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FRACP exam paediatrics > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What are the common side effects of epilim?

A

GI symptoms
Deranged LFTS- CI in children aged <2 years
Teratogenic

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2
Q

What anti-seizure medications can worsen absence seizures?

A

Carbamazapine
Phenytoin
Possibly Vigabatrin

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3
Q

What ant-seizure medication can cause SJS?

A

Lamotrigine

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4
Q

What anti-seizure medications are best used for infantile spasms

A

1st line Vigabatrin

2nd line Topiramate

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5
Q

What ant-seizure medications are best used for absence epilepsy?

A

Ethosuximide

Epilim

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6
Q

What ant-seizure medications are best used for absence epilepsy?

A

Ethosuximide
Epilim
Lamotrigine

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7
Q

What is the main side effect of Levetiracetam

A

Behavioural issues

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8
Q

What is the most concerning side effect of Vigabatrin?

A

Irreversible loss of peripheral vision
Occurs over years
Aim stop vigabatrin after 2 years max

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9
Q

What anti-seizure medication do you have to use at half strength when using sodium valproate?

A

Lamotrigine- sodium valproate doubles circulating amount of Lamotrigine (regardless of the dose of sodium valproate)

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10
Q

What antiseizure medication can worsen myoclonic seizures and is contraindicated in JME?

A

Carbamazepine

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11
Q

What is the first line treatment for myoclonic seizures?

A

Sodium valproate
Levetiracetam
Topiramate

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12
Q

What is the first line treatment for tonic or atonic seizures?

A

Sodium valproate

Lamotrigine

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13
Q

lamotrigine

A

add

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14
Q

carbamazepine

A

-used for generalised seizures and focalseizures
-CI in JME as worsens JME
ADD

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15
Q

levetiracetam

A

add

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16
Q

valproate

A

add

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17
Q

vigabatrin

A

add

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18
Q

phenytoin

A

add

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19
Q

CYP450 inhibitors

A

add

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20
Q

CYP450 inducers

A

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21
Q

Amiodarone

A

ADD

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22
Q

ACEI

A

add

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23
Q

Spironolactone

A

Spironolactone inhibits distal sodium reabsorption by competitive binding to receptors at the aldosterone-dependent sodium/potassium exchange site.

This leads to diuresis and a contraction of the intravascular volume. Volume contraction increases proximal sodium reabsorption by several mechanisms:

  1. reduced peritubular capillary hydrostatic pressure drives Na/H2O reabsorption (pressure gradient);
  2. increased peritubular capillary oncotic pressure drives Na/H2O reabsorption (concentration gradient);
  3. angiotensin II directly stimulates proximal sodium reabsorption;
  4. sympathetic nervous system activation directly stimulates proximal sodium reabsorption
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24
Q

furosemide

A

add

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25
Q

class I antiarrythmic

A

add

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26
Q

class 2 antiarrthymic

A

add

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27
Q

class 3 antiarrthymic

A

add

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28
Q

Entecavir (for Hep B)

A 
Nucleoside analogue (purine base)
Oral agent
Well tolerated
First line Rx Hep B active 
Effective at suppressing hep B virus (HbAge -ve, Anti HbsAb +ve, low viral load)
Have to be on it for 2-3 years
29
Q

Interferon (for Hep B)

A 
Cytokine drug
About 58% respond
More durable response
Only 48 weeks Rx needed
Low resistance of mutant strains
SC Rx (weekly)
\$\$$
S/E sucks --> flu like illness, depression, anorexia, bone marrow suppression
30
Q

Lamivudine (Hep B)

A 
Nucleoside analogue (pyrimidine base)
Only 23% virologic response in children
BUT oral, cheap, well tolerated
Less durability of response 
Increased drug resistance (70% by 5 years)
31
Q

Azathioprine

A

ADD

32
Q

5ASA

A

ADD

Pentasa

33
Q

CCS

A

ADD

34
Q

Mycophenalate motifil

A

-Inhibits synthesis of guanosine monophosphatase enzymes
- blocks purine synthesis preventing proliferation of T cells and B cells
= anti-proliferation

Uses:
Immunosuppressant for autoimmune hepatitis, post transplant, relapsing nephrotic syndrome etc

S/E
1. diarrhoea

  • Cytopaenia (neut, anaemia)
  • N+V
  • Thrombosis/thrombophlebitis (IV formation)
35
Q

Interactions between anti-convulsants

A

Pharmacokinetic interactions between antiepileptic drugs are variable and unpredictable. They can increase or decrease drug concentrations, and either increase risk of toxicity or decrease seizure control.

  • Lamotrigine may increase the concentration of carbamazepine, increasing the adverse CNS effects of carbamazepine.
  • Carbamazepine may decrease the concentration of lamotrigine and decrease its efficacy.
  • Carbamazepine may also decrease clonazepam concentration with loss of seizure control.
  • Treatment with valproate increases lamotrigine concentration necessitating a lower lamotrigine dose.
36
Q

Metformin

A
  • Metformin is a biguanide.
  • Mode of action: reduces hepatic glucose production; increases peripheral utilisation of glucose.
  • Indications: type 2 diabetes in adults, including combinations with: glibenclamide, rosiglitazone, sitagliptin; type 2 diabetes in children >10 years.

Common adverse effects: malabsorption of vitamin B12, nausea, vomiting, anorexia, diarrhoea.

Infrequent adverse effects: rash.

Rare adverse effects: lactic acidosis, acute hepatitis

37
Q

Chemotherapy agents, third spacing and cardiopulmonary effects

A
  • Methotrexate accumulates in 3rd space fluid compartments such as pleural effusion and ascites. This will cause a delayed, prolonged excretion leading to severe toxicity. This is also the reason you do not give high dose MTX in renal failure, or with drugs that can inhibit MTX renal elimination
  • Cyclophosphamide can cause cardiotoxicity; pulmonary injury is rare.
  • Cytosine can cause pericarditis.
  • Doxorubicin – anthracyclines are associated with cardiac toxicity, and are contraindicated in CHF and cardiomyopathy. Mediastinal based effusions do not interfere with LV myocardial function, unless there is a constrictive pericardial collection, and therefore not a contra-indication to anthracycline usage if have large pleural effusion.
  • Vincristine doesn’t tend to have cardiopulmonary side effects.
38
Q

Alkylating agents and steroid dependent/frequent relapsing nephrotic syndrome

A
  • Alkylating agents, such as cyclophosphamide and chlorambucil, can induce longer lasting remissions than prednisone alone in patients who are frequent relapsers or steroid dependent.
  • Data from the literature demonstrate that cyclophosphamide therapy increased sustained remission in frequently relapsing and/or steroid dependent patients of 67 to 93 percent at one year, 36 to 66 percent at five years, and approximately 25 percent at 10 years.
  • The response to cyclophosphamide may be related to whether the patient is steroid dependent or not.
  • Similar efficacy can be achieved with chlorambucil but cyclophosphamide is 1st line
  • The recommended dose is 0.2 mg/kg for two months. Higher daily doses give similar results but have a greater risk of side effects.
39
Q

Pneumoccocus antimicrobial resistance

A

Pneumococcal resistance has been seen to the following classes of antibiotics:

-beta-lactams (penicillins, cephalosporins, carbapenems)
-macrolides (erythromycin, azithromycin, clarithromycin, and lincosamides [clindamycin])
-tetracyclines and folate-inhibitors (cotrimoxazole)
fluoroquinolones (ciprofloxacin, levofloxacin, gemifloxacin, moxifloxacin)

Beta-lactam action and resistance:

  • inhibit pneumococcal growth by irreversibly binding the active site of enzymes that are needed for synthesis of peptidoglycan, the major constituent of the cell wall
  • in strains that have reduced susceptibility to penicillin, the affinity of the antibiotic for these enzymes is reduced à however, this can often be overcome by using HIGHER CONCENTRATIONS (also applies to cephalosporins and carbapenems) –> but depends on the MIC
40
Q

Treatment of JME

A
  1. Sodium valproate.
  2. Lamotrigine, benzodiazepines, levetiracetam or topiramate can be used as second line treatments

Carbamazepine is CI as worsens JME in 68%

41
Q

CCS potencies cf prednisone

A

The following is a list of glucocorticoid potencies if comparing to 5mg prednisone:

Prednisolone: 5mg
Betamethasone: 0.75mg (6-7:1 potency)
Dexamethasone: 0.75mg (6-7:1 potency)
Cortisol: 20mg (1:4 potency)
Cortisone: 25mg (1:5 potency)
42
Q

CCS potencies

A 
The following is a list of glucocorticoid potencies:
HYDROCORTISONE: 1
Cortisone acetate: 0.8
PREDNISONE 3.5-5
Prednisolone: 4
METHYLPREDNISONE: 7-7.5
DEXAMETHASONE: 25-80
BETAMETHASONE: 25-30
Triamcinolone: 5
Beclometasone: (8 puffs QDS equals 14mg oral prednisolone)
Fludrocortisone acetate: 15
DOCA: 0
43
Q

Clonidine overdose

A
  • Symptoms usually appear within 1 hour of oral ingestion of pills or liquids.
  • May mimic opioid intoxication.

Common findings: lethargy, coma, bradycardia, hypotension, respiratory depression, apnea, small pupils

44
Q

Dystonic reaction

A

-These are characterised by intermittent spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, extremities, and even the larynx.

Drug: typical antipsychotics; metoclopramide

45
Q

Malignant hyperthermia

A
  • A rare genetic disorder, malignant hyperthermia is distinguished from neuroleptic malignant syndrome (NMS) by its clinical setting - occurring with use of potent halogenated inhalational anesthetic agents and succinylcholine.
  • Its clinical appearance with hyperthermia, muscle rigidity, and dysautonomia is quite similar to NMS although often more fulminant
46
Q

Neuroleptic malignant syndrome

A
  • This is defined by its association with a class of medications that BLOCK dopamine transmission, e.g. risperidone and other antipsychotics
  • Life threatening
  • Tetrad of distinctive clinical features: HYPERTHERMIA; DIFFUSE RIGIDITY; mental status changes; and autonomic instability.
  • Low BP
  • Takes DAYS –> onset 4-14 days of starting medication

-Lab findings often reflect the clinical manifestations of NMS with more severe rigidity leading to more profound creatine kinase (CK) elevation.

RX: supportive, BZD can help
Resolution in 1-2 weeks

47
Q

Serotonin syndrome

A
  • This is usually caused by use of SSRIs and has a similar presentation that is difficult to distinguish from NMS BUT in SS onset is more abrupt
  • Typical features in these patients that are not often seen in NMS patients are shivering, hyperreflexia, myoclonus, and ataxia.
  • Nausea, vomiting, and diarrhoea are also a common part of the prodrome in serotonin syndrome and are rarely described in NMS.
  • Rigidity and hyperthermia, when present, are less severe than in patients with NMS
48
Q

MIC

A
  • The MIC is the lowest concentration that completely inhibits visible growth of the organism as detected by the unaided eye after a 18 to 24 hour incubation period with a standard inoculum.
  • The most common approach to antibiotic dosing is to adjust the doses to obtain antibiotic plasma concentrations that are above the MIC for the respective pathogen throughout the dosing interval
  • visible growth of the organism as detected by the unaided eye after a 18 to 24 hour incubation period with a standard inoculum.
49
Q

When time above MIC is important in specific antibiotic groups

A

For antibiotics that are time dependent (beta-lactam antibiotics, vancomycin, macrolides), their effect depends on the length of time that the drug is in contact with the bacteria.

-Their effect will increase with increasing concentrations until a finite point (the maximum kill rate) is reached. After that point, increasing concentrations will not produce a corresponding increase in the effect; therefore, high peak concentration will not help.

–The parameter that has been most used to assess the efficacy of time-dependent antibiotics is the time that the antibiotic plasma concentration exceeds the MIC for a particular microorganism, or time above MIC (t > MIC

50
Q

Maximum kill rate

A

-Maximum killing has been seen to occur at concentrations approximately four to five times the MIC.

51
Q

Thyroxine and bioavailability

A

Thyroxine is unstable in light, heat, humidity.

It is absorbed from gut with 40-80% bioavailability. There is increased bioavailability in a fasting state, and it should be taken 30-60 mins before meals.

Thyroxine binds to iron salts, antacids, milk, calcium carbonate, cholestyramine - therefore if taking any of these medications reduced levels of thyroxine are available for absorption.

52
Q

Prophylactic treatment of migraines

A
  • Amitriptyline
  • Cyproheptadine
  • Pizotifen
  • Propranolol
  • Sodium valproate

All cause weight gain except propanolol
Propanolol CI in asthma

53
Q

Methyphenidate

A
  • Anorexia or appetite disturbance occurs in 80%
  • Sleep disturbance occurs in 3-85%
  • Weight loss occurs in 10-15%
  • Approximately 15 to 30% of children who are treated with stimulant medications develop motor tics/exacerbate, most of which are transient. Can use lower doses if already have tic disorder
  • Less common side effects include increased heart rate and blood pressure, headache, social withdrawal, nervousness, irritability, stomach pain, and rebound irritability or moodiness. Deceleration of linear growth may occur, but adult height is not affected
54
Q

Calcineurin inhibitors

A

Cyclosporin and tacrolimus

Used in immunosuppression including RA, nephrotic syndrome and POST TRANSPLANT

55
Q

Cyclosporin and tacrolimus side effects

A
  • gingival hyperplasia
  • hirsutism
  • nephrotoxicity
  • HTN
  • hypercholesterolaemia
  • neurotoxicity (tremor, headache, paraesthesiae)
  • deranged LFTs
  • hypomagnesaemia
  • hyperkalaemia
  • diarrhoea
56
Q

Erythromicin and cyclosporin

A
  • The mechanism of the drug interaction between erythromycin and cyclosporin appears to be decreased hepatic first-pass metabolism
  • Erythromycin INCREASES cyclosporin toxicity
57
Q

Cardiac drugs CI in re-entrant tachycardia (including WPW)

A

-digoxin or calcium channel blockers may increase rate of anterograde conduction and increase risk of ventricular tachyarrthymia

58
Q

Ivacaftor

A

Used in specific class 3 CF defect and in combination with Lumacaftor (which is corrector) (combination orkambi)

  • The PBS subsidises ivacaftor for patients two years and older with cystic fibrosis.
  • The main gene defect for which Ivacaftor is approved corresponds to a class III mutation
  • Ivacaftor targets the G551D mutation
  • Ivacaftor is a potentiator
59
Q

Why MTx need folinic rescue

A

-MTx competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.

  • The affinity of methotrexate for DHFR is about one thousand-fold that of folate.
  • DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate.
  • Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins
  • Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis. Also, folate is needed for purine base synthesis, so all purine synthesis will be inhibited.
60
Q

Folinic acid rescue in mtx

A
  • Leucovorin (folinic acid) is a tetrahydrofolic acid derivative that acts as a biochemical cofactor for carbon transfer reactions in the synthesis of purines and pyrimidines.
  • Leucovorin does not require the enzyme dihydrofolate reductase (DHFR) for conversion to tetrahydrofolic acid.
  • The effects of methotrexate and other DHFR antagonists are inhibited by leucovorin.
  • Approved as a rescue agent after high-dose methotrexate therapy and to counteract the effects of folic acid antagonists (trimethoprim or pyrimethamine)
61
Q

Ifosfomide

A

Hypophosphataemia
Low bicarbonate concentration
Glycosuria
Proteinuria
Borderline low potassium and sodium
Normal creatinine and urea, calcium, magnesium and albumin (normal renal function)
These findings are consistent with a metabolic acidosis - a common side effect of ifosfamide.

62
Q

NMS vs SS

A

Onset:
SS = abrupt
NMS = gradual (days)

Course:
SS= rapidly resolves
NMS= Prolonged –> takes 1-2 weeks to get better

Neuromuscular findings:
SS= myoclonus and tremor
NMS= diffuse rigidity

Reflexes:
SS= increased
NMS= decreased

Pupils:
SS= mydriasis
NMS = normal

Note: sometimes sx overlap. both have anticholinergic and sympathetic effects

Rx: both respond well to BZD in overdose

63
Q

Dopamine

A

This reduces proximal tubule reabsorption thus increasing sodium excretion.

64
Q

Insulin

A

This increases distal tubular sodium resorption.

65
Q

CCB

A

This reduce sodium reabsorption in the distal tubule.

66
Q

CYP450 inhibitors

A 
CRACK AMIGOS
Cimetidine
Ritonavir (protease inhibitor)
Amiodarone
Ciprofloxacin
Ketocanazole (and other azoles)
Acute alcohol use
Macrolides
Isoniazid
Grapefruit Juice
Omeprazole
Sulfonamides
67
Q

CYP450 inducers

A

Guinnes, Corona, PBRS induce Chronic Alcoholism

Griseofulvin
Carbamazepine
Phenytoin
Barbituates
St. John's Wort
Chronic alcoholism
68
Q

Calculate bioavailability

A

AUC oral/AUC injected x 100

FRACP exam paediatrics (25 decks)

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