eScript Flashcards
what side effects can oxybutynin cause?
Oxybutynin is an antimuscarinic drug, the adverse effects of which include dry mouth, constipation, blurred vision and occasionally cognitive impairment
Older adults may be more susceptible to these adverse effects
Cognitive impairment can increase the risk of non-adherence
what is adherence?
“The extent to which the patient’s behaviour matches agreed recommendations from the prescriber”
what is compliance?
the extent to which the patient’s medicines-taking behaviour matches the prescriber’s recommendations
OLD TERM
why do thiazide diuretics cause gout?
increase uricaemia, which may precipitate gout in susceptible patients
what drug commonly causes myalgia?
statins
The risk is increased if the statin is prescribed at a high dose or if it is prescribed in combination with a fibrate, macrolide antibaterial or certain calcium-channel blockers.
Treatment should be discontinued if creatine kinase is 5 times the upper limit of normal or if symptoms are severe.
what common drug may cause mood changes?
systemic corticosteroids
what is bioavailability?
the extent to which a drug reaches the systemic circulation where it is available to act at the ‘effector site’ (e.g. the brain for a sedative effect
what is bioavailability of IV drugs?
100%
what is the pathway of oral drugs into systemic circulation?
mouth-> stomach (disintegration of the formulation)-> small intestine (absorption) -> liver (metabolised)-> absorbed into systemic circulation-> effector site -> kidneys (elimination)
are lipid-soluble drugs absorbed better or worse?
better
are protein-bound drugs absorbed better or worse?
worse
what drug metabolism can erythromycin inhibit?
warfarin
what drug metabolism can phenytoin induce?
antiepileptics
what drug metabolism can rifampicin induce?
oestrogen in COCP
what drugs should not be crushed and why?
MR drugs e.g. nifedipine
Enteric-coated e.g. aspirin
they can alter pharmacokinetic profile of a drug by breaking down coating of a drug which are designed to prevent breakdown, so it is absorbed quicker
other side effects of crushing drugs
bad taste e.g ibuprofen
damage skin of handlers
what is a pro-drug and examples?
when a drug is metabolised in the liver to an active form e.g. codeine to morphine, azathioprine to mercaptopurine
why are drugs metabolised in the liver?
Once absorbed, the body treats all drugs as foreign molecules. It will attempt to metabolise them in the liver to water soluble compounds and excrete them via the urine.
Pre-systemic metabolism of oral drugs (termed the ‘first-pass effect’) can significantly reduce drug bioavailability (propranolol, morphine).
what is Volume of Distribution (Vd)
the theoretical volume of fluid that would be needed to achieve the actual plasma drug concentration
Vd is typically reported in (ml or litre)/kg body-weight
If a 1 gram (1000 mg) dose of drug X, given intravenously gives a plasma-drug concentration (Cp) of 50 milligrams/litre, then
Vd = 1000/50 Vd = 20 litres
will drugs with a high Vd have a high or low plasma concentration
low
what type of drugs have a low Vd?
highly water soluble (e.g. gentamicin, atenolol, and insulin) or extensively protein-bound (e.g. warfarin) as they stay in the plasma (blood)
what type of drugs have a high Vd?
highly lipid soluble (e.g. digoxin, morphine, and diazepam) as they go out of plasma into tissues and organs
when is protein binding important in warfarin?
In general, drugs are not metabolised when they are protein-bound. However, protein-bound drugs can act as a ‘reservoir’ of the active drug. For example, warfarin is 97% protein bound. The remaining 3% - the fraction unbound (fu) is active. If another drug (e.g. sulphonamide component of co-trimoxazole) were to displace warfarin from its plasma-protein, the risk of adverse effects and toxicity will transiently increase
what can affect plasma protein concentration?
disease states
pregnancy
malnutrition
how many half lives does it take for 97% of a drug to be eliminated?
5
what is the difference between first order and zero order elimination?
first order is independent of drug conc- conc is halved every half life
zero order is when there is a fixed amount of the drug reduced every hour, as it is dependent on enzymes that become saturated. e.g. ethanol removal from the body
what is clearance of a drug?
the hypothetical volume of blood from which the drug is completely removed per unit time. It is expressed as units of volume per unit of time (e.g. litre/hour or ml/minute).
what enzyme is mainly responsible for the metabolism of drugs?
P450
what 2 factors determine the proportion of drug metabolised?
Liver function (presence of cytochrome P450 enzyme).
Hepatic blood flow - can be decreased in shock and gastrointestinal surgery, affecting the amount of drug presented to the liver.
name a drug that induces P450
phenytoin
name a drug that inhibits P450
erythromycin
what should be calculated to assess the degree of renal impairment?
creatinine clearance
what drugs require therapeutic drug monitoring?
digoxin
gentamycin
lithium
vancomycin
what are the 3 parameters of pharmacokinetics of a drug?
volume of distribution
half-life
clearance
how can you estimate a child’s weight?
(Age +4) x 2 (kg)
how many micrograms in a milligram (mg)?
1000
what is %w/w, %w/v and %v/v?
%w/w is percentage weight per weight. A 1% w/w preparation contains 1 g of drug in 100 g of diluent
e.g. Hydrocortisone 0.5% w/w contains 0.5 g of hydrocortisone in 100 g of diluent
%w/v is percentage weight per volume. 1% w/v solution contains 1 g of drug in 100 ml of diluent.
e.g. Sodium chloride 0.9% w/v contains 0.9 g of sodium chloride in 100 ml of water for injection
%v/v is percentage volume per volume. A 1% v/v solution contains 1 ml of liquid drug/chemical in 100 ml.
ChoraPrep® contains 70 ml of isopropyl alcohol in 100 ml of solution (i.e. 30 ml of diluent)
convert sodium chloride 0.9% into mg/ml?
0.9%= 0.9g in 100ml
= 900mg in 100ml
= 9mg/1ml
how much glucose is in 5% solution?
5g in 100ml
what does adrenaline 1:1000 and 1:10000 mean?
1: 1000 = 1g in 1000ml= 1mg in 1ml
1: 10000= 1g in 10000ml = 0.1mg in 1ml
how is acetylcysteine prescribed?
calculated on patients body weight (max 110kg)
prescribed in 3 parts:
The first (or loading dose) is given over 1 hour in 200 ml of glucose 5%.
The second is given over the next 4 hours, in 500 ml of glucose 5%.
The third and final is given over the next 16 hours, in 1 litre of glucose 5%.
For the first you need 150 mg/kg.
For the second you need 50 mg/kg.
For the third you need 100 mg/kg.
That’s a total dose of 300 mg/kg over 21 hours
how is severe unexplained hypoglycaemia investigated?
blood samples- lab glucose
serum- insulin, C-peptide, insulin-like growth factor, 3-beta-hydroxybutyrate
what is the first step in management of DKA?
fluid resuscitation
what level of blood glucose is classed as a hypo?
<4
what are the 2 classifications of symptoms of hypos?
Autonomic (adrenergic) symptoms: as a result of activation of the sympathetico-adrenal system. These effects may be suppressed in people taking non-cardioselective beta-blockers (such as propranolol).
Neuroglycopenic symptoms: due to cerebral glucose deprivation. In more serious cases, this can lead to a loss of consciousness, seizures, and death.
examples of adrenergic effects of hypos?
sweating palpitations tachycardia pallor hunger restlessness
examples of neuroglycopenic effects of hypos?
confusion slurred speech drowsiness numbness of nose, lips and fingers anxiety blurred vision
do frequent episodes of hypolglycaemia increase or reduce awareness?
reduce
lifestyle and medical risk factors of hypos?
- lifestyle- diet, age, exercise, impaired awareness, ramadan
- medical- incorrect insulin prescription/administration, comorbidities, illness, discontinuation of long term steroids, dialysis, AKI, learning difficulties
mx of a hypo in a conscious person who is symptomatic with BG >4?
Give a small carbohydrate snack, such as a banana, slice of bread or a usual meal if this is due.
Take a blood glucose concentration at 10 minutes to ensure the hypoglycaemia has resolved.
mx of a hypo in a conscious person with BG <4?
Give 15-20 g of quick acting carbohydrate of the patients choice:
- 4-5 Glucotabs® (5-7 Dextrosol® tablets) or sweets such as 4 large jelly babies or 7 large jelly beans.
- 1 bottle (60 ml) of Glucojuice®.
- 150-200 ml pure fruit juice.
- 3-4 heaped teaspoons of sugar dissolved in water (note: not suitable if taking acarbose).
Repeat the blood glucose 10-15 minutes later.
If the blood glucose is still below 4.0 mmol/litre, repeat the administration of quick-acting carbohydrate for up to three cycles.
If it remains below 4.0 mmol/litre, after three cycles (30-45 minutes) consider administration of intramuscular glucagon 1 mg or glucose 10% infusion 150-200 ml over 15 minutes.
When blood glucose is above 4.0 mmol/litre the patient should consume a small (20 g) long-acting carbohydrate snack such as a slice of toast or a usual meal if this is due to prevent recurrent hypoglycaemia. Patients administered glucagon should be given a larger carbohydrate snack (40 g) or meal to enable glycogen stores to be replenished.
mx of a hypo in a confused or uncooperative person?
1.5-2 tubes of Glucogel® or Dextrogel®
Squeezed into the mouth between the teeth and the gums.
OR
Intramuscular glucagon 1 mg (this may only be administered once)
Note it may take 15 minutes to observe the effect.
(then follow protocol as per)
mx of a hypo in a semi- conscious or unconscious person with IV access?
Give 75-100 ml of glucose 20% over 15 minutes via a standard giving set.
OR
Give 150-200 ml of glucose 10% over 15 minutes. If an infusion pump is available use this, but do not delay administration.
Repeat blood glucose at 10 minutes. If blood glucose remains below 4.0 mmol/litre, repeat administration.
mx of a hypo in a semi- conscious or unconscious person without IV access?
Give intramuscular glucagon 1 mg (GlucaGen Hypokit®, this may only be administered once).
Note that it may take 15 minutes to see the effects.
Glucagon may be less effective or ineffective in patients under the influence of alcohol, taking sulfonylureas, those chronically malnourished or in a prolonged period of starvation
what Ix and Mx to do in an unexplained hypo?
Take blood samples for a laboratory glucose to be measured urgently, and for serum to be stored to measure insulin, C-peptide, and insulin-like growth factor (also 3-beta-hydroxybutyrate if you can).
Give enough glucose orally or intravenously (use 20% glucose solution) to restore the blood glucose to normal (see previous guidance).
possible causes of an unexplained hypo?
Insulinoma- high insulin and C peptide
Insulin poisoning- high insulin
Fasting alcoholic ketosis
when to DVLA need to be informed about a diabetic for lorry drivers and normal vehicles?
For lorry and/or bus drivers, the DVLA should be informed about treatment with any oral antidiabetic or insulin.
For other drivers, the DVLA should be informed if they are treated with insulin.
Other indications for informing?
- Has more than 1 episode of severe hypoglycaemia within the preceding 12 months, or of any severe episode if driving a bus or lorry.
- Has impaired awareness of hypoglycaemia.
- Has suffered a hypoglycaemic episode whilst driving.
3 features of DKA and numbers?
- Hyperglycaemia: with a blood glucose > 11.0 mmol/litre (or known diabetes mellitus).
- Metabolic acidosis: bicarbonate (HCO3) < 15.0 mmol/litre and/or venous pH < 7.3.
- Ketonaemia: blood ketones (3-betahydroxybutyrate) ≥ 3.0 mmol/litre or significant ketonuria (more than 2+ on standard urine sticks).
principles of treatment for DKA?
Replace fluids.
Correct electrolytes abnormalities.
Replace insulin.
Gradually reduce the serum glucose concentration.
Gradually correct ketosis.
Identify treatment of co-morbid precipitants.
protocol for DKA in the 1st hour?
- Commence fluid replacement with 500 ml sodium chloride 0.9% over 15 minutes.
- Give an additional 500 ml sodium chloride 0.9% over 45 minutes (total 1 litre in the first hour).
- Commence a fixed rate intravenous insulin infusion with 50 units of Actrapid® or Humulin S® made up to 50 ml with sodium chloride 0.9%, infused at a rate of 0.1 units/kg/hour (for example, a patient weighing 60 kg would receive 6 units/hour).
- Monitor clinical parameters and biochemical markers.
- Establish a monitoring regimen for blood glucose and ketone concentrations (local protocol is likely to state a frequency).
- Give a prophylactic dose of the formulary low molecular weight heparin (if this is not contraindicated).
what to give if there is a delay in insulin prescribing in DKA?
a single bolus dose of intramuscular insulin (0.1 units/kg) can be administered.
what monitoring to do for DKA for electrolytes?
Ketones: measure every hour. The concentrations should fall by 0.5 mmol/litre/hour. If it is not falling, the patient may require an adjusted rate of insulin infusion.
Capillary glucose: measure every hour. The concentration should fall by 3 mmol/litre/hour.
Ensure the patient’s usual long-acting insulin regimen is prescribed and administered at the normal time.
When DKA has resolved, convert patient back to an appropriate subcutaneous regimen.
