Drugs Flashcards
What are the steps in drug regulation and development?
Research Discovery Preclinical development Phase 1 Phase 2 Phase 3 Approval and launch Phase 4
What happens in research and development?
- Target identification
- Establish MoA of drug
- Lead optimization
What is lead optimization?
The process of finding the most potent, pharmacodynamic, pharmacokinetic and safe version of a compound by modifying its chemical structure slightly
What happens in the preclinical development stage?
ANIMALS
Establish toxicity and other adverse effects in animals, as well as variation in its effects
What happens in phase 1 of drug development?
HEALTHY VOLUNTEERS
Confirm the drugs effects and dose ranging - must not have any adverse effects/interactions
What happens in phase 2 of drug development?
AFFECTED PEOPLE
Look at therapeutic value and adverse effects
What happens in phase 3 of drug development?
AFFECTED PEOPLE INTERNATIONALLY
Look at clinical benefit when compared to placebo
What happens in the approval and launch stage?
Look at quality, safety and efficacy of drug (NOT cost), and approve drug for marketing and licensing.
NICE will assess the drug to see whether it should be available on the NHS
What happens in phase 4 of drug development?
Postmarketing survelliance and regulatory reviews
Which companies can grant drug licenses in the UK and europe?
- Medicine and healthcare products regulatory agency
- European medicines agency
How long is a standard patent?
20 years (although development takes 15 years so leaves only about 5 years for marketing)
How can drugs sales be protected when a patent runs out?
- Continue to promote the product
- Consider prescription to OTC strategies
- Patent the manufacturing process
Who can drug developers advertise their product to?
Healthcare professionals, NOT the public
This is as long as they comply with the ABPI
Which types of drugs have to go through the EMA ‘centralised procedure’ to be licensed, as oppose to only through the MHPA in the UK?
Cancer drugs
HIV drugs
Advanced therapies
Biotechnology
What are the 4 main methods of pharmacoeconomic assessment?
- Cost minimisation
- Cost effectiveness
- Cost utility
- Cost benefit
What is cost minimisation?
Looking purely at price, assuming equal efficacy between drugs?
What is cost effectiveness?
Looking at price and efficacy of drug
What is cost utility?
Looking at price efficacy and QALY impact of the drug?
What is cost benefit?
Looking at net monetary gain of licensing a drug (ie. How much money it will save the economy vs how much it will cost)
What sources of guidance are there for prescribing?
Cochrane - international
NICE, SIGN - national
Local regional guidelines
What is compliance?
The extent to which the patients behaviour matches the prescribers advice
What is adherence?
The extent to which the patients behavior matches the AGREED recommendations from the prescriber
What is concordance?
The relationship between the patient and the prescriber and the degree to which they agree on treatment
How can patient compliance be measured?
Direct - Plasma drug concs, direct observations
Indirect - clinical outcomes, electronic monitors, diaries
What is therapeutic drug monitoring?
Maintaining plasma drug concs within a target range.
There are 3 components:
- Monitoring plasma drug concentration (ie. actual drug conc)
- Monitoring clinical response (eg. frequency of seizures)
- Measuring pharmacodynamic effects (eg. PEFR, BM etc)
What drugs are commonly monitored in this way, and why?
Some antibiotics eg. gentamicin, vancomycin, ciclosporin Anticonvulsants eg. carbamazepine, phenytoin Corticosteroids Digoxin Methotrexate Lithium Theophylline Warfarin
This is either because they have a narrow therapeutic index or are dangerous in overdose
How can poor adherence be improved?
- Identify the reasons for non-adherence and address them.
- Monitor and regularly review
- Minimise drug number and simplify regimens using calendar packs
What is the biggest barrier to shared decision making?
Time constraints
What is a medication error?
A preventable event due to an error in prescribing, dispensing or administration.
How can medication error be prevented?
Appropriate policies Education Clear prescription writing Electronic prescribing Failsafe devices (eg. insulin pumps) Controlled storage or drug dissension Antidote availability
What is an adverse drug reaction?
A response to a drug which is noxious, unintended and occurs at doses used for normal therapy
How are adverse drug reactions classified, and give examples for each?
Augmented - dose related and predictable (e.g. hypo from insulin)
Bizarre - random and unpredictable (e.g. anaphylaxis)
Chronic - occurs after longterm treatment (e.g. cushings from steroids)
Delayed - occurs a long time after admin/withdrawal (eg. thalidomide)
End - immediate when drug is withdrawn (eg. adrenal insufficiency from steroid withdrawal)
How should you respond if you suspect an ADR?
- Assess nature and severity of reaction
- Take history of presenting symptoms
- Take drug history and review allergies or previous ADRs
- Review adverse effect drug profile in BNF
- Consider further investigation
Where can you find information about ADRs?
BNF
Electronic medicines compendium
Interactive drug analysis profiles
District services
How can ADRs be identified?
Drug development (any stage)
Voluntary reporting
Record linkage
When should you report an ADR with the yellow card?
- Serious drug reaction
- Extremes of age
- Any triangle drug (new)
- Medication error
What is the difference between a pharmacodynamic and pharmacokinetic drug interaction?
Pharmacodynamic - Interaction involving the effect of the drug on the body
Pharmacokinetic - Interaction involving the effect of the body on the drug
Give an example of a pharmacodynamic drug interaction that is:
a) synergistic
b) antagonistic
a) rifampicin and isoniazid for TB
alcohol and benzodiazepine at GABA receptor
b) salbutamol and atenolol at B receptor
morphine and naloxone at mu receptor
What are the four ways in which a drug can effect another drug in a pharmacokinetic way?
- Absorption ie. one drug can alter the pH, gastric emptying etc
- Distribution ie. one drug can displace another from albumin, which will affect free levels
- Metabolism ie. inducers/inhibitors
- Excretion ie. one drug can alter tubular re-absorption or secretion in the kidney
How does an enzyme inducer work?
It stimulated increased enzyme production so more drug is cleared. This takes days/weeks
How does an enzyme inhibitor work?
It makes the existing enzyme less effective so more drug is in body. This is immediate onset as drug buildup could cause toxicity
Give some examples of P450 enzyme inducers?
hint: SCRAP GP
Sulphonylureas Carbamazepine Rifampicin Alcohol Phenytoin Giresofulvin (antifungal) Phenobarbital
ALSO st johns wort
Give some examples of P450 enzyme inhibitors?
hint: SICKFACES.COM
Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Alcohol binge Chloramphenicol Erythromycin Sulphonamides Ciprofloxacin Omeprazole Metronidazole
ALSO cranberry and grapefruit juice
What happens if you give methotrexate with trimethoprim?
Folate deficiency
What happens if you give potassium chloride and spironolactone?
Hyperkalemia
What happens if you give warfarin with aspirin/NSAIDS?
Bleeding risk
What happens if you give lithium with NSAIDS or diuretics?
Increased lithium levels
What happens if you give the contraceptive pill with rifampicin/carbamazepine?
Pregnancy - the latter drugs are enzyme inducers
What happens if you give SSRIs with st johns wort/triptans/MAOI?
Serotonin syndrome or hypertensive crisis - enzyme inhibitors
What happens if you give carbamazepine with erythromycin/clarithromycin/fluconazole?
Increased effect of CBZ
What is the difference between pharmacogenetics and pharmacogenomics?
Pharmacogenetics - the study of the genetic basis for variability in drug response
Pharmacogenomics - the use of genetic info to guide the choice of drug on an individualised basis
Give 2 examples of how genetic factors can influence drug use?
- Rate of acetylation of isoniazid is different depending on race, which can either lead to hepatotoxicity
- GENETIC POLYMORPHISMS OF DRUG-METABOLISING ENZYMES - TPMT enzyme activity in metabolism of Thiopurine - polymorphisms can affect activity and cause bone marrow toxicity
According to the legal classification drugs, are subdivided into schedule and class.
What is a schedule 5 drug?
A drug that is considered to have therapeutic value and can be legally obtained OTC
What is a schedule 4 drug? (give examples)
i) tranquillisers, illegal to have without prescription
ii) steroids, legal to have without prescription but illegal to give to others
What is a schedule 3 drug? (give examples)
Drugs available for medical use but need prescription
3A - temezepam, tramadol
3B - barbituates
What is a schedule 2 drug? (give examples)
Drugs available for medical use but need prescription and strict record keeping/storage
2A - diamorphine, methadone, cocaine
2B - amphetamines, dihydrocodeine, ketamine
2C - GHB
What is a schedule 1 drug?
give examples
Drug that has no recognised medical use and possession is illegal
1A - ecstasy, LSD, methamphetamine
1B - methoxetamine, cannabis, SCRAs
1C - khat
What does ‘schedule’ and ‘class’ mean in terms of legality of drugs
Schedule (1-5) - extent to which prescription and possession is legal
Class (A-C) - harm from drug use
Which is the most commonly misused drug?
Cannabis
Where in the UK has the highest rates of drug misuse?
North East
Which drug has the highest associated mortality?
Heroine
What is the definition of drug tolerance?
A higher dose of drug is needed to achieve the same level of initial response
What is the definition of physical dependence?
Develops when neurones adapt to repeated drug exposure and only function normally in the presence of the drug.
Withdrawal precipitates unpleasant side effects
What is the definition of psychological dependence?
Emotional need for a drug or substance without underlying physical need
Name some commonly misused depressants?
Opiods
Benzodiazepines
GHB related
Name some commonly misused stimulants- how do they work?
Amphetamine eg. MDMA, meth Cocaine Piperazines Cathinones eg. mephedrone, khat Benzofurans Aminoindans D-series Piperidines Thiophenes
These mostly work by reuptake inhibition and reverse transportation of dopamine, norepinephrine and serotonin
How does cocaine work?
Sodium channel blocker at the NMDA receptor
Name some commonly misused hallucinogens
Cannabinoids eg. cannabis, SCRA
Arcycyclohexamines eg. ketamine, PCP
Ergolines eg. LSD
Tryptamines eg. DMT, psilocin (shrooms)
What type of drug is LSD?
Ergoline
What type of drug are ketamine and PCP?
Arcyclohexamines
What type of drug are cannabis and SCRA?
Cannabinoids
Name some other misused drugs
Poppers (amyl nitrate)
Nitrous oxide
Solvents (toluene)
What are the symptoms of serotonin syndrome?
- Cognitive behavioural changes
- Neuromuscular dysfunction
- Autonomic dysfunction
- Vomiting
- Seizures
- Rhabdomyloysis
- Renal failure
- Coagulopathies
How do hallucinogens and MDMA work?
Releases a huge surge of serotonin
How do opiates work?
Bind to the mu receptor, causing euphoria
Name some side effects of opioids
Piloerection Pinprick pupils Bradycardia Rhabdomyolysis Respiratory depression Nausea and vomiting
What is the antidote to opioids?
Naloxone
Name some side effects of benzodiazepines
Sedation
Respiratory depression
Recued tone
Hypotension
(these also all occur in opioids)
What is the antidote to benzos?
Flumazenil
Name some side effects of GHB?
Urinary incontinence
Hypersalivation
Seizures
(+ all benzo ones)
Name some side effects of stimulants?
Lock jaw (trismus) Agitation/psychosis Seizures Tachycardia Hyponatremia Tremor
Name some side effects of SCRAs
Dry mouth Agitation Hallucinations Chest pain and ECG changes Dyspnoea Renal dysfunction
Name some side effects of Arcyclohexamines
Hyperthermia Sedation Respiratory depression Seizures Chronic cystitis
Name some side effects of nitrous oxide
Asphyxia
Neurological complications from B12 deficiency (e.g. pins and needles)
Name some side effects of solvents
Early - ataxia, tremor, vomiting, arrhythmias
Late - CNS depression, convulsions, coma, hepatorenal dysfunction
Name some side effects of nitrites (poppers)
Hypotension
Visual disturbances
What is the typical regimen for prescribing maintenance fluids?
1 salty, 2 sweet
0.9% saline + 20mmol K over 8 hours
5% dextrose + 20mmol k over 8 hours (x2)
What is special about prescribing controlled drugs?
Need to include:
- formulation
- strength
- quantity IN WORDS AND FIGURES
How often is methotrexate given?
Once weekly
How do you work out weight to volume ratio?
The result needs to be in mg/ml
How do you calculate NTT?
1/ARR = NNT
i.e - pt with 21.3% Q risk, treatment reduces risk 25%
ARR = 21.3 x 0.25 = 5.3%
NNT = 1/ARR = 1/0.053 = 18.8 = 19 people of the same Q risk needed to treat to save 1 life.
How do you calculate absolute risk reduction?
ARR = Current risk x percentage risk reduction of treatment
i. e - 21.3% Q risk, treatment reduces risk 25%
21. 3 x 0.25 = ARR = 5.3%
What is NTT?
The number of patients that need to be treated in order to have an impact on one person
What is the relative risk reduction?
It takes out the number of people who would have survived anyway, regardless of treatment, so concentrates only on the expected death rate, for example.
Why does NTT not use relative reduction risk?
Because it could make the treatment seem more effective thn it is - ATT is a much better way of standardising it without any deception on behalf of the pharmaceutical companies.
