Quantitative Analysis of Drug-Receptor Interactions (C.I. Valencia, MD) Flashcards
T/F: Pharmacokinetics deals with “dose”, while pharmacodynamics deals with “concentration”.
True
What is the cardinal rule in Pharmacology?
You cannot create a new drug effect. You can only alter cellular function. Drugs are simply modulators.
What does drug molecule-receptor binding lead to?
Enhancement, inhibition or blockade of molecular signals
T/F: Clinical effects are only those we can observe with our five senses.
True
How do you know how much of a drug you need to achieve a certain effect?
Look at the dose-response relationship.
Enumerate the three most important properties of a drug
Efficacy
Safety/Lack of Toxicity
Quality
T/F: More is always better in terms of bioavailability
False
Differentiate generics and innovators
Generics usually have a dirty synthetic pathway but are cheaper than innovators.
How many % of drug actions are not mediated through receptors?
10%
T/F: Mannitol and acetylcystein are example of receptor-mediated drugs.
False
They are not.
What drugs do not bind to receptors?
Antacids
Osmotic diuretics
Acid-base reactions
T/F: A dose does not necessarily translate to an effective drug concentration.
True
How does the ligand interact with its receptor?
Lock-and-key fashion
What is the property that pertains to the orientation of the receptor in three-dimensional space?
Stereospecificity
What are the four types of protein receptors?
- Receptors for endogenous regulatory ligands
- Enzymes of metabolic pathways
- Enzymes in transport processes
- Structural proteins
What determines differences in drug effects in different tissues?
- Drug properties
- Receptor properties
- Tissue properties
Define: enantiomers
These are non superimposable mirror images of the same substance.
Describe: Erasomate
- Sold as an anti-parasitic
2. Made up of levamisol (-) and teramisol (+)
Describe: Stirizine
Antihistamine
Describe the up regulatory effect of propanolol
It is a beta adrenergic antagonist that lowers blood pressure. Next dosage has a greater effect.
Describe the down regulatory effect of sulfonylurea
Overstimulation of agonists in the pancreas leads to decreased efficacy of the drug.
What is the effect of opium analgesics on the brain?
Stimulates mu, delta and kappa receptors leading to analgesia
Give an example of a covalent interaction between drug and receptor.
Acetyl group of ASA and cyclooxygenase
What are the chemical forces involved in drug-receptor interaction?
Covalent bonds
Electrostatic
Hydrophobic bonds
What is the inactive form of ampicillin?
Pivampicillin
What are the types of dose response curves?
Graded Response Curve
Quantal Response Curve
What is the shape of the non-logarithmic graded response curve?
Hyperbolic
T/F: The central portion of the sigmoid graded response curve is nearly linear.
True
What do you call the highest intensity of effect a drug can achieve?
Efficacy
Why is there variability in the dose response curve?
It depends on the person, age, weight, clearance effect, dose, etc.
Describe steep and gradual dose response curves.
Steep: cobra ready to bite
Gradual: resting Buddha
Give the formula for therapeutic index
Therapeutic Index = LD50/ED50
In the presence of a competitive antagonist, the response curve is shifted to the?
Right
Describe: Maximal effect
Point at which a drug’s effect plateaus even with continued increase in dose
Differentiate efficacy and potency
Efficacy - effect of drug irrespective of dose
Potency - effect of drug with respect to dose
Potency is determined by what variable?
EC50 or ED50
If a drug expires, what happens to its potency?
It will degrade.
T/F: Dose is dependent on the smallest concentration available.
False
It is dependent on what is feasible to be taken in by humans.
T/F: Potency is not an important factor.
True
T/F: You should always choose a drug that is more potent than efficient.
False
It should be more efficient. We don’t care about potency.
Describe: Quantal Response Curve
All or none event
Concentration vs. number responding
What do you call patients who respond to a small dose of a drug?
Sensitive
What do you call patients who only respond to high concentrations of a drug?
Tolerant
T/F: Not all persons will manifest with a positive quantal response at the same drug concentration due to variation.
True
How many % of respondents will respond to a median dose of the drug?
68%
What are quantal dose curves used for?
Generating the margin of safety for a particular drug
Enumerate the different examples of non-receptor drug action
- Acid-base neutralisation
- Colligative effects in the bronchi (acetylcysteine-initiated breakage of disulphide bonds)
- Counterfeit incorporation mechanism (purine and pyrimidine analogs in cancer treatment)
- Osmolality effects in the brain (mannitol and brain)
T/F: Therapeutic index = margin of safety
True
What is the desirable margin of safety?
100 - 1000
What harmful effects can phenobarbital cause?
Apnea and coma
Is diazepam a safe sedative?
Yes
T/F: TIs of 5 and below indicate drugs with relatively greater potential for toxicity.
False
Statement is true for TIs of 4 and below.
Describe the mechanism of action of azoles
They possess a heterocyclic ring with sulfur and nitrogen inside, which is used against amoeba and fungi.
Describe: citrizine
- Drug used to treat colorectal cancer
2. Possesses a combination of L-citirizine and D-citirizine
What is the phenomenon that occurs when the diagnostic, preventive and therapeutic action of a drug is modified or altered by another drug when administered concomitantly?
Drug interaction
What are the quantitative aspects of pharmacodynamic drug interactions?
- Synergism/potentiation
- Addition
- Inhibition
What causes pharmacokinetic drug interactions?
Alterations to ADME
What are the clinical classifications of drug interactions?
- Beneficial
2. Adverse
What are the requirements of rational therapy?
- Diagnostic certainty
- Pathophysiological understanding
- Pharmacological understanding
- Optimal drug & dose administration
- Picking efficacy/toxicity end points and monitoring
- Open communication and willingness to alter regimen
Enumerate the factors that affect therapeutic outcomes
- Age
- Drug-drug interactions
- Fixed-dose combination
- Placebo effects
- Tolerance
- Genetic factors
Enumerate the factors that contribute to lack of efficacy
- Misdiagnosis
- Poor compliance
- Poor choice of dosage
- Development of separate illness
- Use of other drugs
- Undetected genetic/environmental variables
- Unknown therapy by another physician