Pharmacology Curriculum Flashcards
How many deaths each year in the UK are directly as a result of drug errors?
700
What are 4 examples of high risk drugs?
- Warfarin
- Opiates
- Insulin
- DOACs
Define pharmacokinetics
What the body does to the drug
Define pharmacodynamics
What the drug does to the body
What are pharmacodynamic interactions?
When 2 drugs work via different pathways to give the same outcome:
This is most commonly seen in cardiology (HF, diabetes, hypertension).
- Aspirin & clopidogrel
- Diuretics & ACE inhibitors
- Digoxin & beta blockers
Pharmacodynamic interactions are used in the treatment of hypertension:
- Beta blockers – atenolol, bisoprolol
- Calcium channel blockers – diltiazem, amlodipine
- Alpha blockers – doxazocin
- Thiazide diuretics – bendroflumethiazide, indapamide
- ACEi – ramipril, lisinopril
Patient has LVF with pulmonary oedema and RVF with ankle oedema. Patient is prescribed furosemide for oedema and ramipril to prevent HF from getting worse.
What adverse effect can this cause?
Both drugs lower BP → hypotension → collapse?
Patient has AF and hypertension. Patient given digoxin (cardiac glycoside) in order to lower HR and atenolol (beta blocker) to treat hypertension. What adverse effect can this cause?
Both beta blockers and digoxin lowers HR → bradycardia
Better solution → Give beta blocker on its own to treat AF and hypertension simultaneously.
Unintended side effects can occur when the two drugs have the same unwanted side effect. This side effect may be minor when prescribed on its own but becomes clinically significant when prescribed together.
E.g. Patient has angina and are prescribed a beta blocker as well as a calcium channel blocker. What unwanted side effects can this have?
Both drugs dilate the coronary vessels:
- In patient with normal or high blood pressure and normal heart rate → may be tolerated
- In patient with hypotension/bradycardia → may cause either to drop to extent that patient becomes symptomatic or collapses
What is first pass metabolism?
A phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation.
This concept explains why some drugs cannot be given orally.
Describe absorption of a drug when taken orally
- Taken via mouth and swallowed
- Passes to stomach
- Absorbed by the splanchnic circulation (which takes blood from the gut → liver)
- Liver then metabolises drug
Where does the splanchnic circulation take blood from/to?
From gut → liver
Why is GTN prescribed sublingually instead of orally?
Oral GTN would be completely metabolised by first pass metabolism so none would enter the circulation.
Some drugs have been specifically designed to take advantage of first-pass metabolism. How?
The drug when given is inactive – the first-pass metabolism process converts the drug into an active form.
Regarding distribution of a drug, the body can be divided into what 2 compartments?
1) the water part (vascular circulation and muscle)
2) the fat part (everything else e.g. fatty tissue)
Some drugs are hydrophilic. What does this mean (i.e. what compartment)?
Remain mostly in blood compartment (plasma) until drug is eliminated
Some drugs are lipophilic. What does this mean?
Distributes through membranes with preference for adipose tissue and muscle, giving a greater volume of distribution as a large proportion of our bodies are made of fat (an increase in the volume of distribution of a drug will generally increase its elimination half-life and vice versa)
Do lipophilic or hydrophilic drugs give a greater volume of distribution?
Lipophilic
Do lipophilic or hydrophilic drugs have a longer elimination half life?
Lipophilic
Is digoxin hydrophilic or lipophilic?
Hydrophilic
Why should you NOT prescribe a larger dose of digoxin for a patient who is 90kg than one who is 65kg if they are the same height?
If they are same height then the additional weight is likely to be fat (unless patient is body builder!) so the volume of distribution is the same
Describe the 2 phases involved in metabolism of a lipophilic drug
Phase 1 – Converts lipophilic molecules into more polar molecules (hydrolysis, oxidation, reduction)
Phase 2 – Further converts lipophilic molecules into more polar molecular through conjugation with glucuronic acid, sulfuric acid, acetic acid or amino acid
I.e. this results in a drug that is more hydrophilic (water soluble)
Define a narrow therapeutic window
There is only a small difference between the minimum effective concentrations and the minimum toxic concentrations in the blood.
Give 5 examples of drugs that have a narrow therapeutic window
- Warfarin
- Phenytoin
- Carbamazepine
- Theophylline
- Oral contraceptive pill
How do drugs that inhibit the P450 system affect the metabolism of drugs? What effect can this lead to?
Slow down metabolism → drug level higher → risk of toxicity
How do drugs that induce the P450 system affect the metabolism of drugs? What effect can this lead to?
Speed up metabolism → lower drug levels → may be ineffective
Give 6 major inducers of the P450 system?
- Phenytoin
- Carbamazepine
- Rifampicin
- St John’s Wort
- Chronic alcohol intake
- Barbecued meat
Note phenytoin and carbamazepine → metabolised by the P450 system (narrow therapeutic window) but also induce their own metabolism
What is rifampicin typically used in the treatment of?
Tuberculosis
What effect does rifampicin have on body fluids?
Turns all bodily fluids bright orange (urine, sweat etc)
What is St John’s Wort typically used for?
Over the counter → Commonly used by people for mild-moderate depression
Give 6 main drugs that are inhibitors of the P450 system?
- Erythromycin & clarithromycin (macrolides)
- Ciprofloxacin
- Miconazole & fluconazole
- Sodium valproate
- Diltiazem
- Amiodarone
What 2 juices are enzyme inhibitors?
Cranberry & grapefruit
For patients on warfarin, what can the prescription of clarithromycin for a chest infection (e.g. in penicillin allergic patients) lead to?
Huge bleeds
When prescribing a new drug, what drugs should you always check if a patient is on (due to risk of interactions)?
- Warfarin
- Phenytoin
- Carbamazepine
- Theophylline
- Oral contraceptive pill
Patient is on warfarin due to previous PE. Patient is prescribed carbamazepine. What effect can this have?
Carbamazepine is an enzyme inducer → speeds up metabolism of warfarin → lowers drug levels → lowers INR → tendency to clot (another PE?)
What does a low INR mean?
Blood clotting too quickly
What does a high INR mean?
Blood not clotting slower → risk of bleeding
Patient is on warfarin due to previous PE. Patient gets chest infection and is started on clarithromycin. What effect can this have?
Clarithromycin → enzyme inhibitor.
This can decrease the speed of metabolism of warfarin → warfarin levels rise → increased INR → risk of bleeding
What is the INR?
International normalised ratio (i.e. prothrombin time).
Patient is on phenytoin due to seizures. Patient develops TB and is started on rifampicin. What effect can this have?
Rifampicin is an enzyme inducer → levels of phenytoin decrease → risk of seizure
Patient is on phenytoin due to seizures. Patient develops chest infection and is started in ciprofloxacin. What might happen?
Ciprofloxacin is an enzyme inhibitor → levels of phenytoin rise → risk of toxicity
What is the key feature of phenytoin toxicity?
Ataxia (patient may describe feeling drunk)
What are the 2 major routes of elimination of a drug?
a) via kidneys
b) via biliary tract (GI)
Which type of drugs out of hydrophilic and lipophilic do not need to undergo metabolism by the liver?
Hydrophilic
Purpose of metabolism of lipophilic drugs by the liver?
Lipophilic drug → liver metabolises → hydrophilic drug (drug needs to be water soluble so it can be excreted.
How are hydrophilic drugs excreted?
They are excreted unchanged by the kidneys (no metabolism by the liver)
Why is digoxin contraindicated in renal failure?
Digoxin is hydrophilic so is excreted unchanged by the kidneys.
Renal failure → digoxin accumulates → toxicity (as still active drug, has not been metabolised by liver)
Why are opioids contraindicated in renal failure?
Opioids are lipophilic BUT are metabolised into active metabolites when they are turned into hydrophilic drugs.
Can accumulate in renal failure
A 72-year-old hypertensive man is started on an alpha-blocker for prostatic hypertrophy. He collapses whilst in the pub. Why?
A. He is drunk
B. He is straining to pass urine
C. He has developed postural hypotension
D. He has had a seizure
E. He has had a ventricular dysrhythmia
He has developed postural hypotension
He is hypertensive and presumably on medication to treat this. He has now been prescribed an alpha blocker for BPH. However, this group of drugs is also used to treat hypertension so his blood pressure may have dropped too low (hypotension), causing him to pass out.
A 66-year-old man on warfarin for AF is admitted with PR bleeding. He was recently treated for a chest infection.
Which antibiotic was he most likely given?
A. Amoxicillin
B. Ciprofloxacin
C. Doxycycline
D. Trimethoprim
Ciprofloxacin
Is an enzyme inhibitor → potentiating the effect of warfarin.
A 19-year-old woman presents with 2 seizures in a month. There is a family history of epilepsy. She is on the oral contraceptive pill.
Which is an appropriate anti-epileptic?
A. Carbamazepine
B. Levetiracetam
C. Phenytoin
D. Sodium Valproate
Levetiracetam
Phenytoin & carbamazepine valproate are all enzyme inducers → can reduce efficacy of pill.
Sodium valproate is teratogenic so contraindicated in women of child-bearing age.
Why is sodium valproate contraindicated in women of child bearing age?
Teratogenic → risk of neural tube defects
A 60-year-old alcoholic smoker on carbamazepine is admitted to hospital with an exacerbation of COPD, for which he is given nebulizers, steroids and clarithromycin.
What would you expect?
A. Fewer fits
B. More fits
C. Nausea and ataxia
D. No effect
Nausea and ataxia
Clarithromycin is a P450 enzyme inhibitor which will increase the effects of carbamazepine, leading potential toxicity. The side effects of carbamazepine toxicity include nausea & ataxia.
A 78-year-old woman takes digoxin for atrial fibrillation. She is started on a diuretic for heart failure. She develops increasing confusion over the following month.
Her U+E are as follows (normal ranges in brackets)
- Na+ 142 (135-145)
- K+ 4.4 (3.5 – 5.1)
- Urea 31 (3-7)
- Creat 251 (60-110)
Why is she confused?
A. Alzheimer’s dementia
B. Dehydration
C. Digoxin toxicity
D. Hypoxia due to heart failure
Digoxin toxicity
Digoxin is excreted via the kidneys without being metabolised, so if a patient develops AKI it can build to toxic levels, causing delirium. She is unlikely to have heart failure as she is significantly dehydrated. To make a diagnosis of dementia you need to elicit a longer history and exclude reversible causes for cognitive decline.
What is the therapeutic window?
This is the range in which a drug is clinically effective without causing toxic side
Describe the therapeutic window of amoxicillin
Wide
Describe the therapeutic window of phenytoin
Narrow
Define half life of a drug
The time taken for the plasma concentration of a drug to decrease to 50% of the original value (it is a measure of the pharmacokinetics for that particular drug)
With drugs with a long half-life, it will take a long time to reach a steady state. What can be given if the patient requires treatment quickly?
A loading dose
What is a loading dose?
A higher level of the drug to speed up the time it takes for the patient to reach the steady state.
Describe the half-life of adenosine
10 seconds
Why does adenosine have to be given IV?
Half life of 10 seconds → has to be given IV and as quickly as possible, otherwise would no longer be effective
Describe the half-life of amiodarone
58 days, would take 4 half-lives (232 days) to reach a steady state
Would you give a loading dose in adenosine or amiodarone?
Amiodarone (half life of 58 days)
Normally when you prescribe you prescribe generically (use the name of the drug itself, not the brand). What are exceptions to this?
HOWEVER – when you use specific slow-release drugs, you use the brand (this can be identified by the addition of MR, SR, CR or XL to the drug name
Give some examples of commonly monitored drugs
- Warfarin
- Phenytoin
- Carbamazepine
- Lithium
- Theophylline
- Certain IV antimicrobials e.g. gentamicin
- Warfarin (via INR)
If a patient complains that a drug is not working, what should you check before increasing dose?
compliance !
What are the 10 principles of good prescribing?
- Be clear about reasons for prescribing
- Consider patient’s medication history before prescribing
- Consider other factors that might alter risks/benefits
- Consider the patients ICE
- Select effective, safe, and cost-effective medicines individualised for the patient
- Adhere to national guidelines and local formularies where appropriate
- Write unambiguous legal prescriptions using the correct documentation
- Monitor the beneficial and adverse effects of medicines (report adverse effects if necessary)
- Communicate and document prescribing decisions and the reasons for them
- Prescribe within the limitations of your knowledge, skills and experience
4 purposes of prescribing?
- Alleviate
- Palliate
- Prevent
- Cure
Advantages of oral medications?
- Cheap
- Convenience/patient compliance & acceptability
Disadvantages of oral medications?
- Nauseated patients
- Nil by mouth
- Swallowing problems
- First pass metabolism may be a problem
- Compliance
- May take time to reach steady state
Advantages of rectal, sublingual & buccal medications?
- Avoids 1st pass metabolism
- Good for nauseated/NBM
- No need for IV access
- Topical treatment
Disadvantages of rectal, sublingual & buccal medications?
- Local irritation
- Patient acceptability
Advantages of IV medications?
- Fast
- Reliable
- Bolus or infusion
Disadvantages of IV medications?
- Requires IV access
- Drug reactions more common
- Avoid in IV drug users (gives them easy route to abuse drugs)
Advantages of IM medications?
- Fast
- Reliable
- No IV access needed
Disadvantages of IM medications?
- Painful
- Not if clotting problems
Advantages of subcutaneous medications?
- Avoids 1st pass metabolism
- No need for IV access
- Relatively painless
- Patients can be taught to self-inject e.g. diabetes
Disadvantages of subcutaneous medications?
- Local irritation
- Patient acceptability
- Needle-phobics
Advantages of topical medications (e.g. inhaled, nasal, creams)?
- Avoids 1st pass metabolism
- Patient acceptability
- Delivers a high dose locally to avoid systemic side-effects
Disadvantages of topical medications (e.g. inhaled, nasal, creams)?
- Local irritation
- May require adequate technique for appropriate dosing – requires education
Define enteral drug administration. Give some examples of enteral routes of administration
This is the administration of drugs via the GI tract.
It includes oral, rectal and administration of drugs given through a feeding tube.
Define parenteral drug administration. Give some examples of parenteral routes of administration
This is the administration of drug via any other route (apart from the GI tract).
It includes IV, IM or subcutaneous.
Define topical drug administration. Give some examples of topical routes of administration
Anything prescribed topically including eye drops, ear drops, nasal sprays, inhalers and nebulisers as well as topical creams.
Main advantage of topical administration?
Most drugs prescribed topically are intended to deliver a high dose of the drug locally whilst avoiding systemic side-effects.
Give some examples of drugs given through a topical patch that are intended for slow release
These include opiate analgesic and nicotine patches.
Define compliance
The extent to which the patient’s behaviour matches the prescriber’s recommendations.
Define adherence
The extent to which the patient’s behaviour matches agreed recommendations from the prescriber (i.e. agreement between patient & doctor).
Define concordance
The consultation process in which the doctor and patient agree therapeutic decisions that incorporate their respective views.
What is compliance affected by?
- Symptoms
- Side effects
- Complexity of regime
- Perceived risks/benefit of treatment
- Trust in healthcare professionals
How can symptoms affect compliance?
- More symptoms = more likely to take medications e.g. more pain
- Asymptomatic conditions e.g. hypertension may cause lower compliance
Give some examples of non-compliance
- Receiving a prescription but not collecting the medication
- Taking the medication at the wrong time or in the wrong dose
- Taking it more or less frequently than prescribed
- Stopping medication before the end of the course
- Taking a ‘drug holiday’ for a few weeks
We can divide issues with compliance into a) intentional and b) unintentional. What are some unintentional compliance issues?
- Patient simply forgets to take a medication
- Lapses may occur due to memory problems
- Due to very complicated medication regimes
Give some patient centered factors that affect compliance?
- Age
- Psychosocial factors
- Ethnicity
- Patient-prescriber relationship
How does age typically affect compliance?
Compliance generally improves as patients get older:
- May be as you get older you are less convinced of your own immortality
- Less stigma to taking medication as you get older
How can age negatively affect compliance?
- Memory problems
- Visual impairment
- Arthritis
- Swallowing problems
- Having to take multiple medicines – complexity of the regime (not the number of medicines) has most effect on compliance
Give some psychosocial factors that can affect compliance
- Health beliefs (may not align with our conventional understanding of how the body works)
- Religious beliefs (God’s will)
- Motivation and attitude towards your illness – this might be negatively affected in a patient with depression for example
How can ethnicity affect compliance?
- Language barrier – can impact on both the patient’s understanding and effectiveness of the doctor-patient relationship
- Cultural background – e.g. a patient’s trust in ‘conventional’ Western medicine
Give some therapy centered factors that affect compliance
- Route of administration
- Duration of treatment
- Complexity of regime
- Side effects
What is compliance with topical medications hugely affected by?
hugely affected by ability to apply technique correctly e.g. inhaler use is often difficult for older people with even a mild degree of cognitive impairment
How can duration of treatment affect compliance?
- Patients more compliant with short courses of treatment (up to 80%) than long-term medication (around 40-50%)
- Probably due to patient taking it for something that is making them feel unwell e.g. antibiotics for infection
- Is not uncommon for patients to miss doses as. they reach end of treatment (feel better, forget, decide side effects outweigh the benefits)
How can side effects affect compliance?
- Symptomless conditions e.g. hypercholesterolaemia/hypertension – patients are unlikely to put up with significant side effects
- Embarrassing side effects e.g. incontinence, erectile dysfunction (patients also less likely to admit this side effect to doctor)
- May have seen side effect of drug in someone they know and not be prepared to risk it themselves
- Ability to tolerate side effects depends on how it impacts their daily life → Prescribe diuretics in morning
Give some system factors that can affect compliance
- Time of work to see GP
- Paying for prescriptions
What is a type A drug reaction?
Predictable → Type A reactions result from an exaggeration of a drug’s normal pharmacological actions when given at the usual therapeutic dose and are normally dose-dependent.
What type of drug reaction is respiratory depression with opioids?
Type A (predictable)
What type of drug reaction is bradycardia with beta blockers?
Type A (predictable)
Describe the side effects seen in type A drug reactions
These side effects are common and rarely fatal.
Some can be managed by appropriate counselling, or by reducing the dose.
What are type B drug reactions?
Bizarre → Type B reactions are novel responses that are not expected from the known pharmacological actions of the drug.
These are less common but can be fatal.
What type of drug reaction is an allergic reaction to penicillin?
Type B
What type of drug reaction is aplastic anaemia with chloramphenicol?
Type B
What are type C drug reactions?
Chronic → These occur after a patient has been taking a medication for a long time.
Whether or not the medication can be stopped will depends on what is being treated, what alternatives are available and the severity of the side effect in question.
What type of drug reaction is osteonecrosis of the jaw with bisphophonates?
Type C
What type of drug reaction is dystonia with L Dopa medications?
Type C
What type of drug reaction is Cushing’s syndrome due to steroids?
Type C
What are type D drug reactions?
Delayed → These are uncommon and occur years after completing treatment.
What type of drug reaction is increased risk of 2ary cancer due to previous chemotherapy?
Type D
What are type E drug reactions?
Type e reactions (end of use) are associated with the withdrawal of a medicine.
What type of drug reaction is insomnia, anxiety and perceptual disturbances following the withdrawal of benzodiazepines?
Type E
What type of drug reaction is serotonin syndrome on stopping SSRIs?
Type E
What type of drug reaction is Addisonian crisis on stopping long-term steroids?
Type E
What is the prescribing cascade?
Occurs when a medication is given to counteract the side-effects of another medication (e.g. opiate analgesia causes constipation, laxatives may be required).
Intentional → Anti-emetics given to patients receiving chemotherapy.
How does bendroflumethiazide affect uric acid
Increases uric acid levels → increases risk of gout
What is ‘augmentin’?
Trade name for co-amoxiclav
Diagnosis?
- ST elevation in the anterior leads (V leads)
- ST elevation in the lateral leads (V5, V6, 1 and AVL)
Acute antero-lateral STEMI
Which type of drug reaction is dose dependent?
Type A
Type C (can be due to dose accumulation)
Which type of drug reaction is time dependent?
Type D
Type C (prolonged use)
