Block 33 PPT

Question 1

anxiety/ panic management - step 1?

Answer 1

STEP 1:All known and suspected presentations of GAD

Identification and assessment; education about GAD and treatment options; active monitoring

Question 2

step 2 in anxiety/ panic management?

Answer 2

STEP 2:Diagnosed GAD that has not improved after education and active monitoring in primary care

Low-intensity psychological interventions: individual non-facilitated self-help, individual guided self-help and psychoeducational groups

Question 3

step 3 in anxiety management?

Answer 3

STEP 3:GAD with an inadequate response to step 2 interventions or marked functional impairment

Choice of a high-intensity psychological intervention (cognitive behavioural therapy [CBT]/applied relaxation) or a drug treatment

Question 4

step 4 in anx management is needed when ?

Answer 4

Complex treatment-refractory generalised anxiety disorder (GAD) and very marked functional impairment, such as self-neglect or a high risk of self-harm

Question 5

what does step 4 in anx management need?

Answer 5

Highly specialist treatment, such as complex drug and/or psychological treatment regimens; input from multi-agency teams, crisis services, day hospitals or inpatient care

Question 6

first line when a pharmacological approach is needed for anxiety?

Answer 6

• SSRI - sertraline first line
• if ineffective, offer alt SSRI or SNRI
• If the person cannot tolerate SSRIs or SNRIs, consider offering pregabalin.

Question 7

how should benzos be used in GAD?

Answer 7

• Don’t offer a benzo for the treatment of GAD except as a short term measure during crises

Question 8

SSRI may need to be prescribed w?

Answer 8

• inc risk of bleeding associated w SSRIs espec for older people or ppl taking other drugs which can damage the GI mucosa or interfere w clotting (NSAIDs, aspirin) - use omeprazole

Question 9

for ppl aged under 30 who are offered a SSRI or SNRI:

Answer 9

• warn them that these drugs are associated w an increased risk of suicidal thinking and self harm
• see them within 1 week of first prescribing
• monitor the risk of suicidal thinking and self-harm weekly for the first month

Question 10

what should be used for rapid tranquilisation?

Answer 10

• IM lorazepam for rapid tranquilisation

Question 11

Tx of acute behavioural disturbance?

Answer 11

• de-escalation: calming techniques and distraction
• offer them the opportunity to move away from the situation in which the violence is occuring
• only use restrictive techniques if all attempts to defuse the situation have failed

Question 12

which other drugs can be used for rapid tranquilisation?

Answer 12

• NICE suggests lorazepam, olanzapine or haloperidol (if using haloperidol, consider an anticholinergic drug).
• oral medications preferred

Question 13

first line in a non-psychotic behavioural disturbance?

Answer 13

• Lorazepam should be considered first for non-psychotic behavioural disturbance - oral if possible but intramuscular if necessary.

Question 14

behavioural disturbance in the context of psychosis?

Answer 14

• Behavioural disturbance in the context of psychosis should be treated with lorazepam combined with an antipsychotic.

Question 15

what should be avoided in patients w dementia?

Answer 15

• Olanzapine (and risperidone) should be avoided in patients withdementia, due to an increased risk of stroke and death.

Question 16

what should be used for maintenance treatment in opiod dependence?

Answer 16

• methadone and buprenorphine for maintenance treatment

Question 17

buprenorphine is associated w ?

Answer 17

• Buprenorphine is associated with reduced risk of fatal overdose in the first weeks of treatment initiation.

Question 18

opiod withdrawal?

Answer 18

• Withdrawal - increasing the dose by small increments until the signs of withdrawal have disappeared

Question 19

For people who wish to stop using heroin completely or want to continue to use some heroin?

Answer 19

• Stop using heroin completely— high-dose methadone or buprenorphine may be more suitable as the blockade effects of both interfere with the subjective effects of additional heroin use.
• Continue to use some heroin— low-dose methadone treatment may be preferred.

Question 20

emergency Tx of opiod overdose?

Answer 20

• IV or IM naloxone: has a rapid onset and relatively short duration of action

Question 21

methadone mechanism?

Answer 21

• methadone is a full agonist of the mu-opioid receptor- binds to these receptors in the brain and fully activates them.
• This action can relieve withdrawal symptoms and cravings.
• Has a long half-life

Question 22

buprenorphine mechanism?

Answer 22

• buprenorphine is a partial agonist of the mu-opioid receptor and an antagonist of the kappa-opioid.
• It binds to the mu-opioid receptors in the brain but only partially activates them.
• This partial activation is enough to alleviate cravings and withdrawal symptoms in individuals with opioid dependence

Question 23

adult patient who wishes to undertake a programme of smoking cessation?

Answer 23

• referral to local NHS stop smoking services
• advised to stop abruptly
• Offered drug treatment to reduce withdrawal symptoms.

Question 24

drug treatment for smoking cessation?

Answer 24

• NRT
• varenicline or bupropion.
• Varenicline or combination NRT (a patch plus a short-acting preparation) have been shown to be the most effective treatments.

Question 25

adult patient who wishes to undertake a programme of alcohol withdrawal?

Answer 25

* Long acting benzodiazepine like chlordiazepoxide hydrochloride or diazepam should be used to attenuate alcohol withdrawal symptpms *

Question 26

Fixed dose regimen in alcohol withdrawal?

Answer 26

* This involves using a standard, initial dose (determined by the severity of alcohol dependence or level of alcohol consumption), followed by dose reduction to zero, usually over 7–10 days

Question 27

what can be used instead or chlorodiazepoxide in alc withdrawal?

Answer 27

* carbamazepine can be used as an alt treatment in alcohol withdrawal

Question 28

management of withdrawal seizures?

Answer 28

* if withdrawal seizures occur, a fast acting benzo like lorazepam should be used to reduce likelihood of further seizures

Question 29

delirium tremens?

Answer 29

* medical emergency * characterised by agitation, confusion, paranoia, and visual and auditory hallucinations

Question 30

first line for DT?

Answer 30

oral lorazepam

Question 31

What be given w lorazapam for DT?

Answer 31

* haloperidol can be given as an adjunctive therapy if symptoms persist

Question 32

In harmful drinkers or patients with mild alcohol dependence what should be offered?

Answer 32

* a psychological intervention (such as cognitive behavioural therapy) should be offered. - drug therapy can be added

Question 33

drugs that can be used for alcohol dependence?

Answer 33

* In those who have not responded to psychological interventions alone:, acamprosate or oral naltrexone can be used in combination with a psychological intervention.

Question 34

Relapse prevention for alcohol dependence?

Answer 34

* acamprosate or naltrexone in comb w CBT are recommended for relapse prevention in moderate- severe alcohol dependence

Question 35

alt to camprosate or naltrexone?

Answer 35

disulfiram

Question 36

How does heroin work - mu?

Answer 36

* acts on CNS opiod receptors mu, kappa, and delta * Mu receptor effects account for both the analgesic effects (Mu1) and the respiratory depression and euphoria (Mu2) * Activation of Mu2 receptors also causes miosis, reduced gastrointestinal (GI) motility, and physiologic dependence.

Question 37

heroin - kappa receptor?

Answer 37

* Kappa receptor activation causes analgesia as well.

Question 38

heroin - delta receptor?

Answer 38

* Delta receptors are more involved in spinal analgesia phenomena.

Question 39

heroin metabolizes to?

Answer 39

* heroin metabolizes to monoacetylmorphine in the CNS - more potent mu-receptor agonist than morphine

Question 40

risks associated with heroin use?

Answer 40

* collapsed veins and skin abscesses * blood borne viruses - HIV and hepatitis * increased risk of pneumonia * loss of relationships * risks of overdose

Question 41

interactions of heroin - benzos?

Answer 41

* benzodiazepine - potentially fatal respiratory depression

Question 42

heroin + ? interaction causes inc risk of opiate withdrawal?

Answer 42

* buprenorphine - inc risk of opiate withdrawal

Question 43

other heroin interactions?

Answer 43

* naltrexone * avoid alcohol - inc risk of overdose

Question 44

side effects of heroin?

Answer 44

* arrhythmias * hallucination * miosis * resp depression w high doses

Question 45

morphine mechansim?

Answer 45

* mu receptor agonist -> analgesia * acts on the descending inhibitory pathway of the CNS

Question 46

opiods with benzos can increase risk of?

Answer 46

increase risk of resp depression, coma and death

Question 47

side effects of morphine?

Answer 47

* arrythmias * dry mouth * resp depression * vomiting on initiation

Question 48

? causes rapid release of morphine?

Answer 48

alcohol

Question 49

inc risk of withdrawal w ? when using morpine

Answer 49

* Buprenorphine - inc risk of withdrawal when given w morphine

Question 50

morphine interacts w ? to increase risk of CNs excitation/ depression

Answer 50

phenelzine

Question 51

Signs of opiod overdose?

Answer 51

- Opioids (narcotic analgesics) cause coma, respiratory depression, and pinpoint pupils.  - antidote: naloxone

Question 52

Mechanism of cannabis?

Answer 52

* acts on cannabinoid receptors of the endocannabinoid system which are found in the PNS, CNS * Binding to different parts of the CNS mediates the different properties, paticularly of THC

Question 53

cannabis on the hippocampus?

Answer 53

impairment of STM

Question 54

cannabis on the basal ganglia?

Answer 54

altered reaction time and movement

Question 55

cannabis on the hypothalamus?

Answer 55

inc appetite

Question 56

cannabis on the NA?

Answer 56

euphoria

Question 57

cannabis on the amygdala?

Answer 57

panic and paranoia

Question 58

Cannabis interactions?

Answer 58

* ciclosporin - cannabidiol increases concerntration * tacrolimus * valproate - inc risk of ALT concs * carbamazepine

Question 59

side effecs of cannabis

Answer 59

* aggression * suicidal behaviour * cough * increased risk of infection * seizure

Question 60

risks w cannabis?

Answer 60

* risks of suicidal thoughts

Question 61

amfetamine mechanism?

Answer 61

* CNS stimulant * increases amounts of dopamine, NE, serotonin in the synaptic cleft * inhibits MAO

Question 62

indications of amfetamine /

Answer 62

* ADHD * narcolepsy

Question 63

interactions of amfetamine?

Answer 63

* bupropion - inc risk of serotonin syndrome * fluoxetine * moclobemide * phenelzine - inc risk of hypertensive crisis

Question 64

side effects of amfetamine?

Answer 64

* arrythmias * arthralgia * depression * palpitations * decreased weight

Question 65

amfetamine overdose?

Answer 65

* Amfetamines cause wakefulness, excessive activity, paranoia, hallucinations, and hypertension * followed by exhaustion, convulsions, hyperthermia, and coma

Question 66

MDMA mechanism?

Answer 66

* releaser and reuptake inhibitor of serotonin, dopamine and NE * -> happiness, inc energy, extroversion, feeling close to others, changed perception of colours and sounds

Question 67

MDMA acute toxicity episodes?

Answer 67

* The serotonin syndrome (increased muscle rigidity, hyperreflexia, and hyperthermia), is characteristic of acute toxicity episodes.

Question 68

Short-term physical side effects of MDMA ?

Answer 68

* dilated pupils * a tingling feeling * tightening of the jaw muscles * raised body temperature * increased heart rate

Question 69

interactions of MDMA - serotonin syndrome?

Answer 69

* serotonergic drugs -> serotonin syndrome * MAOI like phenelzine

Question 70

MDMA interactions - cns depression?

Answer 70

* benzodiazepine - risk of CNS depression

Question 71

cocaine mechanism?

Answer 71

* blocks dopamine transporter preventing dopamine reuptake from the synaptic cleft -> euphoria ans arousal * blocks reuptake of serotonin and NE * stimulates reward pathway in the brain

Question 72

mental effects of cocaine?

Answer 72

* Mental effects may include an intense feeling of happiness, sexual arousal, loss of contact with reality, or agitation.

Question 73

physical effects of cocaine?

Answer 73

*  Physical effects may include a fast heart rate, sweating, and dilated pupils.

Question 74

CV side effects of cocaine?

Answer 74

* coronary artery spasm → myocardial ischaemia/infarction * both tachycardia and bradycardia may occur * hypertension * QRS widening and QT prolongation * aortic dissection

Question 75

Neurological side effects of cocaine?

Answer 75

* seizures * mydriasis * hypertonia and hyperreflexia

Question 76

psychiatric side effects of cocaine?

Answer 76

* agitation * psychosis * hallucinations

Question 77

GI side effect of cocaine?

Answer 77

* ischaemic colitis - should be considered if patients complain of abdominal pain or rectal bleeding

Question 78

# muscle, temp, electrolyte other side effects of cocaine?

Answer 78

* hyperthermia * rhabdomyalysis * metabolic acidosis

Question 79

management of cocaine toxicity?

Answer 79

* first line: benzodiazepines * chest pain: benzodiazepines + glyceryl trinitrate

Question 80

Heroin + cocaine?

Answer 80

overdose

Question 81

cocaine + MDMA - >

Answer 81

an increase the risk of heart attack, heart strain, and psychosis.

Question 82

cocaine and methamphetamine ->

Answer 82

cardiac

Question 83

mild-moderate depression Tx?

Answer 83

* Psychological therapies - low intensity psychosocial intervention and group CBT * AD

Question 84

when should antidepressants be used for depression?

Answer 84

* consider in those with a history of moderate-severe depression, persistent subthreshold symptoms or subthreshold/mild depression that does not respond to non-pharmacological interventions. * Also consider in those in whom mild depression is complicating the management of other conditions.

Question 85

what else needs to be done for depression?

Answer 85

* sleep hygiene advice * early follow up (within 1-2 weeks)

Question 86

Management of moderate-severe depression?

Answer 86

* high intensity psychosocial intervention * AD therapy * sleep hygiene * follow up

Question 87

SSRIs/ SNRIs - increased risk of suicide?

Answer 87

- SSRIs and SNRIs have been implicated in an increased risk of suicide, suicidal ideation and self-harm, particularly below the age of 30. - All patients commenced in this age group should have review within one week of starting therapy with weekly reviews for at least one month.

Question 88

acute mania management?

Answer 88

* AP - haloperidol, olanzapine, quetiapine, risperidone

Question 89

what can be added to the tx response?

Answer 89

* lithium and valproate can be added if inadequate tx response * AP can be used with lithium or valproate in the initital treatment of severe acute episodes

Question 90

asenapine?

Answer 90

* 2nd gen AP * moderate to severe manic episodes w bipolar

Question 91

olanzapine in bipolar?

Answer 91

* LTM management of bipolar

Question 92

benzos in mania?

Answer 92

* benzos: e.g. lorazepam * may be helpful in the initial stages of treatment for behavioural disturbance or agitation.  * Benzodiazepines should not be used for long periods because of the risk of dependence.

Question 93

lithium?

Answer 93

* mania or hypomania

Question 94

carbamazepine?

Answer 94

* LTM management of bipolar * to prevent recurrence of acute episodes in patients unresponsive to lithium therapy

Question 95

AP in bipolar?

Answer 95

- Antipsychotics: used as a therapeutic trial to treat mania. - May be switched to mood stabiliser once the acute episode resolved. Options can include haloperidol, olanzapine or quetiapine

Question 96

lithium?

Answer 96

Lithium: used for many years, still unclear mechanism. Often referred to as the ‘gold-standard’. Used in acute mania, recurrent depressive episodes or long-term maintenance. 

Question 97

antiepileptics in bipolar ?

Answer 97

- Antiepileptics: also used as mood stabilisers in bipolar. - Options include sodium valproate, lamotrigine or carbamazepine. - May be used alone or in combination. - It can help prevent depression relapses.

Question 98

Antidepressants in bipolar?

Answer 98

* Antidepressants: may be restricted due to the risk of inducing mania or rapid-cycling (frequent, distinct episodes). - The selective-serotonin reuptake inhibitor fluoxetine is commonly used.

Question 99

Psych therapies - individual psychoeducation?

Answer 99

trained to identify and cope with early warning signs of mania and/or depression.

Question 100

Psych therapies - CBT?

Answer 100

talking therapy. Focuses on the emotional response to thinking and behaviour.

Question 101

bipolar - interpersonal and social rhythm therapy?

Answer 101

focuses on the role of interpersonal factors (i.e. interpersonal relationships, role conflicts) and circadian rhythm stability (i.e. sleep-wake cycle, work-life balance) in the context of bipolar.

Question 102

bipolar - group psychoeducation?

Answer 102

- high frequency and intensity sessions to help patients become experts in their own condition. - Aims to improve mood stability, medication adherence and self-management.

Question 103

mania - family focused therapy?

Answer 103

- psychoeducation for families with one individual suffering from bipolar. - Looks at risks, communication and problem-solving within the family to prevent relapses.

Question 104

Prior to starting an antipsychotic NICE recommend the following are recorded:

Answer 104

* Weight * Height * Waist circumference * Pulse and blood pressure

Question 105

what should be recorded before AP are commenced?

Answer 105

* Assessment of any movement disorders * Assessment of nutritional status, diet and level of physical activity

Question 106

Monitoring on AP?

Answer 106

* Weight: every week for 6 weeks, then every 12 weeks, then at 1 year, then annually (plot on graph). * Waist circumference: measure yearly (plot on graph). * Pulse and blood pressure: measure at twelve weeks, then at 1 year, then annually. * Fasting glucose, HbA1c, blood lipids: at 12 weeks, then at 1 year, then annually.

Question 107

Clozapine?

Answer 107

* if the patient has failed to respond to 2 different AP - one of which is an atypical that is not clozapine

Question 108

clozapine monitoring?

Answer 108

* The risk of neutropenia and agranulocytosis is high and close monitoring (and regular FBCs) is required.

Question 109

Stopping APs?

Answer 109

* associated w increased risk of relapse * high risk of relapse if treatment is stopped in the first 1-2 years. * Patients need to be followed up for signs of relapse for at least 2 years after stopping medication.

Question 110

psychological therapies for schiz?

Answer 110

* individual CBT * family therapy * advised to use psychological therapies + an AP

Question 111

compliance =

Answer 111

the extent to which a person takes his or her medicine

Question 112

adherence =

Answer 112

the extent to which a patients follow medical advice

Question 113

concordance =

Answer 113

healthcare professional and patient create an agreed plan for treatment (medications) which takes into account the patient wishes

Question 114

reasons for poor aherence ?

Answer 114

* poor knowledge of illness and medication * independent pausing, stopping or controlling of the medication * lack of competence in self management * fear towards drug * diseases where poor control doesn't yet present symptoms * challenges with lifestyle changes * Replacing prescription drugs with self-administered drugs

Question 115

doctor oriented approaches to improving adherence?

Answer 115

* clear communication * setting achievable goals * Continuity of care and permanent doctor–patient relationships * Equal relationships with patients, with a coaching attitude

Question 116

medication oriented approaches to improving adherence?

Answer 116

* Medication reconciliation (nurse or pharmacist) * Medicines optimisation (pharmacist) * Medication review (pharmacist) * Combination of products to minimise the number of medicines * prepacked dispensing boxes

Question 117

patient oriented approaches to improving adherence?

Answer 117

* Focus on health outcomes of self-management and drug therapies * Support for patients to better understand their disease and its management * Pharmacists as coaches for drug therapies * Medication counselling for caregivers

Question 118

how is poor health literacy identified?

Answer 118

* REALM-R is a way of identifying patients w poor health literacy * patient is asked to read 11 words * score of 6 or less out of 9 indicates poor health literacy - only score if pronounced correctly

Question 119

implications of being a CYP2D6 ultra-rapid metaboliser?

Answer 119

* Codeine is a prodrug and its analgesic properties are not manifest until it is metabolized by CYP2D6, primarily to morphine and and codeine-6-glucuronide * ppl who are ultra-rapid metabolizers based upon CYP2D6 genotype have higher than expected morphine levels (an initial "overdose"), with more side effects and a shorter than expected duration of pain control

Question 120

which drugs are affected by being a CYP2D6 ultra-rapid metaboliser?

Answer 120

* hydrocodone, oxycodone, tramadol

Question 121

tramadol mechanism?

Answer 121

* Tramadol & its active metabolite (M1) bind to μ-opiate receptors → inhibition of ascending pain pathways & inhibits reuptake of  norepinephrine and serotonin * metabolised to O-desmethyltramadol which has a 200 fold greater affinity for u-opiod receptors compared to tramadol

Question 122

ultra-rapid metaboliser (CYP2D6) of tramadol?

Answer 122

* ↑ peak plasma concentrations of O-desmethyltramadol after a dose of tramadol * Greater analgesia * Stronger miosis - ↑ nausea

Question 123

TPMT deficiency?

Answer 123

* TMPT metabolises thiopurine drugs such as azathioprine, mercaptopurine, & tioguanine * TMPT gene located on chromosome 6 * Mutations of the gene encoding TPMT → varying functional activity → TMPT deficiency 

Question 124

Azathioprine and TMPT?

Answer 124

* risk of myelosuppression increased in patients with reduced activity of the TPMT enzyme * If TPMT activity is: * Absent: should not receive thiopurine drugs * Reduced: treated under specialist supervision

Question 125

Pharmacogenetics =

Answer 125

single drug-gene interactions

Question 126

pharmacogenomics =

Answer 126

genome-wide association approach, incorporating genomics and epigenetics while dealing with the effects of multiple genes on drug response

Question 127

inter-individual differences in drug action?

Answer 127

Question 128

medicines act 1968?

Answer 128

Question 129

definition of a medicinal product?

Answer 129

“a manufactured article, intended to be taken by or administered to a person or animal, which contains a compound or compounds with proven biological effects, plus excipients, or excipients only, and may also contain contaminants.” **any substance or article administered for a medicinal purpose.**

Question 130

Product licence is from

Answer 130

Marketing Authorisation

Question 131

unlicensed =

Answer 131

no licensing, wholly responsibility of prescriber

Question 132

off label =

Answer 132

licensed drugs not used for a licensed indication or by unlicensed route

Question 133

General sales list products?

Answer 133

* Can be sold anywhere e.g. including supermarket

Question 134

other types of medicinal products?

Answer 134

* Pharmacy Only Medicines (P) * Prescription Only Medicines (POM) * Controlled Drugs (CD)

Question 135

prescriptions in the community?

Answer 135

* FP10 – GPs (SS – computer, NC – hand-written) * FP10HNC (hospital hand-written)

Question 136

POM legal requirements?

Answer 136

* signature * dispensed within 6 months * date * in ink or otherwose indelible * address and role of practioner * name and adress of patient * age if under 12 * dose

Question 137

Scale and consequences of non-adherence?

Answer 137

* studies show that patients with chronic illnesses take only ~50% of medications prescribed * consequences: waste of medication, disease progression, lower QOL, increased hospital admissisions and visits

Question 138

To be able to describe the influence of patients’ beliefs on adherence?

Answer 138

* beliefs about illness, treatment or self efficacy to adhere * higher perceived barrier to treatment -> lower compliance * negative beliefs -> lower adherence * cultural beliefs - herbal remedies

Question 139

the barriers to achieving shared decision making with patients?

Answer 139

* perceived time constraints * perceptions that shared DM cannot be applied bc of patient's characteristics * nature of the clinical situation * difficulties in communication * complexity of info * patient not ready to participate in SDM * patient reluctant to decide

Question 140

what is variability?

Answer 140

* Variability in the response to drugs is due to three principal components—the disease, the responsiveness of tissues, and the concentration of the drug at its site of action (as reflected by its plasma concentration). * variability arises bc of inter-individal differences in rates of drug abs. drug distribution and elimination

Question 141

factors influencing variability in drug response?

Answer 141

* age * drug interactions * impaired metabolism and excretion * degree of plasma protein binding -> influences distribution, action, metabolism and renal excretion of drugs

Question 142

Other factors producing variation in response?

Answer 142

* diet, co-morbidities, age, weight, drug–drug interactions, sex, and genetics. * ethnicity * pregnancy

Question 143

how altered pharmacokinetic handling of drugs produces variation in response - GI?

Answer 143

* arises bc of variable delivery of a dose of a drug to target sites - variability in the relationship between drug dose and plasma and tissue drug concentrations. * Gastrointestinal absorption may be slowed by atropine or opiates, or accelerated by metoclopramide, which hastens gastric emptying.

Question 144

To be able to explain how altered pharmacokinetic handling of drugs produces variation in response - muscle mass?

Answer 144

* Muscle mass is greater and adipose tissue mass smaller in men than in women. * Thus, water-soluble drugs have larger distribution volumes in men and lipid-soluble drugs (e.g. diazepam, propranolol) have larger distribution volumes in women.

Question 145

how altered pharmacokinetic handling of drugs produces variation in response?

Answer 145

* Highly extracted drugs (e.g. propofol, propranolol)  with clearance close to hepatic blood flow are sensitive to changes in hepatic blood flow

Question 146

how can pharmacogenetic variation influence resp to drugs?

Answer 146

* genetic polymorphisms which can result in altered responsivenes in drug targets e.g. receptor function or altered drug handling (enzyme activity) * if patients metabolize certain drugs rapidly, they may require higher more frequent doses to achieve therapeutic concerntrations

Question 147

How can pharmacodynamic factors impact drug responses?

Answer 147

* Pharmacodynamic variability arises because of variability in the relationship between drug concentration and effect. * differences in receptor number and structure * receptor coupling mechanism s * physiological changes in target organs resulting from differences in genetics, age and health

Question 148

Genetic variation's impact on the handling and response to drugs?

Answer 148

* differences in inherited makeup among individuals affects what the body does to the drug and vv * in some cases the level of enzyme can be measured before staring the therapy - should be considered before prescirbing * some ppl metabolise drugs slowly - drug can accumulate -> toxicity * drug can be metabolised so fast that the drug levels never become high enough for the drug to be effective

Question 149

where pharmacogenetic variation influences prescribing - primaquine?

Answer 149

* primaquine induced haemolysis in individuals with glucose 6-phosphate dehydrogenase deficiency whose red blood cells are thereby more susceptible to the effect of oxidative stress

Question 150

where pharmacogenetic variation influences prescribing - methyldopa?

Answer 150

* and immune-mediated haemolytic anaemia caused by methyldopa – a drug that commonly causes antidrug antibodies – whereas only a few individuals expressing such antibodies develop haemolysis

Question 151

where pharmacogenetic variation influences prescribing - HLA?

Answer 151

* polymorphisms in HLA * Structural mutations in HLA can lead to different clinical responses in patients  some variations are responsible for hypersensitivity reactions

Question 152

explain how increasing knowledge of pharmacogenetic variation will influence future prescribing practice?

Answer 152

* as understanding of the human genome improbes, together with the introduction of simoler methods to identify genetic differences between individuals, it will become possible to use genetic information spec to an indiv patient to preselect a drug that will be effective and not cause toxicity - personalised medicine * several human leukocyte antigen (HLA) variants that predict toxicity of abacavir, carbamazepine andclozapine

Question 153

Pharmacokinetic changes w age?

Answer 153

Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life)

Question 154

pharmacodynamic changes?

Answer 154

pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs.

Question 155

special care w dosing needed?

Answer 155

* Children, and particularly neonates, differ from adults in their response to drugs. * Special care is needed in the neonatal period (first 28 days of life) and doses should always be calculated with care.

Question 156

neonates have a higher?

Answer 156

* NB neonates have a higher relative amount of water so for water soluble drugs the dose must be increased to compensate for the high Vd.

Question 157

when is TDM undertaken?

Answer 157

narrow therapeutic index

Question 158

measuring plasma drug concs?

Answer 158

optimize drug dosing and ensure therapeutic efficacy while minimizing the risk of toxicity.

Question 159

measuring clinical outcomes?

Answer 159

* evaluating patients symptoms and signs and disease status to monitor effects of drug therapy on teir health outcomes * This may include subjective assessments (e.g., pain scales, symptom questionnaires) and objective measurements (e.g., vital signs, physical examination findings

Question 160

measuring pharmacodynamic responses?

Answer 160

* by measuring the physiological indices of therapeutic responses such as lipid conc, blood glucose, blood pressure and clotting

Question 161

advantages of measuring plasma drug concentrations?

Answer 161

* precision * individualisation of therapy * minimises risk of toxicity using TDM * early detection of problems - Changes in plasma drug concentrations may indicate issues such as poor adherence, drug interactions, altered drug metabolism, or impaired renal or hepatic function

Question 162

disadvantages of measuring plasma drug concs?

Answer 162

* cost - equipment, trained personnel for sample collection, processing and analysis * time consuming - espec w long half lives * invasiveness - venepuncture, can impact adherence to monitoring protocols

Question 163

- of measuring plasma drug conc - endpoints?

Answer 163

* surrogate endpoint - Plasma drug concentrations are often used as surrogate endpoints in clinical practice, assuming that achieving target concentrations will result in improved clinical outcomes. * limited predictive value - Plasma drug concentrations provide information about drug exposure but may not always correlate directly with therapeutic efficacy or clinical outcome

Question 164

prerequisites for plasma drug conc?

Answer 164

* established therapeutic range * reliable assays * clinical justification - drugs with narrow therapeutic indices, significant interpatient variability in pharmacokinetics, complex dosing regimens, risk of drug interactions, potential for toxicity, * access to monitoring services * patient co-operation and adherence - willingness to undergo blood sampling procedures, provide accurate medication histories, adhere to prescribed dosing regimens, and follow-up with healthcare providers

Question 165

prerequisites of using clinical outcomes?

Answer 165

* established clinical endpoints - Clearly defined clinical endpoints relevant to the therapeutic goals of drug therapy must be identified. * E.g. mortality, morbidity, symptom relief, disease progression, quality of life, and functional status. * clinical justification * outcome emasures - valid reliable and responsive to changes in clinical status

Question 166

using clinical outcomes - baseline?

Answer 166

* baseline assessment - Baseline assessment of clinical outcomes before initiating drug therapy provides a reference point for monitoring treatment effects over time. * Baseline characteristics may include demographic factors, disease severity, comorbidities, functional status, and previous treatment history. * regular follow up assessments to monitor changes in clinical outcomes

Question 167

advantages of using clinical outcomes to monitor drugs?

Answer 167

* Direct Assessment of Treatment Effects: Clinical outcomes provide direct information about the impact of drug therapy on patients' health status, symptoms, and overall well-being * Holistic Approach: Clinical outcomes capture the multidimensional effects of drug therapy on patients' lives, including improvements in symptoms, functional status, quality of life, and long-term prognosis * Patient-Centered Care: Focusing on clinical outcomes promotes patient-centered care by aligning treatment goals with patients' preferences, values, and priorities. * Allows for LT monitoring of treatment effects and disease progression ovetime

Question 168

disadvantages of using clinical outcomes?

Answer 168

* subjectivity - Clinical outcomes may be subjective and influenced by patients' perceptions, expectations, and reporting biases * time and resource intensive * Heterogeneity of Endpoints: Clinical outcomes encompass a wide range of endpoints, each with its own measurement properties, interpretation criteria, and clinical significance * delayed detection of effects - outcomes may take time to mainfest and may not be immediately apparent

Question 169

prequisites of measuring pharmacodynamic response?

Answer 169

* clear understanding of pharmacodynamics - mechanism, receptors and pathways * established pharmacodynamic markers - should be measurable, sensitive to changes induced by the drug and clinically meaningful * Baseline assessment of pharmacodynamic markers before initiating drug therapy provides a reference point for monitoring treatment effects over time. * Baseline characteristics may include pre-existing disease status, baseline levels of pharmacodynamic markers, and other relevant patient factors

Question 170

advantages of measuring pharmacodynamic resp?

Answer 170

* direct measurement of treatment effects * relevence to therapeutic goals - Pharmacodynamic responses are closely linked to the therapeutic goals of drug therapy, such as symptom relief, disease control, or physiological normalization. * quantitative assessment - using objective endpoints, biomarkers, or physiological parameters.

Question 171

pharmacodynamic + - individualization?

Answer 171

* individualization of therapy - personalized approach helps optimize treatment regimens, tailor dosing strategies, and maximize therapeutic benefits while minimizing the risk of adverse effects. * early detection of treatment effects

Question 172

disadvantages of measuring pharmacodynamic effects?

Answer 172

* complexity of assessment * subjectivity and variability * Interpretation Challenges: Interpreting pharmacodynamic responses requires careful consideration of confounding factors, baseline variability, and changes over time * limited PV: Pharmacodynamic responses may not always correlate directly with clinical outcomes or long-term treatment effects.

Question 173

examples where measuring drug conc are imp?

Answer 173

* individualised dosing - Some patients may require dosage adjustments based on their individual pharmacokinetic profiles, which can be influenced by factors such as age, weight, renal function, hepatic function, genetic polymorphisms, and concomitant medication * drug-drug interactions * treatment of spec conditions e.g. epilepsy, organ transplantation, cancer chemo - precise control of drug concentrations is critical for maximizing therapeutic efficacy and minimizing the development of drug resistance or adverse effects. * special populations - neonates, elderly, pregnant women, renal/ hepatic impairment

Question 174

ways in which drug effects can be measured?

Answer 174

1. clinical assessment - observations, examination findings, signs and symptoms 2. lab tests - e.g. blood glucose levels, serum drug levels 3. imaging - visualising changes in response to drug therapy 4. physiological monitoring - ECG, O2 sats, resp rate 5. functional assessments - ability to perform spec tasks 6. measurement of biomarkers - can provide surrogate endpoints for assessing treatment effects

Question 175

why is the impact of drugs on clinical outcomes is difficult to measure?

Answer 175

* multiple factors influencing clinical outcomes * varianbility in patient response - variability in patient response can make it difficult to predict and measure the overall impact of a drug on clinical outcomes across diverse patient populations. * delayed onset of action - can require long term follow up * heterogeneity of clinical endpoints

Question 176

difficulty of measuring clinical outcomes - longitudinal?

Answer 176

* longitudinal nature of disease processes - Many diseases have a chronic or progressive course, and the impact of drug therapy on clinical outcomes may evolve over time. * unforseen adverse effects

Question 177

surrogate outcome =

Answer 177

prediction of clinical benefit. Method of getting drugs to the market faster.

Question 178

surrogate markers are used when...

Answer 178

Surrogate markers are used when the primary endpoint is undesired (e.g., death), or when the number of events is very small, thus making it impractical to conduct a clinical trial to gather a statistically significant number of endpoints

Question 179

what is a hard outcome?

Answer 179

Hard ouctome: Objective or “hard” outcomes are those which are unambiguous and can be consistently measured by different assessor

Question 180

features of a good surrogate outcome - predictive value?

Answer 180

* predictive value - should reliably predict the outcome of interest

Question 181

features of a good surrogate outcome - biological plausibility?

Answer 181

* biological plausibility - There should be a clear biological rationale for why changes in the surrogate marker would be associated with changes in the clinical endpoint * easily measurable and quantifiable

Question 182

features of a good surrogate outcome - sensitivity and specificity?

Answer 182

* Sensitivity: It should be sensitive to changes induced by the intervention being studied, allowing for meaningful detection of treatment effects. * Specificity: Changes in the surrogate outcome should be specifically attributable to the mechanism of action of the intervention rather than confounding factors.

Question 183

surrogate outcome - clinical relevance?

Answer 183

* Clinical Relevance: The surrogate outcome should be meaningful in the context of the disease being treated and should reflect improvements in patient outcomes.

Question 184

surrogate outcome - validation and feasibility?

Answer 184

* Validation: Ideally, the surrogate outcome should be validated through empirical evidence demonstrating its association with the clinical endpoint in relevant populations and settings. * Feasibility: It should be feasible to measure the surrogate outcome in the context of clinical trials, considering factors such as cost, time, and resources required for assessment.

Question 185

variable relation between dose and plasma conc?

Answer 185

* when there is variable relation between drug dose and plasma drug conc, it means that the conc of the drug in the BS does not change proportionally w changes in dose

Question 186

non-linear pharmacokinetics?

Answer 186

* non-linear pharmacokinetics - doubling the dose may not result in a doubling of the plasma concentration. * Nonlinear pharmacokinetics can occur due to saturation of drug-metabolizing enzymes or transporters,

Question 187

variation in drug dose and plasma conc - FPM & binding?

Answer 187

* FPM - Drugs that undergo extensive first-pass metabolism in the liver may exhibit variable plasma concentrations * binding to plasma proteins - because changes in dose can saturate protein binding sites, leading to nonlinear changes in free drug concentrations.

Question 188

variable relation between dose and plasma drug concentration - metabolism?

Answer 188

* Induction or Inhibition of Metabolism: Co-administration of drugs that induce or inhibit drug-metabolizing enzymes can lead to variable plasma concentrations by altering the rate of drug metabolism and clearance.

Question 189

genetic variability?

Answer 189

* Genetic Variability: Genetic factors can contribute to variability in drug metabolism, distribution, and elimination, leading to variable plasma concentrations in response to changes in dose among different individuals.

Question 190

variability between drug conc anc effect - pharmacodynamic variability?

Answer 190

* Pharmacodynamic Variability: Differences in individual patients' pharmacodynamic responses to a drug can result in variable effects at similar drug concentrations. * Factors such as genetic variability, disease state, age, and concomitant medications can influence pharmacodynamic responses.

Question 191

other factors impacting variability between drug conc and effect?

Answer 191

- receptor sensitivity - tolerance - downstream signalling pathways - drug interactions - disease state

Question 192

downstream signalling pathways?

Answer 192

* Downstream Signaling Pathways: The downstream signaling pathways activated by a drug-receptor interaction can vary among individuals, leading to variable effects at similar drug concentrations.

Question 193

tolerance =

Answer 193

* Tolerance: Long-term exposure to a drug can lead to the development of tolerance, **where higher doses are required to achieve the same therapeutic effect.** This can result in a variable relation between drug concentration and effect over time.

Question 194

disease state?

Answer 194

* disease state - conditions with altered receptor expression or function like cancer or HF can lead to an unpredictable response

Question 195

characteristics that make a drug suitable for monitoring by measurement of concentration?

Answer 195

* narrow therapeutic index - closely to ensure therapeutic efficacy while avoiding adverse effects. * variable pharmacokinetics * complex dosing regimes * risk of toxicity - clinical resp variability - patient characteristics

Question 196

clinical resp variability?

Answer 196

* clinical response variability - where clinical response does not correlate well with dose or where there's sig interpatient variability in response

Question 197

patient characteristics?

Answer 197

* patient characteristics - Patient-specific factors such as age, renal function, hepatic function, and concomitant medications can influence drug concentrations

Question 198

List common medicines whose use is facilitated by measurement of drug concentration?

Answer 198

* Antibiotics - vancomycin, gentamicin * cardiac - digoxin, procainamide, lidocaine * phenytoin * immunosuppressants - cyclosporine and tacrolimus * bipolar drugs - lithium, valproic acid

Question 199

Describe the practicalities of measuring plasma drug concentrations.

Answer 199

1. sample collection 2. timing of sampling - Samples may be collected at specific time points relative to drug administration (e.g., peak concentration, trough concentration) or as part of a pharmacokinetic profile to assess ADME over time 3. sampling and processing 4. analytical methods

Question 200

Explain how to interpret drug concentration measurements appropriately?

Answer 200

* establishing therapeutic range * compare measured conc to therapeutic range * If the measured concentration is below the therapeutic range, it may indicate suboptimal drug exposure and insufficient therapeutic effect. * If the measured concentration is above the therapeutic range, it may suggest excessive drug exposure and an increased risk of adverse effects or toxicity. * consider clinical factors - monitor for signs and symptoms of therapeutic failure or toxicity * adjust dosage * follow up monitoring

Question 201

drug conc below the therapeutic range?

Answer 201

* If drug concentrations are below the therapeutic range and clinical response is inadequate, consider increasing the dosage or frequency of administration.

Question 202

drug conc above the therapeutic range?

Answer 202

* If drug concentrations are above the therapeutic range and/or adverse effects are present, consider decreasing the dosage or extending the dosing interval.

Question 203

adjusting dose in light of drug concentration measurements?

Answer 203

* Take into account patient-specific factors such as age, weight, renal function, hepatic function, genetic polymorphisms, and concomitant medications when adjusting dosage.

Question 204

ADR =

Answer 204

An unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug e.g. anaphylaxis

Question 205

adverse drug event =

Answer 205

Untoward occurrence after exposure to a drug that is not necessarily caused by the drug

Question 206

frew of adverse drug reactions?

Answer 206

* 10-20% of hospital inpatients

Question 207

impacts of ADR?

Answer 207

* healrhcare burden * ADRs can cause significant morbidity and mortality, leading to prolonged hospitalizations, disability, and even death * reduced QOL - pain, discomfort, impaired functioning * drug safety concerns - public mistrust

Question 208

explain why all drugs have both beneficial and adverse effects?

Answer 208

* drugs targets often shared by other biological processes leading to unintended effects * indiv variability * off target effects - These effects may be beneficial, such as when a drug used to treat one condition also improves symptoms of another condition, or adverse, resulting in unwanted side effects.

Question 209

ABCDE classification of ADR?

Answer 209

- A - augmented - B - bizzare - C - continuing/ chronic - D - delayed - E - end of use

Question 210

which type of drug reaction is the most common?

Answer 210

type A - 80% of all reactions

Question 211

what happens in type A reactions?

Answer 211

* primary effects - augmentation of therapeutic action * e.g. beta blocker and bradycardia * secondary effects - can rationalise from pharmacology * e.g. BB and bronchospasm

Question 212

other examples of type A reactions?

Answer 212

* constipation w opiods * sedation w antihistamines * dopamine antagonism: galactorrhaea, amenorrhoea, EPS

Question 213

type a reactions tend to be?

Answer 213

* dose dependent and predictable * They often result from the desired pharmacological action of the drug but are exaggerated or intensified beyond the therapeutic range.

Question 214

type b reactions?

Answer 214

* bizzare * Not associated with known pharmacology of the drug  e.g. allergic responses * e.g. steven-johnson syndrome

Question 215

Type c reactions?

Answer 215

* continuing * Occur with long-term drug use e.g. adrenal suppression from steroids * drug induced nephrotoxicity or hepatotoxicity

Question 216

type d reactions?

Answer 216

* delayed * Delayed from onset of the drug use e.g. secondary cancers from alkylating agents or tardive dyskinesia from AP * These effects may occur days, weeks, or even months after starting treatment and can be challenging to attribute directly to the drug.

Question 217

type E reactions?

Answer 217

* end of use * occur when drug course is completed e.g. benzo withdrawal

Question 218

DOTS classification of drug reactions?

Answer 218

- d - definitie - O - probable - T - possible - S - suspected

Question 219

Definite drug reactions?

Answer 219

* where a clear cause-and-effect relationship between the drug and the adverse event has been established through documented evidence, such as rechallenge or specific diagnostic tests.

Question 220

O - probable drug reactions?

Answer 220

* where there is a reasonable likelihood that the drug caused the adverse event, based on temporal relationship, known pharmacological properties of the drug, and absence of alternative explanations.

Question 221

T - possible drug reactions?

Answer 221

ADRs classified as "Possible" are those where a causal relationship with the drug cannot be ruled out, but there is insufficient evidence to establish a definitive or probable association

Question 222

S - suspected drug reactions?

Answer 222

ADRs categorized as "Suspected" are those where there is a clinical suspicion of a drug-related adverse event, but no further evidence or investigation has been conducted to confirm or refute the association. This classification is typically used when there is anecdotal or preliminary evidence suggesting a potential link between the drug and the adverse event

Question 223

risk factors for drug allergy/ anaphylaxis?

Answer 223

* A history of other allergies, such as food allergy or hay fever * A personal or family history of drug allergy * Increased exposure to a drug, because of high doses, repeated use or prolonged use * Certain illnesses commonly associated with allergic drug reactions, such as HIV infection or the Epstein-Barr virus

Question 224

other factors inc anaphylaxis risk?

Answer 224

*History of atopic allergy (hay fever, asthma, eczema) - higher risk *Hx of anaphylaxis, urticaria or rash immediately after penicillin *DO NOT treat with a penicillin, cephalosporin or beta-lactam based antibiotic

Question 225

Common symptoms of a drug allergy include?

Answer 225

* Hives * Itching of the skin or eyes (common) * Skin rash (common) * Swelling of the lips, tongue, or face * Wheezing * Bleeding

Question 226

anaphylaxis symptoms?

Answer 226

* Abdominal pain or cramping * Confusion * Diarrhea * Difficulty breathing with wheezing or hoarse voice * Dizziness * Fainting, lightheadedness * Hives over different parts of the body * Nausea, vomiting * Rapid pulse * Sensation of feeling the heart beat (palpitations)

Question 227

characterisisation of an allergic drug reaction?

Answer 227

* Timing - immedate or delayed (days to weeks after initiation of treatment) * Symptoms - urticaria, pruritus, angioedema, resp symptoms, GI symptoms, CV symptoms * severity: Allergic drug reactions can range from mild, localized symptoms to severe, life-threatening reactions such as anaphylaxis. * reproducibility: allergic drug reactions are often reproducible upon re-exposure * mechanism - IgE mediated or T cell mediated delayed hypersensitivity

Question 228

explain the importance of accurate diagnosis and recording of allergic reactions to drugs?

Answer 228

* patient safety - avoid using the same drugs * treatment planning * prevention of adverse events * avoidance of diagnostic delays - Mislabeling non-allergic adverse drug reactions as allergies can lead to unnecessary avoidance of potentially beneficial medications,

Question 229

explain the precautions that should be taken to prevent allergic reactions?

Answer 229

* thorough history * medication reconcillation and verify allergy info * drug allergy assessment * avoidance of known allergens * allergy testing e.g. skin prick * adverse drug reporting to MHRA

Question 230

describe the principles of assessing drugs as a possible cause of new symptoms and signs?

Answer 230

* Temporal relationship * drug history - look for interactions * symptom profile - is presentation consistent with known adverse effects of the implicated drug or suggests an alternative diagnosis. * are the symptoms consistent w the expected pharmacological effects of the drug * dose - response relationship between exposure and symptom severity

Question 231

explain how to respond if an adverse drug reaction is suspected.

Answer 231

* Report to MHRA via yellow card scheme * assessment and evaluation of clinical significance and contributing factors

Question 232

how to manage a suspected adverse drug reaction?

Answer 232

* Discontinuation or dose adjustment of the offending drug. * Symptomatic treatment to alleviate ADR-related symptoms. * Substitution with an alternative medication that is less likely to cause a similar reaction * Monitoring for resolution of symptoms and assessing for any long-term consequences of the ADR.

Question 233

imp RF that predict susceptibility to adverse drug reactions - age?

Answer 233

* Age - changes in pharmacokinetics and pharmacodynamics, comorbidities, polypharmacy

Question 234

important risk factors that predict susceptibility to adverse drug reactions - polypharmacu?

Answer 234

* polypharmacy - interactions, cumulative toxicity * underlying health conditions - altered drug metabolism and clearance

Question 235

important risk factors that predict susceptibility to adverse drug reactions - drug characteristics?

Answer 235

* drug characteritics - high potency, narrow therapeutic index

Question 236

important risk factors that predict susceptibility to adverse drug reactions - chronic drug use?

Answer 236

* chronic use of drugs - especially w drugs associated w cumulative toxicity, delayed onset reactions, drug induced organ damage

Question 237

important risk factors that predict susceptibility to adverse drug reactions - patient factors?

Answer 237

* patient factors - sex, body weight, genetic predisposition, lifestyle factors (e.g., smoking, alcohol consumption), and adherence to medication regimens

Question 238

how can identification of risk factors for adverse drug reactions can influence prescribing decisions?

Answer 238

* drug selection - using drugs with lower risk of ADRs e.g. enteric coated formulation to minimise risk * dosing adjustments based on renal/hepatic function, age, body weight, genetic variability * monitoring and surveillence * medication reviews

Question 239

sources of information about adverse drug reactions?

Answer 239

* BNF * MHRA safety alerts under the important safety information section * MHRA interactive drug analysis profiles - iDAPs - display data from the Yellow Card Scheme and provide information on the number of “yellow card” reports of suspected adverse drug reactions (ADRs) received for a medicine.

Question 240

explain the importance of warnings in preventing adverse reactions.?

Answer 240

* risk communication * Warnings, including boxed warnings, contraindications, precautions, and adverse reaction information in drug labels and prescribing information, communicate important safety information to healthcare providers and patients. * Informed DM - allows patients to make informed decisions about medication therapy by balancing the benefits of treatment with the potential risks of ADRs. * warnings prompt healthcare professionals to take preventative measures to reduce risk of ADRs

Question 241

Imp of monitoring in preventing ADR?

Answer 241

* risk mitigation * helps identify emerging risks, trends and patterns of ADRs * This information informs regulatory decisions, labeling updates, risk management strategies, and public health interventions to mitigate the risk of ADRs and enhance medication safety. * early detection

Question 242

monitoring of ADR and QI?

Answer 242

* QI - Monitoring ADRs contributes to quality improvement initiatives aimed at enhancing medication safety practices, reducing medication errors, and optimizing patient outcomes.

Question 243

explain why the adverse drug reaction profile of individual drugs is unclear at their launch onto the market.?

Answer 243

* limited clincial trial data - small patient group -> rare ADR missed * short term follow up -> long term outcomes missed * underreporting of ADR - voluntary reporting of ADRs can lead to undereporting due to lack of awareness, uncertainty abt causality, reporting fatigue * limited post marketing data * patient variability - age, sex genetics, concomitant medications The diversity of patient populations encountered in real-world clinical practice may reveal ADRs that were not observed or anticipated during pre-market clinical trials. * off label use

Question 244

What is pharmacovigilance?

Answer 244

* = activites related to the detection, assessment, prevention of adverse effects associated w drugs * encompasses the collection, monitoring, analysis, and dissemination of information on the safety and efficacy of medications throughout their lifecycle

Question 245

pharmacovigilance plays a role in?

Answer 245

* Pharmacovigilance plays a critical role in ensuring the safe and effective use of medications by identifying, evaluating, and preventing adverse drug reactions (ADRs)

Question 246

what are the roles of pharmacovigilance?

Answer 246

* patient safety - by preventing ADRs * public health protection by monitoring the safety profiles of meds * regulatory compliance - Regulatory authorities require pharmaceutical companies to conduct pharmacovigilance activities as part of their ongoing regulatory compliance obligations. * required in drug development and approval * facilitates risk communication

Question 247

prescriber's resp in pharmacovigilance?

Answer 247

* recognising and reporting ADRs * reporting to MHRA - yellow card scheme * educating patients on risks and benefits of medications including the importance of reporting ADRs

Question 248

yellow card scheme?

Answer 248

* Report adverse reactions to drugs - self medication and prescribed, blood products, vaccines, radiographic contrast media, complementary, homeopathic and herbal products * The Yellow Card scheme can also be used to report medical device adverse incidents, defective medicines, suspected falsified (fake) medicines, as well as safety concerns associated with e-cigarettes and their refill containers (e-liquids). * reporting of reactions that are serious, medically sig or result in harm

Question 249

Interaction of ramipril and naproxen?

Answer 249

*ACEi/ARBs - > haemodynamic reduction in glomerular filtration rate due to efferent arteriolar vasodilation *NSAIDs -> inhibition of prostacyclin synthesis -> renal afferent arteriolar vasoconstriction *Combinations such as this increase the risk of AKI due to both impacting renal function, and do so through different mechanisms

Question 250

Drug related acute kidney injury is commonly associated with:

Answer 250

*antiretroviral drugs *aminoglycoside antibiotics *non-steroidal anti-inflammatory drugs (NSAIDs)

Question 251

CYP450 induces?

Answer 251

* carbamazepine * rifampicin * rifabutin * St Johns wort

Question 252

CYP450 inhibitors?

Answer 252

* Fluconazole * clarithromycin * erythromycin * grapefruit juice * ritonavir

Question 253

enzyme induction ->

Answer 253

Enzyme induction → increased metabolism and excretion → tolerance or decreased effectiveness → increased doses → slow development = days to weeks

Question 254

Enzyme inhibition →

Answer 254

Enzyme inhibition → decreased metabolism → sensitivity → decreased doses → drug accumulation → rapid development = days

Question 255

warfarin and carbamazepine interaction?

Answer 255

*Carbamazepine is an enzyme inducer, so will therefore induce metabolism of warfarin *This results in decreased effectiveness of the current warfarin dose & a lower INR *Develops over days-weeks

Question 256

drug development process?

Answer 256

* drug discovery and phase 0 trials * phase 1 * phase 2 * phase 3 * regulatory approval * phase 4

Question 257

phase 1 of drug development?

Answer 257

*Safety & efficacy testing   - computerised models   - cells   - animals *Clinical Trial Approval   - safety & pharmacology in healthy volunteers (20 to 100)

Question 258

phase 2?

Answer 258

*Efficacy of compound in volunteers with disease *Determine effective dose *Further monitoring of  safety

Question 259

phase 3?

Answer 259

*Testing in larger population (1000 - 5000) *Overall risk-benefit *Licensing application based on safety & efficacy data

Question 260

regulatory approval?

Answer 260

* Committee on Safety of Medicines – legal framework for control of medicines (now CHM) * Submission for marketing authorisation (UK – MHRA) manufacturing process, pharmacology and toxicity of the compound, human pharmacokinetics, results of the clinical trials, and proposed labelling.

Question 261

phase 4?

Answer 261

* post marketing studies/ surveillence * Monitoring of long term effectiveness & safety - e.g.  rofecoxib * Cost effectiveness * Yellow Card Scheme

Question 262

potential for interacting drugs to cause beneficial effects?

Answer 262

* Some drug interactions result in synergistic pharmacological effects, where the combined action of two or more drugs produces a greater therapeutic effect than the sum of their individual effects. * For example, combining an opioid analgesic with a nonsteroidal anti-inflammatory drug (NSAID) may provide more effective pain relief than either drug alone.

Question 263

interacting drugs causing beneficial effects - therapeutic effect?

Answer 263

* potentiatuon of therapeutic efficacy - Interacting drugs may potentiate the therapeutic efficacy of one another by enhancing their pharmacological actions or targeting complementary pathways involved in disease pathogenesis. * combination therapy - Drug interactions can be intentionally utilized to achieve therapeutic goals through combination therapy.

Question 264

harmful effects of interacting drugs?

Answer 264

nteracting drugs can increase risk of ADRs by altering drug pharmacokinetics or pharmacodynamics -> unpredictable or exaggerated responses * Drug interactions may result in drug accumulation, overdose, or toxicity due to alterations in drug metabolism, clearance, or distribution * therapeutic failure - Interacting drugs can interfere with one another's therapeutic efficacy by reducing drug bioavailability, antagonizing pharmacological effects, or inducing drug resistance.

Question 265

ways in which interactions occur pharmacokinetic - Abs?

Answer 265

* absorption - Interactions that affect the absorption of drugs from the gastrointestinal tract, such as alterations in gastric pH, chelation, or binding interactions that decrease bioavailability.

Question 266

ways in which interactions occur pharmacokinetic - dist?

Answer 266

* distribution - Interactions that influence the distribution of drugs within the body, such as displacement from protein binding sites, which can increase the concentration of unbound drug in plasma and potentially enhance pharmacological effects or toxicity.

Question 267

ways in which interactions occur pharmacokinetic - metabolism?

Answer 267

* Metabolism (Biotransformation): Interactions that affect the metabolism of drugs in the liver or other tissues, particularly through inhibition or induction of drug-metabolizing enzymes, such as cytochrome P450 (CYP) enzymes. * Inhibition of metabolism can lead to increased plasma concentrations and prolonged half-life of drugs, while induction can result in decreased drug levels and reduced efficacy.

Question 268

ways in which interactions occur pharmacokinetic - excretion?

Answer 268

* excretion - Interactions that affect the renal or hepatic elimination of drugs, such as competition for renal tubular secretion or inhibition of renal or hepatic transporters, leading to altered drug clearance and systemic exposure.

Question 269

ways in which drugs interact - altered pharmacokinetics?

Answer 269

* Altered Pharmacokinetics: Interactions that occur indirectly through changes in physiological processes or disease states that affect drug absorption, distribution, metabolism, or excretion. * For example, alterations in gastrointestinal motility, renal function, hepatic blood flow, or plasma protein binding can influence drug pharmacokinetics and the likelihood of interactions.

Question 270

ways in which drugs interact - pharmacodynamic?

Answer 270

- receptor interactions - enzyme inhibition/ induction - pharm antagonism

Question 271

receptor interactions?

Answer 271

* receptor interactions - interactions that affect the renal or hepatic elimination of drugs, such as competition for renal tubular secretion or inhibition of renal or hepatic transporters, leading to altered drug clearance and systemic exposure.

Question 272

pharm antagonism?

Answer 272

* Pharmacological Antagonism: Interactions where one drug counteracts the effects of another drug by blocking its action at the receptor level or by interfering with the physiological processes involved in drug response

Question 273

explain why the potential for drug interactions in increasing?

Answer 273

* polypharmacy * expanding treatment options * self medications and OTC drugs * electronic prescribing systems - interactions might be missed

Question 274

dentify sources of information about drug interactions to inform prescribing.?

Answer 274

* BNF * electronic medicines compenidum (EMC) * MHRA

Question 275

predicting drug interactions?

Answer 275

* comprehensive medication review - Identify potential interactions based on known pharmacokinetic and pharmacodynamic properties of the drugs involved. * assess patient factors - Consider individual patient factors that may influence the risk of drug interactions, such as age, sex, weight, renal function, hepatic function, genetic polymorphisms, comorbidities, and concurrent use of medications with narrow therapeutic indices. * Evaluate the pharmacokinetic properties of the drugs involved in the interaction, including their metabolism, protein binding, bioavailability, half-life, and route of elimination. * Drugs with similar metabolic pathways or competing for the same drug transporters are more likely to interact.

Question 276

preventing drug interactions?

Answer 276

* minimize polypharmacy - Limit the number of medications prescribed whenever possible to reduce the risk of drug interactions. * Use the lowest effective doses and avoid unnecessary drug combinations, particularly in elderly patients or those with multiple comorbidities. * Educate patients about the importance of medication adherence, potential drug interactions, and strategies for avoiding or minimizing interactions. * Encourage patients to inform healthcare providers about all medications, supplements, and herbal products they are taking to facilitate accurate assessment and monitoring.

Question 277

explain how to adjust drug dosage in anticipation of a drug interaction that cannot be avoided.?

Answer 277

* assess clinical significance - evaluate the clinical impact of the drug interaction based on factors such as severity of the interaction, the therapeutic index of the affected drug, the patient's medical condition, and the availability of alternative treatment options. * review drug interactions - guidelines and pharmacovigilance * Understand how the interaction affects drug pharmacokinetics, including absorption, distribution, metabolism, and elimination. * Adjust drug dosages based on changes in drug clearance, bioavailability, half-life, and plasma concentrations to maintain therapeutic drug levels and minimize the risk of adverse outcomes.

Question 278

imp of liver cytochromes as a point of drug clearance?

Answer 278

* liver cytochromes especially CYP family are resp for the biotransformation of a wide range of drugs, toxins and pollutants * These enzymes catalyze Phase I reactions, such as oxidation, reduction, and hydrolysis, to convert lipophilic drugs into more polar metabolites that are readily excreted from the body. * drug clearance

Question 279

what do liver cytochromes acc do?

Answer 279

* Liver cytochromes are essential for the elimination of drugs from the body by facilitating their metabolism and conversion into water-soluble metabolites that can be excreted via urine or bile. * The rate of drug clearance by hepatic metabolism influences the duration of drug action, the need for dosage adjustment, and the risk of drug accumulation or toxicity with repeated dosing.

Question 280

Drugs that extensively metabolised by hepatic enzymes?

Answer 280

* Drugs that are extensively metabolized by hepatic enzymes are susceptible to interactions with other drugs that affect enzyme activity or expression. * liver metabolism is a critical point of interaction between drugs, influencing drug pharmacokinetics, efficacy, and safety

Question 281

COPS - CYP450 inducers?

Answer 281

* carbamazepine * Oxcarbazepine * phenytoin/ phenobarbital * smoking

Question 282

what do CYP450 inducers acc do?

Answer 282

* faster metabolism amd excretion of the drug * drug may not reach a threshold value of benefit if cleared more rapidly by the body * can cause failure of the oral contraceptive *

Question 283

What do CYP450 inhibitors do?

Answer 283

* causes other drugs to accumulate to toxic levels where overdoses and side effects may occur.

Question 285

mneumonic for CYP450 inhibitors?

Answer 285

SICK FACES. COM * Sodium valproate * Isoniazid * Cimetidine * Ketoconazole * Fluconazole * Alcohol & Grapefruit juice * Chloramphenicol * Erythromycin * Sulfonamides * Ciprofloxacin * Omeprazole

Question 286

how are drugs discovered?

Answer 286

* 1) identification of biological targets implicated in disease * 2) target validation - suitability as therapeutic targets * 3) lead discovery - identification of chemical compounds or molecules that have the potential to modulate the activity of the target and exert therapeutic effects. * 4) lead optimisation * 5) preclinical evaluation - Lead candidates that demonstrate favorable pharmacological and pharmacokinetic properties in vitro undergo preclinical evaluation in animal models to assess their safety, efficacy, and toxicological profiles in vivo * 6) Clinical Development: Promising lead compounds that pass preclinical testing progress to clinical development, where they undergo rigorous evaluation in human clinical trials to assess their safety, efficacy, and tolerability in patients - phase 1-4 trials * 7) regulatory approval * 8) post marketing surveillence

Question 287

Phase 1 involves?

Answer 287

* small studies (e.g. 100) on healthy volunteers * used to assess pharmacodynamics and pharmacokinetics

Question 288

phase 2 involves?

Answer 288

* small studies (e.g. 100-300) on actual patients * examines efficacy, adverse effects

Question 289

phase 3 involves?

Answer 289

* larger studies (e.g. 500-5,000 patients) * examines efficacy, adverse effects * may compare drug with existing treatments * studies of special groups e.g. renal, elderly

Question 290

phase 4 involves?

Answer 290

* post-marketing surveillence

Question 291

risks assoc w drug development?

Answer 291

* Research and discovery costs - includes expenses related to laboratory equipment, personnel, materials, and infrastructure. * lead optimisation and preclinical testing * clinical trials - most costly and time consuming phase of drug development * regulatory compliance costs * manufacturing and scaling up of drug production * intellectual property protection e.g. patents, trademarks and copyrights

Question 292

risks assoc w developing drugs?

Answer 292

* Drug development is inherently risky, with high rates of attrition at each stage of development. * Many drug candidates fail to progress beyond preclinical or clinical testing due to safety concerns, lack of efficacy, or commercial viability. * The costs associated with failed drug development efforts, including sunk costs and opportunity costs, represent significant financial losses for pharmaceutical companies and investors.

Question 293

types of clinica trial?

Answer 293

interventional and obs

Question 294

interventional clinical trials?

Answer 294

* objective - looks at specific interventions * study design - random assigment - RCTs are the gold standard * data collection - prospective

Question 295

+ of intv clinical trials

Answer 295

* controlled conditions - control of key variables e.g. randomisation to minimise bias and confounding * causality - Interventional trials provide strong evidence for establishing causality and making causal inferences about the effects of the intervention on health outcomes * can assess efficacy and safety * standardised data collection

Question 296

- of intv clinical trials?

Answer 296

* resource intensive * ethical considerations * external validity and generalisability - controlled conditions * placebo issues

Question 297

What happens during obs clinical trials?

Answer 297

* Observational trials aim to observe and analyze real-world data on patient characteristics, exposures, treatments, and outcomes in observational studies. * These trials investigate associations, risk factors, prognostic factors, treatment patterns, and natural history of diseases or conditions without intervening or manipulating exposures or treatments

Question 298

obs clinical trials use?

Answer 298

* non randomised designs and no use of control groups * Observational trials collect retrospective or prospective data on patient demographics, medical history, treatments, clinical outcomes, * e.g. cohort, case control, cross sectional, database analyses

Question 299

+ of obs trials?

Answer 299

* real world data - inc generalisability and EV * large sample sizes and long follow up periods * ethical considerations - These studies do not involve experimental interventions or randomization of participants, minimizing risks, burdens, and ethical concerns related to randomization * cost effective and less resource intensive than inteventional trials

Question 300

- of obst trials?

Answer 300

* confounding and bias - non random allocation * limited IV - bias * missing data - reliance on existing data sources and medical records * reverse causality * Observational studies may lack external validity or generalizability due to selection bias, population heterogeneity, or differences in study populations, settings, or healthcare systems.

Question 301

consent and ethics in a trial?

Answer 301

* informed consent process * ethical review and approval needed * participant autonomy * respect for participant dignity, privacy, confidentiality and personal intergrity * beneficence and non-maleficence

Question 302

selection bias?

Answer 302

*Selection bias occurs when there are systematic differences between the characteristics of participants in different treatment groups or between participants and non-participants, leading to an imbalance in baseline characteristics that may influence study outcomes.

Question 303

mitigating selection bias?

Answer 303

randomization, allocation concealment, and blinding/masking to ensure unbiased assignment of participants to treatment groups and minimize differences in baseline characteristics.

Question 304

what is allocation bias?

Answer 304

also known as assignment bias or treatment allocation bias, occurs when the process of assigning participants to treatment groups is influenced by factors other than randomization, such as clinician preference, patient characteristics, or knowledge of treatment assignments.

Question 305

How is allocation bias reduced?

Answer 305

* Randomization, allocation concealment, and blinding/masking help prevent allocation bias by ensuring that treatment assignment is independent of investigator or participant preferences and expectations.

Question 306

what is performance bias?

Answer 306

* Performance Bias: Performance bias occurs when there are systematic differences in the delivery or administration of interventions between treatment groups, leading to differential exposure or adherence to treatment protocols.

Question 306

how is performance bias reduced?

Answer 306

* Blinding/masking of participants, investigators, and outcome assessors helps minimize performance bias by reducing the influence of awareness or expectations regarding treatment assignment on study conduct and outcomes.

Question 306

what is detection/ ascertainment bias?

Answer 306

* systematic differences in the ascertainment, measurement, or interpretation of study outcomes between treatment groups, leading to differential detection or reporting of outcomes.

Question 306

how can ascertainment bias be reduced?

Answer 306

Blinding/masking of outcome assessors and objective, standardized outcome measures help minimize detection bias by ensuring unbiased assessment and reporting of study outcomes.

Question 306

What is attrition bias?

Answer 306

* attrition bias - differences in the completion or retention of participants between treatment groups, leading to biased estimation of treatment effects.

Question 306

how can attrition bias be reduced?

Answer 306

* Strategies to minimize attrition bias include maximizing participant retention, implementing intention-to-treat analysis, and conducting sensitivity analyses to assess the impact of missing data on study conclusions.

Question 306

what is reporting bias?

Answer 306

* reporting bias - difference in reporting/ publication based on the direction/ magnitude of the findings

Question 306

how is reporting bias dealt w?

Answer 306

* To mitigate reporting bias, clinical trials should adhere to transparent reporting guidelines (e.g., CONSORT statement) and register study protocols and outcomes a priori to promote accountability, transparency, and completeness in reporting study findings.

Question 306

PUBLICATION BIAS =

Answer 306

* publication bias - Publication bias occurs when studies with positive or statistically significant results are more likely to be published or reported than studies with negative or non-significant results, leading to an overestimation of treatment effects and an incomplete representation of the evidence base.

Question 306

how can publication bias be reduced?

Answer 306

* To address publication bias, efforts should be made to disseminate study findings through peer-reviewed publications, conference presentations, clinical trial registries, and systematic reviews, regardless of the direction or significance of the results.

Question 307

good clinical trial - statistics- sample size determinaion? ?

Answer 307

* sample size determination - ensuring that the study is adequately powered to detect clinically meaningful differences or effects with sufficient precision and confidence.

Question 307

statistical methods used in good clinical trials?

Answer 307

* randomisation and allocation concealment * statistical analysis plan - outlines the methods and procedures for analyzing the study data, including primary and secondary endpoints, statistical tests, adjustment for confounding factors, handling of missing data, and sensitivity analyses. T * confidence intervals * meta analyses and evidence synthesis to generate summary estimates of treatment effects and assess consistency

Question 307

explain why drugs need to be regulated

Answer 307

* safety * efficacy * quality * clinical use - Drug regulation promotes appropriate and evidence-based use of medications * enhances public confidence

Question 307

MHRA?

Answer 307

* The MHRA is the regulatory agency responsible for regulating medicines, medical devices, and blood components for transfusion in the UK. * The MHRA assesses applications for marketing authorization, conducts inspections of manufacturing facilities, monitors the safety of medicines through pharmacovigilance activities, and enforces regulatory compliance with applicable laws and standards

Question 307

European Medicines Agency (EMA) - European Union (EU):

Answer 307

* responsible for coordinating the evaluation, approval, and supervision of medicines for human and veterinary use within the European Union (EU) a * The EMA assesses marketing authorization applications, provides scientific advice to applicants, conducts pharmacovigilance activities, and facilitates regulatory harmonization and cooperation among EU member states.

Question 307

the european commission - EU

Answer 307

* key role in the regulatory framework for medicines in the EU, overseeing the implementation and enforcement of EU legislation, regulations, and directives related to pharmaceuticals

Question 307

approval process for new drugs?

Answer 307

* preclinical testing - assesing safety, efficacy, pharmacodynamics and pharmacokinetics * clinical trials * marketing authorization application to the MHRA * MHA reviews the MAA to assess the safety, efficacy, and quality of the drug and determine whether it meets regulatory standards for approval.

Question 307

if a drug meets requirements then...

Answer 307

* if the drug meets requirements the MHRA grants marketing authorization allowing the drug to be marketed and sold in the UK * post marketing suveillence - The MHRA continues to evaluate the safety and effectiveness of the drug through pharmacovigilance activities, post-market studies, and periodic safety updates.

Question 308

imp of market exclusitivity and patents?

Answer 308

* Market exclusivity and patents provide pharmaceutical companies with a period of exclusivity during which they can recoup their R&D investment and earn a return on investment - incentivises them * fosters competition

Question 309

imp of patents?

Answer 309

* protecting intellectual property - Patents grant inventors exclusive rights to their inventions for a limited period, typically 20 years from the date of filing. * Patents protect pharmaceutical companies' intellectual property rights and prevent competitors from manufacturing, selling, or distributing the patented drug without authorization. * This protection encourages companies to disclose their innovations and inventions, fostering knowledge sharing and technological advancement.

Question 310

explain how drug sales can be protected when patents expire.

Answer 310

* developing new formulations, strengths, delivery mechanisms * brand loyalty * authorised genertics marketed and distrubuted by the original manufacturer * price adjustments

Question 311

explain the basics of how drugs are marketed by the pharmaceutical industry?

Answer 311

* product positioning and targeting * medical education and scientific communication to educate HCPs e.g. conferences * promotional materials * direct to consumer adveritising campaigns to stimulate demand

Question 312

explain the legal constraints on the marketing process for drugs.

Answer 312

* regulatory oversight - compliance w rules * labelling and packaging inserts need to be accurate and comprehensive * prohibition from promoting off label uses - illegal * false or misleading claims * fair balance in promotional materials by presenting benefits and risks

Question 313

recognize the role of the ABPI code of conduct

Answer 313

* sets ethical standards and guidelines for pharmaceutical companies operating in the UK. * The Code governs the promotion of prescription medicines to healthcare professionals, the provision of information to patients and the public, and interactions with healthcare organizations and patient groups

Question 314

what does the ABPI code of conduct ensure?

Answer 314

* ensures ethical marketing practices * protects patient welfare - means no misleading or deception * promotes transparency and accountability * addresses complaints and disputes related to breaches of the code

Question 315

describe the potential for the marketing process to change attitudes.

Answer 315

* information disseminating - creating awareness of medical conditions, treatment options, and available therapies * perception of need and demand - Marketing efforts can shape perceptions of need and demand for prescription drugs by highlighting the prevalence, severity, and impact of medical conditions, as well as the availability of effective treatments. * Marketing efforts targeted at healthcare professionals, such as detailing visits, promotional materials, sponsored educational events, and peer-to-peer interactions, can influence prescribing behavior and treatment choices * patient empowerment through DTC advertising

Question 316

uses of the drug promotion process?

Answer 316

* education and information * disease awareness * access to treatment by promoting availability, affordability and benefits

Question 317

abuses of the drug promotion process?

Answer 317

* misleading/ inaccurate claims * off label promotion - illegal * undue influence on prescribing * conflict of interest