Flashcards in Pharmo Deck (442):
What are the different sorts of active failure in prescribing?
Violation - Directly contravening known guidelines
Slips - e.g. Copying one dose for multiple drugs
Lapses - e.g. Missing a contraindication
Mistakes - e.g. Not knowing to reduce a drug in renal failure
What is reasons model of accident causation?
A number of factors that come together, all required but non sufficient to cause the error alone. Includes latent conditions, active failure and failure of defences.
Why do errors happen?
High expectations from day 1
Exhaustion on nights
Lack of senior support
Routine task boredom
Lack of familiarity with patients
Increased uses of drugs
Older patients with co morbidities and poly pharmacy
What is the individual vs systems base for medical drug errors?
Individuals fault - fear, retrain, litigation, naming and shaming
System fault - safeguards, barriers, acceptance and improvement
What is pharmacovigilance?
What are the aims?
The process of id and responding to safety issues about marketed drugs.
- id previously unrecognised safety hazards
- what causes the toxicity
- obtain evidence of safety to allow widening of drugs use
- identify false positive adrs
What are type a and type b drug reactions?
A - predictable, exaggerated pharmocological response, dose dependant, common, high morbidity low mortality
B - unpredictable, not expected, in dependant of dose, rare, high mortality
What are the dissadvantages of a clinical trial vs clinical prescription?
Small number of patients vs millions
Restricted age, pmh and dhx vs anyone indicated
Limited duration vs lifelong
Specialists prescribers vs generalists
High level of clinical monitoring vs low
How are adrs identified?
Case control studies
What is the yellow card scheme?
What drugs should be especially reported?
A report of potential adrs to mhra
Mhra then consider the cohort or case control studies
Black triangle drugs (1st year out of trials)
Unusual or serious reactions from established drugs
Problems with yellow card scheme?
Delays in reporting
Poor data - filled in too fast
No control group (how many recieve with no issues)
Difficulty recognising previously unknown adrs
Why is reporting of adrs low?
Failure of pt to report
Adr is trivial
Not knowing report
Lack of time
Uncertainty of causal relationship
Experience with process
What is bioavailability? How is it calculated?
Fraction of administered drug that reaches systemic circulation
F = AUC (oral) / AUC (iv)
What factors effect bioavailability?
Active - gi membrane pumps, enzymatic destruction, first pass metabolism
Passive - lipid solubility, molecular size of drug, pKa of drug
What factors determine drug distribution?
Plasma protein binding
Tissue protein binding
Variation in compartment size etc. (E.g. Obese with more fat)
How do we work out volume of distribution of a drug?
Calculate concentration (C0) in plasma at time zero by extrapolating backwards from successive concentration measurements.
Vd = initial dose / C0
Assumes immediate distribution of the drug
Alternatively plot Vd using initial dose over current concentration against time then extrapolate back to get Vd at time 0
What does Vd show?
What would a reading of 5L, 10L, 200L suggest?
Equivalent volume of plasma a drug is distributed within - indicitive of compartments
5 - in plasma
10 - in ECF
200 - in muscle or fat too
How can Vd be expressed?
Total (e.g. 8L) or as a propotion of weight (e.g. 0.2 L/kg)
What reactions occur in phase 1 metabolism?
Redox reactions, hydroxylation
What enzymes are most commonly involved in phase 1 metabolism? Which subset?
How does phase 1 metabolism contribute to differing half lives of drugs?
CYP enzymes very generalist and therefore have variable rates with different drugs
What non modifiable factors can influence drug metabolism?
What does pharmacogentetics allow?
An understanding how different genotypes will relate to different drugs to determine which drugs are effective and which are safe
Give an example of pharmacogenetics applied to antihypertensive drugs
Why? What is given instead?
Ace inhibitors is less effective in black people
Afro caribbeans patients have lower RAS activity so medication would not be so effective.
Thiazide or calcium channel blocker.
What adr are afrocaribbean pts more likely to suffer from lisinopril?
What is the formula for half life?
T1/2 = 0.7 Vd/CL
What is the definition of half life?
The constant fraction of a drug eliminated over a certain time period
What are routes for drug elimination?
How is steady state concentration calculated in an infusion?
CpSS = dose rate / clearence
How long does it take for a drug given at a constant rate to reach steady state?
Five. Half lives
Roughly how is a loading dose calculated?
Loading dose = Vd x desired CpSS
Should a loading dose be adjusted for renal failure? What about maintainance doses?
Loading no, maintenance yes.
What is the most common drug target?
What are some examples of unconventional drug action?
Being an enzyme (streptokinase)
Reacting with small molecules (antiacids)
Binding free molecules (chelating agents)
What could cause non linear pharmacodynamics?
Limitations in second messengers
Has no intrinsic efficacy blocking the receptor
Define partial agonist
An agonist that is unable to reach a full response even when all receptors are activated as such also acts as a partial antagonist
Define affinity, how is it recorded from a graph of binding vs concentration?
The tendency for a drug to bind to bind to its receptor
Defined by Kd, the concentration at which half the receptors are bound.
What is efficacy, how is it recorded from a graph of concentration against effect?
The maximal response of a drug when bound to. Its receptor
Measured by Emax (response where further increase in drug concentration provides any additional effect)
What is potency? How is it recorded from a concentration response graph?
The drug concentration at which 50% of emax is obtained
Recorded as EC50
What do competitive antagonists change?
Decrease potency, no change to efficacy
What effect on a dose response curve would a non competitive agonist have?
No effect on potency, reduced efficacy
In what situation would a noncompetive antagonist not effect efficacy of a drug"
Low enough dose with spare receptors
What do selectivity and specificity refer to in pharmocology?
Selectivity - the affinity of a drug for a particular receptor (highly selective may still effect others as dose increases)
Sensitivity - the drug effects a specific subtype of receptor (e.g. Beta 1 only)
How is. Therapeutic index calculated?
WHat is therapeutic window?
The range of drugs concentrations that elicit a desired effect without unacceptable adverse effects.
List some pharmacokinetic dd interactions
Absorption - eg. Changes to gut motility (metoclopramide).
Distribution - protein binding interactions (e.g. Aspirin displacing warfarin)
Metabolism - cyp induction or inhibition
Elimination - altered urine pH (e.g. alkanisation of urine to excrete aspirin)
Name some cyp enzyme inducers and inhibitors
Inducers - Rifampicin, chronic alcohol, carbamezapine, st johns wort, sulphonureas
Inhibitors - Cimetidine, acute alcohol, isonazid, valporate, sulphonamides
How do cyp induction and inhibition differ (other than the obvious)!
Induction - onset over several weeks (increasing expression of the enzyme)
Inhibition - onset over several days (competitive and non competitive inhibition)
How can pharmacodynamic ddis be used beneficially?
Enhance therapeutic effect (combination therapy)
Antagonise unwanted effect
Give some examples of direct and indirect unwanted pharmacodynamic ddis
Direct - adrenaline and maoi both causing increased sympathetic stimulation
Indirect - furosemide causing hypokalaemia enhancing digoxin
Which drug classes most commonly cause pharmacodynamic ddis?
What diseases most prevalently cause drug disease interactions?
Enzyme inducers are
st Johns Wort
Enzyme inhibitors are
Side effects of COCP
Ca breast and cervix
Decreased glucose tolerance
When should COCP not be given?
Cured breast cancer
Benefits of COCP beyond pregnancy?
Decrease risk of endometrial, colorectal and ovarian cancer
Which cocp has extra anti acne effect?
What is the associated problem?
Contains cyproterone acetate which acts both as a progesterone and an anti testosterone.
Higher risk of thromboembolism vs other COCPs
What are the constituents of microgynon?
Which generations of progesterone are associated with increased risk of thromboembolism?
Side effects of POP?
What are the advantages of POP?
No associated risk of venous thromboembolism, stroke or MI and Ca breast
Why does cocp increase risk of cancer of the cervix?
Causes inversion of cervix exposing columnar epithelium to acid causing metaplasia then dysplasia.
What drugs are used for emergency contraception? What are the timeframes?
Levenorgestrel (up to 72 hrs)
Ullipristal (up to 120 hrs)
Copper iud (up to 120 hrs)
What is a big risk of emergency contraception?
All increase risk of ectopic pregnancy.
What are the benefits of HRT?
Relieves menopause symptoms
May reduce osteoporosis incidence
What does hrt not change?
What are risks of hrt?
What patients can recieve hrt in pure oestrogen form?
When might antioestrogens be used?
Tamoxifen - ca breast
Clomipnene - infertility due to decreased ovulation
Why may antiprogesterones be used? Example?
Abortion or labour induction
What do the different lipoproteins carry?
Chylomicrons - tag gi to tissues
Vldl - tag liver to tissues
Ldl - cholesterol liver to tissues
Hdl - cholesterol tissues to liver
What is the association between cholesterol, smoking, htn and chd?
Risk of chd is higher than the sum of the parts when combined
What study showed the relationship between chd and raised cholesterol? In which ethnicities?
Framingham - northern europe and usa
What is the relationship between bmi and cholesterol?
Increases with increasing bmi (even within normal range)
How do statins work?
Inhibit hmg coA reductase
Decreases hepatic cholesterol synthesis
Increases expression of ldl receptors
Hepatic cholesterol returns to normal
But increased ldl receptors mean higher clearence
What are the benefits of statins to someone with a high cholesterol? Someone with a normal cholesterol?
Decrease in cholesterol by 10% reduces cvd risk by 15%
- reduced thrombotic risk
- plaque reduction
- improved endothelial cell function
Side effects of statins
Myopathy (up to rhabdomyolitis)
Muscle pain (myalgia)
What are fibric acid derivatives more commonly known as? Give two examples
How do fibrates work?
Stimulate PPAR increasing trasncription of lipoprotein lipase
Causes reduced ldl, increased hdl (both moderate) and marked reduction in tag (30%)
What is a contraindication for fibrates?
What is the interaction between statins and gemfibrozil?
Both additive effect increasing risk of rhabdomyolisis and gemfibrozil inhibits statin glucuronidation increasing its side effect profile greater than the sum of the parts.
What is nicotinic acid also know as? What is its mechanism of action?
Inhibits lipoprotein synthesis in liver reducing vldl, tag and tc.
What are adverse effects of niacin?
What must niacin be given with? Why?
Aspirin, to reduce itching
What is an example of a cholesterol lipase inhibitor? How do they work?
In brush border of gi tract, limiting absorption of cholesterol
Side effects of ezetimibe
Abdo pain, diarrheoa, flatulance
What dietary control can be applied to hyperlipidemia?
Low fats, cholesterol and alcohol
High fish oil, fibre, vit c and e
What are the current nice statin guidelines?
Primary prevention 20mg atorvastatin if qrisk above 10% in next 10 years
Secondary prevention 80mg atorvastatin (reduce if risk of adrs or ddis)
What are the abnormal values of
In diagnosing diabetes?
Classes of non insulin antidiabetics
Alpha glucosidase inhibitors
Example, pd and adrs/benefits of biguanides
Increases insulin sensitivity increasing peripheral glucose uptake and decreasing gluconeogenesis
Adrs - gi upset, lactic acidosis (therefor not in cardiac or resp failure)
Benefits - limited weight gain, low hypo risk, low cost
Example, pd and adrs of sulphonylureas
Increases insulin release by blocking k channels
Adrs - hypos, weight gain, gi upset, rashes
Benefits - can use in renal failure
Example, pd and adrs of glitazones
Increases insulin sensitivity via PPARs
Adrs - weight gain, bladder cancer, chf, fluid retention
Benefits - low risk of hypo
When would you not use a glitazone?
When would you not use a sulphonurea?
When hypos would be an issue (eg driving)
Example, pd and adrs of GLP1 agonist
Mimics glucogon like peptide 1 released from GI tract - causes increased insulin release and decreased gastric emptying, increased satiety, and decreased glucagon release
Adrs - expensive! Injection site problems, gi upset
Benefits - weight loss, good efficacy
Example, pd and adrs of gliptins
Stop dpp4 breaking down glp1, increases glp1 therefore increased insulin, decreased glucagon, satiety and slowed gi emptying
Adrs - gi upset, gord
Benefits - weight loss
Example, pd and adrs of SGLT2 inhibitors
Increases renal glucose excretion
Adrs - thrush, uti, hypos, polyurea
Benefits - weight loss
Rapid acting insulin
Long acting insulin
Side effects of insulin therapy?
Lipodystrophy at injection site
Allergies to suspension
Insulin regime for someone unable to administer their own insulin example:
Twice daily mix of short and intermediate acting insulin (e.g. Humalog 25 - 75% intermediate lispro protamine and 25% rapid acting lispro)
Insulin regime for someone who can monitor their own bm and administer own insulin
Long acting (e.g. Glargine) overnight then short acting (eg. aspart) at meals
In what ways can antibacterials be classifed? Which is the most useful clinically? Why?
Bacteriocidal vs bacteriostatic
Broad vs narrow spectrum
Target site - most useful as we can predict action on certain bacteria
What must an antibiotic be able to do in order to be effective?
Selectively damage pathogen over body cells
Reach the site of action
What are the three main ways a bacteria can become resistant to an antibiotic?
Production of inactivating enzymes
Altering the target site
Altering concentration (decreased influx or increased efflux)
What are the three mechanisms of horizontal bacterial resistance?
How can an appropriate antibiotic be chosen for an infection?
Disk sensitivity testing
What are issues with disc sensitivity testing?
Abx may not be able to reach site of action
Wrong bacteria cultured
Bacteria may develop resistance during treatment
Wrong dose or route may be used for abx
How are doses calculated for sensitive antibiotics like vancomycin?
Calculate minimum inhibitory concentration using an E-test
What are the two GENERAL pharmacodynamic principles of antibiotics? Examples of each
Time dependant killing - cell wall ABX - achieved with regular dosing or infusion
Dose dependant killing - aminoglyosides and quinolones (e.g. 1 does of ciprofloxacin for gonorrhoea
What are the different classes of anti cell wall antibiotics? (Main and subsidiary). Examples from each
What antibiotic would be appropriate in a case of MRSA?
What is the spectrum action of meropenem? What does it not work on?
G pos and neg
No action against mrsa
What is the spectrum of cephalosporin?
What does it not work on?
G pos and neg
Does not work on anaerobes or mrsa
What side effects are associated with cephalosporin?
Clostridium difficile infection
Which penicillin abx is naturally active against beta lactamase producing bacteria?
Which penicillin is active against gram neg?
How do beta lactam abx work?
How do glycopeptides work differently?
Competitively inhibit penicillin binding protein stopping cell wall synthesis
Bind to the petidoglycan cell wall stopping penicillin binding protein from binding
What is the basic structure of the cell wall of a bacteria?
Peptidoglycan - carbohydrate chains joined by amino acid bridges
What common bacteria would penicillin V not be useful against? What penicillin could be used instead
Staphylococci - many produce beta lactamase
What is responsible for enabling the gram neg actions of amoxicillin?
Able to penetrate cell membranes
What is a good use of cephalosporins?
Penetrate csf thus meningitis
On what bacteria would vancomycin not work?
What are the side effects of vancomycin? Which other group of abx share these effects?
What are the three main classes of abx that inhibit protein synthesis? Why are they specific to bacteria?
As they target prokaryotic ribosomes (30s+50s - 70s)
Which of the 3 classes of abx that effect protein synthesis target the 50s subunit? How do they work?
Inhibit peptidyl transferase responsible form moving the growing aa chain from the p site to the a site.
What are the tetracyclins? Moa, adrs, spectrum.
Bind to 30s subunit inhibing trna binding causing misreading of mrna.
Stained teeth in children, gastric prokinetics thus diarrheoa
Example of an aminoglycoside and spectrum.
Gram -ve with slight gram +ve
What are the side effects of the macrolides?
What classes of drugs effect nucleic acid synthesis?
Sulphonamides + trimethoprim (trimethoprim, sulfadazine)
How do the quinilones work? Example
Ciprofloxacin. Inhibits dna gyrase stopping supercoiling of dna
Effect of sulphonamides and trimethoprim?
Inhibit folate synthesis (by inhibiting enzymes including dihydrofolate reductase)
What are the anti tb antibiotics?
What drugs would you give to a fungal infection? How do they work?
Azoles - inhibit cell membrane synthesis
Nystatin - inhibits cell membrane function
Differentiate antigenic shift and antigenic drift in flu
Shift - 2 different flu viruses in one host swap material producing a novel virus - high risk
Drift - slow mutation of the virus seen in the year to year changes in seasonal flu
Which flu subtypes can have an animal resevoir?
What are the surface proteins of influenza virus? What do they do?
Haemogglutanin - binds to salysiliate receptor on host cell
Neuroaminidase - releases the virus from the cell surface after budding out
How does the virus loose its envelope once in the cell?
Ion influx through m2 ion channel for protons (and activated by protons - low pH)
What drugs block M2 ion channels in flu?
Antiparkinsons drugs thus serious cns side effects (nervousness, anxiety, agitation, insomnia, exacerbation of seizures in epileptics, exaggerations of psychotic symptoms in scizophrenics
Why are m2 ion channel blockers poor antivirals?
Severe cns side effects
Rapidly develop resistance
Give an example of a neuramonidase inhibitor. Side effects?
Vomiting, abdo pain, epistaxis
What are the effects of neuraminidase inhibitors?
Shorten illness duration
Decrease risk of death
What is the recommended treatment window for oseltamivir? Too whom should it be given?
At risk patients with flu like symptoms during a suspected current outbreak of flu
How does acyclovir work?
Inhibits viral dna polymerase
What are the aims of asthma therapy?
Minimal use of reliever
No limit to physical activity
Normal lung function
Aim for early control then step up and down as needed
What are the steps of asthma therapy?
1 - SAB2 agonist
2 - add inhaled steroid 400mcg
3 - add LAB2 agonist, consider increasing steroid to 800mcg
4 - increase steroids up to 2000mcg, add novel drug
5 - oral steroid
Why do we try to limit use of SAB2 in asthma?
Indication of poor control
Overuse causes mast cell degranulation
What are the actions of a intermittently used SAB2 agonist?
Relax airway smooth muscle
Inhibit mast cell degranulation
How does beta 2 stimulation relax smooth muscle?
Increase K+ conductance
Give an example of LAB2 agonist that also acts as a SAB2 agonist
What happens if this is used as a reliever too?
Decreases exacerbation number
Example of a long acting beta 2 agonist that does not have short acting effect?
What is the advantage of giving a LAB2 with a steroid combined? 2 examples please.
Ease of use - increase compliance
Ensures steroid is being given, not just beta agonists
Symbicort - formoterol and budesinide
Seretide - salmeterol and fluticosone
How are inhaled steroids modified to reduce systemic side effects? Why does this work?
Lipophilic side chain
Increases receptor affinity, high local uptake, increased hepatic metabolism
How can steroid inhalers get into systemic systems? How can side effects be reduced? Which steroid is good and bad for this?
Swallowed rather than inhaled
Use a steroid that is highly metabolised on first pass eg. budesonide
Beclamethasone undergoes little first pass
What novel drugs can be given in asthma - brief moa and side effects please
Methylxanthines such as aminophyllin antagonise adenosine and is a phosphodiesterase inhibitor (increases cAMP). Can cause arrhythmia and fits
Leukotrine receptor antagonists such as montelukast block action of leukotrines - not very efficacious - can cause angioedema, anaphylaxis and fever
Where does COX act to convert arachidonic acid into prostaglandins?
What do prostaglandins cause generally?
Where do prostaglands act to cause pain? In what ways?
Peripherally - EP1 receptor - GalphaQ
decreases K channels and increases Na channels causing depolarisation of neurones
Increased sensitivity to bradykinin
Centrally - EP2 receptor - GaplhaS
Increased PKA decreases glycline affinity reducing inhibition of second order neurones
How do prostaglandins cause fever?
IL1 stimulates hypothalamus to produce COX2 stimulating Ep3 receptors GalphaI increasing cellular calcium increasing temperature
Where is COX 1 expressed? What about COX2
1 - wide spread - gastric mucosa, renal parenchyma
2 - in inflammed areas, hypothalamus
Which of cox one and two has the larger active site?
How do nsaids inhibit cox?
What is the Pk of Nsaids?
Heavily protein bound
Two groups - t1/2 under 6 hrs or over 10 hrs
Why do nsaids cause gastric symptoms?
Decreased cox1 - decreased mucus secretion and decreased mucosal blood flow
When is nsaids action on the kidneys particually important?
Side effects of nsaids
Stevens johnson syndrome
Give some positive and negative ddis of nsaids
Positive - with opiate - good relief
Negative - protein displacement - e.g. Warfarin, methotrexate
- nsaid + aspirin - competes for cox 1 site of aspirin decreasing efficacy
What are unique facts about aspirin?
Irreversible inhibition of COX1
T1/2 less than 30 minutes but metabolised to salicylate with t1/2 over 4 hours (though this binds reversibly!)
Zero order at higher dose
What is the classification of paracetamol?
Non-Opiate Analgesic Drug
How is. Paracetamol thought to work?
Weak cox 1-3 inhibitor
What are the layers of the adrenal cortex? What do they excrete?
Glomerulosa - minralocorticoids
Fasciculata - glucocorticoids
Reticularis - sex steriods
What does cortisol feed back on?
Negativly on hypothalams (reducing CRH) and pituitary (ACTH)
Metabolic actions of glucocorticoids?
Raises blood glucose - stimulates glygogenolysis and gluconeogeneis
Lipolysis at low concentrations
Lipid deposition at high concentrations
Why might corticosteroids cause hypertension?
Increased sensitivity of blood vessels to vasoconstrictors
Mineralocorticoid effect on kidney increases salt and water reabsorption
Side effects of glutocorticosteroids
Fat redistribution (moon face, buffalo hump, central obesity)
Proteinolysis (striae/thin skin)
Signs of aldosterone deficiency?
Signs of aldosterone excess?
Describe the process of crossover with respect to steroids
Most steroid drugs have both glucocorticoid and mineralocorticoid effects
Which drugs have equal glucocorticoid and mineralocorticoid effects?
Which drugs have very stronger glucocorticoid effects than mineralocorticoid effects? Which ones? much more so
Which steroid is mainly mineralocorticoid
What do you need to consider about a steroid dose before administrating?
Duration of action
Describe the absorption of steroids orally
Highly lipophyllic so well absorbed with high bioavailability
Where are steroids metabolised?
Liver and kidney
Examples of steroid routes of administration
Iv - hydrocortisone
Oral - prendisolone
Inhaled - budesinide
Topical - beclamethasone
How do steroids reduce inflammation?
Inhibition of t and b cell responses
Inhibit nf kappa b - signalling molecule for inflammation
Reduced cytokine transcription
Reduced expression of cell adhesion molecules
Reduced phagocytic function
What is the molecular moa of steroids?
What is a variation on this?
Diffuses in to cell as lipid soluble
Bind to receptor in cytoplasm (often causing it to dissociate from a heat shock protein)
Enters nucleus and binds to point on dna - hormone response element
Activates or inhibits protein transcription
Can bind to receptors within the nucleus as opposed to cytoplasm
What is activation of transcription called by steroids?
What about inactivation?
What do steroids transactivate?
Annexin one - decreases arachodronic acid synthesis
What do steroids cis-repress?
POMC (reducing ACTH production)
Keratin (hence thin skin)
As well as transactivation and cisrepression what do steroids do?
Binding to proteins causing decreased cytokines, chemokines, adhesion molecules and inflammatory enzymes, receptors etc.
Some surface receptor action - this would create a rapid respone
Examples of when to use steroid use
To Suppress Immunity To An Extent
Diagnosis - Dexamethasone Suppression Test
Why do steroids cause osteoporosis?
Reduce calcium absorption
Reduce sex steroid production
How long will it take to suppress the hpa axis with steroids?
What can occur in hypoadrenal crisis?
Other than steroids name two other immunosuppressants (classes and drugs)
Calcineurin inhibitors (ciclosporin, tacrolimus)
How does azathioprine work?
Metabolised to 6mecaptopurine
Decreases dna and rna synthesis
What makes azathioprine unpredictable?
What are the side effects?
Broken down at different rates in different people
Bone marrow supression
Which class of immunosuppressants is dependant on cyp for metabolism?
How do calcinurin inhibitors work?
Bind to eponimous bonding proteins (e.g. Ciclosporin binding proteins)
Inhibiting production of IL2 in t cells needed for costimulation
What are side effects of calcineurin inhibitors?
D and v
What is the odd sounding immunosuppressant? How does it work?
Inhibits guanosine synthesis in b cells only
How does methotrexate work as a dmard
Inhibits purine metabolism increasing adenosine that has a regulatory effect on immune cells.
Side effects of methotrexate
Pnemonitis / intersitial lung disease
What dmard would be used in pregnancy?
Why is methotrexate used only weekly?
Metabolised to polygluyamates with long half life
What does sulphasalazine consist of? What does each component do?
Sulfapyridine - enters body for RA
Salacilate - remains GI for IBD
Overall inhibits t cell proliferation and neutrophil degranulation and chemotaxis
What do you need to be careful of with anti tnf agents?
Reactivation of latent tb
Increased risk of malignancy if there has been prior malignancy
How do anti tnf agents modify disease?
Decreased joint destruction
What are the endogenous opioids?
What are the three sorts of opiod receptors? What are they? Where are they found?
M - supraspinal
K - spinal cord
D - widely distributed
What happens when an opioid receptor is triggered?
M - k efflux therefore hyperpolarisation therefore decreased Ca
K - decreased Ca influx
D - decreased Ca release
All decrease Ca so there is less synaptotagmin activation so less neurotransmitter release
What opiate adrs are associated with the different receptors? What are general ones?
M - nausea, vomiting, resp depression, constipation, drowsiness, hypotension
K - dysphoria
General - allergy, dependance, tolerance
Example of a partial opiate agonist?
T1/2 of morphine?
Why is heroin so active in the brain?
Twin acyl groups so very lipid soluble so crosses bbb prior to metabolism to morphine
What drugs do opiates interact with
Why does morphine cause resp depression?
M receptor mediated decreased co2 sensitivity
How does warfarin work?
Inhibits vit K reductase necessary for the convesion of glu to gla domains on clotting factors 2, 7, 9 and 10
What drugs interact with warfarin indifferent ways?
Cephalosporins kill gut bacteria so low vit K potentiating effects
Cyp inducers and inhibitors influence metabolism
Protein percipitant drugs e.g. Aspirin displace warfarin
Comment on the onset and offset of warfarin. What can be done to mitigate both.
Onset is slow as it takes time to replace fully functional clotting factors with altered ones - give heparin cover until inr acceptable
Offset also takes several days for the reverse reason. Can reverse with - vit K or fresh frozen plasma (if life threatening bleed)
What is INR?
A standardised prothrombin time for the kit used
What is prothrombin time?
Measures extrinsic pathway of coagulation
Blood + citrate
Overwhelm citrate with calcium and add tf
Measure time until clot forms
What are risks of warfarin in pregnancy?
First trimester teratogenic
Risks child cerebral haemorrhage on delivery and bleeding from mother
What inr would you aim for if you had a pe, dvt or af?
What inr would you aim for if you have a prosthetic valve or dvt/pe/af were still problematic at 2-3?
How does unfractionated heparin work?
What is different about LMWH?
Binds to antithrombin III increasing its affinity for factors II and X
LMWH is small so cant span II so only binds X
What are some novel anticoagulants? How do they work?
Fondaparinux - selective factor ten a inhibitor
Dabigitran - direct thrombin inhibitor
Adverse effects of heparin?
What causes thrombocytopenia in heparin use?
Autoimmune response within a couple of weeks directed against platelets
What monitoring is needed in LMWH and UFH?
LMWH - none!
UFH - APTT (activated partial thromboplastin time)
What is APTT
Activated partial thromboplastin time
Overwhelm citrate with calcium, add activator (not TF
How does aspirin work as an anti-platelet
Inhibits cox 1 irreversibly
Decreasing g alpha q stimulation and thus decreasing calcium release via. iP3
How does clopidogrel act as an antiplatelet?
Blocks adp receptor stopping g alpha i stimulation inhibiting cAMP mediated suppression of calcium release (reducing the reduction of a reducer!)
What is an example of a GP IIb/IIIa inhibitor?
What are the different sorts of medications required in anaesthesia?
Premedication - anxiolytic - mirtazapine
Induction agent - IV anaesthetic - ketamine
Maintenance agent - volatile gas - sevoflurine
Paralytic - neuromuscular blocker - rocuronium
Pain relief - opiate - morphine
Antiemetic - dopamine antagonist - metaclopramide
Regional anaesthesia - sodium channel blocker - lidocain
What is the term for general anaesthesia without the use of inhaled anaesthetics?
Total intravenous anaesthetic (TIVA)
When might you use a volatile gas anaesthetic over a intravenous anaesthetic?
What is the most common action of anaesthetic agents?
Bind to GABAa receptors potentiating GABA increasing its potency and its efficacy
Have the same effects at glycine channels in the spinal cord
What are the unusual anaesthetics?
What do they do differently?
Ketamine, Xe, N2O
Bind allosterically to NMDA receptors antagonising glutamate. As allosteric reduces efficacy but not potency
Where do anaesthetics act?
To what ends?
Reticular formation - decreases arousal
Hippocampus - decreased memory
Dorsal horn - decreased pain and decreased reflexes
Brainstem - depressed respiration and cvs function
What does a low blood:gas partition mean for an inhaled anaesthetic?
Faster induction and recovery
What does a high oil:gas partition mean for an inhaled anaesthetic?
High potency but also retention so slow recovery
What is MAC
Minimal alveolar concentration - the minimum concentration of anaesthetic in the alveoli that induces a state in which 50% fail to move to surgical stimuli
What increases MAC (making it harder to anaesthetise
What decreases MAC increasing response to ananesthetic
Other depressants - anaesthetics, opiates, N2O
What is a disadvantage of TIVA?
Less easily reversed due to high protein binding
How do iv anaesthetics distribute?
Initially to target tissue then into fat
When does high blood gas coefficient lead to slower induction?
Indicates higher protein bound state
How is the effect of anaesthesia graded?
Stage 1 - slight decreased eye movement
Stage 2 - increased excitability and tone, erratic breathing
Stage 3 - increasing levels of relaxation, breathing decreases
Stage 4 - flaccid, apnoic, paralysed
What are the 5 aims of anaesthesia?
What is the depolarising neuromuscular blocker? How does it work? What may need to be given alongside it?
Activates prolonged depolarisation that desensitises receptors
Differentiate local and regional anaesthesia
Regional is larger area e.g. Epidural, spinal, femoral
What is directly proportional to potency, speed and duration of local anaesthetics
Potency - lipid solubility
Speed - lower pKa
Duration - degree of protein binding
What is the order of effect of local anaesthetics?
Name 5 classes of diuretics with examples of each
Carbonic anhydrase inhibitors - acetazolamide
Osmotic diuretic - mannitol
Loop diuretic - frusemide
Thiazide diuretic - bendroflumethiazide
Potassium sparing diuretic - spironolactone
MOA of carbonic anhydrase inhibitors
Inhibit luminal CA decreasing CO2 available for reabsorption and increasing luminal HCO3
Due to lower CO2 in cells decreased H+ thus decreased activity of Na/H antiporter thus decreased Na+ reabsorption
Higher HCO3 and H in lumen so increased water.
Problems with carbonic anhydrase inhibitors
Hypokalaemia - increased Na to DCT therefore increased Na/K antiporters and increased DCT flow washes away K+ increasing gradient
What is the characteristic of an osmotic diuretic? When are they used?
Filtered but not reabsorbed
Maintain urine out put during surgery, cerebral oedema
How do loop diuretics work?
Inhibit NKCC2 channels in ascending loop of henle.
Side effects of loop diuretics - why?
Hypokalaemia - high Na in DCT = increased Na/K antiporter, increased flow past DCT carries away K increasing gradient
Hypocalcemia/magnesia = loss of luminal positive potential from re-secretion of absorbed K through ROMK thus less drive for other cation absorption
Ototoxicity = high dose alters endolymph composition
Mechanism of thiazides
Inhibits Na/Cl synporter in DCT
Side effects of thiazides
Gout (thiazide excreted by same channel as uric acid thus competes)
Blocks aldosterone from binding to receptor thus:
Decreased basal Na/K ATPase
Decreased apical ROMK
Decreased apical ENaC
Thus decreased Na absorption and K secretion
Side effects of spironolactone
Uses of carbonic anhydrase inhibitors
Diuretics to use in CHF
Diuretic to use in liver disease
Why would you not use acetazolamide in liver failure?
Excretion of NH3 requires proteination in the kidney tubule
Why is spironolactone beneficial in liver failure?
Avoids hypokalaemia which stimulates ammonia production
Which diuretics are used as antihypertensives?
Spironolactone off label
What is conns syndrome?
An aldosterone producing adenoma
Causes sodium and water retention with concurrent htn.
Treat with spironolactome
Other than spironolactone name another. K sparing diuretic
What should be considered when prescribing in renal failure?
Renal function levels
Reduce renal excreted drugs in line with gfr
Stop nephrotoxic drugs
Give some examples of nephrotoxic drugs
When and why are ace inhibitors 'nephrotoxic'
Bilateral renal artery stenosis
Needs efferent arteriole vasoconstriction to maintaing gfr
Ace inhibitors stop vasoconstriction
What is the prevalence of htn?
What is the benefit of lowering bp by 10mmHg?
Reduces stroke risk by 60% and CHD by 40
What percentage of Htn is secondary? What are causes? What is the commonest?
Renal disease (80%)
Coarctation of aorta
Lifestyle tx of htn?
Decrease weight to normal
Decrease salt intake
Fruit and veg
Smoking cessation to reduce cvd risk factors
What are the cut off values for htn?
Norm - 180/110
What is the initial therapy for HTN?
Second line? Third? Fourth?
White under 55 - ACEi
Black or over 55 - CC blocker/thiazide
Second line is ACEi and one other
Third line is all three
Fourth line is all three and beta blocker and referral to specialist
Side effects of an acei?
Renal failure with bilat renal artery stenosis
What might you use if a pt on ace i complains of dry cough?
Angiotensin receptor blocker eg. Losartan
Example of an alpha 1 blocker
Blocks alpha 1 thus vasodilates
Postural hypotension, dizzyneas, headache
What are the two groups of calcium channel blockers?
Non dihydropyridines (verampamil, diltazem)
Side effects of the dihydropyradines and why
Oedema (no venodilation)
Sweating (increased sympathetics)
Tachycardia (reflex from lower bp)
Side effects of verapamil/diltazem
What study shows the efficacy of the main groups of antihypertensives - what did it conclude about them?
All three classes showed a 8% reduction in event rate at 5 years with the same bp reduction
What medications alter the prognosis of heart failure?
Which trials show the efficacy of spironolactone in chf?
What medications only show symptom relief in heart failure without effecting prognosis?
What is the disadvantage of beta blockade in CHF?
How is this mitigated?
How is it thought beta blockers change long term outcomes?
Decreased rate and contractility worsting CO
Start at low dose
Over time CO returns to normal but PVR is lowered due to reduced renin secretion by sypathetic stimulation
What are mechanisms of SVT generation?
Accelerated automaticity of SA node
Reentry circuit (AVNRT)
Accessory pathway (AVRT)
Ectopic activity (AF/flutter)
Why do people get AF?
Usually secondary to something
What is the term for a AVRT that passes through the AV node, through the ventricles then up the accessory pathway
What is the term for a AVRT that passes through the accessory pathway, through the ventricles then through the AV node in reverse?
Antidromic (will have broad QRS)
Short term measures to control SVT
Cardiovert if unstable
Vasalva / carotid sinus massage
Beta blocker, verapamil or diltiazem
Long term measures to control SVT
How is AF managed if onset has been within 48 hrs?
What is done to control AF rhythm if onset more than 48 hrs ago?
Warfarinise for 6 weeks
What can be used for rate control in AF?
Calcium channel blockers
What drug shouldn't be given alone for atrial flutter? Why?
Will slow atrial rate allowing one to one conduction to the ventricles paradoxically increasing ventricular rate
How should VT be treated graded on severity?
Arrest - ALS
Unstable - DC cardioversion
Stable - amiodarone/lidocain then DC cardiovert if necessary
How should non sustained VT episodes be treated chronically?
Beta blockers, or, if very symptomatic amiodarone/flecainide
What are causes of VT?
LQTS (congenital, acquired)
Examples of each subclass of Na channel blockers and brief MOA
1a. = Disopyamide - binds to open NaC, dissociates slowly so lengthens AP
1b. = lidocain - binds to inactive NaC, dissociates rapidly shortening AP. Use dependant block reducing afterdepolerisations
1c. = flecainide - dissociates very slowly, no effect on AP length
General action of na channel blockers
Blocking voltage gaited na channels decreasing slope of phase 0 of AP. Decreases rate of AP conduction through the heart.
When should Na channel blcokers never be used? Which trial showed this?
Structural heart disease
Side effects of class 1abc na channel blockers
1a - long qt , hypotension
1b - dizzyness, drowsyness
1c - increased ventricular response to atrial flutter
Side effects of beta blockers
How do beta blockers influence cardiac function?
At sa node reduce GalphaS thus decrease cAMP thus decrease HCN and rate
On myocytes decreases PKA reducing calcium channel phosphorylation and activation
What are the class three antiarrhythmics?
Eg amiodarone and solatol
K channel blockers but useful drugs also other functions as though theoretically k channel blocking is beneficial by prolonging AP it actually is proarrhythmic
Amiodarone side effects
Fucks with thyroid
How do the non-dihydrophyramidine ccbs effect heart rate?
Blocks inward calcium flow in the sa and av node slowing initiation and conduction,
Negative chronotrophy and ionotrophy
When would you not give verapamil or diltaziem?
Heart failure - they are negative ionotrophs
Half life of amiodarone
How does adenosine work?
Binds to A1 receptors in av and sa nodes activating K conductance hyperpolarising the cell causing massive slowing in conductance
However, t1/2 very short so wears off quickly
Side effects of adenosine
Sense of doom
What are the two main mechanisms of arrhythmia generation? What are the sub sets of each?
Impulse generation (afterpotentials, ectopic focus, enhanced automaticity)
What are the four classes of chemotherapy?
Antimetabolites - methotrexate
Intercalating agents - doxyrubacin, bleomycin (kind of)
Alkylating agents - cisplatin
Spindle poisons - taxanes, vinca alkaloids
Anticancer actions of methotrexate
Inhibits dhfr stopping production of tetrahydrofolate which is oxidised back to dihydrolate by thymidylate synthase. This oxidation drives DUMP to DTMP the precursor of thymine.
How does cisplatin work in cancer?
Bound to cl- in plasma due to high plasma cl-
Enters cell loosing cl- as low concentration
Now positive it can bind to negative groups on DNA. It has two binding sites so binds two regions interstrand or intrastrand interfering with dna synthesis and rna transcription
How does doxyrubacin work in chemo?
Intercalates between base pairs interfering with replication and trascription
Creates a complex with dna and topoisomerase inhibiting dna breaking and religation triggering apoptosis
Produces free radicals damaging DNA
How does bleomycin act in chemo?
Creates superoxides damaging dna activiating a dna cleaving enzyme
How do the taxanes work in chemo?
Inhibit microtubule degridation by stabilising beta tubulin
Thus cant dissasemble to pull microtubules apart
Cell sticks in metaphase
How do vinca alkaloids work in chemo?
Inhibits microtubule formation by binding to beta tubulin subunit so cells cant divide
In what phases do the different chemo drugs act?
Antimetabolites - S
Alkylating - G1 and S
Intercalating - All
Spindle poisons - M
What are the different compartments of a tumour defined by cell replication? Which is most amenable to chemo?
A - labile
B - stable
C - permanent
A as chemo doesnt tend to work on G0
What is the hypothesis for repeated dosing of chemo?
Fractional kill hypothesis
Repeatedly killing a set fraction of cancer cells until negligible left
What cancers are sensitive to chemo? What arent?
Lymphoma - germ cell are
Prostate and brain arnt
Indications for chemo?
What predicts a bad outcome for chemo?
No molecular target markers
What is the disadvantage of oral chemo?
Taken at home and people think because it is oral it is milder.
People less likely to report serious side effects of chemo as they don't want it to be stopped
General chemo side effects
Bone marrow suppression
Nausea and vomiting
Specific side effect of bleomycin
What can cause variability in chemo pharmokinetics?
A - d/v, compliance
D - ascities, hypoalbuminia
M - liver dysfunction
E - renal dysfunction
DDIs of chemo?
NSAIDs with methotrexate
Enzyme inducers / inhibitors
What are the problems with most antiepileptics and pregnancy?
4 times the risk of OCP failure and teratogenicity (2-8%)
What teratogenic consequences are there to antiepileptics? How can they be mediated?
Neural tube defects
Give folate and vit K supplement
Which antiepileptics act on VGNaC?
How do VGNaC blockers produce a use dependant block?
Bind to inactivation gate and must be depolarised to bind thus voltage dependant
When can carbamezapine be used? When cant it be used?
Complex partial seizures ++
Generalised tonic clonic seizures +
NOT absence seizures
General antiepileptic ADRs
Ataxia, dizzyness, drowsiness, nausea, vomiting
Which antiepileptic can cause stevens johnson syndrome in 2-5%?
Which antiepileptic can disturb BP?
Specific side effect of valpourate?
Specific side effects of phenytoin?
What is special about carbamezapine pharmacokinetics?
Induces own cyp metabolism reducing own t1/2
Are antiepileptics heavily or lightly protein bound? Consequence of this?
What is special about phenytoin pharmacokinetics
Which antiepileptic needs liver monitoring?
Which antiepileptic needs plasma level monitoring? How else can conc. be measured?
By saliva conc
Which antiepileptic can be used in pregnancy? What is the risk of teratogenesis?
Which antiepileptic does not effect cyp? Does it still interact with ocP
Yep - ocp decreases lamotrigine concentration
How does valpourate work?
Inhibits gaba degridation and increases gaba synthesis
Also some action as a VGNaC blocker
What antiepileptics have ddis with aspirin and antidepressants?
What is the antidote to benzo od?
Adrs of benzos?
Resp and cvs depression
Withdrawal and dependance
Clinical features of parkinsons disease?
Pill rolling RESTING tremor
Lead pipe rigidity
Mood changes / cognitive changes
Differentials of parkinsons? What distinguishes them?
Multiple system atrophy - autonomic features
Drug induced parkinsonism (on antipsychotics or metoclopramide)
Progressive supranuclear palsy (opthalmoparesis)
Essential tremor (isolated tremor)
How is parkinsons diagnosed?
Positive response to treatment
DAT scan (tracer absorbed by dopaminergic neurones thus rduced in Parkinson's - can be used to differentiate from essential tremor)
How is adrenaline made?
- tyrosine hydroxilase
- dopa decarboxilase
- dopamine hydroxilase
What breaks down dopamine?
Treatment options for parkinsons?
Levodopa (with carbidopa)
Dopamine receptor agonists
When is ldopa most effective? Why? What class of drug can be used when it isnt useful?
Early disease when there are still dopaminergic neurones
Use a dopamine receptor agonist
Side effects of Ldopa?
On off movements
Pk of LDOPA
How do we alter it
90% inactivated in intestine
9% converted peripherally
1% in the CNS
Alter with carbidopa to stop peripheral conversion allowing smaller dose with less ADRs
What drugs interact with LDOPA
MOIs - HTN crisis
What should you bare in mind when prescribing a COMT inhibitor in parkinsons?
Should not be given alone - needs something to work on!
Example of a COMT inhibitor
MOA for entacapone
Stops peripheral breakdown of LDOPA increasing amount and also reducing competition for transport into cns against its metabolite
Thus prolongs motor response to LDOPA
Example of a MOAI
What does it do?
How should it be used?
Denovo or in combo
Example of a dopamine receptor agonist? When are they used?
End stage when there are very few dopaminergic neurones for LDOPA to act on
Side effect of Apomorphine
Compulsive behaviour (gambling, shopping, hypersexuality)
Advantage of apomorphine over levodopa
Less motor side effects
Why give anticholinergics to parkinsons?
Ach antagonises dopamine thus reduce ACh
Drug induced disease
What do anticholinergics not help with in parkinsons?
Adrs of anticholinergics
What is the pathology of myasthenia gravis?
Autoimmune igg binding to ACh receptor binding site competitivly antagonising acetylcholine
Ach remains in cleft so is broken down by acetylcholinesterase
Symptoms of myasthenia gravis
Fatiguable weakness esp of extraoccular and bulbar muscles
Symetric limb weakness
What exacerbates myasthenia gravis?
Beta blockers, ccbs, aceis
What complications can occur with myasthenia gravis? What participates each?
Overtreatment - cholinergic crisis
Undertreatment - myasthenic crisis
Symptoms of a cholinergic crisis
Treatment of myasthenia gravis
Acetylcholinesterase inhbitors (neostigmine)
Signs of depression?
2 of the following that are persistant (>2 week)
Also poor sleep, hoplessness, self harm, low libido, low appetite
Theories of depression causation
Decreased monoamine transmitters (NA and 5HT)
Abnormality of monoamine receptor
Deficiency in molecular functioning distal to receptor
ADRs of SSRIs
Extrapyramidal side effects
Serotonin sydrome in od
MOA of tricyclics
Inhibit NA reuptake
Inhibit 5HT reuptake
Alpha 1 blocker
ADRs of tricyclics
Poor eye accomodation
Other than ssri and tca, what other class of antidepressant are used? Example?
Serotonin Noradrenaline Reuptake Inhibitor
MOA of SNRI
Low dose increases serotonin
High dose increases NA
Additional side effects of SNRI over SSRI
What drugs work well in bipolar?
Why no antidepressants in bipolar?
Dont effect the depression
Symptoms of mania
Delusions of grandure
How does lithium work?
? Competes with ca/mg channels
? Increases 5HT
? Attenuates second messengers of neurotransmitter
ADRs of lithium
What monitoring does lithium require?
3 monthly levels and thyroid every 6 months
Examples of positive schizophrenia symptoms
Disturbance in thinking
Lack of insight
Causes of schizophrenia?
Biological Genetic Upbringing
Thought to be due to excess dopamine with possible 5HT involvement
What is the target pathway for dopamine antagonists in schizophrenia? What effects does this have? What other pathways are effected? Side effects?
Mesolimbic - therapeutic reduction in positive symptoms
Mesocortical - increases negative symptoms
Nigrostriatal - extrapyramidal side effects
Tuberoinfundibular - hyperprolactiemia
What are extrapyramidal effects?
Acute dystonic reactions (muscle spasms of the neck, jaw, back, eyes, tongue)
Examples of typical antipsychotics
MOA of typical antipsychotics
Alpha adrenoceptor blockers
Advantages and disadvantages of typical antipsychotics?
Ad - known course and side effects
Di - more sedating
Side effects of antipsychotics
Neuroleptic malignant syndrome
Extrapyramidal side effects
Name 2 atypical antipsychotics
Which antipsychotic is most efficacious? Why isnt it used more?
Bad side effects
What factors stimulate vomiting?
Irritation of stomach
Chemoreptor trigger zone
What is released by the stomach on irritation and thus is a drug target for vomiting? What does it stimulate? Where else is this found?
5HT stimulating CNX
Chemoreceptor trigger zone
What does the vestibular apparatus release in response to noxious stimuli?
Where do all stimulants for vomiting come together?
The medullary vomiting centre
What are the different classes of antiemetic?
MOA of domperidone?
Decreases CTZ activation (dopamine antagonist)
Activates gastric emptying (ACh agonist)
Decreases CTZ triggering (D2 antagonist)
Increases gastric emptying (increases ACh)
Decrease stimulation from irritation (5HT atagonist)
Which of domperidone and metoclopramide produces worse extrapyramidal effects? Why?
Metoclopramide, crosses BBB
What other side effects are assocaited with dopamine receptor antagonists used in nausea other than extrapyramidal?
Example of a 5HT antagonist used in nausea and vomiting
How does it work?
Lowers stimulation of CTZ and stimulation of vagus by irritated stomach
Adrs of ondansterone
Example of ach antagonist in nausea and vomiting
How does it work
Blocks ach from vestibular apparatus
What is hyoscine particually useful in?
Adrs of hyoscine
What h1 antagonist is useful in nausea and vomiting? How does it work?
Crosses bbb and decreases histamine from vestibular apparatus
Side effect of cyclizine
Types of laxatives and examples?
Bulk forming - isphaghula husk
Faecal softners - arachis oil
Osmotically active - macrogel and lactulose
Irritant - senna
Wich laxatives are best for soft faeces constipation
Stimulants like senna
Which laxatives are best for impacted faeces?
Osmotic and bulk forming
Lactulose, macrogels and ispaghula husk
Major complication of laxatives - how does it happen?
Hypokalaemia causes decreased bowel inertia and constipation
Laxative decreases amount of absorbed from bowel (+ feedback) also decreases Na absorption so kidneys raise Na reabsorption increasing renal K loss
Worse hypokalaemia and thus back to the top
What is an important consideration when giving a laxative regarding dehydration? Which laxative avoids this problem?
Must be given with fluid
Macrogels - powder so must be dissolved mandating fluid intake
What laxatives have an immidiate (or rapid) onset?
Magnesium enema (osmotic) - within an hour
Senna (Irritant) - 8 to 10 hours
What laxatives are useful in patients with perianal disease?
Faecal softners like arachis oil
What laxative is used in liver failure? Why?
Metabolised by bacteria to acetic and lactic acid acidifying the colon increasing NH4 excretion
How do ispaghula husks work?
Resistant to digestion
Pull h2o into bowel
Distends bowel triggering contraction and movement
Contraindications to bulk forming laxatives
Adhesions and ulceration - cause obstruction!
What happens if you keep using senna?
Colonic atony resulting in constipation
What is a good laxitive to use with IBS
Absorbs water so is a good laxative if constipated and absorbs water from diarrhoea improving faeces composition
Types of anti diarrheoal
What are antimotility antidiarrhoeal?
Opiates / loperamide
Decreases bowel motility so increases fluid reabsorption
What is a risk of antimotility antidiarrhoeals in IBD
What specific diseases treatments can aid in diarrhoea
Bile acid suppressants in chrones
What would antidiarrhoeals worsten?