Clinical Pharmacology Flashcards
Pharmacokinetics
Summary of how a drug is absorbed and distributed around the body
Pharmacodynamics
a) 5 routes that drugs can interact with the patient
b) 2 reasons for drugs being used
a) 1. ion channels 2. nuclear receptors 3. enzymes 4. G-protein coupled receptors 5. receptor kinases
b) 1. initiate a series of biochemical reactions 2. alter cellular physiology
Pharmacodynamics
Define
a) Strong agonist
b) Weak agonist
c) Partial agonist
d) Antagonist
e) Competitive antagonist
a) causes a maximal response even when only a small number of receptors are occupied
b) only causes a maximal response when large number of receptors are occupied
c) drug which fails to produce a maximal response even when all the receptors are occupied
d) drug which binds to the receptor producing no cellular effect, but inhibits access of agonists to the receptor site hence preventing their effects
e) competes with agonist for receptors, increasing concentration of agonist will displace the antagonist from the receptor hence surmounting the antagonist effect
Pharmacodynamics
Define
a) Noncompetitive antagonist
b) Irreversible antagonist
c) Physiological antagonist
d) Antagonism by neutralisation
a) binds to site other than receptor domain inducing a conformation change in the binding site to prevent agonist binding. Increasing concentrations of agonist will not over-come the antagonist as they bind at separate sites therefore the antagonist effect is insurmountable
b) combine permanently with the receptor at the agonist binding site hence antagonist effect is insurmountable
c) two agonists in unrelated reactions cause opposing effects to cancel each other out
d) two drugs bind to each other so that each drug becomes in active
Pharmacodynamics
Define
a) Efficacy
b) Potency
c) EC50
d) LD50
e) Therapeutic index
f) Margin of safety
a) degree to which a drug is able to induce its maximal effects
b) is measured as the amount of drug required to produce 50% of its maximal effects
c) Effective concentration: concentration of drug that induces a clinical effect in 50% of patients
d) Lethal dose: concentration of drug that induces death in 50% of a population
e) measure of drug safety (LD50/EC50)
f) margin between therapeutic and lethal doses of a drug
Pharmacokinetics
Affecting drug absorption - Bioavailability
What does oral bioavailability depend on (7)
The proportion of the administered dose that reaches the central compartment.
Influenced by drug formulation
Oral administration: lower and less predictable bioavailability than other routes
1. pKa of the drug
2. pH at the site of absorption
3. Surface area
4. Feeding
5. Disease
6. Drug transporters
7. First-pass effect
Pharmacokinetics
Affecting drug absorption - How does IM bioavailability compare to oral
Dependent on the site of injection
More consistent absorption, more rapid onset and much better bioavailability than oral route
Rate of absorption depends on perfusion of blood flow to the tissue (decreased with hypotension or local vasoconstriction)
Problems: pain, muscle damage, haematoma, abcessation, inadvertant iv
Pharmacokinetics
How do routes of administration affect drug absorption
a) Subcutaneous
b) Topical
a) Absorbance resembles intramuscular administration, but its more variable -> Influenced by autonomic control over blood flow and dehydration, heat, cold, stress
b) Highly lipid soluble drugs in areas of high blood flow, avoids first pass metabolism
Topical administration of ivermectin in ruminants
Pharmacokinetics
Factors that determine drug distribution (5)
- Membrane permeability
- Plasma protein binding
- Blood flow
- Depot storage
- Apparent volume of distribution (a measure of where drugs are distributed in the body
Pharmacokinetics
Examples of how plasma protein binding can affect drug distribution (4)
- Acidic drugs bind albumin
- Basic drugs bind to α1-acid glycoprotein
- Drugs can also bind lipoprotein and erythrocytes
- Protein bound drug cannot bind receptors, be metabolized (protein binding lengthens half life) or be excreted. The drug reaches an equilibrium of bound and free then equilibrates between blood and tissues
Pharmacokinetics
a) How does depot storage affect drug distribution
b) What specific body sites should drug distribution be considered
a) Lipophilic drugs accumulate in fat -> slow gradual release of drug from the fat depot (thiopentone in an obese patient appears sedated for a longer time that a lean one). Calcium binding drugs such as tetracycline accumulates in bone and teeth
b) 1. Blood-brain barrier 2. Placental barrier 3. Blood-testis barrier (stallions/bulls/rams) 4. Blood-milk barrier (public health)
Pharmacokinetics
Drug metabolism
a) Phase I
b) Phase II
c) Sites of excretion (8)
a) Oxidation by CyP450
b) Conjugation
c) 1. Liver 2. Kidney 3. GI-tract 4. Lung (exhalation) 5. Saliva (ruminants) 6. Skin (very lipophilic drugs; hair -> doping) 7. Milk (public health considerations) 8. Eggs (public health considerations)
Pharmacokinetics
Neonatal considerations
a) Puppies vs foal neonatal period
b) Features of pharmacokinetics in the neonate (6)
a) Puppies - 10-12 weeks, foals - 7 days
b) 1. increased drug absorption
2. lower binding to plasma proteins
3. lower ratio of body-fat to fluids
4. larger extracellular fluid volume
5. increased permeability of the blood-brain barrier
6. slower biotransformation and elimination
Drug interactions
How can drug interactions cause
a) altered absorption (4)
b) altered metabolism (2)
a)
- inhibition of absorption (eg anti-ulcer drugs)
- alteration of gut motility
- change in pH (eg anti-ulcer drugs)
- alteration of bacterial flora (eg broad spectrum antibiotics)
b)
- Cyp P450 inhibition (eg fluconazol, fluoroquinolones, omeprazol)
- Cyp P450 induction (eg broccoli, barbituates, rifampin, omeprazol)
Drug interactions
How can drug interactions cause
a) Plasma protein binding
b) Altered excretion
c) Receptor interactions
d) Physiochemical
a)
- compete for protein bindig sites
- increasing concentration of free drug in plasma
- toxic effects
b)
- drugs altering renal function
- changing urine pH can alter excretion of acidic and basic drugs
c)
- agonists and antagonists being co-administered
d)
- eg inactivation and precipitation of penicillin with phenytoin/B complex vitamins
- eg carbenicillin and gentamicin
Drig interactions
Describing drug interactions
a) Additive
b) Synergistic
c) Potentiated
d) Antagonistic
e) Neutral
a) Response elicited by combined drugs is equal to combined responses of individual drugs
b) Response elicited by combined drugs is greater than the combined responses of the individual drugs.
c) A drug with no effect enhances the effect of a second drug
d) Drug inhibits the effect of another drug
e) No net effect seen despite the pharmacokinetics of one or both drugs being substantially altered
Drug interactions
How can interactions with food affect drugs (7)
- Gastric emptying
- Dissolution of drugs (eating causes gastric pH changes)
- Bile acid activity
- Pancreatic and intestinal mucosal enzyme activity
- Splanchnic blood flow (increasing bioavailability)
- Barrier to absorption
- Pharmacologically active food substances
Therapeutic drug monitoring
What does TDM involve and when to use
- collection of blood from animal receiving drug treatment
- analyse drug concentration, compare to standard range
- use if 1. patient isn’t responding to therapy/showing signs of toxicity 2. long term therapy when drug is known to alter pharmacokinetics
Effect of disease on drug use
How does GI disease affect drug use (4)
- . Vomiting -> decreased gastric emptying
- Diarrhea -> increased GI motility
- Alterations in GI pH -> changes in absorption
- Alterations in absorptive surface -> increased absorption
