Pharma principles Flashcards by Alex Harper

Define pharmacokinetics?

what the body does to the drug

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Define pharmacodynamics

what the drug does to the budy

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Define clearance

Volume of plasma cleared of a drug per unit time

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Define half-life?

Time taken for drug concentration to decline to half its
original value.
 Depends on volume of distribution and clearance

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Define volume of distribution

Volume into which a drug appears to distribute.
 High for lipid-soluble drugs
 Low for water soluble drugs

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Define 1st order kinetics

Clearance of drug is always proportional to plasma

concentration.

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Define zero order kinetics plus examples?

Clearance of drug not always proportional to plasma concentration.
Saturation of metabolism → constant rate of elimination
regardless of plasma levels.

eg. phenytoin, salicylates, ethanol

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Define bioavaliability?

Percentage of the dose of a drug which reaches the

systemic circulation.

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Define multiple dosing? No. of half-lives to reach steady state? TO to reduce time to reach a steady state? Examples?

When a drug is administered on a multiple-dosing regimen, each successive dosage(s) are administered before the preceding doses are completely eliminated. - resulting in accumlation of the drug in plasma

~5 HLs
use of a loading dose reduces time needed to reach a steady state

eg. Phenytoin, digoxin, amiodarone, theophylline

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Indications for therapeutic drug monitoring? examples of when therapeutic drug monitoring is required?

Ix lack of drug efficacy or possibility of poor compliance
Suspected toxicity
Prevention of toxicity

Aminoglycosides (essential)
 Vancomycin (essential)
 Li (essential)
 Phenytoin
 Carbamazepine
 Digoxin
 Ciclosporin
 Theophylline
NB. Warfarin is not monitored per se, it’s the biological effect
which is monitored rather than the plasma drug level.

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Define first pass metabolism? Where does it occur? Examples?

Metabolism and inactivation of a drug before it reaches
the systemic circulation.

Occurs in gut wall and liver
 E.g. propranolol, verapamil, morphine, nitrates

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Define phase 1 metabolism? system used?

Creation of reactive, polar functional groups
 Oxidation: usually by CyP450 system
 Reduction and hydrolysis

Cytochrome P450 most important system in Phase 1 metabolism

CyP3A4 most important subtype

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Define phase 2 metabolism?

Production of polar compounds for renal elimination
 Either the drug or its phase 1 metabolite
 Conjugation reactions
 Glucuronidation, sulfonation, acetylation, methyl

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List the pro-drugs

L-Dopa → dopamine
 Enalapril → enalaprilat
 Ezetimibe → ez-glucuronide
 Methyldopa → α-methylnorepinephrine
 Azathioprine → 6-mercaptopurine (by XO)
 Carbimazole → methimazole
 Cyclophosphamide

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Define pharmacogenetics? examples?

Genetically determined variation in drug response

Acetylation
 Fast vs. slow acetylators (↑↑ fast in Japan vs. Europe)
 Affects: isoniazid, hydralazine and dapsone

Oxidation
 There are genetic polymorphisms for all known CyP450 enzymes except for CyP3A4

G6PD Deficiency
 Oxidative stress → haemolysis
 Quinolones, primaquine, nitrofurantoin, dapsone

Acute Intermittent Porphyria
 AD, ↑ in White South Africans
 Large no. of drugs can → attacks: e.g. EtOH, NSAIDs…

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Types of ADRs?

Type A - Common, predictable reactions, dose related, consequence of known pharmacology of the drug

Type B - rare, idiosyncratic reactions - usually not drug related - eg. allergies and pharmacogenetic variations

Long-term ADRs - dependence, addiction, withdrawal, adaptive changes (eg. tardive dyskinesia)

Delayed ADR - Carcinogenic, teratogenic

Types of allergic reactions?

Type 1: Anaphylaxis - involve immunoglobulin E (IgE)–mediated release of histamine and other mediators from mast cells and basophils
Type 2: Cytotoxic antibodies (eg. causing haemolysis, Rh incompatibility of a newborn, blood transfusion reactions, and autoimmune diseases like Pemphigus Vulgaris, Bullous Pemphigoid, autoimmune hemolytic anemia and Goodpasture’s syndrome
Type 3: Immune complexes eg. Tissue damage present in autoimmune diseases (e.g., systemic lupus erythematosus), and chronic infectious diseases (e.g., leprosy)
Type 4: cell-mediated (delayed hypersensitivity) - initiated by T-lymphocytes and mediated by effector T-cells and macrophages eg. tuberculosis and fungal infections

Types of rashes that can occur due to drug ADR?

Urticaria: Immune: penicillins, cephalosporins; Non-immune: contrast, opiates, NSAIDS
Erythema multiforme: sulfonamides, NSAIDs, allopurinol, phenytoin, penicillin
Erythema nodosum: Sulfonamide, Amoxicillin, Oral contraceptive, Non-steroidal anti-inflammatory drugs
Photosensitivity: amiodarone, thiazides, sulfonylureas
Fixed eruptions: erythromycin, sulphonamides
Lupus-like reactions: hydralazine, isoniazid, penicillamine

Types of hepatotoxicity caused by ADRs?

Cholestatic
hepatocellular damage
chronic hepatitis
gallstones - OCP

Drugs causing cholestatic hepatotoxicity?

Clavulanic acid: may be delayed
Fluclox: may be delayed
 Erythromycin
 Sulfonylureas (glibenclamide)
 OCP
 Tricyclics
 Chlorpromazine, prochlorperazine

drugs causing hepatocellular damage?

Hepatocellular Damage
 Paracetamol
 Valproate, phenytoin, CBZ
 Rifampicine, izoniazid, pyrazinamide
 Halothane
 Methotrexate
 Statins

Drugs causing chronic hepatitis?

Izoniazid
methyldopa
methotrexate

Drugs causing pancytopenia and aplastic anaemia?

Cytotoxics
Phenytoin
Chloramphenicol
Penicillamine
Phenothiazines
Methyldopa

Drugs causing neutropenia?

Carbamazapine
Carbimazole
Clozapine
Sulfasalazine

Drugs causing thrombocytopenia?

Valproate Salicylates Chloroquine

Drugs causing peripheral neuropathy?

``` Izoniazid Vincristine Amiodarone Nitrofurantoin Penicillamine ```

Drugs causing pulmonary fibrosis?

``` Bleomycin Busulfan Amiodarone Nitrofurantoin Sulfasalazine Methotrexate Methysergide ```

Drugs causing gynaecomastia?

``` Spironolactone Digoxin Verapamil Cimetidine Metronidazole ```

Drugs causing SIADH?

``` Carbemezapine Cyclophosphamide Chlorpropamide SSRIs TCAs ```

Drugs causing gingival hypertrophy?

Nifedipine Phenytoin Ciclosporin

Drugs causing prolonged QTc?

FVN MATcH ``` Fluoroquinolones Venlafaxine Neuroleptics: phenothiazine Macrolides Anti-arrhythmics 1a/3: quinidine, amiodarone, sotalol TCAs Histamine antagonists ```

Cholinergic SEs? Causes?

``` SLUDGES Salivation Lacrimation Urination Diarrhoea GI upset Emesis Sweating ``` also bronchoconstriction, miosis

Anti-muscarinic SEs? Causes?

Can't shit, cant spit, cant see, cant pee Constipation, dry mouth, blurred vision, urinary retention also bronchodilation, drowsiness, mydriasis ``` Causes  Ipratropium  Anti-histamines  TCAs  Antipsychotics  Procyclidine  Atropine ```

Causes of dopamine excess? features? Causes of dopamine deficit? features?

Excess: L-dopa, Da agonist Behaviour change, Confusion, Psychosis Deficit: Anti-psychotics, Anti-emetics: metoclopramide, prochlorperazine EPSEs, ↑ prolactin, Neuroleptic malignant syndrome

Cerebellum syndrome symptoms? Drug causes?

``` Dysdiadochokinesis, dysmetria, rebound  Ataxia  Nystagmus  Intention tremor  Slurred speech  Hypotonia ``` alcohol, phenytoin