PPT Flashcards
1
Q
how is AKI defined according to KDIGO?
A
●Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours; or
●Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or
●Urine volume <0.5 mL/kg/h for six hours
2
Q
what does KDIGO use to stage AKI and what is the exception?
A
serum creatinine and urine output not GFR
exception: children under the age of 18 years, for whom an acute decrease in estimated GFR (eGFR) to <35 mL/min per 1.73 m2 is included in the criteria for stage 3 AKI.
3
Q
what are the KDIGO stages of AKI?
A
●Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L), or reduction in urine output to <0.5 mL/kg per hour for 6 to 12 hours.
● Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in urine output to <0.5 mL/kg per hour for ≥12 hours.
● Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 micromol/L), or reduction in urine output to <0.3 mL/kg per hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of renal replacement therapy, or, in patients <18 years, decrease in eGFR to <35 mL/min per 1.73 m2.
4
Q
what is the immediate therapy for a patient with AKI?
A
● optimise IV fluid volume
● optimise BP (withhold drugs that interfere with renal autoregulation (ACEIs, ARBs)
● correct hypovolaemia
●prescribe appropriately (DAMN-AKI = diuretics, ACEi/ARBs, metformin, NSAIDs
5
Q
what is the treatment for hyperkalaemia?
A
give insulin with glucose to increase uptake of potassium
6
Q
what are the 4 major causes of hyperkalaemia due to reduced urinary potassium secretion?
A
●Reduced aldosterone secretion
●Reduced response to aldosterone (aldosterone resistance)
●Reduced distal sodium and water delivery as occurs in effective arterial blood volume depletion
●Acute and chronic kidney disease in which one or more of the above factors are present
7
Q
what drugs interfere with renal perfusion?
A
ACE inhibitors
Angiotensin receptor blockers
NSAIDs
8
Q
what drugs require dose reduction or cessation in patients with AKI?
A
All medications that are metabolized and excreted by the kidneys should be dose adjusted for an assumed eGFR of < 10 mL/min/1.73m2 fractionated heparins opiates penicillin-based antibiotics sulfonylurea-based hypoglycaemic drugs aciclovir metformin
9
Q
what drugs require close monitoring for patients with AKI?
A
Warfarin
Aminoglycosides (Gentamicin, Tobramycin)
Lithium
10
Q
what drugs aggravate hyperkalaemia?
A
All drugs which block renal excretion of potassium should be stopped:
Trimethoprim (co-trimoxazole/septrin)
Spironolactone (risk of hyperkalaemia too high so don’t put patients back on following hyperkalaemia/AKI)
Amiloride
11
Q
what equation can be used to estimate creatinine clearance and is used in drug dosing guidelines?
A
cockcroft and gault
12
Q
what is the cockcroft and gault equation?
A
= [F x (140 - age) x weight-kg] / plasma creatinine
F=1.04 males / 1.23 females
13
Q
what is the best method to determine GFR?
A
cannot be measured directly, the best method for determining GFR is measurement of the urinary clearance of an ideal filtration marker.
14
Q
what is the gold standard of exogenous filtration markers?
A
inulin
Inulin is a physiologically inert substance that is freely filtered at the glomerulus, and is neither secreted, reabsorbed, synthesized, nor metabolized by the kidney. Thus, the amount of inulin filtered at the glomerulus is equal to the amount excreted in the urine, which can be measured
15
Q
what is the issue with using inulin to measure GFR?
A
Inulin, however, is in short supply, expensive, and difficult to assay. Furthermore, the classic protocol for measuring inulin clearance requires a continuous intravenous infusion, multiple blood samples, and bladder catheterization.
16
Q
what is the most common method used to estimate GFR?
A
measurement of the creatinine clearance; and estimation equations based upon serum creatinine such as the Cockcroft-Gault equation, the Modification of Diet in Renal Disease (MDRD) study equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
17
Q
describe how the BNF gives information on dosage in renal impairment?
A
The information on dosage adjustment in the BNF is expressed in terms of eGFR, rather than creatinine clearance, for most drugs (exceptions include toxic drugs and patients at extremes of weight). Although the two measures of renal function are not interchangeable, in practice, for most drugs and for most patients (over 18 years) of average build and height, eGFR (MDRD ‘formula’) can be used to determine dosage adjustments in place of creatinine clearance. An individual’s absolute glomerular filtration rate can be calculated from the eGFR as follows: GFR Absolute = eGFR x (individual’s body surface area/1.73)
18
Q
what should be used to adjust drug dosages for potentially toxic drugs with a small safety margin?
A
, creatinine clearance (calculated from the Cockcroft and Gault formula) should be used to adjust drug dosages in addition to plasma-drug concentration and clinical response.
19
Q
how should drug dosages be adjusted for patients at both extremities of weight?
A
the absolute glomerular filtration rate or creatinine clearance (calculated from the Cockcroft and Gault formula)
20
Q
how many drugs are affected by renal function?
A
Approximately 80% of drugs are not affected by impaired renal function, because they are eliminated predominantly by hepatic metabolism
21
Q
what drugs are eliminated by the kidneys?
A
The kidneys provide the major route of elimination for water-soluble drugs and water-soluble metabolites
22
Q
does renal function affect loading doses needed?
A
no
23
Q
how might you alter prescription of a drug that is mostly excreted through the kidney in a patient with significant renal impairment?
A
lower the dosage
space out the dosage
24
Q
what is the first line treatment of pyelonephritis?
A
gentamicin
25
how is gentamicin given?
IV
26
what is the mechanism of action of gentamicin?
aminoglycosides - bind to 30s ribosomal sub unit
Misreading of the mRNA codon, leading to errors in amino-acid sequencing
Disruption of polysomes, reducing the efficiency of protein synthesis
Inhibition of the translocation of tRNA between A and P ribosomal binding sites
27
what are the adverse effects of gentamicin?
- Damage to the cochlear and vestibular apparatus - loss of balance, tinnitus, loss of hearing.
- May cause renal damage - risk of nephrotoxicity is increased with prolonged treatment.
- Concurrent use of other nephrotoxic drugs may exacerbate renal damage.
- Use with ototoxic diuretics, e.g. furosemide, may increase risk of ototoxicity and nephrotoxicity.
- May cause allergic reactions, nausea, vomiting and rashes.
28
what are the pharmacokinetics of gentamicin?
- Gentamicin is not readily absorbed from GI tract, so is given via intravenous route (may also be given IM).
- Gentamicin is highly hydrophilic, i.e. not distributed into body fat and minimally distributed into tissue fluids.
- When calculating an appropriate dose, consider using the patient's lean mass (mass without excess fat = ideal body weight).
- Usually calculate dose using lower of actual or ideal body weight.
29
describe the elimination of gentamicin?
Gentamicin is excreted unmodified, by the kidneys and so follows "first order kinetics". i.e. drug is cleared from blood at a rate proportional to it's concentration.
After a dose, level in the blood decays exponentially.
30
what are the 2 types of regimens of gentamicin commonly used in the UK?
pharmacokinetic
extended interval
Both regimens had equivalent efficacy, but;
Extended Interval gentamicin had reduced nephrotoxicity.
31
describe extended interval dosing regimen
also known as oral daily dosing/administration or hartford dosing
Regimen maximises bacterial kill whilst minimising toxicity.
32
what factors determine gentamicin dosage and what can the dosage range from?
```
height
sex
Ideal body weight (kg)
360-560mg in men
320-560mg in women
```
33
what follow up is required when patients are on gentamicin?
monitor levels in blood at times after dosage and compare to nomogram
Do not take blood sample from the IV line used for gentamicin administration!
Take one blood sample (ideally 10mL) between 6 and 14 hours after the start of first infusion in a plain tube (clotted blood).
Document on microbiology request form EXACT time and date infusion was set up and EXACT time and date sample was taken
34
what is the initial dose in the hartford extended interval dosing of gentamicin?
7mg/kg
| dose frequency altering according to nomogram based on serum concentration of drug
35
describe the administration of the hartford extended interval dosing of gentamicin?
infusion in 50-100ml in sodium chloride 0.9% over 30 minutes
36
what is the target concentration for hartford extended interval dosing of gentamicin?
no target
| use nomogram to monitor
37
what is the initial dose given in pharmacokinetic dosing of gentamicin?
adults: 2mg/kg loading dose then refer to pharmacy for maintenance
synergistic dosing for endocarditis 1mg/kg TDS
adjust dose and freuency based on serum concentration
38
describe the administration of pharmacokinetic dosing of gentamicin?
bolus over at least 3 minutes
39
when should blood levels be taken on hartford extended interval dosing of gentamicin?
one sample 6-14 hours aftter infusion commences
40
when should blood levels be taken on pharmacokinetic dosing of gentamicin?
just before the dose and 1 hour post dose
41
what is the target concention of gentamicin on the pharmacokinetic dosing?
standard: pre dose = <2mg/L and post dose = 6-10mg/L
| synergistic dosing for endocarditis: pre dose =<1mg/L and post dose =<3-5mg/L
42
what are the different types of incontinence?
urgency urinary incontinence
stress urinary incontinence
mixed urinary incontinence
overflow incontinence
43
what is urgency urinary incontinence?
associated with overactive bladder syndrome
44
what is stress incontinence?
due to urethral sphincter incompetence
45
what is mixed urinary incontinence?
both stress and urgency urinary incontinence
46
what is overflow incontinence?
continuous leakage due to hypotonic bladder or bladder outlet obstruction producing urinary retention
47
describe the aspects of the bladder/prostate structures and the innervation involved in micturition reflex?
Bladder filling provides neuronal signals to the micturition centre via sensory input from purinoceptors on neurons in the urothelium. To accommodate filling and continence, sympathetic stimulation both relaxes the smooth muscle of the bladder via β2- and β3-adrenoceptors and stimulates sphincter mechanisms through α1-adrenoceptor subtypes. Somatic control of the external sphincter also aids continence. Voluntary urination involves parasympathetic stimulation of bladder smooth muscle through M3 and M2 muscarinic receptor subtypes (M), and inhibition of the sympathetic and somatic outflow. Aspects of bladder control may involve other less understood transmitter substances. For example, γ-aminobutyric acid (GABA) interneurons inhibit bladder contraction. P2X, Purinergic receptors.
48
what type of incontinence is the following:
Mary Smith is a 59 year old woman who comes to her GP to discuss her bladder problems.
She wakes at night to pass urine and during the day feels she has to go to pass urine more frequently than she used to.
During the day she gets an urge to pass urine and often leaks urine into her pants, which has made her start to wear pads for incontinence that she saw advertised on TV.
urgency urinary incontinence
49
describe the features of urgency incontinence?
more common in older women and may be associated with comorbid conditions that occur with age. It is believed to result from detrusor overactivity, leading to uninhibited (involuntary) detrusor muscle contractions during bladder filling. This may be secondary to neurologic disorders (eg, spinal cord injury), bladder abnormalities, increased or altered bladder microbiome, or may be idiopathic. The prevalence of involuntary detrusor contractions, or detrusor overactivity, has been found in 21 percent of healthy, continent, community-dwelling older adults
50
what drugs can be used for treatment of urinary urgency?
muscarinic receptor antagonists (oxybutinin, tolterodine)
| beta adrenoreceptor agonist (mirabegron)
51
describe the sympathetic innervation of bladder?
The sympathetic preganglionic neurons innervating the urinary bladder are located in the IML at the T12-L2 level. The sympathetic preganglionic fibers pass through the sympathetic chain and emerge in the lumbar splanchnic nerves. These fibers then synapse on the postganglionic neurons located in the inferior mesenteric ganglion. The postganglionic fibers from this ganglion reach the urinary bladder through the hypogastric plexus. Some preganglionic fibers from L1-L2 spinal segments descend in the sympathetic chain and synapse on postganglionic neurons in the hypogastric plexus. The postganglionic fibers from these neurons then innervate the urinary bladder. Traditionally, it was believed that activation of sympathetic fibers innervating the bladder results in relaxation of the detrusor muscle and contraction of the sphincter located at the neck of the bladder. However, it is now believed that sympathetic fibers innervating the bladder are primarily distributed to the blood vessels in this organ.
The sympathetic nerves innervating the sphincter located at the bladder neck (sphincter vesicae) play a minor role in maintaining urinary continence by contracting this sphincter. However, these nerves also play an important role during ejaculation in the male.
52
describe the parasympathetic innervation of the bladder?
The parasympathetic preganglionic neurons innervating the bladder are located in the IML of the sacral spinal cord at the S2-S4 level. Their preganglionic axons exit from the ventral roots, travel in the pelvic nerves, pass through the hypogastric plexus, and synapse on postganglionic neurons located in the wall of the urinary bladder. Activation of parasympathetic fibers results in contraction of the detrusor muscle of the bladder (smooth muscle of the bladder wall) and relaxation of the sphincter vesicae.
53
describe muscarinic blockade of the bladder?
Antimuscarinic drugs bind to muscarinic receptors, where they act as a competitive inhibitor of acetylcholine. Contraction of the smooth muscle of the bladder is under parasympathetic control. Blocking muscarinic receptors therefore promotes bladder relaxation, increasing bladder capacity. In patients with overactive bladder, this may reduce urinary frequency, urgency and urge incontinence. Antimuscarinics help in overactive bladder through antagonism of the M3 receptor, which is the main muscarinic receptor subtype in the bladder.
54
describe the mechanism of mirabegron?
Stimulation of β3-adrenoceptors in the bladder trigone by mirabegron flattens and lengthens the bladder base, which facilitates urine storage. Mirabegron reduces symptoms of urinary frequency and urgency with efficacy similar to that of muscarinic receptor antagonists. The main adverse effects are an increase in blood pressure and heart rate, and mirabegron is contraindicated in people with severe hypertension.
55
what are the potential side effects of muscarinic blockers?
```
dry mouth
tachycardia
constipation
blurred vision
urinary retention if there is bladder outflow obstruction
```
56
the following case is an example of what type of incontinence?
Ginnie Arbuttle is a 49 year old woman who comes to her GP to discuss her bladder problems.
She is experiencing worsening urinary incontinence when she laughs or sneezes.
Now she has started to urinate when she goes to Zumba classes and it is embarrassing her more and more.
stress incontinence
57
describe the treatment options for stress incontinence?
Pelvic floor muscle training for at least 8–12 weeks is the recommended treatment. Minimal access surgical sling procedures or colposuspension to provide urethral support are among the surgical options.
Drug therapy is limited and only recommended if surgical treatment is not suitable.
58
what are the therapies for stress incontinence?
- Pelvic floor exercise
- Surgery
- Vaginal oestrogens (peri-menopausal)
- Duloxetine – SNRI - Duloxetine significantly reduces the frequency of incontinence episodes in about half of those treated. It is recommended for people who are averse to surgery or who are poor candidates for surgery
59
how is the severity of BPH assessed?
international prostate severity score
60
what are the treatment options for a patient that has a IPSS score of 21 and scored 5/6 on the 'bother' score?
```
alpha blocker eg tamsolusin
Alfuzosin
Doxazosin
Tamsulosin
Terazosin
```
61
what is the mechanism of alpha blockers
Although often described using the broad term ‘α-blocker,’ most drugs in this class (including doxazosin, tamsulosin and alfuzosin) are highly selective for the α1-adrenoceptor. Alpha1-adrenoceptors are found mainly in smooth muscle, including in blood vessels and the urinary tract (the bladder neck and prostate in particular). Stimulation induces contraction; blockade induces relaxation
62
what are the adverse effects of alpha blockers?
vasodilatation and a fall in blood pressure, and reduced resistance to bladder outflow.
63
describe the risk of progression of BPH?
The risk of progression of symptoms from benign prostatic enlargement is higher in older men and in men with poorer urine flow, higher symptom scores, evidence of bladder decompensation (such as chronic urinary retention), larger prostates, or higher prostate specific antigen (PSA) levels.
64
what should be done if a man has bothersome moderate to severe voiding symptoms and prostatic enlargement?
consider offering a combination of an alpha-blocker and a 5-alpha reductase inhibitor.
65
what are the adverse effects of 5 alpha reductase inhibitors?
```
Breast enlargement
Breast tenderness
Decreased libido
Ejaculation disorders
Impotence
```
66
what are drug interactions with 5 alpha reductase inhibitors?
Verapamil and diltiazem increase concentrations of dutasteride. (yellow alert).
67
what is the risk of 5 alpha reductase inhibitors in pregnancy?
Exposure of a male fetus to 5α-reductase inhibitors may cause abnormal development of the external genitalia. It is therefore important that pregnant women do not take these drugs and are not exposed to them, e.g. by handling broken or damaged tablets or through semen during unprotected sex with a man taking these drugs.
68
what is the mechanism of 5 alpha reductase inhiibitors?
5-alpha-reductase inhibitors are more effective in men with larger prostates. They act by reducing the size of the prostate gland and have demonstrated the potential for long-term reduction in prostate volume and need for prostate surgery. The type 2 form of 5-alpha-reductase catalyzes the conversion of testosterone to dihydrotestosterone in the prostate, hair follicles, and other androgen-sensitive tissues. 5-alpha-reductase inhibitors act by reducing the size of the prostate gland and have demonstrated the potential for long-term reduction in prostate volume and need for prostate surgery.
69
how longe is treatment needed for prostate size to be reduced?
In patients who desire medical therapy but cannot tolerate alpha-1-adrenergic antagonists and do not have predominately irritant symptoms or concomitant erectile dysfunction, treatment with a 5-alpha-reductase inhibitor is reasonable. Patients should understand that treatment for 6 to 12 months is generally needed before prostate size is sufficiently reduced to improve symptoms.
70
what are the drugs used to treat prostate cancer?
Antiandrogens (Flutamide)
Gonadorelin analogues (Leuprolide, Goserelin, Buserelin)
71
describe the mechanism of action of GnRH analogues?
Gonadotropin-releasing hormone [GnRH] analogues cause an initial increase in luteinizing hormone (LH) and follicle stimulating hormone (FSH), chronic administration of gonadorelin analogues results in a sustained suppression of pituitary gonadotropins. Serum testosterone falls to levels comparable to surgical castration. The exact mechanism of this effect is unknown, but may be related to changes in the control of LH or down-regulation of LH receptors
72
describe the treatment of bladder cancer?
Urothelial bladder cancer is most sensitive to cisplatin-based combination chemotherapy
Platinum-based chemotherapy is the preferred initial approach for systemic therapy in patients with metastatic disease.
73
what is the treatment of renal cell carcinoma?
```
-Inhibitors of tyrosine kinases and other protein kinases
Sorafenib
Sunitinib
-mTOR inhibitor
Everolimus
-Tyrosine kinase receptor inhibitor
Bevacizumab
```
74
give examples of oral iron salts?
Ferrous sulfate
Ferrous fumarate
Ferrous gluconate
75
give examples of parenta
Iron dextran
Iron sucrose
Ferric carboxymaltose
Iron isomaltoside 1000
76
describe the use of parental iron?
Parenteral iron is generally reserved for use when oral therapy is unsuccessful because the patient cannot tolerate oral iron, or does not take it reliably, or if there is continuing blood loss, or in malabsorption.
77
describe iron absorption?
After uptake into enterocytes, iron is oxidised to the ferric state and transported to the circulation by the protein ferroportin. Iron transport from enterocytes is regulated by the peptide hormone hepcidin, which is an acute-phase reactant synthesised in the liver. When circulating and tissue iron levels are high, or in the presence of systemic inflammation or infection, hepcidin is increased and binds to ferroportin, promoting its degradation. Conversely iron deficiency, increased erythropoiesis, and tissue hypoxia suppress hepcidin production and promote iron absorption.
In blood, ferric ions are bound to the globulin apotransferrin and transported to the bone marrow and iron stores as transferrin where cellular iron uptake occurs via transferrin receptors. In most cells, iron is complexed with the protein apoferritin and stored as ferritin. In some tissues iron is also found as relatively insoluble aggregates of degraded forms of ferritin, known as haemosiderin. Two-thirds of the iron in the body is present in circulating red cells, and about half of the remainder is found in macrophages, reticuloendothelial cells and hepatocytes. The rest is present in myoglobin in muscle cells or associated with various intracellular enzymes.
When ageing red cells are broken down by the reticuloendothelial system, most of the released iron is recycled via macrophages for further erythropoiesis. Iron loss from the body is normally low, and occurs through shedding of mucosal cells containing ferritin; there is negligible renal loss of iron.
78
what are the adverse effects of iron salts?
```
Constipation
Diarrhoea
Epigastric pain (dose related)
Faecal impaction
Gastro-intestinal irritation
Nausea (dose related)
```
79
what are the drug interactions iron salts?
Mostly by reducing absorption
- Levothyroxine
- Bisphosphonates
- Ciprofloxacin
- Tetracyclines
- Calcium and zinc salts
These medications should therefore be taken at least 2 hours before oral iron.
80
what is the oral dose of iron?
The oral dose of elemental iron for iron-deficiency anaemia should be 100 to 200 mg daily.
Some oral iron preparations contain vitamin C, but the therapeutic advantage is minimal compared to the ferrous salt alone and the cost is often greater
81
how long should iron therapy be?
The haemoglobin concentration should rise by about 100–200 mg/100 mL (1–2 g/L) per day or 2 g/100 mL (20 g/Litre) over 3–4 weeks.
When the haemoglobin is in the normal range, treatment should be continued for a further 3 months to replenish the iron stores. Epithelial tissue changes such as atrophic glossitis and koilonychia are usually improved, but the response is often slow.
82
why is folic acid used in pregnancy?
Folic acid supplementation can reduce the risk of neural tube defects (NTDs), presumably by preventing nutritional deficiency and by overcoming disruptions in folate metabolism related to underlying genetic variation in folate-related genes. Folic acid may enhance cell proliferation for neural closure directly or it may be involved in the epigenetic regulation of expression of genes that control neural closure.
83
why is folate important?
Folate is required for a number of cellular biochemical processes, including DNA synthesis, and is essential for cell replication, including the formation of red cells. Folic acid (pteroylglutamic acid) is ingested as conjugated folate polyglutamates, found mainly in fresh leaf vegetables (in which it is heat-labile) and in liver (where it is more heat-stable). Before absorption, the polyglutamates are deconjugated to the monoglutamate. Folate monoglutamate is absorbed principally in the duodenum and jejunum, and is methylated and reduced to 5-methyltetrahydrofolate by dihydrofolate reductase during absorption. Methyltetrahydrofolate enters cells, where it is demethylated and converted back to folate polyglutamates. These are coenzymes in the synthesis of pyrimidines and purines and hence of DNA. (from Waller and Samson ch 47).
84
describe folate in the circulation?
In the circulation, folate is mainly present as 5-methyltetrahydrofolate (5-MeTHF), which is taken up by cells via specific carriers or receptors. In the cell, folate donates one-carbon units for use in methylation reactions and in purine and thymidine synthesis. Alternatively, folate can also accept one-carbon units from several amino acids, including serine. Methylenetetrahydrofolate reductase (MTHFR) competes with thymidylate synthase (TS) and methylenetetrahydrofolate dehydrogenase (MTHFD) for the one-carbon units of 5-MeTHF. MTHFR activity is regulated by S-adenosylmethionine (AdoMet), which inhibits enzyme activity. Vitamin B12 is a cofactor of methionine synthase (MTR) and is involved in the transfer of the methyl group from 5-MeTHF to homocysteine. (this is more detail than you need to remember - DH)
85
what dose of folic acid should women attempting to get pregnant take?
- 400mg daily before conception until week 12 pregnancy
| - high risk groups - 5mg daily before conception and until week 12 pregnancy
86
what groups of women are at high risk of having child with neural tube defects?
Women with a previous child with a NTD and those taking anticonvulsants associated with development of NTDs (eg, valproate, carbamazepine) are at highest risk of having an affected child in a future pregnancy
sickle cell disease
87
why should b12 be given before folic acid if treating macrolytic anaemia with suspected b12 deficiency?
Risk of subacute combined degeneration of the cord
88
what is the clinical presentation of sub acute combined degernration of the cord?
The clinical presentation of SACD is usually with loss of vibration and proprioception in the hands and feet, with eventual progression to sensory loss of all modalities, sensory gait ataxia, and distal muscle weakness, especially of the legs. Features of dementia may also become apparent.
89
what causes most vitamin b12 deficiency?
The vast majority of vitamin B12 deficiency is due to inability to absorb B12 in the terminal ileum (e.g. lack of intrinsic factor, terminal ileal Crohn’s disease)
90
how should hydroxycobalamin be given when treating macrolytic anaemia due to vitamin b12 deficiency?
parenterally
91
what type of insulin is novorapid (insulin aspart)?
quick acting analogue insulin
92
give examples of short acting human insulins?
Actrapid and Humulin S
93
give examples of short acting analogue insulins?
Humalog, Novorapid and Apidra
94
what is the difference between short acting human insulins and short acting analogue insulins?
Humalog and Novorapid have had their molecular structures altered to render them quicker acting through improving separation into insulin dimers and monomers at the injection site thus speeding up absorption from the injection site (insulin usually exists in hexamers in pharmacological insulin in cartridges or vials).
95
describe rapid acting analogue insulins?
```
novorapid (aspart)
humalog (lispro)
apidra (glulisine)
less risk of hypoglycaemia
onset over 5-15 mins
peak onset 0.5-1.5 hours
duration 3-5 hours
```
96
describe short acting insulins?
```
soluble insulin
actrapid, humulin S, insuman rapid
slower onset, longer duration
onset: 30 mins
peak: 2-4 hours
duration: 6-8 hours
```
97
what is levemir insulin and how does it work?
Long-acting analogue insulin – can be given once daily but often used twice daily for multiple daily injection insulin regimens
98
how are analogue insulins made long acting?
Glargine insulin is injected subcutaneously at a slightly acidic pH (at which it is soluble) – at subcutaneous pH it crystallizes into microprecipitates that cannot be absorbed – these slowly dissociate until the insulin is absorbed as dimers and monomers – this effect is created by altering the pKa value of the insulin molecule by changing the amino acid primary structure.
Degludec insulin is rendered long-acting by adding a fatty acid moiety to the insulin molecule that results in it forming multihexamers at the injection site from which gradual dissolution occurs into dimers and monomers that can be absorbed across the capillary wall.
99
what are the different types of insulin regimens and what type of diabetes are they usually used in?
- multiple daily injection regimens (mostly T1)
- Biphasic insulin twice (T2, T1)
- long acting once daily (T2 usually with oral drugs)
- continuous subcutaneous insulin infusion (T1)
100
what is DAFNE?
dose adjustment for normal eating (how much carbs in food eaten and how much insulin is needed)
101
why is carbhydrate counting taught to diabetics?
CHOC is used to match the quick-acting insulin dose to the carbohydrate being ingested at that meal time
102
what is the first choice medication for T2DM?
Offer standard-release metformin as the initial drug treatment for adults with type 2 diabetes.
103
what lifestyle advice should be given to a patient with T2DM?
Weight reduction with calorie restricted diabetes diet
104
what would need to be considered before prescribing metformin?
Renal function – avoid if eGFR below 30 – risk of accumulation and theoretically of lactic acidosis
BNF states: Use with caution in renal impairment— increased risk of lactic acidosis.
In adults with type 2 diabetes, review the dose of metformin if the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73m2. Stop metformin if the eGFR is below 30 ml/minute/1.73m2.
Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function and those at risk of eGFR falling below 45 ml/minute/1.73m2.
105
how should metformin be introduced to a patient?
Gradually increase the dose of standard‑release metformin over several weeks to minimise the risk of gastrointestinal side effects in adults with type 2 diabetes. So start on 500 mg od or bd then slowly increase to 1 gram bd. (you don’t need to remember doses).
106
what are the side effects of metformin?
Common:
Abdominal pain; anorexia; diarrhoea (usually transient); nausea; taste disturbance; vomiting
Rare:
Decreased vitamin-B12 absorption; erythema; lactic acidosis (withdraw treatment); pruritus; urticaria
Gastro-intestinal side-effects are initially common with metformin, and may persist in some patients, particularly when very high doses are given. A slow increase in dose may improve tolerability.
107
what is the mechanism of action of metformin?
Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilisation
108
how long should T2DM be given before intensification?
4 months
109
what are the potential adverse affects of sulfonylureas?
Can cause hypoglycaemia
Weight gain
GI side effects
110
how is sulfonylureas administered?
multiple daily dosing
111
what is the mechanism of action of sulfonylureas?
Sulfonylureas bind to and close ATP-sensitive K+ (KATP) channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca2+ channels
112
what are the potential adverse effects of pioglitazone?
```
Weight gain
Oedema
Heart failure (esp when given alongside insulin)
Small bone fractures (esp women)
Small increased risk of bladder cancer
```
113
describe the mechanism of action of pioglitazone?
Glycaemic mechanism of action of thiazolidinedione “insulin sensitizers” (using an adipocyte for illustration purposes). These drugs are synthetic ligands for the transcription factor PPARγ, a member of a superfamily of nuclear receptors including thyroid and steroid receptors. PPARγ is expressed in multiple tissue types (e.g. skeletal muscle, fat & liver). PPARγ stimulation upregulates the expression of genes involved in lipid & glucose metabolism, insulin signal transduction, and adipocyte differentiation. As illustrated, one mechanism contributing to the hypoglycaemic effect of thiazolidinediones is an increased expression of the glucose transporter GLUT4. The increased expression of GLUT4 (in addition to mediators of insulin signal transduction) increases the ability of cells (e.g. adipocytes) to take up glucose when stimulated by insulin. Pioglitazone, which also stimulates PPARα (e.g. a mechanism shared with fibrate hypolipidaemics) exerts more significant lipid-lowering effects compared to rosiglitazone (a pure PPARγ agonist – no longer available in the UK)
114
describe the mechanism of DPP4 inhibitors?
DPP-4 is a serine protease that is expressed on the surface of endothelial cells, T-lymphocytes & in a circulating form. An important role is to inactivate incretins (GLP-1 & GIP). Inhibition of incretins by DPP-4 inhibitors prolongs the half-life of incretins (GLP-1 & GIP) and is associated with increased insulin release & reduced glucagon release. DPP-4 inhibitors do not have significant effects on GI motility or appetite that are observed with more efficacious (DPP-4 resistant) GLP-1 agonists.
115
what are some important considerations when prescribing DPP4 inhibitors?
No hypoglycaemia as monotherapy
Weight neutral
Low potency
Sitagliptin and saxagliptin need dose adjustment for renal impairment
Linagliptin no need for renal dose adjustment
116
what are some important considerations when prescribing SGLT2 inhibitors?
```
No hypoglycaemia as monotherapy
Weight neutral (may aid weight loss)
Good glucose lowering effect
Urinary infections + candidiasis
Hypovolaemia (uncommon)
DKA (rare)
Fournier’s gangrene (rare)
```
117
describe the mechanism of SGLT2 inhibitors?
Glucose is filtered by the renal glomeruli and is reabsorbed in the proximal tubule. Approximately 90% of glucose reabsorption is produced by a sodium-glucose transporter (SGLT-2). Its inhibition results in increased glucose in the urine (glycosuria) and a lowering of plasma glucose level in patients with type 2 diabetes.
118
what are some important considerations when prescribing GLP1 analogues?
```
No hypoglycaemia as monotherapy
Weight loss
Good glucose lowering effect
Injectable
GI side effects – N & V
Risk of pancreatitis
Avoid in medullary Ca thyroid
```
119
describe the mechanism of action of GLP1 analogues?
Potent GLP-1 agonists exert effects by multiple mechanisms including increased glucose-dependent insulin secretion, delayed gastric emptying, reduced glucagon levels, and reduced food intake by CNS effects to cause appetite suppression. Short acting agents exert their effect mostly by slowing gastric emptying, which reduces post-prandial glucose levels. In contrast, long-acting agonists have a stronger effect to reduce fasting glucose levels mediated by their effect on insulin and glucagon release. Long-acting GLP-1 receptor agonists have little effect on gastric emptying due to the development of tolerance to GLP-1 effects mediated by changes in parasympathetic tone.
120
diabetic with fingerprick ketones of 6.1mmol/L (<0.6). likely diagnosis?
Likely diabetic ketoacidosis – but we need a pH from a VBG or ABG to confirm this diagnosis
121
what is DKA?
DKA consists of the biochemical triad of ketonaemia (ketosis), hyperglycaemia, and acidaemia.
Ketonaemia > 3.0mmol/L or significant ketonuria (more than 2+ on standard urine sticks)
Blood glucose > 11.0mmol/L or known diabetes mellitus
Bicarbonate (HCO3-) < 15.0mmol/L and/or venous pH < 7.3
122
what is the initial management for a patient with DKA?
ABCDE
Fluids IV 0.9% NaCl 500 mLs over 15 min initially
Hour 1: Immediate management upon diagnosis: 0 to 60 minutes.
T = 0 at time intravenous fluids are commenced. If there is a problem with intravenous access, critical care support should be requested immediately
Aims:
Commence IV 0.9% sodium chloride solution
Commence a Fixed Rate Intravenous Insulin Infusion (FRIII) but only after fluid therapy has been commenced
Establish monitoring regime appropriate to patient; generally hourly blood glucose (BG) and hourly ketone measurement, with at least 2 hourly serum potassium and bicarbonate for the first six hours
Clinical and biochemical assessment of the patient
123
how does intravenous insulin work?
Reduction in blood glucose and even more importantly suppression of lipolysis and resolution of ketonaemia
124
what are the main aims in DKA treatment?
Fluid resuscitation and therapy
Treatment of ketosis and hyperglycaemia with IV insulin
Management of potassium effects
125
what is the difference between HHS (hyperosmolar hyperglycaemic state) and DKA?
HHS:
IV fluids before insulin – essential
No IV insulin until glucose stops falling by 5 mmol/hr using IV fluids
If IV insulin needed then use low dose (0.5 units/kg/hr)
Need for thromboprophylaxis
Look for infection + treat
Foot care
126
what are the characteristic features of a person with HHS?
hypovolaemia
marked hyperglycaemia without significant hyperketonaemia or acidosis
osmolarity >320
127
give examples of quick acting carbohydrates used in treating hypoglycaemia in adults who are conscious, orientated and able to swallow?
5-7 Dextrosol® tablets (or 4-5 Glucotabs®)
1 bottle (60ml) Glucojuice®
150-200ml pure fruit juice e.g. orange
3-4 heaped teaspoons of sugar dissolved in water
128
if a patient is hypoglycaemia but unable to swallow oruncooperative what should be given?
give either 1.5 -2 tubes 40% glucose gel (Glucogel) squeezed into the mouth between the teeth and gums or (if this is ineffective) give glucagon 1mg IM (may be less effective in patients prescribed sulfonylurea therapy/patients currently under the influence of alcohol).
129
what treatment of hypoglycaemia can be given to patients who are unconscious and/or having seizures and/or very aggresive?
in hospital:
If IV access available, give 75-100ml of 20% glucose over 15 minutes, (e.g. 300-400ml/hr).
If IV access available, give 150-200ml of 10% glucose (over 15 minutes, e.g. 600-800ml/hr).
If no IV access is available then give 1mg Glucagon IM.
at home:
Glucagen hypokit
130
describe perioperative care for diabetics?
Depends on surgery (minor vs major)
Day surgery may only need reduction in insulin dose or omission/continuation of oral drug
Use of variable rate insulin infusion + Glucose
Prevention of hyperglycaemia
Prevention of hypoglycaemia
Transition back to usual diabetes regimen
131
what are the sick day rules for patients with T1DM?
Never stop insulin
Try and drink/sip clear sugar free fluids to prevent dehydration (100 mL/hr)
Insulin correction doses may be needed
132
describe perioperative use of acarbose?
day before surgery: normal
morning surgery: no morning dose
afternoon surgery: morning dose, no lunchtime dose
133
describe perioperative use of meglitinide?
day before surgery: normal
morning surgery: no morning dose
afternoon surgery: morning dose, no lunchtime dose
134
describe perioperative use of metformin?
day before surgery: normal
if OD : don't stop
if BD: don't stop
if TID: omit lunchtime dose
135
describe perioperative use of sulphonylureas?
day before surgery: normal
morning surgery: if OD in morning- omit / if BD -no morning dose
afternoon surgery: if OD in morning omit / if BD-omit both doses
136
describe perioperative use of thiazolidinediones?
day before surgery: normal
morning surgery: normal
afternoon surgery: normal
137
describe perioperative use of DPP4 inhibitors?
day before surgery: normal
morning surgery: no morning dose
afternoon surgery: no morning dose
138
serum thyroid-stimulating hormone < 0.05 mU/L (0.4–5.0)
serum free T4 43 pmol/L (10.0–22.0)
serum free T3 14 pmol/L (3.0–7.0)
anti-thyroid receptor antibodies 76 U/L (<10)
likely diagnosis?
Graves’ thyrotoxicosis
| less likely - toxic nodule or toxic multinodular goitre.
139
what is the initial therapy to control hyperthyroid symptoms and how does this work?
A beta blocker should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before confirming that the cause of hyperthyroidism is Graves’ disease.
Beta blockers ameliorate the symptoms of hyperthyroidism that are caused by increased beta-adrenergic tone. These include palpitations, tachycardia, tremulousness, anxiety, and heat intolerance. Thus, a beta-blocker should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before determining the cause of the hyperthyroidism. They should be continued until resolution of hyperthyroidism.
In addition to reducing sympathoadrenal symptoms beta-blockers can also influence mono-deiodination.
140
how does propranolol influence mono-deiodination?
Propranolol in high doses (above 160 mg/day) also slowly decreases serum triiodothyronine (T3) concentrations by as much as 30 percent, via inhibition of the 5'-monodeiodinase that converts thyroxine (T4) to T3. Propranolol is highly lipid soluble, allowing it to become sufficiently concentrated in tissues to inhibit monodeiodinase activity. This effect of propranolol is slow, occurring over 7 to 10 days, and contributes little to the therapeutic effects of the drug.
141
describe the metabolism of carbimazole?
converted by first-pass metabolism to the active derivative methimazole
142
how does carbimazole work?
Thionamides inhibit thyroid peroxidase and, therefore, the synthesis of thyroid hormone. The long half-life of T4 means that changes in the rate of synthesis take 4–6 weeks to lower circulating T4 and T3 concentrations to within the normal range. These drugs also appear to have an immunosuppressant effect in individuals with autoimmune thyroid disease. They reduce the levels of thyroid-stimulating immunoglobulin, although the clinical importance of this is uncertain.
143
describe the steps in thyroid hormone synthesis?
- iodide trapping by thyroid follicular cells
- diffusion of iodide to apex of cells
- transport of iodide into colloid
- oxidation of inorganic iodide to iodine and incororation if iodine into tyrosine residues within thyrogloulin molecules in colloid
- combination of 2 DIT molecules to form tetraiodothyronine or of MIT with DIT to form T3
- uptake of thyroglobulin from colloid into follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4, T3, DIT and MIT, T3,T4 release into circulation
- deiodination of DIT and MIT to yield tyroisine. T3 is formed from monodeiodination of T4 in thyroid and peripheral tissues
144
How long does it take for carbimazole to low free T4 to normal?
Carbimazole is converted by first-pass metabolism to the active derivative methimazole.
Thionamides inhibit thyroid peroxidase and, therefore, the synthesis of thyroid hormone. The long half-life of T4 means that changes in the rate of synthesis take 4–6 weeks to lower circulating T4 and T3 concentrations to within the normal range. These drugs also appear to have an immunosuppressant effect in individuals with autoimmune thyroid disease. They reduce the levels of thyroid-stimulating immunoglobulin, although the clinical importance of this is uncertain.
145
what is often used as an alternative to carbimazole in pregnant women?
Propylthiouracil (PTU)
146
what are the principle differences between PTU and carbimazole?
PTU but not MMI (methimazole – active metabolite of carbimazole) inhibits the 5'-monodeiodinase that converts thyroxine (T4) to triiodothyronine (T3) in extrathyroidal tissue. However, MMI has several important pharmacokinetic advantages over PTU:
The serum half-life of MMI is four to six hours, whereas that of PTU is 75 minutes.
The intrathyroidal MMI concentration, which can reach a thyroid-to-serum ratio of 100:1, remains high for up to 20 hours, considerably longer than that of PTU.
Perchlorate discharge tests, which are a measure of inhibition of iodine organification, demonstrate the superiority of MMI over PTU. In one study, perchlorate discharged 37 percent of the radioiodine tracer 24 hours after a single 15 mg dose of MMI, versus only 8.6 percent after a 300 mg dose of PTU
147
describe the mode of action of thioamide?
They are actively transported into the thyroid gland where they inhibit both the organification of iodine to tyrosine residues in thyroglobulin and the coupling of iodotyrosines.
148
Why might we use PTU as the preferential thioamide in early pregnancy?
All three antithyroid drugs (ATDs) have been associated with possible teratogenic effects, but teratogenic effects are more common and more severe with MMI and CBZ compared to PTU. All cross the placenta.
There are several case reports of aplasia cutis, a scalp defect, in newborns of mothers treated with (or exposed to) MMI. More serious congenital malformations, such as tracheoesophageal fistulas, patent vitellointestinal duct, choanal atresia, omphalocele, and omphalomesenteric duct anomaly, have been observed with maternal MMI and CBZ, but not PTU use. BNF recommends PTU as drug of choice for first trimester but that one consider a switch to Carbimazole in the second and third trimesters due to the risk of hepatoxicity with PTU.
149
Why don’t we use PTU as first line therapy in non-pregnant adults?
PTU: Severe hepatic reactions have been reported, including fatal cases and cases requiring liver transplant—discontinue if significant liver-enzyme abnormalities develop. Patients should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, or pruritus develop
150
what are the most important issues with carbimazole (PTU to a lesser extent)?
neutropenia and agranulocytosis – the BNF states:
Patients should be asked to report symptoms and signs suggestive of infection, especially sore throat
A white blood cell count (FBC) should be performed if there is any clinical evidence of infection
Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia
151
what are the important considerations when prescribing carbimazole?
Women of child-bearing potential should use effective contraception during treatment with Carbimazole.
PTU has been associated with severe hepatic reactions – discontinue if significant liver enzyme abnormalities develop
Patients should be told how to recognize signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, jaundice, dark urine or pruritus develop.
152
what are the 2 regimes for medically treating thyrotoxicosis?
Titration therapy and block and replace therapy.
153
what are the risks of using block and replace therapy to treat thyrotoxicosis?
Block and replace should not be used in pregnancy due to the higher doses of Carbimazole used and risk of neonatal hypothyroidism
154
Anti-thyroid drugs are one of the three ways to treat thyrotoxicosis – what are the other two treatment pathways?
In the only randomized trial comparing these three therapies, each was equally effective in normalizing serum thyroid hormone concentrations within six weeks; after treatment, 95 percent or more of the patients were satisfied with their therapy.
155
what radioiodine is used in treatment of hyperthyroidism?
I 131
156
Anti-thyroid drugs are one of the three ways to treat thyrotoxicosis – what are the other two treatment pathways?
In the only randomized trial comparing these three therapies, each was equally effective in normalizing serum thyroid hormone concentrations within six weeks; after treatment, 95 percent or more of the patients were satisfied with their therapy.
157
slide 14
slide 14
158
what radioiodine is used in uptake scans?
I 123
159
when is radioiodine used as first line treatment?
Graves' disease, especially for people over 50 years of age, or for relapse after antithyroid drug treatment.
160
what issue can radioiodine make worse and how can this be prevented?
Radioiodine can make thyroid ophthalmopathy worse, but this can be prevented by treatment with a corticosteroid such as prednisolone for 2–3 months.
161
is radioiodine safe to use in pregnancy?
no
162
Why do we generally pre-treat with Carbimazole before giving radioiodine?
Before radioiodine treatment it is often recommended that the thyrotoxicosis should be stabilised with carbimazole. This reduces the risk of exacerbation of hyperthyroidism from radiation thyroiditis immediately after isotope treatment. However, carbimazole must be stopped for at least 2 days before radioactive iodine is given (2 weeks for propylthiouracil), or it will prevent uptake of the radioiodine by the thyroid cells. A β-adrenoceptor antagonist can be useful in this period to prevent symptomatic relapse. The antithyroid drug can be restarted 7 days after radioiodine, to cover the period of up to 8 weeks before radioiodine is fully effective.
163
describe how subacute thyroiditis will look on I123 uptake scans?
thyrotoxicosis is secondary to leakage of stored hormone from a inflamed gland rather than unregulated secretion
very low radio-iodine uptake (1.9%)
both lobes visible on scan but very patchy
164
describe how Graves disease will look on I123 uptake scans?
high radio-iodine uptake (56%)
thyroid will have homogenous uptake
pyramidal lobe visualisation supports the diagnosis
(both lobes appear solid white centre, pyramidal lobe slightly visible above)
165
describe how toxic nodule will look on I123 uptake scans?
almost always benign
focal increased uptake with suppression of surrounding tissue
high radio-iodine uptake (39%)
on scan appears as dense white dot
166
describe how toxic nodule will look on I123 uptake scans?
almost always benign
focal increased uptake with suppression of surrounding tissue
high radio-iodine uptake (39%)
on scan appears as dense white dot
167
if a patient who has previously been treated for thyrotoxicosis later gains weight and feels most of the time with high TSH, low T3,T4. what is the diagnosis and treatment?
Post radioiodine hypothyroidism
| Commence levothyroxine
168
what important information should you give to a patient starting levothyroxine?
Levothyroxine has a long half life and it can also take TSH up to 6 weeks to reach an new plateau once the dose has been adjusted.
Some drugs interfere with the absorption of levothyroxine from the gut. These include iron, calcium carbonate, mineral supplements, colestyramine and sucralfate. The metabolism of levothyroxine is accelerated by the concurrent use of the hepatic enzyme-inducing drugs phenobarbital, phenytoin, carbamazepine and rifampicin.
169
How does hormone replacement therapy differ between primary and secondary adrenal insufficiency?
Primary adrenal insufficiency needs glucocorticoid and mineralocorticoid replacement therapy whereas secondary hypoadrenalism (hypopit) needs only glucocorticoid replacement as RAAS is intact.
170
How does hormone replacement therapy differ between primary and secondary adrenal insufficiency?
Primary adrenal insufficiency needs glucocorticoid and mineralocorticoid replacement therapy whereas secondary hypoadrenalism (hypopit) needs only glucocorticoid replacement as RAAS is intact.
171
how would you treat a patient with acute adrenal (addisonian) crisis)?
IV fluid resuscitation
IV hydrocortisone
Prevention of hypoglycaemia
Treatment of any precipitating cause
Please immediately inject 100mg hydrocortisone i.v. or i.m. followed by rapid rehydration with i.v. administration of 0.9% saline solution (or equivalent).
Adrenal crisis can be a manifestation of previously undiagnosed adrenal failure.
Adrenal crisis can also occur in patients with known adrenal insufficiency if existing cortisol replacement does not meet the increased need for cortisol, e.g. due to illness with fever, persistent vomiting or diarrhoea, trauma or childbirth. Preparation for invasive diagnostic procedures such as colonoscopy and surgery requiring general anaesthesia are further risk factors for adrenal crises.
172
how would you treat a patient with acute adrenal (addisonian) crisis)?
IV fluid resuscitation
IV hydrocortisone
Prevention of hypoglycaemia
Treatment of any precipitating cause
Please immediately inject 100mg hydrocortisone i.v. or i.m. followed by rapid rehydration with i.v. administration of 0.9% saline solution (or equivalent).
Adrenal crisis can be a manifestation of previously undiagnosed adrenal failure.
Adrenal crisis can also occur in patients with known adrenal insufficiency if existing cortisol replacement does not meet the increased need for cortisol, e.g. due to illness with fever, persistent vomiting or diarrhoea, trauma or childbirth. Preparation for invasive diagnostic procedures such as colonoscopy and surgery requiring general anaesthesia are further risk factors for adrenal crises.
173
what pharmacological therapies can be given to treat hyperprolactinaemia?
Treatment options include dopamine agonists as first line therapy.
174
describe hyperprolactinaemia and the differences in men and women?
These can usually be seen in men much more commonly than women – in men the traditional symptoms of hyperprolactinaemia are often absent and the prolactinoma can grow very large ultimately presenting with signs of other hormone deficiency or visual disturbance due to optic chiasm compression.
In women hyperprolactinaemia presents early due to effects on fertility, disturbance of menstruation, anovulation, galactorrhoea, so that the prolactinoma is often small and confined to the pituitary without disturbance of other hormone production.
175
describe the different dopamine agonists?
Cabergoline – is an ergot dopamine agonist that is administered once or twice a week and has much less tendency to cause nausea than bromocriptine – usually first line
Bromocriptine – needs to be taken daily
Quinagolide – non-ergot alternative
176
describe the use of dopamine agonists in treating macroprolactinomas?
For a microadenoma, a dopamine D2 receptor agonist such as cabergoline can be used to suppress prolactin secretion and shrink the adenoma.
Normal plasma prolactin concentration is achieved in up to 90% of cases using cabergoline or quinagolide. Pituitary surgery may be considered for treatment failure, or when there is a large adenoma that is producing pressure effects, although often even very large macroprolactinomas respond to dopamine agonist therapy
177
what is the emergency treatment of hypercalcaemia?
Hypercalcaemia >3.5 mmol/L = emergency
IV 0.9% sodium chloride
IV Zoledronic acid 4mg over 15 min (once fully rehydrated)
178
what is the emergency treatment of hypercalcaemia?
Hypercalcaemia >3.5 mmol/L = emergency
IV 0.9% sodium chloride
IV Zoledronic acid 4mg over 15 min (once fully rehydrated)
179
describe the mode of action of bisphosphonates?
Pyrophosphate analogues that bind to hydroxyapatite crystals in the bone matrix
Inhibit osteoclast resorptive action on bone
Bisphosphonates are poorly absorbed from the gut
180
how should bisphosphonates be taken?
Orally best taken once weekly on an empty stomach to avoid binding by Ca2+ in food
Care with swallowing – take with large glass of water and stay upright for 30 min – oesophageal injury reported
181
give examples of non nitrogen containing bisphosphonates?
sodium clodronate
incorporation into non-hydrolizable analogues of ATP leading to accumulation of atp metabolites
182
how is hypocalcaemia treated?
Usually treated with Vit D compounds
Remember role of Kidney in 1α-Hydroxylation as an essential step for activation of vitamin D
alfacalcidol (1α-hydroxycholecalciferol)calcitriol (1,25-dihydroxyvitamin D3 or 1,25-dihydroxycholecalciferol) – can be used in renal failure
colecalciferol (vitamin D3), ergocalciferol (vitamin D2) – need a functioning kidney
183
how is hypocalcaemia treated?
Usually treated with Vit D compounds
Remember role of Kidney in 1α-Hydroxylation as an essential step for activation of vitamin D
alfacalcidol (1α-hydroxycholecalciferol)calcitriol (1,25-dihydroxyvitamin D3 or 1,25-dihydroxycholecalciferol) – can be used in renal failure
colecalciferol (vitamin D3), ergocalciferol (vitamin D2) – need a functioning kidney
184
in a patient with hypocalcaemia with concomitant hypomagnesaemia why is it important to treat hypomagnesaemia?
PTH activity is affected by hypomagnesaemia and PTH resistant occurs so until the low magnesium is corrected the hypocalcaemia will be difficult to correct.
If there is concurrent hypomagnesaemia, it must be corrected; otherwise maintaining a normal serum Ca2+ will be difficult.
185
in a patient with hypocalcaemia with concomitant hypomagnesaemia why is it important to treat hypomagnesaemia?
PTH activity is affected by hypomagnesaemia and PTH resistant occurs so until the low magnesium is corrected the hypocalcaemia will be difficult to correct.
If there is concurrent hypomagnesaemia, it must be corrected; otherwise maintaining a normal serum Ca2+ will be difficult.
186
what are the possible therapies used to treat osteoporosis?
```
Bisphosphonates
Raloxifene
Teriparatide
Strontium ranelate
Denosumab
Calcitriol can be used when bisphosphonates are unsuitable
```
187
why is it important to treat severe hyponatraemia correctly?
Risk of osmotic demyelination syndromeToo rapid rise or fall in serum NaLimit to no greater than 10 mmol/L/ change in first 24 hours
188
what are the likely causes of hyponatraemia with urine osmolarity <100
primary polydipsia
innapopriate IV fluid
low solute intake
189
what are the likely causes of hyponatraemia in a patient with urine osmolarity >100 and urine na <30?
```
heart failure
portal hypertension
nephrotic syndrome
hypoalbuminaemia
third space loss
GI loss
previous diuretic use
```
190
how is hyponatraemia treated?
IV infusion 150ml 3% hypertonic salive over 20 mins
check na
repeat until 5mmol/l increase in Na
191
how is hyponatraemia treated?
IV infusion 150ml 3% hypertonic salive over 20 mins
check na
repeat until 5mmol/l increase in Na
192
Which specific drug could an expert use to treat SIADH?
Tolvaptan is a competitive antagonist at vasopressin V2 receptors. Its major action is in the renal collecting ducts to reduce water reabsorption and produce aquaresis without sodium loss, thus increasing free water clearance and correcting dilutional hyponatraemia. Tolvaptan is effective for the treatment of hyponatraemia, secondary to inappropriate ADH secretion and also for correction of diuretic-induced hyponatraemia in cirrhosis and in heart failure.
