Common asked Exam Q Flashcards
(15 cards)
Finding a drug target is crucial to the success of mechanism-based drug discovery.
Using diagrams and specific examples, discuss three classes of drug target under
the following headings:
Q3 (c)
Mechanisms of action of drug examples given [40 Marks]
Receptors: Betablockers work on the effects of the hormone adrenaline which causes the heart to beat slower and less forceful which lowers Bp i.e. Propanalol
Angiotensin receptor blockers work by blocking receptors that the hormone angiotensin works on (ATI receptors) by blocking Angiotensin II. The Bp is lowered i.e. Losartan
Ion Channels: Cocaine inhibits the receptor of serotonin and dopamine. It does this by blocking the presynaptic transporters which causes euphoria in the CNS.
Nifedine blocks the c type Ca2+ channels which prevent calcium entry into smooth muscle this results in vasodilation and low Bp
In enzymes, Statins inhibit HMG CoA reductase which lowers cholesterol
Aspirin inhibits Cox1 and proton pump inhibitors like omeprazole which blocks gastric H,K ATPase
Discuss the process of drug distribution in the human body using the subheadings
below in your answer
Physiological factors influencing drug distribution
The circulatory system is used to transport mediacations through the body. Factors such as decreased blood flow can effect the delivery of the drugs
Distribution occurs more rapidly into tissues with a large number of blood vessels. The permeability of capillaries is tissue dependant, Liver and kidney is more pourous which means its more permeable
The BBB’s tight junctions result in distribution being slower
The placental barrier limits fetal drug exposure but some drugs can still cross i.e. Tetratogenic drugs like thylidamide
Discuss the process of drug distribution in the human body using the subheadings
below in your answer.
Drug factors affecting volume of distribution (Vd)
Lipophilicity: Lipophilic drugs can cross the membrane easily into tissue and fat. They tend to have a high VD i.e. diazepam Hydrophilic drugs remain in the plasma.
A drug confined to the plasma will have a low VD whereas a drug distributed throughout total body water will have a larger VD
The ability of a drug to cross membrane affects its distribution. Lipophilic drugs partition into cell membranes whereas drugs that cant cross stay in the extracellular fluid which lowers VD.
Drugs that bind to fat or bone may become sequestered which increases VD i.e. tetracycline
Discuss the process of drug distribution in the human body using the subheadings
below in your answer.
Plasma protein binding and its influence on drug distribution
A free drug refers to molecules that are not bound to any components in the blood, they’re in solution and are pharmacologically active.
A bound drug is attached to plasma proteins or RBC’s and are inactive. Only a free drug can cross cell membranes and be metabolised.
High protein plasma binding reduces the amount of free drug available for distribution which restricts the drug to the vascular compartment = low VD
In albumin there are two drug binding sites which bind to acidic drugs (warfarin)
Physiological factors influencing drug distribution
Physiological factors affecting drug absorption.
Area of absorptive surface, the larger the surface area, the greater the absorption This means the small intestine is the primary site of absorption.
Vascularity, highly vascularised areas like the lungs allow the drugs to enter the blood stream rapidly which improves absorption. Poor vascularisation can reduce drug uptake.
The presence of other substances like food, drugs or other chemicals can interfere with drug absorption i.e. Grapefruit juice can inhibit CYP450 which alters absorption,
Drug factors affecting drug absorption
Lipid water solubility: Lipophilic drugs cross cell membranes easier
Particle size: Smaller molecules are absorbed easier than large
Degree of ionisation: Only unionised drugs are able to cross
Physical forms: Liquids are easier to absorb than tablets
Concentration: Higher drug concentration enhances diffusion gradient
Reasons for loss of drug following oral drug administration
Incomplete drug release from dosage form
Incomplete dissolution from GI fluid (Generally low solubility drugs)
Chemical instability in GIT- stomach can breakdown sensitive drugs
Incomplete transport across mucosa - large molecules can struggle
Liver metabolism
Discuss the following types of drug delivery under the
headings: structure, applications and advantages.
Q 1(a) [30 Marks]
Liposomes
Liposomes are spherical vesicles that are composed of one or more phospholipid bilayers surrounding an aqueous core.
They can encapsulate both hydrophilic (core) and lipophilic drugs (Bilayer)
They can range in size from nanometers to micrometers .
They are widely used in cancer therapies, antibiotic delivery and vaccines i.e. Covid
Liposomes are capable of self assembly, carrying large drug loads and having little toxicity
Discuss the following types of drug delivery under the
headings: structure, applications and advantages
Nanoparticles
Nanoparticles are typically 100-500nm in size
They have high surface area to volume ratio which improves solubility and enhances interactions.
By modifying properties, it optimises Bioavailability and decreases clearance.
They can be used for disease diagnostics, gene delivery and targeted therapy
They have controlled release, targeted delivery and can cross the BBB
Understanding drug-receptor interactions are pivotal for predicting therapeutic
response and adverse effects of a drug. Using diagrams discuss the following
topics:
Drug specificity
Drug specificity refers to the requirement that a useful drug must act selectively on particular cells and tissues.
The drug should show a high degree of binding site specificity
They have a high degree of ligand specificity and will recognise ligands of a certain type and ignore the close relatives.
An example is angiotensin II which acts in the renal tube and vascular smooth muscle but no affect on other muscles.
Discuss absorption using the following
headings:
Relative bioavailability
Its the determination of the rate and extent of active drug delivered to the systemic circulation
It’s dependent on the rate of drug absorption
Factors like pH, dosage form and first pass metabolism have an effect on bioavailability.
FPM is a significant factor in reducing it. It occurs when the drug is metabolised before reaching systemic circulation i.e. the liver. Iv passes it
Discuss the pharmacokinetic
variability under the following headings:
Q 1(a) [35 Marks]
Age related effects on pharmacokinetic variability
In neonates gastric emptying is delayed and doesnt reach adult rates until 3 yrs.
This slows down the time it takes for drugs to reach the small intestines where absorption occurs.
The GIT is also more basic which affects the solubility and absorption of drugs.
In children and young adults, absorption is generally faster due to gastric motility
Discuss the pharmacokinetic
variability under the following headings:
Pharmacogenetics
The study of how genetic variation of individuals affects the responses to drugs, including therapeutic affects and adverse reactions.
Genetic polymorphisms are variations in the DNA sequence. They can result in altered drug metabolism efficiency and toxicity.
These polymorphisms may cause the production of Iso enzymes with increased/decreased/ absent activity which impacts the processing of drugs
Discuss the pharmacokinetic
variability under the following headings:
Effects of enzyme inducers and inhibitors
Drug inhibition occurs when a drug decreases the activity of the metabolic enzymes.
Slowing the breakdown of other drugs.
This results in an increased activity of drug conc in the body which can cause toxicity or prolonged drug effects.
Examples include grapefruit inhibiting CYP3A4 enzymes which increases plasma conc i.e. warfarin
Drug induction occurs when a drug increases the production of activity of metabolic enzymes.
This enhances drug breakdown which results in reduced drug conc and decreased drug efficacy leading to treatment failure.
CYP3A4 induced by st johns wort
They result in faster drug metabolism and reduced drug state
Discuss the pharmacokinetic
variability under the following headings:
Disease state of patient
Disease conditions (liver and kidney) are significant factors which effect drug metabolism.
In absorption they can effect GI motility and the intensity of absorptive spaces.
Distribution can be altered by diseases like odema which can be a deterrant of BD
Liver disease can alter drug metabolism. Phase lands of metabolisms use enzymes like cyp450 . The efficacy of liver clearing drugs can be expressed by hepatic extraction ratio. This decreases blood flow.
In elimination, the kidneys are the most important.
In kidney disease, patients need dosage reduction as the disease effects protein binding which influences the amount of free drug available
