Pharmacology First Aid Review Flashcards
In enzyme kinetics, how do Vmax and Km change with competitive and non-competitive inhibitors?
Competitive: acts as if to decrease the affinity of the receptor for the substrate to Km will increase but Vmax will remain the same
Non-competitive: acts as if to remove some of the enzyme from the equation so affinity (Km) remains the same but Vmax is diminished
Define volume of distribution
Amount of drug in body divided by plasma concentration
For low, med, high volume of distribution, what are the compartments and drug types?
Low: Blood compartment, large or charged molecules; plasma protein bound
Med: ECF, small hydrophilic molecules
High: All tissues including fat, small lipophilic molecules, especially if bound to tissue protein
Equation for half life
T1/2=0.7*Vd/CL
How does time to steady state change with dose and dosing frequency?
It doesn’t
Time to steady state generally is only affected by t1/2
Equation for loading dose
Target Concentration* Vd/bioavailability
Equation for maintenance dose
(Cp) x (CL) x tau / (F)
Cp= target plasma concentration
CL=clearance rate
tau=dosage interval
F=bioavailability
What is a tachyphylactic drug response?
Acute decrease in response to drug after initial/repeated administration
3 drugs with zero order elimination
Phenytoin, Ethanol, Aspirin
How is pH of urine changed to increase clearance of drugs?
Remember that ionized particles are trapped in the urine and excreted.
Bicarbonate makes the urine more basic which ionizes acids
Ammonium chloride make urine more acidic ionizing bases
What are the phases of drug metabolism?
Phase I: reduction, oxidation, hydrolysis by p450; lost first in geriatric patients
Phase II: Conjugation–Methylation, Glucuronidation, Acetylation, Sulfation; ultimately inactivates drug; Geriatric patients still have this phase
Efficacy vs potency
Efficacy = Effect Potency = how much drug needed for effect
What is EC50?
Amount of drug needed to achieve 1/2 maximal effect
How does potency and efficacy of a drug change with administration of a competitive antagonist vs noncompetitive or partial agonist given alone?
Competitive antagonist: decreased potency but unchanged efficacy because can be overcome by increased concentration
Noncompetitive: removes some receptors from the equation so efficacy is lost but potency is unchanged
Partial agonist given alone: efficacy is lost and potency is completely independent from original drug
Therapeutic index vs window
Index = TD50/ED50; it is the ratio of dose that is toxic to 50% of patients over dose effective in 50%
Window is the dosage range that can safely and effectively treat the disease
In all of the first synaptic terminals in the ANS and Somatic NS, what is the NT and receptor?
Acetylcholine and Nicotinic
What two structures or functions in the body are unique in that they are Sympathetically innervated but NT is ACh? What receptor?
Sweat glands: ACH on muscarinic
Adrenal medulla: ACH on Nicotinic
How do Nicotinic and Muscarinic receptors exert their effects?
Nicotinic: ligand gated Na/K channels
Muscarinic: G-protein coupled
In order to remember the G-protein associated with each receptor, what is the order to list the receptors?
Alpha 1,2 Beta 1,2,3 M 1,2,3 D 1,2 H 1,2 V 1,2
QISSS QIQ SIQ SQS
What are the effects of alpha-2 receptor?
Decreases: sympathetic outflow, insulin release, lipolysis, aqueous humor production
Increases: platelet aggregation
Beta-1 receptor effects
Increases: HR, contractility, renin release, lipolysis
Beta-2 receptor effects
Vasodilation, bronchodilation
Increased: lipolysis, insulin release, aqueous humor production
Decrease: uterine tone, ciliary muscle tension
Beta-3 receptor effects
Increase: lipolysis, thermogenesis in skeletal muscle
M1 receptor effects
CNS and enteric nervous system
M2 receptor effects
Decrease HR and contractility
M3 receptor effects
Increase: exocrine gland secretions (lacrimal, sweat, salivary, gastric), gut peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter, ciliary muscle
D1 receptor effects
Relaxes vascular smooth muscle
D2 receptor effects
Modulates transmitter release in brain especially
H1 receptor effects
Increase: nasal and bronchial mucous production, vascular permeability, contraction of bronchioles, pruritis, pain
H2 receptor effects
Increase gastric acid
V1 receptor effects
Vascular smooth muscle contraction
V2 receptor effects
Increase H2O permeability and reabsorption in the collecting tubules of the kidneys
Describe the Gq pathway
Gq activates Phospholipase C that turns PIP2 into DAG and IP3
DAG stays at the membrane while IP3 releases Ca
Ca signals DAG to activate Protein Kinase C and also signals the contraction of smooth muscle
How do Amphetamines work?
Use NE Transporter (NET) to enter presynaptic terminal and then use VMAT to enter vesicles and displace NE
Once NE reaches high level in presynaptic terminal, NET action is reversed and NE spills into synapse and re-uptake is inhibited
What happens when a patient on MAOI’s eats something with Tyramine?
Tyramine normal in food and processed by MAO in the gut
Increased Tyramine enters noradrenergic nerves and produces increased NE and leads to increased sympathetic stimulation and often an HTN crisis
With all cholinomimetic agents, including AChE inhibitors, what should be watched out for?
Exacerbation of COPD, asthma, and PUD
What is the antidote for Cholinesterase inhibitor poisoning?
Atropine and Pralidoxime
Effects of Atropine overdose
No sweating —> Dry as a bone —> increased body temp (Hot as a hare) and skin flushing (Red as a beet)
Cycloplegia (Blind as a bat)
Disorientation (Mad as a hatter)
What Dopamine agonist might you give for HTN crisis?
Fenoldopam: D1 agonist
Vasodilator–coronary, peripheral, renal, splanchnic
What is the action of Phenylephrine?
agonist at alpha-1 > alpha-2
Epinephrine receptor action?
Beta over Alpha
Alpha predominates at high dose
Significantly stronger Beta-2 than NE
Dopamine receptor actions
D1=D2 > beta > alpha
Used for unstable bradycardia, HF, and shock
Heart effects at lower doses (beta) and vasoconstrictive effects at higher doses (alpha)
What should never be given if cocaine intoxication is suspected and why?
Never give a Beta blocker because would result in unopposed alpha activation leading to HTN crisis
MOA of Ephedrine
Releases stored catecholamines from presynaptic terminal similar to Amphetamine
NE receptor activation
Alpha’s over Beta’s and no Beta-2
NE, Epi, Isoproterenol compared activation of beta vs alpha
NE: alpha over beta
Epi: alpha = beta
Iso: beta over alpha
Of NE, Epi, and Isoproteronol, which will cause the greatest increase in MAP? Which causes an increase in diastolic pressure?
NE and Epi both increase MAP, but NE is greater
NE is only one to increase diastolic pressure
What sympatholytic agent is given for HTN in pregnancy?
alpha-methyldopa
What drug can be given to patients on MAOI’s who eat tyramine containing foods?
They will have a HTN crisis
Treat with Phentolamine to block alpha receptors and bring down BP
Mirtazapine
Alpha 2 selective blocker
Depression treatment
How do reversals by Phentolamine differ between Epi and Phenylephrine?
Because Epi has alpha and beta action, administration of Phentolamine will reverse the overall effects of Epi by blocking the pressor effects and leaving the beta effects unopposed
Phenylephrine’s effects will be diminished, but not reversed because it only has alpha effects
General rules for the selectivity of Beta blockers
Beta-1 selective blockers tend to go from A to M in the alphabet
Nonselective blockers tend to go from N to Z
Nonselective beta and alpha blockers tend to have modified suffixes other than -olol
How is Nebivolol unique?
Combines cardiac-selective beta-1blockade with stimulation of beta-3 which activates NO synthase in vasculature
What is Methemoglobin?
A form of hemoglobin that has a heme group in the ferric (3+) state instead of the ferrous (2+) that makes it so it cannot bind O2
Has a bluish, chocolate brown color
An NADH dependent enzyme–methemoglobin reductase–is responsible for reducing it back to hemoglobin
What drugs can cause coronary vasospasm?
Cocaine, Sumatriptan, ergot alkaloids
What drugs can cause cutaneous flushing?
Think VANCE Vanco Adenosine Niacin Ca channel blockers Echinicandins
What drugs can lead to dilated cardiomyopathy?
Anthracyclines (doxorubicin, daunorubicin)
Prevent with dexrazoxane
What drugs can cause Torsades?
Think ABCDE AntiArrhythmics (class IA, III) AntiBiotics (like macrolides) Anti"C"ychotics (like Haloperidol) AntiDepressants (like TCA's) AntiEmetics (like ondansetron)
What drugs can cause gingival hyperplasia?
Phenytoin, Ca channel blockers, Cyclosporine
What drugs can cause hyperuricemia?
Pyrazinaminde, Thiazides, Furosemide, Niacin, Cyclosporine
What drugs can cause pulmonary fibrosis?
Methotrexate, Nitrofurantoin, Carmustine, Bleomycin, Busulfan, Amiodarone
What are the P-450 inducers?
Think: Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs Chronic alcohol use St. Johns Wart Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine
What are the P-450 inhibitors?
Think: AAA RACKS IN GQ Magazine Acute Alcohol Abuse Ritonavir Amiodarone Cimetidine/Ciprofloxacin Ketoconazole Sulfonamides Isoniazid (INH) Grapefruit Juice Quinidine Macrolides (except azithromycin)
MOA of the antivirals ending in -ivir
Neuraminidase inhibitors
MOA of antivirals ending in -navir
Protease inhibitor
MOA of antivirals ending in -ovir
DNA polymerase inhibitor
