M1 L4: Drug Reactions

Question 1

Adverse Drug Reactions

Answer 1

harmful or unintended responses from drug

side effects could be bad or okay - ADRs are very bad

Question 2

2 causes of ADR

Answer 2

1. iatrogenic
   - error in prescribing, transcribing, dispensing, or administering drug
2. unexpected drug toxicity
   - unintended drug response

Question 3

2 types of ADR

Answer 3

1. pharmacodynamic
   - extension of therapeutic effect
   - effects in non-target tissues or organs
2. non-pharmacodynamic
   - unrelated to main drug action
   - drug idiosyncrasy
   - allergic reactions
   - tolerance, addiction, and physical dependence
   - teratogenesis (when mom takes something and it affects the baby)
   - idiopathic drug reaction

Question 4

2 types of ADR: Pharmacodynamic

Answer 4

1. extension of therapeutic effect
   - overdose
2. effects in non-target tissues or organs
   - drug receptors exist in other tissues

Question 5

7 types of ADR: non-pharmacodynamic

Answer 5

• unrelated to main drug reaction
• drug idiosyncrasy
• allergic reactions
• adverse biotransformation reactions
• tolerance, addiction, physical dependence
• teratogenesis
• idiopathic drug reaction

Question 6

types of ADR mneumonic

Answer 6

A - Augmented: dose-related
B - Bizarre: non-dose related
C - Chronic: dose related and time related
D - Delayed: time related
E - end of use: withdrawal
F - failure: failure of therapy

Question 7

Drug-Drug Interactions

Answer 7

effect one drug has in the presence of another
the more drugs a pt takes the more likely

can be beneficial which:
- increases effectiveness, decreases toxcicity
or the opposite and be harmful

Question 8

risk factors for DDI

Answer 8

• age
• polypharmacy
• genetic factors
• drug properties
• pathological conditions

Question 9

5 types of DDI

Answer 9

1. addition
2. synergistic
3. antagonistic
4. potentiation
5. altered physiology

Potentiation can overlap with synergistic

Question 10

Addition DDI

Answer 10

1+1=2
2 drugs bind to the same receptor to produce the same effect (sedation)
greater effect greater sedation

ex: 2 benzodiazepine drugs given together -> additive effect

Question 11

Synergism DDI

Answer 11

1+1=3
2 drugs bind to diff receptors - increase sedative effect
2 do the same job
ex: barbiturate + alcohol = increased CNS depression

Question 12

Antagonism DDI example

Answer 12

1+1=0

ex: naloxone inhibits the effects of morphine at the opioid receptor.

Question 13

Potentiation

Answer 13

One drug does not elicit a response on its own but enhances the response of another drug.

Ex: penicillin + clavulanic acid = increased penicillin effect

(clavulanic acid: not an antibiotic, prevents antibiotic resistance in bacteria that secrete beta lactamase enzyme, inactivates most penicillin

Question 14

Altered Physiology

Answer 14

ex: hydrochloro (HCT; diuretic) = increased digitalis toxicity

HCT - K+ excretion - hypokalemia

digitalis toxicity increased by hypokalemia

Question 15

what is the link btwn DDI’s and pharmacokinetics

Answer 15

one drug alters ADME of another drug - alters concentration of drug - alters the drug response

Question 16

DDI and absorption

Answer 16

drug rate may alter the rate and/or extent of absorption of another drug
Ca+ rich sources interfere with tetracycline antibiotics
laxatives enhance intestinal motility - decrease absorption of other drugs

anticholinergics delay rate of absorption
prokinetic drugs enhance rate of absorption

• Tetracycline - usually taken orally
• Calcium tends to combine tetracycline kelates (idk how to spell it) and be secreted together
• With tetracycline dairy products would cause the drug not to be absorbed
• Anticholinergic - tend to reduce motility of the intestine, they interfere with absorption

Question 17

DDI and distribution

Answer 17

one drug may alter the distribution of another
ex: competition on the same protein binding sites in blood (sulphonamide displaces warfarin)

Anything to interfere with delivery will affect distribution of drug
Warfarin - is a oral anticoagulant to help the blood fluid without clotting
Sulphonamide - compete with warfarin

Question 18

DDI and biotransformation

Answer 18

some drugs affect the activity of the cytochrome P450 (CYP) enzymes
- CYP’s are important in metabolism of many drugs, and endogenous substances

enzyme induction - increases CYP activity - increases rate of drug metabolism - decreases drug’s effect - decreases drug’s benefit

enzyme inhibition - decreases CYP activity - decreases rate of drug metabolism - increases drug effect - increases ADR

Takes care of metabolism of drugs
If you have liver disease or something that inhibits this, adverse effects will rise because the drug will not exit the body
Enzyme induction: some will stimulate the system, become too active and break down the drugs quickly
Enzyme inhibition: some drugs will inhibit the system, these drugs will accumulate and make adverse effects in the body

Question 19

Ex of enzyme inducers

Answer 19

Barbiturates and anti-convulsant
phenytoin
carbamazepine
rifampicin

smoking

Question 20

Ex of enzyme inhibitors

Answer 20

cimetidine
ciprofloxacin
erythromycin
fluoxetine

grapefruit

Question 21

DDI and excretion

Answer 21

one drug may alter rate of excretion of another drug by the kidneys
(anything that affects kidneys affects excretion!)
enhancing excretion: diuretics increase amount of urine - increase excretion of other drugs

delaying excretion:
- probenecid competitively inhibit penicillin excretion - increase therapeutic effect (beneficial)
- NSAIDs competitively inhibit methotrexate excretion - increase toxicity (harmful)

Question 22

Drug-Food Interactions (2)

Answer 22

1. Grapefruit
   - Decreases CYP 3A4 (this is the grapefruit enzyme inhibitor very important and metabolizes 50% of medications) and increases drug response
   ex: calcium channel blockers
2. Tyramine-containing food
   - tyramine: has sympathomimetic effect, is inactivated by MAO enzyme
   - MAOI prevent tyramine inactivation - severe hypertension
   ex: some types of cheese