Science Underpinning Practice

?
  • Created by: LBCW0502
  • Created on: 20-04-21 10:36
State features of pharmacokinetics
Drug needs to get to the site of action, at the right concentration for a suitable length of time. Factors - dose, frequency, dosage interval, time to clinical effect, elimination time, dosage adjustment
1 of 48
How are drug molecules absorbed?
Crossing a biological membrane (passive diffusion, facilitated passive diffusion, active transportation). Extent of absorption (area, pH, blood flow, GI motility and food, first pass, disease state, particle size)
2 of 48
What is bioavailability?
The proportion of drug (amount) that enters the systemic circulation. F = amount of drug absorbed/amount of drug administered
3 of 48
What is hepatic ratio?
The proportion of drug eliminated by the liver on one single pass through (efficiency). F = 1 - E
4 of 48
What is apparent volume of distribution?
Vd = A/Cp
Total amount of drug in the body (dose)/plasma concentration of drug
5 of 48
What are first-order kinetics?
-dC/dt=KC. Cp = Cpoe^-kt. Rate of elimination is directly proportional to drug plasma concentration. The higher the plasma concentration of drug, the greater the rate of elimination
6 of 48
What are zero-order kinetics?
If metabolising enzymes become saturated then reaction can only proceed at a maximum rate. Rate of elimination doesn't equal plasma concentration of drug (but equals km). Rate of administration x S x F = Vmax s Cpss/km + Cpss
7 of 48
Which equation is used to determine the concentration at time t?
Cp = Cp0e^-kt
8 of 48
What is half-life?
The time required for the amount of drug in the body to reduce by 50%
9 of 48
What is clearance?
The volume of blood cleared of drug per unit time is a combination of metabolism and excretion. For drugs where excretion is mainly via the kidneys, and the drug remains unchanged, then CL is proportional to renal function
10 of 48
How are Kelim, Vd and Cl related?
Kelim = CL/Vd
11 of 48
How many half-lives does it usually take for a drug to reach steady-state concentrations?
~4.5 half-lives. Steady state (rate in = rate out in mg/hr).
12 of 48
What is the equation for maintenance dose?
(Maintenance Dose x S x F)/t = Cpss x Cl
13 of 48
Does dose affect time to steady state?
No. Increased doses - higher steady state concentration, higher peak/tough variation. Tau > t1/2 - lower steady state concentration, larger peak to trough variation. Tau < t1/2 - higher steady state concentration but less to trough variation
14 of 48
What is a drug interaction?
An interaction is said to have occurred when the effect of one drug is changed by the presence of another drug, herbal medicine, food, drink or some environmental chemical agent.
15 of 48
What are the main outcomes of drug interactions?
Enhanced effect of one or more drugs. Antagonism of the effect of 1 or more drugs. A mixture of the two (many ADRs have caused hospital admissions)
16 of 48
What is the clinical significance of drug interactions?
When a combination of medicines results in an unexpected change or complication in the condition of the patient.
17 of 48
Give examples of at-risk patients
Polypharmacy. Hepatic/renal impairment or disease. Long-termW therapy for chronic disease (HIV, epilepsy, diabetes, CVD). Critically ill, transplant patients, complicated surgery. Elderly. Many doctors involved in prescribing
18 of 48
Give examples of drugs likely to cause ADRs due to concentration-dependent toxicity
Digoxin, warfarin, cytotoxics
19 of 48
Give examples of drugs likely to cause ADRs due to steep dose-response curve
Sulphonylureas, verapamil, loop diuretics
20 of 48
Give examples of drugs likely to cause ADRs due to patient dependent on therapeutic effect
Oral contraceptives, glucocorticoids, antiepileptics, antiretrovirals
21 of 48
Give an example of a drug likely to cause ADRs due to saturable hepatic metabolism
Phenytoin
22 of 48
What are pharmacodynamic drug interactions?
Pharmacodynamic Drug Interactions occur when the effects of one drug is changed in the presence of another at the site of action. Competition for specific receptors. Interference with physiological systems
23 of 48
Give examples of pharmacodynamic drug interactions (1)
Atenolol (antagonistic) interacts with salbutamol, causing bronchospasms and exacerbation of asthma. BDZ (additive/synergistic) interacts with opiate analgesics or alcohol to increase sedation. Warfarin interacts with aspirin/clopidogrel with an increased
24 of 48
Give examples of pharmacodynamic drug interactions (2)
Aspirin interacts with NSAIDs, causing gastric irritation. Ferrous sulphate interacts with dihydrocodeine, causing increased constipation
25 of 48
Give examples of pharmacodynamic drug interactions (3)
Electrolyte imbalance: Digoxin interacts with loop diuretics (increased risk of hypokalaemia and digoxin sensitivity). ACE-I interacts with spironolactone (increased risk of hyperkalemia). ACE-I interacts with NSAIDs causing a hypotensive effect.
26 of 48
Give examples of pharmacodynamic drug interactions (4)
Indirect: oral hypoglycaemic agents interact with thiazides and steroids (loss of blood sugar control). MAOIs interact with SSRIs/TCAs, causing serotonin syndrome
27 of 48
How can pharmacodynamic interactions be overcome?
Timing of doses (if sedating, give at night, educate patient with regard to symptoms). Monitor signs/symptoms (blood sugar, blood pressure, serum potassium concentrations, peak flow). Drug selection (avoid certain combinations)
28 of 48
What are pharmacokinetic drug interactions?
Pharmacokinetic drug interactions are those that affect the processes by which drugs are absorbed, distributed, metabolised or eliminated. These types of drug interactions can be predicted but due to patient variability the extent is often uncertain
29 of 48
Give examples of drugs with a narrow therapeutic range
Digoxin, carbamazepine, phenytoin, theophylline, phenobarbitone, ciclosporin, lithium, gentamicin, vancomycin, warfarin, sodium valproate (increased risk of ADR)
30 of 48
What are the mechanisms of ADR? (1)
Altered absorption, altered distribution (lower protein binding), altered metabolism (enzyme induction, enzyme inhibition), altered elimination (change in enterohepatic recycling, decrease in renal function).
31 of 48
What are the mechanisms of ADR? (2)
Metabolism and elimination changes are responsible for most clinically significant interactions
32 of 48
Where is the main site of metabolism?
Liver and SI epithelium
33 of 48
State features of phase I metabolism (1)
Oxidation, hydrolysis, reduction. CYP450 mixed function oxidase system. Isoenzymes responsible for metabolism of most commonly used drugs - CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 (CYP3A most important family). Drugs may be substrates, inhibit or
34 of 48
State features of phase I metabolism (2)
The substrate for the enzyme is the drug affected. The inhibitor - drugs/compounds that reduce metabolism, net effect is decreased clearance (potential toxicity). The inducer - drugs/compounds that increase metabolism (potential loss of efficacy) - see di
35 of 48
State features of phase II metabolism
Conjugation of drug with glucuronic or sulphyric acid
36 of 48
Describe features of CYP450 enzyme inducers (1)
Most powerful enzyme inducers are: rifampicin, antiepileptics (phenytoin, carbamazepine), others (smoking, chronic alcohol use, St John's Wort). Develops over several days/weeks. Effects persist for similar period once drug stopped.
37 of 48
Describe features of CYP450 enzyme inducers (2)
Inducers with short t1/2 have more rapid effect than those with longer t1/2. Increased metabolism, reduced effect e.g. rifampicin & OHC
38 of 48
Describe features of CYP450 enzyme inhibitors
Often responsible for common, significant drug interactions. Inhibition is often dose-related and occurs quickly – reaching maximal effects when Css reached. Takes approximately 4-5 t1⁄2 of drug. Enzyme inhibition results in reduced metabolism, increased
39 of 48
Give examples of enzyme induction (1)
Oral contraceptive interacts with carbamazepine (enzyme inducer) resulting in contraceptive failure (wanted pregnancy). Warfarin interacts with rifampicin (enzyme inducer) resulting in under-anticoagulation (risk of thrombosis).
40 of 48
Give examples of enzyme induction (2)
Ciclosporin interacts with St John's Wort, resulting in loss of immunosuppression and graft rejection. Protease inhibitors interacts with St John's Wort (rise in viral load)
41 of 48
Give examples of enzyme inhibition (1)
Warfarin is affected by the following enzyme inhibitors (amiodarone, isoniazid, tamoxifen, omeprazole) - increased INR and risk of bleeding. Theophylline is affected by the following enzyme inhibitors (ciprofloxacin, erythromycin) - theophylline toxicity
42 of 48
Give examples of enzyme inhibition (2)
Carbamazepine is affected by the enzyme inhibitors, isoniazid, erythromycin - CBZ toxicity
43 of 48
State other interactions (effect on drug transporter proteins) - 1
Drugs and endogenous substances cross membranes by carrier-mediated processes. P-glycoprotein (P-gp) present in cell membranes especially - renal proximal tubule, hepatocytes, intestinal mucosa, BBB
44 of 48
State other interactions (effect on drug transporter proteins) - 2
P-gp is an efflux pump exporting substances into urine, bile & GI lumen. Can be inhibited (and induced) by some drugs. Verapamil and amiodarone inhibit renal tubule P-gp causing a rise in digoxin plasma concentrations.
45 of 48
What is the influence of other products?
Herbal medications (St John's Wort, potent CYP3A4 inducer). Food (grapefruit juice, CYP3A4 inhibitor). Tobacco smoke (CYP1A2 inducer, affects carbamazepine). Alcohol (induction with chronic use)
46 of 48
Describe features of altered elimination
Most drugs metabolised in liver excreted in kidneys. Unless very water-soluble – rely on kidneys. Alteration in renal elimination due to - change in GFR, tubular secretion and urinary pH. Reduced renal elimination of active drug results in increased effec
47 of 48
Give examples of altered elimination
Quinine, amiodarone, verapamil - ↑ digoxin (inhibition of renal clearance via P-gp). Thiazides - ↓ excretion lithium = toxicity (thiazides ↑ re-absorption at proximal tubules). Probenecid - ↑ effect penicillin (Probenecid decreases tubular secretion of an
48 of 48

Other cards in this set

Card 2

Front

How are drug molecules absorbed?

Back

Crossing a biological membrane (passive diffusion, facilitated passive diffusion, active transportation). Extent of absorption (area, pH, blood flow, GI motility and food, first pass, disease state, particle size)

Card 3

Front

What is bioavailability?

Back

Preview of the front of card 3

Card 4

Front

What is hepatic ratio?

Back

Preview of the front of card 4

Card 5

Front

What is apparent volume of distribution?

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Other resources:

See all Other resources »See all Pharmacy resources »