Pharmacology and Microbiology Flashcards
1
Q
Describe noradrenaline?
A
Noradrenaline: released from the sympathetic nerve fibre ends - beloved in the management of shock in the ICU
2
Q
Describe adrenaline?
A
Adrenaline: released from the adrenal glands - fight or flight and management of anaphylaxis
3
Q
What is dopamine?
A
Precursor of adrenaline and noradrenaline
4
Q
Describe alpha 1 receptors?
A
Agonists: NAd > Ad
Mechanism: increases intracellular calcium, Gq signalling
Consequence: Contracts smooth muscle e.g. pupils, blood vessels
5
Q
Describe alpha 2 receptors?
A
Agonists: NAd = Ad
Mechanisms: Gi signalling, inhibition of cAMP generation
Consequence: Mixed effects on smooth muscle
6
Q
Describe beta 1 receptors?
A
Agonists: NAd = Ad
Mechanism: Gs, raises cAMP
Consequence: Chronotropic and inotropic effects on the heart
7
Q
Describe beta 2 receptors?
A
Agonists: Ad»_space; NAd
Mechanism: Gs, raises cAMP
Consequences: relaxes smooth muscle
8
Q
Describe beta 3 receptors ?
A
Agonists: NAd > Ad
Mechanism: Gs, raises cAMP
Consequences: enhances lipolysis, relaxes bladder detrusor
9
Q
Describe alpha blockers?
A
Opposite effect to agonists
- Block alpha 1 to lower BP e.g. doxazosin
- Tamsulosin blocks a specific subtype (alpha 1a) in the prostate, helps treat prostatic hypertrophy
- No useful alpha 2 blocker
10
Q
Describe beta blockers?
A
Propranolol: blocks beta 1 and beta 2. Will slow heart rate, reduce tremor, but may cause wheeze
Atenolol: beta 1 selective, main effects on heart.
Lower blood pressure (by reduction in cardiac output and gradual reduction in central sympathetic outflow activity), reduce cardiac work, treat arrhythmias
11
Q
What are some uses of beta blockers?
A
Angina
MI prevention
High blood pressure Anxiety
Arrhythmias
Heart failure
12
Q
Side effects of beta blockers?
A
Tiredness Cold extremities Bronchoconstriction Bradycardia Hypoglycaemia Cardiac depression
13
Q
What is ‘druggablilty’ ?
A
The ability of a protein target to bind to small molecules with a high affinity
14
Q
Describe the difference between exogenous and endogenous ligands?
A
Exogenous - drugs
Endogenous - hormones, neurotranmitters
15
Q
What are the different types of chemicals detected by receptors?
A
1. Neurotransmitters – acetylcholine, serotonin 2. Autacoids (local) – cytokines, histamine 3. Hormones – testosterone, hydrocortisone
16
Q
What are the different types of receptors?
A
- Ligand-gated ion channels
- nicotinic ACh receptor - G protein coupled receptors
- beta-adrenoceptors - Kinase-linked receptors
- receptors for growth factors - Cytosolic/nuclear receptors
- steroid receptors
17
Q
How are cholinergic receptors characterised?
A
Receptor = nAChR Agonist = nictotine Antagonist = curare
Receptor = mAChR Agonist = muscarine Antagonist = atropine
18
Q
How are H2 (histamine) receptors characterised?
A
• Histamine (agonist) – contraction of ileum – acid secretion from parietal cells • Mepyramine (antagonist) – reversed contraction of ileum – no effect on acid secretion
19
Q
Define: affinity?
A
Affinity describes how well a ligand bids to the receptor and is property shown by BOTH agonists and antagonists
20
Q
Define: efficacy?
A
Describes how well a ligand activates the receptor and is a property shown ONLY by agonists
21
Q
Define: tolerance?
A
It is a reduction in the agonist effect over time due to continuous repeated high concentration
22
Q
Define: desensitisation?
A
Happens when the proteins are uncoupled, internalised or degreated
23
Q
Describe receptor reserve?
A
Where agonist needs to activate only a small fraction of the existing receptors to produce the maximal system response.
Holds for a full agonist in a given tissue
– reserve can be large or small; depends on tissue
24
Q
Describe adverse drug reactions?
A
ADRs are 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, has to be noxious and unintended
25
What are the classifications of ADRs?
1. Toxic effects (beyond therapeutic range) can occur if dose is too high or drug excretion is reduced
2. Collateral effects (therapeutic range)
3. Hypersceptibility effects (below the therapeutic range)
26
What is a side effect?
Side effect is an unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment
27
What are the different reaction time classifications within ADRs?
1. Rapid reactions – red man syndrome due to histamine release with rapid administration of vancomycin
2. First dose reactions - hypotension and ACE inhibitors
3. Early reactions – nitrate induced headache
4. Intermediate reactions – eg delayed immunological reactions such as Stevens-Johnson syndrome with carbamazepine
5. Late reactions – adverse effects of corticosteroids, seizures on withdrawal of long term benzodiazepines
6. Delayed reaction – Thalidomide and phocomelia
28
What are the Rawlins Thompson classifications of Adverse Drug reactions?
A to F!
• Type A (Augmented pharmacological)– predictable, dose dependent, common (morphine and constipation, hypotension and antihypertensive)
• Type B (Bizarre or idiosyncratic)– not predictable and not dose dependent (anaphylaxis and penicillin)
• Type C (Chronic) – osteoporosis and steroids
• Type D (Delayed) – malignancies after immunosuppression
• Type E (End of treatment) – occur after abrupt drug withdrawal eg opiate withdrawal syndrome
• Type F (Failure of therapy) – Failure of OCP in presence of enzyme inducer
29
What are some of the risk factors for ADRs?
Patient Risk
* Gender (F>M)
* Elderly
* Neonates
* Polypharmacy (21% 5 or more drugs)
* Genetic predisposition
* Hypersensitivity/allergies
* Hepatic/renal impairment
* Adherence problems
Drug Risk
* Steep dose-response curve
* Low therapeutic index
* Commonly causes ADR’s
30
When should we expect an ADR?
- Symptoms soon after a new drug is started
- Symptoms after a dosage increase
- Symptoms disappear when the drug is stopped
- Symptoms reappear when the drug is restarted
31
Name some common drugs to have ADRs?
* Antibiotics
* Anti-neoplastics
* Cardiovascular drugs
* Hypoglycaemics
* NSAIDS
* CNS drugs
32
Name some common systems to be affected by ADRs
* GI
* Renal
* Haemorrhagic
* Metabolic
* Endocrine
* Dermatologic
33
Name some common ADRs?
- Confusion
- Nausea
- Balance problems
- Diarrhoea
- Constipation
- Hypotension
34
Describe what to report on a yellow card, who can report and info to include?
What: All suspected reactions for herbal medicines, or black triangle drugs
Who: doctors, dentists, any medical staff and patients
Info:
- Suspected drugs
- Suspectied reactions
- Patient details
- Reporter details
- Additional useful information
35
Define: pathogen?
An organism that causes or is capable of causing disease
36
Define: commensal?
An organism which colonises the host but causes no disease in normal circumstances
37
Define: opportunist pathogen?
A microbe that only causes disease if the host defences are compromised
38
Define: virulences/pathogenicity?
The degree to which an organism is pathogenic
39
Define: asymptomatic carriage?
When a pathogen is carried harmlessly at a tissue site where it causes no disease
40
What are the three main shapes of bacteria?
Coccus (sphere)
Bacillus (rod)
Spriochaete
41
What colour do gram positive bacteria stain?
Purple
42
What colour to gram negative bacteria stain?
Red
43
What are the different formations of cocci?
Diplococcus (two attached cocci) = gram +ve
Chains of cocci = gram +ve
Cluster of cocc i= gram +ve
44
What are the different formations of bacilli?
Chain of rods = gram +ve
Curved rod = -ve
Spiral rod = -ve
45
Describe bacterial DNA?
Bacteria have a chromosome of circular double stranded DNA
46
What does Ziehl Neelsan stain for?
Acid-fast bacilli .
47
What is an endotoxin?
Endotoxin is a component of the outer membrane of the bacteria e.g. lipopolysaccharide in Gram negative bacteria
48
What is an exotoxin?
Secreted proteins of Gram positive and Gram negative bacteria
49
Where does obligate intracellular bacteria grow?
Has to be grown inside cells, examples include Rickettsia, Chlamydia and Coxiella
50
Example of bacteria growing as filaments?
Actinomyces, nocardia, streptomyces
51
Example of bacteria growing as spriochetes?
Leptospira, treponema and borrelia
52
How does gram stain work?
1. Apply a primary stain such as crystal violet (purple) to heat fixed bacteria
2. Add iodide which binds to crystal violet and helps fix it to the cell wall
3. Decolorise with ethanol or acetone
4. Counterstain with safranin (pink)
53
What happens in gram negative bacteria with gram stain?
- the decoloriser interacts with the lipids and cells lose their outer lipopolysaccharide membrane
- the crystal violet-iodide (CV-I) complexes, thus they appear pink with counterstain
54
What happens in gram positive bacteria with gram stain?
- Positive bacteria the decoloriser dehydrates the cell wall
- the CV-I get trapped in the multi-layered petidoglycan
55
Do mycobacteria stain with Gram stain?
NO
High lipid content with mycolic acids in cell wall makes Mycobacteria resistant to Gram stain - acid fast bacilli
56
Give some examples of mycobacteria of clinical importance?
M.tuberculosis - tuberculosis
| M.leprae - leprosy
57
Describe the microbiology of tuberculosis ?
- Aerobic (non spore forming bacillus)
- Cell wall: high molecular weight, weakly gram positive, survive inside macrophages
- Slow growing
- Slow response to treatment
58
Desscribe the risk of TB reactivation after exposure?
- 10% lifetime risk
- Most in first two years then 0.1% per year
Increased risk in:
– Age (infants, young adults, elderly)
– Malnutrition
– Intensity of exposure
– Immunosuppression – e.g. HIV 10% per year
59
What would an induration of 5 or more millimetres indicate in tuberculosis?
A positive result in:
- HIV infected persons
- Recent contact with someone else with TB
- Person with fibrotic change on radiograph
- Immunosuppressed for any reason
60
What would an induration of 10 or more millimetres indicate in tuberculosis?
A positive result in:
- Recent immigrants
- Injection drug users
- Mycobacteriology lab users
- Children <4
61
What would an induration of 15 or more millimetres indicate in tuberculosis?
A positive result in persons with no know risk of TB
62
What are the different stages of tuberculosis?
1. Primary Tuberculosis - bacilli takin in lymphatics to hilar lymph nodes
2. Latent Tuberculosis - cell mediated immune response from T cells, primary infection
3. Pulmonary Tuberculosis - granuloma forms around bacilli that settled in apex, CMI and necrosis results in abcess of bacilli forming and caseous material leaving cavity
4. TB spreads beyond the lungs - Milliatry, TB meningitis, genito-urinary, bone TB
63
Whats makes up a primary complex in TB?
Granuloma + lymphatics + lymph nodes = primary complex
64
What is an enzyme inhibitor?
A molecule that binds to an enzyme and decreases its activity
65
What are the two types of enzyme inhibitors?
* Irreversible inhibitors usually react with the enzyme and change it chemically (e.g. via covalent bond formation).
* Reversible inhibitors bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, the enzyme-substrate complex, or both.
66
What are the three main types of protein posts in cell membranes?
1. Uniporters: use energy from ATP to pull molecules in.
2. Symporters: use the movement in of one molecule to pull in another molecule against a concentration gradient
3. Antiporters: one substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient.
67
Give an example of a symporter?
The Na-K-Cl cotransporter (NKCC) is a protein that transports Na, K, and Cl into cells
68
What is transport?
Its when molecules move across a cell membrane
Needs energy (usually ATP)
69
Describe voltage-gated calcium channels?
Voltage-gated ion channels (VDCC) are found in the membrane of excitable cells (e.g., muscle, glial cells, neurones, etc.)
At physiologic or resting membrane potential, VDCCs are normally closed.
70
What is an action potential?
A momentary change in electrical potential on the surface of a cell, especially of a nerve or muscle cell, that occurs when it is stimulated, resulting in the transmission of an electrical impulse.
71
Give examples of irreversible enzyme inhibitors?
Omeprazole - proton pump inhibitor
| Aspirin - COX inhibitor
72
What are xenobiotics?
are compounds foreign to an organism's normal biochemistry, such any drug or poison
73
What are pharmokinetic principles of ADME?
Absorption
Metabolism
Distribution
Excretion
74
What is the study of drug metabolism?
Pharmokinetics
75
What are the three types of haemolysis?
α- partial, greening
– e.g. S.intermedius
– H2O2 reacts with Hb
β- complete lysis
– e.g. S.pyogenes
– Haemolysins O & S
non (or γ)
- no lysis
– e.g. some S.mutans
76
What are the three ways of classifying streptococci?
1. Haemolysis
2. Lancefield typing
3. Biochemical properties
77
What is lancefield grouping
A method of grouping catalase negative, coagulase negative bacteria based on bacterial cell surface antigens
Antiserum to each group added to a supension of bacteria - clumping indicated recognition
78
Describe staphlyococcus?
- Gram positive
- 40 species coagulase+ve or -ve
- S. aureus most important (coag -+e)
- Normal habitat is nose and skin
79
How is staph aureus spread?
aerosol and touch - carriers and shedders
80
What is MRSA and what is it resistant to?
Methicillin Resistant Staphylococcus Aureus
Resistant to:
– β-lactams
– gentamicin, erythromycin, tetracycline
81
Describe the virulence factors of MRSA
- Pore forming toxins
- Proteases
- Toxic shock syndrome toxin - cytokine release
- Protein A
82
Describe some pyogenic associated conditions of staphylococci?
- wound infections
- abscesses
- impetigo
- septicaemia
- pneumonia
- endocardidis
83
Describe some toxin mediated associated conditions of staphylococci?
- scaled skin syndrome
- TSS
- Food poisoning
84
Describe some coagulase negative associated conditions of staphylococci?
- infected implant
- endocarditis
- septicaemia
85
What colour does Gram positive stain and why?
Purple because it contains peptidoglycan that is stained by crystal violet
86
What colour does Gram negative stain and why?
Pink because it has a lot less pepidoglycan so is stained by safranin
87
Difference between staphylococcus and streptococcus?
Staph - clusters
Strep - chains
88
Describe the catalase test?
H2O2 + staphylococci = gas babbles
```
+ve = staph
-ve = non staph
```
89
When would you use the catalase test?
To determine whether or not a bacteria is a staphylococcus or not
90
Describe the coagulase test?
+ve = s.auereus because it produces coagulase that converts fibrinogen to fibrin
-ve = coagulase -ve staph
91
When would you use the coagulase test
To determine wether no not a staphylococcus is staph. auereus
92
If you saw clusters on a gram positive film what would this infer and what would you do next?
Staphylococcus
Do a coagulase test to determine whether or not it is s.aureus
93
If you saw chains on a gram positive film what would this infer and what would you do next?
Streptococcus
Look at the type of haemolyis on a blood film
94
What doe alpha haemolysis look like, what does it infer and what would you do next?
Alpha = partial
OPTOCHIN TEST:
```
Resistant = viridans strep
Sensitive = s.pneumoniae (+ve, clear ring around optochin disc)
```
95
What does beta haemolysis look like, what does it infer and what would you do next?
Beta = complete lysis
LANCEFIELD TEST:
A: Streptococcus pyogenes
B: Streptococcus agalactiae
D: Enterococcus, Strep bovis (group D is not beta-haemolytic
96
Name some importan Gramt +ve bacteria?
Listeria monocytogenes
Propionibacterium acne – acne
Clostridium difficile – diarrhoea from antibiotic overuse (those starting with C)
97
What does MacConkey agar contain?
Contains bile salts, lactose and neutral red pH indicator
Identifies bacteria that can ferment lactose
Ferment lactose - produces acid - pH drop - <6.8 - pink
98
Why doesnt Gram positive bacteria grow on MacConkey agar?
Because of the bile salts
99
What grows on the yellow MacConkey agar?
Non fermentors e.g. salomella, shigella
100
What grows on the pink MacConkey agar?
Fermenters e.g. e.coli
101
What to do if the cultures growing on MacConkeys agar are yellow?
PERFORM OXIDASE TEST
Black/purple = +ve = pseudomonas or Neisseria(note it is cocci not bacilli)
Colourless = shigella, salmonella, proteus
102
Describe proteus mirabillis?
Swarms on many agars, diffiicult to identifiy other bacteria growing
CLED is used to inhibit proteus
To identify - postitive urease test
103
Give an example of gram -Ve cocci?
Any neisseria on microscopy: gram -ve diplococci
104
Give some examples of Gram -ve rods?
Curved shaped: cholera
Helical shape: helicobacter pylori
Coccobacilli: haemphilus influenza
105
What does fastidious bacteria need to grow?
Fastidious bacteria requires chocolate agar which is blood agar but with lysed RBCs due to heating to 80 degrees C
106
Name the most important mycobacteria?
Tuberculosis
107
How do you identify mycobacteria?
Mycolic acid in the cell wall does not absorb normal Gram staining
Requires Ziehl Neelsen stain to identify acid-fast bacilli
108
Which antibiotics are used for the following:
1. MRSA
2. entamoeba histolytica, giardia
3. PCP
4. pneumonia
5. C.difficile
1. Vancomycin - MRSA
2. Metronidazole - entamoeba histolytica, giardia
3. Co-trimoxazole - PCP
4. CURB65 score for pneumonia and their respective antibiotic regimens
5. Vancomycin/metronidazole - C.difficile
109
Which types of antibiotics inhibit cell wall synthesis?
1. Glycopeptides - vancomycin, teicoplanin
| 2. Beta lactams - penicillins, cephalosporins, carbapenems
110
Give some examples of penicillins
Penicillins (beta lactams)
- Benzylpenicillin
- Flucloxacillin
- Ampicillin/amoxicillin
111
Give some examples of cephalosporins?
Cephalosporins (beta lactams)
1st gen cephalexin
2nd gen cefuroxime
3rd gen ceftazidime
112
Give some examples of carbapenems?
Imipenems
Ertapenem
113
Which types of antibiotics inhibit protein synthesis?
1. Chloramphenicol
2. Macrolides
3. Tetracyclines
4. Aminoglycosides
114
Give examples of macrolides?
Clarithromycin
| Erythomycin
115
Give some examples of tetracyclines?
Tetracycline
| Doxycyline
116
Give some examples of aminoglycosides?
Gentamycin
| Streptomycin
117
Give some examples of how some antibiotics inhibit nucleic acid synthesis?
1. Inhibit folate synthesis - trimethoprim, sulphonamides, both = co-trimoxazole
2. Inhibit DNA gyrase - fluroquinolones
3. Binds to RNA polymerase - Rifampicin
4. DNA strand breaks - Nitroidimazoles, metronidazole
118
Where are fungal infects usually found and give some examples?
Usually in immunocompromised individuals
- Candida albicans = treat with antifungal
- Pnuemocystis pneumonia - treat with co-trimoxazole
- Aspergillosis
119
Name some helminths
Wucheria bancroftii – filariasis causing lymphoedema
Enterobius vermicularis – common in uk, itchy bum, spreads in household
Schistosomiasis – causes squamous cell bladder cancer
Hookworm - Worldwide cause of iron-deficiency anaemia
Treatment: normally mebendazole
120
Name some protazoa?
Entamoeba histolytica: bloody diarrhoea, liver abscess
Treat with metronidazole
Malaria: learn in haematology, 5 types, plasmodium falciparum most important
Giardia: diarrhoea due to alteration of intestinal villi, reducing absorption
Treat with metronidazole
121
Describe some routes of administration?
- Oral
- Intravenous
- Intramuscular
- Subcutaneous
- Inhalation
- Topical
- Rectal
122
Define pharacokinetics?
Pharmacokinetics is what the body does to a drug
123
What are some mechanisms of absorption?
- Passive diffusion
- Facilitated diffusion
- Active transport
- Endocytosis
124
Define bioavailiability?
Rate and extend to which an administered drug reaches the systemic circulation
(IV = 100% )
125
What factors effect bioavailiability?
- First pass hepatic metabolism
- Solubility
- Chemical instability
126
What is first pass hepatic metabolism?
The hepatic transformation of drug to inactive metabolites
127
What is the definition of distribution?
Drug reversibly leaves the bloodstream and enters the extracellular fluid and tissues
128
What factors effect distribution?
Blood flow: e.g. brain>muscles
Capillary permeability
Plasma protein binding
Tissue protein binding
Lipophilicity (ability to cross cell membranes)
129
Define: metabolism?
Process of elimination mainly through hepatic, renal and billary routes
130
What is first order metabolism?
Catalysed by enzymes, rate of metabolism, directly proportional to drug concentration
131
What is zero order metabolism?
Enzymes saturated by high drug doses, rate of metabolism is constant
132
What is phase 1 metabolism?
Polarise lipophilic drugs, reduction / oxidation / hydrolysis, catalysed by cytochrome P450 system
133
What is phase 2 metabolism?
Conjugation, e.g. glucuronic acid, polarisation of drugs to be excreted by renal or biliary systems
134
What are some inducers and inhibitors of cytochrome P450
INDUCERS
Antiepileptics
Rifampicin
St Johns wort
Chronic alcohol intake
INHIBITORS
Cirproflaxin, erythromycin
Isoniazid
Amiodarone
Allopurinol
135
Describe drug elimination?
Renal (excretion via urine, must be sufficiently polar, renal dysfunction = drug acumilation)
Intestines, bile, lungs, breast milk
136
What is pharmacodynamics?
What the drug does to the body
| Its effect on cellular receptors via signal transduction
137
What is signal transduction?
Binding of drug to extracelluar or intracellular receptor
Via variery of receptors e.g. ligand gated ion channels and G protein coupled receptors
138
What are the factors of drug effect?
Drug concentration (dose of drug + pharmacokinetic profile)
Receptor availability (maximal effect once receptors are saturated irrelevant of increasing dose)
139
Describe the neurotransmitter pathways of sympathetic and parasympathetic systems?
Sympathetic =
Acetylcholine > nicotinic receptor > norepinephrine > adrenergic receptor
Parasympathetic =
Acetylcholine > nicotinic receptor > acetylcholine > muscarinic receptor
140
What are some alpha 1 agonists and antagonists, and what are their effects?
```
Agonists = decongestants
Antagonists = tamsulosin, doxazosin
Effects =
- vasconstriction
- increased peripheral resistance
- increased blood pressure
- mydriasis
- Increased closure of internal bladder sphincter
```
141
What are the effects of alpha 2 receptors?
- inhibiton of norepinephrine release
- inihbition of acetylcholine release
- inhibition of insulin release
142
What are some beta 1 agonists, antagonists and what are their effects?
```
Agonists = inotropes (epinephrine, dopamine) Antagonists = Selective / non selective beta blockers
Effects =
- tachycardia
- increased lipolysis
- increased myocardial contractility
- increased release of renin
```
143
What are some beta 2 agonists, anatgonists and what are their effects?
```
Agonists = SABA / LABA
Antagonists = non selective beta blockers
Effects =
- vasodilation
- decreased peripheral resistance
- bronchodilaton
- increased muscle and liver glycogenolysis
- increased release of glucagon
- relaxed uterine smooth muscle
```
144
Name some parasympathetic muscarinic receptor agonists and antagonists?
```
Agonists = glaucoma, donepezil, rivastigmine
Antagonists = atropine, SAMA/LAMA
```
145
What are some CNS receptors
Dopamine (ant psychotics)
GABA (ag benzodiazepine)
Histamine-1 (ant certizine)
Histamine 2 ( ant ranitidine)
146
What are the associated antibiotics for these common infections?
```
CAP
Atypical CAP
IECOPD
HAP
TB
Cellulitis
UTI
```
```
CAP - amoxicillin+/- clarithrmycin
Atypical CAP - clarythromycin
IECOPD - amoxicillin
HAP co-amoxiclav / cefuroxime /tazocin
TB - RIPE
Cellulitis -flucloxacillin
UTI - trimethoprim, nitrofurantoin
```
147
What are the associated antibiotics for these common infections?
```
Gonorrhoea
Chlamydia
Syphilis
Gastroeneritis
C.Difficile
Acute abdo infections (appendicitis)
```
Gonorrhoea - ceftriaxone (IM) + azithromycin (PO)
Chlamydia - doxycline /azithromycin (PO)
Syphilis - benzathine benzylpenicillin
Gastroeneritis -
Campylobacter - clarithromycin
Salmonella/shieglla - ciprofloxacin
C.Difficile
1st - metronidazole
2nd - vancomycin
Acute abdo infections (appendicitis)
Cef +met
148
How do NSAIDs work?
Non selective competitive reversible COX inhibition
149
How does heparin work?
Activates antithrombin (decreased thrombin and factor Xa), short half life
150
How does warfarin work?
Anti-vitamin K = decreased FII (prothrombin) /VII/ IX/X and protein C/S
Reversal = vit K
151
Give some examples of direct factor X inhibitors?
Apixaban, Rivaroxaban
Directly inhibit FXa
Side effect - bleeding
152
How do thrombolytics work?
Activate plasminogen -> plasmin
E.g. strepokinase
side effect - bleeding
153
What do juxtaglomerular cells release renin in response to?
- DECREASED BP detected by barorecepotrs in afferent vascular walls
- Decreased Na+ delivery to macula densa cells
- Increased sympathetic stimulate (beta-1)
154
What are the functions of ACE?
- Catalyses conversion of angiotensin 1 to angiotensin 2
| Degraded by bradykinin
155
What are some of the effects of angiotensin 2?
1. Systemic arteriole vasoconstriction
2. Kidney efferent>afferent constriction = increased glomerular pressure = maintain GFR despite lowered overall kidney bloodflow
3. Kidney PCT/thick ascending limb exchanged stimulation = increased Na+/HCO3/H2O reabsorption
4. Adrenal cortex = aldosterone release
5. Posterior pituitary = ADH release
156
Describe how loop diuretics work?
e. g. Furosemide, bemetanide
- Inihibit Na/K/Cl cotransport of thick limb
IND: Oedematous States (HF, Cirrhosis, Nephrotic Syndrome, Pulmonary Oedema), HTN, Hypercalcaemia
SE: ototoxicity, hypokalaemia, dehydration, AKI, gout
157
Describe how thiazide diuretics work?
e. g. Bendroflumethiazide
- Inhibit Na/Cl contransporter of distal tubule
IND: HTN, HF, Nephrogenic DI
SE: hypokalaemic metabolic alkalosis, hyponatraemia, hyperglycaemia, hypercalcaemia, hyperuricaemia
158
Describe how spironolactone works?
Spironolactone = competitive aldosterone receptor antagonists in collecting tubules
IND: HF, Hyperaldosteronism, Hypokalaemia
SE: hyperkalaemia, antiandrogen effects, e.g. gynaecomastia, loss of libido, erectile dysfunction
159
Give an example of a biguanide, mechanism and SE?
e.g. = Metformin
Mechanism = increased insulin sensitivity, decreased hepatic gluconeogenesis
SE = GI disturbance, lactice acidosis
160
Give an example of a sulphonylurea, mechanism, and SE?
e.g. glicazide
mechanism = Increased insulin secretino
SE = hypoglycaemia, weight gain, SIADH
161
Give an example of a gliptin, mechanism and SE?
e.g. sitagliptine
mechanism = decreased glucagon secretion
162
Give an example of thiazolidinediones?
e.g. Pioglitazone
mechanism = increase adipogenesis
SE = weight gain, fluid retention
163
Describe the pathology of a paracetamol overdose?
- Phase 2 conjugation pathway saturated
- Alternative pathway used - NAPQI = glutathione depletion
- Glutathione depletion = liver/renal necrosis
164
What are the risk factors of a paracetamol overdose?
Psychiatric Hx
Elderly/low weight
P450 inducers
165
What investigation would be carried out for a paracetamol overdose?
- Serum paracetamol level
| - U and E, LFT, glucose clotting, ABG
166
What is the management for a paracetamol overdose?
IV N-acetylcysteine
On/above nomogram line
Staggered overdose
Doubt over investigation time
Liver transplant
167
What would be done for the following overdoses?
```
Aspirin
Opioid
Digoxin
Carbon monoxide
Organophosphate insecticide
```
```
Aspirin - haemodialysis
Opioid - naloxone
Digoxin - digoxin specific antibody fragments
Carbon monoxide - 100% oxygen
Organophosphate insecticide = atropine
```
168
Define: antibiotic?
Antibiotics agents produced by micro organisms that kill or inhibit the growth of other micro organisms in high dilution - they work by binding to a target site on a bacteria
169
Which antibiotics work by cell wall synthesis interference?
penicillins, cephalosporins, carbapenems
170
Which antibiotics work by nucleic acid synthesis interference?
metronidazole, rifampicin
171
Which antibiotics work by DNA gyrase interference?
Fluroquinolones
172
Which antibiotics work by inhibition of ribosomal activity?
Aminoglycosides, tetracyclines, lincosamides, macrolides, chloramphenicol
173
Which antibiotics work by inhibition of folate synthesis and carbon unit metabolism?
Sulphonamides and trimethoprim
174
How do bacteriostatic antibiotics work?
Bacteriostatic antibiotics prevent bacteria multiplying
also reduce exotoxin production
175
How do bactericidal antibiotics work?
Bactericial antibiotics kill the bacteria
Generally inhibit cell wall synthesis
176
Does the lowest MIC = best antibiotic?
NO!
177
What are the two major determinants of anti bacterial effects?
Concentration
(concentration dependent killing - key parameter is how high the concentration is above MIC)
Time
(time dependent killing - key parameter is the time that serum concentrations remain above the MIC during the dosing intervals)
178
Define pharmacokinetics?
The movement of a drug from its administration site to its place of pharmacological activity
179
What are the key considerations when choosing an antibiotic?
* What is the appropriate or available route of administration?
* Which antibiotics will penetrate that site?
* What is the pH of the site?
* Is the antibiotic lipid soluble?
* Half life and elimination – What dosage interval / duration?
180
How do bacteria resistant antibiotics?
1. Change antibiotic target
2. Destroy antibiotic
3. Prevent antibiotic access
4. Remove antibiotic from bacteria
181
What does intrinsically resistant mean?
Naturally resistant
All subpopulations of a species will be equally resistant
182
How do bacteria acquire resistance?
1. Spontaneous gene mutation
2. Horizontal gene transfer
In acquired a bacterium which was previously susceptible obtains the ability to resist
183
What are the different types of horizontal gene transfer?
Conjugation > sharing of extra chromosomal DNA plasmids (bacterial sex)
Transduction > Insertion of DNA by bacteriophages
Transformation > Picking up naked DNA
184
How do CRE infections work?
1. Lots of germs, 1 or 2 are CRE
2. Antibiotics kill off good germs
3. CRE grow
4. CRE share genetic defencces to make other bacteria resistant
185
What are yeasts?
Small single celled organisms that divide by budding, account for less that 1% of fungi but include several highly medical ones
186
What are moulds?
Moulds form multicellular hyphae and spores
187
Describe the overall burden of fungus?
= enormous e.g. fungal asthma, fungal keratitis, nappy rash but life threatening fungus rare in healthy hosts
188
How is fungal disease treated?
Selectvive toxicity: aim of antimicrobial drug therapy is to achieve inhibitory levels of agent at the site of the infection without host cell toxicity
189
Describe the ideal vaccine?
1. Safe - this could mean attenuated live if suitable or subunit if pathogen is lethal
2. Should induce a suitable immune response - for example mucosal if pathogen uses this route, high antibody titre if antibody is most useful protective agent
3. Generate T and B cell memory
4. Stable and easy to transport - for use in remote areas
5. Should not require repeated boosting
190
What are the choices of antigen for vaccine design?
A. Whole organism (live attenuated or killed inactivated)
B. Subunits (toxoids or antigenic extracts)
C. Peptides
D. DNA vaccines
E. Engineered Virus
191
Give some advantages and some disadvantages of using a whole organism for vaccines?
ADVANTAGES:
activation of full natural immune response
prolonged contact with immune system
memory response in T and B cell compartments
often only single is required
DISADVANTAGES:
immunocompromised could become infected
attenuated can revert to virulent e.g. polio sabin
192
Give some examples of subunit vaccines?
ADVANTAGES:
safe
no risk of infection
easier to store and preserve
DISADVANTAGES
immune response less powerful
repeated vaccinations and adjuvants
consider genetic heterogeneity of the population
193
Give some advantages and disadvantages of DNA vaccines?
ADVANTAGES:
safe - especially in immunocompromised
No requirement for complex storage and transportation
drug delivery can be simple and adaptable for widespread vaccination programs
DISADVANTAGES
DNA vaccines are likely to produce a mild response and require subsequent boosting
No transient infection
Limited to proteins, could induce tolerance or anti-DNA antibodies
194
What is an adjuvant?
Any substance added to a vaccine to stimulate the immune system
195
What are the four major groups of protozoa?
Protozoa - one celled eurkaryotic organisms
1. Flagellates
2. Amoebae
3. Sporozoa > plasmodium
4. Cilliated
196
What are the 5 types of malaria?
- Plasmodium falciparum > most severe
- Plasmodium ovale
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium knowlesi
197
How is malaria transmitted?
Bite of the female anopheles mosquito
198
Describe the liver stage of malaria?
1. Mosquito takes a blood meal and injects sporozoites
2. These travel to the liver and infect the liver cells
3. Mature into Shizonts
4. Shizontes rupture into merozoites
199
Describe the blood stage of malaria?
1. Merozoites enter circulation and infect RBCs
2. Enter the ring stage trophozoites mature into Schizonts
3. Schizonts rupture releasing more merozoites
4. Some immature trophozoites differentiate into sexual stage gametocytes
200
Describe the vector stage?
1. Another mosquito takes a blood meal ingesting gametocytes
2. These mature into an oocyst which ruptures releasing sporozoites
3. Sporozoites are injected into the next host
201
What are the symptoms of malaria?
```
FEVER but may also have
Chills
Headache
Myalgia
Fatigue
Diarrhoea
Vomiting
Abdo pain
```
202
What are some complications of malaria and how are they supported?
- Cerebral: antiepileptics
- ARDS: oxygen, diuretics, ventilation
- Renal failure: fluids, dialysis
- Sepsis: broad spectrum antibiotics
- Bleeding/Anaemia: blood products
- Exchange transfusion if huge parasite burden
203
What is the treatment of complicated malaria?
IV artesunate
| IV quinine + doxcycline
204
Describe the natural history of a HIV infection?
1. Acute primary infection
2. (i) asymptomatic phase (years)
(ii) early symptomatic HIV
3. AIDS (CD4<200)
205
What markers are used to measure HIV infection?
1. CD4 T cell count /µl
| 2. HIV viral load (RNA copies/ml)
206
What are some respiratory diseases associated with HIV?
Kaposi's sarcoma
| Pneumocystitis jeroveci
207
How does HIV infect cells?
HIV infects cells that express CD4, the interaction between CD4 and gp120 is conserved among all primate lentiviruses
208
Describe how HIV replicates?
HIV replication consists of 9 steps?
1. Attachment
2. Entry
3. Uncoating
4. Reverse transcription (error prone so genomic variability)
5. Genome intergration
6. Transcription of viral RBA
7. Splicing of mRNA and translation into proteins
8. Assembly of new virons
9. Budding
209
Describe the immune response to HIV?
Humoral immunity:
- neutralising antibodies
- poor /slow to develope effectively
- envelpe glycoprotein is poorly immunogenic an has high genetic diversity
Cell mediated immunity:
CD8 = qualitatively and quantitatively poor, virus escapes CTL responses through mutations
CD4 = Failure of CD4+ proliferation
The lack of identification of protective immune responses remains a major barrier to development of an effective vaccine against HIV-1.
210
What are the immune system consequences of HIV?
*HIV results in gradual damage to the immune system mainly through the depletion of CD4 T cells *
Progressive decline in number and function of CD4 T-lymphocyte characterises HIV infection and leads to susceptibility infection
Mechanisms of CD4+ T lymphocyte depletion
