Pharm General Flashcards
Drugs involved with first pass metabolism
Nitrates have Large Pre-Systemic Metabolism Vary Its Administration Type
- Nitrates (isosorbide dinitrate glyceryl trinitrate)
- Hydrocortisone
- Lignocaine
- Propranolol
- Salbutamol
- Morphine
- Verapamil
- Isoprenaline
- Aspirin
- testosterone
What is pharmacokinetics & phases
what the body does to the med
absorption
distribution
metabolism
Distribution
What is First past metabolism & mnemonic?
Concentration of a drug is greatly reduced before it reaches the systemic circulation thus doses or give other routes.
Solution = different administration
Nitrates have Large Pre-Systemic Metabolism Vary Its Administration Type
What is Zero-order kinetics & mnemonic
a constant amount of drug is eliminated per unit time.
Pea WHEATT
Drugs that have zero order Kinetics/ elimination
Pea WHEATT
Phenytoin
Warfarin
Heparin
Ethanol
Aspirin (high dose )
Theophylline
Tolbutamide
How does liver failure and Kidney failure lead to reduced volume of distribution
Drug bound to plasma are filtered out before getting to the circulation
First -order kinetics/ emlination
kinetics occur when a constant proportion of the drug is eliminated per unit time.
Define phase I reactions:
oxidation, reduction, hydrolysis
are typically more active and potentially toxic
Cytochome P450
Define phase II reactions:
conjugation
typically inactive and excreted in urine or bile
Acetylator status: Deficient in Hepatic N-acetyltransferase
Drugs affected by acetylator status (Deficient SHIP)
* dapsone
- sulfasalazine
- hydralazine
- isoniazid
- procainamide
Define competitive antagonist
medication that reversibly binds to the same receptor site where an agonist binds, but it does not activate it. decrease the agonist potency, but do not affect the agonist efficacy
It just blocks site
Define Non-competitive antagonist-
Where do they bind
What happens after binding
What type of binding
- bind to “allosteric site” or agonist binding site
When they bind, the shape of the receptor changes so the ligand can no longer recognize & can’t produce the agonist effect.
Binding is irreversible or it dissociates very slowly.
Alpha-1 adrenergic receptors fx and location
Blood vessel
Eye
Bladder
are mainly located on the walls of blood vessels, and when stimulated, they cause vasoconstriction, thus decreasing blood flow to tissues.
2. In the eyes
trigger mydriasis, or pupil dilation.
- bladder, -sphincter constriction and urinary retention, or holding the urine within the bladder.
And in males, they trigger ejaculation.
Alpha-2 adrenergic
Fx
Location
Example
receptors are primarily found on the presynaptic neuron inhibits further release of norepinephrine and serves as a mechanism of negative feedback control.
Mirtazapine
Alpha-1 adrenergic Blker
Non-Selective drug
Examples
non-selective blockers, Phenoxybenzamine, -irreversible antagonist, Rx for pheochromocytoma;
Phentolamine, a reversible antagonist, mainly used to treat hypertensive crisis caused by the combination of MAOIs, and tyramine-rich foods.
Alpha-1 adrenergic Blker
Selective drug Examples/ uses
Hypertension treatment: prazosin, terazosin, and doxasozin,
Tamsulosin, which relieves the symptoms of benign prostatic hyperplasia.
Side effects of Alpha adrenergic inhibition
-blocks the action of adrenaline on the alpha receptors.
1. tachycardia and arrhythmia
2. nasal congestion
3. sexual dysfunction
Where are Beta1 receptors found (2)
- Heart- increase HR & contractility
- Kidney stim juxtaglomerular cells,=release renin = increase BP
Where are Beta2 adrenergic receptors (5)?
-
Smooth muscle cells in the walls of blood vessels of skeletal mscls & brain, = vasodilation & increased blood flow to these tissues.
bronchodilation, and that increases oxygen delivery to cells. - GI tract, = decrease motility & slow digestion.
- Eyes, = promote the secretion of aqueous humor,
- Liver, = release glucose into blood & the release of glucagon=raise blood glucose levels.
- Breaks down triglycerides into free fatty acids and cholesterol.
First generation non- selective beta blockers,
Examples
- antagonists on both beta1 and beta2 adrenergic receptors.
1. propranolol,
timolol,
nadolol,
sotalol
pindolol.
SE. & Contraindications non- selective beta blockers,
What happens with Sudden stoppage
- Bradycardia
- Hypotension
- Sudden stoppage = severe rebound tachycardia, Htn , or even arrhythmias,
- Propanol effects CNS = dizziness, depression, insomnia,
- Wheezing- not used in COPD or asthma
- Diarrhea
- Hypertriglyceridemia,
- Hypoglycemia,
2nd generation of beta blockers are selective for
effects
Examples
Beta1 adrenergic receptors
Lower BP (decreasing HR & contractility),
kidneys decrease renin release = lower BP
metoprolol and bisoprolol safe in obstructive d’s & DM
3d generation of beta blockers
Effects (2)
Examples (2)
blocking beta1 receptors, these medications also block alpha1 receptors in the blood vessels,
labetalol and carvedilol
Direct cholinomimetics
- Receptors acted
- reaction Acetylcholinesterases
-Examples
mimic the action of acetylcholine by directly acting at muscarinic or nicotinic receptors.
- NOT degradation by Acetylcholinesterases. and have a long lasting or more potent effect.
bethanechol, carbachol, methacholine, and pilocarpine
Fx Muscarinic and nicotinic stimulation & mnemonic:
DUMB HAVES
Defecation;
Urination;
Muscle excitation; Bronchospasm;
Heart bradycardia;
Autonomic ganglia stimulation;
vasodilation;
Eye miosis/constriction & accomadation
Secretions from the lacrimal, salivary, sweat & glands of the GI tract
Name the 2 Cholinergic Receptors types
- Muscarinic –Found in parasympathic Neurons post gangilion
- Nicotinic- Ligand gated ion receptors; Found in the post ganglionic neurons in both sympathetic and parasympathetic systems. Passive gradient bring Na in & K out = depolarsation of cell
Where are Muscarinic receptors found and what type of receptors are they
Muscarinic – G-Proteins; Found in parasympathic Neurons post gangilion. Activated by actylcholine
Nicotinic- Ligand where are they found and what type of receptors are they
gated ion receptors; receptors open with actylcholine. Found in the post ganglionic neurons in both sympathetic and parasympathetic systems. Passive gradient bring Na in & K out = depolarsation of cell
What are Direct Agonist Cholinergics
and what receptors do they work on ?
mimic acteylcholine
Muscarinic and nicotinic stimulation
How do indirect cholinomimetics, also called anti-cholinesterases
inhibit the enzyme acetylcholinesterase that normally degrades acetylcholine in the synaptic cleft.
What is Sick faces. com stand for
- Sodium valproate
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Acute Alcohol & allopurinol, amiodarone, (triple A) Grapefruit juice
- Chloramphenicol
- Erythromycin
- Sulfonamides & SSRI’s
- Ciprofloxacin
- Omeprazole
- Metronidazole
Higher levels in the blood
levels
-think sepsis, or binge drinking higher Conc in the blood
BS CRAP GP induce rage
- barbiturates: phenobarbitone
- St John’s Wort
- Carbamazepine
- Rifampicin
- Alcohol chronic
- Phenytonin
- Griseofulvin
- Phenobarbital
smoking (affects CYP1A2, reason why smokers require more aminophylline)
Lower levels in blood
think alcoholic GP having reduced effect
Zero-order kinetics define
And mnemonic
- constant amount of drug being eliminated per unit time
Pea WHEATT
Phenytoin
Warfarin
Heparin
Ethanol
Aspirin (high dose)
Theophylline
Tolbutamide
First -order kinetics
-First order kinetics occur when a constant proportion of the drug is eliminated per unit time.
Deficient in hepatic N-acetyltransferase
(Deficient SHIP) nb z
* dapsone
* sulfasalazine
* hydralazine
* isoniazid
* procainamide
What Ligand-gated ion channel receptors
When ligand bind channel ion opens= ion flow into cell generally mediate fast responses. e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate receptors
What are Tyrosine kinase receptors-
involving phosphorylation of targets, =effects like cell growth and differentiation:
Examples
insulin, insulin-like growth factor (IGF), epidermal growth factor (EGF).
non-receptor tyrosine kinase: PIGG(L)ET: Prolactin, Immunomodulators (cytokines IL-2, Il-6, IFN), GH, G-CSF, Erythropoietin and Thromobopoietin
what are Nuclear receptors?
Examples
receptors within nucleus of the cell and
activation or inhibition of these receptors = increased or decreased gene transcription. Must be lipid soluble to get into cell.
Example Steroids such as prednisolone and other hormone replacements such as levothyroxine.
Which G proteins sub units work on adenylate cyclase
Gs Stimulates adenylate cyclase → increases cAMP
Gi Inhibits adenylate cyclase
G protein-coupled receptors-
Subunits
Inactive and active form
mediate slow transmission and affect metabolic processes
* 7-helix membrane-spanning domains
* consist of 3 main subunits: alpha, beta and gamma
* the alpha subunit is linked to GDP when inactive.
Ligand binding =conformational =GDP is phosphorylated to GTP, and the alpha subunit is activated.
*
G proteins sub units Gq function
Activates phospholipase C → splits PIP2 to IP3 & DAG → activates protein kinase C
active open Ca2+ channels= changes the electrical charge of the cell= depolarisation
