Intro to Pharmacology Flashcards
A molecule on the surface of the cell (or inside it) that receives an external signal and produces some type of cellular response is known as a ________-__________ interaction.
drug-receptor
A protein recognition molecule for a chemical mediator
Receptor
“Ligand-binding theory” describes how the right molecule binds to the receptor, which leads to a conformational change in the ________, leading to cellular changes.
protein
Drugs can change the ________ and _________ of body functions
amplitutde and speed
___________ prevent the binding of endogenous compounds.
Antagonists
The site on a receptor where a non-competitive antagonist binds is called an
allosteric binding site or allosteric effect
Name some examples of competitive reversible antagonists
Beta blockers, atropine, naloxone, and Prazosin
Drugs that have opposing physiological actions at different receptors
Functional or physiological antagonists
The effect of adrenaline on histamine produced in anaphylaxis is what type of antagonism?
Functional or physiological
What is a chemical antagonist?
A substance that binds to and inactivates the agonist itself (as opposed to something that binds to an inactivates a receptor)
This describes how tightly a ligand binds to a receptor
Affinity
The probability that a drug molecule will bind to an available receptor at any given instant in time is expressed numerically as the _______ ________ (__)
dissociation constant (Kd)
The dissociation constant is the concentration of ________ required to occupy ____% of the available receptors.
agonist, 50%
The lower the dissociation constant (Kd), the _________ the affinity.
higher
The ability of an agonist to produce a biological effect
Drug efficacy
Drug efficacy is expressed numerically as
R Max (maximum response)
What numerical expression is used to compare whether one drug is as effective as another?
R Max
A measure of drug activity expressed in terms of the amount required to produce an effect of given intensity
Drug potency
Drug potency depends on both _______ and ________.
affinity, efficacy
One measure used to look at drug potency is _____
EC 50
Half maximal effective concentration is represented as .
EC 50
This is the concentration of a drug, anitbody, or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time
EC 50
The ________ the EC50, the _________ the potency.
lower, higher
How can drugs be classified? (List 3 ways)
- Site or mode of action
- Therapeutic use
- Chemical structure
“What the body does to the drug”
Pharmacokinetics
“What the drug does to the body”
Pharmacodynamics
List the four main phases of pharmakokinetics (ADME)
Absorption
Distribution
Metabolism
Excretion
This is the process of transfer of the drug from the site of administration into the general/systemic circulation.
Absorption
How much of the drug, if taken orally, reaches the systemic circulation after first-pass metabolism?
20%
The process by which a compound is transferred from the general circulation to other parts of the body and into the tissues is known as
Distribution
The process by which a drug is chemically altered in a way that facilitates its action or enhances its elimination from the body
Metabolism
The main site of drug metabolism in the body
the liver
Name the sites of drug metabolism in the body
Liver Kidneys GI tract Lungs Skin
The superfamily of enzymes that metabolise >75% of drugs used in medicine
Cytochrome p450
What is the effect on the drug in the body with enzymatic induction?
Faster clearance
What is the effect on the drug in the body in cases of enzymatic inhibition?
Accumulation of drug in the system
The process by which drugs or their metabolites are removed from the body
Excretion
What are routes of drug excretion?
Renal, biliary, respiratory, dermal, faecal
Pharmacodynamics mainly has to do with the interaction of the drug with rthe body’s _______
proteins
What occurs when the drug interacts with the same type of receptor at different sites around the body, and/or interacts with more than 1 type of receptor?
Side effects
True or false: No drug is free of side effects
True
Individual drug response can be influenced by
Age Gender Genetics Previous exposure Disease Interactions Body composition Variability in PK and PD
Briefly list the key stages of drug development
Non-clinical testing Phase I, II, and III clinical studies Registration with MHRA Launch phase Post-launch research and development
What is “2 species toxicology” in the non-clinical testing phase?
Testing on 1 rodent species and 1 non-rodent species for a minimum of 14 days to determine PK and ADME
What does the non-clinical testing phase look for?
Effects on: Pharmacokinetics ADME Pharmacodynamics Local tolerance/phototoxicity/immunotoxicity Genotoxicity
This phase of clinical trials tests a new drug on a small group of humans- usually multiples of 10, in healthy volunteers or patients affected with the particular disease.
Phase I clinical trials
Phase I trials look for:
*SAFETY/TOLERABILITY* Data on PK/PD Guide to therapeutic dose Drug/food interactions Drug/Drug interactions QT prolongation potential
Why would ECG’s be performed on volunteers in Phase I clinical trials?
To look for QT prolongation- abnormal heart rhythm
How long do Phase I trials typically last?
1-4 months
Distribution of phase I clinical trials?
Single centre, one country
This phase of clinical trials involves several hundred partipants (multiples of 100) who are living with the condition the new medication is meant to treat.
Phase II clinical trial
These are randomised clinical trials to show that the candidate drug results in a biological and/or clinical change associated with the disease or mechanism of action.
Phase II clinical trial
This phase of clinical trial enables dose selection (most effecacious dose) for the next phase
Phase II clinical trial
How long do phase II clinical trials typically last?
3-6 months
This phase of clinical trials is known as the “therapeutic exploratory” phase
Phase II
This phase of clinical trials usually involves multiples of 1000 patients who have the condition that the new medication is meant to treat
Phase III
Trials in phase III can last for __________
several years
The main purpose of this phase of clinical trials is to evaluate how the new medication works in comparison to existing medications for the same condition.
Phase III
How many randomised controlled trials take place in Phase III?
At least two
What are the end points of Phase III clinical trials?
Safety is essential!
Regulatory acceptance
Patient reported outcomes for QOL
In phase III clinical trials, the safety and efficacy of the new drug is compared to
the current standard of care
Distribution of phase III clinical trials?
> 10 centres, multinational
This is the phase where further scientific data is collected on efficacy or safety objectives. Can look for new disease indications.
Phase IIIb or phase IV
Prior to the invention of antibiotics, _________ __________ were the leading cause of death.
infectious diseases
What are the three ideal characteristics of antiobiotic therapies?
- Selective toxicity
- Slow emergence of resistance
- No interference with other drugs
Name some of the PATIENT FACTORS to consider that might affect either the PK or the patient response to treatment
Decreased liver or kidney function
Whether they are immunocompromised
List the six principal mechanisms of antiobiotic actions
- Cell wall
- DNA replication
- RNA synthesis
- Antimetabolites
- Protein synthesis against Rb 50
- Protein synthesis against Rb 30
What is the mneumonic for remembering protein synthesis ihibitors?
Ma life AT cell
Macrolides- Lincosamides (clindamycin)- Aminoglycoside, Tetracyclines- Clindamycin, Erythromycin
50s 30s 50s
NITu MET SULtan in CEPtember with a FLUid PEN and a CAR
Nitrofurans = DNA synthesis inhibitor Metronidazole= DNA replication inhibitor Sulfonamides = Antimetabolites Cephalosporin = cell wall inhibition Fluoroquinolone = DNA replication Penicillin= cell wall inhibition Carbapenem= cell wall inhibition
Name the two types of drugs affecting the bacterial cell wall
- Beta lactams
2. Glycopeptides
Beta lactams bind bacterial _____________
transpeptidases
What are the enzymes that are essential for peptidoglycan synthesis?
Transpeptidases
Beta lactams prevent the cross-linking peptides from binding to the
tetrapeptide side chains
Are beta lactam drugs bactericidal or bacteristatic?
Bactericidal
The two main classes of beta lactams commonly used in practice include:
- Penicillins
2. Cephalosporins (Cephalexin, Cefuroxime)
The beta lactam drugs generally reserved for difficult to treat infections include
Carbapenems and monobactams
Vancomycin, Teicoplanin, and Telavancin are in what type pf drug class?
Glycopeptides (inhibit cell wall synthesis)
When are glycopeptides used?
Only for Gram + bacteria, in serious infections where bacteria is producing beta-lactamase. Generally administered IV.
What is the treatment for C.Difficile infection?
Oral Vancomycin
What is the main adverse effect associated with glycopeptides?
Nephrotoxicity
Ciprofloxacin, Nalidixic acid, Norfloxacin, and Ofloxacin are what class of drugs?
Quinolones
Mechanism of action for this drug class: Inhibits DNA gyrases needed for DNA supercoiling, replication and separation
Quinolones
What types of infections are quinolones used for?
UTI (not first line), pseudomonal infection, GI infections, STI’s
Gram negative, Gram positive, anaerobes, mycoplasma, chlamydia
Metronidazole is a pro-drug. This means that only _________ organisms can metabolise it into its active form. Metabolites that are produced are toxic to the DNA.
anaerobic
List some of the potential adverse effects associated with extended use of metronidazole
Mutagenic, carcinogenic, teratogenic
Drug that inhibits RNA synthesis
Rifampicin
Which drug is bactericidal in mycobacteria?
Rifampicin
How does Rifampicin inhibit mRNA synthesis?
By binding to RNA polymerase
Rifampicin is a strong inducer of which enzyme?
Cytochrome p450
Which drug produces an unusual side effect of orange-coloured saliva, tears, sweat, and urine?
Rifampicin
Trimethoprim and sulfonamides are what type of drugs? (MOA?)
Anti-metabolites
Trimethoprim and sulfonamides-
bacteriocidal or bacteriostatic?
Bacteriostatic
Co-trimoxazole (Trimethoprim combibned with sulfamethoxazole)- Bacteriocidal or bacteriostatic?
Bacteriocidal
Which group of drugs work by inhibiting synthesis of tetrahydrofolate?
Anti-metabolites:
Trimethoprim & sulfonamides
What are the classes of drugs that inhibit the 30s subunit of the bacterial ribosome?
AT
Aminoglycosides
Tetracyclines
What is the class of drugs that inhibit the 50s subunit of the bacterial ribosome?
Macrolides
What type of drug is gentamycin?
Aminoglycoside
Aminoglycosides like gentamycin- bactericidal or bacteristatic?
Bactericidal
Side effects associated with gentamycin (aminoglycosides)?
Nephrotoxicity and ototoxicity
Are Tetracyclines bactericidal or bacteriostatic?
Bacteriostatic
Which type of drug has the following side effects: Phototoxicity, chelation of metal ions leading to discolouration of teeth, bone growth inhibition?
Tetracyclines
Erythromycin, Azithromycin, and Clarithromycin belong to which drug class?
Macrolides
What is the MOA of macrolide antibiotics?
Inhibit protein synthesis at the 50s subunit of bacterial ribosomes (70s)
Which class of broad-spectrum antibiotic is often prescribed in cases of penicillin allergy
Macrolides
What types of bacteria are macrolides effective against?
Both gram positive and gram negative- broad spectrum
The ability of bacteria and other microorganisms to resist the effects of an antibiotic to which they were once sensitve.
Antiobiotic resistance
Bacteria produce _____ _____________ which catalyse the hyrolysis of the beta lactam ring, inactivating beta lactam antibiotics.
beta lactamases
Describe the ways in which bacteria can develop resistance to antibiotics
Mutations in cell genes Gene transfer (vertical or horizontal) Inactivation or modification of the antibiotic Alteration of microbial enzymes Alteration of the target Reduced uptake of the antibiotic Development of alternative pathways
Drug class of amoxicillin
Beta lactam (chemically modified penicillin)
MOA of Amoxicillin
Inhibition of cell wall synthesis
Activty of Amoxicillin
Broad spectrum. Used to treat sore throat, skin infections, respiratory infections, UTI’s
Half life of Amoxicillin
One hour
Excretion of Amoxicillin
Urine
Interactions with Amoxicillin
Can increase levels of other protein-bound drugs
Adverse effects of Amoxicillin
ALLERGY.
Damage to commensal microflora (GI disturbance, thrush)
Clarithromycin drug class
Macrolide
Clarithromycin MOA
Inhibition of protein synthesis in the 50s subunit of bacterial ribosome
Activity of Clarithromycin
Broad spectrum. Similar to penicillin. Used in cases of Penicillin allergy
Clinical uses of Clarithromycin
Similar to amoxicillin (sore throat, skin infections, resp infections, UTI) also used in CHLAMYDIA
Protein binding of Clarithromycin
High
Metabolism of Clarithromycin
Hepatic
Half life of Clarithromycin
1-6 hours
Excretion of Clarithromycin
Metabolites in bile
Adverse effects of Clarithromycin
Nausea and diarrhea. May alter cardiac conduction (arrythmias)
Vancomycin drug class
Glycopeptide
MOA of Vancomycin
Inhibition of cell wall (peptidoglycans)
Activity of Vancomycin
ONLY GRAM POSITIVE BACTERIA
Vancomycin has a ___________ therapeutic window.
narrow
GI absorption of Vancomycin
Very low
Protein binding of Vancomycin
50%
Metabolism of Vancomycin
None
Half life of Vancomycin
4-8 hours
Excretion of Vancomycin
Urine
Major adverse effects of Vancomycin
Nephrotoxicity and ototoxicity
Interactions of Vancomycin
Other ototoxic or nephrotoxic drugs
