3rd Year Pharmacology Revision:!

Anti-arrhythmia drugs and antibiotics!

Keri McLean !
Intercalating in MRes in Clinical Science (Eye and Vision)!
1
 Aim  
  ‘Ten  ways  to  kill  a  pa0ent’    -­‐    summary  of  Dr  Fitzgerald’s  lecture.        
Possible  exam  ques0on.  
  Narrow  therapeu0c  index  drugs  
  Inducers  and  inhibitors  of  cytochrome  P450  

An&-­‐arrhythmics    
  Vaughan-­‐Williams  classifica0on  of  An0-­‐arrhythmic  drugs  

  An0-­‐arrhythmic  drug  mechanism  of  ac0on,  side  effects,  indica0ons  

  Treatment  of  common  arrhythmics  

An&bio&cs  
•  Gram  +/-­‐  bacteria  and  common  organisms  of  infec0on  
•  Mechanism  of  ac0on,  side  effects  
•  Rough  guide  to  an0bio0cs  

2!
Ten  ways  to  kill  a  pa&ent…CAUTION!  
  Methotrexate  and  trimethoprim  (both  block  dihydrofolate  reductase  
causing  severe  bone  marrow  depression)  
 
  Allopurinol  and  azathioprine  (Increases  6  mercaptopurine  leading  to  
severe  bone  marrow  depression)  

  Beta-­‐blockers  and  cardioselec&ve  CCB  i.e  dil0azem  and  verapamil  

(Inhibit  both  SA  and  AV  node  =  severe  bradycardia)  
 
  Lithium  and  bendroflumethiazide  (decreases  sodium  adsorp0on  
therefore  increases  lithium  absorp0on  leading  to  toxicity)  
 
  Lithium  and  drugs  which  decrease  GFR  i.e.  NSAIDs  and  ACE  inhibitors  

3! Adapted from Dr Fitzgerald lecture!

Ten  ways  to  kill  a  pa&ent…CAUTION!  
  5-­‐fluoroquinolones  (ciprofloxacin,  levofloxacin,  norfloxacin)  lowers  
the  seizure  threshold  -­‐>  grand  mal    
 
  Gentamicin  can  cause  dose  related  ototoxicity  and  nephrotoxicity  ARF  
  Penicillin  allergy:    give  carbapenems  and  cephalosporins  with  cau0on  
 
  Monoamine  oxidase  inhibitors  and  tricyclic  an&depressants  =  
‘sympathe0c  surge’  of  NA  and  5-­‐HT  =  malignant  hypertension  etc.    
Leave  3  weeks  between  stopping  MAOi  and  commencing  other  
an0depressants.  
 
  Drug  route:    Never  give  vincris0ne  intrathecally  =  neurotoxic  =  death.  

4!
 Narrow  Therapeu&c  Index  
These  drugs  need  to  be  monitored    
  Digoxin  

  Amiodarone  

  Lithium  

  Methotrexate  

  Warfarin  

  Carbamazepine  

  Theophylline  

  Gentamicin  and  vancomycin  

  Digoxin  toxicity:    Nausea,  vomi0ng,  yellow  halos  and  blurred  

vision.    Arrhythmias:  classic  atrial  tachycardia  with  AV  block  
  Lithium  toxicity:  D&V,  course  tremor,  cerebellar  signs  (DANISH),  
low  BP,  increase  reflexes,  seizures,  coma  
5!
 Cytochrome  P450  Inducers  
Increase  drug  metabolism/breakdown  =  reduces  the  effects  
of  other  drugs  metabolised  by  CYP450.    Takes  2-­‐3wks  to  
develop  
 

P  henytoin  
C  arbamazapine   Can cause
 
failure of COCP
B  arbiturates  
R  ifampicin  
A  lcohol  (chronic)  
S  ulhonylureas   6!
 Cytochrome  P450  Inhibitors  
Reduces  drug  metabolism/breakdown  =  increased  effect  of  other  
drugs  metabolised  by  CYP450.    Immediate  effect!  
 
S  odium  valporate  
I  soniazide    
C  iprofloxacin  
K  etoconazole   E.g. Macrolide antibiotics
(inhibitor) and warfarin (reduced
F  luconazole  
metabolism)
A  lcohol  (Acute)  
C  ime&dine  
E  rythomycin  
S  ulphoamides    
.  
C  hloramphenicol  
O  meprazole  
M  ethronidazole                                                                                          (Grapefruit  juice)  
7!
 An&-­‐arrhythmic  drugs  
Vaughan-­‐Williams  classifica&on:  
 

Class  I:  Fast  Na+  channel  inhibitors  

Ia  -­‐  lengthens  AP  
Disopyramide:  Parasympathe0c  S/E  
Ib  -­‐  shortens  AP  
Lidocaine:  used  in  VT,  S/E  drowiness,  paraesthesia,  convulsions  
Ic  -­‐  No  net  effect  on  AP  
Flecainide  (Pill  in  pocket  for  paroxysmal  AF)  
Slows  conduc0on  through  purkinje  fibres,  prolongs  QRS.    
Contraindicated  in  prior  MI  pa0ents.  
 
Class  II  :  An&sympathe&cs  i.e.  Beta-­‐blockers  (bisoprolol,  atenolol,  
propanolol)  
Slow  conduc0on  through  AV  node  
Used  for  supra  ventricular  arrhythmias  
8!
 An&-­‐arrhythmic  drugs  
Vaughan-­‐Williams  classifica&on:  
 

Class  III:  Prolong  AP  dura&on  i.e.  Amiodarone  

Inhibits  repolarisa0on  therefore  increases  QT  length.  
Best  for  use  in  heart  failure  
Significant  non-­‐cardiac  toxicity:  
 
 
  Slate-grey discolouration!
Corneal micro-deposits!
  pulmonary fibrosis!
  Hyper/hypothyroidism!
  Peripheral neuropathy!
 
Class  IV  :  Calcium  channel  blockers  i.e  verapamil  and  dil&azem  
Prophylaxis  in  SVT  

9!
Beta-­‐blockers:  
  Block  beta-­‐adrenoreceptors  =>  reduce  exer0onally-­‐induced  rise  in  HR  and  
reduce  cardiac  contrac0lity.    Reduces  systolic  BP  and  myocardial  demand  
for  O2.    
Blocking  Beta1  receptors  =  -­‐ve  inotropic  and  -­‐ve  chronotropic  
Blocking  Beta2  receptors  =  peripheral  vasoconstric0on  and  
bronchospasm.  
Propranolol  is  non-­‐selec0ve  and  bisoprolol  is  rela0vely  B1  selec0ve  
 
  Indica&ons:  angina,  arrhythmia,  heart  failure  (bisoprolol  and  carvedilol  

licensed),  prophylasis  post-­‐MI,  hypertension.  

 
  S/E:  Bronchspasm,  cold  peripheries,  bradycardia  and  hypotension,  

erec&le  dysfunc&on,  reduced  glucose  tolerance,  hyperkalaemia,  

headache,  heart  block.  

  Contraindicated  in  Asthma/COPD,  bradycardia,  heart  block,  hypotension  

and  severe  peripheral  artery  disease,  with  CCBs.  
10!
Calcium  channel  blockers  (CCB):  
  Block  L-­‐type  calcium  channels  into  cells    =>  reduce  myocyte  contrac0on    
Dihydropyridine  (nifedipine,  amlopidine,  felopidine)  are  highly  
vascular  selec0ve  therefore  cause  peripheral  and  coronary  vasodila0on  
(Heart  rate  neutral).    Cause  cause  reflex  tachycardia…may  need  to  be  used  
with  beta-­‐blockers.  
Verapamil  and  dil0azem  are  cardioselec0ve  =>  reduce  cardiac  
contrac0lity  and  slow  conduc0on  at  the  AV  node.    (Heart  rate  limi0ng).  
 
  Indica&ons:  hypertension  and  SVT  (verapamil  and  dil0azem)  

 
  S/E:  Bradycardia  (verapamil  and  dil0azem),  reflex  tachycardia  

(dihydropyridines),  hypotension,  vasodilatory  effect  (flushing,  headaches,  

ankle  swelling,  palpita0ons)  
 
  Verapamil  and  dil0azem  contraindicated  in  LVF,  heart  block,  bradycardia  

and  with  beta-­‐blockers.  

11!
Digoxin:  
  Blocks  Na+/K+  pump.    Used  to  slow  pulse  in  fast  AF.  
  Weak  +ve  inotrope    
 
S/E:  
•  GI  disturbance  
•  Dizziness  
•  Arrhythmias  
•  Rash  
Toxicity:  
•  Blurred  or  yellow  vision  (xanthopsia)  
•  Abdominal  pain  
•  Arrhythmias  
 
Contraindica&ons:  
•  Complete  heart  block  and  second  degree  heart  block  
•  VT  /  VF  
Interac&ons:  
•  Risk  of  hypokalaemia  with  diure0c  =>  arrhythmias  
•  Risk  of  AV  block  and  symptoma0c  bradycardia  with  beta-­‐blockers  

12!
 Superventricular  tachycardia  (SVT)  

ECG features:
P waves absent or inverted after the QRS!
Narrow complex (QRS <120ms) tachycardia (>100bpm)!
13!
 Superventricular  tachycardia  (SVT)  
Treatment:
!

1)  Carotid sinus massage, valsalvas, diving reflex!

2)  If haemodynamically stable: IV adenosine!
Stimulates alpha1 receptors on myocardiocytes to
influence adenosine-sensitive K+ channel and cAMP to
prolong conduction through AV node => Cause a
transient AV block!
Warn patient about the ‘feeling of impending doom’,
chest pain, dyspnoea and flushing.!
Cardiac monitor and defib!!
If this fails try a cardioselective calcium channel
blocker !
i.e verapamil or a beta-blocker!
3) DC cardioversion, pacing or radiofrequency ablation!
14!
!
 Atrial  Fibrilla&on  

Three  main  causes:  

Ischaemic  heart  disease  
Rheuma0c  heart  disease  
Thyrotoxicosis  
ECG  features:  
Absent  P  waves  
Irregular  QRS  complexes  
! 15!
 Atrial  fibrilla&on    
Acute:
If pt is stable chemically cardiovert with IV Flecainide (No structural
damage) or Amiodarone (if structure damage i.e. previous MI). !
If unstable DC cardiovert.!
Anticoagulate with warfarin.!
!
Paroxysmal: AF >30 mins 3-4 times yearly.!
Pill in the pocket: Flecainide !
!
Persistent: >48hrs but <2years !
First Rate control: Beta-blocker. !
Warfarin followed by echocardiogram and elective cardioversion.!
!
Permanent: >2yrs, failed DCCV, dilated LV, mitral stenosis !
Beta-blocker, ±digoxin, ±amiodarone with anticoagulation
!
16!
 Atrial  Flu_er  

ECG  features:  
Ventricular  rate  approx  150bpm  (due  to  2:1  block,  atrial  
rate  ~300bpm)  
‘Saw-­‐tooth’  baseline  
 Treatment:!
!1)  Carotid massage!
2)  IV adenosine to block AV node and reveal flutter waves !
3)  DC Cardioversion or amiodarone!
! 17!
 Ventricular  Tachycardia  

ECG  features:  
Tachycardia  with  broad  QRS  complexes  
 
Treatment:  
Correct  hypokalaemia  and  hypomagnesia  
IV  amiodarone  
DC  Shock  
Maintenance  oral  amiodarone  
! 18!
 Ventricular  fibrilla&on    
Defibrillator  

Bardycardias  and  Heart  Block  

Atropine  (An0muscarinic)  
 
An&-­‐muscarinic  S/E:  Cons0pa0on,  Urinary  reten0on,  Dry  
mouth,  Blurred  vision,  Drowiness  
Cau&on/contrainidica&on:  myasthenia  graves,  paraly0c  
ileus  
 
Pace  marker  

19!
Bacteria  
Blue/Purple Red/pink

20!
 Bacteria  
Gram +ve cocci Gram -ve cocci
Staphylococci! Neisseria meningitidis!
Streptococci! Neiserria gonorrhoea!
Enterococci! Moraxella catahalis!
Acinetobacter!
Gra!
Gram -ve rods
Bacteroides!
E.coli!
Gram +ve rods Klebsiella!
Enterobacter!
Clostridia (Anerobe)! Proteus!
Salmonella!
Listeria! Shigella!
Pseudomonas!
Bacillus! Haemophilis!
Helicobacter, Campylobacter!
! Legionella!

21!
22!
Sulphonamides, trimethoprim, quinolone
and nitroimidazoles: Inhibit nucleic acid
synthesis

23!
 Trimethoprim
Binds to bacterial dihydrofolate reductase and
irreversibly inhibits production of dihydrofolate, which is a
precursor for the synthesis of thymidine = inhibits
bacterial DNA synthesis!
!
Indication: UTI

S/E: GI disturbance, pruritis, rashes and

hyperkalaemia

Caution: Blood dycrasias and patients with renal

impairment

24!
 Quinolones: ciprofloxacin, levofloxacin!
Inhibits type I (DNA gyrase) and type IV topoisomerases
required for bacterial DNA replication, transcription, repair
and recombination!
!
Indication: UTI, GI infections, bronchopulmonary
infections, typhoid, gonorrhoea and anthrax
Cipro- is active against E. coli, Pseudomonas aeruginosa,
salmonella and campylobacter

S/E: GI disturbance, tendonitis, headaches, seizures

confusion, anxiety and depression
Contraindicated : Hx of tendon disorders related to
quinolones, pregnant, children and growing adolescents
(Risk of joint arthropathy), epileptic pts
25!
 Metronidazole:
!
Indication: Anaerobic infections (dental and abdominal sepsis),
Aspiration pneumonia, protozoal infections and Pelvic
inflammatory disease

S/E: GI disturbance, metallic taste in mouth, anorexia,

hepatitis, pancreatitis, peripheral neuropathy

Active against most anaerobic bacteria

26!
 Penicillins, cephalosporins and
!
vancomycin: inhibit cell wall synthesis

27!
 Penicillins: benzylpenicillin, flucloxacillin,
ampicillin, amoxicillin, Co-amoxiclav !
!
Beta-lactem binds to and inhibits the transpeptide required to
form peptidoglycan cross-links within the bacterial cell wall =
defective cell wall synthesis => cytolysis!
!
Indication: Tonsillitis (Pen V), Pneumonia (amoxicillin), cellulitis
(flucloxacillin), meningitis (BenPen), endocarditis, Rheumatic
Fever (Pen V), Osteomyelitis!
Amoxicillin is broad spectrum
S/E: Urticarial rash, anaphylaxis, GI disturbance, Antibiotic-
associated colitis, Steven-Johnston syndrome
Contraindicated : Hypersensitivity
Beta-lactamases produced by bacteria breakdown Beta-lactem
ring and give resistance.
28!
 Cephalosporins: 1st gen: cefalexin; 2nd gen:
cefuroxime; 3rd gen: cefotaxime, ceftriaxone!
Carbapenems: meropenem, piperacillin!

Similar mechanism to penicillin but these are highly resistant to

staphylococcal Beta lactamases.!
Tazocin: pipercillin + tazobactam (Beta lactamase inhibitor) =
good for Pseudomonas
!

Indication: Pneumonia, sepsis, Biliary tract infection, UTI,

peritonitis, meningitis
S/E: 10% pts hypersensitive to penicillin will have reaction with
cephalosporins Urticarial rash, anaphylaxis, GI disturbance,
Antibiotic-associated colitis, Steven-Johnston syndrome,
cholestatic jaundice (ceftriaxone)

Contraindicated : Hypersensitivity
29!
 Glycopeptide antibiotics: Vancomycin
and teicoplanin!
Inhibit bacterial cell wall synthesis by streakily and irreversibly
blocking the elongation of peptidoglycan chains = bactericidal !
!

Indication: gram +ve MRSA and penicillin resistant

pneumococci, endocarditis, C. difficile
S/E: Nephrotoxicity, ototoxicity, fevers and chills, hypersensitvity,
neutropenia, thrombophlebitis at IV admin site.

Contraindicated : Hypersensitivity

Monitor: FBC and U&Es!

!
High molecular weight = cannot penetrate gram -ve bacteria!
Poor oral absorption, useful for treating C. difficile.
30!
 Aminoglycosides, tetracyclines, macrolides
and chloramphenicol: inhibit protein synthesis

31!
 Aminoglycosides: Gentamicin,
neomycin, streptomycin
!
!
Block protein synthesis by binding to bacterial 30s ribosome
subunit. Prevents tRNA attachment and mRNA translation is
disrupted!
!
Indication: Septicaemia, biliary tract infection, acute
pyelonephritis and prostatitis, endocarditis, adjunct in Listeria
meningitis

S/E: GI disturbance, nephrotoxicity, rash, ototoxicit, blood

dyscrasias

Contraindicated : Myasthenia graves and renal impairment

32!
 Macrolides: Erytheromycin,
azithromycin and
!
clarithromycin!
Inhibit bacterial RNA-dependent protein synthesis by reversibly
binding to 50S subunit of ribosomes within the organism = affects
growth either bacteriostat or bactericidal !
!
Indication: RTI, campylobacter enteritis, Pertussis, skin and soft
tissue, otitis media, Helicobacter pylori

S/E: GI disturbance, Hepatitis, anorexia, pancreatitis,

headaches

Contraindicated : Liver disease and hypersensitivity

P450 inhibitor

33!
 Tetracyclines: Doxycyclin,
tetracycline, ! oxytetracyclin!
Active uptake resulting in inhibition of protein synthesis. Binds to
30s ribosomal subunit and inhibits aminoacyl tRNA and mRNA
ribosomal complex formation!
!

Indications: Urogenital infections (salpingitis, Chlamydia

urethritis), LTRI (Haemophilus in COPD pts), Acne vulgaris and
rosacea, malaria prophylaxis
S/E: GI disturbance, dysphagia and oesophageal irritation,
blood disorders, hypersensitivity and photosensitivity
Contraindicated : Hypersensitivity, children under 12,
pregnancy and breast feeding (teratogenic), acute porphyria,
CKD

P450 inhibitor
34!
 Chlorampheicol
Inhibit transpeptidation.!
!

Indications: Bacterial conjunctivitis, typhoid fever, H.

influenzae miningitis
S/E: Bone marrow aplasia (Usually fatal), peripheral and optic
neuritis, reversible (dose-related) suppression of red and
white blood cells.
Contraindicated : Renal impairment, Pregnant pts at term and
infants under 3mths (risk of haemolytic anaemia of the newborn)

35!
 Nitrofurantoin
Metabolites damage a number of macromolecules within
bacterial cells including ribosomal proteins and DNA =
bactericidal !
!

Indications: Uncomplicated UTI. Active against most urinary

pathogens E. coli, Enterococcus faceless, Klebsiella and
staphylococcus
S/E: GI disturbance, peripheral neuropathy, hyersensitivity,
pulmonary fibrosis (Prolonged use), haemolytic anaemia,
hepatic dysfunction
Contraindicated : Renal impairment, Pregnant pts at term and
infants under 3mths (risk of haemolytic anaemia of the newborn)

36!
‘4 Cs’ for antibiotic causes of Clostridium difficile

Cephalosporin
Clindamycin
Co-amoxiclav
Ciprofloxacin

37!
 Tuberculosis treatment: RIPE

Rifampicin: Orange secretions, Hepatitis,

P450 inhibitor

Isoniazid: Peripheral neuropathy, hepatitis,

agranulocytosis, pyrodoxine deficiency (B6)

Pyrazinamide: Arthralgia and hepatitis

Ethambutol: Optic neuritis (Red desaturation!

38!
EBV and amoxicillin reaction: Don’t prescribe
for tonsillitis

39!
 Rough guide to antibiotics
Upper RTI
Bacterial tonsilitis!
Acute sinusitis!
Otitis media!
Lower RTI
Community acquired pneumonia!
Exacerbation of COPD!
Atypical pneumonia!
Hospital acquired pneumonia
>48hrs after admissionA!
Aspiration pneumonia!
Common organisms Antibiotic
Penicillin V 7 days Allergic:
Group A Beta haemolytic strep!
Cefalexin!
Amoxicillin 7 days
Persistant: Co-amoxiclav!
Streptococcus pneumoniae! Amoxicillin 5 days Allergic:
Haemophilus influenzae! Cefalexin!
Common organisms Antibiotic
Streptococcus pneumonia
Haemophilus influenzae! Amoxicillin 5 days!
Mycoplasma pneumoniae!
Haemophilus influenzae! Amoxicillin or doxycycline 5 days!
Erythromycin!
Gram -ve bacilli! Tazocin (Pipercillin and
Pseudomonas! Tazobactam)!
Anaerobes!
Cefuroxime and metronidazole!
Streptococcus pneumonia!
40! Cheshire antibiotic guidelines!
 Rough guide to antibiotics
UTI Common organisms Antibiotic

Uncomplicated (woman <65yo, 1st

E. coli! Trimethoprim or nitrofurantoin 3
prescription, not pregnant, no GU
abnormalities)! Enterococcus faecalis, Klebiella! days!

UTI in pregnany! Nitrofurantoin 7 days!

Pyelonephritis! Co-amoxiclav 14 days!

Prophylaxis of recurrent UTI! Trimethoprim 100mg nocte!

Skin and soft tissue Common organisms Antibiotic

Impetigo! Staphalococcus aureus! Fucidin topical of flucloxacilllin!

Cellulitis! Group A staph and strep! Flucloxacillin 7 days!

Staph and strep. i.e. strep Chloramphenicol continue 48hrs

Eye conjunctivitis!
pneumoniae! after resolution!

Bite wounds animal /human! Co-amoxiclav 7 days!

41! Cheshire antibiotic guidelines!

 Rough guide to antibiotics
GI tract Common organisms Antibiotic

Diarrhoea! Retrain. Take oral rehydration.!

Metronidazole 10-14 days!
Clostridium difficile! 2nd episode/severe = Vancomycin!

Campylobacter! Clarithomycin 5 days!

Giardiasis! Metronidazole 3 days!

Genital tract infections Common organisms Antibiotic

Vaginal candidiasis! Candida albicans! Clotriazole 500mg pessary!

Trichomonas vaginalis! 2mg metronidazole PO stat!

Gardnerella vaginalis, mycoplasma
Bacterial vaginosis! hominis!
2mg metronidazole stat!

Chlamydia trachomatis! Azithromycin 1g stat!

Syphillis! Treponema pallidum! Benzthine or Penicillin !

Gonorrhoea! Neisseria gonorrhoea! Ceftriaxone stat!

Neisseria gonorrhoeae or
Pelvic inflammatory disease (PID)! Chlamydia trachomatis!
Ofloxacin and metronidazole BD 14 days!

Epididymitis! Chlamydia, neiserria gonnorhoea! Ofloxacin BD 14 days!

Coliforms, chlamydia, neiserria
Prostatitis! Ciprofloxacin BD 28days!
42!
gonnorhoea! Cheshire antibiotic guidelines!
 Rough guide to antibiotics !

Meningococcal disease: !
!
In the community give IM benzylpenicillin!
!
Then 3rd generation cephalosporin i.e. IV Ceftriaxone!
!
If patient under 3months old cover for Listeria with
addition of Ampicillin !

43!