CPT Flashcards
Def: pharmacokinetics
Study of factors which determine the amount of drugs at their sites of biological effect at various times.
Includes
ADME
Absorption
Distribution
Metabolism
Excretion
Def: Pharmacodynamics
What the drug does to the body
Def: clearance
Volume of plasma cleared of a drug per unit time
Def: half-life
Time taken for drug concentration to decline to half its original valu
Depends on volume of distribution and clearance
Def: volume of distribution
Volume into which a drug appears to distribute
Theoretical volume that would be necessary to contain the total amount of a drug administered at the same concentration that it is observed in the blood plasma.
High for lipid-soluble drugs
Low for water-soluble drugs
What factors can increase the volume of distribution?
Higher Vd indicates a greater amount of tissue distribution.
High lipid solubility (non-polar drugs), low rates of ionisation or low plasma binding capabilities have higher volumes of ditribution than drugs which are more polar, more highly ionised or exhibit high plasma binding.
Vd may be increased by renal failure (due to fluid retention) and liver failure (due to altered body fluid)
Vd=
Total amount of drug in body/drug blood plasma concentration
What is first order kinetics?
Clearance of durg is always proportional to plasma concentration
Most drugs are in this category
What is zero order kinetics?
Clearance of drug is not always proportional to plasma concentration
Saturation of metabolism-> constant rate of elimination regardless of plasma levels
Give some examples of drugs with zero order kinetics
Phenytoin
Salicylates
Ethanol
What is bioavailability?
Percentage of the dose of a drug which reaches the systemic circulation
100% for IV administration
How long is ~ required for a drug to reach a steady state?
Around 5 half lifes
What does a loading dose do?
Reduces the time needed to reach a steady state, useful if long or short half life
What are some drugs that use loading doses?
Phenytoin
Digoxin
Amiodarone
Theophylline
What are the indications for therapeutic drug monitoring?
Ix lack of drug efficacy (possibility of poor compliance)
Suspected toxicity
Prevention of toxicity
What are three drugs that must have therapeutic drug monitoring?
Aminoglycosides
Vancomycin
Li
What are some dugs that have therapeutic monitoring?
Phenytoin
Carbamazepine
Digoxin
Ciclosporin
Does Warfarin undergo therapeutic drug monitoring?
Not monitored per se, it is the biological effect that is monitored rather than the plasma drug level
What is first pass metabolism?
Metabolism and inactivation of a drug before it reaches the systemic circulation
i.e. pre-systemic elimination
Occurs in gut wall and liver
Gives some examples of drugs that undergo FPM
Propranolol
Verapamil
Morphine
Nitrates
What are the pathways of drug metabolism and elimination?
Excreted unchanged by the kidney e.g. frusemide
Phase 1 metabolism and then renal excretion
Phase 2 metabolism and then renal excretion
What is phase 1 metabolism
Creation of reactive, polar functional groups.
Oxidation: usually by cytochrome P450 system
Reduction and hydrolysis
What is phase 2 metabolism?
Production of polar compounds for renal elimination
Either the drug or its phase 1 metabolite
Conjugation reactions: glucuronidation, sulfonation, acetylation, methylation
What is the principle method of elimination?
Renal, depends on GFR
How many subtypes of CyP450 are there?
>11
What is the most important CyP?
What proportion of drugs does it metabolise?
CyP3A4
>30% e.g. CCBs, beta blockers, statins, benzos
What is the second most important CyP?
What proportion of drugs does it metabolise?
CyP2D6
>20% e.g. antidepressants, some beta blockers, opiates
Prodrugs: –>
L-DOPA
Dopamine
Prodrugs: –>
Enalpril
Enalprilat
Prodrugs: –>
Ezetimibe
Ez-glucuorinde
Prodrugs: –>
Methyldopa
alpha-methylnorepinephrine
Prodrugs: –>
Azathioprine
6-mercaptopurine (by xanthine oxidase)
Prodrugs: –>
Carbimazole
Methimazole
Prodrugs: –>
Cyclophosphamide
4-hydroxycyclophosphamide
What are pharmacogenomics?
Genetically determined variation in drug response
What is the significance of acetylation in terms of pharmacogenomics?
Fast vs slow acetylators e.g. fast in Japan vs Europe
Variations in acetylation affects which drugs?
Isoniazid
Hydralazine
Dapsone
Which CyP doesn’t have polymorphisms?
CyP3A4
What is the signifcance of G6PDD?
Oxidative stress-> haemolysis
What are some drugs that can precipitate haemolysis in G6PDD?
Quinolones, primaquine, nitrofurantoin, dapsone
How can ADRs be classified?
Type A
Type B
Long term ADR
Delayed ADR
Features of Type A ADR
Common, predictable reactions
Dose-related but may occur at therapeutic doses
Consequences of known pharmacology of the drug
Features of Type B ADR
Rare, idiosyncratic reactions
Usually not dose related
E.g. allergies and pharmacogenetic variations
Features of LT ADR
Dependence, addiction
Withdrawal phenomena
Adaptive changes e.g. tardive dyskinesia
Features of delayed ADR?
Carcinogenesis
Teratogenesis
What are the drug determinants of ADR?
Pharmacodynamics
Pharmacokinetics
Dose
Formulation
Route of administration
Rate of administration
What are the patient specific determinants of ADR
Age
Co-morbidities
Renal- digoxin, aminoglycosides
Hepatic: warfarin, opiates
Organ dysfunction
Genetic predisposition
Examples of drug that can cause T1HS?
Penicllins, contrast media
Anaphylaxis
Examples of drugs that can cause T2HS?
e.g. causing haemolysis
Penicillins, cephalosporins, oral hypoglycaemics
Methyldopa
Examples of drugs that can cuase T3HS reactions
Immune-complex
Serum sickness-like reaction
Penicillins, sulphonamides
Examples of drugs that can cause T4HS
Cell-mediated
Topical Abx, antihistamine cream
What are pseudoallergies?
Pharmacological ADRs not immune
NSAID pseudoallergy
Bronchospasm
Shift metabolism from prostaglandins-> leukotrienes-> bronchoconstriction
May occur in non-asthmatic populations but commoner if asthmatic
ACEI pseudoallergy
Cough and angioedema (anaphylactoid)
ACEI inhibit bradykinin metabolism
Drugs associated with withdrawal
Opiates
Benzos
Corticosteroids
Def: rebound
Worse on withdrawing the drug than before starting
Drugs in which rebound ADR may be seen?
Clonidine
Beta-blockers
Corticosteroids
Adaptive LT ADR?
Neuroleptics-> tardive dyskinesia
Delayed ADRs
Oestrogens
Endometrial Ca
Breast Ca
Delayed ADRs
cytotoxics
Leukaemia
Drugs causing immune urticaria
Penicllins
Cephalosporins
Drugs causing non-immune urticaria?
Contrast
Opiates
NSAIDs
Drugs causing erythema multiforme?
SNAPP
Sulfonamides
NSAIDs
Allopurinol
Phenytoin
Penicllin
Drugs causing erythema nodosum
Sulponhamides
OCP
Drugs causing photosensitivity?
Amiodarone
Thiazides
Sulfonylureas
Drugs causing fixed eruptions
Erythromycin
Sulphonamides
Drugs causing lupus like reactions
Hydralazine
Isoniazid
Penicillamine
Drugs causing cholestatic hepatotoxicity
Clavulanic acid (may be delayed)
Fluclox: may be delayed
Erythromycin
Sulfonylureas (glibenclamide)
OCP
Tricyclics
Chlorpromazine, prochlorperazine
Drugs causing hepatocellular damage
Paracetamol
VPA, phenytoin, CBZ
Rifampicin, Isoniazid, Pyrazinamide
Halothane
Methotrexate
Statins
Drugs causing chronic hepatitis
Isoniazid
Methyldopa
Methotrexate
Drugs causing gallstones
OCP
Drugs causing pancytopenia/aplastic anaemia
Cytotoxics
Phenytoin
Chloramphenicol
Penicillamine
Phenothiazines
Methyldopa
Drugs causing neutropenia
Carbamezapine
Carbimazole
Clozapine
Sulfasalazine
Drugs causing thrombocytopenia
Valproate
Salicylates
Chloroquine
Drugs causing peripheral neuropathy
Isoniazid
Vincristine
Amiodarone
Nitrofurantoin
Penicilliamine
Drugs causing pulmonary fibrosis
Bleomycin
Busulfan
Amiodarone
Nitrofurantoin
Sulfasalazine
Methotrexate
Methysergide
Drugs causing gynaecomastia
Spironolactone
DIgoxin
Verapamil
Cimetidine
Metronidazole
Drugs causing SIADH
Carbamezapine
Cyclophosphamide
Chlorpropamide
SSRIs
TCAs
Drugs causing gingival hypertrophy
Nifedipine
Phenytoin
Ciclosporin
Drugs causing prolonged QT
FVN MATCH
Fluoroquinolones: ciprofloxacin
Venlafaxine
Neuroleptics: phenothiazines, haldol
Macrolides
Anti-arrhythmics 1a/III: quinidine, amiodarone, sotalol
TCAs
Histamine antagonists
Cholinergic side effects
SBLUDGEMS
Caused by?
Salivation
Bronchoconstriction
Lacrimation
Urination
Diarrhoea
GI upset
Emesis
Miosis
Sweating
e.g. anti-cholinesterases
Anti-muscarinic side effects
CUMBBD
Constipation
Urinary retention
Mydriasis
Blurred vision
Bronchodilation
Drowsiness
Dry eyes/skin
Causes of anti-muscarinic side effect profile?
Ipratropium
Anti-histamines
TCAs
Anti-psychotics
Procyclidine
Atropine
Causes of dopamine excess
L-Dopa
Da agonists
Clinical features of dopamine excess?
Behaviour change
Confusion
Psyhcosis
Causes of dopamine deficit
Anti-psychotics
Anti-emetics: metoclopramide, prochlorperazine
Features of dopamine deficit?
EPSEs
Increased prolactin
Neuroleptic malignant syndrome
Cerebellar disease
DANISH
Dysdiadochokinesia, dysmetria, rebound
Ataxia
Nystagmus
Intention tremor
Scanning dysarthria/slurred speech
Hypotonia
Pharmacological causes of cerebellar syndrome
EtOH
Phenytoine
Causes of EPSEs?
Typical antipsychotics
Rarely: metoclopramide, prochlorperazine: especially in youing women
Dyskinesias and dystonias are common with anti-parkinsonian drugs
Mechanism of EPSEs?
D2 block in the nigrostriatal pathway
Excess AChM- hence the effect of anti-AChM
What are the types of EPSEs?
Parkinsonian
Acute dystonia
Akathisia
Tardive dyskinesia
Neuroleptic malignant syndrome
Explain mechanism of EPSEs
Features of Parkinsonian EPSEs?
Occurs within months
More common in the elderly
Bradykinesia tremor, rigidity
Rx of parkinsonian EPSEs?
Procyclidine
Features of acute dysonia
Occurs within hours-days of starting drugs
Commoner in young males
Involuntary sustained muscle spasm
e.g. lock jaw, spasmodic torticollis, oculogyric crisis
Rx in acute dystonia?
Procyclidine
Features of akathisia
Occurs within days to months
Subjective feeling of inner restlessness
Rx of akathisia?
Propranolol (crosses BBB)
Features of tardive dyskinesia?
Rhythmic involuntary movement of head, limbs and trunk
Chewing, grimacing
Protruding, darting tongue
Occur in 20% of those on long term neuroleptics
Rx in tardive dyskinesia?
Switch to atypical neuroleptic
Clozapine may help
Procyclidine worsens symptoms
Features of neuroleptic malignant syndrome
4-10d after initiation or change of dose
Mostly in young males
Motor: severe muscular rigidity
Mental: fluctuating consciousnsess
Autonomic: hyperthermia, increased HR, sweating, hyper/hypotensive
Blood: rasied CK, leukocytosis
Rx neuroleptic malignant syndrome?
Dantrolene: inhibits muscle Ca release
Bromocriptine/apomorphine: reverse Da block
Cool patient
Where do pharmaceutical drug interactions take place?
Outside the body
Mainly with IV drugs being mixed together
e.g. Ca and NaHCO3-> precipitation
What are the pharmacokinetic forms of drug interactions
Altered absorption
Displacement from plasma proteins
Metabolism- inhibitors and inducers
Excretion
Give an example of altered absorption
Tetracyclines and quinolones with Ca, Fe, Al
Drugs chelate the metals and are not absorbed
Give an example of drug displacement from plasma proteins
Warfarin + some NSAIDs
often clinically insignificant as clearance increases proportionally with displacement
What are some enzymes that can be inhibited by drugs?
P450
Xanthine oxidase: allopurinol
DOPA decarboxylase: carbidopa
Acetaldehyde dehydrogenase: disulfiram, metronidazole
How do diuretics affect Li?
Reduce Li clearance
How do loop diuretics affect aminoglycosides
Increase aminoglycoside ototoxicity
What are some examples of indirect drug interactions
Diuretics and steroids-> increase risk of digoxin toxicity by reducing K
NSAIDs and warfarin increase risk of GI bleed
Abx and warfarin increase bleeding risk as Abx kill GI microflora that make Vit K
What are some important P450 inducers
PC BRAGS
Phenytoin
Carbamezapine
Barbiturates
Rifampicin
Alcohol (chronic)
Griseofulvin
St John’s Wort
What are some important P450 Inhibitors?
VIP C CEO GFF
Valproate
Isoniazid
Protease inhibitors
Ciprofloxacin
Cimetidine
Erythromycin and clarithromycin
Omeprazole
Grapefruit juice
Fluconazole, fluoxetine
What are some important drugs metabolised by p450?
COWEST
Ciclosporin
OCP
Warfarin
Epileptic drugs: phenytoin, CBZ
Statins
Theophylline
What classes of drugs increase Warfarin action?
Enzyme inhibitors
EtOH
Simvastatin
NSAIDs
Dipyridamole
Amiodarone
What drugs reduce warfarin action?
Enzyme inducers
What drugs do diuretics potentiate?
ACEI
Li
Digoxin
What do k-sparing diruetics do with ACEI?
Increase risk of hyperkalaemia
Pharmacokinetics of the edlerly: Distribution
Reduce body water- increased {water soluble drugs}
Increased body fat- {reduced fat soluble drugs}
Reduced albumin- [increased protein bound drugs]
Reduced weight: therefore at standard dose- {increased]
Pharmaokinetics in the elderly: metabolism
Reduced oxidation
Reduced FPM
Reduced induction of liver enzymes
Therefore with age there is an increased t1/2 of hepatically metabolised drugs
Pharmacokinetics in the elderly: elimination
Reduced GFR
Reduced tubular secretion
Bottom line of pharmacokinetics in the elderly
Increased age tends to lead to greater and longer drug effects
Altered organ sensitivity in the elderly
ANS
Defective compensatory mechanisms
Reduced beta receptor density: therefore reduced effectiveness of drugs targeting them
Altered organ sensitivity in the elderly:
CNS
Increased sensivity to anxiolytics and hypnotics
Altered organ sensitivity in elderly:
Reduced cardiac function
Reduced perfusion of liver and kidneys: reduced function: reduce metabolism or elimination of drug
What are some issues with compliance in the elderly
Confusion
Reduced vision
Arthritic hands
Living alone
Polypharmacy
What are the major problem drugs in the elderly affecting the CVS?
Anti-HTNs
Digoxin
Diuretics
What are the major problem drugs in the elderly affecting the CNS?
Anti-depressants
Anti-parkinsonian
Hypnotics
Pharmacokinetics in the neonate
A: reduced gastric motility
D: immature BBB
Increased body water: {reduced water soluble drug]
Reduced body fat [increased fat soluble drugs]
Reduced albumin {increased]
M:
Reduced P450 activity
Reduced conjugation
E:
Reduced GFR and tubular secretion
Bottom line: reduced age leads to greater and longer drug effects
Mechanisms of teratogen action?
Orally active= crosses placenta
Implantation-> abortion
Embryonic-> structural defets
Fetogenic-> relatvely less dangerous
Common teratogens and their effects
ACEI: affect kidney growth
AEDs: NTDs
LI: Ebstein’s anomaly
Anti-folate e.g. trimeth-> NTDs
Tetracyclines-> stains teeth
Warfarin: cardiac defects, reduced IQ, saddle nose, blindness
Statins
What are some drugs to avoid in late pregnancy and why?
Asprin: haemorrhage, kernicterus
Aminoglycosides: CN8 damage
Anti-thyroid: goitre, hypothyroidism
Benzos: floppy baby syndrome
Chloramphenicol: grey baby syndrome
Warfarin: haemorrhage
Sulphonylureas: kernicterus
Mx of HTN in pregancny
NB don’t prescribe ACEI to fertile young women
Labetalol
Methyldopa
Nifedipine
Hydralazine
Mx of DM in pregnancy
Poor glucose control associated with increased congenital abnormalities
Use insulin and or metformin
Mx of epilepsy in pregnancy
Folic acid pre-conception
Drug level tends to fall in pregnancy
Increased risk of malformations
Increased risk of haemorrhagic disease of newborn
Avoid VPA
Use LTG or CBZ
Atnicoagulation in 1st trimester
LMWH
Anticoagulation in 2nd trimester-36w
LMWH or warfarin
Anticoagulation 36w- term
LMWH
Mx of anticoagulation term onwards
Warfarin
Sedatives and breast feeding
Drowsiness
Anti-thyroid and breast feeding
Goitre
Tolbutamide and breast feeding
Hypoglycaemia in infant
What are some important drugs affected by renal impairment?
DGAAC
Digoxin
Gentamicin
Atenolol
Amoxicillin
Captopril
Digoxin in renal impirment
T1/2: 36-90 hours
Low therpaeutic index, shoulde be monitored
Nausea, xanthopsia, gynaecomastia
AV tachyarrythmias, heart block
Digoxin toxicity
Gentamicin in renal disease
T1/2:2.5-> 50h
MUST be monitored
Increased risk of toxicity if reduced Na e.g. diuretics or dehydrated
Hearing and vestibular issues
Nephrotoxicity
Gentamicin
Atenolol in renal disease
T1/2: 6->100hours
CI to atenolol
Asthma/bronchospasm
Severe heart failure
PVD
Bradycardia, hypotension
Worsening of PVD and HF
Confusion
Atenolol toxicity
Amoxicillin in renal disease
T1/2 2-> 15hrs
Toxcity:
seizures (in meningitis, impaired BBB), rashes
Hypotension
Taste distrubrance
Cough
reduced GFR
Angioedema
Captopril toxicity
What form of VitD should be used in renal impairment?
Alfacalcidol (1 alpha-hydoxylated)
What are some important nephrotoxic drugs?
Gentamicin
Li
Ciclosporin
ACEI/ARB
NSAIDs
Gentamicin: renal toxicity mechanism
Renal tubular damage-> accumulation-> increased nephro and ototoxcicity
MUST monitor levels
Li: renal toxicity mecahnism
Inhibits Mg-dependant enzymes e.g. adenylate cyclase
ADH requires adenylate cyclase therefore Li causes nephrogenic DI
Also causes direct tubular damage
Must monitor drug levels
How does Li cause nephrogenic DI
ADH requires adenylate cycle, an Mg-dependant enzyme inhibited by Li
Ciclosporin: renal toxciity mechanism
Reduced GFR: reversible
Damages renal tubules: irreversible
P450 substrate
Consider monitoring
ACE/ARB nephrotoxcity mechanism
Reduce GFR: inhibit efferent arteriolar vasoconstriction may be profound in RAS or CoA
NSAIDs: nephrotoxicity mechanism
Reduce GFR: prevent afferent arteriolar vasodilation
Leading to papillary necrosis
What should be considered in prescribing in hepatic impairment
Albumin levels
Clotting factors synthesis
Reduced FPM
Reduce alpha 1 acidic glycoprotein
Encephalopathy
Hepatorenal syndrome
Prescribing in hyopalbuminaemia
Increased proportion of free drug
e.g. phenytoin, CBZ, predniosolne, diazepam, tolbutamide
Redcued FPM, what Rx should be assessed
Opiates
Phenothiazine
Imipramine
What are some drugs bound by alpha-1acidic glycoprotein
Chlorpromazine
Quinidine
Imipramine
What is a consideration in hepatic encephalopathy regarding Rx
Sedatives/opiates-> coma
Caution with drugs that may cause constipation
Anxiolytis: temazepam safest due to short t1/2
TCAs safer but avoid MOAIs
Considerations in Rx with hepatorenal syndrome
Withdraw nephrotoxic drugs
Modify doses of renally-excreted drugs
What are some drugs causing cholestatic heaptotoxicity
Clavulanic acid: may be delayed
Fluclox: may be delayed
Erythromycin
Sulfonylureas
OCP
Tricyclics
Chlorpromazine, prochlorperazine
What drug is associated with gallstones?
OCP
What drugs are associated with chronic hepatitis
Isoniazid
Methyldopa
What drugs are associated with hepatocellular damage
Paracetamol
VPA, Phenytoin, CBZ
Rifampicin, isoniazid, pyrazinamide
Halothane
Methotrexate
Statins
Drugs and doses used as morning after pill
Levonorgesterl 1.5mg PO STAT
Ulipristal 30mg PO STAT
MOA of beta agonists
Act at bronchial B2 receptors:
SM relaxation and reduce secretions
Side effects of beta agonist bronchodilators
Tachycardia
Tremor
Interactions of beta agonist bronchodilators
Reduce K in high doses with corticosteroids, loop/thiazide diuretics/theophylline
SABA features
Short acting, fast onset
2-4 hrs
Give 2 examples of SABA
Salbutamol (ventolin)
Terbutaline (Bricanyl)
MOA muscarinic antagonist bronchodilation
Bronchodilation
Mucus secretion
Side effects of muscarinic antagonist bronchodilators
Dry mouth
Caution re muscarinic antagonist bronchodilators
Closed angle glaucoma
Prostatic hypertrophy
Features of SAMAs
3-6hrs
Short acting
e.g. SAMA
Ipratropium (Atrovent)
e.g. LAMA
Tiotropium (Spiriva)
e.g. of ICS
Beclometasone: Becotide
Budenoside: Pulmicort
Fluticasone: Flixotide
What is symbicort?
Budenoside and fomoterol
Gives examples of LABA
Salmeterol
Formoterol
What is seritide
Fluticasone and salmeterol
MOA of ICS
Act over weeks to reduce inflammation:
Reduce cytokine produciton
Reduce prostaglanding/leukotriene synthesis
Reduce IgE secretion
Reduce leukocyte recruitment
Prevent long term decline in lung function
Side effects of ICS
Oral candidiasis
High doses may lead to typical steroid SEs
Fluticasone vs other ICS
2x as potent: use lower dose
Symbicort usage
Can be used as a preventer or a reliver because of formoterol’s fast onset
Use of ICS advice
Use a spacer
Rinse mouth after use
Theophylline MR
Aminophylloine
Drug class
Methylxanthines
Methylxanthine MOA
PDE inhibitors: increase cAMP-> bronchodilation
Side effects of methylxanthines?
Nausea
Arrhythmias
Seizures
Hypokalaemia
Interactions of methylxanthines leading to reduced levels
Smoking
EtOH
CYP inducers
Interactions of methylxanthines to increase levels
CCBs
CYP inhibitors
Additional detail re methylxanthines
Aminophylline is IV form:
give IVI slowly
Too fast -> VT
Monitor with ECG and check plasma levels
CYP metabolism
NB if pt already on theophylline cannot have IV aminophylline
MOA
Montelukast
Zafirlukast
Leukotreine receptor antagonists
Block cysteinyl leukotrienes
Side effects for leukotriene R antagonists
?Churg Strauss
What are leukotriene antagonists particulalrly useful for?
NSAID and exercise induced asthma
Roflumilast MOA
PDE-4i
Side effects roflumilast
GI
CI for roflumilast
Severe immunological disease
Omalizumab MOA
Humanised anti-IgE mAb
Features of omalizumab
SC injection every 2-4w
Used for severe asthma
Carbocysteine
Mucolytic
Side effects of carbocysteine
GI bleed (rare)
CI carbocystiene
Active peptic ulceration
Dornase ALFA (Dnase) MOA
used in?
Mucolytic
CF
Non-sedating H1R antagonists
Certrizine
Loratidine
Fexofenadine
Sedating H1R inverse agonists (antagonists)
Chlorphenamine
Inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to thatagonist. A neutral antagonist has no activity in the absence of an agonist or inverse agonistbut can block the activity of either
Side effects of H1R inverse agonists
hypotension
Arrhythmia: long QT
Older agents: drowsiness
Anti-AChM
CI for H1R inverse agonists
Severe hepatic disease
Caution in H1R inverse agonists
Long QT
BPH
Closed-angle glaucoma
LMWH in pregnancy
Does not cross the placenta
ST effects of pred in asthma
Candidiasis
Hypokalaemia
What is important to remember re LMWH in pregnancy
Must remember to stop it due to risk of osteoporosis
Indapamide
Thiazide like diuretic
Which 2 of the following are most likely to cause hyponatraemia
INdpamide
Perindopril
Rivaroxaban
Amlodipine
Citalopram
Simvastatin
Paracetamol
Indapamide- will cause sodium loss-> hyponatraemia
Citalopram-> SIADH (obscure adverse effect)
Periondopril will cause hyponatraemia but hyperkalaemia
Why should you take short acting statins at night (simvastatin)
Because cholesterol synthesis is thought to happen prinicipally during the night
%w/v units
grams in 100 millilitres gives you the percentage
v/v %
millilitres in 100 millllitres
Abciximiab
2b3a antagonist
Cough ADR in ACEi
Dose independent
Colchicine in gout
Recommended in patients with HF as unlikely to make HF worse.
Diclofenac should not be used as it has a high risk of cardiovascular events
1:1000 adrenaline
1mg per ml
1:10000
0.1mg per ml
Mx of acute dystonia
Procyclidine 5mg IM
What is the limit of morphine per 24h
200mg/24 hours
Which medication is often associated with gout
Thiazide diuretics: increase Na clearance at the expense of uric acid excretion
Two common side effects of metronidazole
N+V
Furred tongue
Metallic taste in mouth
Reversal of warfarin overdosing with Vit K PO or IV
IV and PO both same onset of action
If plan is to restart warfarin, give IV as PO action takes longer to turn off than IV
What drugs require obligatory TDM?
Aminoglycosides
Vancomycin
Lithium
What are some drugs that commonly have TDM?
Aminoglycosides
Vancomycin
Lithium
Digoxin
Phenytoin
Does Warfarin have TDM?
Technically not as it is not the [plasma] being monitored, rather the biological effect
What are the 3 pathways of drugs through the body?
Excreted unchanged by the kidney e.g. furosemide
Phase 1 metabolism-> kidney or phase 2
Phase 2 metabolism: undergoes phase 2 transformation and then excreted
Phase 1 metabolism=
Oxidation
Reduction
Hydrolysis
Molecule itself is directly altered usually by cytochrome p450 (oxidation)
Phase 2 metabolism
Either the original drug or its modified form is then conjugated e.g. glucuronidation, sulphation, acetylation
This tends to make compound more polar, allowing excretion more readily
What is the most important cytochrome subtype
CYP3A4: accounts for 30% of prescribed drugs e.g. CCBs, statins, BZDs
CYP2D6
Next most important cytochrome, metabolises 20% of drugs e.g. antidepressants, beta blockers, some opiates
CYP1A2 metabolises
Paracetamol
Caffeine
Theophylline
CYP2C9 metabolises
Warfarin
Ibuprofen
CYP2C19 metabolises
Diazepam
Omeprazole
Enalpril
Prodrug, ACEi
converted to enlaprilat
Azathioprine
Prodrug, converted to 6-mercaptopurine
Ezetimibe
Ez-glucuorine
Converted to the glucuronide in the liver which is the active form. This reaches the lumen of the small intestine where it blocks cholesterol absorption
What is the single most important determinant in the elimination of most drugs?
GFR
What is pharmacogenetics?
The study of genetically determined varaitions in the response to drugs
What is the significance of acetylation polymorphisms?
A small number of drugs are metabolised by acetylation, there are fast and slow acetylators, which is genetically determined and which may have different side-effects
Drugs that udnergo acetylation include isoniazid, hydralazine, dapsone
What are some examples of variations in clinical pharamacogenetics?
Pseudocholinesterase
G6PD
Porphyria
Significance of pseudocholinesterase
Patients lacking this enzyme had prolonged recovery after anaesthesia
Type A ADRs
Predictable reactions
Common
Dose-related but can occur at therapeutic doses
Consequence of known pharmacology of drugs
What is a type B ADR
Idiosyncratic reactions
Rare to very rare
Usually not dose related
Include true allergies
Include some pharmacogenetic variations
What are long term ADR?
Dependence/addiciton e.g benzos
Withdrawal phenomena inc rebound e/g/ clonidine
Adaptive changes e.g. typical antipsychotics-> tardive dyskinesia
What are delayed ADR
Carcinogenesis
Teratogenesis
ABCDE classification of ADRs
Augmented pharmacological effect
Bizarre
Chronic
Delayed
End of treatment
What are the drug determinants of ADRs?
Pharmacodynamics:
pharmacokinetic properties e.g. digoxin
Dose e.g. beta blockers
Formulation e.g. digoxin
ROA e.g. phenytoin
Rate of administration e.g. aminophylline
Digoxin excretion
Renally
ROA phenytoin
Oral- rarely CV problems
IV: bradycardia/hypotension
Rate of administration aminophylline
Given too quickly-> ventricular arrythmia
liver disease + opiates
Increases risk of hepatic encephalopathy and worsening liver failure
What are some examples of pseudoallergies
Non-immune mechanisms, pharmacolgoical
e.g. salicylates, other NSAIDs-> bronchospasm. shift metabolsim from prostaglandins to leukotrienes which leads to bronchospasm
ACEi-> cough, angioedema (anaphylactide)
Drugs causing urticaria
Penicllins, contrast media, opiates
Drugs causing erythema multiforme
Penicllins, sulfonamides
Drugs causing erythema nodosum
Sulfonamides, OCP
Drugs causing photosensitivity
Amiodarone
Thiazides
Sulfonylureas
Drugs causing fixed eruptions
Erythromycin
Sulfonamides et.c
Drugs causing lupus-like reactions
Penicllins, isoniazid, hydralazine
Fixed eruption
Drug causes rash in a fixed distribution
Drug stopped, if restarted rash appears in same distribution
Drugs causing intrahpeatic cholestasis
Phenothiazines (formerly used as an antihelminthic)
TCA
Sulfonylurea
Erythromycin
Clavulanic acid (may be delayeed)
Carbimazole
Anabolic steroids (dose related)
Drugs causing hepatocellular damage
Isoniazid
Pyrazinamide
Methyldopa
TCA
Phenytoin
All of the above can occur from acute or chronic use
Pracetamol (dose dependant)
Methotrexate (dose dependant) (causes liver fibrosis)
Drugs causing chronic hepatitis
Isoniazid
Methyldopa
Drugs causing gallstones
Fibrates
Oestrogens
Drugs causing pancytopenia (aplastic anaemia)
Cytotoxics (Type A)
Type B:
Chloramphenicol( (1/10000, tends to be lethal)
Phenytoin
Peniclliamine
Phenothiazines
Drugs causing neutropenia
All type B
Carbamazepine
Carbimazole
Clozapine
Mianserin- withdrawn
Sulfasalazine
Mianserin
It is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA)
Drugs causing thrombocytopenia
All type B
Chloroquine
Captopril
Quinidine
Salicylates
VPA (most important)
Drugs causing peripheral neuropathy
Amiodarone
Nitrofurantoin
Penicillamine
Isoniazid
Dose dependant:
Vincristine
Cis-platin
Drugs causing pulmonary fibrosis
BBC MAN
B-Bleomycin
B-Busulfan
C-Cyclophosphamide
M-Methylsergide
A-Amiodarone
N-Nitrofurantoin
Methotrexate
Azathioprine enzyme moniotring
Azathioprine is a purine analogue that interferes with DNA synthesis and inhibits the proliferation of quickly growing cells, especially cells of the immune system. It is used as an immunosuppressant in patients undergoing organ transplantation, and its metabolite 6-mercaptopurine is used in the treatment of autoimmune diseases and acute lymphoblastic leukemia.
During metabolism, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) converts 6-mercaptopurine to cytotoxic 6-thioguanine nucleotide analogues, while thiopurine methyltransferase (TPMT) inactivates 6-mercaptopurine through methylation to form 6-methylmercaptopurine.
Approximately 11% of the population has reduced TPMT activity and 0.3% of the population has true deficiency of TPMT. [1] In these patients, active 6-mercaptopurine accumulates, and a larger proportion of 6-mercaptopurine is converted to the cytotoxic 6-thioguanine nucleotide analogues, which can lead to bone marrow toxicity and myelosuppression
Withdrawal reactions
important drugs
Opiates
BZDs
Corticosteroids
Rebound reactions
common drugs
Clonidine
Beta-blcokers
Corticosteroids
Oestrogen carcinogenesis
Endometrial ca
?breast ca
Types of clinical trials
Phase 1: normal volunteers (50)
Phase 2: patients, open study (200)
Phase 3: clinical trials: DB-RCT
Phase 4: post marketing
What are the 3 methods for detecting ADR post approval
Post-marketing: yellow card
Cohort studies
Prescription event monitoring
Black triangle drugs
Newly licensed usually <2y
Report any suspected adverse reaction
Established drugs in yellow card scheme
Only report serious adverse reactions: fatal, life-threatneing, needing hospital admission, disabling
What are pharmacetuical drug interactions
Ones taking place outside the body
Generally IV drugs being mixed together e.g. Ca and bicarbonate precipitating out
Always read instruction
Altered absorption: drug interactions
Tetracyclines, quinolones + Ca, Fe, Al
Altered absorption if given with any metal due to chelation
Think about drug timing
Displacement from plasma proteins
Most important
Warfarin + NSAIDs
Cytochrome p450 inhibitors
SICKFACES.COM Group
Sodium VPA
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol- binge drinking
Chloramphenicol
Erythromycin and other macrolides
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Grapefruit juice
Allopurinol + 6 mercaptopurine
Makes it more cyotoxic
Cheese reaction
MAOI and cheese-> hypertensive reaction. e.g. cheese, marmites (foods containing tyramine)
P450 inducers
CRAP GPS
Carbamezapine
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbitone
Sulphonylureas
Diuretics + lithium
Increased Na clearance but decreased Li clearance
Loop diuretics + aminoglycosides
Inihbit each others excretion and increase toxicitiy, particularly ototoxicity
What are some exmaples of indirect interactions?
Diuretics, corticosteroids + digoxin (low K)
NSAIDs and warfarin: damage to stomach, increased risk of GI bleed
Antibiotics and warfarin. reduced gut bacteria (involved in K production)
How can renal disease impact pharmacology
Drugs that are eliminated by the kidney
Drugs that are metabolised by the kidney
Nephrotoxic drugs
What are the clinically most important drugs effected by renal impairment
DIgoxin
Gentamicin
Atenolol
Amxocivillin
Captopril
Nause
Dysrhythmias
Anthopsia
Breast enlargement
Digoxin
Ototoxcitiy
Nephrotoxicity
Increased risk of toxicity in hyponatraemia and dehydration
Gentamicin
Bradycardia
Confusion
Hypotension
Fatigue
PVD
Heat failure at higer doses
Atenolol
Hypotension
Reduced GFR
Cough
Taste distrubance
Angioedema
GI distrubance
Captopril
When dose amoxicllin toxicity become important and why
Generally nontoxic
In patients with renal impairment the half life of the drug is substantially increased( 14h)
In patients with menigitis, the BBB is disrupted and this allows amoxiillin to accumulate in the CSF
These patients may develop seizures.
The allergic manifestation of drugs may also appear more commonly in this group of patients
Dry cough proportion of ACEi patients
15%
What is an important drug metabolised by the kidney and the significance of this?
Vit D3 (cholecalciferol- formed in skin). Vit D (made by uv irradiation of ergosterol)
Both forms are activated sequentially. 25a in liver
1a in the kiney
to yield 1,25 di(OH)D3 and 1,25 di(OH)D2
Mechanism of 2o hyerparathyroidism
Hypocalcaemia with relative conseuqence of hypophosphataemia lead to hyperparathyroid
Consequnece of failure in VtiD/ renal pathway
Gentamicin mechanism of nephrotoxicity
Renal tubular damge
Important in that damage occus with an accompanying degree of reduciton in GFR leading to gentamicin accumulation.
Causes a cycle.
Importance of appropriate gentamicin TDM
LI mecahnism of nephrotoxicity
Nephrogenic DI: through inhibiting Mg dependent enzymes (adenylate cyclase) which is activated in renal tubule by ADH.
and
Tubular damage
Cyclosporin A mechanism of nephrotoxicity
Reduced GFR
and
Tubular function
Used in renal transplant immunosuppression. Physician needs to distinguish between rejection episode causing decline in renal function or cyclosporin toxicity.
Cyclosporin AEs
TDM
Hypertension
Reduced GFR
Mechanism of ACEi nephrotoxicity
A2Rs located principally on the efferent arteriole. Have a vasoconstrictive effect.
If you administer ACEi which blocks biosynthesis of AngII or you give ARB there will be dilatation of the efferent arteriole.
As a consequent of that, renal blood flow through glomerulus increases.
However, the pressure within the glomerular tuft decreases.
The GFR is dependent on the perfusion pressure within the glomerular tuft, as perfusion pressure reduces, GFR reduces.
If a patient has a pathological reduction in pressure in the afferent arteriole e.g. RAS,(or more rarely in CoARc sited proximally to the renal arteries) there is a danger that if you inhibit ACEI/ARB for the pressure within glomerular tuft to reach pathologically low levels with a consequent critical reduction in GFR.
NSAIDs mechanism of toxicity
Inhibit COX and reduce PG concentration.
In the kidney and renal vasculature, most of the PGs are vasodilator. Effects are mediated by prostaglandin E2 and prostacycline.
These molecules regulate the diameter of blood vessels around the glomerulus.
LT use of NSAIDs. particularly in patients with preexisting renal damage, may result in a further reduciton in GFR and Na retention.
May also cause papillary necrosis. Papilla receives blood supply from surrounding bvs that require PGs to maintain their diameter, thus patients receiving high concentrations of NSAIDs may develop relative ischaemia of the renal papilla-> necrosis if sustained. Necrotic papilla may become detached from renal cortex, fall into renal pelvis and block ureturs
What are the hepatic synthetic functions important in pharmacology
Albumin: hypoalbuminaemia may increase proportion of the free drug, more of a problem if drug clearance is reduced.
e.g. Diazepam, tolbutamide, phenytoin
A1-acidic glyocoprotein: binds basic drugs
e.g. quinidine, chlorpromazine and imipramine
Reduced synthesis of Clotting factors
Warfarin and synthesis of Vit-K dependant clotting factors
What are the Vit K dependent clotting factors?
2, 7, 9, 10
What are drugs that should be prescribed with care in current or recent encepahlopathy?
Opiates (most important):
prolonged elimination, may precipitate encephalopathy
Anti-psychotics: phenothiazine and butyrophenones
Anxiolytes and hyponotics: oxazepam and temazepam are safest
Antidepressants: TCAs are safest, avoid MAOs: idiosyncractic hepatotoxicity
Hepatorenal syndrome precipitated by
Opiates
Major tranquilisers etc.
Patient with hepatic disease and declining renal function
?hepatorenal syndrome
R/v drug chart and withdraw drugs that may be contributing
What are the groups of drugs that are likely to present problems in patients with liver disease?
Those with high FPM
High plasma protein binding
Low TI
Those with CNS depressant effect
Importance of drugs with extensive FPM
Normally only a small proportion of ingested blood enters blood, liver disease-> very reduced FPM
e.g.
Clormethiazole
Chlorpromazine
Imipramine
Morphine
Pethidine
Importance of drugs with high plasma protein binding in context of liver disease
Combination of high protein binding and reduced elmination likely to precipitate a prolbem
e.g.
Chloral hydrate
Phenytoin
Importance of durgs with low TI in context of liver disease
Any incapacity of liver to metabolise drug and reduce toxic levels likely to precipiate toxicity
e.g. barbiturates
Importance of drugs with CNS effect in context of liver disease
Principally because of capacity to control through autonomic NS the important CV and respiratory functions likely to become hypotensive, develop bradycardias and stop breathing.
Drugs include opiates, phenothiazine and othrers with known sedative effects
How can the mecahnisms of hepatotoxicity be classified?
Non-covalent
or
Covalent
What are the mechanisms of non-covalent hepatotoxcitty?
Occur as a consequence of the activity of cytochrome p450.
During these reaction oxygen radicals can be generated e.g. peroxides, superoxides, hydroxyl radicals. Highly reactive molecular species that may damage the structure of lipids, aas and other molecules.
Normally glutathione is there to protect the cell and serves as free radical scavenger, however in established liver disease glutathione may become depleted and this may increase the propensity of oxudative products to cause issues
What is the mechanism of covalent hepatotoxicity
Involve adduct formation between drug/metabolite and DNA/proteins/lipids within the cell
What are the common hepatotoxic drgus?
Hepatocellular necrosis:
Paracetamol- reactive intermediate
Halothane: repeated use
Anticonvulsants Carbamazepine, phenytoin and valproate
MAOIs, isoniazid, nitrofurantoin, sulphonamides
Hydralazine, methyl dopa
Cholestasis:
Chlorpromazine
Sulphonylureas (glibenclamide)
Carbimazole
This drug has 100% bioavailability in an oral formulation
A.
Metformin
B.
Captopril
C.
Levodopa
D.
Amiodarone
E.
Gentamicin
F.
Methotrexate
G.
Isoniazid
H.
Ciprofloxacin
I.
Phenytoin
J.
Diltiazem
Ciprofloxacin
Probenecid competitively inhibits the secretion of which drug?
A.
Lithium
B.
Beclometasone
C.
Penicillin
D.
Metronidazole
E.
Theophylline
F.
Azathioprine
G.
Suxamethonium
H.
Lignocaine
I.
Propofol
J.
Dapsone
Penicillin
A.
Lithium
B.
Beclometasone
C.
Penicillin
D.
Metronidazole
E.
Theophylline
F.
Azathioprine
G.
Suxamethonium
H.
Lignocaine
I.
Propofol
J.
Dapsone
A prodrug that interacts with allopurinol
Azathioprine
Drug metabolised by acetylation, used to treat leprosy
Dapsone
Smoking increases the metabolism of this drug.
A.
Lithium
B.
Beclometasone
C.
Penicillin
D.
Metronidazole
E.
Theophylline
F.
Azathioprine
G.
Suxamethonium
H.
Lignocaine
I.
Propofol
J.
Dapsone
Theophylline
An anti-platelet drug that may cause a rare thrombotic syndrome that is characterised by a classic triad
Clopidogrel
A drug used to treat Wilson’s disease, that may cause a myasthenia gravis-like syndrome
Penicillamine
A centrally acting antihypertensive that may give rise to a positive Coombs test
Methyldopa
If this antidepressant is given with amiodarone it increases the risk of an arrhythmia
Amitryptilline
If this drug is given to a patient with bipolar affective disorder, there is increased risk of toxicity of a particular mood stabiliser
Frusemide
Which drug causes ‘floppy baby syndrome’?
Diazepam
Which drug, when given to a mother in the late stages of pregnancy, can cause a low platelet count in the neonate?
Bendroflumethiazide
Which drug causes Ebstein’s anomaly in the baby?
Li
Effects of this drug on the fetus include frontal bossing, midface hypoplasia, saddle nose, cardiac defects, short stature, blindness and mental retardation.
Warfarin
Drug that may cause liver adenoma.
A.
Penicillamine
B.
Sumatriptan
C.
Oral contraceptive
D.
Cimetidine
E.
Hydroxychloroquine
F.
Methotrexate
G.
Rifampicin
H.
Cyclophosphamide
I.
Atenolol
J.
Diclofenac
Rifmapicin
Renally excreted drug that can cause impotence, nightmares and type 2 Diabetes
atenolol
Renally excreted drug used to treat Zollinger Ellison Syndrome
Cimetidine
Detemir
Longer acting insulin that binds to albumin in the circulation
Glargine
Longer acting aa-altered insulin, thus prolonged absorption from subcutaneous tissue
Action of insulin at the liver
Switches off hepatic glucose output:
gylcogenolysis
gluconeogensis
Inhibits ketogenesis
Action of insulin at adipose tissue
Increaes lipoprotein lipase activity:
reduces hypertriglyceridaemia
Increases GLUT4 activity-> glucose stored as fat
Decreased lipolysis: reduced [glycerol], [non-esterified fatty acids reduced]
Insulin action at muscle
Decreased proteolysis: decreased aa delivery to liver for gluconeogenesis
Increased GLUT4 activity-> [reduced glucose]
Can a bolus of insulin be useful?
Short t1/2 of IV insulin means bolus is never useful. Should be given by infusion
When is human insulin used?
IV
Features of basal-bolus QDS insulin
Short acting with breakfast
Second dose with lunch
Third with evening meal
Intermediate insulin given OD
ACTrapid given 15 mins before meal
Intermediate given before patient goes to bed
Preprandial glucose
Doesn’t tell you how much insulin is needed
Post prandial tell you how much you should have given
Fasting glucose
Tells us how much long acting needs to have been given night before
Issues with actrapid
Human insulin.
Forms hexamers under skin and is abosrbed over 3-4h
Needs to be given 15 mins before meal
Can lead to late post prandial hypoglycaemia
Can lead to immediate post-prandial hyperglycaemia that may lead to diabets cx
Insulin lispro
Short acting insulin that has modified aa so doesn’t form hexamers under skin
Faster onset and shorter duration of action
Can be given at beginning of food or even after food.
Possible T2D insulin regimes
Long acting insulin + sulphonylurea
BD mixtrrd
Full basal bolus
Insulin + metformin
Advantage of metformin and insulin
Didn’t gain weight that is seen in intensive insulin alone
Glucagon in EtOH induced hypo
May not be as effective as EtOH uses glycogen in metabolism
Dietary advice in T2DM
Control total calories/increase exercise
Reduced refined carbohydrate
Increase complex carbohydrate as a proportion of carbohydra
Reduce fat as proportion of caloires
Increase unsaturated fat as a proprotion of fat
Increase soluble fibre
Address Na intake
Oriistat dose
120mg TDS
Metformin
Insulin sensitiser
Biguanide
Increases hepatic insulin sensitivity
Inhibits hepatic gluconeogenesis
Insulin sensitiser
Biguanide
Increases hepatic insulin sensitivity
Inhibits hepatic gluconeogenesis
Metformin
Metformin iniitial dose
500mg BD
Side effects of metformin
GI disturbance: nausea and diarrhoea
Lactic acidosis (rare)
Do not use if severe liver, severe cardiac, or mild renal failure (elevated Cr + radiological contrast media)
Act on beta cell to acutely cause insulin release independent of glucose concentration
Stimulate second phase insulin secretion
Sulphonylureas
Metaglinides
Sulphonylurea MOA
Act on insulin secretagogue
Act on beta cell to acutely cause insulin release independent of glucose concentration
Stimulate second phase insulin secretion
Starting dose of sulphonylureas
2.5mg BD
Draw MOA of sulphonylureas
Cx of sulphonylureas
Hypoglycaemia: can be severe, prolonged, or even fatal
Especially a problem in elderly, alcoholics and those with poor nutirtion- not enough stored glyocgen
Weight gain
Rarer complications: rashes, blood dyscrasia
Hypoglycaemia: can be severe, prolonged, or even fatal
Especially a problem in elderly, alcoholics and those with poor nutirtion- not enough stored glyocgen
Weight gain
Rarer complications: rashes, blood dyscrasia
Sulphonylureas
What are the non-sulphonylurea secretagogues?
Repaglanide
Nataglinide
Gliclazide
Glibenclamide
Sulphonylureas
MOA Thiazolidinediones
Reduce lipotoxicity
Increase muscle insulin sensitivity
Favourable fat distribution
Suppression off fatty acid release through PPARg agonism
Reduce lipotoxicity
Increase muscle insulin sensitivity
Favourable fat distribution
Suppression off fatty acid release
All rthrough PPARg agonism
Thiazolidinediones
Rosiglitazone
Pioglitazone
Glitazone: PPARg agonists
MOA PPARg
Act on intranuclear PPARg
Adipose tissue>liver and muscle
Affect lipoprotein lipase, FA transporter, CoA synthase, GLUT4
Insulin resistance reduced
Act on intranuclear PPARg
Adipose tissue>liver and muscle
Affect lipoprotein lipase, FA transporter, CoA synthase, GLUT4
Insulin resistance reduced
PPARg agonist e.g. glitazone
Side effects of pioglitazone
Peripheral weight gain
Oedema
Should not be used with insulin
E.g. of alpha glucosidase inhibitors
Acarbose
MOA acarbose
Delay oligosaccharide absorption
S/E acarbose
Flatulence
MOA GLP-1
Inhibit glucagon release
Cause acute insulin release
Stimulate insulin biosynthesis
Improve beta cell differentiation
Inhibit glucagon release
Cause acute insulin release
Stimulate insulin biosynthesis
Improve beta cell differentiation
GLP1
Pramitide MOA
Slow gastric eptying
Inhibit glucagon release
Cause acute insulin release
Why should thyroxine be introduced gradually, especially in the elderly
Can exacerbate pre-existing ischaemic heart disease
What are the risks of suppressing TSH
Osteopenia/osteoporosis
AF (especially in older patients)
Should not aim to suppress TSH, should aim to bring it within normal range
Mx of low uptake thyroxtocisosis
Use beta blockers as thionamides won’t work
Sore throat on carbimazole
Warn patient to stop due to risk of agranulocytosis
When is 131I not used in thyroid disease
Opthalmopathy/tracheal compression
MOA Mg Triscillate
Antacid
Neutralises gastric acid
MOA AI hydroxide
Antacid
Neutralises gastric acid
MOA Gaviscon
Alginate
Reduces reflux: increased stomach content viscosity
Forms a raft on top of stomach contents
MOA
Omeparzole
Lansoprazole
Pantoprazole
PPIs
Activated in acidic pH
Irreversibly inhibit H/K ATPase
More effective than H2R antagonsits
MOA
Cimetidine
Ranitidine
H2 R antagonists
Reduce gastric parietal cell H secretion
MOA
Misoprostol
Prostaglandin analgoue
Acts on parietal cells to reduce secretion
Side effects:
Mg Triscillate
Diarrhoea
Side effects: AI hydroxide
Constipation
Side effects: PPIs
GI distrubance
Headache
Side effects: H2R antags
Mainly with cimetidine: GI disurbance
Side effects:
Misoprostol
Diarrhoea is very common
Interactions:
Mg Triscillate
Interfere with drug absorption- take separately
Interactions:
AI hydroxide
Interfere with drug absorption- take separately
Interactions:
PPIs
P450 inhibitor
Interactions:
Cimetidine
P450 inhibitor
Additional notes:
Mg Triscillate, AI hydroxide
Take when symptoms occur/expected
Additional notes:
PPIs
Masy mask symptoms of gastric carcinoma
Additional notes:
H2R antags
May mask symptoms of gastric Ca
Additional notes:
Misorpostol
Mainly used to prevent NSAID-associated PUD
Often in combination with NSAID e.g. diclogenac + misoprostol= arthrotec
MOA:
Bran Ispaghula
Bulk laxatives
Increase feacal mass-> increased peristalsis
MOA:
Docusate
Glycerin (PR)
Senna
Picosulfate
Stimulant laxatives
Increase intestinal motility
MOA:
Lactulose
Macrogol
Phosphates
Mg Salts
Osmotic laxatives
Increse stool water content
MOA:
Liquid paraffin
Stool softener
Side effects:
Bulk forming laxatives
Bloating
Side effects:
Liquid paraffin
Reduced ADEK absorption
Granulomatous reactions
Contraindication to all laxatives
Bowel obstruction
What is co-danthrusate
A mild stimulant laxative used in Rx of opioid induced constipation
MOA:
Hyoscine butylbromide (Buscopan)
Antimuscarinic- antispasmodic
MOA:
Mebeverine
Peppermint oil
Antispasmodic
MOA:
Loperamide
Opioid receptor agonist
Doesn’t cross BBB therefore no central effects
MOA:
Sulfasalzine
Mesalazine
5-ASA
Unknown MOA
MOA:
Budesonide
Steroid
More potent than prednisolone
High FPM therefore less systemic effects
MOA:
Infilixmab
Chimeric anti-TNF mAB
MOA:
Etanercept
P75 TNFRFc fusion protein
MOA:
Adalimumab
Human anti-TNF mAb
Side effects:
Hyoscine
Anti-AChM SEs: dry mouth, palpitations
Side effects:
Loperamide
Abdo cramps
Side effects:
5-ASAs
Sulfasalzine has increased SEs:
blood dyscrasias
hepatitis
rash, urticaria
Oligospermia
pulmonary fibrosis
Side effects:
Infliximab, etanercept, adalmimuab
Severe infections
TB
Allergic reactions
CCF
CNS demyelination
Points of interest:
5-ASA
Monitor FBC
Topical in distal disease
Points of interest:
Budesonide
Use to induce remission in ileal crohn’s
Points of interest:
Biologics used in IBD
Screen for TB before parenteral admin
Give hydrocortisone to reduce allergic SEs
SABAs
Salbutamol
Terbutaline
LABAs
Salmeterol
Formoterol
MOA:
beta agonists
Act @ bronchial B2 receptors- smooth muscle relaxation
reduced mucus secretion
MOA:
Muscarinic antagonists
Bronchodilation
Mucus secretion
SAMA
Ipratropium
LAMA
Tiotropium
E.g. ICS
Beclometasone
Budesonide
Fluticasone
Symbicort
Budesonide + formoterol
Seretide
Fluticasone + salmeterol
MOA:
ICS
Act over weeks to reduce inflammation
Reduce cytokine production
Reduce prostaglanding/leukotriene synthesis
Reduce IgE secretion
Reduce leukocyte recrutiement
Prevent long term decline in lung function
MOA:
Theophylline
Aminophylline
Methylxanthines
PDE inhibitors: increse cAMP-> bronchodilation
MOA:
Montelukast
Zafirlukast
Leukotriene antagonists
Block cysteinyl leukotirenes
MOA:
Roflumilast
PDE4 inhibitor
MOA:
Omalizumab
Humanised anti-IgE mAb
MOA:
Carbocystine
Mucolytic
MOA:
Dornase ALFA
DNAse (mucolytic)
MOA:
Certirizine/loratidine/fexofenadine
Chlorphenamine (piriton)
Selective H1R inverse agonists aka H1 antagonists
What are the non-sedating antihistamines
Certirizine
Des/ loratidine
Feoxfenadine
Give an example of a sedating antihistamine
Chlorphenamine
Side effects:
H1R partial agonists
Hypotension
Arrhthmia: long QT
Older agents:
drowsiness
Anti-AChM
Side effects:
Carbocystiene
GI bleed (rare)
Side effects:
Roflumilast
GI
Side effects:
Leukotriene antagonsits
?Churg-Strauss
Side effects:
Methylxanthines
Nausea
Arrhythmias
Seizures
Hypokalaemia
Side effects:
ICS
Oral candidiasis
High doses may -> typical steroid SEs
Side effects:
Muscarinic antagonsits
Dry mouth
Side effects:
Beta agonsits
Tachycardia
Tremor
CI:
Muscarinic antagonists
Closed angle glaucoma
Prostatic hypertrophy
CI:
Roflumilast
Severe immunological disease
CI:
Carbocysteine
Active peptic ulceration
CI:
H1R inverse agonsists
Severe hepatic disease
Caution:
long QT
BPH
Closed angle glaucoma
Interactions:
Methylxanthines
Reduced levels:
smoking, EtOH, CyP inducers
Increased levels:
CCBs
CyP inhibitors
Interactions:
Beta agonsits
Reduced K in high doses with corticosteroids, loop/thiazide diuretics
Theophylline
Additional info:
Salbutamol
Can be given IV in acute severe asthma
Additional info:
ICS
Decreases risk of complications: use spacer, rinse mouth after use
Fluticasone is 2x as potent so use at lower dose
Symbicort can be used as a reliever or a preventer because of formoterol’s fast onset
Additional info:
Methylxanthines
Aminophylline is IV form
Give IVI slowly, too fast-> VT
Monitor with ECG and check plasma levels
Additional info:
Leukotriene antagonsits
Particularly useful for NSAID and exercise induced asthma
Additional info:
Omalizumab
SC injection every 2-4w
Used for severe asthma
Use: carbocystine
COPD
Use: DNAse
CF
Standard dose:
Amoxicillin
500mg TDS PO
Standard dose:
Clarithromycin
500mg BD PO
Standard dose:
Trimethoprim
200mg BD PO
Standard dose:
Co-amox
1.2g TDS IV
Standard dose:
Simvastatin
20mg OD Nocte PO
Standard dose:
Nifedipine MR
20mg OD PO
Standard dose:
Lisinopril HTN
10mg OD PO
Standard dose:
Lisinopril HF
2.5mg OD PO
Standard dose:
Bisorprolol HF
1.25mg OD PO
Standard dose:
Paracetamol
1g QDS PO
Standard dose:
Codeine phosphate
30mg every 4h PRN PO
Max 240mg daily
Standard dose:
Tramadol
50mg ever 4h PRN PO
Ma 300mg daily
Standard dose:
Enoxaparin
Treatment: 1.5mg/kg/24h SC
Prophlyaxis: 40mg OD SC
MOA:
Cyclophosphamide
Alkylates DNA
Affects B cells> T cells
MOA:
Cisplatin
Alkylates DNA
MOA:
Azathioprine
Blocks de novo nucleotdie synthesis
Affects T cells > B cells
MOA:
Mycophenolate mofetil
Blocks de novo nucleotide synthesis
Affects T cells > B cells
MOA:
Methotrexate
Dihydrofolate reductase inhibitor
MOA:
Chlorambucil
Alkylates DNA
Antiproliferative agents
Cyclophosphamide
Cispaltin
Azathioprine
Mycophenolate mofetil
Methotrexate
Chlorambucil
Inihibitors of cell signalling
Ciclosporin
Tacrolimus
Sirolums
MOA:
Ciclosoprin
Tacrolimus
Calcineruin inhibitors
Block IL-2 production
MOA:
Sirolimus
Blocks mTOR pathway
What are the anti-T cell monoclonal antibodies
Murnomab-CD3
Basiliximab
Toilizumab
Abatecept
MOA:
Muromonab-CD3
Blocks CD3 on T cells
MOA:
Basiliximab
Blocks CD25R (alpha chain of Il-2R)
MOA:
Tocilizumab
Blocks IL-6 R
MOA:
Abatecept
Anti CTLA-4 Ig
Blocks costimulation of T cells
MOA:
Prednisolone
Inhibits phosophilapse A2:
Reduces platelet activating factor
Reduced arachidonic acid
Reduced trafficlking of phagocytes (hence transient increase in phagocyte count)
Lymphopenia, apoptosis of T+V cells
MOA:
Ustekinumab
Binds to p40 subunit of IL-12 and IL-23
MOA:
Rituximab
Anti-CD20
Redcues B cells (not plasma cells)
used for lymphoma and autoimmune disease
MOA:
Alemtuzumab
Binds to CD-52
Used in CLL
MOA:
Natalizumab
Anti-a4 integrin
Used in MS and Crohn’s
Side effects:
Cyclophosphamide
Bm suppresswion
Haemorrhagic cystitis
Alopecia
Sterility
Side effects:
Cisplatin
BM suppression
Severe n/v
Nephrotoxic
Ototoxic
Peripheral neuropathy
Side effects:
Azathiorpine
Bm suppression
Hepatotoxicity
n/v/d
Arthralgia
Side effects:
Mycophenolate
BM suppression
Skin malignancy
GI upset
Side effects:
Methotrexate
Pulmonary fiboris
Hepatotoxic
Mucositis
Side effects:
Chlorambucil
BM suppression
EM-> SJS
Side effects:
Ciclosporin
Nephrotoxic
Hepatic dysfunction
Tremor
Hypertrichosis
Gingival hypertrophy
Encephalopathy
Side effects:
Tacrolimus
Nephrotoxic < cf ciclosporin
Diabetogneic
Neurotoxic > cf ciclopsoinr
Side effects:
Sirolimus
Dyslipidaemia
Side effects:
Pred
Diabetes
Central obesity
Adrenal suppression
Cataracts
Glaucoma
Pancreatitis
Osteopororis
Cushingoid
Hirstutism
Neutrophilia
Interactions:
Azathioprine
Allopurinol-> increased toxicity
Interactions:
Methotrexate
Increased toxicity with NSAIDs, ciclosporin, Crohn’s
Interactions:
Ciclosporin
Tacrolimus
P450 inhibitors
Use:
Cyclophosphamide
Cancer
RA
SLE
Systemic sclerois
Wegener’s
Use:
Cisplatin
Cancer
Use:
Azathioprine
Prevent Tx rejection
Steroid sparing agent: IBD, SLE, RA
Use:
Mycophenolate
Prevent Tx rejection
AI disease
Use:
Methotrexate
Cancer
RA
Psoriasis
Crohn’s
Use:
Chlorambucil
Cancer e.g. CLL
Use:
Ciclopsporin
Prevent Tx rejection
GvHD
UC
RA
Psoriasis
Use:
Tacrolimus
Prevent Tx rejection
Additional info:
Cyclophosphamide
Give mensa to prevent haemorrhagic cystitis
Activated by p450
Additional info:
Cisplatin
Carboplatin is associated with less severe SEs
Requires pre-admin hydration
Additional info:
Azathioprine
Do TPMT assay before use
50% of patients intolerant of azathioprine tolerate 6-MP
Additional info:
Methotrexate
Give folinic acid to reduce risk of myelosuppression
Monitor U+E, FBC, LFT
Additional info:
Ciclosporin
Monitor LFTs
What are the important cytotoxic classes
Aklyating agents
Antimetabolites
Cytotoxic Abx
Microtubule inhibitors
Topoisomerase inhibitors
Immune modulators
MAbs
Tyrosine kinase inhibitors
Endocrine modulators
Alkylating agents
Cyclophosphamide
Chlorambucil
Busulfan
Cisplatin
MOA alkylating agents
DNA x-linking
Base mis pairing
Excision of alkylated DNA-> strand breaks
Antimetabolites
Methotrexate
5-FU
Cytotoxic Abx
Anthracycline: doxorubicin, daunorubicin
Bleomycin
MOA cytotoxic Abx
Intercalate with DNA
Free radical formation
MT inhibitors
Vinca alklaoids: vincristine, vinblastine
Taxanes: paclitaxel
Topoisomerase inhibotrs
Etoposide
Immune modualtors
Thalidomide, lenalidomide
Trastuzumab
Anti-Her 2: breast Ca
Bevacizumab
Anti-VEGF
Cetuximab
Anti-EGFR (CRC)
Rituximab
Anti-CD20 NHL
Tyrosine kinase inhiibots
Erlotonib
Imatinib
Sinitimib
Erlotinib
Lung Ca
Imaitinb
CML
Sunitinib
RCC
Common side effects of CTx
N/v: prophylactic anti-emetics
Alopecia
Neutropenia: 10-14d post chemo
Extravasation of chemo agents:
pain, burning brusing at infusion site. Stop infusion, give steroids, apply cold pack. Liaise early with plastics
Hyperuricaemia
Oral mucositis
Specific problems:
Cyclophosphamide
Haemorrhagic cystitis: give mensa
Hair loss
BM suppression
Specific problems:
Doxorubicin and other anthracylcines
Cardiomyopathy
Extravasation reactions
Specific problems:
Bleomycin
Pulmonary fibrosis
Specific problems:
Vincristine
Peripheral neuropathy
Don’t give intrathecal
Specific problems:
Paclitaxel
Peripheral neuropathy
Hypersensitivity
Pre rx with anti-histamines and steroids
Specific problems:
5-FU
Palmar-plantar erythrodysthesia
Mucositis
Mx of chemo-induced emesis
Low risk: domperidone/metoclopramide started pre Rx
High risk:
ondanestron + dex + aprepitant
Breast Ca: FEC
5- FU
Epirubicine
Cyclophospamide
Breast Ca: CMF
Cyclophosphamide
Methotrexate
5-FU
Testicular teratoma: BEP
Bleomycin
Etoposide
cisPlatin
CTx ovarian
Carboplatin
Pacliatzel
R-CHOP
NHL
Ritxuimab
Cyclophosphamide
Hydroxydaunomycin (doxorubicin)
Oncovin
Pred
ABVD
HL
Adriamycin
Bleomycine
Vinblastine
Dacarbazine
Advies with pred
Don’t stop steroids suddenly
Consult doctor when unwell
Increase does with illness or stress
Carry steroid card
Avoid OTcs e.g. NSAID
Osteoporosis and PUD prophylaxis (Ca+ vit D, bisphosphonates, PPI)
SEs of steroids
GI:
Candidiasis, PUD, oesophageal ulceration, pancreastitis
Cardio:
HTN, CCF
MSK:
Proximal myopathy
Osteoporosis
Endo:
Growth suppression, HPA suppression, Cushing’s
Metabolic:
Na and fluid retention
Raised PMN
Reduced K
CNS:
Depression, psychosis
Eye:
Cataracts, glaucoma
Immune:
Increased susceptibility to infection
Liver transplant regime
Tacrolimus
Azathioprine
Pred: withdraw at 3m
Renal transplant regime
Pre-op:
Alemtuzumab
Post op
Pred
Tacrolimus LT
Drugs used in rheumatic disease
5-ASAs
Methotrexate
Hydroxychloroquine
Penicllamine
Infliximab
MOA:
Hydroychloroquine
Reduced activation of dendritic cells
Anti-Gout Drugs
Colchcine
Allopurinol
Feboxustat
Probenecid
Rasburicase
MOA:
Allopurinol
XO inhibitor
MOA:
Feboxustat
XO inhibitor
MOA:
Probenecid
Urcisouric
MOA:
Rasburicase
Recombinant uric oxidase
MOA:
NSAIDs
Non-selective COX inhibitors
Analgesic
Antipyretic
Anti-inflammatory
MOA:
Celecoxib
Selective COX2 I
Rank NSAIDs from least to most toxic
Ibuprofen
Diclofenac
Aspirin
Naproxen
Indomethacin
Ketoprofen
Neuromusuclar durgs
Stigmines
Baclofen
Dantrolene
MOA:
stigmines
Anticholinesterases:
Increase ACh in the synpatic cleft
Enhacne neuromuscular transmission
MOA:
Baclofen
GABA agonist
Skeletal muscle relaxant
MOA:
Dantrolene
Prevents Ca release from sarcoplasmic reticulum
Skeletal muscle relaxant
Side effects:
Hydroxychloroquine
Visual change: rarely retinopathy
Seizures
BM suppression
Side effects:
Penicillamine
Nephrotic syndrome
Drug-induced lupus
Taste change
Side effects:
Infliximab
Severe infectsion
TB
Allergic reactions
CCF
CNS demyelination
Increased AI disease and C
Side effects:
Colchicine
Diarrhoea
Renal impairment
Side effects:
Allopurinol
Severe skin reactions -> SJS
GI upset
Hepatotoxic
Side effects:
Feboxustat
Headache
Rash
Abnormal LFTs
Side effects:
Probenecid
GI upset
Side effects:
NSAIDs
Gastritis and PUD
Reduced GFR
Interstitial nephritis
Papillary necrosis
hyperkalaemia
Peripheral oedema
Bronchospasm
EM-> SJS
Side effects:
Stigmines
Cholinergic
Side effects:
Baclofen
Sedation
Reduced tone
Nausea
Urinary distrubance
Side effects:
Dantrolene
Hepatotoxicity
GI upset
CI:
Hydroxychloroquine
Caution in G6PDD
CI:
Penicillamine
SLE
CI:
Infliximab
TB
CI:
Colchicine
Caution in renal impairment
CI:
Allopurinol
Caution in R + L: reducce dose
CI:
Methotrexate
R+L disease
CI:
Febroxustate
R+L disease
CI:
NSAIDS
Renal or cardiac failure
PUD
Severe hepatic impairment
Caution in: the elderly, asthma
CI:
Celecoxib
IHD
Cerebrovascular disease
L+R disease
CI:
Stigmines
Asthma
Inestinal/urinary obstruction
CI:
Baclofen
PUD
CI:
Dantrolene
Hepatic impairment
Interactions:
Allopurinol
Reduces metabolism of azathioprine: avoid
Interactions:
NSAIDs
Increased bleeding with warfarin
Reduces effects of ACEi and ARBs
Increases toxicity of methotrexate
Interactions:
Celecoxib
Reduces effects of ACEis and ARBs
Increases toxicity of methotrexate
Interactions:
Baclofen
Increased by TCAs
Additional notes:
Hydroxychloroquine
Monitor vision
Additional notes:
Penicillamine
Chelates Cu and Pb
Prevents stones in cystinruia
Additional notes:
Allopurinol
Initial Rx can increase gout
Initiate with NSAID/colchicine cover
Additional notes:
NSAIDs
Can be given with other agents for gastroprotection: PPI, H2Ras, misoprostol
Additional notes:
Celecoxib
Assess CV risk before use
Only used for short periods in young patients with intolerance for other NSAIDs
Additional notes:
Stigmines
Edrophonium preferred for Dx of MG
Pyridostigmine preferred for the Rx of MG (long t1/2)
Additional notes:
Dantrolene
Used to relieve chronic spasiticity and malignant hyperthermia
A 62-year-old man with a history of type 2 diabetes mellitus and ischaemic heart disease presents to his GP with erectile dysfunction. Which one of the following medications would contraindicate the prescription of sildenafil?
Metformin
Isosorbide mononitrate
Gliclazide
Atorvastatin
Clopidogrel
Viagra? - contraindicated by nitrates and nicorandil
Patients taking nitrates cannot take sildenafil concurrently as this may potentiate the vasodilating effects of such drugs
Contraindications to sildenafil
Patients taking nitrates and related drugs such as nicorandil
Hypotension
Recent stroke or MI (NICE recommend waiting 6 months)
Side effects of Sildenafil
Visual disturbances e.g. blue discolouration, non-arteritis anterior ischaemic neuropathy
Nasal congestion
Flushing
GI side-effects
Headache
Aldosterone antagonsits following MI
Patients who have had an acute MI and who have symptoms and or signs of heart failure and left ventricular systolic dysfunction should be treated with an aldosterone antagonist licensed for post-MI therapy e.g. eplerenone 3-14d post MI, preferrably after ACEI therapy
Causes of raised prolactin- the p’s
Pregnancy
Prolactinoma
Physioloical
PCOS
Primary hypothyroidism
Phenothiazines, metocloPramide, domPeridone
(oestrogens, acromegaly)
Drugs causing raised prolactin
Metoclopramide, domperidone
Phenothiazines
Haloperiodl
SSRIs, opioids
What cardiovascular drugs require drug monitoring
Statins
ACEi
Amiodarone
Statin drug monitoring
LFTs at baseline, 3m, 12m
ACEi drug monitoring
U+E,
Prior to treatment
After increasing dose
at least annually
Amiodarone drug monitoring
TFT, LFT
TFT, LFT, U+E, CXR prior to treatment
TFT, LFT every 6m
Rheumatology drugs that require monitoring
Methotrexate
Azathioprine
Methotrexate drug moniotring
FBC, LFT, U+E
The Committee on Safety of Medicines recommend ‘FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months’
Azathioprine drug monitoring
FBC, LFT
FBC, LFT before treatment
FBC weekly for the first 4 weeks
FBC, LFT every 3 months
Neuropsychiatric drugs that require monitoring
Lithium
LFT
Lithium drug monitoring
Lithium level, TFT, U&E
TFT, U&E prior to treatment
Lithium levels weekly until stabilised then every 3 months
TFT, U&E every 6 months
VPA drug monitoring
LFT
LFT, FBC before treatment
LFT ‘periodically’ during first 6 months
Glitazones drug monitoring
LFT before treatment
LFT ‘regularly’ during treatment
Drugs causing pulmonary fibrosis
Amiodarone
Cytotoxic agents: busulphan, bleomycin
Anti-rheumatoid drugs: methotrexate, sulfasalazine, gold
Nitrofurantoin
Ergot-derived dopamine R antagonists: bromocriptine, cabergoline, pergolide
Alpha 1 agonist
Decongestants e.g. phenylephrine/oxymetazoline
Alpha 2 agonist
Topical briminodine in glaucoma
Alpha R antagonist
BPH e.g. tamsulosin
HTN e.g. doxazosin
Beta 1 agonist
Inotropes e.g. dobutamine
Beta 2 agonist
Bronchodilators e.g. salbutamol
Dopamine agonist
PD e.g. ropinirole
Prolactinoma
GABA agonist
BZD
Baclofen
Muscarinic agonist
Glaucoma e.g. pilocarpine
Nicotinic agonist
Nicotine
Varenicline (uesd for smoking cessation)
Depolarising muscle relaxant e.g. suxamethonium
Oxytocin agonist
Inducing labour e.g. syntocinon
Serotonin agonist
Triptans e.g. for acute migraine (zolmitriptan)
Beta 1 antagonists
Non-selective and selective e.g. atenolol and bisoprolol
Beta 2 antagonists
Non-selective beta-blockers e.g. propranolol, labetalol
Dopamine antagonists
Schizophrenia e.g. haloperidol
Anti-emetics e.g.s metoclopramide/domperidone
GABA antagonists
Flumezanil
H1R antagonists
Antihistamines e.g. loratidine
Muscarinic antagonists
Atropine e.g. for bradycardia
Bronchodilator e.g. ipratropium bromide, tiotropium
Urge incontinence e.g. oxybutynin
Nicotinic antagonists
Non-depolarising muscle relaxants e.g. atracruium
Oxytocin antagonists
Tocolysis e.g. atosiban
Serotonin antagonists
Anti-emetics e.g. ondansetron
Where is the site of action of furosemide?
Proximal collecting duct
Ascending loop of Henle
Descending loop of Henle
Distal collecting duct
Macula densa
Loop diuretics
Furosemide and bumetanide are loop diuretics that act by inhibiting the Na-K-Cl cotransporter (NKCC) in the thick ascending limb of the loop of Henle, reducing the absorption of NaCl. There are two variants of NKCC; loop diuretics act on NKCC2, which is more prevalent in the kidneys.
Indications for loop diuretics
heart failure: both acute (usually intravenously) and chronic (usually orally)
resistant hypertension, particularly in patients with renal impairment
Adverse effects of loop diuretics
hypotension
hyponatraemia
hypokalaemia
hypochloraemic alkalosis
ototoxicity
hypocalcaemia
renal impairment (from dehydration + direct toxic effect)
hyperglycaemia (less common than with thiazides)
gout
Submit answer
A 52-year-old man with a history of hypertension is found to have a 10-year cardiovascular disease risk of 18%. A decision is made to start atorvastatin 20mg on. Liver function tests are performed prior to initialising treatment:
Bilirubin10 µmol/l (3 - 17 µmol/l)
ALP96 u/l (30 - 150 u/l)
ALT40 u/l (10 - 45 u/l)
Gamma-GT28 u/l (10 - 40 u/l)
Three months later the LFTs are repeated:
Bilirubin12 µmol/l (3 - 17 µmol/l)
ALP107 u/l (30 - 150 u/l)
ALT104 u/l (10 - 45 u/l)
Gamma-GT76 u/l (10 - 40 u/l)
What is the most appropriate course of action?
Continue treatment and repeat LFTs in 1 month
Check creatine kinase
Reduce dose to atorvastatin 10mg on and repeat LFTs in 1 month
Stop treatment and consider alternative lipid lowering drug
Stop treatment and refer to gastroenterology
Treatment with statins should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range.
Statins and intracerebral haemorrhage
there is some evidence that statins may increase the risk of intracerebral haemorrhage in patients who’ve previously had a stroke. This effect is not seen in primary prevention. For this reason the Royal College of Physicians recommend avoiding statins in patients with a history of intracerebral haemorrhage
Indications for statin
All people with established CV disease
Anyone with QRISK >10%
T2DM: QRISK >10
T1DM: diagnosed >10 years ago or are >40 or have established nephropathy
Side effects of bendroflumethiazide
Gout
Hypokalaemia
Hyponatraemia
Impaired glucose tolerance
Side effects of CCBs
Headache
Flushing
Ankle oedema
Side effects of beta-blockers
Bronchospasm
Fatigue
Cold peripheries
Side effects of doxazosin
Postural hypotension
Drugs to avoid in renal failure
antibiotics: tetracycline, nitrofurantoin
NSAIDs
lithium
metformin
Drugs likely to accumulate in chronic kidney disease - need dose adjustment
most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
digoxin, atenolol
methotrexate
sulphonylureas
furosemide
opioids
Drugs relatively safe - can sometimes use normal dose depending on the degree of chronic kidney disease
antibiotics: erythromycin, rifampicin
diazepam
warfarin
A 34-year-old postman is seen in the Emergency Department following a dog bite to his right hand. What is the most appropriate antibiotic therapy?
Metronidazole + amoxicillin
Erythromycin
Co-amoxiclav
Metronidazole
Flucloxacillin + penicillin
Animal bite - co-amoxiclav
A combination of doxycycline and metronidazole is recommended in the BNF if the patient is penicillin allergic. If facilities are not available to cleanse the wound the patient should be referred to the Emergency Department
Nitrate tolerance
many patients who take nitrates develop tolerance and experience reduced efficacy
the BNF advises that patients who develop tolerance should take the second dose of isosorbide mononitrate after 8 hours, rather than after 12 hours. This allows blood-nitrate levels to fall for 4 hours and maintains effectiveness
this effect is not seen in patients who take modified release isosorbide mononitrate
Adverse effects of thiazide diuretics
Dehydration
Postural hypotension
Hyponatraemia, hypokalaemia, hypercalcaemia
Gout
Impaired glucose tolerance
Importence
Rare adverse effects of thiazide diuretics
Thrombocytopenia
Agranulocytosis
Photosensitivity rash
Pancreatitis
MOA Thiazides
Thiazide diuretics work by inhibiting sodium absorption at the beginning of the distal convoluted tubule (DCT). Potassium is lost as a result of more sodium reaching the collecting ducts. Thiazide diuretics have a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide was in the management of hypertension but recent NICE guidelines now recommend other thiazide-like diuretics such as indapamide and chlortalidone.
A 69-year-old man with terminal lung cancer is reviewed. He currently takes MST 60mg bd for pain. He has become unable to take oral medications and a decision is made to set-up a syringe driver. What dose of diamorphine should be prescribed for the syringe driver?
60 mg
40 mg
120 mg
30 mg
20 mg
To convert from oral morphine to diamorphine the total daily morphine dose (60 * 2 = 120mg) should be divided by 3 (120 / 3 = 40mg)
MOA phenytoin
Binds to Na channels increasing their refractory period
How can the adverse effects of phenytoin be classified?
Acute
Chronic
Idiosyncratic
Teratogenic
Acute adverse effects of phenytoin
Initially: dizziness, diplopia, nystagmus, slurred speech, ataxia (i.e. cerebellar signs)
Later: confusion, seizures
Chronic adverse effects of phenytoin
Common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, histutism, coarsening of facial featrues, drowsiness)
Megaloblastic anaemia (secondary to altered folate metabolism)
Peripheral neuropathy
Enhanced Vit D metabolism causing osteomalacia
Lymphadenopathy
Dyskinesia
Idiosyncratic adverse effects of phenytoin
Fever
Rashes including TEN
Hepatitis
Dupuytren’s contracture
Aplastic anaemia
Drug-induced lupus
Teratogenic effects of phenytoin
Cleft palate and congenital heart disease
Monitoring of phenytoin
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
A 52-year-old man presents to his GP as he is concerned about a discharge from his nipples. Which one of the following drugs is most likely to be responsible?
Ranitidine
Isoniazid
Digoxin
Spironolactone
Chlorpromazine
Chlorpromazine
Each of the other four drugs may be associated with gynaecomastia rather than galactorrhoea
Theme: Side-effects of diabetes mellitus drugs
A.Metformin
B.Acarbose
C.Glimepiride
D.Nateglinide
E.Pioglitazone
F.Diazoxide
G.Repaglinide
Select the drug most likely to cause each one of the following side-effects
Syndrome of inappropriate ADH secretion
Lactic acidosis
Fluid retention
Sulphonylurea i.e. glimepiride
Metformin
Pioglitazone
A 70-year-old lady presents to your GP clinic complaining of ankle swelling. The swelling is present throughout the day but worse in the evenings and is causing significant discomfort to the patient. The swelling began last month. She has no other symptoms. There is no past medical history of cardiovascular disease, diabetes mellitus or hyperlipidaemia. The patient has never smoked. The patient began treatment last month with amlodipine 5mg once daily for stage 2 hypertension. On examination her blood pressure is 135/90 mmHg, heart sounds are normal, jugular venous pulse is non-elevated, and respiratory examination is normal. Examination of the lower limbs reveals bilateral peripheral oedema with no other abnormalities.
What is the best treatment for the patient’s ankle oedema?
Prescribe furosemide
Swap amlodipine to furosemide
Prescribe indapamide
Recommend lifestyle modifications
Swap amlodipine to indapamide
Peripheral oedema is a common side effect of calcium blockers and the clinical picture is very suggestive of this. As the oedema is causing the patient concern then it would be appropriate to swap the amlodipine for a second line anti-hypertensive diuretic agent (e.g. indapamide). This helps to prevent polypharmacy and any further side effects/complications from adding an additional drug. If this does not resolve the oedema then further investigations would be required to identify the cause.
Recommending lifestyle modifications would likely offer partial relief to the patient, but since it is affecting her throughout the day and night this is not a practical solution as would substantially affect her quality of life. However, lifestyle recommendations would also be advisable in addition to swapping amlodipine to indapamide.
What are the dihydropyridine CCBs?
Nifedipine
Amlodipine
Felodipine
What are the non-dihydropyridine CCBs?
Verapamil
Diltiazem
Indications for verapamil
Angina, HTN, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block
Side effects/CI of verapamil
HF
Constipation, hypotension, bradycardia, flushing
Side-effects/CI of diltiazem
Hypotension, bradycardia, heart failure, ankle swelling
Side effects of dihydropyridine CCBs
Flushing, headache, ankle swelling
MOA
Frusemide
Bumetanide
Loop diuretics
Inihibta NaKCl triple transporter in ascending loop of henle-> increased NaCl excretion
MOA:
Bendofluazide
Metolazone
Chortalidone
Thiazide diuretics
Inhibt NaCl transporter in DCT
Increase NaCl excretion
MOA:
Spironolactone
Elperenone
Aldosterone R antagonists
Increase Na excretion
Reduce K and H excretion
MOA:
Amiloride
Triamterine
Block Na channels in collecting tubules
Increase Na excretion
Reduce K and H excretion
MOA:
Acetazolamide
Carbonic anhydrase inhibotr
Increase HCO3 excretion
MOA:
Mannitol
Osmotic diuretic
Side effects:
Loop diuretics
Reduced Na
Reduced K
Reduced Ca
Reduced Mg
Raised urate
Postural hypotension
Tinnitus/deafness (rare)
Side effects:
Thiazide diuretics
Reduced Na
Reduced K
Raised Ca
Raised urate
Postural hypotension
Impaired glucose tolerance
Side effects:
Aldosterone R antagonists
Raised K
Gynaecomastia
Side effects:Side effects:
Amiloride
Triamterine
Raised K
GI upset
Side effects:
Acetazolimide
Rash: EM-> SJS
Peripheral tingling
Contraindications:
Loop diuretics
Refractory hypokalaemia
Anuric renal failure
Contraindications:
Thiazide diuretics
Refractory hypokalaemia
Gout
Severe renal failure
Contraindications:
Aldosterone R antagonists
Raised K
Raised P
Addison’s
Contraindications:
Acetazolamide
Sulfonamide hypersensitvity
Interactions of:
Loop diuretics
Increased toxicity of:
digoxin (due to hypokalaemia)
NSAIDs
Gent
Li
Interactions of:
Thiazide diuretics
Increased toxicity of:
digoxin
Li
Interactions of:
Aldosterone R antagonsits
Increased toxicity of:
digoxin
Li
Additional notes:
Loop diuretics
Monitor U+Es
May add K sparing diuretic to reduce K loss
Additional notes:
Aldosterone antagonists
Spiro doses:
25mg OD for HF
100-400mg OD for diuresis
Additional notes:
Amiloride
Typically used in combination with K-wasting diuretics
Additional notes:
Acetazolamide
Sulphonamide
Used in open/closed angle glaucoma
MOA:
-prils
ACEi
Inhibit conversion of AngI-> AngII
MOA:
-artans
ARBs
AngII R antagonists
Don’t inihbit kinin breakdown- therefore no cough
Side effects:
ACEi
Hypotension: especially with diuretics, HF
RF
Hyperkalaemia
Dry cough: 10-20% (secondary to raised bradykinin)
Angioedema
Side effects:
ARBs
As for ACEi but no cough
Contraindications:
ACEI
Suspected or confirmed bialteral RAS
Angioedema/hypersensivity to ACEi
Salt substitutes (contain K) P/B
Contraindications:
ARB
P/B
Caution in RAS
Interactions:
ACEI
Increased risk of renal failure with NSAIDs
Diuretics, TCAs and antipsychotics-> increased risk of hypotension
Caution when used in conjunction with drugs that raie K
Interactions: ARB
As for ACEi
Additional notes for ACEI
Monitor U+Es: raise in creatinin >30%-> MRA
Titrate dose
Avoid in young women who might become pregnant: consider beta blockers
Reduce dose in renal failure
Phyisology of the renin angiotensin system
Angiotensinogen is an a2-globulin released by liver
Renin from the JGA converts angiotensinogen-> AngI
ACE is produced by pulmonary epithelial cells and converts AngI-> AngII
AngII acts via AT1R:
Vasoconstriction
Sympathetic activation
Aldosterone release from adrenal coretx
Increased renal Na absorption
ADH release
Ang2 is degraded by angiotensinases in RBCs
Principle indications for drugs affectingt the RAAS
HF
HTn
Post-MI
Angina
Diabetic nephropathy
Physiology of beta 1 receptors
Heart: increase rate and contractility
Kidney: increase renin release from JGA
Physiology of B2 Rs
Bronchi, GI: SM relaxation
Skeletal muscle: arteriolar dilatation
Liver + skeletal muscle: glycogenolysis and gluconeogenesis
Physiology of B3Rs
Adipose tissue: lipolysis
Pharamacology of beta blockers
Some beta-blockers have arteriorlar dilating effects which reduce TPR through blocking a1 R (e.g. carvedilol, labetalol, nebivolol)
Cardioselective agents have redcuced B2 effects
ISA (intrinsic sympathomimetic activity): partial agonist activity at adrenoreceptors: reduce bradycardia, reduce cold extermitites
Lipophilic compounds are more likely to lead to CNS effects- propranolol, metoprolol
Hydrophillic compounds may accumulate in renal failure: atenolol, sotalol
Esmolol is V short acting and used IV
Principle indications for beta blockers
Angina
HF
Acute MI
Arrhythmias
HTN
LongQT
Prophylaxis vs variceal haemorrhage
Migraine prophylaxis
Thyrotoxicosis
Glaucoma
Anxiety
What are the cardioselective beta blockers
Bisoprolol
Atenolol
Metoprolol
Esmolol
Nebivolol
What class of beta blockers are
Bisoprolol
Atenolol
Metoprolol
Esmolol
Nebivolol
Cardioselective
What are the non-selective beta blockers
Carvedilol
Propanolol
Sotalol
Labetalol
What class of beta blockers are
Carvedilol
Propanolol
Sotalol
Labetalol
Non-selective
What are the beta blockers with ISA?
Acebutolol
Pindolol
Oxprenolol
What are the vasodilating beta blockers
Carvediolol
Labetaolol
Nebivolol
MOA: beta blockers
Block beta Rs
Actiions via Beta 1: reduce CO
Reduce HR
Reduce contracility
Small reduction in BP: central effect + reduce renin
Effects:
Increase diastolic perfusion
Reduce O2 demand
Reduce afterload
Side-effects of beta blcokers
Bronchospasms inc. cardioselective
Reduced HR and BP
Peripheral vasonconstiction: cold extremities
Worsened Raynaud’s/PVD
Lethargy/fatigue
Nightmares
Metabolic:
Reduce HDL
Raised TGs
Increased risk of new onset DM (especially with thiazides)
Contraindications to beta blockers
Asthma/bronchospasm
PVD
Severe bradyacrdia
Severe HF
2nd/3rd degree AV block
Caution in DM as increased likelihood of hypoglycaemia and can mask symptoms
Reduce dose in renal impairment
May reduce dose in hepatic impairment
Interactions of beta blockers
Verapamil and diltiazem (risk of AV block and reduced HR)
Enhanced antihypertensive effects with other anti-HTN drugs
Block symptoms of hypoglycaemia with insulin
Additional notes: beta blockers
Propranolol is very lipid soluble and easily crosses the BBB-> CNS effects (nightmares)
Atenolol is water soluble and doesn’t cross the BBB
What are the non-selective alpha blockers
Phenoxybenzamine
Phenotalmine
What are the alpha 1 R blockers
Dozazosin
Prazosin
MOA:
Phenoybenzamine
Phentolamine
Doxazosin
Prazosin
Alpha blockers
A1:
systemic vasodilation
Relaxation of internal urethral sphincter
Effect of alpha 2 R
The α2-adrenergic receptor is classically located on vascular prejunctional terminals where it inhibits the release of norepinephrine (noradrenaline) in a form of negative feedback.[3] It is also located on the vascular smooth muscle cells of certain blood vessels, such as those found in skin arterioles or on veins, where it sits alongside the more plentiful α1-adrenergic receptor.[3] The α2-adrenergic receptor binds both norepinephrine released by sympathetic postganglionic fibers and epinephrine (adrenaline) released by the adrenal medulla, binding norepinephrine (noradrenaline) with slightly higher affinity.[4] It has several general functions in common with the α1-adrenergic receptor, but also has specific effects of its own. Agonists (activators) of the α2-adrenergic receptor are frequently used in veterinary anaesthesia where they affect sedation, muscle relaxation and analgesia through effects on the central nervous system (CNS).[5]
MOA:
Clonidine
Centrally acing alpha2 agonist
Reduced CO
Reduced PVR
MOA:
Methyldopa
Centrally acting alpha 2 agonist
Prodrug-> alpha methyl NA
MOA:
Hydralazine
Vasodilator
arteries>veins
MOA:
Nitroprusside
Vasodilator
arteries>veins
MOA:
Minoxidil
Vasodilator
Side effects:
Alpha 1 R antagonists
Postural hypotension
Dizziness
Headache
Urinary incontinence (especially women)
Blurred vision
Side effects:
Clonidine
Rebound HTN or withdrawal
Postural hypotension
Vonstipation
Nausea
Dry mouth
Side effects:
Methyldopa
Blood dyscrasias
Hepatotoxic
Drug-induced lupus
Drowsiness
Side effects:
Hydralazine
Drug induced lupus
Increased HR
GI upset
Headache
Side effects:
Minoxidil
Hypertrichosis
Contraindications:
alpha blockers
Breastfeeding
Contraindications:
Methyldopa
Liver disease
Depression
Contraindications:
Hydralazine
SLE
Reduce dose in hepatic or renal impairment
Interactions:
alpha blockers
Increase hypotensive effects of
diuretics
beta blockers
CCBs
Interactions:
Methyldopa
Avoid within 2w of MAOI
Additional notes:
Alpha blockers
Phentolamine is short-acting and can be used to control BP in phaeo
Phenoxybenzamine is long acting and can be used to maintain alpha blockade once BP controlled
Doxazosin and tamsulosim are used in Rx of BPH
Additional notes:
Methyldopa
Hydralazine
Mainly used in pregnancy
Additional notes::
Nitroprusside
Hypertensive crisis
MOA of CCBs
Bind alpha subunit of type-L Ca channel at distinct sites
Prevent channel opening and inhibit Ca entry
Effects of CCBs
All CCBs are vasodilators and reduce afterload.
Also dilate coronary arteries
Pre-capillary vasodilation-> transudative oedema
Dihydropiridines act only @ arterial Sm and can lead to reflex tachycarda, avoid short acting preparations
Verapamil is highly negatively inotropic: CI in HF and with beta blockers
Verapamil is also negatively chronotropic
Diltiazem is less negatively inotropic and chronotropic than verapamil
Indications for verapamil and diltiazem
HTN
Angina
AF
Indications for nifedipine MR and amlodipine
HTN (long acting)
Angina: esp. good for Prinzemtal’s
Raynaud’s
What are the dihydropyridine CCBs?
Nifedipine
Amlodipine
What are the non-dihydropiridines?
Diltiazem
Verapamil
MOA:
Dihydropyridines
Mainl arterial SM activity
Vasodilation (inc. coronary)
Particularly pre-capillary arterioles
Reduced TPR-> increased sympathetic tone-> increased HR
MOA:
non-dihydropyriines
Mainly cardiac activity
Negative inotropic effect (esp. verapamil)
Verapamil also slows conduction at SA and AV nodes
Some activity at arterial SM
Side-effects:
Dihydropyridines
Flushing
Headache
Ankle oedema (especially amlodipine)
Dizziness
Hypotension
Gingival hypertrophy (esp. nifedipine)
Side-effects:
Non-dihydropyridines
Headache
Flushing
AV block
HF
Reduced BP
Ankle oedema
Constipation
Gynaecomastia (verapamil)
Contraindications:
Dihydropyridines
Cardiogenic shock
Unstable angina
Significant AS
Within 1m of MI
Contraindications:
Non-dihydropyridines
HF
2nd/3rd degree AV block
Interactions:
Dihydropyridines
Risk of reduced BP with alpha/beta-blockers
Fx increased by grapefruti
Fx reduced by: rifampicin, CBZ + phenytoin
Nifedipine only: increases effects of digoxin
Interactions:
Non-dihydropyridines
Risk of AB block, HF and asystole with beta blockers
Increases effects of digoxin
Fx of verapamil increased by:
grapefruit juice
macrolides
Increased risk of myopathy with simvastatin
Additonal notes:
Dihydropyridines
Indications:
Angina
Prinzmetal’s angina
HTN
Raynaud’s
Additonal notes:
Non-dihydropyridines
Indications:
Angina
HTN
Arrhythmias (verapamil)
MOA:
GTN
NO donor with rapid onset and short duration (30 minutes)
High FPM
Mainly venodilation-> reduced preload
Small increase in coronary vasodilation
MOA:
ISMN/ISDN
Long-acting nitrates
ISMN is active metabolite of ISDN
MN avoids unpredictable FPM of DN
Tolerance develops quickly: need 8h drug free period (usually at night)
Side effects of nitrates
Reduced BP (inc postural)
Headache
Syncope
Dizziness
Flushing
Reflex tachycardia
Contraindications to nitrates
AS and MS
Reduced BP
Constrictive pericarditis
Tamponade
HOCM
Reduced Hb
Glaucoma (closed)
Hypovolaemia
Raised ICP
Interactions of nitrates
Sildenafil, tadakafil and vardenefil are all CI due to reduced BP
Recued effects of heparin if given IV
Additonal notes GTN
SL spray or tabs
300ug
Used for relief of pain in angina, ACS
MOA:
Nicorandil
K+ATP channel activator + nitrate component
Arterial and venous dilator
MOA:
Ivabradine
Inhibits funny current in SAN-> reduced pacemaker activity-> reduced HR
MOA:
Trimetazidine
Inhibits fatty acid oxidation-> increased myocardial glucose use
MOA:
Ranolazine
Inhibits late Na current
Side-effects:
Nicorandil
Headache
Flushing
Dizziness
GI ulcers
Side-effects:
Ivabradine
Visual changes
Reduced HR and HB
Contraindications:
Nicorandil
Cardiogenic shock
Contraindications:
Ivabradine
Reduced BP or HR
ACS
Strong CYP inhibitor
Interactions:
Nicorandil
Sildenafil-> low BP
Interactions:
Ivabradine
Subject to hepatic induciton/inhibition
Inidcations:
Nicorandil
Uncontrolled angina
Inidcations:
Ivabradine
Angina (useful if beta-blocker CIed)
Inidcations:
Trimetazidine
Angina
Inidcations:
Ranolazine
Angina
MOA Warfarin
Inhibit Vit K epoxide reductase
Prevents recycling of Vit K-> functional Vit K deficiency
Inhibits synthesis of factors 2, 7, 9, 10, C and S
Initially procoagulant as protein S is depleted first
Indications for Warffarin
Treatment:
VTE
Prophylaxis:
VTE
AF
Mechanical heart valves
Large anterior MI
Dilated cardiomyopathy/LV aneurysm
Patients with Ca-associated VTE should be treated for 6m with therapeutic dose of LMWH rather than warfarin
Pharmacokinetics of warfarin
Long t1/2: 40hrs
Takes 16h to affect INR
Peak INR effect of a dose seen @ 2-3d
Effect of a given dose lasts 4-5d
Highly albumin bound
CyP metabolism
Side effects of Warfarin
Haemorrhage, bruising
Skin necrosis (due to protein S deficiency)
Purple toe syndrome (cholesterol embolism)
Osteoporosis
Hepatic dysfunction
Cautions in Warfarin use
Hepatic impairment: avoid if severe
Renal impairment: avoid if severe
Alcoholics
CI to Warfarin
Pregnacny: teraogenic in 1st trimester, foetal haemorrhage in 34d
PUD
Severe
HTN
Caution if R/L, recent surgery, risk of falls
Interactions leading to increased warfarin effects
Enzyme inhibitors
EtOH
Simvastatin
NSAIDs
Dipyridamole
Amiodraone
Abx (may also reduce)
Cranberry juice
Interactions leading to reduced Warfarin effects
CBZ
Rifampicin
OCP
Phenyotin
Barbs
St John’s Wort
INR target:
DVT prophlyaxis
2-2.5
INR target:
Calf DBT
2.5
INR target:
Above knee DVT
2.5
INR target:
PE
2.5
INR target:
Recurrent DBT/PE
- 5
- 5 if happen on warfarin
INR target:
Mitral valve disease
2.5
INR target:
Antiphospholipid
3.5
INR target:
Metal heart valve
3.5
Warfarinduration:
Calf DVT
Cause known: 6w
No cause: 3m
Warfarin duration:
Above knee DVT
Cause known: 3m
No cause: 6m
Warfarin duration:
PE
Cause known: 3m
No cause: 6m
Warfarin duration:
Recurrent DVT/PE
Indefinite
Warfarin duration:
AF
Indefinite
Warfarin duration:
Mitral valve disease
Indefinite
Warfarin duration:
Antiphospholipid syndrome
Indefinite
Warfarin duration:
Metal valves
Indefinite
Vit K dependent factors mneumonic
1972
Factors precipitating digoxin toxicity
classically: hypokalaemia*
increasing age
renal failure
myocardial ischaemia
hypomagnesaemia, hypercalcaemia, hypernatraemia, acidosis
hypoalbuminaemia
hypothermia
hypothyroidism
drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in distal convoluted tubule therefore reduce excretion), ciclosporin. Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics
Acid base disturbance in salicylate overdose
A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate
Indications for haemodilaysis in salicylates
serum concentration > 700mg/L
metabolic acidosis resistant to treatment
acute renal failure
pulmonary oedema
seizures
coma
Side effects (malaria prophylaxis):
Atovaquone + proguanil
GI upset
Side effects (malaria prophylaxis):
Chloroquine
Headache
Contraindicated in epilepsy
Taken weekly
Side effects (malaria prophylaxis):
Doxycycline
Photosensitivity
Oesophagitis
Side effects (malaria prophylaxis):
Mefloquine
Dizziness
Neuropsychiatric distrubance
Contraindicated in epilepsy
Taken weekly
Time to begin and end malaria prophylaxis during travel:
Atovaquone + proguanil
1-2d
7d
Time to begin and end malaria prophylaxis during travel:
Chloroquine
1w
4w
Time to begin and end malaria prophylaxis during travel:
Doxy
1-2d
4w
Time to begin and end malaria prophylaxis during travel:
Mefloquine
2-3w
4w
Time to begin and end malaria prophylaxis during travel:
Proguanil
1w
4w
Time to begin and end malaria prophylaxis during travel:
Proguanil and chloroquine
1w
4w
Which antimalarial should be give with folate supplementation to pregnant women
Proguanil
A 25-year-old woman is diagnosed with a urinary tract infection. She has a past history of epilepsy and is currently taking sodium valproate. Which one of the following antibiotics should be avoided if possible?
Co-amoxiclav
Nitrofurantoin
Cefixime
Trimethoprim
Ciprofloxacin
Whilst many antibiotics can lower the seizure threshold, this effect is seen particularly with quinolones. The BNF advises that quinolones ‘should be used with caution in patients with a history of epilepsy, or conditions that predispose to seizures’
A 77-year-old male is recovering on the ward after being admitted with a community acquired pneumonia. He has finished a course of antibiotics and his latest chest radiograph is clear. He is currently awaiting social services input before discharge. On the morning ward round the patient complains of new symptoms of muscle pain, weakness and tiredness. He feels nauseous and has vomited once this morning. He has a past medical history of osteoarthritis, gout, type 2 diabetes, hypercholesterolaemia, atrial fibrillation and an appendicectomy as a child. He is currently taking regular paracetamol, allopurinol, metformin, simvastatin, bisoprolol and warfarin.
On examination his respiratory rate is 25/min, blood pressure is 131/85 mmHg, heart rate is 95 bpm and temperature is 36.4ºC.
Recent blood tests show:
Na+140 mmol/l
K+4.8 mmol/l
Urea12 mmol/l
Creatinine190 µmol/l
eGFR26 ml/min
Creatine kinase174 iu/l (normal range 25-195 iu/l)
CRP12 mg/l
A recent arterial blood gas (ABG) shows:
pH7.29
pO212.1 kPa
pCO24.4 kPa
Bicarbonate18 mmol/l
What is the most likely cause of these symptoms and investigation results?
Simvastatin
Metformin
Gout
Pneumonia
Allopurinol
Metformin can cause lactic acidosis in patients with impaired renal function. NICE recommend that the dose should be reviewed in patients an eGFR<45 ml/min and stopped in patients with an eGFR<30 ml/min. The patient here is on metformin and has an eGFR<30 ml/min with an ABG showing a non-hypoxic metabolic acidosis. His symptoms are also typical of metabolic acidosis.
While statins do pose a risk of rhabdomyolysis, which would also produce symptoms of muscle pain, the normal creatinine kinase excludes this. It also does not explain the abnormal ABG.
The other options are inconsistent with the presentation and blood results.
Drug causes of gingival hyperplasia
Phenytoin
Ciclosporin
CCBs (especially nifedipine)
Drugs causing corneal opacities
Amiodarone
Indomethacine
Drugs causing optic neuritis
Ethambutol
Amiodarone
metronidazole
A 66-year-old woman comes to see you as he has ongoing symptoms of dyspepsia which are relieved by omeprazole. He has been using omeprazole 20 mg once a day for the past 2 years.
Which one of the following is a disadvantage of using a proton-pump inhibitor (PPI) long-term?
Increased risk of myocardial infarction
Increased risk of stroke
Increased risk of fractures
Increased risk of liver impairment
Increased risk of developing diabetes
The BNF states that PPI’s are used at the lowest effective dose for the shortest period and the need for long-term treatment should be reviewed periodically.
Long-term use of PPI’s can mask the symptoms of gastric cancer. They can also increase the risk of osteoporosis and fractures -due to malabsorption of calcium and magnesium.
A 24-year-old woman presents following a sudden, acute onset of pain at the back of the ankle whilst jogging, during which she heard a cracking sound. Which one of the following medications may have contributed to this injury?
Metronidazole
Nitrofurantoin
Fluconazole
Ciprofloxacin
Terbinafine
This patient has classical signs of Achilles tendon rupture. Tendon damage is a well documented complication of quinolone therapy. It appears to be an idiosyncratic reaction, with the actual median duration of treatment being 8 days before problems occur
A 62-year-old man visits his GP with some enlarging of his chest. He is quite embarrassed and thinks that he is developing breast tissue. You examine him and find nothing sinister other than bilateral gynaecomastia. His medical history includes hypertension, high cholesterol, type 2 diabetes and benign prostatic hyperplasia
Which of the following medication is most likely to cause this condition?
Metformin
Gliclazide
Ramipril
Finasteride
Simvastatin
There are a number of causes of gynaecomastia in males and it is important to rule out sinister ones such as kidney failure, endocrine disturbances, liver failure or malignancy.
Another key cause is medication related, in this case the finasteride taken by this patient can cause gynaecomastia.
Finasteride works by blocking 5-alpha-reductase inhibitors those reducing the production of dihydrotestosterone and therefore shrinking the prostate, however side effects can include gynaecomastia and sexual dysfunction.
A patient develops a broad complex tachycardia two days following a myocardial infarction. Intravenous amiodarone is given. Which one of the following best describes the mechanism of action of amiodarone?
Blocks potassium channels
Shortens QT interval
Blocks sodium channels
Opens sodium channels
Blocks calcium channels
Amiodarone - MOA: blocks potassium channels
Cx of opioid abuse
Viral infection 2o to sharing needles
Bacterial infection 2o to injection
VT
OD may lead to respiratory depression and death
Psychological problems
Social problems
rhinorrhoea
pinpoint pupils
drowsiness
watering eyes
yawning
Opioid misuses
5-HT3 antagonists
5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy related nausea. They mainly act in the chemoreceptor trigger zone area of the medulla oblongata.
Examples
ondansetron
granisetron
Adverse effects
constipation is commo
What are the factors that increase the risk of developing hepatotoxicity following paracetamol OD?
Patients taking liver enzyme-inducing drugs
Malnourished patients
Patients who have not eaten for days
O2 therapy in COPD patients
Management of COPD patients
prior to availability of blood gases, use a 28% Venturi mask at 4 l/min and aim for an oxygen saturation of 88-92% for patients with risk factors for hypercapnia but no prior history of respiratory acidosis
adjust target range to 94-98% if the pCO2 is normal
A 54-year-old man with a history of epilepsy and ischaemic heart disease is seen in clinic with a 3 month history of lethargy. Blood tests are as follows:
Hb9.6 g/dl
MCV123 fl
Plt164 * 109/l
WCC4.6 *109/l
Which one of his medications is most likely to be responsible?
Clopidogrel
Atorvastatin
Carbamazepine
Atenolol
Phenytoin
Phenytoin may cause a megaloblastic anaemia by altering folate metabolism
Adverse effects of ciclosporin
(note how everything is increased - fluid, BP, K+, hair, gums, glucose)
nephrotoxicity
hepatotoxicity
fluid retention
hypertension
hyperkalaemia
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlipidaemia
increased susceptibility to severe infection
A 57-year-old woman is referred to urogynaecology with symptoms of urge incontinence. A trial of bladder retraining is unsuccessful. It is therefore decided to use an muscarinic antagonist. Which one of the following medications is an example of a muscarinic antagonist?
Tolterodine
Teriparatide
Toremifene
Finasteride
Tamsulosin
Other examples of muscarinic antagonists used in urinary incontinence include oxybutynin and solifenacin. Examples of muscarinic antagonists used in different conditions include ipratropium (chronic obstructive pulmonary disease) and procyclidine (Parkinson’s disease).
Tamsulosin is an alpha blocker.
An 85-year-old female is admitted under the general medical unit with acute thoracic back pain from a T6 crush fracture following a fall. She has a past history of systolic heart failure, depression and osteoporosis.
Her regular medications included aspirin, frusemide, spironolactone, bisoprolol, sertraline and calcium, vitamin D and weekly alendronate. These are continued throughout her admission.
Two days into her admission, the nurses note that she is agitated and a bit confused.
On examination, she looks flushed and is tachycardic with a heart rate of 120 beats/min and is hypertensive with a blood pressure of 185/70 mmHg, but is afebrile. Both her pupils are mildly dilated, she is mildly tremulous and is noted to have deep tendon hyperreflexia with easily inducible clonus.
Use of which of the following analgaesic medication could explain her current symptoms?
Paracetamol
Ibuprofen
Oxycodone
Tramadol
Hydromorphone
Serotonin syndrome is a disorder characterised by serotonin excess, usually due to the use of 2 or more serotonergic drugs. Manifestations of the syndrome include changes in mental status, neuromuscular changes and autonomic overactivity. Clinically, this can be observed as hypertension, tachycardia, flushing and sweating, hyperflexia, clonus and muscle rigidity. Other potential signs include fever and changes in mental status, including agitation.
Serotonergic drugs that are associated with serotonin syndrome include tramadol, selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI), triptans and St Johns wort.
The management of serotonin syndrome involves discontinuation of all serotonergic drugs and supportive care. If required, benzodiazepine can be administered to control agitation. In moderate to severe cases, 5-HT antagonists (e.g. cyproheptadine and chlorpromazine) are sometimes administered.
When to take lithium levels
12hrs post dose
When to take ciclosporin levels
Trough levels immediately before dose
When to take digoxin levels
At least 6h post-dose
A 83-year-old woman presents with increasing confusion, decreasing mobility and weakness in her left leg. She has a past medical history of atrial fibrillation, hypothyroidism and hypertension. Her GP recently prescribed ciprofloxacin for a urinary tract infection. Her INR three weeks ago was 2.4 and it has been stable since beginning treatment. Her current medication includes: warfarin, levothyroxine, perindopril, St John’s Wort and furosemide. A diagnosis of subdural haematoma is suspected and this is confirmed by CT brain.
What drug may have precipitated the haemorrhage?
Ciprofloxacin
Perindopril
Furosemide
Levothyroxine
St John’s Wort
Ciprofloxacin is a synthetic fluoroquinolone with a broad antimicrobial spectrum. Fluoroquinolones have been reported to enhance the effect of warfarin, and appropriate laboratory tests should be routinely monitored. The exact mechanism of the warfarin-ciprofloxacin interaction is unknown. Ciprofloxacin is postulated to affect gut flora, displace warfarin from albumin, and interfere with hepatic metabolism by inhibiting the cytochrome P-450 enzyme system
Vincent, 28, has treatment resistant schizophrenia, with his usual symptoms being auditory hallucinations and persecutory delusions. He was recently prescribed clozapine, fluoxetine and lactulose. He has been complaining of constipation recently, but now presents to the emergency department with acute abdominal pain and vomiting. On examination abdomen is distended. What is the most likely cause?
Intestinal obstruction
Appendicitis
Constipation
A bezoar
Ingestion of foreign object
The most likely cause of this patients presentation is intestinal obstruction. Intestinal obstruction is one of the more under-recognised complications of clozapine therapy, yet one of the more serious. Gastric hypomotility is common in patients who are treated with clozapine, and its presentation can range from a simple constipation to more severe conditions such as intestinal obstruction, bowel ischaemia and necrosis.
The important pieces of information to consider when answering this question are the recent prescription of clozapine, the presence of constipation previous to current presentation, and his physical presentation of acute abdominal pain and vomiting with distension. When answering a question such as this, recent prescriptions of medications prior to the deterioration of their physical condition should raise the thought that maybe one of the medications is causing the symptoms. In this scenario, the patient has recently been prescribed clozapine, fluoxetine and lactulose. Therefore, considering each of these medications and their side effects is a must.
The patients presentation, and recent past medical history, provides a good indication of what could be the underlying issue. The patient has presented with acute abdominal pain and vomiting. When you consider this with the recently experienced constipation, it becomes clear that this patient is likely suffering from an obstruction, as opposed to the other options on offer.
Constipation would be an inappropriate answer to this question. Although he has had constipation recently, and abdominal pain could be a presentation of constipation, vomiting is not generally observed in constipation. This would means that this diagnosis is less likely.
Bezoars are indigestible masses that become trapped in the gastrointestinal tract. They can occur when individuals consume a variety of items, including hair, soil, chewing gum etc. These items form a mass, which ultimately becomes lodged in the gastrointestinal tract, often requiring surgical intervention to relieve the obstruction. The symptoms that the patient in this scenario has experienced could be explained by a bezoar, however, we do not have any evidence that he consumes any items that may lead to a bezoar. Furthermore, the recent commencement of clozapine means that we cannot select a bezoar as the most likely cause of this patients symptoms above intestinal obstruction. Similarly, we do not have any evidence that the patient ingests foreign objects, meaning that this cannot be classed as a likely cause in this question.
Appendicitis could explain the acute presentation of this patient. However, the fact that the patient experienced constipation prior to him developing acute abdominal pain and vomiting means that appendicitis is less likely.
A 72-year-old man with metastatic small cell lung cancer is admitted to the local hospice for symptom control. His main problem at the moment is intractable hiccups. What is the most appropriate management?
Chlorpromazine
Codeine phosphate
Diazepam
Methadone
Phenytoin
Management of hiccups
chlorpromazine is licensed for the treatment of intractable hiccups
haloperidol, gabapentin are also used
dexamethasone is also used, particularly if there are hepatic lesions
A 23 year old male presents to his GP with a history of hallucinations, schizophrenia, and anxiety.
Misuse of Drugs Regulation 2001 divides controlled drugs into 5 Schedules. Which of the following drugs fall into Schedule 1, and therefore cannot be used, unless with a controlled drug license?
Cocaine
Cannabis
Midazolam
Anabolic steroids
Codeine
Schedule 1 includes drugs that can only be used with controlled licence i.e. permission from Home Secretary. Includes LSD and cannabis
Schedule 2 - Special permission for storage of the drug is required. Includes heroin, cocaine, amphetamines
Schedule 3 - Controlled with no register, includes Barbituates, midazolam,
Schedule 4 - No need safety custody or register but all invoices needed and proper destruction - anabolic steroids, some benzodiazepines
Schedule 5 - Drug invoices only needed - e.g. codeine
A 67-year-old with chronic kidney disease stage 4 and metastatic prostate cancer presents as his pain is not controlled with co-codamol. Which one of the following opioids is it most appropriate to use given his impaired renal function?
Buprenorphine
Morphine
Hydromorphone
Diamorphine
Tramadol
Alfentanil, buprenorphine and fentanyl are the preferred opioids in patients with chronic kidney disease.
Which one of the following drugs is not associated with galactorrhoea?
Metoclopramide
Bromocriptine
Chlorpromazine
Haloperidol
Domperidone
Bromocriptine is a treatment for galactorrhoea, rather than a cause
A 55-year-old man develops a rash two days after starting a new medication. The rash is mildly pruritic and mainly affects the arms, torso and neck. The palms of his hand are shown below:
© Image used on license from DermNet NZ
Which one of the following drugs is most likely to have been started?
Levetiracetam
Olanzapine
Carbamazepine
Fluoxetine
Diazepam
This patient has developed erythema multiforme which is a known complication of carbamazepine use.
A heroin user is referred to the local drugs unit for community based detoxification. Which heroin substitutes is he most likely to be offered?
Methadone or morphine
Lofexidine or naloxone
Methadone or buprenorphine
Methadone or naloxone
Methadone or lofexidine
Methadone or buprenorphine
heme: Cytotoxic agents: side-effects
A.Doxorubicin
B.Cisplatin
C.Methotrexate
D.Dactinomycin
E.Vincristine
F.Fludarabine
G.Bleomycin
H.Cyclophosphamide
I.Paclitaxel
J.Pentostatin
For each of the following side-effects please select the cytotoxic agent which is most likely to be responsible:
Hypomagnesaemia
Myelosuppression, liver fiborsis and mucositis
Cardiomyopathy
Cisplatin
Methotrexate
Doxorubicin
Caution should always be exercised when combining diuretics. However, which one of the following combinations is always contraindicated?
Metolazone + bumetanide
Bendroflumethiazide + furosemide
Amiloride + spironolactone
Bendroflumethiazide + triamterene
Spironolactone + furosemide
Amiloride and spironolactone are both potassium-sparing diuretics. Combining the two may result in life-threatening hyperkalaemia.
A 72-year-old man is prescribed a dipyridamole in addition to aspirin following an ischaemic stroke. What is the mechanism of action of dipyridamole?
Phosphodiesterase inhibitor
Glycoprotein IIb/IIIa inhibitor
Inhibits ADP binding to its platelet receptor
Agonist of thromboxane synthase
Irreversibly acetylating cyclooxygenase
Dipyridamole inhibits phosphodiesterase
Characteristic side effect:
Amoxicillin
Rash with infectious mononucleosis
Characteristic side effect:
Coamoxiclav
Fluclox
Cholestasis
Characteristic side effect:
Erythromycin
GI upset
Prolonged QT
Characteristic side effect:
Ciprofloxacin
Lowers seizure threshold
Tendonitis
Characteristic side effect:
Metronidazole
Reaction following EtOH ingestion
Characteristic side effect:
Doxy
Photosensitivity
Characteristic side effect:
Trimethoprim
Rashes, including photosensitivity
Pruritus
Suppression of haematopoeisesis
A 55-year-old diabetic man presents to clinic concerned about erectile dysfunction. What is the mechanism of action of sildenafil?
Phosphodiesterase type V inhibitor
Nitric oxide synthetase inhibitor
Nitric oxide donor
Non-selective phosphodiesterase inhibitor
Phosphodiesterase type IV inhibitor
Sildenafil is a phosphodiesterase type V inhibitor
An alcoholic man is brought to the Emergency Department. His friend says he has drunk two bottles of antifreeze
The correct answer is Fomepizole
A farmer is admitted with suspected organophosphate insecticide poisoning
The correct answer is Atropine
A 65-year-old man is on the surgical ward. He underwent a laparotomy for small bowel obstruction yesterday. He is on patient controlled analgesia with morphine. The nurses report that he has a decreased conscious level and respiratory rate of 4 breaths per minute. On attending the patient he suffers a respiratory arrest. You initiate bag mask ventilation.
What treatment should he receive?
40 microgram increments of naloxone titrated to effect
300 micrograms of flumazenil
Defibrillation
400 microgram bolus of naloxone
Intubation and ventilation
This patient has suffered a respiratory arrest likely due to opioid toxicity. Therefore a 400 microgram bolus of naloxone should be administered. It is important to remember that naloxone has a short half life and therefore further naloxone will likely be required.
A 44-year-old man is diagnosed with a duodenal ulcer. CLO testing performed during the gastroscopy is positive for Helicobacter pylori. What is the most appropriate management to eradicate Helicobacter pylori?
Lansoprazole + clindamycin + metronidazole
Lansoprazole + amoxicillin + clindamycin
Lansoprazole + amoxicillin + clarithromycin
Omeprazole + amoxicillin + clindamycin
Omeprazole + penicillin + metronidazole
H. pylori eradication:
PPI + amoxicillin + clarithromycin, or
PPI + metronidazole + clarithromycin
The BNF recommends a regimen containing amoxicillin and clarithromycin as first-line therapy
BZD vs Barbs
BZDs increase the frequency of opening
Barbs increase the duration of channel opning
A 76-year-old woman is diagnosed with Alzheimer’s disease. Which one of the following could be a contraindication to the prescription of donepezil?
History of depression
Sick sinus syndrome
Concurrent simvastatin therapy
Concurrent citalopram therapy
Ischaemic heart disease
Donepezil may cause bradycardia and atrioventricular node block.
Drugs causing haemolysis in G6PDD
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
You are considering prescribing mefloquine as malarial prophlaxis for a 25-year-old woman. Which one of the following is the most important contraindication to consider?
G6PD deficiency
Asthma (requiring inhaled corticosteroids)
A history of anxiety or depression
Combined oral contraceptive pill use
A family history of venous thromboembolism
Mefloquine (brand name Lariam) is used for both the prophylaxis and treatment of certain types of malaria. There has long been a concern about the neuropsychiatric side-effects of mefloquine. A recent review has however led to ‘strengthened warnings’ about the potential risks.
The following advice is therefore given:
certain side-effects such nightmares or anxiety may be ‘prodromal’ of a more serious neuropsychiatric event
suicide and deliberate self harm have been reported in patients taking mefloquine
adverse reactions may continue for several months due to the long half-life or mefloquine
mefloquine should not be used in patients with a history of anxiety, depression schizophrenia or other psychiatric disorders
patients who experience neuropsychiatric sife-effects should stop mefloquine and seek medical advice
Theme: Side-effects of anti-anginals
A.Anal ulceration
B.Reduced seizure threshold
C.Hyponatraemia
D.Thrombocytopaenia
E.Constipation
F.Drug-induced lupus
G.Tachycardia
H.QT interval prolongation
I.Sleep disturbances
Verapamail
Atenolol
ISMD
Constipation
Sleep distrubances
Tachycardia
You are doing a medication review on a 64-year-old man with a history of cerebrovascular disease (having had a stroke 3 years ago), depression and knee osteoarthritis. His medication list is as follows:
clopidogrel 75mg od
simvastatin 20mg on
amlodipine 5mg od
ramipril 10mg od
diclofenac 50mg prn
sertaline 50mg od
What is the most appropriate change to make to his medications?
Switch sertaline to citalopram
Switch diclofenac for an alternative NSAID
Add aspirin
Reduce the dose of simvastatin
Switch clopidogrel to aspirin
Diclofenac is now contraindicated with any form of cardiovascular disease
A 58-year-old man who is taking lithium for bipolar disorder presents for review. During routine examination he found to be hypertensive with a blood pressure of 166/82 mmHg. This is confirmed with two separate readings. Urine dipstick is negative and renal function is normal. What is the most appropriate medication to start?
Amlodipine
Ramipril
Losartan
Bendroflumethiazide
Doxazosin
Diuretics, ACE-inhibitors and angiotensin II receptor antagonists may cause lithium toxicity. The BNF advises that neurotoxicity may be increased when lithium is given with diltiazem or verapamil but there is no significant interaction with amlodipine. Alpha-blockers are not listed as interacting with lithium but they would not be first-line treatment for hypertension.
The NICE hypertension guidelines suggest amlodipine wouldn’t be a bad first choice, even if we ignore his lithium treatment.
A 26-year-old female is commenced on carbamazepine for complex partial seizures. She has no previous medical history of note and consumes a moderate amount of alcohol. Three months later she is admitted due to series of seizures and carbamazepine levels are noted to be subtherapeutic. A pill-count reveals the patient is fully compliant. What is the most likely explanation?
Auto-inhibition of liver enzymes
Prescription of omeprazole
Prescription of fluoxetine
Auto-induction of liver enzymes
Alcohol binge
Carbamazepine is an inducer of the P450 system. This in turn increases the metabolism of carbamazepine itself - auto-induction
Vaughan-Williams Classification MOA:
Class I
Na channel blockers (local anaesthetics)
All slow conduction: subclasses have additional effects on AP
Use-dependent: preferentially block open or refractory Na channels
Class Ia drugs
Quindine, procainamide, disopyramide
Class 1a sites of action
A, SAN, AVN, V
Replorasiation Class 1a drugs
Prolonged-> increased AP duration
Indications for class 1a drugs
Ventricular arrhythmias
SEs of class 1a drugs
Anti-AChM
Negative inotropes
Class 1b drugs
Lignocaine, mexiletine
Ventricular only
Shorten repolarisation-> normal or reduced AP durations
Indications for 1b drugs
Ventricular arrhythmias following MI
1c drugs
Flecainide
Sites of actioin: A, SAV, AVN, V
Little effect on repolarisation
Used in pre-excited AF (WPW) and acute AF
Vaughan-Williams Classification MOA:
Class II drugs
Beta blockers: metorpolol, propranolol, esmolol, atenolol
Sites of action: A, SAN, AVN, V
MOA:
Increase refractory period of AVN-> slow AVN conduction
Prevent arrhythmias due to sympathetic discharge e.g. following MI
INdicated Post-MI, rate control in AF, SVT
Caution: negative inotropes
Vaughan-Williams Classification MOA:
Class II drugs
Amiodarone and sotalol
Sites of action: A, SAN, AVN, V
MOA: K channel blockers
Increase refractory period and prolong QTc
Indications: V and SV arrhythmias, pre-excited AF
Can-> arrhythmias esp. TdeP
Vaughan-Williams Classification MOA:
Class IV
CCVs: verapamil and diltiazem (non-DHPs)
Site of action: AVN
MOA: SLow AVN conduction
Indications: prevent SVT recurrence, AF (rate), acute SVT
Caution: negative intropes
Unclassified anti-arrhythmics
Digoxin
Adeonsine
Features of digoxin
Cardiac glycoside
MOA:
Positive inotrope: inhibits myocye Na/K ATPase-> raised Na and Ca
Negative chronotrope: slows AV conduction-> reduced rate and increased AVN refractory period
Only slows resting rate, not exercise rate
Indications: SVT and AF
Features of adenosine
Acts @ A1 Rs in cardiac tissue-> myocyte hyperpolarisation
Transient AV block
Indicated in SVTs
Clinical classification of ant-arrhythmics:
AVN
Adenosine
beta-blcoker
Verapamail
Digoxin
Use: AF, SVT
Clinical classification of ant-arrhythmics:
Atria and ventricles
Class 1a, 1c and amiodarone
Clinical classification of ant-arrhythmics:
Ventricles only
Class 1b
VW Class:
Disopyramide
1a
VW Class:
Lignocaine
1b
VW Class:
Flecainide
1c
VW Class:
Amiodarone
3
VW Class:
Digoxin
Cardiac glycoside
Indications:
Disopyramide
Ventricular arrhythmias (esp. post-MI
Indications:
Lignocaine
Ventricular arrhythmias (esp. post-MI)
Indications:
Flecainide
Pre-excited AF (WPW)
Cardioversion in AF
Suppression of ventricular ectopics
Indications:
Amiodarone
SVT
AF/flutter
Pre-excited AF
V. arrhythmias
Indications:
Digoxin
AF/flutter
SVT
(HF)
Indications:
Adenosine
SVT: Dx and Rx
Side effects:
Disopyramide
VT, VF, TdeP
Anti-muscarinic
Side effects:
Lignocaine
Drowsiness
Paraesthesia
Dizziness
Bradycardia-> cardiac arrest
Side effects:
Flecainide
Strong -ve inotrope
Oedema
Dyspnoea
Side effects:
Amiodarone
Eye: corneal microdeposits
Thyroid: hyper/hypo
Lung: pulmonary fibrosis
GI/liver: raised LFTs, N/V
Neuro: peripheral neuropathy
Skin: photosensitvity, blue-grey discolouration, phlebitis (give centrally)
Side effects:
Digoxin
Toxicity:
Any arrhythmia
Nausea
Xanthopsia
Confusion
Hyperkalaemia
Chronic:
Gynaecomastia
Reverse tick ECG (not a sign of toxicity)
Side effects:
Adenosine
Bronchospasm
Chest pain
Flushing
Nausea
Light-headedness
Contraindications
Disopyramide
Heart block (2/3)
Contraindications
Lignocaine
Heart block
Contraindications
Flecainide
Structural heart disease
Post-MI
Contraindications
Amiodarone
Thyroid disease
Sinus bradycardia
TdP
Contraindications
Digoxin
Complete heart block
VF/VT
HOCM
SVTs 2o to WPW
Contraindications
Adenosine
Asthma
Heart-blcok (2/3)
Sick sinus syndrome
Interactions:
Lignocaine
Cimetidine increases lidocaine levels
Interactions:
Amiodarone
beta blocker and CCB-> increased risk of HV
Increased levels of:
digoxin
warfarin
phenytoin
Increased risk of ventricular arrhythmias with:
Class 3/1a antiarrhythmics
TCAs, antipsychotics
Erythromycin
Interactions:
Digoxin
Dig fx/toxicity increased by:
CCB (especially verapamil)
Amiodarone (halve dig dose)
Diuretics (loop/thiazide use due to redcued K)
Reduced digoxin intestinal absorption with:
antacids
cholestyramine
Interactions:
Adeonsine
Function prolonged by dipyridamole
Function decreased by theophylline
Additional notes:
Lignocaine
IV use only
Additional notes:
Amiodarone
Accumulates in body
Very long t1/2 (10-100d)
Extensively tissue bound hence requires loading dose
Monitor:
TFTs, LFTs
K
CXR
Avoid sunlight
Additional notes:
Digoxin
Caution:
Renal excretion therefore beware of renal impairment
Monitor:
U+Es
Drug levels
Load then maintenance
Additional notes:
Adenosine
t1/2= 9-10s
MOA:
Aspirin
Irreversible, non-selective COX inhibitor
Redces platela TxA2-> reduced paltelet activation-> reduced platelet adhesion, aggregation
Relatively platelet-specific @ low dose
75-100mg
MOA:
Clopidogrel
Thienopyridine
irreversible adenosine R antagonist: inhibits ADP-induced fibriongen binding to GPIIb/IIIa
MOA:
Apicixmab
Tirofiban
Eptifibatide
MAb or synthetic inhibitors of GPIIb/IIIa
MOA:
Dipyridamole
PEDI: increased cAMP inhibits plt aggregation
TxA2 synthetase inhibitor
Ticregalor/prasgurel
Also antiADP
These agents reduce the aggregation (“clumping”) of platelets by irreversibly binding to P2Y12 receptor
Side-effects:
Aspirin
Gastritis
Gastric ulceration
Bleeding
Bronchospasm
Renal failure
Gout
Otototixc in OD: tinnitus
Side-effects:
Clopidogrel
Bleeding: esp. GI or intracranial
GI upset
Dyspepsia/PUD
TTP (rare)
Blood dyscrasias (rare)
Side-effects:
GpIIb/IIIa inhibitors
Bleeding
Thrombocytopneia
Side-effects:
Dipyridamole
Headache
Contraindications:
Aspirin
<16y (Reyes syndrome) except in Kawasaki;s
Active PUD
Bleeding disorders
Gout
Renal disease (GFR <10ml/min)
P/B
Caution:
asthma
uncontrolled HTN
Contraindications:
Clopidogrel
Severe liver disease
B
Contraindications:
Dipyridamole
MG
Interactions:
Aspirin
Increased risk of bleeding with other anti-coagulants and anti-platelets
Increases function of sulphonylureas, methotrexate
Interactions:
Clopidogrel
Avoid with warfarin
Interactions:
Dipyridmole
Enhances effects of adensoine
Additional notes:
Aspirin
Stop 7d before surgery if significant bleeding expected
Max dose: 4g/d
Additional notes:
Clopidogrel
Prodrug converted by heaptic CYP enzymes
Used following bare-metal or drug eluting stents
Stop 7d before sx
Additional notes:
Abciximab
Tirofiban
Eptifibatide
Only abiciximab can be given PO
Given to high-risk patients with NSTEMI
Additional notes:
Dipyridamole
May be used with aspirin in 2o prevention of stroke
MOA:
Statins
HMG-CoA reductase inhibitors: block rate-limiting step in cholesterol synthesis
Leads to reduced hepatocyte cholesterol-> increased hepatic LDLRs-> reduced LDL cholesterol
Raises HDl Reduces TGs (mild)
MOA:
Bezafibrate
Gemfibrozil
Fibrates
Stimulate lipoprotein lipase:
reduce TG, reduce LDL, increase HDL
MOA:
Cholestyramine, cholestipol
Anion exchange resin
Bind bile acids and prevent enterohepatic recyclig, therefore liver must synthesis more bile acids from cholesterol-> increased LDLRs
MOA:
Nicotinic acid
Inhibit cholesterol and TG synthesis
Raises HDL
MOA:
Ezetimibe
Inhibits intestinal cholesterol absorption
Pro-drug
MOA:
Omega 3 FAs
Reduce TGs
MOA:
Orlistat
Pancreatic lipase inhibitor-> impaired absorption of dietary fat
Side effects:
Statins
Myositis- stop if CK 5x ULN as can lead to rhabdo and ATN
Deranged LFTs
GI upset
Side effects:
Fibrates
Gallstones
GI upset
Reduced appetite
Myositis
Blood dyscrasias
Side effects:
Cholestyramine
GI upset: bloating, constipation, N/V
Can raise TGs
Impairs absorption of fat soluble drugs and vitamins (ADEK)
Side effects:
Nicotinic acid
Flushing
NV
Side effects:
Ezetimibe
GI upset
Myalgia
Side effects:
Omega 3Fas
GI upset
Side effects:
Orlistat
GI upset
Steatorrhoea
Abdominal distension
Reduced absorption of fat-soluble drugs and vitamins
Contraindications:
Statins
Liver disease
Pregancy
Contraindications:
Fibrates
GB disease
PBC
Reduced albumin (esp. nephrotic syndrome)
R L P B
Contraindications:
Cholestyramine
Complete biliary obstruction
Contraindications:
Nicotinic acid
Peptic ulcer
Contraindications:
Orlistat
Cholestasis
Interactions:
Statins
Increased risk of myositis with:
fibrates
macrolides
azoles
grapefruit juice
protease inibitors
ciclosporin
nicotinic acid
Milw W+
Interactions:
Fibrates
Increased risk of myositis
Increased function of anti-diabetics
W+
Interactions:
Cholestyramine
Reduces absorption of other drugs e.g. digoxin
Interactions:
Ezetimibe
Increased risk of myositis with statins
Interactions:
Orlistat
Warfarin: difficulty controlling INR
Additional notes:
Statins
Monitor: LFTs and CK
Take statins nocte as increased cholesterol synthesis overnight
Additional notes:
FIbrates
Use: hyperTG
Additional notes:
Cholestyramine
Don’t take within 3h of other drugs
Features of PCC
Factors 2, 7, 9, 10
Immediate reversal of anticogaulation
Temprorary effect- give Vit K
Risk of VTE and very expesnive
Vit K
Onset of actions = 6h
Oral is as efficacious as IV
Oral Vit K can-> prolonged anticoagulant resitsance. avoid if continuing anticoagulation
Continuing warfarin: 0.5mg slow IV
Discontinuing Warfarin 2.5-5mg IV
Mx of VTE prophylaxis on long-haul flights
Low risk: avoid dehydration, regularly flex ankles
Mod risk: as above + compression travel socks. Previous VTE, GA within last 1-2m
High risk: as above, consider LMWH before flight. Sx under GA within last m
MOA heaprin
Co-factor for ATIII: inhibits 2, 10, 11 and 12
LMWH and fondaparinux only inhibit factor 10
LMWH vs UH
LMWH has longet t1/2 and response is more predictable- no monitoring required
UH has rapid onset and short t1/2: useful when rapid control over effects needed e.g. risk of bleeding
Less risk of HIT and osteoporosis with LMWH
Indications for heparin
Treatment:
VTE
ACS
Acute arterial obstruction
Prophylaxis:
VTE
Coagulation in extra-corporeal circuits
Side effects: heparin
Thrombocytopenia: immune mediated. Develops 6d after intitiaion-> thrombosis
Osteoporosis: LT use
Hyperkalaemia: heparin inhibits aldosterone
Contraindications to heparin
Bleeding disorders
Plt <60
Previous HIT
PU
Cerebral haemorrhage
Severe HTN
NeuroSx
Dosing of LMWH
e.g. enoxaparin
Prophylaxis: 20-40mg pre and post-surgery
Treatment: 1.5mg/kg/24h
Dosing UH
5000iU bolus IV over 30 mins
Infuse UH @ 18iu/kg/h
Check APTT @ 6h (aim for 1.5-2x control)
Side effects of streptokinase
Bleeding
Allergic responses: rash, anaphylaxis
Reperfusion dysrhythmias after MI
Hypotension
Development of Abs: can only use once
Administration of streptokinase
Over 1h
Side effects of Rh-TPA
Bleeding, hypotension, reperfusion dysrhythmias
Administration of RhTPA
Alteplase: infuse
Give with UH heparin IV for 24-48h to avoid rebound hypercoagulable state
Absolute contraindications to thrombolytics
Haemorrhagic stroke at any time
Ischaemic stroke in last 6m
CNS trauma or neoplasms
Major trauma/surgery in last 3w
GI bleed within last 1m
Known bleeding disorders
Aortic dissection
Non-compressible puncture e.g. LP
Relative contraindications to thrombolysis
TIA in last 6m
Warfarin
Pregnancy or within 1w post-partum
Refractory resus
Refractory HTN (>180/110)
Advanced liver disease
Infective endocarditis
Acute peptic ulcer
A patient who is intolerant of aspirin is started on clopidogrel for the secondary prevention of ischaemic heart disease. Concurrent use of which one of the following drugs may make clopidogrel less effective?
Warfarin
Omeprazole
Codeine
Long-term tetracycline use (e.g. For acne rosacea)
Atorvastatin
Omeprazole
A clinical trial is evaluating the effect of a new drug X on all-cause mortality. The rate of death in the group receiving drug X is 8%, compared with 16% in the control group. What is the number needed to treat with drug X to prevent a death?
2
8
12
13
50
The absolute risk reduction is 8% (16% - 8%). 100/8 = 12.5, so rounding up the the next integer this gives at NNT of 13. i.e. you would need to give the new drug to 13 people to ensure that you prevented one death.
Numbers needed to treat and absolute risk reduction
Numbers needed to treat (NNT) is a measure that indicates how many patients would require an intervention to reduce the expected number of outcomes by one
It is calculated by 1/(Absolute risk reduction) and is rounded to the next highest whole number
Experimental event rate (EER) = (Number who had particular outcome with the intervention) / (Total number who had the intervention)
Control event rate (CER) = (Number who had particular outcome with the control/ (Total number who had the control)
A 75-year-old male with a long history of intravenous drug use is admitted with fevers, rigors and back pain. Three sets of blood cultures taken at admission grow positive for gram positive cocci in clusters. He is suspected of having Staphylococcus aureus bacteraemia and is commenced on intravenous vancomycin.
Half an hour after the infusion is commenced, he is noted by the nurse to be flushed. On examination, he is noted to have erythema over his neck, face and trunk but denies any significant distress or discomfort.
His observations are as follow: blood pressure 125/70 mmHg, heart rate 85/min, temperature of 36.8ºC, respiratory rate of 18/min and oxygen saturation of 98% on room air.
Which of the following is the most appropriate management?
Stopping the vancomycin infusion, administering 200mg of IV hydrocortisone and informing the patient that he is allergic to the medication
Stopping the vancomycin infusion and administering a single dose of 0.5mcg intramuscular adrenaline
Stopping the vancomycin infusion until symptoms resolve and then re-starting a slower rate
Stopping the vancomycin infusion and prescribing topical 1% hydrocortisone cream to affected areas
Continuing the vancomycin infusion and administering 1000 ml of 0.9% saline solution over 1 hour
Red man syndrome is associated with rapid intravenous infusion vancomycin. It is a common adverse reaction of intravenous vancomycin use and is a distinct entity from anaphylaxis due to vancomycin use. Typical symptoms include redness, pruritus and a burning sensation, predominantly in the upper body (face, neck and upper chest). Severe cases can be associated with hypotension and chest pain.
The pathophysiology of red man syndrome is attributed to vancomycin-related activation of mast cells with release of histamine.
The management of red man syndrome involves cessation of the infusion, and when symptoms have resolved, recommencement at a slower rate. In patients who are more symptomatic antihistamines can be administered, and may require intravenous fluids if the syndrome is associated with hypotension.
A 25-year-old man with a history of Crohn’s disease presents asking for advice. He currently takes methotrexate and asks if it is alright for him and his partner to try for a baby. What is the most appropriate advice?
He should wait for at least 3 months after stopping treatment
He should wait for at least 12 months after stopping treatment
He should have semen analysis 8 weeks after stopping treatment prior to trying to conceive
There is no limitations on male patients
He should wait for at least 6 months and his partner should take folic 5 mg od
He should wait for at least 3 months after stopping treatment
A 65-year-old female with metastatic breast cancer is reviewed in clinic. Her husband reports that she is increasingly confused and occasionally appears to talk to relatives that are not in the room. Following investigations for reversible causes, what is the most appropriate management?
Subcutaneous midazolam
Oral lithium
Oral haloperidol
Oral diazepam
Oral fluoxetine
Underlying causes of confusion need to be looked for and treated as appropriate, for example hypercalcaemia, infection, urinary retention and medication. If specific treatments fail then the following may be tried:
first choice: haloperidol
other options: chlorpromazine, levomepromazine
In the terminal phase of the illness then agitation or restlessness is best treated with midazolam
Which one of the following side-effects is least recognised in patients taking isotretinoin?
Hypertension
Teratogenicity
Nose bleeds
Depression
Raised triglycerides
Isotretinoin adverse effects
teratogenicity - females MUST be taking contraception
low mood
dry eyes and lips
raised triglycerides
hair thinning
nose bleeds
A 49-year-old presents with hot flushes and irregular periods. She has a past history of migraine and is keen for hormone replacement therapy (HRT). What is the most appropriate management?
HRT is contraindicated
HRT can be given but may worsen migraine
HRT can only be given if the women has not a migraine in the past 12 months
Tell the patient HRT does not affect migraine
Suggest a progestogen only formula
Migraine and hormone replacement therapy (HRT)
safe to prescribe HRT for patients with a history of migraine but it may make migraines worse
A 70-year-old woman is prescribed bumetanide for congestive cardiac failure. Where is the site of action of bumetanide?
Descending loop of Henle
Macula densa
Ascending loop of Henle
Distal collecting duct
Proximal collecting duct
Bumetanide, like furosemide, is a loop diuretic.
A 14-year-old girl is taken to the Emergency Department, after being found lying on her bed next to an empty bottle of pills prescribed for her mother. On examination she is agitated, has a clenched jaw and her eyes are deviated upwards. Which drug is she most likely to have consumed?
Phenytoin
Metoclopramide
Amitriptyline
Carbamazepine
Nifedipine
This is a classic description of an oculogyric crisis, a form of extrapyramidal disorder
A 37-year-old woman who was investigated for progressive shortness-of-breath is diagnosed with primary pulmonary hypertension and started on bosentan. What is the mechanism of action of bosentan?
Activator of soluble guanylate cyclase
Phosphodiesterase type 5 inhibitors
Endothelin receptor antagonist
Prostanoid
Slow calcium channel blocker
Bosentan - endothelin-1 receptor antagonist
Which one of the following may reduce the effects of adenosine?
Dipyridamole
Diltiazem
Clopidogrel
Amiodarone
Aminophylline
Adenosine
dipyridamole enhances effect
aminophylline reduces effect
Drug causes of thrombocytponeia
Quinine
Abciximab
NSAIDs
Diuretics: furosemide
Abx: penicllins, sulphonamides, rifampicin
Anticonvulsants: carbamazepine, VPA
Heparin
An 89-year-old man attends your clinic, complaining of bright spots in his vision that come and go. He has a past medical history of asthma, triple vessel coronary artery disease opting for medical management of his anginal symptoms, and has just completed a course of itraconazole for a fungal infection. His heart rate is 60bpm and blood pressure 120/70mmHg.
Which of his regular medications is most likely responsible for his symptoms?
Amlodipine
Bezafibrate
Ivabradine
Ranolazine
Ventolin
Ivabradine is indicated for the symptomatic relief of angina in patients with a heart rate >70, as an alternative to first line therapies. It is also indicated for the treatment of chronic heart failure (NYHA II-IV) in addition to standard therapy, in patients with a heart rate of >75.
The mode of action of ivabradine is by inhibition of If channels (known as funny channels), I = current, f =funny. These funny channels are so called because of their unusual features compared to other ion channels. They are mixed sodium and potassium channels found in spontaneously active regions of the heart such as the sinoatrial node and are triggered by hyperpolarisation. Activated funny channels allow an influx of positive ions, triggering depolarisation and are therefore responsible for the spontaneous activity of cardiac myocytes.
By inhibiting If channels ivabradine delays depolarisation in the sinoatrial node and therefore selectively slows heart rate.
The commonest side effect caused by ivabradine is transient luminous phenomenon (reported by up to 15% of patients), such as bright spots appearing in their field of vision. Less commonly blurred vision is reported. Patients should be informed of this common side effect before starting the medication. The visual side effects of ivabradine are likely to be mediated by inhibition of a channel similar to the If channel found in the retina called the Ih channel. The h = hyperpolarisation-activated, these channels were formerly called IQ channels, Q = queer, again for their unusual characteristics.
Ivabradine is metabolised by oxidation through cytochrome P450 3A4 (CYP3A4) only. Therefore drugs that induce (e.g rifampicin) or inhibit (e.g erythromycin, itraconazole) CYP3A4, will decrease or increase the plasma concentration of ivabradine respectively. In this case the patient has been taking the potent CYP3A4 inhibitor Itraconazole, this would have increased the plasma concentration of ivabradine, resulting in the visual side effects experienced.
A 79-year-old man with a known history of mixed type dementia (Alzheimer’s and vascular) is assessed in memory clinic as his family have noticed a further deterioration in his memory and cognition. His mini-mental state score is 12 and as such he is commenced on memantine.
Which of the following best describes the mechanism of action of memantine?
Serotonin receptor agonist
Dopamine receptor antagonist
Acetylcholinesterase inhibitor
Butyrylcholinesterase and acetylcholinesterase inhibitor
NMDA antagonist
A 79-year-old man with a known history of mixed type dementia (Alzheimer’s and vascular) is assessed in memory clinic as his family have noticed a further deterioration in his memory and cognition. His mini-mental state score is 12 and as such he is commenced on memantine.
Which of the following best describes the mechanism of action of memantine?
Serotonin receptor agonist
Dopamine receptor antagonist
Acetylcholinesterase inhibitor
Butyrylcholinesterase and acetylcholinesterase inhibitor
NMDA antagonist
A 35-year-old man presents to the emergency department after a night out, having taken an unknown substance. He is known to have a history of depression.
On examination his Glasgow coma scale (GCS) is 13/15, pupils are dilated and divergent. He is tachycardic with a heart rate of 110/min, his blood pressure is 124/70mmHg. His ECG shows sinus rhythm, with a lengthened QTc duration of 480msec. He is dry to the touch.
Which substance is he most likely to have ingested?
Cocaine
Sertraline
Diazepam
Amitriptyline
MDMA
The correct answer here is Amitriptyline - a tricyclic antidepressant (TCA) overdose.
Whilst the main effect of TCAs is to increase serotonin and noradrenaline in the brain by slowing re-uptake, they also block histamine, cholinergic and alpha 1 receptors. Therefore in overdose the anti-cholinergic effects give dilated pupils, dry skin, confusion, urinary retention and tachycardia. Divergent pupils are a common finding in tricyclic overdose. TCAs are also cardiotoxic by inactivating sodium channels in the heart leading to, as seen here, a potential prolongation of the QTc interval and a widened QRS complex. This can potentially lead to ventricular arrhythmias.
Other effects of TCAs not included here include seizures and a metabolic acidosis.
In overdose sertraline may present with serotonin syndrome. The Glasgow coma scale may be reduced and pupils dilated, but skin would not be dry. A classic feature of serotonin syndrome is hyperreflexia, often with muscle rigidity and tremor, which is not described here. Additionally QTc prolongation is unlikely with selective serotonin reuptake inhibitors (citalopram is an exception).
Cocaine produces sympathetic effects - agitation, restlessness, increased heart rate and blood pressure. In severe toxicity hyperthermia and rhabdomyolysis may occur. It would not cause a reduced GCS or altered QRS duration on ECG.
MDMA (ecstasy) excess presents similarly to cocaine, with increased psychomotor agitation, palpitations and hyperthermia. Additionally teeth grinding (bruxism) is noted frequently.
Diazepam ingestion could cause a reduced GCS due to its sedative effects. However it would not generally affect pupil size, heart rate or ECG. It is associated with respiratory depression.
A 65-year-old man with a history of type 2 diabetes mellitus and ischaemic heart disease presents with erectile dysfunction. It is decided to try sildenafil therapy. Which one of the following existing medications may be continued without making any adjustments?
GTN spray
Nicorandil
Nateglinide
Doxazosin
Isosorbide mononitrate
Nateglinide
The BNF recommends avoiding alpha-blockers for 4 hours after sildenafil
A patient who was commenced on a simvastatin six months ago presents with generalised muscles aches. Which one of the following is not a risk factor for statin-induced myopathy?
Female gender
Large fall in LDL-cholesterol
Low body mass index
Advanced age
History of diabetes mellitus
Large fall in LDL-cholesterol
A 48-year-old female who has just completed a course of chemotherapy complains of difficulty using her hands associated with ‘pins and needles’. She has also experienced urinary hesitancy. Which cytotoxic drug is most likely to be responsible?
Doxorubicin
Cyclophosphamide
Methotrexate
Vincristine
Bleomycin
Vincristine is associated with peripheral neuropathy. Urinary hesitancy may develop secondary to bladder atony.
Inhibits 14α-demethylase which produces ergosterol
Azoles
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl) leakage
Amphotericin B
Inhibits squalene epoxidase
Terbinafine
Interacts with microtubules to disrupt mitotic spindle
Griseofulvin
Converted by cytosine deaminase to 5-fluorouracil, which inhibits thymidylate synthase and disrupts fungal protein synthesis
Flucytosine
Inhibits synthesis of beta-glucan, a major fungal cell wall component
Caspofungin
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl) leakage
Nystatin
A 45-year-old man presents with pain and swelling of his left big toe. He has recently started treatment for active tuberculosis. Which one of the following medications is likely to be responsible?
Streptomycin
Rifampicin
Ethambutol
Isoniazid
Pyrazinamide
Pyrazinamide
mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
MOA:
Levodopa
Dopamine pro-drug
Crosses BBB and converted to Da by dopa-decarboxylase
MOA:
Apomorphine
Non-selective Da agonist
MOA:
Bromocriptine
Cabergoline
Pergolide
Ergot-derived Da agonists
MOA:
Ropiirole
Rotigotine
Pramipexole
Synthetic Da agonists
MOA:
Selegiline
Rasagiline
Selective MAO-B inhibitors
Prevent intraneuronaol Da degradation
Buccal preparations have better bioavailability
MOA:
Entacapone
Tolcapone
COMTI
Inhibit peripheral Da degradation
MOA:
Amantadine
Da release
Inhibit peripheral Da degradation
MOA:
Procyclidine
Benzhexol
Muscarinic antagonsits
Reduce tremor
Side effects:
L-DOPA
DOPAMINE
Dyskinesia
On-off
Psychosis
ABP reduced
Mouth dryness
Insomnia
N/V
EDS
Side effects:
Apomorphine
Very emetogenic
Give domperidone for 2d before starting Rx
Injection site reactions
Side effects:
Bromocriptine
Cabergoine
Pergolide
Fibrosis
Vasopsapasm: cardiac, digital
GI upset
Posural hypotension
Drowsiness
Neuropsychiatric synbdromes
Side effects:
Synthetic Da agonists
GI upset
Insomnia (selegiline)
Postural hypotension (no cheese reaction)
Side effects:
COMT inhibitors
Reddish brown urine
GI distrubance
Dyskinesias
Tolcapone is hepatotoxic
Side effects:
Amatadine
GI uspet
Sleep disturbance
Livedo reticularis
Neuropsychiatric syndromes
Side effects:
Procyclidine
Benzhexol
Anti-AChM
Memory impairment
Confusion
Contraindications:
L-DOPA
Closed angle glaucoma
MAO-Is
Melanoma
Contraindications:
Ergot derived Da agonists
CV disease
Prophyria
Psychosis
Contraindications:
Amantadine
Gastric ulcer
Epilepsy
Interactions:
L-DOPA
Function reduced by antispchotics
HTN crissis with non-selective MAOIs
Anti-HTNs enhance hypotensive function
Food affects absorption (proteins specifically)
Interactions:
Ergot-derived Da agonists
Levels increased by:
Octreotide
Macrolides
Interactions:
COMTI
Interact with sympathomimetics
Additional notes:
L-DOPA
Always give wih peripheraly dopa-decarboxylase inhibitor e.g. carbidope, benserezide
Loss of response within 2-5y
Give domperidone for N/V
Short T1/2 so requires at least TDS dosing
Additional notes:
Apomorphine
Only give S/C
Rescue pen for freezing
Additional notes:
Ergot derived Da agonists
Not often used in parkinsonism due to SEs
Additional notes:
MAO-BIs
Used alone to delay need for L-DPPA
Adjunct to L-DOPA to reduced end-of-dose effects
Additional notes:
COMTI
Reduces off period of L-DOPA
Tolcapone has better efficacy but requires LFT monitoring
Additional notes:
Amantadine
May be used in PD for late onset dyskinesia
Additional notes:
Procyclidine
Benzhexol
Useful in drug-induced parkinsonism and mild PD in young patients, esp. tremor
What are the L-DOPA motor fluctuations
Peak dose dyskinesias
End of dose dyskinesia/akinesia: deterioration as dose wears off
On-off effect: unpredictable fluctuations in motor performance unrelated to timing of dose
MOA:
VPA
CZM
PHE
Na channel blockers
Use-dependant
Inhibit action potential generation
MOA:
LTG
Ihibits glutamate release
MOA:
Ethosuximide
Ca channel blocker
Side effects;
VPA
ALPROATE
GI upset
Hepatotoxicity
Appetitie increased
Liver failure
Pancreatitis
Reversible hair loss
Oedema
Ataxia
Teratogenicity, tremor, thrombocytopenia
Encephalopathy due to raised ammonia
Side effects:
CZM
Skin reactions e.g. SJS
Blood dyscrasia (reduced WCC0
Reduced Na (SIADH)
Foetal NTDs
GI upset
Dose-related:
dizziness/vertigo
Ataxia
Diplopia
Side effects:
Phenytoin
Acute:
Drowsiness
Cerebellar fx
Rash
Chronic:
Gingival hyperplasia
Hirsutism and acne
Reduced folate
Side effects:
LTG
Rashes (SJS, TEN, lupus)
Cerebellar effects
Blood dyscrasias
Hepatotoxic
Side effects:
Ethosuximide
GI upset
Side effects:
Vigabatrin
Visual field defects
Contraindications:
VPA
Acute porphyria
Personal/FHx of severe liver dysfunction
L/P
Contraindications:
CZM
Unpaced AV conduction defects
Hx of BM depression
Porphyria
MAOIs
Contraindications:
PHE
Don’t give IV if cardiac dysrythmias
Caution: DM, hypotension, L/H, P
Contraindications:
LTG
Liver disease
Contraindications:
Ethosuximide
?makes tonic-clonic seizures worse
Interactions:
VPA
Function reduced by:
antimalarials
antidepressants
antipsychotics
some anti-epileptics
Levels increased by cimetidine
Increases fx of:
aspirin
LTG
Warfarin
Interactions:
CZM
PHE
Reduces FX of:
COCP
Doxy
corticosteroids
Anti-elipetics
Nifedipine
Warfarin
Levels increased by:
macrolides
cimetidine
diltiazem and verapamil
EtOH
NSAIDs
Esomeprazole
Levels reduced by:
rifampicin
antipsychotics
Interactions:
LTG
Fx reduced by:
OCP
PHE, CZM
TCAs and SSRIs
Levels increased by VPA
Additional notes:
VPA
CYP inhibitor
1st line for generalised seizures
Monitor: FBC, LFTs
Most teratogenic AED
Additional notes:
CZM
Has active metabolite produced in the liver
CYP inducer
Monitor:
serum levels
U+E, LFT, FBC
Additional notes:
PHE
V. albumin bound
CYP idnucer
0 order kinetics
Monitor: FBC
Additional notes:
LTG
Monitor: U+Es, LFTs, FBS, clotting
Stop if any sign of rash
Safest for pregnancy
Additional notes:
Ethosuximide
Only used for childhood absence seizures
MOA:
Rizatriptan
Sumatriptan
5HT 1b/1d R agonist
Reverses dilatation of cerebral vessels
MOA:
Ergotamine
Partial 5HT R agonist
MOA:
Pizotifen
5HT2 R antag and antihistamine
MOA:
Amitritpylline
5HT and Na reuptake inhibitor
Side effects:
Rizatriptan
Sumatriptan
Sensation of tingling/heat/ tightness/pressure
Dizziness
Flushing
Side effects:
Ergotamine
GI upset
Dizziness
Side effects:
Pizotifen
Drowsiness
Increased appetite and weight
Side effects:
Amitryptilline
Anti-cholinergic
Anti-adrenergic
Anti-histamine
OD: prolonged QTc
Contraindications:
Triptans
IHD
Coronary vasopasm
PVD
Hx of MI, CV, TIA
HTN (moderate/severe)
Contraindications:
Ergomatine
As for triptans
Contraindications:
Amitryptilline
Recent MI (w/i 3m)
Heart block
Liver disease
Interactions:
Triptans
Increased risk of CNS toxicity with SSRIs
Interactions:
Amitryptilline
MAOIs-> HTN and CNS excitiation
Levels increased by SSRIs, cimetidine
Increased risk of arryhthmias with amiodarone
Additional notes:
Triptans
Used for Rx of acute attacks
Don’t use for 2-3x /w –> chronic migraine
Additional notes:
Pzitofen
Migraine prophylaxis
Additional notes:
Amitryptilline
Hepatic metabolism
Used for prophylaxis
MOA:
Methylpred
Inihibts PLA-> reduced PG and PAF
Reduced PMN extravasation-> increased PMN in blood
Lymphopenia
Phagocytosis
Reduced Ab proudction
Reduce cytokines and protelytic enzymes
MOA:
Glatiramer
Random polymer of amino acids found in MBP
?acts as decoy
MOA:
Natalizumab
Anti-a4 integrin
MOA:
Alemtuzumab
Anti-CD52
MOA:
Baclofen
GABAb agonist
Skeletal muscle relaxant
MOA:
Dantrolene
Prevents Ca release from SR
Skeleatl muscle relaxant
MOA:
Oxybuytinin
Antimuscarinic
Side effects:
Methylpred
Cushings
Side effects:
IFNB
`Flu-like symptoms
Injection site reactions
Side effects:
Glatiramer
Flu-like symptoms
Injection site reactions
Side effects:
Baclofen
Sedation
Reduced tone
Nausea
Urinary distrubance
Side effects:
Dantrolene
Hepatotoxicity
GI upset
Side effects:
Oxybutynin
Dry mouth
GI upset
Blurred vision
Contraindications:
IFNB
Decompensated L
Severe depression
Contraindications:
Baclofen
PUD
Contraindications:
Dantrolene
Liver disease
Contraindications:
Oxybutynin
Myasthenia
GI/bladder obstruction
Additional notes:
Methylpred
High dose up to 1g/d for acute MS flares
Short course: 3-5d
Additional notes:
IFNB
Relapsing remitting or secondary progressive MS
Monitor for hepatotoxicity
Additional notes:
Glatrimaere
Relapsing remitting MS
Additional notes:
Baclofen
Rx painful muscle spasms
Don’t withdraw abruptly:
hyperthermia
increased spasticity
Additional notes:
Oxybutynin
Used for detrusor instability
Phsyiology of nausea
Vomiting regulated by comiting centre and CTZ, both located in the medulla
CTZ:
Oustide BBB therefore accessible to drugs
Also receives input from vestibular system regarding motion
Express D2 and 5HT3 Rs
CTZ projects to vomiting centre
Vomiting centre:
Controls visceral and somatic functions incolved in vomiting
Receives input from CTz
Also receives muscarinic and histaminergic input (H1)
What are the emetogenic receptors
D2R
H1
5HT3
mACh
MOA:
Metoclopramide
Prochlorperazine
Domperidone
D2 R antagonist
Prokinetic action in GIT: increased absorption of other drugs
MOA:
Ondanestron
Granisetron
5HT3 R antag
MOA:
Cylcizine
Cinnarizine
H1 R antagonist
MOA:
Hyoscine
Hydrobromide
Anti-muscrainic
MOA:
Dexamethasone
Steroid: unknown anti-emetic effect
MOA:
Aprepitant
Neurkonin R blocker
Side effects:
D2R antagonists
EPSEs: dystonias, oculogyric crisis
Drowsiness, rash, allergy, raised prolactin
Side effects:
5HT3 antagonsits
Constipation
Headache
Side effects:
H1 R antagonists
Anti-AChM
Side effects:
Hyoscine
Anti-muscrainic
Contraindications:
D2R antags
<20y
GI obstruction
L
Prolacitnoma
Contraindications:
Ondanestron
Granisetron
Avoid if prolonged QT
Contraindications:
H1 R antags
Severe HF
MAOIs can increase antimuscarinic fx
Contraindications:
Anti-muscarinics
Closed angle gluacoma
BPH
Interactions:
D2R antags
Increased risk of EPSEs with antipsychotics, TCAs, SSRIs
Interactions:
5HT3 R antagonists
Levels reduced by
Rifampicin
CBZ, PHE
Avoid with drugs that prolong QTc
Interactions:
Hyoscine
Redcues function of SL GTN
Additional notes:
D2R antags
Indications:
GI causes of nausea
Chemo, morning after pill, opiates
PD
Migarine
Vestibular (prochlorperzine)
Domperidone doesn’t cross BBB so less EPSEs cf. others
Additional notes:
5HT3 R antags
Indications:
post-op
CTx
CYP metabolism
Additional notes:
H1 R antags
Indications:
Opioids but not in ACS
Vestibular
Additional notes:
Hyoscine
Indications:
prophylaxis vs motion sickness
Hypersalivation
Additional notes:
Aprepitatn
Indications:
Chemo (adjunct)
Features of serotonin syndrome
Cognitive: headache, agitaition, confusion, coma
Autonomic: sweating, increased HR, palpitations, HTN, hyperthermia
Somatic: myoclonus, clonus, hypertonia
Features of monoamine oxidase
Metabolises monoamines
MAO-A: adrenaline, norad, sertoonin, tyramine, dopamine
MAO-B: dopamine
Features of TCA toxcity
Metabolic acidosis
Anti-AChM: dialted pupils
CNS: hypertonia, hyperreflexia, extensor plantars, seizures
Cardiac: increased HR, prolonged QT
Pulmonary: hypoventilation
Rx: NaHCO3
MOA:
Paroxetine
Citalopram
Fluoxetine
Sertraline
SSRIs
MOA:
Venlafaxine
SNRI
MOA:
Amitryptiline
lofepramine
Clomipramine
Imipramine
Doxepin
Norttriptyline
TCA
Inhibit 5HT and NA uptake
MOA:
Phenelzine
Isocarboxacid
Moclobemide (A)
Selegeline (B)
MAOI
Inhibit monomaine metabolism
A: 5hT
B: Da
Side effects:
SSRIs
N/V/Diarrhoea
Insomnia
Headache
Sexual dysfunction
SIADH
Withdrawal effects
Side effects:
Venlafaxine
HTN
GI upset
Long QT
SIADH
Rash
Side effects:
TCAs
alpha1: postural hypotension
sedation
H1:
drowsiness
weight gain
AntiAChM
Arrhthmias, esp. heart block
Side effects:
MAOI
Sedation
Hypotension
Anti-AChM
Contraindications:
SSRO
Active mania
Children <18y (except fluoxetine)
Contraindications:
Venlafaxine
HF (3/4)
Uncontrolled HTN
Contraindications:
TCAs
Recent MI
Arrhythmias
Severe L
Mania
Caution:
Glaucoma
BPH
Contraindications:
MAOI
Phaeo
Interactions:
SSRI
P450 inhibitor- increase levels of TCAs
Benzos
Clozapine
Haldol
CBZ and PHE
SSRI + MAO-> serotonin syndrome
Increased risk of bleeding with aspirin
Interactions:
Venlafaxine
SSRI + MAOI-> serotonin syndrome
Increased risk of bleeding with aspirin
Interactions:
TCAs
MAOIs-> HTN and CNS excitiation
Levels increased by SSRIs
Increased risk of arrhythmias with amioarone
TCAs lower seizure threshold- reduced AED effects
Increased fx of antipsychotics
Interactions:
MAOIs
Hypertensive crisis: tyramine containing foods
Opioids- esp. pethidine
SSRIs + TCAs-> serotonin syndrome
Additional notes:
SSRI
Takes 4-6w for full clinical effect
Don’t stop suddenly
Avoid within 2w of MAOI
Used:
depression
OCD
Eating disorders
Anxiety disorders
Additional notes:
Venlafaxine
2nd line anti-depressant
Stop if signs of rash
Additional notes:
TCAs
Avoid within 2w of MAOI
Additional notes:
MAOI
Moclobemide is reversible and is selective for MAOI-A- less chance of interactions
MOA:
Paracetamol
Antipyretic
Analegsic
What are the strong opioids
Morphine
Diamorphine
Buprenorphine
Fentanyl
Pethidine
Oxycodone
What are the weak opioids?
Codeine
Dihydrocodeine
Tramadol
MOA:
Opiids
Analgesic effect mediated by u receptor
MOA:
Gabapentin as analgesic
Unknown
Side effects:
Paracetamol
Hepatic failure in OD
Side effects:
Opiates
CNS:
resp depression
sedation
N/V
euphroia
miosis
anti-tussive
dependance
Non-CNS
constipation
urinary retention
pruritus
bradycardia, hypotension
Side effects:
Gabapentin
Sedation
Cerebellar fx
Dizziness
Peripheral oedema
Contraindications:
Paracetamol
Severe L
Contraindications:
Opioids
Aboid in patients with acute resp depression
Head injury: can’t assess pupils
Interactions: Gabapentin
FX reduced by antidepressants
antimalarials
Additional notes:
Opioids
Rx OD with naloxone
Reduce does in: R, L, elderly
MOA:
Li
Mood stabiliser
MOA:
Chlorpromazine
Haldol
Sulpiride
Zuclopnehixol
Typical antipsychotics
Da antagonists
MOA:
Clozapine
Olanzapine
Quetiapine
Risperidone
Atypical antipsychotics
Da antagonists
MOA:
BZDs
Promote GABA binding to GABA A Rs
MOA:
Phenobarbitol
Potenitate GABAA receptors
Side effects:
Li
Polyuria and polydipsia
Nephrotoxic
CI upset
FIne tremor
Hypothyroidism
Toxicity:
Coarse tremor
Cerebellar signs
AKI
Hyper-reflexia
Coma
Side effects:
Typical antispychotics
Sedation
Anti-AChM
EPSE
Neuroleptic malignant syndrome
Prologned QT, postural hypotension
Increased PRL
Sexual dysfunction
Increased weight
Side effects:
Atypical antipsychotics
Clozapine: agranulocytosis, increased weight DM
Olanzapine: increased weight, DM, sedation
Quetiapine: sedation
Risperidone: increased weight, increased PRL
Side effects:
BZDs
Sedation
Respiratory depression
Withdrawal
Side effects:
Barbs
Sedation
Resp depression
Contraindications:
Li
Hypothyroidism
P/R/H
Interactions:
Li
Toxicity increased by NSAIDs
Diuretics (esp. thiazides)
ACEi/ARB
Interactions:
Typical antipsychotics
FX incresed by:
Li
TCAs
Interactions:
BZDs
Levels increased by:
antipsychotics
azoles
marcolides
Additional notes:
Li
Monitor: drug levels, U+Es, TFTs
Use: acute mania, prophylaxis of BAD, resistant depression
Increased toxicity when hyponatraemic or dehydratied- increased Li absoprtion in renal PCT
Additional notes:
Typical antipsychotics
Monitor FBC , U+Es, LFTs
Additional notes:
Atypical antipsychtoics
Can still-> EPSEs @ high doses (apart from clozapine)
Clozapine used in Rx of refractory schizophrenia and better at treating negative symptoms
Additional notes:
BZDs
Rx OD with flumazenil
Hepatic metabolism
IV diazepam is given as an emulsino to reduce risk of thrombophlebitis
Additional notes:
Phenobarbitol
CYP inducer
Primidone is phenobarbitol prodrug
What are the beta lactams?
Penicillins
Cephalosporins
Carbapenems
MOA:
Penicillins
Bactericidal
Inhibit bacterial transpeptidase enzyme required for wall construction
MOA:
Cephalosporins
Bactericidal:
Inhibit bacterial transpeptidase enzyme, required for cell wall construction
Generations have increasing activity vs gram negative
MOA:
Carbapenems
Bactericidal: inhibit bacterial transpeptidase enzyme required for cell wall construciton
V. broad spectrum: gram -ve, positive and anaerobes
Pseudomonas
Imipenem is rapidly inactivated by the kidney and must be given with cilastatin which blocks its metabolism
Use:
Pen V
Pen G (IV)
Streps
N. meningitidis
Syphillis
What are the broad spectrum penicllins?
Amoxicillin
Ampicillin
Use:
Amoxicillin
Ampicillin
Pneumococcus
Listeria
E. coli
Enterococci
Use:
Fluclox
Penicillinase resistant e.g. MSSA
Antipseudomonal beta lactams
Piperacillin
Ticarcillin
Use:
Co-amox
Severe CAP
UTI
Use:
Tazocin
Severe HAP
Sepsis
e.g. 1st gen ceph
Cephalexin
Cefaclor
e.g. 2nd gen ceph
Cefuroxime
e.g. 3rd gen ceph
Ceotaxime
Ceftriaxone
Ceftazidime
Cefixime
Use:
1st gen ceph
UTI
Use:
2nd gen ceph
Mod/severe CAP
GI sepsis
Pre-op
Use:
3rd gen ceph
Meningitis
Epiglottitis
Gonorrhoea
SBP
Use:
Imipenam
Meropenam
Ertapenam
All GM+Ve except MRSA
Most G-ve
Neutropenic sepsis
Side effects:
Penicllins
Hypersensitivity: rash, EM, anpahylaxis
GI upset
Maculopapular rash with EBV
Side effects:
Cephalosporins
GI upset
AAC
Side effects:
Carbapenems
GI upset
CIs:
Penicillins
Hypersensitivity (10% cross-reactivity with cephs)
Interactions: penicllins
May reduce Fx of OCP
Increased by probenecid
What are the Abx inhibiotrs of protein synthesis?
Chloramphenicol
Aminoglycosides
Tetracyclines
Oxazilidinones
Macrolidse
Streptogramins
Lincosamides
MOA:
Chloramphenicol
Bacteriostatic: 50s subunit
MOA:
Gentamicin
Amikacin
Tobramycin
Neomycin
Streptomycin
Aminoglycosides
Bactericidal: amino-acyl site of 30s subunit
MOA:
Tetracycline
Doxyclcine
Tetracyclines
Bacteriostatic: 30s subunit
MOA:
Linezolid
Oxazolidinones
Bacteriostatic, 23s component of 50s subunit
MOA:
Erythromycin
Clarithromycin
Azithromycin
Macrolides
Bacteriostatic: 50s subunit
MOA:
Synercid
Streptogramins
Bacteriostatic: 50s subunit
MOA:
Clindamycin
Lincosamides
Bacteriostatic- 50s subunit
Use:
Chloramphenicol
Conjuncitivits
Use:
Aminogylcosides
Gm sespsi
Neutropenic sepsis
Otitis externa
Anti-pseudomonal
Use:
Tetracyclines
COPD exacerbation
Acne
Chalmydia
Rickettsia
Brucella
Lyme disease
Use:
Linezolid
MRSA and VRE
No activity vs Gm-ve
Use:
Macrolides
Pen allergic
Aytpical pneumonias
Chlamydia
H. pylori
Use:
Synercid
VRE
MRSA
Use:
Clindamyicin
Acitve vs gm + ve cocci and bacteroides
Osteomyeltisis
MRSA
Side effects:
Chloramphenicol
Irreversible aplastic anaemia
Grey baby syndrome
Side effects:
Aminoglycosides
Nephrotoxic
Ototoxic
Side effects:
Tetracyclines
GI upset
Hypersensitivity
Bone deposition
Side effects:
Linezolid
Blood dyscrasias
Side effects:
Macrolides
Prolonged QT
Dry skin
Cholestatic hepatitis
Side effects:
Clindamycin
AAC
Hepatotoxicity
CIs:
Chloramphenicol
PLR
CIs:
Aminogylcosides
MG
Caution in R: alter dose and time
CIs:
Tetracyclines
Children M12
L
R
CIs:
Oxazolidinones
Caution in R and L
CIs:
Macrolides
Caution if prologned QT
CIs:
Clindamycin
Diarrhoea
Interactions:
Aminogylcosides
Reduced absorption with milk, antacids
Interactions:
Tetracyclines
Toxicity increased by:
frusemide
cephs
vanc
ciclopsorin
Interactions:
Macrolides
P450 inhibitor
increase W effects
Increase digoxin
Additional notes:
Aminogylcosides
MUst monitor levles- peak and trough
Must be given IV
Additional notes:
Linezolid
Linezolid is a non-selective MAOI- avoid SSRI, TCAs and tyramine
Monitor FBC
Additional notes:
Macrolides
Also have GI prokinetic action
Additional notes:
Synercid
Only used when other agents failred
Additional notes:
Clindamycin
Stop drug if patient develops diarrhoea
MOA:
Vancoymcin
Teicoplanin
Glycopetides:
inhibit cell wall synthesis
Unable to penetrate Gm-ve outer wall
Poor oral absoprtion
MOA:
Ciprofloxacin
Levofloxacin
Ofloxacin
Moxifloxacin
Fluoroquinolones
Inhibit DNA synthesis
MOA:
Metronidazole
Nitrofurantoin
Tinidazole
Nitroimidazole
Bactericidal
Inhibits DNA synthesis
MOA:
Rifampicin
Rifaximin
Rifabutin
Rifamycins
Bactercidal
RNA synthesis inhibitors
MOA:
Daptomycin
Cell membrane toxin
MOA:
Colistin
Cell membrane toxin
MOA:
Ethambutol
Bacteriostatic
Inhibits MTB cell wall synthesis
MOA:
Pyrazinamide
Bactericidal
MOA:
Isoniazid
Bacteriostatic
MOA:
Fusidate
Bacteriostatic
Use:
Glycopeptides
Aerobic and anaerobic Gm +ve
RMSA
HAN
Infective endocarditis
AAC (PO)
Use:
Fluoroquinolones
Broad spectrum esp. Gm-ve
GI infections: campy, shig
Pseudomonas esp. in CF
Prostatitis, PID
Anthrax
Use:
Nitroimidazoles
Anaerobes
GI sepsis
Aspiration pneumonia
AAC
H. pylori
PID
Protozoa: Giardia
Use:
Rifamycins
Mycobacteria
Legionella
Prophylaxis vs meningitis
Use:
Folate antagonist abxs
UTI
PCP
Toxoplasmosis
Use:
Daptomycin
MRSA: alternative to linezolid and syndercid
Use:
Colistin
Active vs Gm-ve
|nhaled for CF
Use:
Ethambutol
Pyrazinamide
Isoniazid
Anti-TB
Use:
Fusidate
Active vs staphs
Impetigo (topical)
Blepharitis (topical)
Osteomyelitis (PO)
Side effects:
Glycopeptides
Nephrotoxic
Ototoxic: tinnitus, SNHL
Hypersensitivity rash
Neutropenia
Side effects:
Fluoroquinolones
Long QT
Gi upset
Tendoninitis +/= rupture
Reduced seizure threshold
Photosensitivity
Side effects:
Nitroimidazoles
Metallic taste
GI upset
Metro: gynaecomastia`
Side effects:
Rifamyxins
Yellow secretions
Hepatitis
Side effects:
Folate antagonist Abxs
Blood dyscrasias
EM-> SJS
EN
Nephro + hepatotoxicity
Side effects:
Colistin
MG
Side effects:
Ethambutol
Optic neuritis
Side effects:
Pyrazinamide
Hepatitis
Gout
Side effects:
Isoniazid
Peripheral neuropathy
Hepatitis
Side effects:
Fusidate
Hepatitis
CIs:
Glycopeptides
Reduce dose in renal impairment
CIs:
Fluoroquinoones
P
CIs:
Rifamyxin
Jaundice
CIs:
Folate antagonist Abxs
Severe R and L
P
CIs:
Pyrazinamide
Caution in gout
Interactions:
Fluoroquinolones
P450 inhibitor
Antacids-. reduce absoprtion
Interactions:
Metronidazole
Avoid EtOH- disulfiram-like reaction
Interactions:
Rifamycins
P450 inducer:
reduced W
Reduced OCP
Redcued AEDs
Interactions:
Isoniazid
P45 Inhibitor
Additional notes:
Glycopeptides
Must monitor levels
Pre-dose trough
Additional notes:
Nitroimidazole
Aldehyde dehydrogenase inhibitor
Additional notes:
Rifamycins
Rifaximin has v poor oral absoprtion and is used in hepatic encephaloapthy
Additional notes:
Trimethoprim
Stop immediately if rash or dyscrasias occur
Additional notes:
Ethambutol
Monitor vision- colour goes first
Additional notes:
Pyrazinamide
Monitor LFts
Additional notes:
Isoniazid
Increaesd risk of SEs if slow acetylator
Give with pyridoxine
Additional notes:
Fusidate
Needs 2nd abx to prevent resistance
What is malarone
Proguanil and atovaguooone
What is riamet
Artemether and lumefantrine
Use:
Chloroquine
Benign malaria
Prophylaxis
Use:
Primaquine
Bening malaria- eliminate liver stage
Use:
Malarone
Falciparum malaria
Prophylaxis
Use:
Mefloquine
Prophlyaxis
Use:
Riamet
Falciparum malaria
Side effects:
Chloroquine
Visual change: rarely retinopathy
Seizures
EM-> SJS
Side effects:
Primaquine
Haemolysis if G6PDD
Methaemogolbinaemia
Side effects:
Malarone
Abdo pain
GI upset
Side effects:
Mefloquine
Nausea and dizziness
Neuropsychiatric signs
Side effects:
Riamet
Prolonged QTc
Abdo pain
GI upset
CIs:
Chloroquine
Caution in G6PDD
CIs:
Primaquine
Caution in G6PDD
CIs:
Malarone
Avoid in renal impairment in possible
CIs:
Mefloquine
Hx of epilepsy or psychosis
CIs:
Riamet
Hx of arrythmias
Prolonged QT
Caution in R/L
MOA:
Aciclovir
Guanosine analogue
Phosphorylated by viral thymidine kinase
Di and triphosphorylatd by cellular kinase
Acicilovir triphosphate inhibites viral DNA pol and is a poor substrate for host DNA pol and TK
MOA:
Valaciclovir
Aciclovir prodrug
Converted to aciclovir by hepatic esterases during FPM
Better oral bioavailability
MOA:
Famcilcovir
Pro drug with same MOA as aciclovir
MOA:
Ganciclovir
2-deoyguanosine analagoue
Phosphorylated to dGTD analoge by viral UL97
Triphosphate competitively inhibits viral DNA pol
IV only
MOA:
Valganciclovir
Ganciclovir prodrug with better oral bioavailability
MOA:
Foscarnet
Binds to pyrophosphate binding site and inhibits viral DNA pol
Doesn’t require viral TK
IV only
MOA:
Cidofovir
Inhibits viral DNA pol
No activation required
Use:
Aciclovir
Valaciclovir
Famciclovir
Genital herpes
Herpes meningitis
Herpes zoster
Varicella zoster
Bells palsy
Use:
Ganciclovir
Valganciclovir
CMV Rx: retinitis, pneumonitis
CMV prophylaxis
HHV-6 Tx disease
Use:
Foscarnet
CMV Rx
Use:
Cifodovir
Resistant CMV infections
Side effects:
Acilcovir etc
GI upset
ARF
Encephalopathy
Side effeccts:
Ganciclovir etcs
BM suppression
Side effects:
Foscarnet
Nephrotoxic- avoid in renal tx
Side effects:
Cidofovir
Nephrotoxic
CIs:
Aciclovir etc
Caution in renal impairment
CIs:
Foscarnet
Renal tx
Interactions:
Gancilcoivr
Increased risk of BM suppression with zidovudine
MOA:
Emtricitabine
Stuavudine
Tenofovir
Albacavir
Didanosine
Lamivudine
Zidovudine
Nucleoside reverse transcriptase inibitors
Except Tenofovir which is a nucleoTide RT inhibitor
MOA:
Ritonavir
Indinavir
Saquinavir
Lopinavir/ritonavir
PIs
Inhibit viral protease required for viral assembly
Ritonavir is used to boost levels of other PIs
MOA:
Efavirenz
Nevirapine
Non-competitive inhibition of reverse transcripatse
NB nevirapine is used to prevent HIV transmission during pregnancy
MOA:
Raltegravir
Elvitegravir
Inhibit integration of transcribed viral DNA into host genome
MOA:
Maraviroc
CCR5 inhibitor
Binds CCR5 preventing interaction with gp120 inhibiting attachment of HIV
MOA:
enfuviritide
Fusion inhibitor
Binds gp41 and inhibits fusion
Side effects:
NRTI
Hepatitis: stop if raised LFTs
Lactic acidosis (type B)
Painful peripheral neuropathy
Rash
GI distrubance
Side effects:
PIs
Metabolic syndrome
Lipodystrophy
Side effects:
NNRTI
Insomnia
Vivid dreams
EM-> SJS
Side effects:
Enfuviritied
Hypersensitivity at injection site
Lipodystrophy
Fat redistribution: reduced SC fat, increased abdo fat, buffalo hump
Insulin resistance
Dyslipidaemia
IRIS
Immune reconstitution inflammatory syndrome
Improvement in immune function 2o to ARV Rx
Marked inflammatory reaction vs residual opportunistic organisms
Paradoxical worsening of symptoms on initiaion of ARVs
What class of antifungals are:
Amphotericin B
Nystatin
Polyenes
What class of antifungals are:
Ketoconazole
Miconazole
Clotrimazole
Imidazoles
What class of antifungals are:
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Tirazoles
What class of antifungals are:
Terbinafine
Allylamines
What class of antifungals are:
Capogunfing
Echinocandins
MOA:
Polyenes
Interacts with ergotsterol-> pore formation
Fungicidal
MOA:
Imidazoles
Tirazoles
Blocks ergosterol synthesis by inhibiting 14a-demethylase-> reduced membrane fluidity
Inhibits replication
Prevents hyphae formation
Broad spectrum
Fungistatic
MOA:
Allylamines
Block ergosterol synthesis by inhibiting squalene epoxidase-> membrane disruption
Fungicidal
MOA:
Echinocandins
Inhibit beta-glucan synthesis
Fungicidal vs yeasts
Fungistatic vs moulds
MOA:
Flucytosine
Inhibits DNA/RNA synthesis
MOA:
Griseofulvin
Disrupts spindle formation in mitosis
Indication:
Amphotericin B
Severe systemic fungal infections (IV):
cryptococcal meningitis
pulmonary asperigollosis
systemic candidiasis
Indication:
Nystatin
Candidiais: cutaneous, vaginal, mucosal, oesophageal
Indication:
Ketoconazole
Chronic mucocutaneous candidiasis
Indication:
Miconazole
Clotrimazole
Dermatophyte infections
Mucocutabeous candidiasis
Indication:
Fluconazole
Oral/vag/oesophagus candida
Alternative to ampho B for systemic infections
Indication:
Itraconazole
Blasto/histo/coccidio
Sporotrichosis
Chromomycosis
Aspergillus
Indication:
Voriconazole
Invasive candida or aspergillus in immunocompromised
Indication:
Posaconazole
Invasive candida, mucor and asperigullus in immunocompromsied
Indication:
Allylamines
Dermatophyte infections
Indication:
Caspofungin
Invasive aspergillosis or candidiasis
Empiric Rx for fungal infection in febrile neutropenia
Indication:
Flucytosine
Cryptococcal meningitis in combination with amphotericin B
Indication:
Griseofulvin
Dermatophyte infections of skin/hair/nails
SEs:
Amphotericin B
Nephrotoxic
IV reaction (after 1-3h): fever, hypotension, n/v
SEs:
Nystatin
Toxic if given IV
SEs:
Ketoconazole
Hepatotoxic
Reduces androgen synthesis
SEs:
Voriconazole
Photophobia
Rash
Hepatotoxic
SEs:
Terbinafine
GI effects
Hive
Deranged LFTs
Reversible agranulocytosis
SEs:
Echinocandins
V low toxicity
GI upset
Hypersensitivity
SEs:
Flucytosine
Bone marrow suppression
Deranged LFTs
Additional notes:
Amphotericin B
Monitor Cr
PO version is non toxic
Additional notes:
Nystatin
PO or topical
Additional notes:
Fluconazole
P450 inhibitor
Additional notes:
Caspofungin
IV only
Additional notes:
Griseofulvin
Very slow acting
MOA:
Metformin
Biguanide
Insulin sensitiser: reduced gluconeogensis, increased peripheral glucose use, reduced LDL and VLDL
MOA:
Pioglitazone
Thiazolidinedione
Peripheral insulin sensitiser
PPAR gamma ligand (nuclear receptor involved in glucose and lipid homeostasis)
MOA:
Glclazide
Tolbutamide
Glipizide
Glibenclamide
Sulfonylureas
Insulin secretagogues
Block hyperpolarising K channels on beta cells-> depolarisation and insulin release
MOA:
Nateglinide
Repaglinide
Meglitinides
Insulin secretagogues
Block hyperpolarising K channel
MOA:
Exenatide
Liraglutide
Insulin secretagogue
GLP-1 analgoue: increased insulin and sensitisation
MOA:
Sitagliptin
Vildagliptin
Insulin secretagogues
DPP-4 inhibitor (DPP4 breaks down endogenous GLP-1)
MOA:
Acarbose
Intestinal alpha-glucosidase inhibitor
Delays carbohydrate absortion-> reduced post prandial glucose
Little effect on fasting lgucose
Side effects:
Metformin
Lactic acidosis
GI upset
Anorexia-> weight loss
Side effects:
Pioglitazone
Weight gain
Fluid retention
Hepatotoxicity
May exacerbate HF
Side effects:
Sulphonylurea
Hypogylcaemia (can be prolonged)
Weight gain (increased appetite)
GI upset
Headache
Side effects:
Nateglinide
Repaglinide
Hypoglycaemia
Side effects:
Exenatide
Hypoglycaemia
GI upset
Side effects:
gliptins
Hypoglycaemia
GI upset
Side effects:
Acarbose
Flatulence
Loose stools/diarrhoea
Abdo pain/bloating
Hepatotoxicity
Contraindications:
Metformin
Caution in R/H
Contrastmdia
General anaesthesia
Recent MI
Contraindications:
Pioglitazone
H/L
Insuline use
ACS
Contraindications:
Sulphonylureas
Severe L/R
Acute prophyria
Contraindications:
Acarbose
IBD
L
Interactions:
Sulphonylureas
Fx increased by:
sulphonamides
trimethoprim
NSAIDs
Warfarin
Fibrates
Additional notes:
Metformin
Renally excreted: reduce dose or avoid if reduced eGFR
Cannot cause hypos
Additional notes:
Pioglitazone
Don’t use with insulin
V. protein bound
Hepatic metabolism
Monitor LFTs
Additional notes:
Sulphonylureas
Renally excreted
V. albumin bound
Caution in elderly with reduced renal function
Avoid lon-acting in elderly
Additional notes:
Meglitinides
V short acting- reduced risk of hypo
Additional notes:
Exenatide
Administer by SC injection
Additional notes:
Acarbose
Monitor LFTs
MOA:
Octreotide
Somatostatin analgoue
MOA:
Pegvisomant
GH R antagonist
MOA:
Metyrapone
11beta hydroxylase inhibitor: inhibits adrenal cortisol production
Side effects:
Octreotide
Diarrhoea
Gallstones
Side effects:
Metyrapone
Hypoadrenalism
Use of Da agonists in pit disease
Use:
prolactinoma
can be used in acromegaly
Monitor heart with echo
Use of octreotide
Acromegaly
Carcinoid
Use of pegvisomant
Acromegaly
Use of metyrapone
Can be used in Cushing’s
particularly if resistant to surgery
MOA:
Cinacalcet
Calcimimetic- reduces PTH secretion
MOA:
Sevelamer
Phosphate binder
MOA:
Alendronate
et.c
Bisphosphonates- reduce osteoclastic bone resorption
MOA:
Strontium
Increased bone formation
Reduced bone resorption
MOA:
Teriparetide
Recombinant PTH
pulsatile admin-> increased bone formation and reduced resorption
MOA:
Denosumab
Anti- RANKL
reduced osteoclast activation
MOA:
Ergocalciferol
D2
MOA:
Cholecalciferol
Vit D3
Alfacalcidol
1a (OH) Vit D3
Calcitriol
1,25 (OH) D3
Side effects:
Sevelamer
GI upset
Side effects:
Bisphosphonates
GI upset
Oesophagitis
Osteonecrosis of the jaw
Diffuse MSK pain
Side effects:
Strontium
DRESS syndrome: Drug Rash
Eosinophilia
Systemic symptoms
Side effects:
Teriparetide
GI upset
Contraindications:
Sevelamer
GI obstruction
Contraindications:
Bisphosphonates
Achalasia
Oesophageal stricture
Contraindications:
Teriparetide
Skeletal malignancies
Paget’s
Severe R
Additional notes:
Cinacalet
Used for Rx of 2o HPT in ESRF
Additional notes:
Sevelamer
Used to reduce PO4 in ESRF
Additional notes:
Bisphosphonates
Used to:
prevent osteoporotic fractures
prevent osteoporosis
Hypercalcaemia of malignancy
Paget’s
Take with glass of water on an empty stomach 30 mins before breakfast and sit uprighht
Use of strontium or denosumab
Used if bisphosphonates not tolerated
Benefits:
POP
Contraception
Reduces dysmenorrhoea, menorrhagia, PMT, benign breast disease, ovarian and endometrial cancer, risk of PID
Benefits:
HRT
Reduces: hot flushes, vaginal dryness, increased libido
Redcued urinary frequency/urgency
Reduced risk of bowel Ca
Reduced risk of osteoporotic #s
Side effects:
COCP
Increased risk of VTE
Increased risk of breast Ca
Small increased risk of IHD
Gallstones
Cholestatic jaundice
Breast tenderness
Hepatoma
Side effects:
POP
N/V
Headache
Increased weight
Breast tenderness
Side effects:
HRT
Increased risk of Ca: breast, endometrial, ovarian
increased risk of VTE
Increased risk of stroke and IHD
Cholestatic jaundice
Contraindications:
COCP
Personal Hx of VTE
Risk of VTE
Risk of arterial disease
Hx of breast Ca
Migraine
Contraindications:
POP
Severe arterial disease
Hx of breast cancer
Contraindications:
HRT
Oestrogen dependant breast Ca
Hx of breast Ca
UnDx vaginal bleeding
VTE
VTE risk in COCP
FHx of VTE
BMI >30 (avoid if over 35)
LT immobilisation
Hx of superficial thombrophlebitis
>35y/o, avoid if >50
Smoking
Arterial risk in OCP
FHx of arterial disease
DM
HTN
Smoking (avoid if >40/d)
>35y, avoid if >50
Migraine without aura, avoid if migraine with aura
Interactions:
COCP
P450 metabolism: reduced effectiveness with enzyme inducers
Increases fx of steroids
Interactions:
POP
P450 met: reduced effectiveness with enzyme inducers
Additional notes:
OCP
Don’t need extra contraception when taking with oral Abx that don’t induce liver enzymes unless D/V
Additional notes:
HRT
Excess Ca risk disappears within 5y of stopping
Which opioids are recommended in CKD?
Fentanyl
Buprenorphine
Indications for gradual withdrawal of corticosteroids
>40mg pred for >7d
>3w treatment
Recently received repeated courses
