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CPTP > Pharmacokinetics and Dynamics > Flashcards

Pharmacokinetics and Dynamics Flashcards

1
Q

Principles of drug regulation

A

Safety - Relative absence of harm, there is never a guarantee of absolute safety

Efficacy - Has to be shown to have a positive effect, does it work QoL

Quality - Contains active ingredients and everything it states

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2
Q

Drug licensing

A

Purely risk benefit analysis. No element of cost. Must be proven evidence of safety and efficacy at certain doses. Relevant to target population and SE profile

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3
Q

Off license drugs

A

Drugs can be used off license but the doctor is then liable

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4
Q

To license a drug in the UK

A

Centralised procedure by the EMA obligatory for all HIV/AIDS, cancer, AI, diabetes, neurodegenerative. Also new technology including gene therapy and genetic engineering

National bodies - MHRA

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5
Q

Drug marketing

A

Direct to consumer advertising is banned in the EU and UK. Money is spent on healthcare professional advertising. MHRA must license a drug before this occurs

Attached to the license is a summary of product characteristics and a patient information leaflet

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6
Q

NICE

A

Crucial to determine cost effectiveness. They appraise new technologies and treatments, produce guidelines for treatment and care and recommend interventional procedures

Decide whether funding for specific drugs are available on the NHS. If green light added to formulary

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7
Q

No NICE approval

A

Apply to exceptional cases fund

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8
Q

Patents

A

Drugs are granted exclusivity for 20 yrs (+/-5) Typically development takes 10-15yrs so a drug only has a 8-10yr clinical lifespan. Commercial success if crucial

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9
Q

Local formularies

A

Subset of the BNF stating medications preferable in their locality. Aren’t legally binding just guidelines. Generic presricibing in encouraged to save money. Individual factors must be controlled

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10
Q

Preclinical development

A

1 - Establishing pharmacological action usually on enzymes, cell culture, perfused organs, bacteria or intact animals

2a - Safety assessment in animals. Toxicity - acute and chronic (4wks - lifetime), mutagenicity, teratogenicity, fertility and reproductive performance

2b - Species variation. 2 animals, 1 non rodent, 2 routes of administration

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11
Q

Required before 1st in man studies

A

Drug substance characterisation impurities, large scale compound synthesis,

Toxicology in 2 preclinical species, identification of major organ function effects, target organs for toxicity, assessment of monitoring toxic effects.

Drug metabolism and distribution

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12
Q

Lead optimisation

A

Potency, safety optimisation, cellular optimisation

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13
Q

Phase 1

A

First use in humans - often healthy volunteers, used to confirm pharmacology established from animal studies

  • Pharmacokinetics (absorption, metabolism, elimination and distribution)
  • Pharmacological actions

Detailed monitoring, dose ranging usually in 20-50 people over a year

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14
Q

Phase 2 requirements

A

Safe and well tolerated with single and multiple dosing

Characterisation of drug interactions and effects of food

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15
Q

Phase 2

A

Establishes therapeutic value and dose range
Explore common ADR
Assess pharmacokinetic actions in special pt groups
50-300 over 2-5yrs

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16
Q

Phase 3

A

Large multi centre often international comparisons with placebo or existing treatments.
RCT to prove efficacy and SE profile

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17
Q

Cost minimisation

A

Simple technique assumes equal efficacy between treatments, assumes all other factors i.e. SE are equal

Therefore cheapest option

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18
Q

Cost effectiveness

A

Cost A - Cost B
Efficay A - Efficacy B

20,000 pounds per life saved is the usual limit

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19
Q

Cost utility

A

Quantifies benefit using QALY.

QALY = survival years x QoL during those years

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20
Q

Cost benefit

A

Rarely used aims to value all inputs and outputs in monetary terms. Final result expressed as net monetary gain or loss / cost:benefit

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21
Q

Medication error

A

Any preventable event that may cause or lead to inappropriate medication use or harm while under control of health professional

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22
Q

ADR

A

Response to a drug either noxious or unintended occurs at normal doses for prophylaxis or therapy

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23
Q

Causes of medication error

A

Poor communication, lack of knowledge of drug, wrong patient, calculation errors, poor history skills - not eliciting allergies, poor handwriting, carelessness.

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24
Q

Avoiding errors

A 
Systems and policies to prevent error.
Checking pt identity
Education 
Electronic records - no handwriting,
Involvement of pt and family
Good documentation  and control of high risk drugs
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25
Q

Additional safe guards

A

Removal of hazards from clinical areas - control use of vincristine only specialists, make drugs look different, high risk in bright colours

Safer in children - drugs given by weight, training and competence in paeds

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26
Q

Concordance

A

Relationship between patient and prescriber and the degree they agree about treatment

Poor concordance is linked to chronic treatment, unacceptable side effects, poor understanding of treatment, polypharmacy and drug interactions and disability - poor eyesight, swallowing difficulty

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27
Q

Improving concordance

A

Adequate explanation and ICE, simple regimes (OD vs QDS), Warn of ADR, motivation and family onside, Compliance aids - dosset box, tablet crushers or cutters, alarms

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28
Q

Therapeutic monitoring

A

Measure clinical response - body weight during diuretic therapy, angina attacks

Pharmacodynamic effect - INR for warfarin, blood glucose for insulin, peak flow for bronchodilators

Plasma drug concentration often reserved for drugs with low therapeutic window, no active metabolites or an unpredictable effect

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29
Q

Drugs which may require therapeutic drug monitoring

A

Warfarin, digoxin, methotrexate, theophylline, phenytoin, carbamazepine, lithium

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30
Q

Indications for TDM

A

Start of therapy - titrating up, change in renal function, suspected toxicity, treatment failure?, drug interactions

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31
Q

Digoxin

A

Blocks AV node to give bradycardia plasma conc correlates to toxic effects. Range 1-3.8

Metabolised by the kidney. PC = nausea, gynecomastia, hypokalemia leading to tachyarrhythmias and HB

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32
Q

Gentamicin

A

Bactericidal efficacy linked to peak concentration needs to be >5mg/l. If levels @ 1hr post dose >12mg/L high risk of oto and nephrotoxicity

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33
Q

Lithium

A

Toxic effects occur >1.4

PC - vomiting, reduced appetite, ataxia, confusion, nystagmus and seizures. AV and 1st degree HB.

Increased risk in renal impairment, dehydration and with ACEi and diuretics

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34
Q

Phenytoin

A

Highly protein bound so liver failure may precipitate toxicity.

PC nystagmus, ataxia, slurred speech, coma and seziures all dose related. If IV can = cardiac arrthymias

Chronic SE - gum hypertrophy, rash, osteoporosis, hirsutism, megaloblastic macrocytic anaemia, CI pregnancy

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35
Q

Classification of ADR

A 
Augmented
Bizarre
Chronic
Delayed effects
End of treatment
36
Q

Augmented

A

Dose related and often predictable. Ie insulin OD - hypoglycaemia, warfarin - bleeding

37
Q

Bizzare

A

Unpredictable usually not dose related, penicillins - anaphylaxis, halothane - hepatitis,

38
Q

Chronic effects

A

Steroids - Cushings, osteoporosis, cataracts

Benzodiazepines - tolerance

39
Q

Delayed effects

A

Often variable after treatment cessation fetal abnormalities, strictures and cancer

40
Q

End of treatment due to withdrawal

A

Adrenal insufficiency due to steroids, post SSRI seizures and depression

41
Q

Stevens Johnson syndrome

A

Type IV hypersensitivity reaction. Minor form of TEN involving <10% of body skin attachment

42
Q

PC of steven johnson syndrome

A

Prodromal phase of fever, sore throat and painful eyes often for 1-5 days. This is followed by very tender areas of maculopapular erythema on the torso.

Target lesions on the hands and feet. Involves mucosal ulceration @ oral, genital or ocular

43
Q

Causes of SJS

A

Infections - mycoplasma, recent viral URTI (EBV, mumps, influenza)

DRUGS - Abx - penicillins, sulpha and ciprofloxacin, analgesics, anti epileptics (lamotrigine, valproate, carbamazepine and phenytoin)

44
Q

Toxic epidermal necrolysis

A

> 30% body skin attachement. Mortality of >25 %. Widespread flaccid blistering with skin that wrinkles like wet wallpaper on gentle pressure.

Features of skin failure can ensure - mass dehydration, defective fluid and temperature regulation, high risk of sepsis

45
Q

Erythema mulitforme

A

Self limiting symmetrical rash characterised by target lesions on the palms, soles and distal limbs. They are concentric rings of erythema with a dusky centre may occasionally blister.

46
Q

Triggers for erythema multiforme

A

90% due to HSV and mycoplasma. Drugs - anticonvulsants, sulphamides

47
Q

Gynecomastia

A

Osteogenic effects increased ratio of oestrogen:androgens.

25% due to drugs - spironolactone, digoxin, methyl dopa

48
Q

Galactorrhea

A

Increased prolactin levels. Spontaneous production of milk not linked to pregnancy

May be due to hyperprolactinoma or increased TSH

Dopamine antagonist can cause = TCAs, metacloprimide, antipsychotics,

49
Q

Pharmacogenomics

A

Genetically determined variation in drug response

50
Q

Pharmacodynamics

A

How the drug effects the body

51
Q

Pharmacokinetics

A

How the body effects the drug. Absorption - drug transporters, distribution - albumin bound, metabolism - CYP450, excretion @ renal tubules,

52
Q

Pharmacovigilance

A

Cohort studies, case control, voluntary yellow card reporting. This continues well after a drug is brought to market. Important to recognise rare side effects which only happen in a large sample size over a long period of time

53
Q

Acetylation variation

A

Fast acetylator - Japanese/Eskimos rapid metabolism of isoniazid leading to hepatotoxicity

Slow acetylators - Accumulation of isoniazid leading to neurotoxicity

54
Q

Synergism

A

Agonise each others effects

Alcohol and benzodiazepines @ GABAa

55
Q

Antagonism

A

Salbutamol and atenolol @ B adrenoeceptors

Naloxone and morphine @ u opiod receptors

56
Q

Pharmockinetics

A

Absorption, distribution, metabolism and excretion

57
Q

Absorption

A

SI is principle site for administration and absorption of most drugs due to surface area of villi. Factors that affect absorption = gastric pH and motility

58
Q

pH and gastric motility

A

Antacids increase the pH of the stomach leads to more drug ionisation and slower absorption. Conversely drugs which reduced the pH of the stomach such as alcohol lead to less ionisation hence faster absorption

Drugs that reduce gastric emptying - opiates, TCA and antimuscarinics

Drugs that increase gastric emptying - metacloprimide and muscarinic agonists

59
Q

Activated charcoal

A

Binds to drugs preventing absorption

60
Q

Antacids (Magnesium and aluminium)

A

Form insoluble complexes with tetracyclines, quinolones and bisphosphanates leading to reduced absorption

61
Q

Distribution

A

Drug must reach the blood and different body compartments either dissolved in solution or bound to plasma proteins.

If the drug is most carried in the plasma it has a small volume of distribution and dialysis can be useful.

62
Q

Drugs that are highly plasma protein bound

A

Phenytoin, carbamazepine, warfarin, statins. If the plasma protein concentration falls rapidly can lead to increased drug concentration

63
Q

CYP450 Inducers

A

Chronic alcohol, carbamazepine, phenytoin, rifampacin, st johns wort

64
Q

CYP450 inhibtiors

A

Macrolides, sodium valproate, quinolones, SSRI’s, PPI,amiodarone, antifungals, grapefruit and cranberry juice

65
Q

COCP and Abx

A

COCP is a conjugate that needs to be broken-down by bacteria in the gut to increase its effectiveness. Abx kill friendly gut bacteria leading to reduced effectiveness of the COCP

66
Q

Excretion

A

Body eliminates drugs following partial/complete conversion to water soluble metabolites

67
Q

Thiazides and lithium

A

Interact due to thiazides causing Na+ loss and a diuresis lithium is retained and can have toxic effects

68
Q

Methotraxathe and trimethoprim

A

Both dehydrofolate reductase enzyme inhibitors can lead to bone marrow suppression due to folate deficiency.

69
Q

Seretonin syndrome

A

SE of overdose of SSRIs, TCA, MAOIs, MDMA and amphetamines. PC = dilated pupils, hyperthermia, hyponatremia, SIADH, increased reflex = ankle clonus,

70
Q

Tolerance

A

Higher dose of the drug is needed to achieve the same level of response initially achieved

71
Q

Psychological dependence

A

Emotional need for drug or substance that has no physical need

72
Q

Physical dependence

A

Develops when neurones adapt to repeated drug exposure and only function normally in the presence of the drug. Withdrawal leads to unpleasant physiological effects.

73
Q

Societal impacts for drug misuse

A

Compromised employment and education, financial hardship and homelessness. Criminal behaviour such as theft and prostitution.

74
Q

Health impacts of drug use

A

Wound site infections, hep B and C, TB, HIV, STD, intoxication injuries, unwanted pregnancy.

75
Q

Depressant drugs

A

Opioids - heroin, morphine, methadone and fentanyl

Benzodiazepines

76
Q

PC of depressants

A

PC = hypothermia, reduced tone and reflexes, sedation, confusion, bradycardia and hypotension leading to respiratory depression

77
Q

PC of opiods

A

Specific - piloerection, bilateral pupil constriction, ileus, non cardiogenic pulmonary oedema.

Mx - naloxone IV

78
Q

PC of benzodiazepines

A

Ataxia, slurred speech, confusion, hypothermia

Mx = flumanzenil

79
Q

GHB PC

A

Hyper salivation, urinary incontinence, seizures and amnesia

80
Q

Stimulants

A

Cocaine, MDMA, amphetamines

81
Q

PC of stimulants

A 
Euphoria, sweating, anorexia and hypothermia
Tachycardia, HTN and arrhythmias
Tremor, rhabdomyolyisis
Hyponatremia and metabolic acidosis 
Confusion, agitation and seziures
82
Q

Complications of stimulants

A

SIADH - hyponatremia, leads to increased h20 intake
Arrhythmias and MI - Cocaine
DIC, rhabdomyolysis in MDMA

83
Q

Seretonin syndrome

A

Neuromuscular dysfunction = tremor, teeth grinding, hyperreflexia, ankle clonus

Autonomic dysfunction = tachycardia, fever, flushing and diarrhoea

Cognitive = agitation, confusion, hallucinations, vomiting and seizures

84
Q

Hallucinogens

A

Cannabinoids, cannabis, Ketamine, LSD

85
Q

Nitrous oxide

A

Can leads to B12 deficiency if used long term. Acute risk of asphyxia

86
Q

Ketamine

A

Hyperthermia, sedition, ataxia, HTN and tachycardia

Chronic = chronic cystitis

CPTP (11 decks)

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