline) & injected
- epinephrine prevent rapid absorption + enhance duration of action –> prevent systemic toxicity
Name a vasoconstricting substance that could be combined with local anesthetics.
What is its purpose.
Epinephrine
prevent rapid absorption + enhance duration of action + prevent systemic toxicity
For the factor concerning gastric emptying time, when should drugs be taken to allow rapid absorption?
on an empty stomach
What kind of meals retard absorption?
meals with high fat content
What class of drugs are anti-cholinergic drugs?
inhibit the action of acetylcholine, a neurotransmitter in the nervous system
What are anti-cholinergic drugs used to treat?
- Overactive Bladder
- Management of Parkinson’s Disease
- Motion Sickness
Name a anti-cholinergic drug
propantheline
Should anti-cholinergic drugs be taken before or after meals? Why?
one hour before meals
Because anti-cholinergic drugs can inhibit secretion of gastric juice
What are antacids for?
neutralize excess acid
State how acid-peptic disease (APD) could be managed
anti-cholinergic drugs taken one hour before meals and antacids taken one hour after meals
What is acid-peptic disease?
excessive production of acid in the stomach and damage to the stomach lining by pepsin and acid
For the management of acid-pepsin disease (APD), anti-cholinergic drugs are taken one hour before meals and antacids taken one hour after meals. Why?
onset of action of anti-cholinergic drugs is between 1.5- 2 hrs
–> exert their peak effects at a time when the antacid remains in the stomach
What are some possible reasons for inadequate plasma concentration of a drug following oral administration?
- destroyed by acid hydrolysis
- Forms insoluble complexes with polyvalent ions such as Ca2+
- Not absorbed
- first-pass effect
Name 2 drugs that are destroyed by acid hydrolysis if orally administered.
penicillin G & erythromycin
Name a class of drug that forms insoluble complexes with polyvalent ions such as Ca2+ if orally administered.
tetracyclines
Name a drug that is not absorbed when it is orally administered
neomycin
By far the most important reason for an inadequate plasma concentration following the oral or parenteral administration of a drug is the first-pass effect, which consists of the loss of a drug as it passes through the liver for the first time.
True
How is drug transported from the small intestine to the liver?
through hepatic portal system after being absorbed into it by passive diffusion from small intestine
What happens after it is metabolised by the liver?
enters systemic circulation or
gall bladder–> bile–> small intestine
Through what transport mechanism is the metabolised drug transported from the liver to the gall bladder?
carrier-mediated transport (active)
What can happen to the drug in the small intestine?
absorbed, metabolised or excreted
What is the drug ‘nitroglycerin’ for?
treating angina pectoris
How is nitroglycerin administered?
sublingually
Why is nitroglycerin administered sublingually?
- to bypass liver b/c in liver it can be inactivated –> inadequate conc
- perfuses the coronary circulation more directly
For nitroglycerin, apart from being taken sublingually to bypass the liver and to maintain adequate conc, how else could take first-pass effect be overcome? What problem is associated with it?
raising the dose
but could create secondary problems such as hypertension
The rate of distribution is the major determinant of the shape of the plasma concentration versus time curve following rapid intravenous administration.
true or false
true
The rate and extent of drug distribution from plasma are both highly variable between different drugs, and to a lesser degree, between individual patients.
true or false
true
Drugs interact with macromolecules in various body fluids and tissues, and this
interaction influences both the pharmacokinetic and pharmacodynamic parameters.
True or false.
True
Are drugs distributed non-uniformly throughout the body?
Yes
Whether given orally or parenterally, drugs are distributed non-uniformly throughout the body. Factors that regulate the drug distribution are:
◼ The lipophilic characteristics of the drugs
◼ The blood supply to the tissues
◼ The chemical composition of various organs and tissues
The distribution of drugs not only influences their onset of action, but also at times determines their duration of action. State an example.
Thiopental (an intravenous anesthetic)
–> onset in 10-20 secs bc rapid transport to brain
–> duration of action 20-30mins because of subsequent redistribution to other tissues e.g. muscle and fat
What are some plasma proteins?
Albumin (most abundant)
prealbumin
lipoproteins
globulins
What do site 1 and site 2 of albumin bind to?
Site 1: binds structurally unrelated substances
Site 2: binds drugs in a selective manner
Name drugs that bind to albumin at its site 1
warfarin, phenytoin, and sulfonamides
Name drugs that bind to albumin at its site 2
diazepam , phenylbutazone, and ibuprofen
What is the significance of plasma albumin?
exerts 80% of the colloid osmotic pressure of blood
Apart from binding to albumin, what other proteins could drugs in plasma bind to?
Alpha1-acid glycoprotein
Other glycoproteins such as corticosteroid-binding globulin and thyroxine-binding globulin
Lipoproteins
Does drug bound to plasma protein exert any pharmacologic effect?
No
What is the interaction between proteins and drug governed by?
the law of mass action, in that the proportion of bound drug remains constant, provided the binding sites are not saturated.
What kind of interaction may exist between a drug and protein?
NOT A CHEMICAL RXN, but a reversible attachment –>half-life in order of ms
◼ Electrostatic
◼ London-Van der Waals
◼ Hydrogen binding
◼ Combinations of the above
The response to a drug is determined by the unbound fraction present in the
plasma.
True or false
True.
The concentration of unbound drug is often a better index of a drug’s
effective therapeutic level than the total drug
What measurement does he clinical laboratory assessment of the plasma level of a drug in most cases involve?
measurement of bound-plus-unbound amounts of the agent
The greater the amount of bound drug, the less rapidly will the plasma level of unbound drug ____________, as it is continuously being replenished through dissociation of the complex
decline
The greater the amount of bound drug in plasma, ___________________________________.
the less rapidly will the plasma level of unbound drug decline
Why is the binding of drug to plasma protein not usually a disadvantage?
less rapidly will the plasma level of
unbound drug decline, as it is continuously being replenished through dissociation of the complex
–>without binding = drug too transient
Therapy is easier to control when a drug is stable in the body and its plasma concentration does not fluctuate widely.
True or false
True
Name a drug that does not become bound in plasma
heparin
Name a drug that binds extensively (98%) to plasma proteins
phenylbutazone
Toxic manifestations of drugs are frequent and considerably higher in individuals suffering from ___________________.
hypoalbuminemia (低血清蛋白)
or altered plasma and tissue protein conc
What happens when drug is administered after binding sites of plasma protein are saturated?
toxicity since excess drug remains free
Can drugs alter the proteins binding of other agents? Give examples
Yes
-Aspirin decreases the binding of thyroxine
-binding of bilirubin hindered by many pharmacologic agents
The more tightly bound drugs
can displace the less firmly bound agents.
True or false
true
