GP

Question 1

Discuss the influence of age on PK

Answer 1

Decrease in total body water (due to decrease in muscle mass) and increase in total body fat affects volume of distribution

Water soluble drugs: lithium, aminoglycosides, alcohol, digoxin
Serum levels may go up due to decreased volume of distribution

Fat soluble: diazepam, thiopental, trazadone
Half life increased with increase in body fat
Absorption: Not highly impacted by aging

Variable changes in first pass metabolism due to variable decline in hepatic blood flow;
Typically reduced with age but variable (can be normal)
Acetylation and conjugation do not change appreciably with age

Oxidative metabolism through cytochrome P450 system does decrease with aging, resulting in a decreased clearance of drugs – half life’s increase with age

GFR generally declines with aging, but is extremely variable
30% have little change
30% have moderate decrease
30% have severe decrease

Question 2

Discuss the impact of age on PD

Answer 2

Some effects are increased – particularly true of drugs that act on the CNS
Alcohol
Opiates
Sedatives
Theophylline

Some effects are decreased
Diminished HR response to isoproterenol and beta -blockers

Question 3

Discuss the concerns around ADRs in the elderly

Answer 3

About 15% of hospitalizations in the elderly are related to adverse drug reactions

The more medications a person is on, the higher the risk of drug-drug interactions or adverse drug reactions

The more medications a person is on, the higher the risk of non-adherence

Question 4

List some examples of drug-disease interaction

Answer 4

Patient with PD have increased risk of drug induced confusion – particularly at risk of drugs which affect the dopamine system i.e., haloperidol

NSAID (and COX-2’s) s can exacerbate CHF – cause fluid retention

Urinary retention in BPH patients on decongestants or anticholinergics

Constipation worsened by calcium, anticholinergics, calcium channel blockers – common concern in elderly

Neuroleptics and quinolones lower seizure thresholds i.e., epilepsy, stroke history at risk of drug induced seizure

Question 5

List some common drug-drug interactions

Answer 5

Statins and clarithromycin and other antibiotics
Verapamil and beta-blockers – shouldn’t be used together
Warfarin and multiple drugs (incl aspirin)
ACE inhibitors increase hypoglycemic effect of sulfonylureas – may or may not be important

Question 6

Discuss the concern of undertreatment in the elderly

Answer 6

People worry about risk of intervention so don’t do it – even if robust evidence of overall benefit

Address risk rather than avoid prescribing if symptom is having an impact on the person

i.e., underdosing pain meds due to fears of sedation, looser control of HTN due to risk of postural hypotension and falls

Question 7

Discuss the prescribing cascade and list a common example

Answer 7

Prescribe a drug to deal with the side effect of another drug
Could be avoided by using a different drug

NSAID ->HTN->antihypertensive therapy
Thiazide diuretic ->gout->NSAID ->2nd antihypertensive

Question 8

List the effects of renal disease on PK

Answer 8

Decreased elimination – both through decreased elimination from the renal system and decreased hepatic metabolism in advanced renal disease
Decreased protein binding
Decreased hepatic metabolism

Question 9

List the effects of renal disease on PD

Answer 9

Altered sensitivity to drug effect
Increased adverse effects

Question 10

List drugs which have decreased excretion in renal failure

Answer 10

Aminoglycosides
Lithium
Digoxin
Methotrexate
Penicillin’s

Question 11

List prescribing considerations needed in renal disease

Answer 11

Determination of renal function – not always straightforward (precise answer to a non-precise question)
- eGFR calculation assumes renal function is stable – not always the case in hospital patients – creatinine may be lagging behind renal function by several days
- Why not useful in AKI

Do they need alteration of dosing schedule

What monitoring of drug concentrations is needed

Question 12

Discuss the effect of protein binding in renal disease and the impact this has on drugs

Answer 12

Renal failure leads to acid retention

“Acidic” drugs less bound to albumin:
Conformational change in albumin, less ionised drug to bind
Increased free (active) drug in plasma

Usually of little clinical relevance;
Phenytoin (acidic)
Less bound drug (more free drug)
Target concentration lower in renal failure
Increased clearance by HD

Can really be an issue in advanced renal failure – need careful monitoring

Question 13

Discuss hepatic metabolism in renal disease

Answer 13

Hepatic metabolism of some drugs is slower in renal failure

? Endogenous inhibitor in uraemic plasma – can stop metabolic enzymes having effect
Normalised by HD
Tends to occur in patients with high urea and creatinine

Longer half life’s even in drugs that don’t go near the kidney

Question 14

Discuss increased sensitivity to sedatievs in renal disease

Answer 14

Increased sensitivity to sedatives
? BBB permeability – uremic plasma tends to damage the tight junctions around the BBB letting more drug in
Increased sensitivity to sedatives (CNS agents)
- High risk of opiate and benzo toxicity

Question 15

List other considerations to take into account with renal disease

Answer 15

nephrotoxic drugs - gentamycin
drugs which cause fluid retention - NSAIDs
increasing ureamia - tetracyclines
drugs which cause electrolyte disturbances - digoxin

Question 16

Summarise prescribing changes in renal disease

Answer 16

Same hepatic metabolism – may be decreased in severe renal disease
Same/increased VD and prolonged elimination (t1/2 increased)
Thus, increased dosing interval

VD may be increased due to fluid retention

Drugs excreted by the kidney
Prolonged half life
Need prolonged dosing interval and possibly decreased dose

Question 17

List the impact hepatic impairment has on PK

Answer 17

Altered first pass metabolism
Altered activation of prodrugs
Decreased protein binding – due to decreased serum albumin
Decreased elimination – due to decreased hepatic metabolism

Question 18

List the impact hepatic impairment has on PD

Answer 18

Altered sensitivity to drugs

Question 19

State why it is more difficult to know how to change prescribing in hepatic impairment

Answer 19

Harder to measure hepatic function – prescribe with more uncertainty to what is going on

Question 20

State what changes occur due to decreased first pass metabolism in hepatic impairment

Answer 20

profound changes in bioavailability
- increased in drugs
- decreased in pro-drugs

reduction of first pass activation of prodrugs - may lead to reduced bioavailablitiy

Question 21

Describe high extraction drugs

Answer 21

High extraction – greatest risk of increased F in hepatic impairment

Metabolised at high rate by liver – quick metabolism and short half life – first pass metabolism tends to be particularly important for these drugs – high peaks in hepatic impairment

Rate varies with delivery

Affected by changes in blood flow

i.e., Morphine, verapamil, lignocaine

Question 22

Describe low extraction drugs

Answer 22

Low extraction:
Metabolised at low rate by liver – tends to be less dependent on blood flow, hepatic enzymes tend to be saturated at levels encountered in clinical practice

Slower metabolism, longer half life

Wont see a peak – just a longer half life – can impact dosing adjustments

Independent of blood flow

Sensitive to changes in liver enzyme activity

I.e. Chloramphenicol, theophylline

Question 23

Discuss the changes in PK in hepatic impairment

Answer 23

Difficult to predict
Many factors involved
No simple test (cf renal impairment)

Start with low dose
TDM

Effects on PK are difficult to predict
Many factors
No simple test of liver function (LFTs don’t always correlate)

When worried about hepatic impairment
Start with low dose
Be cautious
Half-life may be greatly prolonged = go slowly in increasing dose
i.e., benzos – metabolised extensively by the liver and have a long half life – drug takes a long time to build up in liver impairment
Should do therapeutic drug monitoring if available

Question 24

Discuss the effect of hepatic impairment on PD

Answer 24

Sensitivity to sedatives
Sensitivity to oral anticoagulants – many DOACs contraindicated in cirrhosis – may need to use warfarin in
Precipitation of encephalopathy due to drugs – impacting liver function or adverse affect on brain function that make you more susceptible to encephalopathy
Fluid retention – can alter drug concentrations
Hepatorenal syndrome – difficult to manage – combination of hepatic dysfunction and renal dysfunction – can often be disguised (people with hepatic impairment tend to have low muscle mass and therefore might have a lower serum creatinine than expected – can miss renal dysfunction)

More sensitive to drugs

Be careful particularly in sedative drugs that they don’t precipitate encephalopathy
Constipation can also precipitate encephalopathy and opioids can cause constipation

Encephalopathy is caused by accumulation of ammonia in the body and a lot of the ammonia that enters the systemic circulation comes in from the portal vein and is produced by bacteria in the large bowel – if the large bowel is full of faeces – amount of ammonia hitting the liver goes up and susceptibility for serum ammonia to go up if the liver cant handle the increase
- Shouldn’t occur in someone with a healthy liver
- Cirrhosis can make you prone to encephalopathy
- Encephalopathy can make brain more susceptible to affects of other drugs i.e., sedatives

Question 25

List drugs to be cautious prescribing in hepatic impairment

Answer 25

Some antibiotics i.e., antibiotics metabolized by the liver – rifampicin Valproate (antiepileptics tend to be metabolized by the liver) Warfarin – extensively metabolized by the liver and narrow TI Sedatives – increased sensitivity Verapamil

Question 26

Summarise changes in prescribing in hepatic impairment

Answer 26

Hepatic Disease Same renal elimination (fluid retention may cause some changes) Same/increased VD and slower rate of enzyme metabolism (t1/2 / F increased) Thus decreased dosage, increased dosing interval Slower enzyme metabolism = increased half life and increased bioavailability Start low and increase slow – dosing interval and time to steady state increased Increase drugs carefully

Question 27

Discuss changes which occur in CHF (which affect prescribing)

Answer 27

Absorption – can be significantly decreased due to gut oedema Hepatic elimination – decreased due to liver becoming engorged with fluid and less effective Renal elimination – decreased as the renal blood supply is decreased in HF Can have a number of impacts on drug metabolism, largely because of organs in the body suffering from fluid retention Sitting duck for drug toxicity

Question 28

Discuss prescribing chnaged in GI disease

Answer 28

Achlorhydria – can be drug induced i.e., by PPIs, reduces absorption of certain medications i.e., iron which needs to be converted from ferrous to ferric do be absorbed Crohn’s disease (and any disease that affects the ability of the gut to absorb can cause issues) Post-operative issues – gut a bit sluggish/bit of an ileus Usually relates to absorption  Ileus is a slowing of gastrointestinal motility that is not associated with mechanical obstruction.

Question 29

Define child protection and the child protection register

Answer 29

- Service dedicated to protect children from abuse or neglect - List of kids/families at risk – local authority in the area is in charge of this list

Question 30

Discuss how a NOC (notification of concern) is made

Answer 30

Question 31

List the Scottish legislation in place regarding the rights of children

Answer 31

GIRFEC - getting it right for every child - this includes SHANARRI - safe, healthy, active, nutured, achieving, responsible, respected, included Not related to rights of the child but there is also the named person scheme which is related to CP

Question 32

Discuss the GMC guidance on disclosing information regarding children

Answer 32

All doctors must take action if they believe a young person may be being abused or neglected.

Question 33

State times when confidentiality can be broken

Answer 33

Confidentiality is not an absolute duty, and confidential information can be shared about a person if any of the following apply (6): (1)You must do so by law or in response to a court order (2)The person the information relates to has given you their consent to share the information (or a person with parental responsibility has given consent if the information is about a child who does not have the capacity to give consent). (3)It is justified in the public interest – for example, if the benefits to a child or young person that will arise from sharing the information outweigh both the public and the individual’s interest in keeping the information confidential.

Question 34

List examinations you would perform in a patient presenting with ED

Answer 34

General- Blood Pressure, Pulse, & BMI- assess cardiac risk factors (2) External Genitalia Penile abnormalities- premalignant or malignant conditions Phimosis, Peyronie’s Disease Signs of secondary sexual characteristics- testicular size/ testicular consistency. Digital Rectal Examination (DRE) Prostate exam in older men (> 50 years of age) History of prostate cancer Prostate symptoms Ejaculatory dysfunction- caused by enlarged prostate Phimosis Condition in which the foreskin cannot be pulled back past the glans of the penis Peyronie's disease is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Specifically, scar tissue forms in the tunica albuginea, the thick sheath of tissue surrounding the corpora cavernosa, causing pain, abnormal curvature, erectile dysfunction, indentation, loss of girth and shortening.

Question 35

List investigations you would do in a patient presenting with ED

Answer 35

Fasting Glucose or HbA1c-assess glycaemic control Fasting Lipids- calculate 10 yr CVD risk for patient LFTs inc GGT Total Testosterone- requires sample between 8am-11am. Additional tests- LH/FSH/Prolactin/TFTs- if testosterone low Consider PSA if male > 50 / DRE – enlarged prostate  (check level prior to initiating testosterone therapy)

Question 36

Define ED

Answer 36

It is defined as the inability to achieve and maintain a penile erection adequate for satisfactory sexual intercourse

Question 37

List the main causes of ED

Answer 37

organic - can be explained by an abnormality in a body system i.e, CV, endocrine - diabetes, hypertension, abnormal curvature, phimosis pyschogenic - stress - performance anxiety - would likely still get nocturnal/morning erections - when their brain is off

Question 38

List common drugs which cause ED

Answer 38

Question 39

Discuss differentiation of organic or pyschogenic cause

Answer 39

Question 40

Discuss management of ED

Answer 40

Firstly identify and treat any reversible causes of ED:     - Testoterone deficiency –establish cause of hypogonadism. - Hyperthyroidism / Hyperprolactinaemia -treatment underlying cause - Drug-induced ED – change or withdraw medication thought to cause ED, caution in those patients on anti-psychotic medication as this would require psychiatrist review. - Sexual problems – Consider patient referral to psychosexual counselling or relationship counselling for couples. Lifestyle modifications: Dietary changes Smoking cessation Reduction in alcohol- encourage ‘drink free’ nights. Increase exercise as BMI raised and systolic BP is elevated at consult Suggest counselling or mindfulness to help with stress accompanying new position.  If this patient had a pre-existing cardiovascular disease then it would be important to assess his ’risk of sexual activity’, which has been studied by the Princeton consenus (4). Sexual activity requires the same effort as gardening It would be appropriate to start drug therapy. PDE-5 inhibitors are first-line treatment for ED except if there are contra-indications.

Question 41

Describe the mechanism of action of PDE-5 inhibitors

Answer 41

Drugs such as sildenafil are potent and selective inhibitors of phosphodiesterase type 5 (PDE5)  These drugs act by inhibiting cGMP-specific PDE5  cGMP promotes smooth-muscle relaxation, increased blood flow to the penis, leading to compression of the subtunical  venous  plexus resulting in penile erection Inhibiting PDE5 maintains concentrations of cGMP necessary for achieving and maintaining erections

Question 42

List things you should discuss witht he patient before starting sildenafil

Answer 42

Contra-indications Cautions Dosing regime Side effects Cost

Question 43

List contraindications of sildenafil

Answer 43

Nitrates and guanylate cyclase stimulators (ie riociguat). Severe/unstable heart disease. Non-arteritic anterior ischaemic optic neuropathy (NAION) Hypotension (systolic blood pressure below 90/50 mmHg). Unstable angina or angina occurring during sexual intercourse Recent stroke or MI- see BNF for specific prescribing guidelines on each PDE5 inhibitor

Question 44

List cautions of using sildenafil

Answer 44

CVD-risk stratify according to Princeton Consenus II (ref). Left ventricular outflow obstruction (eg aortic stenosis) Anatomical penile abnormalities (eg Peyronie’s) Predisposition to priapism (eg sickle-cell disease) Additional precautions: Varendafil- elderly men and men with active peptic ulceration, bleeding disorders, long QT interval. Sildenafil and Avanafil - active peptic ulceration or bleeding disorders.

Question 45

Discuss dosing of sildenafil

Answer 45

50mg taken around 1 hour before sexual activity - max 100mg per day patient needs to have some form of arousal to achieve erection even with use of sildenafil

Question 46

List side effects of sildenafil

Answer 46

Common Backpain, dyspepsia, flushing, migraine, myalgia, nasal congestion, dizziness, nausea, and vomiting. Uncommon Visual disturbances, including non-arteritic anterior ischaemic optic neuropathy (NAION). Stop with immediate effect, if sudden visual impairment occurs. Sudden hearing loss. Priapism (persistent erection). Warn the man to seek advice if he has an erection lasting longer than 4 hours.

Question 47

List patients who are exempt from paying for sildenafil

Answer 47

Diabetes mellitus Parkinson’s disease Multiple sclerosis Polio Single-gene neurological disease (eg Huntington’s) Spinal cord injury Spina bifida Renal dialysis Radial pelvic surgery Prostate cancer Treatment was initiated before 1998 Severe stress secondary to ED (as judged by a specialist)

Question 48

Discuss secodnary management of ED

Answer 48

Referral to a secondary care specialist ED clinic where other management options can be discussed.   Second line therapy for ED is the synthetic prostaglandin E1 analogue- alprostadil. It acts by increasing cGMP levels thus increasing smooth muscle relaxation and penile blood flow. This drug therapy can be given directly into the penis by two methods:   MUSE -a small pellet is inserted directly into the urethral opening of the penis. Caverject- direct intracavernosal injection into the penis VED -vacuum erection device is another alternative treatment for ED. Whereby a cylinder is placed over then of the penis and air is removed with a pump. This results in a vacuum, causing penile blood flow which results in an erection. However, caution is needed as a constriction ring is placed at the base of the penis to maintain an erection, but must not remain on for more than 30 minutes. The side effects include pain, bruising, and penile numbness, and more seriously events such skin necrosis.  

Question 49

State the 3rd line management of ED

Answer 49

Third line therapy is penile prosthesis surgery and is only suitable for patients with severe organic erectile dysfunction which has not responded to drug treatments.