P33 Flashcards

Question

Adverse Drug Event

Answer 1

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

Answer 2

Adverse drug event - Patient having a road traffic accident while on a specific medication - Untoward occurrence after exposure to a drug that is not necessarily caused by the drug Adverse drug reaction - Patient experiencing anaphylaxis shortly after taking a drug - An unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug

Answer 3

Type A reactions (augmented): - Common, 80% of all reactions - Are predictable from the known pharmacology of a drug - Exaggerated response to pharmacological action - Usually dose dependent - High incidence (morbidity), low mortality. Type B reactions: - Idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. Type C (continuing), Type D (delayed use)

Answer 4

Type A adverse drug reaction

Answer 5

- Drugs that block the action of dopamine = dopamine antagonists - Atypical antipsychotics have less extrapyramidal symptoms - Clozapine, olanzapine, risperidone - Less affinity for D2 receptors

Answer 6

D2 receptor antagonist. Indications: - Migraine headache treatment - Prevent N+V - Increase stomach emptying - GORD SE: - Fatigue - Diarrhoea - Restlessness More serious side effects include: - Movement disorder like tardive dyskinesia - Neuroleptic malignant syndrome - Depression Causes hyperprolactinemia due to inhibitory effect on prolactin leading to: - Galactorrhoea, amenorrhoea, breast tenderness

Answer 7

``` Haloperidol Chlorpromazine Fluphenazine Flupentixol Sulpiride Loxapine ``` SE: - Extrapyramidal: > Akathisia (severe restlessness) > Tardive dyskinesia (involuntary choreoathetoid movements, most common is chewing and pouting of jaw) > Acute dystonia (e.g. torticollis, oculogyric crisis) > Dystonia (involuntary muscular contraction) > Pseudoparkinsonism - Hyperprolactinemia - Decreased seizure threshold - Postural hypotension - Sedation - Weight gain - Prolonged QT interval (particularly haloperidol) - Antimuscarinic

Answer 8

``` Risperidone Paliperidone Clozapine Olanzapine Quetiapine Aripiprazole Amisulpride ``` ``` SE: - Metabolic syndrome: > Weight gain > Cholesterol abnormalities > DM II + obesity ``` - Reduced seizure threshold (greater with atypicals) - Extrapyramidal (akathisia, dyskinesia, dystonia) - Salivation - Myocarditis - Agranulocytosis, neutropenia [clozapine]

Answer 9

Non-selective NSAIDs (COX inhibitors) The COX-1 enzyme is constitutive and produces prostaglandins associated with GI cytoprotection. The inhibition of these prostaglandins by traditional NSAIDs increases the susceptibility of the GI tract to risk for damage from gastric acid, pepsin, and bile. COX-1 also is associated with prostaglandin production related to the regulation of platelet function (primarily aggregation) and renal function. The COX-2 enzyme generally is considered to be inducible. It produces prostaglandin secondary to proinflammatory mediators such as cytokines as a response to pain, fever, and inflammation. SE: - Heartburn - Dyspepsia - Ulceration - Bleeding - Perforation

Answer 10

Beta-lactamase inhibitor combo: (tazocin & co-amoxiclav) Contain a beta lactam ring (imipenem & meropenem, carbopenem antimicrobial agents)

Answer 11

Combinations of drugs may increase the risk of acute kidney injury, as each has the potential to affect kidney function through different mechanisms. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers cause a haemodynamic reduction in glomerular filtration rate due to efferent arteriolar vasodilation, and NSAIDs cause inhibition of prostacyclin synthesis leading to renal afferent arteriolar vasoconstriction.

Answer 12

Inhibitors - Fluconazole - Clarithromycin - Erythromycin - Grapefruit juice - Ritonavir Inducers - Carbamazepine - Rifampicin - Rifabutin - St. John’s wort ``` Enzyme induction leads to: - Tolerance or decreased effectiveness - Increased doses - Increased metabolism and excretion - Slow development -days to weeks ``` ``` Enzyme inhibition leads to: - Sensitivity - Decreased doses - Drug accumulation - Rapid development -days ```

Answer 13

CYP2D6 is highly polymorphic, with over 90 known allelic variants. Codeine is a prodrug and its analgesic properties are not manifest until it is metabolized by CYP2D6, primarily to morphine and and codeine-6-glucuronide. Subjects who are ultra-rapid metabolizers based upon CYP2D6 genotype have higher than expected morphine levels (an initial "overdose"), with more side effects and a shorter than expected duration of pain control.

Answer 14

Codeine Hydrocodone Oxycodone Tramadol

Answer 15

Antiproliferative immunosuppressant Action: decreases clonal proliferation of T and B cells during induction phase of immune response MOA: interferes with purine synthesis. cytotoxic on dividing cells Use: UC and Crohn's. prevent organ rejection. chronic autoimmune disease, rheumatoid arthritis, granulomatosis with polyangiitis. SE: myelotoxicity. GI disturbance. hypersensitivity reactions NOTE: monitor blood for myelosuppression

Answer 16

Pharmacogenetics focuses on single drug-gene interactions. Pharmacogenomics encompasses a more genome-wide association approach, incorporating genomics and epigenetics while dealing with the effects of multiple genes on drug response

Answer 17

Hyperkalaemia

Answer 18

●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

Answer 19

Although GFR cannot be measured directly, the best method for determining GFR is measurement of the urinary clearance of an ideal filtration marker. The gold standard of exogenous filtration markers is 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. 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. The most common methods utilised to estimate the GFR are: 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.

Answer 20

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. Absorption! ---------- Dietary iron is absorbed from the duodenum and upper jejunum. Haem dietary sources (fish, poultry, and meat) have a higher bioavailability than do non-haem (vegetable) sources (30 versus 10 percent). = Ascorbic acid (Vitamin C) enhances the absorption of non-animal sources of iron. = Phosphates, and phytates inhibit iron absorption. Absorption of ferric iron is facilitated by several factors: - Gastric acid, which increases its solubility - Conversion to ferrous iron by ferric reductase on the brush border of enterocytes, which is enhanced by dietary reducing agents such as ascorbic acid (vit C), fructose and some amino acids, - Intestinal absorption mediated by the divalent metal transporter (DMT-1), mainly in the duodenum. Expression of DMT-1 is increased in iron deficiency and in hereditary haemochromatosis. Transportation! ----------- Within enterocytes, iron is oxidized to the ferric state and transported to the circulation by the protein ferroportin. In the blood, ferric iron is bound to the globulin transferrin and transported to the bone marrow and iron stores. Cellular iron uptake occurs via transferrin receptors, and in most cells iron is stored as ferritin (a complex of iron with the apoferritin protein).