Showing posts with label Pharmacology. Show all posts
Showing posts with label Pharmacology. Show all posts

Tuesday, 4 May 2010

Prescribing Safely

  • Know a lot about drugs
  • Only prescribe for a narrow list of drugs that you know really well
  • Use more established drugs, and avoid new drugs unless they really are an advance
  • Be careful prescribing drugs to young women
  • Use low doses in the elderly
  • Double check with the BNF if you are prescribing a drug

–For the first time
–To someone on lots of other drugs
–To someone with liver or kidney disease

ALWAYS WRITE
–Name

–Date of birth
–Hospital Identity number
–Allergies
–Date of admission
–Consultant’s name
–Prescriber’s name and bleep no.

Avoid decimal points

Units
–g: grams
–mg: milligrams
–mcg: micrograms
–ng: nanograms
–U: units

Formulation of the drugs:
-tabs (tablets)
-caps (capsules)

Frequency:
–od–once a day
–bd–twice a day
–tds–three times a day
–qds–four times a day
–PRN(still need to give maximum dose)
–1ยบ-1 hourly

Route of Administration
–po-orally
–iv -intravenously
–im-intramuscularly
–top–topical (state where)
–s/c-subcutaneously

Special instructions
e.g. take before food

Finally
SIGN and DATE

Sunday, 2 May 2010

Adverse Drug Reactions

Drugs with low therapeutic ratio:
Anticoagulants
Antidiabetic drugs
Anticonvulsants
Digoxin
Cancer drugs


Patient Fx:
Elderly
Polypharmacy
Co-existing liver/kidney disease

Young women with child-bearing potential
IV drugs

Drug Reaction Classifications:
Type A - common, dose related, low mortality
Type B - uncommon, not dose related, high mortality
Type C - uncommon, dose and time related eg cumulative dose

Statins
AE
Myositis
Measure CK & LFTs before and 1-3 months after
If CK >x10 normal = stop drug (risk of rhabdomyolysis)
If Transaminases rise >x3 normal = stop drug

Erythema Nodosum
...from...
- oestrogens
- sulphonamides
- phenytoin
- penicillins

Stevens-Johnson Syndrome (toxic epidermal necrolysis)
Immune response to drug in skin and mucous membranes
- sulphonamides (including sulphasalazine)
- co-trimoxazole
- penicillins
- lamotrigine & phenytoin
- barbiturates

Yellow Card scheme
- intensive event monitoring
- doctors, pharmacists and pharm industry
- report suspected AE in newly licensed drugs as well as in older medicines
- cards in back of BNF
- new drugs highlighted in BNF, MIMS and ABPI by black triangle

NB More difficult to identify common adverse events

Acute Poisoning - TCAs, Lithium & Digoxin

Tricyclic Antidepressants

2.5-3.5g of amitriptyline

Anticholinergic effects = Neuro & Cardio problems
Usually w/i 6 hrs = severe effects:
- Ventricular arrhythmias
- Seizures
- Hypotension
- Respiratory depression


Lithium

Different forms:
- liquid peaks at 30mins
- tablets peaks at 4-5hrs
1/2 life = 8 - 45hrs

Higher toxicity - in HT, DM, CCF


Digoxin
Plasma = >10ng/mL

Toxicity
Fatigue, blurred vision, disturbed colour perception (Van Gogh's halos)
Anorexia, nausea, vomiting, diarrhoea, abdominal pain
Headache, dizziness, confusion, delirium, and occasionally hallucinations
Cardiac arrhythmias - most common cause of mortality & most common pattern =  SVT + AV Block

Hypokalaemia predisposes
Hyperkalaemia a consequence

Ix
Upper normal limit = 2ng/mL (without predisposing factors)
Measure plasma levels 6hrs after last dose

Tx
Activated charcoal (within 6-8hrs) or cholestyramine
Correct electrolyte abnormalities - careful replacement of potassium (too rapid can increase AV block)
Hyperkalaemic = glucose, insuline and sodium bicarbonate
Digoxin-specific antibody Fab fragments - binds to circulating digoxin
if >10mg ingested in adults
if >4mg ingested in children
or plasma concentration >10ng/mL
or >5mmol/L with life-threatening arrhythmia - VT, VF, progressive bradycardia/high-degree AV nodal block

Partial response/resistance
Underlying heart disease/late administration/ too small a dose

NB dramatic hypokalaemia can occur after digibind threapy at 1-4hrs therefore MONITOR!!

Extracorporeal techniques
Haemodialysis/haemoperfusion
- helps with hyperkalaemia/volume overload with renal failure
h/e less helpful due to digoxin's large distribution and binding to tissue

Acute Poisoning - Paracetamol & Salicylates


Paracetamol

Overwhelming of body's glutathione, in its inactivation of paracetamol's toxic metabolite
Safe up to 150mg/kg
>350mg/kg = extensive damage
Hepatotoxic
Nephrotoxic
High risk - malnourished, immunocompromised, anti-epileptics, anti-TB medication, alcohol excess

Ix
Levels
Standardised Treatment Graph - normal and high risk treatment lines

Tx
N-acetylcysteine - supplies glutathione
Side-effects - wheezing, flushing hypotension, bronchospasm, anaphylactoid reation
Alternative is methionine PO (<12hrs)


Salicylates
1 tube of bonjela cream = 970mg

Ix
Levels at every 4 hrs
>500mg/L Moderate-Severe
>700mg/L Lethal

Tx
Activated charcoal
Rehydrate
>500mg/L alkaline diuresis
>700mg/L haemodialysis

Alkaline diuresis - elimination of salicylate ions increased in alkaline urine
- Optimum urine pH = 7.5-8.5
- Serum pH = upper limit at 7.6
Correct any hypokalaemia

Acute Poisoning - Carbon Monoxide & Alcohols

Carbon Monoxide

Children more susceptible - higher rate of intake

Ix
CarboxyHb
- higher in smokers, urban joggers
- not suitable for LEVEL of exposure, only to confirm exposure
- if not high still doesn't rule out CO poisoning
ECG - non-specific ischaemia
CXR - inhalation injury
CoHb/ABGs - metabolic acidosis, hypokalaemia, increased anion gap
Increased CK - from rhabdomyolysis

Tx
HbO
Hyperbaric oxygen


Alcohols
Ethanol
Methanol
Ethylene glycol
Isopropyl alcohol

Ix
Specific levels only useful is raised - not good indicator of outcome

Anion gap
- difference b/w plasma concentrations of cations and anions
- increased anion gap = increased presence of unmeasured anions 
eg alcohols/overproduction of organic acids/decreased excretion eg in renal failure
- can be used to monitor progress

[Na+ + K+] - [HCO3- + Cl-]

>20mmol/L = lactate, formate, oxalate

Osmolar gap
- difference b/w measured and calculated osmolality
- osmolar gap in metabolic acidosis = presence of unmeasure osmoles ie methanol, ethanol, ethylene glycol

2(Na+ + K+) + Urea + Glucose

Tx
Methylpyrazole
- inhibits alcohol dehydrogenase
- predictable elimination, no CNS depression
- expensive

Fatal dose of ethanol:
- Adults = 6-10ml/kg
- Children = 4ml/kg

Acute Poisoning - General Principles

Hx
Can be very unreliable
What, when, how much was taken?
?empty bottles
?witness reports
?emesis

Ex
DR ABCDEs as usual
Pay special attention to:
- Odours
- Mucous membranes
- Eyes

Ix
Temperature
Blood glucose
Toxicology - blood & urine
ALWAYS - paracetamol and salicylate levels

Other tests...
U&Es, LFTs, Clotting, Bicarbonate, ABGs
Osmolality, Osmolar gap, Anion gap
ECG, CXR, AXR
etc

Pills seen on AXR

ATE CHIPS

Arsenic
Theophylline
Enteric Coated Pills

Chloral Hydrate
Heavy Metals
Iron
Phenothiazines
Salicylates

Mx
Principles
- Supportive
- Correct abnormal electrolytes and obs (hypoxia, hypotension, dehydration, hypo/hyperthermia, acidosis)
1) Reduce absorption
2) Increase elimination
3) Give antidotes
- Monitor - TPR, BP, ECG, Oxygenation, GCS

Elimination

Emesis
- Activated Charcoal
(good for organic compounds, not lithium/iron/alcohol, 1G/kg or x10 ingested dose, C-I corrosive ingestion)
- Gastric Lavage
- Whole Bowel Irrigation
(Klean Prep, polyethylene glycol, up to 12hrs p-ingestion, poss use in lithium/arsenic/iron/lead oxide/body packers)

Enhanced Emesis
- Forced Diuresis
- Chelation
- HBO
- Haemodialysis
- Haemoperfusion

Predisposing factors to toxicity
- Old age
- Cardiac disease - myocarditis, active ischaemia
- Metabolic abnormalities - hypokalaemia, hypomagnesaemia

Monday, 25 January 2010

CYP450 Inducers and Inhibitors

Argh - the CYP450 inducers and inhibitors are another thing that we HAVE to know that I have spent 3 years avoiding, like following after a fat man for an airplane toilet...

....hmmm. I appear to get more offensive when irritated and sleepy.

CYP 450 - in case pharmacology wasn't complicated enough.


INHIBITORS - act acutely

•Valproate
•Ketoconazole
•Ciprofloxacin
•Cimetidine
•Erythromycin
•Grapefruit juice
•Isoniazid

Venerated Key Pros I Met STOP Eating Grapefruit, Son

(Valproate, Ketoconazole, Ciprofloxacin, Cimetidine, Erythromycin, Grapefruit, Isoniazid)


INDUCERS - act slowly

•Phenytoin
•Alcohol
•Tobacco
•Rifampicin
•Griseofulvin
•Carbamazepine

Penny QUICKLY Drinks and Smokes but Refuses Greasy Carbs.

(Phenytoin, Alcohol, Tobacco, Rifampicin, Griseofulvin, Carbemazepine)

CYP 450 drugs with Narrow Therapeutic Window (DUM DUM DA!!!!)

Phenytoin
Cyclosporin
Estradiol
Theophylline
Warfarin

Penny Cycled Straight by The Wharf
(Phenytoin, Cyclosporin, Estradiol, Theophylline, Warfarin)

Narrow Therapeutic Window Drugs + CYP 450 inhib/inducer = Pot Drug AE!!!

These took forever to come with... yes I am that unimaginative.

xx