Pharmacology Flashcards
What is pharmacokinetics?
How the body affects the drug
absorption, distribution, metabolism, excretion
State the calculation for rate of elimination
CL x Cp
Most drugs exhibit first-order kinetics. What is meant by this?
The rate of elimination is directly proportional to drug concentration
Define clearance (CL)
Volume of plasma cleared of a drug in unit time
What determines the maintenance dose rate of a drug?
Clearance
What is meant by ‘steady state’ of a drug?
Rate of drug administration = rate of drug elimination
Define volume of distribution (Vd)
The volume into which a drug appears to be distributed in fat with a concentration equal to that of plasma
What is the purpose of using a loading dose of a drug initially?
Decreases time to steady state for drugs with long half lives
Define half life of a drug
The time for the concentration of drug in plasma to halve
How is half life of a drug calculated?
0.693 x Vd / CL
A few drugs are administered by zero order kinetics. What is meant by this?
The drug is eliminated at a constant rate
List the four possible mechanisms of action of drug metabolism
Convert drugs to less active metabolites
Convert inactive to active compounds
Have unchanged activity
Possess a different type of action
What is the main organ of drug metabolism?
Liver
Describe phase 1 of drug metabolism
Makes drugs more polar by adding a chemically reactive group, permitting functionalization
Describe phase 2 of drug metabolism
Adds an endogenous compound to increase polarity (conjugation)
What is the function of CYP450 monoygenases?
Mediate oxidation reactions (phase 1) of many lipid soluble drugs
Convert substrate into hydroxyl product
What are the three basic processes of renal excretion?
- Glomerular filtration
- Active tubular secretion
- Passive reabsorption by diffusion
All drugs can enter the filtrate via glomerular filtration. True/False?
False
Only unbound drugs, thus if a drug binds to a plasma protein there will be less of it than the total plasma concentration
___% of renal plasma flow is filtered through the glomerulus, the remaining ___% is delivered to proximal tubule
20%
80%
State the two transporter systems that actively secrete drugs into the lumen of the nephron
Organic anion transporter (acidic drugs)
Organic cation transporter (basic drugs) e.g. metformin
At the basolateral membrane, organic anions enter cell by…
Diffusion
Or in exchange for alphaKG via OATs
At the apical membrane, organic anions enter cell by…
Multi-drug resistance protein 2 (MRP2)
OAT4 in exchange for alpha KG
At the basolateral membrane, organic cations enter cell by…
Diffusion
OCT
At the apical membrane, organic cations enter cell by…
Multi-drug resistance protein 1 (MRP1)
OC+/H+ antiporters (OCTN)
How are drugs that are highly protein bound excreted by the kidney?
Via tubular secretion
How do you calculate the therapeutic ratio of a drug?
Maximum tolerated concentration/
Minimum effective concentration
What is meant by ED50?
Median effective dose in 50% of the population
What is meant by TD50?
Median toxic dose in 50% of the population
What is meant by LD50?
Median lethal dose in 50% of the population
What is meant by a pharmacodynamic drug interaction?
Drug A modifies the effect of drug B without altering its concentration in tissue fluid
What is meant by a pharmacokinetic drug interaction?
Drug A modifies the concentration of drug B that reaches its site of action
What is the main difference between a pharmacodynamic and pharmacokinetic drug interaction?
Pharmacodynamic interactions are usually predictable
Drugs that increase or decrease the rate of emptying of the stomach may affect what aspect of pharmacokinetics?
Absorption
Drugs bound to a plasma protein may affect what aspect of pharmacokinetics?
Distribution
Drugs that induce hepatic enzymes may affect what aspect of pharmacokinetics?
Metabolism
Drugs that share a common transporter may affect what aspect of pharmacokinetics?
Excretion
What effect does competitive enzyme inhibition have on Km and Vmax respectively?
Higher Km
Same Vmax
What effect does non-competitive enzyme inhibition have on Km and Vmax respectively?
Same Km
Lower Vmax
Renal impairment can affect drug elimination. What measurement can be taken to help adjust drug dosage?
Creatinine clearance
Which one of the following drugs is most likely to cause hyperkalaemia? A. Allopurinol B. Simvastatin C. Omeprazole D. Ramipril E. Metformin
Ramipril
Decreased secretion of aldosterone, therefore less absorption of sodium and less potassium secreted
Furosemide causes hypokalaemia
Which one of the following drugs does not interact pharmacodynamically with the others listed to cause hypotension? A. Allopurinol B. Simvastatin C. Omeprazole D. Ramipril E. Metformin
Simvastatin
The combination of which PPI with clopidogrel should be avoided?
Omeprazole
Which of the following drugs does not need to be used with caution in patients with renal impairment? A. Allopurinol B. Simvastatin C. Omeprazole D. Ramipril E. Metformin
Omeprazole
Almost completely metabolised by the liver
Describe how you calculate the loading dose of a drug (per kg)
Vd x target Cp (for IV adminstration)
Vd x target Cp)/ bioavailability (oral administration
State the calculation for Vd of a drug
Dose of a drug given by IV bolus /
Drug concentration at t=0
For drugs eliminated by first-order kinetics, half life is constant regardless of concentration. True/False?
True
What is meant by bioavailability of a drug
Fraction of an administered dose of unchanged drug that reaches the systemic circulation
e.g. 0.5 = half of drug will reach circulation (need twice as much to create the same effect)
Offer all patients who have had an MI the following drugs…
ACE inhibitor
Dual antiplatelet therapy (aspirin + second antiplatelet)
Beta-blocker
Statin
State how you calculate the steady state plasma concentration of a drug
Maintenance dose rate /
Clearance
State the calculation for the concentration of a drug at time t
Ct = Co x (0.5)n
where n is the number of half lives
Mr SH obtains sildenafil from an internet pharmacy. Whilst waiting for the beneficial effect he collapses. What is the likely pharmacodynamic interaction that is most likely to have occured?
Isosorbide mononitrate
NO causes an increase in cGMP in smooth muscle and erectile tissue increasing blood flow.
Organic nitrates cause venodilation by producing NO (also increases cGMP)
Mrs SH is taking warfarin for AF and has had no problems for several months. Her GP diagnoses a fungal infection and prescribes treatment for this. Later, the women notices blood in her urine. What is the likely pharmacodynamic interaction that is most likely to have occured?
Fluconazole
Inhibits CYP450 enzyme that metabolises warfarin
Mr SH suffers from gout for which he takes allopurinol. From the list below select which medication might plausibly exacerbate this?
Furosemide (or another diuretic)
Entry to the renal tubules is mediated by secreting OAT transporters, these also secrete urate
Mr SH starts to consume large quantities of grapefruit juice. After a few days he begins to experience muscle pains. What pharmacokinetic reaction is most likely to explain this event?
Simvastatin with a component of the juice
The effectiveness of which one of the following drugs taken by Mr SH may be decreased by his impaired renal function? A. Metformin B. Simvastatin C. Furosemide D. Aspirin E. Bisoprolol
Furosemide
Reduced secretion of furosemide at the proximal tubule, and binds to protein in urine
Mr SH sees his GP with a flare up on gout despite being on allopurinol. He has a PMHx of LVF and renal impairment. Which agent would you not consider to treat his acute flare? A. Colchicine B. Naproxen C. Oral prednisolone D. IM steroid E. IA steroid
Naproxen
He has LVF and renal impairment, glomuleral filtration relies more on prostaglandins to maintain pressure in the glomerulus
What is included in the triple whammy combo to precipitate acute renal failure?
ACEi
Diuretic
NSAID
Mr TP takes warfarin as an anticoagulatn for the prophylaxis of chronic AF. He suffers from moderate OA pain. Which of the following analgesics would be most suitable? A. Aspirin B. Diclofenac C. Paracetamol D. Ibuprofen E. Naproxen
Paracetamol
NSAIDs could precipitate GI bleeding
Mr TP is scheduled for a THR of his OA hip. For ho many days before surgery should his warfarin medication for chronic AF be withdrawn?
5 days
Half life of warfarin is around 40 hours
A man presents to A&E following a suicide attempt, 6 hours after the incident. He reports taking a paracetamol overdose. What is the most appropriate treatment?
IV N-acetylcysteine
It is effective up to 8 hours after the reported incident of overdose
A man presents to A&E following a suicide attempt, less than one hour after the incident. He reports taking a paracetamol overdose. What is the most appropriate treatment?
Oral administration of activated charcoal
It should be used if the incident occurred within the previous hour
If a patient becomes hypotensive after a spinal anaesthetic, the normal course of action would be to give the patient oxygen, IV fluids and a drug to bring up the blood pressure. Which drug is typically used?
Ephedrine
It has an indirect sympathomimetic causing release of noradrenaline
It has some B-agonist and A1-agonist activity
Rate of elimination is independant of Vd. True/False?
False
Rate of elimination is related to the Vd, larger Vd results in a slow elimination
Vd may exceed the total volume of the body. True/False?
True
Vd is typically a very large value
A patient is given a spinal anaesthetic before surgery to replace is OA hip. Spinal anaesthesia most commonly causes hypotension by what mechanism?
Blockade of sympathetic transmission (loss of Ap generation in cell bodies of preganglionic neurones) to blood vessels, causing vasodlatation
