ICS 2 Flashcards
Definition of ‘pharmacodynamics’
The drug’s effect on the body (mechanism of action)
4 examples of pharmacodynamic interactions
Sometimes drugs don’t have an effect - summation (1 + 1 = 2)
Sometimes drugs will enhance each other’s effects - synergistic (1 + 1 > 2)
Sometimes drugs will inhibit each other’s effects - antagonists (1 + 1 = 0)
Drug A has the same effect, but drug B gets affected - potentiation (1 + 1 = 1 + 1.5)
Definition of ‘pharmacokinetics’ - 4 parts
The body’s effect on the drug - Absorption, Distribution, Metabolism, Excretion
What is ‘bioavailability’?
What is the bioavailability of oral compared to IV?
The proportion of a drug which enters the circulation into the body.
Oral: lower (eg, 0.7)
IV: absolute (1.0)
What is the (apparent) volume of distribution?
High means…
Low means…
The distribution of a medication between plasma and the rest of the body (how much of the drug is lost to other organs/tissues, or bound to proteins)
High: moves to no effect tissues, bound to proteins
Low: stays is blood, only moves to effect tissue
Definition of ‘potency’
What is EC50?
The amount of a given drug that is required to produce a given effect
The concentration that gives half the maximal response
Definition of ‘efficacy’
The maximum effect that a given drug will produce - irregardless of the dose
EFFICACY vs POTENCY on a graph
Drug Conc - x axis
Response - y axis
Difference in height = efficacy
Difference in width = potency
AFFINITY vs EFFICACY
Affinity: how well a ligand binds to a receptor
Efficacy: how strong is the signal after binding (maximal effect)
2 natural opioids?
Chemical modified opioids? (3)
Synthetic opioids? (2)
Opioid antagonist?
NATURAL: Morphine, Codeine MODIFIED: Diamorphine, Oxycodone, Dihydrocodeine SYNTHETIC: Fentanyl, Tramadol ANTAGONIST: Naloxone
List the types of opioid receptors?
How do the receptors work?
What receptor do the drugs target?
MOP, KOP, DOP, (mu, delta, kappa), NOP
G-protein that inhibit neurotransmitter release
All the drugs are MOP agolnists
Why is morphine dangerous with renal failure?
Morphine is metabolised into morphine 6 glucuronide - which is more potent than morphine.
Will build up in those with renal failure and cause opioid-induced respiratory depression.
What is prodrug?
Two opioid examples?
Significance?
A medication that is metabolised by the body to become active.
Codeine & Tramadol
Response will be different to each person - effects could be exaggerated or inhibited
Catecholamine production order (5)
Tyrosine L-DOPA Dopamine Noradernaline Adrenaline
Alpha 1 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gq-protein, increasing calcium
Contracts smooth muscle
Vascular smooth muscle, GI sphincters, pupil
Alpha 2 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gi-protein (inhibitory to Adenyl Cyclase)
Inhibits neurotransmitter release
Pre-synaptic terminals, pancreas, platelets, salivary glands etc
Beta 1 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Heart and Kidney
Increases heart rate and renin secretion
Beta 2 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Vasodilation, Bronchodilation, Stimulates insulin release
Vascular smooth muscle, Bronchioles, Liver, Proprioceptors
Beta 3 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Lipolysis, Bladder relaxation
Adipose tissue, Bladder
What is the structure of cholinergic nicotinic receptors?
Two types and where they are found?
Ligand-gated ion channels
NN - autonomic ganglia and CNS (cognitive function)
NM - neuromuscular junction (skeletal muscle)
What is the structure of cholinergic muscarinic receptors?
5 types and where they are found, which G protein?
M1 (Gq): brain, parietal cells
M2 (Gi): heart (activation slows the heart, eg atropine = blocks slowing of heart)
M3 (Gq): glandular and smooth muscle (bronchoconstriction, sweating, salivary
glands)
M4 (Gi): CNS
M5 (Gq): CNS
Drug development process:
Discovery/Preclinical:
Proof of concepts, animal studies, safety data
Clinical Phase 1: Healthy volunteers (safe?)
Clinical Phase 2: Limited patients (safe and effective?)
Clinical Phase 3: Larger sample of patients (safe and effective?)
Licensing from MHRA/ERA, NICE/NHS,
What is ATOPY?
What makes up the ATOPIC TRIAD?
Inherited tendency for overproduction of IgE antibodies to common environmental antigens
Asthma
Eczema (atopic dermatitis)
Hay Fever (allergic rhinitis)
Gell and Coombs
Mechanism, Examples
TYPE 1 (allergy)
Sensitisation. IgE of mast cells is activated, release of histamine and chemokines
Atopic triad, Anaphylaxis, Hives
TYPE 2 (cellular)
IgG and IgM bind to cell-surface antigens
Haemolytic disease of newborn (Rhesus), Blood transfusions, Goodpasture’s syndrome
TYPE 3 (immune complexes)
IgG binds to soluble antigens forming circulatory immune complex, cause local inflammation
System lupus erythematosus, Farmer’s lung
TYPE 4 (delayed Delayed t-helper cells activated leading to inflammation and granulomatous diseases Contact, dermatitis, Sarcoidosis?, TB?
Define “adverse drug reactions”
How are they different from side effects?
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug
Side effects can be beneficial
Name of classification system with adverse drug reactions?
Name the groups with an example
Rawlins Thompson Classification
• Augmented: extension of primary effect (bronchospasm in beta-blockers)
• Bizzare/Idiosyncratic: unpredictable, not dose dependant (allergy, idiosyncrasy)
• Chronic: steroids leading to iatrogenic Cushing’s syndrome
• Delayed: carcinogenesis, cyclophosphamide (chemotherapy) damages bladder
• End of treatment: glucocorticoid withdrawn leading to adrenocortical insufficiency
Failure of therapy: OCP failure
3 shapes of bacteria?
Cocci (spherical)
Bacilli (rod-like)
Spriochaete (spiral)
Two important spirochaete bacteria?
Treponema pallidum (Syphilis) Borrelia Burgdorferi (Lyme disease)
Stages of the gram stain?
What stains -ve instead?
What differentiates +ve and -ve?
- Fixation
- Crystal Violet
- Iodine treatment
- Decolourisation
- Counter stain with Safranin
+ve has much larger peptidoglycan cell wall - which stains
What does the catalase test do? What is the test? What is positive result?
Differentiates between staphylococci and streptococci.
Combine w/ hydrogen peroxide (will form bubbles with catalase enzyme present
+ve = staph, -ve = strep
What does the coagulase test do? What is the test? What is a positive result?
Differentiates between staph. aureus and coagulase -ve staph (eg, staph. epidermidis)
Coagulase enzyme will convert fibrinogen to fibrin (clumps or clots)
+ve = S. aurues, -ve = coagulase -ve staph
Staphylococcus vs Streptococcus
Which is clusters, which is chains?
Are these gram +ve or -ve?
Staphylococcus = clusters (grapes)
Streptococcus = chains
Both GRAM-POSITIVE
What is the test used to differentiate between different streptococcus organisms?
Results in each 3
Placed on a BLOOD AGAR plate.
Alpha haemolysis: partial
Beta haemolysis: complete
Gamma haemolysis: none
What are the two important alpha-haemolytic organisms? What test is used to differentiate between them? How?
Strep. pneumoniae
Strep. viridans
Optochin test (chemical disc on plate) If sensitive: clear ring = S. pneumoniae If non-sensitive, resistant = S. viridans
What is the main example of gram +ve diplococci? Second example?
Streptococcus pneumoniae
also Enterococcus spp. - Gamma haemolytic, Group D Lancefield
How to differntiate between beta-haemolytic streptococcus organisms? What is the test?
Examples?
Lancefield test/classification
(Positive = agglutination to a cell wall antigen, clumping)
A: Streptococcus pyogenes
B: Streptococcus agalactiae
D: Enterococcus, Streptococcus bovis (not beta-haemolytic)
4 important gram +ve bacilli? What do they cause?
Listeria monocytogenes (listeriosis)
Propionibacterium acne
Clostridium difficle (diarrhoea from antibiotic overuse)
Corynebacterium diptheriae (diptheria)
What is the test to differentiate between gram -ve bacilli? How does it work? Examples
Place on MacConnkey agar (lactose test)
+ve = ferments lactose, produces acid, ph drop below 6.8 = pink
(E. coli, Klebisella pneuomoniae)
-ve = doesn’t ferment, normal pH, normal colour
(salmonella, shigella, pseudomonas aeruoginosa, proteus mirabilis)
What does an oxidase test differentiate between? How does the test work? Examples?
Differentiate between non-lactose fermenting gram -ve bacilli.
Does it contain cytochrome c oxidases?
+ve = black/purple: pseudomonas or Neisseria (cocci)
-ve = colourless: Shigella, Salmonella, Proteus
How do you identify Proteus mirabilis? What is special about it on agars?
Use an urease test
Shows ‘swarming’ motility
What are the 2 important gram -ve cocci?
How do you differentiate one of these in particular?
Neisseria (meningitidis, gonorrhoea)
Moraxella catarrhalis
Neisseria = GRAM -VE DIPLOCOCCI
Main example of a coccabacilli/parvobacteria?
Haemophilus influenzae
What is the vibrio shape in bacteria?
3 examples
Curved shape:
Vibrio cholera
Helical shape:
Campylobacter jejuni - diarrhoea
Helicobacter pylori - gastric/duodenal ulcer
2 examples of fastidious bacteria?
What does it mean?
Haemophilus influenza
Neisseria meningitidis
Special nutrient requirements: require chocolate agar (blood agar heated)
Endotoxins vs Exotoxins
Endotoxins:
Component of the outer membrane of bacteria
Examples: lipopolysaccharide in GN bacteria
Exotoxins:
Secreted proteins of GP and GN bacteria
Specific, leading to immune response
Differences between gram +ve and gram -ve?
Gram +ve =
inner membrane
Large peptidoglycan cell wall
capsule
Gram -ve = Inner membrane Small peptidoglycan cell wall Outer membrane LPS Capsule
What does LPS stand for? 3 components?
Lipopolysaccharide
Lipid A
O antigen
Terminal sugar
Antbiotics that affect cell wall synthesis: Cidal or static? 1 - 3 1 - 1 1 - 2
All cidal
BETA-LACTAMS
Penicillins
Co-amoxiclav (Amoxicillin & Clavulanic Acid)
Cephalosporins
GLYCOPEPTIDES
Vancomycin
CARBAPENEMS
Imipenem
Doripenem
How many generations of cephalosporins? Early gens effective against? Later gens effective against
5 generations
Cefalexin, Cefuroxime, Ceftriaxone…
Early = Gram +ve
Later = Gram -ve
Antibiotics that affect protein synthesis? 50s or 30s? Cidal or static? 1 - 2 1 - 3 1 - 2
MACROLIDES (50s - static)
Erythromycin
Clarithromycin
Azithromycin
AMINOGLYCOSIDES (50s - cidal)
Gentamicin
Tobramycin
Streptomycin
TETRACYCLINES (30s - static)
Doxycycline
Lymecycline
Antibiotics that affect folic acid?
Cidal or static?
1 - 3
All static SULPHONAMIDES Sulfamethoxazole Trimethoprim Co-trimoxazole (both of the above)
Antibiotics that affect DNA/RNA synthesis?
Cidal or static?
1 - 2
(4)
All cidal
QUINOLONES/FLUROQUINOLONES (topoisomerase)
Ciprofloxacin
Levofloxacin
Nitrofurantoin
Metronidazole
Daptomycin
Rifampicin
How can bacteria become resistant?
Properties
Genetic mechanisms
Target site mutation
Antibiotic destruction
Prevent antibiotic entry
Remove antibiotic from bacterium
Intrinisic (natural resistance)
Acquired (mutations, gene transfer (sex))
4 examples of antibiotic resistance?
MRSA (methicillin resistant S. aureus)
VRE (vancomycin-resistant enterococci)
CRE (carbapenam-resistant enterobacteria)
CPE (carbapenemase-producing enterob)
Two main diagnostic tests for viruses?
PCR test Serological tests (antibody/antigen)
Virus structure?
Genetic material (DNA or RNA) Capsid Lipid Envelope (somtimes)
List of viral diseases: Name as many as possible
Common cold and flu MMR Chicken pox and shingles Hepatitis Herpes (HSV) Polio Rabies HIV and AIDS Infective mononucleosis (glandular fever) (Epstein-Barr) Zika and Ebola
3 common fungal infections?
Vulvovaginal candidiasis (Thrush) Tinea pedis (Athlete's foot) Onychomycosis (Fungal nail infections) - difficult to treat, high failure, long treatment
What is the main genus for fungal?
3 examples of species
Ascomycota
Aspergillus, Pneumocystis, Candida
Stages of virus replication?
- Attachment (viral and cell receptors)
- Cell entry (only core enters)
- Interaction with host cells (virus uses cell materials to replicate)
- Replication (production of progeny viral nucleic acid and viral proteins
- Assembly - occur in nucleus/cytoplasm/cell membrane
- Releases (lysis, exocytosis)
Fungi:
Two types?
Eukaryotic or Prokaryotic?
Yeast - single celled organsisms
Moulds - multicellular, spores
EUKARYOTIC, therefore harder to target
Two fungi specific treatments?
ECHINOCANDINS (target the chitin cell wall)
AZOLES
target ERGOSTEROL in plasma membrane
Two main diseases caused by mycobacteria?
M. tuberculosis - lung TB, meningitis
M. leprae (leprosy)
How do you stain mycobacterium? Postive test?
Special culture medium?
Ziehl-Neelsen stain
Red/Pink for acid-fast bacilli/rods (mycobacteria)
Lowenstein-Jensen medium
Protozoa: 4 classifications? Single cell or multi-cell? Eukaryotic or Prokaryotic?
Single cell eukaryote
Amoeboids, Ciliates, Sporozoa, Flagellates
MALARIA
5 types?
Vector?
3 parts of the cycle?
Plasmodium…
Falciparum, Malariae, Ovale, Vivax, Knowlesi
Female Anopheles Mosquito
Liver, Blood, Vector Stage
