Pharmacology Flashcards
1
Q
what affects does cyclosporine have on the body and what is it used for
A
used as an immunosuppressant to reduce rejection of organ transplants
Causes Gingival Hyperplasia
Particularly affects T cells by affecting IL-2 production
2
Q
what is pharmacology
A
study of drugs on living organisms
3
Q
what is pharmacodynamics
A
deals with the study of the biochemical and physiological effects of drugs and their mechanism of action. Effect of the drug on the body.
4
Q
what is pharmacokinetics
A
absorption, distribution, biotransformation and excretion of drugs. Effect of the body on the drug.
5
Q
Drugs do not create new pathways but they alter existing ones. which 2 ways can they act?
A
Returns a function to normal operation
Changes a function away from the normal condition
6
Q
what is a drug
A
a chemical substance of known structure which, when given to a living organism, produces a biological effect.
7
Q
what is specificity
A
The capacity of a drug to manifest only one kind of action
Goal of theraputics is to reach specificity
8
Q
what is selectivity
A
Drug ability to predominantly produce one effect. One effect predominates over a particular dose range – this is called the “therapeutic window” – within this range, the drug may be termed “selective”.
9
Q
compare specificity and selectivity
A
Selectivity is concerned with site of action; specificity, with the kinds of action at a site
10
Q
at what point does a drug become toxic and what happens before this
A
when above the therapeutic window
in the high end of the therapeutic window we can get adverse effects
11
Q
what are the 4 types of effect a drug can have
A
Therapeutic effect: The desired or anticipated effect - specificity
Side effect: Other than therapeutic effects occurring at therapeutic doses
Toxic or adverse effect: Deleterious effects usually occurring at higher doses
Lethal effect: Death caused by very high drug dose
12
Q
what is the therapeutic effect
A
Therapeutic effect: The desired or anticipated effect - specificity
13
Q
what is a side effect (2)
A
Side effect: Other than therapeutic effects occurring at therapeutic doses
14
Q
what is a toxic/adverse effect
A
Toxic or adverse effect: Deleterious effects usually occurring at higher doses within the therapeutic window
15
Q
what is lethal effect
A
Lethal effect: Death caused by very high drug dose
16
Q
what is an acceptor
A
Acceptor: Substances drugs bind to without causing any effect (e.g. plasma proteins)
17
Q
what is a receptor
A
Component of a cell or organism that interacts with a drug and initiates the chain events leading to the drug’s observed effect.
18
Q
what type of receptor is a target for all therapeutic drug
A
heptahelical G-coupled receptors
19
Q
what is efficacy
A
Efficacy: relationship between receptor occupancy and ability to initiate a response at molecular, tissue or cellular level.
20
Q
what is affinity
A
Affinity: ability to bind a receptor. Drug/Receptor interaction
21
Q
what is EC50
A
EC50: [drug] that produces 50% of the maximal effect on semilog scale - above this, we get the toxic effect
22
Q
what is potency
A
how much drug is required to produce a particular effect. Depend on both affinity and efficacy
Adrenalin similar affinity than propranolol but very different efficacy
23
Q
how can we differentiate a full agonist from a partial agonist
A
Full agonist or Partial agonist: based on the maximal pharmacological response that occurs when all the receptors are occupied.
on a graph, partial agonist will plateau at lower concentration
24
Q
what affect does an effective antagonist have on the action of an agonist
A
shifts its affect to the right
agonist requires higher concentrations to have the same affect
antagonist reduces effects of agonist
25
give examples of where receptors are found in the cell
cell membrane receptors: G-coupled receptors, ion channels, enzyme linked
cytoplasm: lipophilic receptors e.g. steroid receptors
nucelus: tyrosine receptors, insulin sensitivity
26
explain how an adrenal receptor works
can be beta (stimulating) or alpha (inhibiting)
binding of ligand leads to G protein activation
by swapping inactive GDP for GTP on G protein
leads to conversion of cAMP for ATP of adenylyl Cyclase
If beta - stimulates cascade of phsophrylation, if alpha - inhibits
27
which protein does a G protein effect ad how
```
Adenolyl Cyclase
either activates (beta) or inhibits (alpha) cAMP --> ATP
```
28
what type of adrenal receptors are there
Alpha 2 blood vessels
β1 Heart
β2 Lung
β3 Bladder
29
where are beta 1 receptors found
heart
30
where are beta 2 receptors found
lungs
31
where are beta 3 receptors found
bladder
32
where are alpha 2 receptors found
smooth muscle, vessels
33
how does adrenal beta receptor activation cause smooth muscle contraction
heptahelical receptor activated swaps GDP for GTP
causes swapping of ATP for cAMP on adenylyl cyclase
increases intracellular cAMP
which is used for muscle contraction
34
how do benzodiazepines work
ion channel activater by binding to GABA
increases frequency of chloride channel opening
hyperpolarization
CNS depression
35
what is GABA and what works on this
an amino acid that functions as the primary inhibitory neurotransmitter for the central nervous system
Benzodiazepines bind to this to cause Cl- channel opening = hyperpolarization = CNS depression
36
compare Benzodiazepines and Barbiturates
Benzodiazepines increase FREQUENCY of chloride channel opening
Barbiturates increase DURATION of chloride channel opening
both cause hyperpolarization and depress CNS
37
how do omeprazole and other anti- acids work
Act by irreversibly blocking the H+/K+ ATPase (gastric proton pump)
reducing acid release in stomach
38
how many hospitalization are due to adverse effects of drugs
3-4%
39
how many hospitalized patients experience adverse drug effects
20-30%
40
what is a type A adverse effect
pharmacological or toxic effect
Exaggerated therapeutic responses - determined by pharmacokinetics
Secondary unwanted action
More predictable or anticipated effects and preventable
41
what is a type B adverse effect
Pharmacologically unexpected, unpredictable, or idiosyncratic adverse reactions
Immunologic (Allergic or anaphylactic)
Idiosyncratic (Qualitatively abnormal adverse reactions that occur in a given individual and whose mechanism is not yet understood)
42
what does the theraputic index lie between
MTC and MEC
minimum toxic concentration
maximum effective concentration
43
what medicines have low therapeutic index
Anticoagulant i.e. warfarin
Aminoglycoside antibiotics i.e. gentamicin
Anticonvulsants i.e. phenytoin
44
state some major and minor concerns of type A adverse effects
```
Major concerns
Respiratory depression (i.e. narcotic agents)
Cardiac toxicity (i.e. overdose of intravascular injection of local anaesthetic)
```
Minor concerns
Diarrhoea (Broad spectrum antibiotics)
Dry mouth (Anticholinergics i.e. antidepressant)
Drowsiness (CNS drugs i.e. benzodiazepines)
45
what are some risk situations for type A adverse effects
```
Childhood - **
Elderly - polypharmacy, disease
Pregnancy - placental diffusion
Lactation - diffusion into milk
Renal failure - metabolised in the kidney/excreted
Haemodialysis
```
46
what are the four stages of pharm kinetics
```
Absorption
Distribution
Metabolism
Excretion
Each step is a target for adverse effect
```
47
what is chelation and how might this affect pharmokinetics
bonding to metal ions
| some drugs chelate leading to less/more absorption
48
who should not receive tetracycline antibiotic and why
Distribution sequestration of tetracycline in bone (tissue binding) leading to depression of bone growth in children and irreversible staining of tooth enamel
Not to be prescribed in pregnant women and children under 12.
49
what can affect absorption of drugs
if we have eaten
what we have eaten
when e have eaten
chelation to metal ions e.g. tannins prevent absorption of iron
50
give some possible factors that effect drug metabolism
Diseases may alter drug metabolism (i.e. renal and hepatic dysfunction)
Abnormal drug metabolism may be due to inherited factors of either
Phase I oxidation
Phase II conjugation
Polypharmacy risk of drug interactions
51
what may lead to in-proper excretion of drugs
renal failure
Kidney disease
Polypharmacy
52
compare type A and B adverse effects
A:
- predictable
- dose dependence
- high incidence
- low mortality
- treatment = lower dose
B:
- unpredictable
- not dose dependent
- low incidence
- high mortality
- treatment = stop treatment
53
what is and what causes VPS
```
Valproate syndrome
Valproic acid used for anticonvulsant in pregnant women
causes child to have:
Broad forehead
Odd finger numery
Thin upper lip
Long philtrum
```
54
what is valproic acid, when should it be avoided and why
anticonvulsant
avoid in pregnancy
causes VPS in children
55
what is Cross sensitisation
reactivity either to drugs with a close structural chemical relationship or to immunochemical similar metabolites
56
what age are we most likely to get allergic reactions
20 and 49
57
what host factors effect susceptibility to allergic reactions
Age (between 20 and 49 at higher risk of allergic reactions)
Sex (slightly more common in women) - related to hormones e..g oestrogen
Genetic factors
Diseases
Previous exposure
58
what is the incidence in drug related anaphylaxis and how many die from it
3 per 100,000
| 1-2 die per 100,000
59
what are the 3 most likely causes of death within dentistry
Penicillin (75% of anaphylactic deaths)
Aspirin
Local anaesthetics: procaine, lidocaine (rare)
60
what percent of anaphylactic deaths are from penicillin
75%
61
what is treatment for anaphylaxis
Adrenaline (im)
Antihistamine (chlorphenamine)
Steroids (hydrocortisone)
Bronchodilator (β agonist/aminophylline)
62
what is stephan/johnson syndrome and what causes it
spots all around the body
| type B adverse reaction due to anticonvulsants, anti-gout medications, pain relivers, peniccilin
63
pt gets spots all around the body after taking anti-gout medication,. What is this likely to be?
Stephan/Johnson Syndrome
64
what food should be avoided when on warfarin and why
grapefruit
| enhances function of warfarin making blood too thin
65
what does teratogenic mean
'monster baby'
| deformaties in baby due to medicine for mother
66
what antibiotic should be avoided with warfarin
Metronidazole
67
what antibiotic shouldn't be given to pregnant women and why
metronidazole = teratogenic
68
are penecillins water or lipid soluble
water
69
what is cytochrome P450 and why is it important
superfamily of enzymes containing heme as a cofactor
these proteins oxidize and metabolise steroids, fatty acids, and drugs in the liver
any drugs which act on cytochrome p450 will alter metabolism in the liver
70
what is a major inhibitor of p450 and what affects does this have on warfarin and other drugs metabolised in liver
Erythromyocin
| inhibits metabolism = prolongs effect of drug = lower dose of other drug or lower dose of ertyhromyocin
71
what drugs/foods might affect midazolam plasma concentrations and what might this lead to
Cytochrome p450 inhibitors e.g. Erythromycin, omeprozole, grapefruit juice
lead to over sedation and respiratory failure
72
what are some inducers of cytochrome p450
phenytoin
carbamazapeine
Rifampicin
Glucocorticoids
73
What is Rifamapcin used for
TB treatment
74
what is st johns wort and when should we avoid this and why
flower extract
used for depression
avoid when having organ transplant or on OCP
induces cytochrome p450 = more metabolism of drugs = less effective
75
what must we tell a patient on metronidazole
side effects = call 111
no alcohol = increase side effects
Nausea, vomiting, flushing, tachycardia, shortness of breath, headache
76
what does alcohol chemically do when taken with metronidazole
decreases acetaldehyde dehydrogenase
| so increases acetaldehyde from alcohol
77
what are the initial and after effects of local anaesthetic
Initially CNS stimulation by depressing inhibitory pathways: tremor/convulsion
Followed by CNS depression: lethargy, respiratory depression, unconsciousness
78
what is local anaesthetic metabolised by and what alters clearence time
CYP3A4
| Clearance limited by hepatic blood flow rather than metabolism (45 min half life)
79
how does adrenaline act on the body
alpha 1 receptors = vasoconstriction of smooth muscle and blood vessels
beta 2 receptors = muscle relaxation (lungs)
80
what drugs affect adrenaline action
Non selective β blockers
Tetracycline antidepressants – inhibit uptake
Cocaine – inhibit uptake
Ritalin – ADHD (release endogenous norepinephrine)
Parkinson’s disease (COMT inhibitors reduce breakdown)
81
what are benzodiazepines a major substrate of
cytochrome p450
82
what might affect benzodiazepine plasma levels
inducers/inhibitors of cytochrome p450enzyme
Inhibition (increased plasma levels)
Calcium channel blockers /macrolide / azole antifungal/protease inhibitors
Induction (decreased plasma levels)
Anti-TB, anti epileptic
83
where are most drugs absorbed and why
small intestine
| highest surface area
84
what is bioavailability of a drug
Fraction of unchanged drug reaching the system circulation following any route of administration - IV has 100% bioavailability
85
what drug administration method has 100% bioavailability
IV
86
what is first pass metabolism
drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation
87
what 3 factor affect bioavailability of a drug
Absorption
First pass metabolism
Food: can decrease the oral availability of sparingly lipid soluble drugs (i.e. atenolol oral availability decreased by 50% by food) - fed or fasting
88
give 3 physiochemical factors affecting distribution of drugs
Molecular size
Oil/water partition coefficient
Degree of ionisation that depends on pKa
Protein binding
89
give 3 physiological factors affecting distribution of a drug
Organ or tissue size
Blood flow rate
Physiological barriers blood capillary membrane cell membrane specialised barriers
90
what plasma protein do most acidic drugs bind to
albumin
91
what plasma protein do most basic drugs bind to
α1-acid glycoprotein
92
what is perfusion
bathing an organ or tissue in a fluid
93
what is perfusion limited distribution
perfusion is the bathing of an organ in a fluid e.g. blood
| the perfusion of an organ alters the distribution of a drug to a organ
94
what are some high and low perfusion organs
```
high = kidney, liver, heart
low = fat, bone, muscle
```
95
what 3 barriers affect Permeability rate limitations
Blood brain barrier
Blood testis barrier
placenta
96
describe brain blood vessels
The blood brain vessels are very tight with little porosities with no pores for water
only small lipid soluble substances can cross this barrier
supported by glial cells
Acidic brain cell ‘traps’ ionised weak bases e..g morphine
97
describe the movements that occur at the placental barrier
Sugars, fats and oxygen diffuse from mother’s blood to foetus
Urea and CO2 diffuse from foetus to mother
Maternal antibodies actively transported across placenta Some resistance to disease (passive immunity)
Most bacteria are blocked
Many viruses can pass including rubella, chickenpox, mono, sometimes HIV
Many drugs are toxins and can pass including alcohol, heroin, mercury
98
why can most drugs cross the placental blood barrier
Drugs that are lipid soluble and mostly un-ionised can easily pass the barrier to the foetus compared to the more polar and ionised ones.
99
compare active and deactive metabolism
active:
pre-drugs are given and metabolised to their active state
they increase in therapeutic effect and toxic effect
deactive:
Structure changed
Decrease of pharmacological effect
Decrease of toxicity
100
breifly explain the metabolism pathways of drugs
either phase 1 or 2 initial reaction
if phase 1:
- phase 2 = conjugate
- OR straight to excretion
If phase 2:
- conjugate
- to excretion
101
explain phase I excretion reaction
Introduction, or exposure, of a polar group by oxidation, reduction or hydrolysis (catalysed by cytocrhomeP450 CYP450 - family of enzymes to produce metabolites in phase 1)
At this point if the metabolites are sufficiently polar can be excreted
A C-H group can be turned into a C-OH converting non pharmacological active compound into active.
Production of primary metabolite and can be excreted or go through phase II into conjugate
DANGER: Toxic compound can be created as well if activated
102
do excreting products have to be more polar or more non-polar
more polar to be excreted
103
what is a conjugate when referring to phase 2 reactions
a near 100% inactivated metabolite ready for excretion
104
what is phase II reaction
Attachment of an endogenous molecule (Transferases: Glucoronyl- Sulpho- AcetylMethyl- ) to a drug or Phase I metabolite, glucuronide, sulphate, acetyl forms a conjugate = ~100% inactive
105
what is the major comparison between phase I and phase II reactions
Phase I predominantly produces more active compounds while Phase II produces less active
106
how does genetic polymorphisms affect drug metabolism
CYP2D6 Polymorphism
8% of Caucasian lack CYP2D6
Are POOR METABOLIZERS for cardiovascular, psychiatric and opiate drugs
107
what enzyme do some caucasians lack, what percent lack it and what does this affect
CYP2D6
8% lack this enzyme
POOR METABOLIZERS for cardiovascular, psychiatric and opiate drugs
108
what is the major comparison of biliary excretion and renal excretion
biliary (stool) = non-polar (conjugates, stable)
| renal = polar (metabolites etc)
109
what is the likely excretion pathway of a phase II reaction product
Biliary as non-polar
110
what cells produce bile
hepatic cells of the liver
111
what percent of bile is re-absorbed in small intestine
90%
112
how does polarity effect excretion of drugs
Metabolites are more excreted in bile than parent drugs due to increased polarity
113
how might liver secretion of drugs with bile prolong effect of drug?
Some drugs and metabolites excreted by the liver cells into bile, pass into the intestine. Reabsorption from the gut during the process of enterohepatic recycling may prolong the pharmacological effect of a drug
114
describe the 3 processes that occur in nephron function
Glomerular filtration
Active secretion
Passive reabsorption
115
what is the average glomerular filtration rate
120ml.min
116
what is filtered at glomerular filtration
unbound proteins - usually not drugs
117
what occur as passive reabsorption
non-ionised drugs are re-absorbed into the blood
| ionised water soluble drugs are taken to the bladder for urination
118
in terms of secretion, filtration and re-absorbtion. What does excretion =
and what is the term for this
excretion = filtration+ secretion - reabsorbtion
| CLR rate of renal excretion
119
what is CLR
rate of renal clearance
120
what if CLR < GFR
net secretion
121
what if CLR > GFR
net re-absorption
122
why might there be a high level of rug in a body
reduced metabolsim/excretion
| excessive dosing
123
give some reaosn why we might have decreased drug clearence
```
Saturable metabolism
Genetic enzyme deficiency
Renal failure
Liver failure
Age (neonate or elderly)
Enzyme inhibition
```
124
give some reasons why drug clearance might be too high
```
Normal variation
Poor absorption
High first pass metabolism
Non compliance
Enzyme induction
```
125
what is pain
An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of tissue damage or both (IASP definition).
126
how many people in the UK suffer from persistent pain
About 40%, or as many as 28 million people, in the UK suffer from persistent pain.
127
what can SCN9A gene mutations or Nav1.7 voltage-gated sodium channel mutations in the subunit cause
loss of pain sensation
128
describe the pain nervous pathay
Pain is transduced and travels through sensory fibres to meet the CNS
where it is then taken to the limbic system (perception/learning)
thalamus (transmission)
and somatosensory cortex for pain perception
129
give 4 dental explanations for pain
Infection causes Acute and chronic inflammation = prostaglandins, bradykinin
Exposed nerve endings = neurogenic pain
Swelling in confined space = pressure effects
Fear and anxiety
130
give ways in which we can treat dental pain
```
Reduce tissue damage:
-Non steroidal anti inflammatory drugs (NSAIDS)
-Steroids
-Cooling
Nerve block: Local anaesthetics
Spinal Cord: opioids
Central Nervous system:
-Opioids
-Psychological factors
```
131
what are the WHO's guidelines on pain management
```
Believe the patient
History of symptoms
Assessment of severity
Physical examination
Appropriate pain management
```
132
what is Synergism in pharmacology
where multiple drugs have the same effect
133
how has the WHO ladder been since updated from the 1980's (2)
co-analgesics added e.g. nerve blocks, psychological issues, radiotherapy
More specific with types of drugs e.g. NSAIDs and paracetamol instead of ‘non-opioids’
134
what is the WHO ladder
progression of treatment with increasesing severity of pain = stronger analgesics
NSAIDs --> weak opiods +- NSAIDs --> strong opiods
135
what is paracetamol and when is it used and what effects does it have
it is a weak non-NSAID COX inhibitor
other mechanisms unknown
Analgesic, antipyretic, not much anti-inflammatory effect
used with mild, non-inflammatory pain
136
how many tablets = overdose of paracetamol and what is the treatment
>30 tablets in a day or toxic dose >4g
| N-acetyl-cysteine NAC
137
what can newer NSAIDs do compared to old ones and why is this good
differentiate between COX1 and COX2
anti-platelet and GI tract adverse effects usually come from COXI
selective COX2 inhibitors reduce these effects
138
what side/adverse effects do we get with NSAIDs
GI Tract: Occult GI blood loss from minor breaches in mucosa (loss of PGE). Peptic ulceration. General GI upset, indigestion
Renal Function: Reduction in intrarenal blood flow can cause renal failure
Platelets: COX inhibition, bleeding tendency, Thromboxane inhibition
Cardiovascular: As a result of altered renal function, fluid retention can precipitate heart failure
Respiratory: Some ‘aspirin sensitive’ asthmatics
139
do COX I or COX II affect platelet function
COX I
140
what are some risks with COXII inhibitors
Parecoxib, Celecoxib
Slightly pro thrombotic
Increased risk MI and Stroke
Contraindicated in cardiovascular disease
141
what must we do with NSAIDs before surgery and why
stop 5 days before elective surgery
platelets have 4 day lifespan and they are irreversibly reduced
need proper platelet function
142
when are weak opioids prescribed and how do they work
moderate pain
| codeine is metabolised to morphine
143
how might metabolism effect weak opiods
e.g. codeine is metabolised by enzymes = morphine
| if pt has educed enzymes or inhibition, effect will be less
144
what are some adverse effects of weak opiods
Cardiovascular: Reduced sympathetic outflow, increased vagal tone. Bradycardia, hypotension, excitation.
Respiratory: Inhibit cough reflex, respiratory depression.
GI Tract: Reduced gastric motility. Constipation, nausea and vomiting.
145
what are some actions of weak opiods
Sedation, euphoria, (dysphoria), excitation
ANALGESIA
Spinal Cord : Reduced pain fibre transmission kappa opioid receptors
Brainstem: Reduced pain projection to higher centres. Mu opioid receptors
Respiratory depression, reduced brainstem response to hypoxia and hypercarbia.
146
what receptors do opioids act on in the body
Spinal Cord : Reduced pain fibre transmission kappa opioid receptors
Brainstem: Reduced pain projection to higher centres. Mu opioid receptors
147
what is the reversal agent for weak opiods
Naloxone 400 mcg i.v. dramatic reversal of mu receptor opioid effects.
Far less effective on newer synthetic opioid like substances as their effects in the CNS are less well defined.
148
explain opioids dependancy
Chronic opioid use: reduced effect as CNS becomes more tolerant. Dose increases.
Acute withdrawal: Hypertension, tachycardia, tachypnoea, diarrhoea, sweating, anxiety, hallucinations.
Any chronic opioid medication will precipitate some withdrawal reaction if stopped suddenly.
149
name 2 newer opiods and why might they be better than codeine
Tramadol and Nefopam
As effective as codeine, less variability, much less constipation hence very frequently prescribed. “Oramorph” lower dose oral morphine.
150
why might tramadol not be a good alternative to codeine
```
Increasing number of fatalities from overdose causing respiratory depression.
Dependency develops with long term use which is difficult to withdraw.
New legislation: Controlled drugs (class 3). Limit to maximum prescription. Must be signed for.
```
151
can you give paracetamol, NSIADs or opiods to patietns with damaged liverkidney?
```
paracetamol = possibly
NSAIDS = no
Opiods = no
```
152
what might we take for severe pain
Morphine; oral, s.c., i.v.
Diamorphine s.c., i.v.
Fentanyl patch (transdermal)
153
if we were to take an opiod PO, what would we do to the IV dose
x3 due to less bioavailability
154
why is patient delivered morphine better than nurse deliver morphine post op
studies show that patients deliver 1/3 the amount nurses do
155
if a patient is on morphine IV what is co-prescribed
anti-emetic
156
what is the minimum morphine given for a patient post op
1mg every 5 minutes
157
how much morphine do we give post op until pt is comfortable
2mg in 3 minute increments
158
how much morphine is usually needed for recovery setting
10-20mg
159
what are Gabapentin and Pregabalin
type of Adjuvant therapy
Effective for chronic neurogenic pain
Reduce central transmission and pain projection
Adverse effect: sedation, dizziness, nausea, occasionally hypotension
160
when might antidepressant be used clinically
Adjuvant therapy for chronic or neurological pain
161
how might we psychologically support a patient with unexplained pain
Sharing experience with other patients, talking about it, BELIEVE the patient
Highly underestimated with pain as it is not related to death or serious illness but it really reduced quality of life
Adjuvant techniques like anti-depressants or Gabapentin and Pregabalin pain killers
162
what are the three antibiotic typs that attack the cell wall
β-lactams – penicillins and cephalosporins - inhibit gp formation
Glycopeptides – vancomycin, teicoplanin
Cycloserine – inhibits alanine racemase & D-alanine ligase. TB treatment.
163
how do beta lactams work
contain a beta lactam ring and similar structure to D-Alanyl D-alanine
bind to cell wall of bacteria via PBP or DD-transpeptidase
and prevent proper function and formation of crosslinkages
164
what is the structure of penicillin (2)
very similar structure to D-alanyl-D-alanine - structural homologue
and contains beta lactam ring 5 member ring
165
how does penicillin work (4)
structure very close to D-alanyl-D-alanine
This binds to DD-Transcriptase (PBP)
enzyme needed to form peptidoglycan cross-linkages
when bound, cannot form new cell walls = cell death
166
what is vancomycin and what is it effective against
Glycopeptide antibiotic
Effective against Gram positive organisms
Used in MRSA patients
167
how does Vancomycin work
Binds to D-alanyl D-alanine dipeptide on side chain of newly synthesised peptidoglycan subunits, preventing them from being incorporated into cell wall by penicillin binding proteins (PBPs)
168
how does Erythromycin work
Erythromycin blocks exit of nascent chain during transcription of bacterial DNA
169
how does Tetracyclines work
Tetracyclines inhibit tRNA binding to amino acids preventing any synthesis
Inhibit binding of tRNA to mRNA/Ribosome complex
Bacteriostatic compounds
All broad spectrum
penetrates mammalian cells to reach intracellular organisms
Incorporated into developing bone and teeth - contraindicated for children
Use restricted due to widespread resistance
170
how do aminoglycosides selectively work against bacteria (3)
bacterias mRNA sub-units are 30s and 50s
humans mRNA sub-untis are 40s and 60s
Bind to 30S subunit = misreading of genetic cod
171
what do aminoglycosides work against
Effective against aerobes and facultative anaerobes- Not active against anaerobes
Not effective against anaerobes as bacterial up-take requires oxygen- or nitrate-dependent electron transport
172
how and why do we administer Aminoglycosides
Not absorbed from the gut
| must be given intravenously or intramuscularly for systemic treatment
173
why can Tetracyclines not be given to children
can get implemented into growing teeth and bone
174
are tetracyclines bacteriostatic or bacteriocidic
bacteriostatic
175
are macrolides bacteriostatic or bacteriocidic
bacteriostatic
176
how do macrolides work and give an example and when it is used
Bind to 50S subunit blocking exit of nascent polypeptide chain
Erythromycin
Penicillin allergy
177
what type of antibiotic are metronidazole
Nitromidazoles
178
what are nitromidazoles affective against
anaeorbic bacteria and parasites
179
how does metronidazole work
activated in cell by redox enzyme pyruvate-ferredoxin oxidoreductase
In anaerobes, ferredoxin is an e- transporter molecule that reduces (gives electrons to) Metronidazole
This single electron transfer reduces the nitro group of met. creating highly reactive anion – disrupts DNA helix
intermediate is short-lived and decomposes
Metronidazole is active only against strictly anaerobic organisms
because only these can produce the low redox potential necessary to reduce the drug
180
what is ferredoxin
an e- transporter molecule that reduces (gives electrons to) Metronidazole
found in anaerobes
181
which type of antibacterial affect DNA polymerase
Rifamycins
182
how many antibiotic prescriptions come from dentists
10%
183
how much of dental prescriptions are amoxicillin and metronidazole
60%amoxicillin
| 30£ metronidazole
184
how many dental prescriptions did not fit the NICE guidelines in 2015
1 in 5
185
what is the general clasificatio of most anti-virals
very narrow and low in number
| virostatic not virocidal
186
give a few methods of antiviral machinery
Prevent fusion of viral envelope with cell membrane
Zidovudine (AZT - HIV) acts as substrate for & inhibitors of viral reverse transcriptase (viral enzyme to create DNA copy of its RNA, necessary for integration into host genome)
Acyclovir – inhibits HSV DNA polymerase
187
what is Zidovudine used for
antiviral for HIV
acts as substrate for & inhibitors of viral reverse transcriptase (viral enzyme to create DNA copy of its RNA, necessary for integration into host genome)
188
what is
| Acyclovir used for
HSV antiviral
| inhibits HSV DNA polymerase
189
for a dental abscess, what anti-biotic can we provide under NICE guidelines
Amoxicillin 500mg tds x 5/7
| Penicillin V 500mg qds x 5/7
190
what is the treatment for a localised dental abscess
pulpectomy/drainage
analgesia
not recommended to use antibiotics
191
when are antibiotics indicated with a dental abscess
No possibility of immediate attention by a dental practitioner,
Signs of severe infection e.g. fever, lymphadenopathy, cellulitis, diffuse swelling.
Systemic symptoms e.g. fever or malaise.
A high risk of complications e.g. people who are immunocompromised or diabetic or have valvular heart disease.
192
a pt has a large swollen neck. What are some other diagnosis other than abscess (non-infectious, neoplasm and viral)
Non infectious
Localised lymphadenopathy due to other inflammation or a neoplasm.
Salivary gland problem due to stone, infection (parotitis), or dehydration/dry mouth.
Neoplasm: Intraoral, Salivary gland.
Unerupted teeth.
Viral : Mumps
193
what do we prescribe for an odontogenic neck space infection
Oral metronidazole 8 hourly
194
what can we treat MRSA bacteraemia with
Vancomycin
Intravenous
Twice daily
2 weeks
195
what is the 5 C's
five drugs starting with C that may lead to out competition of good bacteria and lead to a drug induced C. Difficile infection
196
briefly explain antimicrobial stewardship
start smart:
- thorough drug allergy history
- immediate therapy with narrow spectrum antibiotics if sepsis
- blood samples before if possible but do not delay
- document everything
then focus:
-reviewing the clinical diagnosis and the continuing need for antibiotics at 48*-72 hours
and documenting a clear plan of action - the ‘antimicrobial prescribing decision’
-possible switch from IV to PO
-specific antibiotics
197
what are the five ‘antimicrobial prescribing decision’ options
Stop antibiotics if there is no evidence of infection
Switch antibiotics from intravenous to oral
Change antibiotics – ideally to a narrower spectrum – or broader if required
Continue and document next review date or stop date
Outpatient Parenteral Antibiotic Therapy (OPAT)
198
compare floxacillin and Vancomycin
Flucox is first line, broad as it is small and may not land on target site
Vancomycin is much larger and has more effect, needed IV as not absorbed in gut
199
expalin the indication of no,large and small zone of inhibition
no zone = not effective against bacteria
small zone = effective but need very high concentrations = not suitable
largezone = effective and suitable
200
how can we avoid C.Difficle outbreaks
good hygiene and hand washing
avoid unnecessary antibiotics
avoid the 5 C's antibiotics
