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Animal Disease 1 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Define drug.

A

A chemical substance of known structure other than a nutrient or an essential dietary ingredient which when administered to a living organism produces a biological effect.

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2
Q

Define medicine.

A

A chemical preparation which usually contains 1 or more drugs and is administered with the intention of producing a therapeutic effect.

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3
Q

Define pharmacology.

A

The study of how drugs interact with biological organisms.

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4
Q

Why may drugs not be beneficial?

A

Therapeutic – may be beneficial. Side effects or toxicity – may be harmful.

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5
Q

What are 4 reasons drugs are given?

A
  • To produce a cure
  • To suppress symptoms
  • To prevents a disease or symptom (prophylactic)
  • (For recreation, largely man)
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6
Q

What determines whether to give a drug?

A
  • The likely benefit to the patient
  • The probability of an adverse event and its severity
  • The healthcare/social cost of adverse effects
  • The financial cost of the drug to be used in relation to the benefit
  • Is it licensed for use in this species for this condition? If not could still give drug – veterinary cascade
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7
Q

What are the properties of a therapeutic drug?

A
  • Specific effects
  • Beneficial vs adverse effects of the drug
  • Selectivity of action – does the drug bind selectively to target?
  • Does drug binding to target produce wanted effect without side effects?
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8
Q

Why might drugs not work?

A
  • Insufficiently selective
  • Changes in structure and function
  • Lack of knowledge of disease process
  • Species variability
  • Drug interactions
  • Idiosyncratic reactions
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9
Q

What is the therapeutic index of a drug?

A

Licensed small molecules drugs tend to work in the therapeutic effect range of low concentrations. As concentration is increased, drug may start interacting with other proteins in the body, which is when we begin to see side effects. When increased even more, it reacts with many proteins, receptors and enzymes and effecting many parts of the body. So giving an animal more drugs for greater beneficial effect may work within that therapeutic window but any further, serious side effects may begin to appear.

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10
Q

What happens when a drug is administered?

A
  1. Absorption
  2. Distribution
  3. Exertion of its pharmacological effects
  4. Metabolism
  5. Excretion
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11
Q

Define pharmacodynamics and pharmacokinetics.

A

Pharmacodynamics – the effects of the drug on the body.

Pharmacokinetics – the way the body deals with the drug.

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12
Q

Name the 6 molecular targets for drug action.

A

Receptors – transduce signal from drug

Enzymes – activate or switch off

Transporters – carry molecules across membrane

Ion channels – open or close

Nucleic acids – affect gene transcription (some anti-cancer drugs)

Miscellaneous – lipids, metal ions, etc

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13
Q

What is tetrodotoxin?

A

Tetrodotoxin (TTX) is a blocker of sodium ion channels (problem for action potentials and cardiac cycle) and is produced by puffer fish. LD50 in man is 5m/kg. 1-2mg is lethal.

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14
Q

Describe fluoxetine/Reconcile as a selective serotonin reuptake inhibitor.

A
  • Serotonergic neurones contain vesicles of serotonin which is released from action potentials and enters the synaptic cleft.
  • Activates post and pre-synaptic receptors.
  • After it has had its action, it is re-taken back up into the neurone by the serotonin transporter.
  • Fluoxetine will block that serotonin transporter and stop serotonin re-uptake in the synapse.
  • Serotonin can stay longer in the synaptic cleft to interact with receptors.
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15
Q

How did Langley investigate effects of nicotine and curare in 1905?

A

Took a preparation of muscles with a nerve attached. Muscle contracts when the nerve is stimulated. This can be mimicked using a variety of drugs:

  • Nicotine – causes twitch.
  • Curare – blocks nicotine and nerve stimulation, muscle stimulation unaffected.

He proposed that ‘there is a chemical combination between the drug and a constituent of the cell – receptive substance’ which we now know as receptors.

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16
Q

Name the 4 receptor superfamilies.

A

Ionotropic (receptor operated channel)

Metabotropic (G protein coupled)

Tyrosine kinase

DNA linked

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17
Q

Give the speed and locations of each of the receptor superfamilies.

A

Ionotropic: fast (ms). Cell membrane and some on membranes inside the cell.

Metabotropic: medium (sec-min). Cellular membrane.

Tyrosine kinase: medium (sec-min). Cellular membrane.

DNA linked: slow (hours). Intracellular, many present in cytoplasm

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18
Q

What is the effect of ionotropic receptors?

A

Extracellular amino terminal, where the ligand binds. Regions which span the membrane and loop into the membrane, which are important to form the pore of ion channels. Intracellular carboxyl terminus. Made up of a number of subunits, which opens when the ligand binds.

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19
Q

What is the effect of metabotropic receptors?

A

They are associated with G proteins, which are made up if 3 subunits: alpha, beta and gamma.
Alpha is bound to GDP, which unbinds when the agonist binds. Dissociated to GTP and the alpha subunit which can go off to effect things in the cell. Beta and gamma stay together and can go off and effect things in the cell.

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20
Q

What is the effect of tyrosine kinase receptors?

A

When ligand binds, there is phosphorylation of tyrosine residues on the receptors.May also get dimerization – 2 receptor molecules come together and lead to an enzyme cascade.

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21
Q

What is the effect of DNA linked receptors?

A

When ligand binds, move to nucleus. Activate or inhibit gene transcription. Activated by hormones.

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22
Q

What are the 3 G coupled proetins classified by G-alpha?

A

Gs – stimulate adenylate cyclase, increase cAMP production, PKA activation

Gq – stimulate phospholipase C, increase IP3 and diacylglycerol DAG, lead to PKC activation and calcium release from endoplasmic reticulum

Gi/o – inhibit adenylate cyclase, decrease cAMP production,  subunit inhibit Ca2+ channels and activate K+ channels

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23
Q

What are receptor subtypes?

A

The existence of multiple receptor subtypes provides the opportunity to develop more specific drugs.

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24
Q

Describe the 4 different histamine receptors as an example of receptor subtypes.

A

Histamine has different effects on different tissues:
- Contracts in smooth muscle for H1 receptors in bronchi
- Stimulates gastric secretion in H2 receptors

Histamine analogues can be designed to be selective for only one receptor subtype:
- H1 antagonists = anti-allergy
- H2 antagonists = anti-ulcer

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25
Q

Distinguish agonists and antagonists.

A

Agonists activate a receptor and antagonists reduces/blocks an agonist response. Both bind to receptors

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26
Q

What occurs when an agonist and when an antagonist bind to a receptor?

A
  • Receptor and a drug forms a drug receptor complex.
  • When the agonist binds to the receptor, it activates it, leading to a transduction mechanism, depending on the receptor, and cellular change.
  • When the antagonist binds to the receptor, it prevents an agonist binding to the receptor bit does not cause a transduction mechanism in itself, but prevents cellular change.
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27
Q

Define affinity.

A

How many drug-receptor complexes are formed.

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28
Q

Define efficacy.

A

The maximum response achieved by a dose.

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29
Q

Define specificity.

A

Influenced by affinity and efficacy. How specific is a particular drug for activating/inhibiting a particular receptor? (no drug is truly specific – as the concentration is increased it will exert other actions).

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30
Q

What is the dissociation constant, Kd?

A

The KD is the concentration of the drug that occupies 50% of the receptors. Lower the KD and the higher the affinity.

Kd = [D][R] / [DR]

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31
Q

What is the receptor occupancy equation?

A

Proportion of receptors occupied, P.

P = [D] / [D] + Kd

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32
Q

How can receptor binding be measured?

A

Can use radiolabelled drug to measure binding in a tissue: for example. H3, C14, S35, I125, P32. Incubate tissue with different concentrations of drug, measure how much binds to the tissue.

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33
Q

Describe a P - [D] curve.

A
  • Rectangular hyperbola
  • Rt, total number of receptors is asymptote on y-axis
  • Kd can be found by drawing axis at the curve at P=0.5
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34
Q

Distinguish linear and semi-log P-[D] graphs.

A

Greater sensitivity on log graph, making it more accurate

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35
Q

What are the 2 parameters that determine the ability of an agonist to produce a pharmacological effect?

A
  1. Binding of drug to receptor, determined by affinity
  2. Following binding, activation of et receptors and production of response, determined by efficacy – how well a drug will activate a drug-receptor complex.
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36
Q

What is non-linear response with occupancy?

A

Steps are likely to amplify the signal several fold, with the EC50 value to the left of the Kd.

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37
Q

Define EC50.

A

Effective concentration 50. The concentration of drug that gives 50% of the maximum response.

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38
Q

How do agonists and antagonists differ in efficacy?

A

Agonists have the same efficacy and produce a response. Antagonists have no efficacy and bind to the receptor but do not produce a response. Different agonists have different levels of efficacy.

Separation is less between curves of response and occupancy for different agonists, as they have different efficacies.

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39
Q

Explain how magnitude of response is not proportional to receptor occupancy due to receptor reserve.

A
  • Some agonists produce a maximum response with only a very low occupancy, such agonists have high efficacy.
  • The greater the efficacy, the bigger the separation between KD and EC50.
  • The receptor reserve will vary between different agonists that act at the same receptor.
  • KD / EC50 gives a rough measure of the reserve
  • Weak agonists have low efficacy and have an EC50 close to the KD. DR complex is mostly DR(inactive) form
  • Strong agonists have high efficacy, where the KD is much greater than the EC50. DR complex is mostly DR* form
  • If KD gives a rough measure of the reserve, if efficacy is lowered, EC50 gets larger and reduces receptor reserve. The concentration-response curve moves to the right.
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40
Q

When does a response-concentration graph shift right?

A

Lowered efficacy

Lowered number of receptors

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41
Q

Define potency.

A

Relates to how much drug is needed to produce a particular response. Both agonist and antagonists.

42
Q

What is partial agonism?

A

Partial agonist is an agonist that has to occupy all the receptors to evoke the agonists response. Their maximum response is less than the full response the tissue is capable of.

Partial agonists have low efficacy and so high occupancy is required to get a response. They are characterised by having EC50 values close to their KD values.

43
Q

Name the 4 types of drug antagonism.

A
  • Competitive – binds at the agonist recognition site preventing access of normal ligand
  • Non-competitive – does not bind at the agonist site but inhibits agonist binding in another way
  • Uncompetitive – this is when binding occurs to an activated form of the receptor (use dependent)
  • Physiological
44
Q

What is competitive antagonism?

A

Reducing number of receptors that can bind to agonist, being taken up by antagonist. Increasing agonist, there is a better chance of agonist displacing antagonist.

45
Q

What happens to a response-concentration curve when concentration of antagonist is increased?

A

Parallel shift in concentration-effect curve to the right (if reversible)

No reduction on maximum response

46
Q

What is competitive irreversible antagonism?

A

Antagonist competes with the agonist for the same site bit binds irreversibly/covalently, as antagonists can bind reversibly or irreversibly.

47
Q

What is non-competitive antagonism?

A
  • Allosteric modulation – bind to somewhere other than where the agonist binds
  • Ligand gated ion channel blockers
  • Block later in pathway from receptor activation to response: such as enzyme inhibitors and calcium channels blocker

Reduced maxima when concentration increases.

48
Q

What is physiological antagonism?

A

One drug may antagonise the action of another via an action on an independent molecular target.

49
Q

Give 4 examples of physiological antagonism.

A
  • Noradrenaline increases heart rate and acetylcholine decreases heart rate
  • Noradrenaline dilates the pupil and acetylcholine constricts the pupil
  • Endothelin increases blood pressure and nitrates decreases blood pressure
  • Histamine constricts bronchioles and salbutamol relaxes bronchioles
50
Q

Describe the concept of constitutive activity.

A
  • Zero level of activity
  • If agonist, there is a response
  • If antagonist, blocks receptor but has no response on its own
  • But G protein coupled receptor have a basal level of activity, even with no agonist present, there is slight activation of the receptors.
  • This is constitutive activity/level
  • Adding antagonist increases this and antagonist had no effect
  • And inverse agonist will switch receptor to a less active state/off
51
Q

What are inverse agonists?

A

Drugs that exhibit efficacy. Actions are blocked by competitive antagonists.

  • Agonist binds to receptor or stabilise activated receptor
  • Inverse agonist binds to activated receptor and inactivates it/stabilises receptors in an inactive DR complex
  • Can switch off receptor fully or can be partial inverse and just switch receptors to less active state
52
Q

Define pharmacokinetics.

A

Interpreting data on changing concentrations or amounts of a drug and its metabolites in blood, plasma, urine and other body tissues and fluids.

53
Q

What is the meant by the acronym ADME?

A
  1. Dose of the drug administered and A bsorbed
  2. Drug in systemic circulation
  3. Drug in tissues of D istribution and can go back into systemic circulation
  4. Drug can be M etabolised or E xcreted, either from systemic circulation or tissues of distribution
54
Q

What is enteral drug administration?

A

Via the GI tract. So, the route for enteral is oral or rectal. Drugs are given orally because it is easy. Compliance, have to rely on owner to give animal drugs.

55
Q

What is parental drug administration?

A

Not via the GI tract. Routes:

  • Intravenous, effects are very rapid, for example fentanyl
  • Intramuscular, for example morphine
  • Subcutaneous, for example insulin
56
Q

Define oral bioavailability.

A

Oral bioavailability (F) of a drug – the fraction of the orally administered drug that reaches the systemic circulation.

57
Q

What are the factors affecting oral bioavailability of a drug?

A
  • Poor absorption from the gut
  • Breakdown of drug in the gut
  • Fist pass effect
58
Q

What is the first pass effect?

A

Orally administered drug breaks down in the stomach or intestine and enters via the portal blood system to the liver before it can be released to the systemic circulation. In the liver, drug can be broken down into metabolites. For example, morphine is not always taken orally, as only a quarter will reach the systemic circulation, as the rest is broken down in first pass through the liver.

59
Q

What are the factors affecting drug absorption at a membrane?

A
  • To be absorbed, drugs usually have to cross membranes, such as GI mucosa, mainly by passive diffusion. So a major factor in lipid solubility of the drug.
  • pKa of the drug (pH at whicg it is 50% ionised
  • pH of the absorbing surface
60
Q

Why are pH and pKa important to consider with drugs?

A

Many drugs are either weak acids or weak bases, and so can exist in either ionised or unionised forms, depending upon the pKa of the drug and the pH of the solution. Ionised drugs do not cross membranes.

61
Q

State the Henderson-Hasslebach equation for weak acids and for weak bases.

A

Weak acid: pH = pKa + log ([ionised] / [unionised])

Weak base: pH = pKa + log ([unionsed] / [ionised])

62
Q

What is the main site of drug absorption?

A

Small intestine is the main site of absorption, as its surface area is much bigger than the stomachs.

63
Q

What is drug distribution?

A

Drug distribution – penetration of drug into tissues and organs from the blood.

Distribution can be considered in terms of body compartments. These will vary between species.

64
Q

What are the factors affecting drug distribution?

A

The degree of distribution often depends upon:
- Lipid solubility
- Plasma protein binding – if binds to albumin, for example, it is less likely to leave that tissue and enter another.

Rate of distribution depends on:
- Blood flow – for example, high to the brain and low to fat

65
Q

Define apparent volume of distribution and what it is used for.

A

(Vd) – volume of water in which drug would have to be distributed to give its plasma concentration (litres/kg).

  • Partly determines plasma half-life of the drug – how long it stays around in the body
  • Used in pharmacokinetic calculation to design dosing schedules
66
Q

What are the 3 pharmacokinetic parameters?

A

Volume distribution (Vd)
Plasma half life (t0.5)
Clearance

67
Q

Define elimination.

A

The excretion and metabolism of drugs together constitute elimination.

68
Q

Define excretion.

A

Movement of drug or metabolites form the inside to the outside of the body. Major routes via urine, faces, milk, bile, vomit

69
Q

Define metabolism.

A

Distinct chemical change in drug structure. Major routes via liver, plasma

70
Q

Define half-life of a drug.

A

T0.5 – the plasma half-life of a drug is the time it takes for the plasma concentration of the drug to fall to half its initial value.

A short half-life means that the body eliminates the drug quickly and that doses have to be given more often than drugs with long half-lives.

71
Q

How can elimination be quantified?

A

Rate of elimination of mass/time seems straightforward but clearance is the usual parameter used with regard to drug elimination, as rate of elimination changes all the time.

Rate of elimination = clearance x plasma concentration

Rearrange: clearance = rate of elimination / plasma concentration

72
Q

What is clearance?

A

Equal to the amount of plasma which is cleared of its drug content in unit time. It is a useful measure since the rate of elimination of most drugs varies with plasma concentration, but clearance stays fairly constant. Unit is mlmin-1 or Lh-1. Note that clearance is not a constant lie a binding constant, it can change under certain circumstances, such as liver or renal disease.

73
Q

Describe the first order of drug elimination.

A

Most common order. Cp-t graph.
- The half-life is constant.
- Clearance is not changing but the rate of elimination depends on how much drug is present and is faster the higher the plasma concentration.
- Described by exponential equation: Ct = C0 x e^-ket, where k is the rate of constant elimination.
- T0.5 = 0.693 x Vd / clearance

74
Q

Describe the zero order of drug elimination.

A

Less common. Rate of process is independent of drug concentration. The half-life can vary. Few drugs eliminated this way. Alcohol, phenytoin and overdoses are eliminated this way. Line 1 has a longer half-life, as there is higher Cp.

75
Q

Distinguish a Cp-t graph for a bolus injection and an orally administered drug.

A
  • Rising phase on oral curve represents absorption
  • Decreasing phase on oral curve represents elimination
  • Peak of oral curve is when absorption and elimination rates are equal
  • IV bolus is decreasing exponential
76
Q

How can the rate of elimination and the rate of infusion be calculated?

A

In a 1st order process, Cp rises until a steady state is reached (Css), when rate of infusion = rate of elimination.
This is because as the Cp rises, so does the rate of elimination. So shape of curve due to changing rate of elimination.

Rate of elimination = Cp x Cl = Css x Cl

Rate of infusion = Css x Cl

77
Q

How many half-lives does it take to reach steady state?

A

5

78
Q

Describe the Cp-t graph for an overdose of an orally administered drug.

A
  • Each peak is an oral dose
  • There is a Css average = individual dose (D) x oral bioavailability (F) / time x clearance
  • By increasing individual dose (purple) and increasing interval between doses, you get the same Css average.
  • Difference between peaks and trough changes. Be careful as this, as Cp does not want to be too high at some stages and too low at others to be effective.
79
Q

What aspects of a drug can be excreted by the kidney?

A

This can involve the drug, its metabolites, or both. Some drugs are subject to extensive renal excretion, so they are unchanged/not metabolised, for example gentamicin and methotrexate. Generally, drugs and metabolites that are not lipid soluble are excreted by this route.

80
Q

What are the 3 renal processes that determine drug excretion?

A
  • Glomerular filtration at the Bowmans capsule
  • Proximal tubule – active secretion of metabolites into the lumen of the nephron
  • Distal tubule – reabsorption of drugs into the blood from the tubule

So only drugs into the urine are non-lipid soluble drugs.

81
Q

How can changes in urinary pH alter drug excretion?

A

For a weak acid, urinary excretion can be increased by making the urine more alkaline, for example with sodium bicarbonate.

For a weak base, urinary excretion can be increased by making the urine more acidic, for example with ammonium chloride.

82
Q

If a weak base is being excreted from the kidney, what happens if the nephron is made more acidic?

A
  • Excretion of weak base, methamphetamine, over time.
  • More alkaline decreases excretion and more acidic increases excretion massively.
  • Methamphetamine gets into the lumen of the nephron and some is reabsorbed into the distal tubule.
  • But if made more acidic in the nephron, more of the methamphetamine will become ionised and so cannot be reabsorbed, and so is excreted into the urine.
83
Q

How can the effect of pH on ionisation be proven mathematically?

A

For a weak base: pH = pKa + log ([unionised] / [ ionised])

7 = 8 + log ([unionised] / [ionised])
-1 = log ([unionised] / [ionised])
0.1 = [unionised] / [ionised]

At pH6, -2 = log ([unionised] / [ionised]) > 0.01 = [unionised] / [ionised]

By reducing the pH by 1, the fraction of weak based ionised increases 10 fold and so less is reabsorbed.

84
Q

What do metabolites do?

A
  • Drug > inactive metabolite
  • Durg > active metabolite
  • Drug > toxic metabolite
  • Drug or prodrug > active drug. This is because the active drug does not have a good bioavailability so prodrug > active drug can reach the target site.
85
Q

What is the process of hepatic drug metabolism?

A
  1. Drug
  2. Phase 1
  3. Derivative
  4. Phase 2
  5. Conjugate
86
Q

Describe phase 1 of hepatic drug metabolism.

A

Drug derivative formed by oxidation, reduction or hydrolysis, often introducing a reactive site into or exposing a reactive site on, the drug molecule.

  1. Drug metabolising enzymes in the endoplasmic reticulum of the liver (and some other tissues) are called microsomal enzymes.
  2. In particular, mixed function oxidases are important in the oxidation reactions listed above. Several enzymes are involved, the most important being cytochrome P450.
  3. Product is more reactive than the drug.
87
Q

Describe phase 2 reactions of hepatic drug metabolism.

A

Conjugation/joining together of the species formed in phase 1 with polar molecules making the metabolite less lipid soluble, and hence easier to excrete in urine.

  1. Generally occurs in the cytosol of liver cells.
  2. Polar molecule added to drug and makes the whole molecule more polar.
88
Q

Describe the hepatic drug metabolism of paracetamol.

A
  1. In the liver, paracetamol normally undergoes phase 2 reactions and doesn’t normally have to undergo a phase 1 reaction.
  2. In an overdose, these pathways become saturated and paracetamol must be metabolised by a different pathway.
  3. This is a phase 1 pathway and produces N-acetyl-p-benzoquinone imine/NAPQI.
  4. There can be some glutathione conjugation, but this runs out quickly.
  5. NAPQI reacts with cell proteins to cause hepatic cell damage, which can be fatal.
89
Q

Why are cats so much more sensitive to paracetamol?

A

In cats, there is very little glutathione so they are very susceptible to producing NAPQI. In cats, this can also react with haemoglobin in blood and prevents them carrying oxygen, which paired with liver damage, is often fatal. Dogs do have some glutathione oxidation so are not as susceptible as cats.

90
Q

What are the factors affecting drug metabolism?

A
  • Enzyme induction
  • Enzyme inhibition
  • Genetic polymorphism
  • Disease
  • Age
91
Q

How does enzyme induction affect drug metabolism?

A

Some drugs and environmental pollutants induce increased expression of cytochrome P450 enzymes over a number of days/weeks. This can cause the failure of some drugs and itself to produce a significant therapeutic effect.

  • Non induced patient has 1st order intravenous bolus injection curve.
  • T0.5 – 0.693 x Vd / Cl
  • Induced state has a shorter half-life and so reduces the effectiveness of these other drugs and itself
92
Q

How does enzyme inhibition affect drug metabolism?

A

Some drugs directly inhibit cytochrome P450 enzymes. This can increase ethe likelihood of seeing adverse effects/toxicity in the patient. Unlike enzyme induction, this occurs rapidly and as soon as the drug is given.

  • Normal patient has 1st order curve
  • Half life increases in inhibition patient
  • Leads to too much of a drug in the plasma and increases the incidence of adverse or even toxic effects.
93
Q

How does genetic polymorphism affect drug metabolism?

A

Poor ability to metabolise drugs by some groups of people. For example, a human experiment with isoniazid:

  • At time=0h, people given isoniazid
  • 6 hours later measured Cp of isoniazid.
  • Frequency with that Cp vs Cp graph.
  • Some people had higher Cp of isoniazid 6 hours later than others
  • This is due to genetic polymorphism
  • Defect in phase 2 enzyme (acetylators)
94
Q

Name 4 different disease and how they affect drug metabolism.

A
  • Liver function for drugs mainly metabolised in the liver (hepatitis, liver cancer, cirrhosis)
  • Renal function for drugs mainly excreted unchanged in urine
  • Thyroid function (affects liver metabolising enzymes)
  • Cardiovascular disease – rate of delivery of drug to liver/kidney

For example, half life for diseased heart increased

95
Q

Define a biologic.

A

Products produced from living organisms, and are larger molecules, such as monoclonal antibodies. Not as common in veterinary medicine but increasing popularity.

96
Q

How do biologics work differently from small molecule drugs?

A
  • Absorption is always parental, usually subcutaneously or intravenously
  • Time to peak plasma volume is a long time/days
  • Small distribution volume
  • Often move in lymph for distribution
  • Half-life tends to be long/weeks
  • Mechanisms for elimination may include proteolysis by lysosomes for example.
97
Q

What are drug interactions?

A

Response to a combination of drugs can be different to that which is predictable from actions of drugs administered alone. These can be beneficial or harmful.

98
Q

What are pharmacodynamic drug interactions?

A

Based on mechanism. Aspirin and warfarin for example both have anticoagulant effects but can both lead to stomach bleeding. So given at the same time, there is an increased likelihood of stomach bleeding based on their mechanism of action.

99
Q

What are pharmacokinetic drug interactions?

A
  • Absorption: tetracycline antibiotics can react with milk and reduce absorption
  • Distribution
  • Metabolism – induction and inhibition
  • Excretion: methotrexate can react with NSAIDs and to inhibit methotrexate release and increases its Cp and can have serious adverse/toxic effects
100
Q

A drug is filtered at a high rate into the lumen of the nephron, yet almost none is detected in the urine. Why might this be? How do you think that drug is eliminated from the body? The metabolite of another drug is poorly filtered at yet is heavily excreted in urine. Why might this be?

A

The drug is unionised so is able to be reabsorbed over the lipid membrane of the nephron. Metabolised by the liver. Actively secreted by proximal tubule.

101
Q

A patient with congestive heart failure is administered an antibiotic drug that is eliminated by a combination of hepatic metabolism and renal excretion. The value of clearance of the drug in this patient is one third of that in a healthy person. What will be the plasma half-life of the drug in the diseased patient compared to the healthy person?

A

3 times longer. Clearance reduces, meaning half life increased 3 fold provided that Vd stays constant.

Animal Disease 1 (25 decks)

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