Pharmacology 2 Flashcards
what is the Bowans principle when considering drug action>
lower potency requires larger clinical intubating dose, which means more molecules of drug being given and so onset is faster according to law of mass action.
pKa can also mean larger amounts of unbound unionised drug therefore higher gradient between drug in blood and brain, therefore faster onset
which drug is useful as a marker of gastric emptying and why?
Paracetamol
because it has 100% bioavailability
rapidly absorbed from small intestine
often used as a marker of gastric emptying
what is the treatment of bradycardia due to third degree HB with broadened QRS. CVS stable but risk of asystole
(regular p waves rate of 80, regular QRS rate of 30)
according to ALS guidelines:
- Atropine 500 mcg IV (can repeat to max 3mg)
If no response:
2. Trans cutanous pacing
or
-Adrenaline infusion 2-10mcg/min
-Isoprenaline 5cmg/min
*Glucagon may be indicated if Beta-blocker or CCB OD is suspected
NB transvenous pacing involves Central venous access to pass an electrode into right ventricle- temp until permanent pacemaker can be implanted.
how to calculate renal clearance of a drug?
e.g 60kg, steady state, 240ml urine collected over 4 hours.
urine conc 2.5mg/ml
plasma conc= 25mcg/ml
What is the renal clearance
urine conc/plasma conc x vol (ml/mins)
in this example:
2500/25mcg x 1ml/min =100ml/min
which antibiotics target folic acid metabolism of bacterial cells (? needed for DHF A -> THF A (for DNA)
Trimethoprim
Sulphonamides e.g sulfasalazine - interfere with PANA uptake into bacteria 9metabolite involved in the synthesis of nucleic acids)
Trimethoprim can not be used in pregnancy for this reason as folate antagonists are teratogenic.
Pregnant women need to take folate supplements if also taking sulfasalazine for this reason.
Which antibiotics target DNA replication (DNA gyrase inhibitors)
-quinolones e.g ciprofloxacin, levofloxacin (bactericidal)
-Nalidixic acid
+?metronidazole intereferes with DNA helical structure
Cipro & levo replicate their floxacins by gyrating their hips
+Metronidazole diffuses into bacterial cells and is reduced to its active form by ferrodoxin, it disrupts the DNA Helical structure.
Which Abxs target protein synthesis (50 S inhibitors)?
Clindamycin
Erythromycin
Chloramphenicol
Linda, Eryth & Chlora are all in their 50s
Which Abx target protein synthesis (30 S inhibitors)
-Tobramycin
-Tetracycline
-Gentamicin
-Spectinomycin
-Streptomycin
-Amikacin
TOBi TETRA is GENntle in their 30s to not make a SPECTicle or get STREP
Which Abx target DNA-dependent RNA polymerase
Rifampicin ( a potent CYP450 inducer)
-causes orange-red secretions
By binding, Rifampicin prevents the polymerase enzyme from initiating the transcription process.
broad spectrum, used to treat TB.
Which Abx target Cell wall synthesis
-Penicillin
-Cephalosporins (Ceftriaxone, Cephalexin)
-Vancomycin
-Monobactams
-Carbapenems (Meropenem, Ertapenem)
-Cycloserine
-Fosfomycin
-Bacitracin
PENny is a CEF who went to VANCouver on her own (MONO) and said MERO ERTA me because no cell signal
Tell me the importance of Penicillins structure and clinical significance of this
Pencillin has a b-lactam ring which resembles one of the amino acids (D-alanyl-D-alanine) attached to NAM & is required in bacterial cell wall synthesis. It acts as a suicide subtrate for transpeptidase enzymes, resulting in weak cell wall and osmotic lyis.
Therefore, transpeptidase enzymes are known as penicillin binding proteins (PBP)
*** RESISTANCE-> bacteria may produce b-lactamase which degrades the b-lactam ring
which Abx are B-lactamase resistant?
Flucloxacillin (commonly used for B-lactamase-producing staphylococcus aureus) (Note though Fluclox wont work in MRSA, Vancomycin & teicoplanin are effective to be used instead)
-Meropenem
-Ertapenem
Methicillin
Clavulanic acid & Tazobactam are b-lactamase inhibitors
β-lactamase resistance refers to the ability of certain antibiotics to resist inactivation by β-lactamase enzymes produced by bacteria. These enzymes break down β-lactam antibiotics, such as penicillins and cephalosporins, rendering them ineffective. β-lactamase-resistant antibiotics are structurally modified or naturally resistant to these enzymes, allowing them to retain their antimicrobial activity against β-lactamase-producing bacteria.
1.Tell me about use of oral vancomycin
2. How is it excreted?
3. side effects of vanc
- vanc is poorly absorbed orally therefore its PO preparation is only for C.diff infections.
- Vanc is 90% excreted unchanged in urine thus needs monitoring due to toxicity
- SE:
-ototoxicity -discontinue if tinnitus occurs
-histamine release- hypotension, tachy, widespread rash (red-man syndrome)
-phlebitis- dilution of IV required
metronidazole Side effects
Metronidazole interferes with bacterial DNA helical structure
Side effecrs:
-nausea, metallic taste
-Alcohol-> dilsulfiram like reaction (drug that causes reaction to ETOH)-> nausea, vomiting, headache, flushing, hypotension
metronidazole has 100% bioavailability
Tell me about bioavailability
Bioavailability refers to the fraction of an administered drug that reaches the systemic circulation in its active form and is available for therapeutic effect. It is expressed as a percentage (%). For instance, a drug with 100% bioavailability means the entire dose administered reaches the bloodstream.
F(bioavailability)= PO/IV x100
Key Points About Bioavailability
Oral vs. Intravenous (IV):
Drugs administered intravenously (IV) have 100% bioavailability because they directly enter the bloodstream without undergoing absorption or metabolism.
Drugs given via other routes (e.g., oral, sublingual, rectal) often have reduced bioavailability due to absorption barriers and first-pass metabolism.
Factors Affecting Bioavailability:
Absorption: The drug must cross biological membranes (e.g., intestinal epithelium) to enter the bloodstream. Poor solubility or permeability reduces bioavailability.
First-Pass Metabolism: Drugs absorbed via the gastrointestinal tract are transported to the liver via the portal vein, where they may be metabolized before reaching systemic circulation.
Drug Formulation: The physical and chemical properties of the drug (e.g., solubility, stability) and the type of dosage form (e.g., tablet, capsule) influence absorption.
Route of Administration: Non-oral routes (e.g., transdermal, inhalation) may bypass first-pass metabolism, improving bioavailability.
Physiological Factors: Gastric pH, motility, enzyme activity, and interactions with food or other drugs can impact absorption and metabolism.
Types of Bioavailability:
Absolute Bioavailability: Compares the bioavailability of a drug given via a non-IV route (e.g., oral) to its IV form.
Relative Bioavailability: Compares the bioavailability of one formulation of a drug to another (e.g., generic vs. brand-name).
Clinical Implications:
Drugs with low oral bioavailability may require higher doses or alternative administration routes (e.g., IV).
Bioavailability variations between formulations are critical when switching medications, as they may affect therapeutic outcomes.
Understanding bioavailability is essential for drug design, pharmacokinetics, and dose adjustments.
Examples of Bioavailability
High bioavailability drugs: Ciprofloxacin, levofloxacin (≥90% when given orally).
Low bioavailability drugs: Propranolol, nitroglycerin (significant first-pass metabolism)
how does acyclovir work?
-Tx HSV & varicella zoster
-Inhibits nucleic acid synthesis
-cells infected with these viruses contain an enzyme called thymidine kinase (acyclovir is a substrate for this)
Which antibiotics are bacteriostatic?
-macrolides (e.g erythromycin, clarithromycin)
-lincosamides (clindamycin)
-Chloramphenicol
-Tetracyclines
-Trimethoprim
how do antifungals work?
Azoles (Fluconazole, miconazole, ketoconazole) - prevent conversion of lanosterol-> ergosterol which is an essential component of the cell membrane.
inducers
inhibitors
how do you measure clearance using a graph of
1. IV
2.PO
1.Cl=dose/AUCiv
2. We can only workout clearance of PO if we know the bioavailability fraction.
IF BF= AUCo/AUCiv
then Cl=(dose x BF)/ AUCo
which drugs can saturate their enzyme system & go from zero order kinetics to first order as the concentration drops & enzymes are no longer at maximal activity
thiopental
phenytoin
what is the limiting factor in first order kinetics and why
Hepatic blood flow, because enyzyme system is not fully saturated.
Propofol & Fentanyl are both dependent on hepatic blood flow (therefore follow first order kinetics) & have high HER (concentration gradient between plasma & hepatocytes).
Drugs at concs above their KM have a low ER as intracellular conc is close to plasma.
How much of the following volatiles are metabolised?
1. Halothane
2. Sevo
3. Enflurane
4. Isoflurane
5. Desflurane
1.Halothane: 20-40%- metabolised in liver to TFA, bromide & chloride. Increased risk of halothane hepatitis.
2.Sevo: 2-5%- (CYP2E1) -associated with fluoride & hexafluoroisopropanol ion production which are renally excreted
3.Enflurane: 2-3%- produces fluoride ions
- Iso: 0.2%- metabolised into trifluoroacetic acid (TFA) & small amount of fluoride ions
- Des: 0.02% - almost entirely eliminated via exhalation
How to calculate loading dose?
What would loading dose be if a target of 6mcg/ml is required in a volume of distribution of 16L?
loading dose= Cdesired x Vd / F
Where bioavailability (F)= 1 (100%)
The central compartment is the initial volume of distribution. This is used to calculate the initial dose for a target concentration in the plasma.
96mg
how to calculate Vd using half life?
E.g A drug behaves according to a single-compartment model. Experimentally you find that it has a half-life of 70 min and a clearance of 100 ml/min. What would be its approximate volume of distribution?
t1/2= (0.693.Vd)/Cl
Vd= (t1/2.Cl )/0.693giv
70x100/0.693 =10.1L
Drugs that remain in the intravascular space have a small VoD (<10L)
What drugs remain intravascularly, give an example?
Drugs need to be large and polar & highly protein bound to remain intravascular, e.g heparin, with an inital VoD of about 40-70ml/kg
Heparin is a large glycosaminoglycan molecule composed of long chains of carbohydrate molecules.
5000-30,000 Daltons in size
It binds to antithrombin III, which then inhibits thrombin & factor Xa, preventing blood clotting.
Because of its large size, heparin does not easily cross BBB or placenta.
What is the VoD of drugs restricted to extracellular space & why?
Give an example
14L, restricted due to being small & polar, unable to pass through cell membranes.
e.g muscle relaxants
- what is the volume of total body water?
- Which drugs can be intracellular? give an example
- What can be used to measure total body water?
- 42L
- drugs must be small and able to pass through cell membranes e.g ethanol.
- Deuterium (an isotope of hydrogen) can be used to measure total body water as it distributes freely.
- what are the components of hartmanns?
- what is the osmolality of hartmanns?
- blood osmolality?
1.
-Na: 131
-CL: 111
-K: 5
-Calcium: 2
-Lactate: 29
- Osmolality of Hartmanns: 278 mosmol/kg
3.Osmolalty of blood:280-300 mosmol/kg
- components of 0.9% NaCl
- osmolality
154 Na
154 Cl
Osmolality 308 mosmol/kg
what are michaelis menten kinetics?
describe the reaction of substrate and enzyme to form enzyme substrate complex (ES)
kinetics are saturatable therefore start as first order (Rate is proportional to substrate conc), becoming zero order (rate constant), as enzyme sites become occupied.
constant Km is conc of substrate at half maximal reaction velocity (1/2 Vmax)
an enzyme is a protein catalyst, as as defined is not consumed by the reaction it catalyses
which Abx are bactericidal
-penicilins
-aminoglycosides ( gentamicin, tobramycin, streptomyycin)
