drug therapy Flashcards

Question

Answer 1

In order for a drug to be active it must be free in the plasma. A drug is not active when bound to plasma protein. If a drug is 96% protein bound then only 4% of the drug is free and available for action. If the unbound drug level changes to 6% then plasma levels of free drug will increase by 50% which will result in toxicity.

Answer 2

the volume of plasma that's necessary to account for the total amount of drug in a patient's body if that drug were present throughout the body at the same concentration as found in the plasma. Vd = drug mass/conc drugs move away from the blood into the organ systems, we tend to measure a higher Vd as the concentration in the blood goes down. So a higher Vd = more amount of drug moving into tissues i.e. less in the blood So a lower Vd = less amount of drug moving into tissues i.e. more in the blood

Answer 3

* Clearance is defined as the theoretical volume from which a drug is completely removed over a period of time. * Measure of drug elimination. * Measured in units of time (ml/min).

Answer 4

renal - Dependent on drug concentration and urine flow rate hepatic - Dependent on metabolism and biliary excretion * Disease states and age (young and elderly) will reduce hepatic and renal clearance

Answer 5

the time taken for the drug concentration in the blood to decline to half of the current value. → Help us to work out how often a drug needs to be administered. e.g. if it takes 4 hours for the concentration of a drug in the bloodstream to drop from 10mg/L to 5 mg/L then the half-life is 4 hours depends on the volume of distribution and rate of clearance. If we know the volume of distribution and clearance we can show that the half-life t1/2 = 0.693 x Vd/Cl

Answer 6

increase plasma levels and hence toxicity of a drug. → due to reduction in renal/hepatic clearance → due to a large volume of distribution

Answer 7

therapeutic benefit - drugs need to be given chronically Plasma levels of a drug take many doses before they stabilise, usually 4-5 half-lives. drug levels into the therapeutic range - loading dose may be necessary.

Answer 8

removal of active drugs and metabolites from the body. determines the length of action of the drug. [1] Drug Metabolism (liver) [2] Drug Excretion (kidney but also biliary system/gut, lung, and milk)

Answer 9

Three principal mechanisms are used: * Glomerular filtration * Passive tubular reabsorption * Active tubular secretion

Answer 10

glomerulus filters 190 litres of fluid a day. All unbound drugs will be filtered at the glomerulus → as long as their molecular size, charge or shape are not excessively large. ----------- Any factor that reduces the glomerular filtration rate will reduce the clearance of a drug - lead to prolongation of the half-life and increasing blood levels, leading to toxicity. e.g. renal disease, hypovolaemia, hypotension

Answer 11

Some drugs are actively secreted into the proximal tubule (acidic and basic compounds) → The most important system for eliminating protein-bound cationic and anionic drugs.

Answer 12

As the filtrate moves down the renal tubule any drug present is concentrated as water is reabsorbed. Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation. → Passive diffusion occurs in the distal tubule and collecting duct. → Only un-ionised drugs such as weak acids are reabsorbed

Answer 13

liver secretes 1 litre of bile a day. → Drugs are passively or actively secreted into the bile. Biliary secretion accounts for 5-95% of drug elimination for many drugs. entero-hepatic circulation - drugs that are reabsorbed from the bile into the circulation. It continues until the drug is metabolised in the liver or excreted by the kidneys.

Answer 14

Drug Metabolism in the liver - leads to the conjugation of the drug to make it more water-soluble. The conjugated drug is not reabsorbed from the intestine

Answer 15

reduces the rate of conjugation and biliary secretion leads to the build-up/ reabsorption of the drug with resultant toxicity.

Answer 16

drugs that increase in activity, more active metabolites, following drug metabolism.

Answer 17

biochemical modification of pharmaceutical substances by living organisms through specialized enzymatic activity. ---------------- lipid soluble, nonpolar compounds → water soluble and polar allows them to undergo excretion, whereas lipid-soluble substances are passively reabsorbed into the blood. ----------------- * Liver * Lining of the gut * The kidneys * The lungs.

Answer 18

[1] Loss of pharmacological activity. [2] Decrease in activity, with metabolites that show some activity. [3] Increase in activity, more active metabolites. → Activation of a prodrug. [4] Production of toxic metabolites. - Direct toxicity - Carcinogenic. - Teratogenic

Answer 19

they have a wide substrate specificity individual drugs can be metabolised by more than one enzyme Enzyme induction leads to increased metabolism of drugs - leads to ineffective treatment. Some enzymes are: → regulated at several levels → expressed constitutively, constantly. → expressed in the presence of a particular substrate

Answer 20

phase 1 - oxidation, reduction, hydrolysis leads to drug activation/ inactivation phase 2 - glucuronidation leads to the conjugation products

Answer 21

[1] Hydrolysis, oxidation, reduction [2] Increasing the polarity of the drug by adding a polar group (provides an active site for Phase 2 metabolism) [3] Metabolising enzymes: Cytochrome P-450 - Drug specificity is determined by the isoforms of the cytochrome P-450. - Specificity tends to be relative rather than absolute.

Answer 22

[1] CYP3A4 → major constitutive enzyme in the human liver → also found in the gut and is responsible for the pre-systemic metabolism of several drugs * Example drugs – diazepam, methadone, simvastatin, CCBs. [2] CYP2D6 → responsible for the metabolism of some antidepressants, antipsychotics and the conversion of codeine to morphine. [3] CYP1A2 → induced by smoking and is important in the metabolism of theophylline.

Answer 23

Because the reduced or absent expression of CYP2D6 is found in 5-10% of the population.

Answer 24

* Other drugs/herbals/natural substances * Genetics * Hepatic blood flow * Liver disease * Age * Sex * Ethnicity * Pregnancy

Answer 25

[1] Conjugation [2] Increases water solubility and enhances excretion Conjugation involves the attachment of glucuronic acid, glutathione, sulphate or acetate to the metabolite - generated by Phase 1 metabolism. Conjugation results in inactivation - a small number of drug metabolites may be active.

Answer 26

smokers have higher levels of CYP1A2 - induced by smoking. And that isoform of cytochrome P-450 is involved in the metabolism of theophylline

Answer 27

increased enzyme synthesis - therefore increased activity. drug metabolising enzymes can be induced by other compounds - Increased metabolism of drugs by that enzyme → Resulting in loss or decrease in drug effect. e.g. Indinavir & John's wort

Answer 28

alcohol and smoking

Answer 29

Drugs, herbal medicines, and foodstuffs may inhibit drug-metabolising enzymes. Common culprits include: cimetidine, valproate, erythromycin, clarithromycin, ketoconazole, CCBs, and grapefruit juice. e.g. Effects of grapefruit juice on felodipine pharmacokinetics and pharmacodynamics

Answer 30

Wide variability in the response to drugs among individuals - Consequences may be a therapeutic failure or an adverse drug reaction Drug metabolising enzymes are expressed in multiple forms (Genetic Polymorphism) within the same individual and between different individuals → therefore inter-individual differences in gene expression are common. Gene mutations result in excess or deficiencies or complete absence of a particular metabolising enzyme activity → eventually may lead to toxicity or insufficiency, depending on the condition

Answer 31

ph, bacterial flora, git motility

Answer 32

Changes in pH lead to changes in the degree of drug ionisation H2 antagonists, proton pump blockers and antacids reduce H+ - increase the pH

Answer 33

Bacterial flora are usually found in the large bowel → Broad-spectrum antibiotics destroy normal gut flora This may lead to failure of oral contraceptives or digoxin toxicity

Answer 34

oral medicines - absorbed in small intestines Gastric emptying - rate limiting step [1] drugs delay gastric emptying - delay absorption e.g. anticholinergics, tricyclic anti-depressants, opiates [2] drugs increase gastric emptying and accelerate absorption i.e. migraine treatment with paracetamol and metoclopramide

Answer 35

Direct Indirect Antagonistic e.g. using both atenolol and salbutamol → atenolol causes bronchoconstriction while salbutamol causes bronchodilation Synergistic / Agonistic When two drugs with the same pharmacological effect acting on different receptors are given together → additive or multiplicative

Answer 36

benzodiazepines and tricyclics/ alcohol - sedation warfarin and nsaids - bleeding atenolol and verapamil - bradycardia

Answer 37

[1] NSAIDs increase blood pressure (opposite of what is needed in antihypertensive medication) [2] NSAIDs increase water retention (opposite of what is needed in heart failure

Answer 38

[1] Multiple Drug Therapy → Incidence of ADRs increases exponentially with the number of medications → Polypharmacy Increases Potential for Drug Interactions [2] Inter-current Disease → Renal and hepatic impairment [3] Race and Genetic Polymorphisms [4] Age → Elderly and neonates [5] Sex → ADRs more common in women

Answer 39

Yellow card system → Online reports made for all medicines including vaccines, blood factors and immunoglobulins, herbal medicines and homoeopathic remedies, and all medical devices. Green-card system

Answer 40

dispersions of coarse drug particles in a liquid phase. → dose can be contained in a small volume → Good for drugs which are insoluble & unpalatable as they are better tolerated

Answer 41

delivery systems used to administer drugs to the young, elderly and patients who can’t swallow tablets or capsules. May be given via a nasogastric or PEG tube → Absorbed extremely rapidly * Absorption depends on {{c2::gastric emptying}} and is most rapid from the {{c2::small intestine}}

Answer 42

delays the disintegration of the tablet until it reaches the small intestine Tablets are enteric-coated to: → Protect the drug from stomach acid - Omeprazole → Protect the stomach from the drug - Aspirin

drug therapy Flashcards

(69 cards)