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.